Disclaimer: I am not a medical professional. Nothing on this blog should be interpreted as medical advice.
CHAPTER 5: NUTRITIONAL SUPPLEMENTS AND
BOTANICALS
INTRODUCTION
This section encompasses nutritional
supplements, botanicals (herbs), and compounds that are naturally
found in the body. Although some of these are also classed as
pharmaceuticals, nearly everything in this section can be purchased
without a prescription. (The exception is injectables.) We have not
included each and every supplement that is available on the market,
but have limited our selection to those for which there is relevant
medical research, or which are in common use either by CFS/ME
clinicians or by CFS/ME patients themselves.
Nutritional supplements are an
essential component of any CFS/ME treatment protocol. Research has
shown that people with CFS/ME are routinely deficient in many
important nutrients (notably zinc, magnesium, and carnitine). These
deficiencies, in and of themselves, can decrease the degree to which
the body can absorb and make use of other nutrients. Even when there
are no clinical nutritional deficiencies, the physiological demands
of a chronic illness make it necessary to provide additional
nutritional support – especially in light of the numerous GI
problems prevalent in the CFS/ME population, which may lead to
malabsorption. For these reasons, and because most CFS/ME doctors
recommend supplements, this section attempts to be as inclusive as
possible.
There is a method to taking nutritional
supplements. As with pharmaceuticals, supplements should initially be
taken in very small doses to test for sensitivity. Even if a
supplement consists of something “natural” there is nothing
natural about taking it in concentrated doses. Your body reacts to
these as it would to any chemical. For that reason, it is wise to
take supplements with food, unless instructed otherwise.
“Take with food” means eat a little
first, then take the supplement, then eat some more. By sandwiching
the supplement within a meal, you lower the risk of reactions, as the
supplement is processed along with food. Sandwiching supplements also
reduces the risk of heartburn. When a supplement is taken with water
only it floats to the top of the stomach, where it can easily flow
back into the esophagus, causing irritation.
New supplements should be taken one at
a time. That is, don't start several supplements at once, even if
they act synergistically. Take the new supplement for three or four
days before introducing another. This allows you to evaluate the
supplements for possible negative reactions or sensitivities.
Supplements can be quite expensive and
are not usually covered by health insurance. But purchasing the
cheapest brand is not always the wisest course to take. There is a
wide range in quality when it comes to nutritional supplements. Some
of the cheapest brands may not even contain the ingredients on the
label. It is best to stick to well-known brands and to purchase from
reputable suppliers. (See Appendix D: Mail Order Suppliers.)
Purchasing online, rather than from retail outlets can cut the cost
of expensive supplements in half. Whenever possible, we have included
recommendations in each entry.
Most online suppliers include product
label information on their websites, but for those who wish to
compare the product labels of a supplement made by different
manufacturers, or check into recalls or FDA notices for specific
supplements, there are several helpful websites that will provide
this information:
- The Dietary Supplements Labels Database. This is a very useful website that allows searches for product labels by manufacturer and by product. From the website: “The Dietary Supplements Labels Database offers information about label ingredients in more than 6,000 selected brands of dietary supplements. It enables users to compare label ingredients in different brands. Information is also provided on the "structure/function" claims made by manufacturers.” http://dietarysupplements.nlm.nih.gov/dietary/index.jsp
- Natural Products Foundation. The NPF keeps an excellent database of supplements, as well as the medical conditions they are used for. From the website: “The Dietary Supplement Information Bureau™ (DSIB™) was founded in 2001 to promote the responsible use of vitamins, minerals, herbs and specialty supplements. In June 2008 DSIB became part of the Natural Products Foundation, a not-for-profit organization whose mission is to promote and facilitate research and education related to natural products for the benefit of consumers and industry.” http://www.naturalproductsinfo.org/
- Consumer Healthcare Products Association. The CHPA website provides a search for government warnings and decisions regarding most OTC medications and supplements. From the website: “The Consumer Healthcare Products Association (CHPA), founded in 1881, is a member-based association representing the leading manufacturers and distributors of nonprescription, over-the-counter (OTC) medicines and dietary supplements.” http://www.chpa-info.org/
FURTHER READING
Dowson, David, MD. “Nutrition
Toxicity and ME/CFS.”
http://www.annhilltrust.org/nutrition-toxicity-and-me.html
5-HTP
DESCRIPTION. 5-Hydroxytryphophan
(5-HTP) is a naturally occurring amino acid which serves as a
precursor to the neurotransmitter serotonin.
BACKGROUND. 5-HTP is a precursor as
well as a metabolic intermediate in the synthesis of serotonin and
melatonin from tryptophan. Through the action of vitamin B6, 5-HTP is
converted in the liver and nervous system to 5-HP (serotonin). Most
commercially marketed 5-HTP is derived from the seeds of the
Griffonia simplicifolia. a woody climbing shrub native to West
Africa.
Serotonin is the most abundant
neurotransmitter in the human body. In the brain it plays a crucial
role in sleep, mood, learning, memory and appetite. However, the vast
majority of serotonin, 90%, is produced in the lining of the
intestines, which has led Dr. Michael Gershon, chairman of the
department of anatomy and cell biology at Columbia University, to
refer to the gut as the “second brain.” This eponym is apt, for
today gastroenterologists routinely prescribe serotonin enhancers for
treating GI motility problems.
USES IN CFS/ME. Several studies have
shown that 5-HTP is an effective overall treatment for fibromyalgia.
For people with CFS/ME, 5-HTP is most often used as a sleep aid.
PROTOCOL. Dr. Rodger Murphree, a
chiropractor and nutritionist who has been treating CFS/ME for over
15 years, recommends taking 5-HTP 30 minutes before bed, on an empty
stomach, with four ounces of juice. Start with 100 mg, then go to 150
and then to 200. Don’t go above 300 mg. It may take several nights
to take effect. If it doesn’t work in two weeks, Dr. Murphree
suggests stopping and switching to melatonin. According to Dr.
Murphree, patients who stay on 5-HTP for more than three months
should take a broad-based amino acid supplement to balance out the
other neurotransmitters.
PROS AND CONS. 5-HTP, like many
antidepressants, can cause strange, vivid dreams. These dreams
usually diminish over time. Excessively high serotonin levels can
cause insomnia, hyperactivity, headache, and increased heart rate.
CFS/ME patients who have a negative reaction to 5-HTP should either
lower the dose or stop.
AVAILABILITY AND COST. 5 HTP is sold in
most health food stores and by online distributors. A bottle of 60
tablets can cost as little as $8.00.
CAUTION: High doses of 5-HTP can cause
serotonin syndrome, a condition in which serotonin is raised to
dangerous levels. Taking 5-HTP with serotonin-enhancing
pharmaceuticals such as triptans (for migraines), antidepressants,
Demerol, Robitussin, and Ultram can also lead to serotonin syndrome.
FURTHER READING
Good summary of 5-HTP as a CFS/ME
treatment: http://www.immunesupport.com/98wtr002.htm
Discussion of 5-HTP as a CFS/ME
treatment: http://aboutmecfs.org.violet.arvixe.com/Trt/5-HTP.aspx
Dr. Teitelbaum on 5-HTP and other
natural sleep aids: http://www.healthy.net/scr/Column.aspx?Id=647
General information on 5-HTP:
http://www.herbwisdom.com/herb-5-htp.html
PATIENT REVIEWS
CFS/ME patient reviews of 5-HTP:
http://www.revolutionhealth.com/drugs-treatments/rating/5-htp-5-hydroxytryptophan-for-chronic-fatigue-syndrome-cfs-cfids-me
RESEARCH
Caruso I, Sarzi Puttini P, Cazzola M,
Azzolini V. “Double-blind study of 5-hydroxytryptophan versus
placebo in the treatment of primary fibromyalgia syndrome.” J Int
Med Res. 1990 May-Jun;18(3):201-9.
http://www.ncbi.nlm.nih.gov/pubmed/2193835 (Abstract)
Sarzi Puttini P, Caruso I, “Primary
fibromyalgia syndrome and 5-hydroxy-L-tryptophan: a 90-day open
study.” J Int Med Res.1992 Apr;20(2):182-9.
http://www.ncbi.nlm.nih.gov/pubmed/1521674 (Abstract)
ALPHA KETOGLUTARATE
DESCRIPTION. Alpha ketoglutarate (AKG)
is an ionic form of alpha ketoglutarate acid, an intermediate in the
tricarboxylic cycle (Krebs cycle, or citric acid cycle).
BACKGROUND. Alpha ketoglutarate (AKG)
fulfills a vital role in the metabolism and utilization of
carbohydrates, proteins, and long-chain fatty acids. Its best known
function is as a component of a number of energy-producing cycles at
the cellular level. The first of these, the Krebs cycle, breaks down
and transforms citric acid through a series of enzyme-controlled
reactions to produce adenosine triphosphate (ATP), a crucial energy
source for many cell processes. AKG, as an early intermediate in the
Krebs cycle, forms the basis for all further transformations. It is
also required for catabolism of many amino acids, another process
that generates energy.
Another important function of AKG
involves the formation of nonessential amino acids (amino acids that
are biosynthesized in the body), notably glutamate and, through its
action, proline, alanine, aspartic acid, and asparagine. AKG is also
one of the most important transporters of cellular nitrogen,
combining with nitrogen in the cell to prevent an overload of ammonia
in the body.
USES IN CFS/ME. AKG is used as a
short-term energy enhancer and for Krebs cycle support in patients
with CFS/ME. Because of its essential role in energy production and
carbohydrate metabolism, it may be useful as a general CFS/ME
treatment as well. AKG is also beneficial for the intestines. Many
people with CFS/ME suffer from digestive problems, including food
sensitivities, dysbiosis, slow transit time, small intestine
bacterial overgrowth (SIBO) and a host of other disorders. AKG is
converted in the intestines into glutamate, which regulates gastric
emptying and provides an environment for healthy gut flora. AKG also
prevents damage to the mucosal lining of the intestines by inhibiting
oxidative stress.
PROTOCOL. The suggested dosage of AKG
is one or two 300 mg capsules per day, which can be taken with meals.
Because of its location in the Krebs cycle, alpha ketoglutarate is
generally more effective if taken with other Krebs cycle supports
such as vitamin C, B vitamins, essential fatty acids (evening
primrose oil, borage oil, or fish oil), magnesium, nutritional
supplements, and NAC (N-acetyl-L-cysteine).
PROS. Because alpha ketoglutarate is
not a stimulant but works through natural metabolic pathways, it is a
relatively risk-free source of energy. People who take alpha
ketoglutarate usually do not "crash" afterward. It has no
reported side effects at recommended doses. Patients with low levels
of AKG (as confirmed by an Organic Acids Test) have noted significant
improvement in energy levels with alpha ketoglutarate
supplementation.
CONS. Results tend to be less dramatic
than those obtained with CoQ10, which may make this product less
attractive to those who want a greater boost. Among its many
function, AKG leads to production of nitric oxide (NO), which Dr.
Pall has implicated in many CFS/ME symptoms. He has recommended that
NO should be down regulated in people with CFS/ME. Because AKG is
normally combined with excitatory amino acids, it can cause insomnia.
AVAILABILITY AND COST. Pure AKG is
difficult to find. Most suppliers combine AKG with an amino acid,
such as arginine or glutamine. Douglas Labs sells a 90-tablet bottle
of AKG (300 mg) combined with vitamin B6, calcium and phosphorus for
$18.
FURTHER READING
Benefits of AKG and its functions in
the Krebs cycle:
http://www.ei-resource.org/articles/general-environmental-health-articles/influencing-your-krebs-cycle/
A detailed description of Krebs cycle
intermediaries, including AKG. Very technical.
http://www.nutritionreview.org/library/krebs.php
RESEARCH
Hou Y, Wang L, Ding B, Liu Y, Zhu H,
Liu J, Li Y, Kang P, Yin Y, Wu G. “Alpha-Ketoglutarate and
intestinal function.” Front Biosci. 2011 Jan 1;16:1186-96.
http://www.ncbi.nlm.nih.gov/pubmed/21196226 (Abstract)
ALPHA LIPOIC ACID
DESCRIPTION. Alpha lipoic acid, or
lipoic acid, is a an organic compound derived from caprylic acid. It
is both fat and water soluble.
BACKGROUND. Alpha lipoic acid (ALA) has
been referred to as the “mother” of all antioxidants. This
well-deserved epithet is due to the fact that not only does it act as
a potent free radical scavenger, it can transform an oxidant into an
antioxidant. Notably, when glutathione is oxidized, ALA can transform
it back into its reduced form, thus increasing the pool of
glutathione.
ALA is produced throughout the body
through the biosynthesis of fatty acids. Although it is found in many
foods (especially organ meats, yeast extract and leafy green
vegetables), alpha lipoic acid is not readily available through
dietary sources. As a consequence, all alpha lipoic acid supplements
must be synthesized.
Alpha lipoic acid has been studied for
its effects on many disease states, including treatment for
cardiovascular disease, prevention of migraines, preventing organ
dysfunction, slowing the progression of Alzheimer's disease, reducing
inflammation, and the treatment of chronic diseases involving
oxidative stress. A study conducted in 1999 by Kishi et al found that
the reduced glucose uptake in diabetes was completely reversed with
alpha lipoic acid, which not only corrected the deficit, but improved
the peripheral neuropathy found in diabetics.
A detailed proposal submitted to the
National Cancer Institute by the Chemical Selection Working Group
(see below) indicates that ALA may work best when combined with
acetyl L-carnitine. Acetyl-L-carnitine facilitates the movement of
fatty acids into the mitochondria for energy and is also used to
generate acetyl coenzyme A, while ALA is involved in mitochondrial
ATP production and can recycle other antioxidants. The authors
propose that the combination of acetyl L-carnitine and ALA may have
significant synergistic effects – increasing energy and reducing
oxidative stress.
USES IN CFS/ME. A number of CFS/ME
clinicians and researchers, notably Martin Pall and Dr. Myhill, have
pointed out that oxidative stress is a primary component in the
cascade of CFS/ME symptoms. Oxidative stress can affect every system
in the body, and has particularly deleterious effects on oxygen
transport systems (blood). ALA has been shown to improve the
integrity of red blood cells (which are often abnormal in CFS/ME
patients) leading to elevated glutathione levels. Glutathione, one of
the body's most potent antioxidants, is often diminished in CFS/ME
patients.
PROTOCOL. The “R” form is the most
bioavailable and stable form of alpha lipoic acid. (The “S” form
deteriorates rapidly.) There is no set protocol for ALA. CFS/ME
patients who have tried ALA recommend beginning at the lowest dose
(100 mg) to avoid detox symptoms (headache, “hungover” feeling).
PROS. ALA has no documented side
effects at low doses. Many people have noted an increase in energy,
muscle strength, and mental alertness, particularly when taken with
acetyl-L carnitine.
CONS. Too high a dose can cause
insomnia and stomach upset. ALA lowers blood sugar, which may pose a
problem for people with hypoglycemia. There is one study that
suggests that ALA competes with biotin (vitamin B7) in rats, but the
results have not been confirmed in humans. Those who take large
quantities of lipoic acid may wish to independently supplement with
biotin.
AVAILABILITY AND COST. ALA is widely
available in health food stores and through online distributors. It
is not expensive. A 60-capsule bottle of R-ALA (100 mg) can cost less
than $10.
FURTHER READING
This article questions the necessity of
supplementing lipoic acid with biotin.
http://www.geronova.com/content/lipoic-acid-biotin
RESEARCH
Kishi, Yutaka, James D. Schmelzer,
Jeffrey K. Yao, Paula J. Zollman, Kim K. Nickander, Hans J.
Tritschler, and Phillip A. Low. “ a-Lipoic Acid: Effect on Glucose
Uptake, Sorbitol P a t h w a y, and Energy Metabolism in Experimental
Diabetic Neuropathy.” Diabetes, VOL. 48, October 1999
http://diabetes.diabetesjournals.org/content/48/10/2045.full.pdf
Mirjana M, Jelena A, Aleksandra U,
Svetlana D, Nevena G, Jelena M, Goran P, Melita V. “Alpha-lipoic
acid preserves the structural and functional integrity of red blood
cells by adjusting the redox disturbance and decreasing O-GlcNAc
modifications of antioxidant enzymes and heat shock proteins in
diabetic rats.” Eur J Nutr. 2011 Nov 18.
http://www.ncbi.nlm.nih.gov/pubmed/22094580 (Abstract)
“Acetyl-L-Carnitine/a-Lipoic Acid
Supplements.” This is a proposal prepared for the National Cancer
Institute by the Chemical Selection Working Group (CSWG) on behalf of
Technical Resources International, Inc. It contains a thorough and
exhaustive account of the mechanisms of alpha lipoic acid.
http://ntp.niehs.nih.gov/ntp/htdocs/chem_background/exsumpdf/carnliposupp.pdf
AMINO ACIDS
Carnitine, Glutamine, Lysine, Taurine
DESCRIPTION. Amino acids are
nitrogen-containing chemical units (amines) that, bound together,
make up protein.
BACKGROUND. The amino acids, in various
combinations, form the hundreds of types of proteins present in every
living organism. These proteins are essential for nearly all
processes that induce cell growth and repair, as well as for
continued maintenance of every body tissue, organ, and structure
within the body. Amino acids link together to form tens of thousands
of proteins and enzymes, each of which has a specific function. They
can also perform as individual units. Single amino acids can act as
neurotransmitters or as precursors to neurotransmitters in the
central nervous system. Therefore, not only are they responsible for
providing and maintaining the very substances of which we are made,
but also for the communications system that enables us to plan,
dream, think, feel, and direct our every action.
There are 20 primary amino acids. About
80% are produced in the liver and the remaining 20% must be obtained
from food. Whether an amino acid can be produced within the body is
what distinguishes the essential from nonessential amino acids. The
essential amino acids (those which must be obtained from food
sources) are arginine, histidine, isoleucine, leucine, lysine,
methionine, phenylalanine, threonine, tryptophan, and valine.
Nonessential amino acids (those which can be produced within the
body) include alanine, glutamine, asparagine, glycine, proline, and
serine. Given the countless functions that amino acids perform, a
protein shortage or congenital defect in amino acid synthesis can
lead to problems that involve every system in the body.
Amino acids occur in two isomers: L and
D. The L isomer is the form most commonly found in nutritional
supplements.
USES IN CFS/ME. Specific amino acids,
both essential and nonessential, have been recommended as treatments
by a number of CFS/ME clinicians. Their applications include
mediation of hyperactive nervous system responses, repair of leaky
gut and other intestinal disturbances, and regulation of the
fundamental CFS/ME metabolic dysfunction that results in loss of
cellular energy.
A number of researchers have documented
imbalances in amino acid ratios among people with CFS/ME. In an
article published in 1994, Dr. Alexander Bralley and Dr. Richard Lord
noted that people with CFS/ME commonly have deficiencies in
tryptophan, phenylalanine, taurine, isoleucine, and leucine. They
also found lower than normal amounts of arginine, methionine, lysine,
threonine, and valine in a smaller number of CFS/ME patients. It is
significant that the most common deficiencies found by Drs. Bralley
and Lord are of phenylalanine and tryptophan because these two amino
acids are precursors to the catecholamines and serotonin,
neurotransmitters that are closely involved with sleep function,
stress responses, and regulation of pain and mood.
Dr. Scott Rigden has also noted that
many of his patients with metabolic abnormalities have an imbalance
in amino acid ratios. The implication is that, for these patients,
amino acids may be either synthesized or utilized at a slower rate or
appear in such disequilibrium that they no longer function together
with full efficiency – perhaps giving a clue to the origins of the
collagen formation problems and enzyme disturbances common in many
patients with CFS/ME.
An extensive study published in 2005 by
Jones et al compared organic acids in people with CFS/ME, major
depression, and rheumatoid arthritis. The researchers found lower
levels of taurine, GABA, histidine and tyrosine in the group with
CFS/ME. The researchers also found low levels of histidine in plasma
from rheumatoid arthritis patients, leading the team to speculate
that a similar etiology might be involved for the two illnesses (i.e.
inflammation).
A more recent study by Niblett et al
confirms specific deficiencies in CFS/ME patients of asparagine,
phenylalanine, leucine, isoleucine, valine, and the organic acid,
succinic acid, as well as increases in 3-methylhistidine (an amino
acid associated with protein loss) and tyrosine. The authors
concluded that “urinary excretion and blood parameters data
supported the hypothesis that alterations in physiologic homeostasis
exist in CFS patients.”
In 2012 a team of Australian
researchers identified low levels of glutamine and ornithine, along
with other metabolites that participate in the urea cycle, in a group
of CFS/ME patients. (CFS/ME patients are consistently low in uric
acid.) The researchers suggested that a specific disturbance of amino
acid and nitrogen metabolism was implicated in CFS/ME which might
potentially serve as a biomarker.
Amino acid supplementation has received
particular attention as a treatment for CFS/ME from nutritionists.
Using an amino acid analyzer to measure specific imbalances, Drs.
Bralley and Lord tailored a supplement to correct amino acid
deficiencies. In a study of 25 CFS/ME patients, they found that
correcting specific amino acid imbalances resulted in 50% to 100%
improvement in symptoms (Journal of Applied Nutrition, 1994). The
greatest effect was noted in energy levels. Two patients who had had
CFS/ME symptoms for 15 years experienced dramatic improvement.
Patients also reported improvement in cognitive function and
elimination of "brain fog."
It should be noted that single amino
acids taken as dietary supplements may not be well tolerated by
patients with serious metabolic disturbances. Also note that
tyrosine, an amino acid often found to be deficient in CFS/ME
patients, is seldom recommended. Tyrosine is a dopamine precursor
which triggers symptoms in patients with inflammatory disorders such
as migraine, interstitial cystitis, and rosacea. Dr. Bell has
observed that in CFS/ME patients, dopamine precursors make the
majority of CFS/ME patients feel much worse.
FURTHER READING
Bralley J., Alexander and Richard S.
Lord. “Treatment of Chronic Fatigue Syndrome with Specific Amino
Acid Supplementation.” Journal of Applied Nutrition, Vol 46, No 3,
1994.
http://www.metametrix.com/files/learning-center/articles/Chronic-Fatigue-Amino-Acids.pdf
Dr. Michael Rosenberg's amino acid
protocols for treating CFS/ME.
http://www.prohealth.com/library/showarticle.cfm?id=4337&t=CFS/ME_FM
RESEARCH
Armstrong, Christopher W., Neil R.
McGregor, John R. Sheedy, Ian Buttfield, Henry L. Butt, Paul R.
Gooley. “NMR metabolic profiling of serum identifies amino acid
disturbances in Chronic Fatigue Syndrome.” Clinica Chimica Acta.
Available online 21 June 2012.
http://www.sciencedirect.com/science/article/pii/S0009898112003270
http://www.sciencedirect.com/science/article/pii/S0009898112003270
Jones, Mark G., Elizabeth Cooper, Saira
Amjad, Stewart C. Goodwin, Jeffrey L. Barron, Ronald A. Chalmers.
“Urinary and plasma organic acids and amino acids in chronic
fatigue syndrome.” Clin Chim Acta. 2005 Nov;361(1-2):150-8.
http://www.cfids-cab.org/cfs-inform/Hypotheses/jones.etal.05.pdf
Niblett SH, King KE, Dunstan RH,
Clifton-Bligh P, Hoskin LA, Roberts TK, Fulcher GR, McGregor NR,
Dunsmore JC, Butt HL, Klineberg I, Rothkirch TB. “Hematologic and
urinary excretion anomalies in patients with chronic fatigue
syndrome.” Exp Biol Med (Maywood). 2007 Sep;232(8):1041-9.
http://www.ncbi.nlm.nih.gov/pubmed/17720950 (Abstract)
CARNITINE
DESCRIPTION. Carnitine (L-carnitine) is
one of the methyl group donors. It is crucial for the transport of
long-chain fatty acids into the mitochondria of cells, providing
energy to skeletal and heart muscle. Carnitine also aids in reducing
toxic buildup of organic acids which are a natural byproduct of cell
metabolism. Carnitine deficiency produces fatigue, muscle weakness,
malaise, exercise intolerance, heartbeat abnormalities, and tissue
acidosis. Carnitine deficiency can result from congenital metabolic
defects as well as the administration of antibiotics containing
pivalic acid (e.g., Pondocillin).
USES IN CFS/ME. Japanese researchers
have shown that CFS/ME patients have a deficiency in intracellular
levels of acylcarnitine. They found no deficiency in serum levels of
free carnitine, however, indicating the deficiency is not the result
of lack of carnitine in the system but of its derivative,
acylcarnitine. Acylcarnitine deficiency can be expected to produce
not only the fatigue and weakness characteristic of interruption in
mitochondrial processes but also the malaise typical of
autointoxication. Dr. Hiroko Kuratsune and colleagues discovered that
in their sample group of 38 CFS/ME patients, low levels of
acylcarnitine covaried with the severity of the illness (Clinical
Infectious Diseases, 1994). As symptoms improved, so did
acylcarnitine levels. In a study comparing amantadine and carnitine,
Dr. Audrius Plioplys and Dr. Sigita Plioplys found "statistically
significant clinical improvement" after eight weeks of treatment
with L-carnitine (Neuropsychobiology, 1997).
A subsequent study in 2004 by Okada et
al, found secondary proof for acetyl-carnitine deficiency in CFS/ME
patients. Using MRI imaging, they found that there was a reduction in
gray matter in the prefrontal cortex of CFS/ME patients as compared
to controls. The researchers concluded that their results were
“consistent with previous reports of an abnormal distribution of
acetyl-L-carnitine uptake, which is one of the biochemical markers of
chronic fatigue syndrome, in the prefrontal cortex. Thus, the
prefrontal cortex might be an important element of the neural system
that regulates sensations of fatigue.”
In a recent study conducted in 2011,
researchers from the University of South Australia compared
L-carnitine levels of 44 CFS/ME patients to 49 controls. They found
that levels of acylcarnitine was 30-40% lower in CFS/ME patients. The
authors hypothesized that the administration of omega-3 fatty acids
in combination with L-carnitine would improve chronic fatigue
syndrome symptomology.
PROTOCOL. Carnitine can be taken in
liquid or pill form as an over-the-counter nutritional supplement. As
a food supplement, the general recommended dosage is 1000 mg/day
taken with a meal. The liquid is often better tolerated than the pill
form although patients with chemical sensitivities should note that
the liquid may also contain artificial flavors, colors, preservatives
(methylparaben), and sucrose.
Dr. Teitelbaum has observed that in his
experience acetyl-L-carnitine is much more effective that
L-carnitine. This is due to the fact that acetyl-L-carnitine crosses
the blood-brain barrier, as opposed to L-carnitine, which is too
rapidly excreted by the kidneys to be adequately utilized by the
brain. Dr. Teitelbaum recommends taking 500 mg of pure
acetyl-L-carnitine 2-3 times a day. In low doses, acetyl-L-carnitine
can mimic the effects of pyridostigmine and galantamine, increasing
the availability of acetylcholine in both the peripheral and central
nervous systems.
Because carnitine interferes with
thyroid hormone production, thyroid levels (free T3 and T4, as well
as TSH) should be taken before beginning supplementation. Even if
thyroid hormone levels fall within the normal range, carnitine should
not be taken for more than a month. Signs of thyroid suppression are
dry skin, low energy level, weight gain, excessive sleep, and
hormonal disturbances.
PROS. L-Carnitine as a food supplement
is widely available. Patients have reported increased muscle
function, decreased weakness, and overall improved stamina and
well-being after a few weeks of carnitine supplementation. In some
cases, the benefits remain even after finishing the course of
treatment.
CONS. Carnitine is not recommended for
patients with low thyroid function, as it interferes with thyroid
hormones. Excess amounts of carnitine can cause diarrhea and stomach
upset, so start with low doses.
AVAILABILITY AND COST. A 12 oz bottle
of the liquid nutritional supplement Mega L -Carnitine (Twin Labs)
can be purchased online at Vitacost for $10. At the recommended
dosage of 1 tablespoon a day, the bottle will last for 1 month. A
30-capsule bottle of acetyl-L-carnitine costs around $18. (There are
many brands. Check Vitacost for a cost comparison.)
FURTHER READING
Dr. Teitelbaum's carnitine protocol:
http://www.endfatigue.com/health_articles_c/CFS_FM-acetyl-l-carnitine_for_cfs.html
RESEARCH
Benvenga S, Amato A, Calvani M,
Trimarchi F. “Effects of carnitine on thyroid hormone action.”
Ann NY Acad Sci. 2004 Nov;1033:158-67.
http://www.ncbi.nlm.nih.gov/pubmed/15591013 (Abstract)
Colucci S, Mori G, Vaira S, Brunetti G,
Greco G, Mancini L, Simone GM, Sardelli F, Koverech A, Zallone A,
Grano M. “L-carnitine and isovaleryl L-carnitine fumarate
positively affect human osteoblast proliferation and differentiation
in vitro.” Calcif Tissue Int. 2005 Jun;76(6):458-65.
http://www.ncbi.nlm.nih.gov/pubmed/15906015 (Abstract)
Eder K, Felgner J, Becker K, Kluge H.
“Free and total carnitine concentrations in pig plasma after oral
ingestion of various L-carnitine compounds.” Int J Vitam Nutr Res.
2005 Jan;75(1):3-9. http://www.ncbi.nlm.nih.gov/pubmed/15830915
(Abstract)
Ho JY, Kraemer WJ, Volek JS, Fragala
MS, Thomas GA, Dunn-Lewis C, Coday M. Häkkinen K, Maresh CM.
“L-Carnitine l-tartrate supplementation favorably affects
biochemical markers of recovery from physical exertion in middle-aged
men and women.” Metabolism. 2010 Aug;59(8):1190-9.
http://www.ncbi.nlm.nih.gov/pubmed/20045157 (Abstract)
Holme, Elisabeth, Carl-Eric Jacobson,
Ingalill Nordin, Joachim Greter, Sven Lindstedt, Bengt Kristiansson,
Ulf Jodal. “Carnitine Deficiency Induced by Pivampicilin and
Pivmecillinam Therapy.” The Lancet. Volume 334, Issue 8661, Pages
469 - 473, 26 August 1989.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(89)92086-2/abstract
(Abstract)
Kuratsune H, Yamaguti K, Takahashi M,
Misaki H, Tagawa S, Kitani T. “Acylcarnitine deficiency in chronic
fatigue syndrome.” Clin Infect Dis. 1994 Jan;18 Suppl 1:S62-7.
http://www.ncbi.nlm.nih.gov/pubmed/8148455 (Abstract)
Okada T, Tanaka M, Kuratsune H,
Watanabe Y, Sadato N. “Mechanisms underlying fatigue: a voxel-based
morphometric study of chronic fatigue syndrome.” BMC Neurol. 2004
Oct 4;4(1):14. http://www.ncbi.nlm.nih.gov/pubmed/15461817 (Abstract)
Patano N, Mancini L, Settanni MP,
Strippoli M, Brunetti G, Greco G, Tamma R, Vergari R, Sardelli F,
Koverech A, Colucci S, Zallone A, Grano M. “L-carnitine fumarate
and isovaleryl-L: -carnitine fumarate accelerate the recovery of bone
volume/total volume ratio after experimentally induced osteoporosis
in pregnant mice.” Calcif Tissue Int. 2008 Mar;82(3):221-8.
http://www.ncbi.nlm.nih.gov/pubmed/18265928 (Abstract)
Plioplys AV, Plioplys S. “Amantadine
and L-carnitine treatment of Chronic Fatigue Syndrome.”
Neuropsychobiology. 1997;35(1):16-23.
http://www.ncbi.nlm.nih.gov/pubmed/9018019 (Abstract)
Reuter SE, Evans AM. “Long-chain
acylcarnitine deficiency in patients with chronic fatigue syndrome.
Potential involvement of altered carnitinepalmitoyltransferase-I
activity.” J Intern Med. 2011 Jul;270(1):76-84.
http://www.ncbi.nlm.nih.gov/pubmed/21205027 (Abstract)
Spiering BA, Kraemer WJ, Vingren JL,
Hatfield DL, Fragala MS, Ho JY, Maresh CM, Anderson JM, Volek JS.
“Responses of criterion variables to different supplemental doses
of L-carnitine L-tartrate.” Journal of Strength and Conditioning
Research. 2007 Feb;21(1):259-64.
http://www.ncbi.nlm.nih.gov/pubmed/17313301 (Abstract)
Vermeulen RC, Scholte HR. “Exploratory
open label, randomized study of acetyl- and propionylcarnitine in
chronic fatigue syndrome.” Psychosom Med. 2004
Mar-Apr;66(2):276-82. http://www.ncbi.nlm.nih.gov/pubmed/15039515
(Abstract)
GLUTAMINE
DESCRIPTION. Glutamine is the most
abundant nonessential amino acid in the body. It is a precursor to
glutathione.
BACKGROUND. Glutamine plays an
important role in many biological functions, including protein
synthesis, providing cellular energy, and as a non-toxic transporter
of ammonia in the bloodstream. When converted to glutamic acid, it
acts as an excitatory neurotransmitter in the brain.
In the intestinal tract, glutamine
strengthens the gut's function as an immune barrier by supporting the
production of secretory immunoglobulin A (sIgA), which helps maintain
the structure, metabolism, and function of the mucosal lining of the
intestines. Glutamine can help heal injured gut mucosa after surgery
and, in a high percentage (92%) of patients, completely heals ulcer
damage. Glutamine is an important detoxifying agent for ammonia, a
neurotoxin and one of the toxic by-products of protein metabolism. It
is used to treat sugar craving, fatigue, ADHD, peptic ulcers, and
personality disorders. Dietary sources of glutamine include beef,
chicken, fish, eggs, milk, dairy products, wheat, cabbage, beets,
beans, and spinach.
USES IN CFS/ME. Because it is so
important in gastrointestinal growth and function, glutamine is
primarily used to treat leaky gut. Clinicians recommend taking 1000
mg of glutamine daily on an empty stomach, divided into equal doses
(Patients with many sensitivities may want to test a very small
amount of this amino acid before taking the full dose.)
PROS. A number of CFS/ME patients have
noted improvement in gut function and increased food tolerance with
this treatment as well as a decrease in “brain fog.” Side effects
from this amino acid are relatively rare (but see below).
CONS. L-glutamine can cause
gastrointestinal symptoms such as nausea and diarrhea. In patients
with small intestinal bacterial overgrowth (SIBO) glutamine may
actually worsen symptoms. Because glutamine is an excitatory
neurotransmitter it may cause insomnia in individuals who do not
tolerate stimulants. People who are sensitive to MSG should not take
glutamine.
AVAILABILITY AND COST. Glutamine is
available at health food stores and online in both powder and pill
form. It is inexpensive. A 100-tablet bottle can cost as little as
$6. Glutamine is also available from some compounding pharmacies as
enteric coated tablets which are formulated to bypass the stomach and
increase bioavailability.
RESEARCH
Blachier,
François, Claire Boutry, Cécile Bos, Daniel Tomé. “Metabolism
and functions of L-glutamate in the epithelial cells of the small and
large intestines.” Am J Clin Nutr September 2009 vol. 90 no. 3
814S-821S. http://www.ajcn.org/content/90/3/814S.abstract
LYSINE
DESCRIPTION. Lysine is an essential
amino acid. (It cannot be synthesized in the body.)
BACKGROUND. Lysine is needed for bone
growth in children and to maintain nitrogen balance in adults. It
also aids in the production of antibodies, hormones, and enzymes as
well as helping in collagen formation, muscle building, and tissue
repair. Lysine deficiency can result in hair loss, anemia, bloodshot
eyes, loss of energy, and irritability. Food sources of lysine
include meat, eggs, legumes and milk.
USES IN CFS/ME. Lysine is recommended
chiefly because of its ability to inhibit reproduction of
herpesviruses (herpes simplex virus, varicella zoster virus, human
herpesvirus 6, and Epstein-Barr virus), which require arginine in
order to reproduce. Lysine's structure is similar enough to arginine,
however, that herpesviruses can be fooled into using lysine instead.
Since the virus cannot use lysine for replication, the virus loses
its ability to reproduce, effectively halting the spread of the
infection. Some CFS/ME doctors recommend lysine to treat frequent
outbreaks of cold sores (herpes simplex) or shingles (herpes zoster).
PROTOCOL. Dr. Charles Lapp recommends
1000 to 2000 mg of lysine, taken daily with meals. Foods high in
arginine, such as chocolate, nuts, raisins, whole wheat, cereal, and
brown rice, should be avoided.
PROS. Lysine appears to be a safe,
effective treatment for cold sores.
CONS. Side effects of lysine can
include dizziness, sweating, nausea, appetite loss, and difficulty
swallowing. Lysine should be discontinued if these symptoms develop.
AVAILABILITY AND COST. Lysine is
available in most health food stores and can be purchased
inexpensively. Most brands retail for less than $10 for a 100-capsule
bottle (500 mg).
RESEARCH
Griffith RS, Walsh DE, Myrmel KH,
Thompson RW, Behforooz A. “Success of L-lysine therapy in
frequently recurrent herpes simplex infection. Treatment and
prophylaxis.” Dermatologica 1987;175(4):183-90.
http://www.ncbi.nlm.nih.gov/pubmed/3115841 (Abstract)
TAURINE
DESCRIPTION. Although taurine is
usually classified as an amino acid, it is actually an organic acid,
which is an organic compound with acidic properties but without a
carboxyl group.
BACKGROUND. Taurine acts as a building
block for all other amino acids and consequently is present in every
cell in the body. It is a prime component of bile (thus aiding in fat
digestion and vitamin absorption) and is found in high concentrations
in heart muscle, skeletal muscle, white blood cells, and the central
nervous system (CNS). Anxiety, hyperactivity, and poor brain function
are related to taurine deficiency. Taurine can be synthesized in the
body from cysteine, with the aid of vitamin B6.
Taurine is unusual in that it not only
functions as a neurotransmitter, but as a potent antioxidant. When
taurine interacts with the oxidant hypochlorous acid it forms taurine
monochloramine, which inhibits the transcription iNOS gene as well as
the expression of COX-2 protein, both of which are primary sources of
inflammation.
Taurine lowers NF-kappaB activity, which helps inhibit another important inflammatory pathway. It also acts to reduce intracellular calcium levels, thus lowering the production of nitric oxide. In its role as a neuromodulator, taurine stimulates the synthesis of GABA, the primary inhibitory neurotransmitter. It also stimulates glycine receptors, leading to a down regulation of excitatory NMDA receptors. (Glycine is also used in the biosynthesis of hemoglobin, which is very important in the maintenance of red blood cell integrity and oxygen transport.)
Taurine lowers NF-kappaB activity, which helps inhibit another important inflammatory pathway. It also acts to reduce intracellular calcium levels, thus lowering the production of nitric oxide. In its role as a neuromodulator, taurine stimulates the synthesis of GABA, the primary inhibitory neurotransmitter. It also stimulates glycine receptors, leading to a down regulation of excitatory NMDA receptors. (Glycine is also used in the biosynthesis of hemoglobin, which is very important in the maintenance of red blood cell integrity and oxygen transport.)
USES IN CFS/ME. Dr. Majid Ali, author
of The Canary and Chronic Fatigue, makes extensive use of taurine as
an antioxidant and has reported excellent results in treating fatigue
and chronic constipation. Dr. Cheney has observed that taurine may
also be of benefit in treating hyperactive nervous system responses.
CFS/ME patients have been shown to have high amounts of glutamate in
the brain, which increases neuroexcitatory responses. Because taurine
slows CNS impulses, it may help relieve symptoms such as insomnia,
anxiety, and restlessness, especially when taken in conjunction with
magnesium. Taurine is transported easily across the blood-brain
barrier, allowing taurine supplements to work in the brain.
PROTOCOL. Dr. Ali recommends a dosage
of 250 mg/day, along with magnesium and potassium. Dr. Cheney
recommends ½ cc of injectable magnesium (250 mg) accompanied by ½
cc injectable taurine.
PROS AND CONS. Taurine has very few
side effects, however, excess doses can cause GI upset (yellow
diarrhea, gas, pale stools).
AVAILABILITY AND COST. Taurine can be
purchased in most health food and vitamin stores and costs less than
$10 a bottle. Powdered forms can be purchased, for those who prefer
to titrate dosage.
FURTHER READING
Very thorough discussion of the role of
taurine: http://me-cfsmethylation.com/viewtopic.php?f=3&t=149
RESEARCH
El Idrissi A , Trenkner E. “Taurine
as a modulator of excitatory and inhibitory neurotransmission.”
Neurochem Res. 2004 Jan;29(1):189-97.
http://www.ncbi.nlm.nih.gov/pubmed/14992278 (Abstract)
Liu, Y, Tonna-DeMasi, M, Park, E,
Schuller-Levis, G, Quinn, MR. "Taurine chloramine inhibits
production of nitric oxide and prostaglandin E2 in activated C6
glioma cells by suppressing inducible nitric oxide synthase and
cyclooxygenase-2 expression. "Brain Res. Mol. Brain Res.
59,189-195.
http://www.sciencedirect.com/science/article/pii/S0169328X98001454
Nakagawa K, Kuriyama K. “Effect of
taurine on alteration in adrenal functions induced by stress.” Jap.
J. Pharmacol. 1975 Dec;25(6):737-46.
http://www.ncbi.nlm.nih.gov/pubmed/6814 (Abstract)
Park E, Jia J, Quinn MR, Schuller-
Levis G. “Taurine chloramine inhibits lymphocyte proliferation and
decreases cytokine production in activated human leukocytes.” Clin
Immunol. 2002 Feb;102(2):179-84.
http://www.ncbi.nlm.nih.gov/pubmed/11846460 (Abstract)
ANTIOXIDANTS
DESCRIPTION. Antioxidants are a group
of vitamins, minerals, and enzymes that help protect cells from free
radical damage.
BACKGROUND. Antioxidants have long been
used as preservatives because of their ability to retard the
oxidation that causes oils to become rancid. However, they have
garnered increased attention over the past few years for their
medical value. The same process that allows them to prevent oils from
becoming rancid also protects the body from damage caused by free
radicals. Free radicals are atoms or groups of atoms that have lost
an electron. These molecules containing unpaired electrons are highly
unstable and can easily pick up other elements, causing volatile
reactions. When large numbers of free radicals are formed, whether
from exposure to radiation, toxic chemicals or rancid oils, or
because of prolonged illness and immune activation, significant
damage can result. When dangerously high levels of free radicals are
present, they can cause changes in protein structure. The body may
identify the altered proteins as foreign elements and launch an
immune system attack.
The body has its own defenses against
excess free radical formation. The three most potent antioxidants
produced in the body are superoxide dismutase (SOD), CoQ10, and
glutathione peroxidase. However, the group of biochemicals known as
antioxidants are also found abundantly in nature in the form of
vitamins, minerals, and enzymes. Among the most widely used
antioxidants are vitamins A, C, and E, alpha lipoic acid (ALA),
gamma-linoleic acid (GLA), the amino acid cysteine, glutathione,
taurine, the mineral selenium, CoQ10, and the bioflavonoids in
pycnogenol, milk thistle, and gingko.
Antioxidants operate in concert to
prevent free radical damage. A single antioxidant, once it has
neutralized the free radical, can itself cause cell damage. The
action of other antioxidants is necessary to return antioxidants to
their reduced state, in which they can continue to scavenge free
radicals. Therefore, antioxidants should be taken in combination
rather than single forms. An article in the New England Journal of
Medicine reports that heavy smokers in Finland who took very high
doses of the antioxidant beta carotene had a higher rate of lung
cancer than those taking a placebo (CFIDS Chronicle, Spring 1995).
However, when beta carotene was combined with vitamin E, this was not
the case.
Due to the potential of antioxidants to
mitigate the more damaging effects of chronic illnesses (including
cancer and diabetes) research on antioxidants is rapidly evolving. In
2004 Rezk et al proposed a new class of antioxidants based on the
mechanism of vitamin E. In a study comparing the activities of
different forms of vitamin E, the researchers discovered that vitamin
E phosphate prevented the transfer of free radicals by forming a
detergent barrier.
USES IN CFS/ME. Several studies have
confirmed oxidative damage in CFS/ME patients. In 2000 a team of
Italian researchers investigating the source of muscle pain found
oxidative damage to DNA and lipids (fats) in the muscle tissue of
CFS/ME patients. They also found significant differences in the
composition of muscle membranes as compared to controls and patients
with FM. The researchers concluded that their data “support an
organic origin of CFS, in which muscle suffers oxidative damage.”
Patients with CFS/ME who experience
depression also show evidence of free radical formation. In a 2001
study conducted by Maes et al, glutathione peroxidase levels were
found to correlate with depressed mood and autonomic symptoms. The
lower the glutathione levels, the greater the depression. The
researchers recommended supplementation with glutathione, NAC and
selenium.
Two studies conducted independently in
2000 and 2005 found that oxidative stress in CFS/ME patients could be
measured through blood samples. In Australia, Richards et al measured
methemoglobin in CFS/ME patients and controls. Methemoglobin
(pronounced “met-hemoglobin”) is an altered form of hemoglobin
that does not bind well to oxygen, limiting the blood's ability to
carry oxygen to tissues and organs. The formation of methemoglobin
can be caused by various health problems and is a sign of oxidative
stress. The study found that in CFS/ME patients, symptoms such as
sleep disturbance, pain, and fatigue correlated with methemoglobin
levels. They concluded that their data suggested that “oxidative
stress due to excess free radical formation is a contributor to the
pathology of CFS and was associated with symptom presentation.”
A second study by Kennedy et al.
investigated free radical damage in CFS/ME symptoms using the “gold
standard” of oxidative stress: isoprostanes. Isoprostanes are
prostaglandin-like compounds which are formed after free radicals
catalyze essential fatty acids. They have long been recognized as an
accurate predictor of oxidative stress. Kennedy et al found that in
CFS/ME patients, raised levels of isoprostanes correlated with
post-exertional malaise. They postulated that in CFS/ME the excessive
free radical formation could be due to persistent viral infection, to
inflammation, or to metabolic abnormalities in mitochondria and
lipids.
Antioxidants fall into many classes.
The most commonly recommended antioxidants for CFS/ME patients are:
- Vitamins: A, C, E
- Vitamin co-factors: CoQ10
- Minerals: Manganese, selenium, zinc
- Hormones: Melatonin
- Flavonoids: Quercetin, pycnogenol, grape seed extract, Ecklonia cava
- Phenols: Silymarin
- Plant sources: Capsaicin, bilberry
- Enzymes: SOD
- Various Others: N-acetyl cysteine, alpha lipoic acid, essential fatty acids, glutathione, taurine
PROTOCOL. Most, if not all, CFS/ME
doctors have included some form of antioxidant therapy into their
protocols. Usually they recommend a broad-spectrum approach, as
opposed to single-supplement therapy, accompanied in many cases by
bioflavonoids such as pycnogenol (which is a potent antioxidant),
grape seed extract, or “super foods” such as blue-green algae.
Vitamin E, because it is the only fat-soluble antioxidant, is
particularly good in combination with other antioxidants.
- Martin Pall, one of the leading researchers of oxidative stress in CFS/ME, recommends vitamin C, flavonoids, Ecklonia cava extract, B12, CoQ10, vitamin E, lipoic acid, as well as a host of other antioxidants to combat free radical damage.
- Dr. Cheney recommends daily doses of 2000-4000 mg vitamin C, 400-800 IU of Vitamin E, 200 mg of CoQ10, 100-300 mg of lipoic acid, omega-6 and omega-3 essential fatty acids and flavonoids. He stresses that because high doses of antioxidants can increase oxidative stress, flavonoids should be taken to mitigate potential free radical damage stemming from excessive antioxidant activity.
- Dr. Myhill recommends 300 mg of CoQ10 daily for three months, then reduced to 100 mg daily, 250 mg of glutathione daily together with 20 mcg of selenium as well as minerals to help produce the powerful free radical scavenger, superoxide dismutase. (Please see below for her discussion of antioxidants.)
FURTHER READING
Dr. Myhill's excellent discussion of
antioxidants: http://drmyhill.co.uk/wiki/Antioxidants
Logan, Alan C. and Cathy Wong. “Chronic
Fatigue Syndrome: Oxidative Stress and Dietary Modifications.”
Altern Med Rev 2001;6 (5): 450-459.
http://www.altmedrev.com/publications/6/5/450.pdf
This article contains an excellent
summary of research concerning oxidative stress in CFS/ME as well as
a proposed list of antioxidant treatments.
Martin Pall's supplement list:
http://esme-eu.com/supplements/supplements-in-me-cfs-by-prof-martin-pall-article276-139.html
Dr. Cheney's talk on CFS/ME treatments,
including antioxidants: http://www.me-cfs.info/cheneyII3.pdf
RESEARCH
Fulle S, Mecocci P, Fan G, Vecchiet I,
Vecchini A, Racciotti D, Cherubini A, Pizzigallo E, Vecchiet L, Senin
U, Beal MF. “Specific oxidative alterations in vastus lateralis
muscle of patients with the diagnosis of chronic fatigue syndrome.”
Free Radic Biol Med. 2000 Dec 15;29(12):1252-9.
http://www.ncbi.nlm.nih.gov/pubmed/11118815 (Abstract)
Kennedy, Gwen, Vance A. Spence,
Margaret McLaren, Alexander Hill, Christine Underwood, Jill J.F.
Belch. “Blood parameters indicative of oxidative stress are
associated with symptom expression in chronic fatigue syndrome.”
Free Radical Biology & Medicine 39 (2005) 584 – 58.
http://www.cfids-cab.org/rc/Kennedy.pdf
Maes M, Mihaylova I, Kubera M,
Uytterhoeven M, Vrydags N, Bosmans E. “Lower whole blood
glutathione peroxidase (GPX) activity in depression, but not in
myalgic encephalomyelitis /chronic fatigue syndrome: another pathway
that may be associated with coronary artery disease and
neuroprogression in depression.” Neuro Endocrinology letters.
2011;32(2):133-40. http://www.ncbi.nlm.nih.gov/pubmed/21552194
(Abstract)
Miwa K, Fujita M. “Fluctuation of
serum vitamin E (alpha-tocopherol) concentrations during exacerbation
and remission phases in patients with chronic fatigue syndrome.”
Heart Vessels. 2010 Jul;25(4):319-23.
http://www.ncbi.nlm.nih.gov/pubmed/20676841 (Abstract)
Rezk BM, Haenen GR, Van Der Vijgh WJ,
Bast A. “The extraordinary antioxidant activity of vitamin E
phosphate.” Biochim Biophys Acta. 2004 Jul 5;1683(1-3):16-21.
http://www.ncbi.nlm.nih.gov/pubmed/15238215 (Abstract)
Richards RS, Roberts TK, McGregor NR,
Dunstan RH, Butt HL. “Blood parameters indicative of oxidative
stress are associated with symptom expression in chronic fatigue
syndrome.” Redox Rep. 2000;5(1):35-41.
http://www.ncbi.nlm.nih.gov/pubmed/10905542 (Abstract)
Saransaari, P, Oja S. “Nitric oxide
is involved in taurine release in the mouse brainstem under normal
and ischemic conditions.” Amino Acids. 2008 Apr;34(3):429-36
http://www.ncbi.nlm.nih.gov/pubmed/17665274 (Abstract)
BETAINE HCl
DESCRIPTION. Betaine HCl is a
synthesized chemical compound consisting of betaine, a methyl group
donor, and hydrochloride, a salt.
BACKGROUND. Betaine is a vitamin-like
substance that was originally derived from beets. For many years
Betaine HCl was added to over-the-counter digestive aids, until in
1993 the FDA determined that it has not been proven “generally safe
and effective.” At that point Betaine HCl began to be sold as a
separate supplement.
Betaine HCl is still marketed as a
digestive aid, particularly for the treatment of hypochloridia, a
condition in which the stomach does not produce enough acid.
Hypochloridia can occur after taking stomach acid suppressors
(antacids, proton pump inhibitors), through H. Pylori infections
(which interfere with stomach acid production), as well as any
disease process that causes inflammation in the stomach lining.
Stomach acid is often low in the elderly.
Lack of stomach acid can lead to the
phenomenon known as “dumping,” in which the stomach's contents
(chyme) are released into the small intestines before having been
adequately broken down. The ability of the small intestines to
further break down the chyme can result in poor absorption of
nutrients, leading to deficiency states, particularly of minerals,
which require acid to be absorbed. One of the most common symptoms of
hypochloridia is reflux, which is frequently misdiagnosed as excess
acid.
The most reliable test to determine
hypochloridia is the Heidelberg Capsule test. The capsule contains a
high frequency transmitter attached to a string. When the capsule is
swallowed and drawn back up the esophagus, it gives an instant pH
reading.
USES IN CFS/ME. A number of clinicians
have proposed that low levels of stomach acid are responsible for
many of the GI symptoms found in CFS/ME patients. Dr. Cheney
routinely recommends Betaine HCl as a supplement to correct
hypochloridia and prevent dumping. Dr. Myhill also maintains that
people with CFS/ME chronically suffer from low levels of stomach
acid.
PROTOCOL. Dr. Cheney recommends
starting with a capsule (or ½ capsule) with meals. Paradoxically,
too low a dose may actually increase reflux, as there still isn't
enough stomach acid to trigger the opening of the sphincter that
releases chyme into the intestines. The food that then returns
through the esophagus contains not only normally occurring stomach
acid, but the additional Betaine HCl as well. According to Dr.
Cheney, increasing the dose will actually reduce reflux.
PROS AND CONS. Although Betaine HCl
does not contain hydrochloric acid (the HCl, in this case, is a
salt), some people report improved digestion. The supplement does
have mild acidifying properties, which is perhaps why people report
having to take so many capsules with their meals (up to seven). It is
quite possible that many of its benefits may actually come from the
betaine, which acts as a liver support.
AVAILABILITY AND COST. Betaine HCl is
easily available from health food stores and from online suppliers.
It is inexpensive. Vitacost markets a 100-capsule bottle of Twinlab's
Betaine HCl for about $7.
FURTHER READING
Dr. Sara Myhill's excellent discussion
of hypochloridia:
http://www.drmyhill.co.uk/wiki/Hypochlorhydria_-_lack_of_stomach_acid_-_can_cause_lots_of_problems
Basic information about Betaine HCl:
http://www.encyclopedia.com/doc/1G2-3435100086.html
A good explanation of the Heidelberg
capsule test and hypochloridia.
http://www.antiagingwellnesscenter.com/phcapsule.shtml
Dr. Paul Cheney on dumping,
hypochloridia, and Betaine HCl supplementation.
http://www.prohealth.com/library/showarticle.cfm?libid=8037
BIOFLAVONOIDS
Grape seed extract, Pycnogenol,
Quercetin
DESCRIPTION. Bioflavonoids are
glycosides (sugars) derived from citrus, paprika, and other plants,
which serve to protect capillaries. Although formerly known as
"vitamin P," bioflavonoids are not vitamins.
BACKGROUND. Bioflavonoids were first
extracted from paprika in 1936 by a scientist who claimed that the
substance had a greater effect than vitamin C in reducing capillary
bleeding. It was later shown that the substance, or rather
substances, helped maintain capillary strength by inhibiting
permeability of the walls (rather than maintaining the actual
structure, as does vitamin C). This may be because bioflavonoids
inhibit oxidation of epinephrine (adrenaline), the hormone directly
responsible for capillary wall integrity. Bioflavonoids enhance
absorption of vitamin C and, when taken together, can help protect
and preserve capillaries, increase circulation, prevent cataracts,
and produce a mild antibacterial effect. Flavonoids have
anti-allergic, anti-inflammatory and anti-microbial effects.
Dietary sources include buckwheat,
black currants, peppers, and the white part of citrus peel. There are
many bioflavonoids available for purchase through health food stores
and online vitamin suppliers.
Bioflavonoids are rapidly absorbed in
the system, and almost as rapidly excreted through the kidneys. Peak
blood levels occur roughly two hours after ingestion, which means
that to be effective, they should be taken throughout the day.
USES IN CFS/ME. Bioflavonoids are
poorly absorbed, so for better utilization its best to take several.
The most active intracellular free radical scavengers are lycopene, a
carotenoid found in red fruits (except strawberries) and lutein,
found in green leafy vegetables. Dr. Pall recommends FlaviNOx, which
is a combination of standardized bioflavonoids derived from herbs
(gingko, bilberry, milk thistle, grape seed extract, decaffeinated
green tea extract, cranberry and hawthorn). The combination of
antioxidants in FlaviNOx is designed to scavenge peroxynitrite and
superoxide, two highly damaging free radicals.
AVAILABILITY AND COST. A 90-capsule
bottle of FlaviNOx (Allergy Research Group) costs roughly $35.
GRAPE SEED EXTRACT
DESCRIPTION. Grape seed extract is a
polyphenolic compound derived from grape seeds.
BACKGROUND. Grape seeds contain
polyphenols, procyanidins, and proanthocyanidins, which are
antioxidants many times more powerful than vitamin C or E. Grape seed
extract is reported to be a potent peroxynitrite scavenger, and
therefore can protect the cells from intracellular damage. The
effects of polyphenols are far-reaching, including the inhibition of
skin cancer, reduction of inflammation, neuroprotective action,
improvement of cerebral circulation, acceleration of wound healing,
modulation of intestinal flora, repairing leaky gut, and immune
system regulation.
USES IN CFS/ME. Grape seed extract is
often used as a less expensive alternative to pycnogenol. Patients
report that it helps with pain.
PROTOCOL. One 100 mg tablet taken with
food.
AVAILABILITY AND COST. Grape seed
extract is widely available in health food stores and through online
distributors. A bottle of 120 capsules can cost as little as $13.
Grape seed extract is frequently combined with other bioflavonoids,
such as green tea and resveratrol (found in grape skin) to increase
its antioxidant effects.
FURTHER READING
Sloan Kettering's review of the
mechanisms of grape seed extract. Includes a list of studies.
http://www.mskcc.org/cancer-care/herb/grape-seed
RESEARCH
Afaq F, Katiyar SK. “Polyphenols:
Skin Photoprotection and Inhibition of Photocarcinogenesis.” Mini
Rev Med Chem. 2011 Oct 28.
http://www.ncbi.nlm.nih.gov/pubmed/22070679 (Abstract)
Lin, B. “Polyphenols and
Neuroprotection against Ischemia and Neurodegeneration.” Mini Rev
Med Chem. 2011 Oct 28 http://www.ncbi.nlm.nih.gov/pubmed/22070681
(Abstract)
Vendrame S, Guglielmetti S, Riso P,
Arioli S, Klimis-Zacas D, Porrini M. “Six-week consumption of a
wild blueberry powder drink increases bifidobacteria in the human
gut.” J Agric Food Chem. 2011 Nov 7.
http://www.ncbi.nlm.nih.gov/pubmed/22060186 (Abstract)
PYCNOGENOL
DESCRIPTION. Pycnogenol
(proanthocyanadin) is a bioflavonoid antioxidant derived from the
bark of the French maritime pine tree.
BACKGROUND. Pycnogenol is a potent free
radical scavenger. Studies have shown that, as an antioxidant,
pycnogenol is up to 50 times more effective than other antioxidants
to clear free radicals created from chemical sources (air pollution
and food additives). It is 20 times more effective than vitamin C in
scavenging superoxide, hydroxyl, and peroxide radicals. Pycnogenol is
reported to enhance immune system function, increase energy, promote
healing, and reduce allergic reactions. It is particularly effective
in the brain.
USES IN CFS/ME. Pycnogenol has not been
widely investigated for use in CFS/ME patients although it has been
researched for other virally induced diseases. Some patients who have
used pycnogenol report small increases in mental and physical energy
and better resistance to bacterial and viral infections as well as
stress.
PROTOCOL. The recommended dosage is 50
mg a day, taken with food. Some CFS/ME patients report that
pycnogenol is more effective on an empty stomach.
AVAILABILITY AND COST. Pycnogenol can
be purchased from health food stores and vitamin catalogs. Twinlab
markets a 60-capsule bottle of pycnogenol (50 mg) for $25 through
Vitacost.
FURTHER READING
Sloan Kettering's excellent summary of
the mechanisms of pycnogenol. Contains a list of research studies:
http://www.mskcc.org/cancer-care/herb/pine-bark-extract
Iravani S., and B. Zolfaghari.
“Pharmaceutical and nutraceutical effects of Pinus pinaster bark
extract.” PhD. Res Pharm Sci. 2011 Jan-Jun;6(1): 1–11.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3203267/
A thorough review of all research
articles investigating pycnogenol.
RESEARCH
Feng WY, Tanaka R, Inagaki Y, Saitoh Y,
Chang MO, Amet T, Yamamoto N, Yamaoka S, Yoshinaka Y. “Pycnogenol,
a procyanidin-rich extract from French maritime pine, inhibits
intracellular replication of HIV-1 as well as its binding to host
cells.” Jpn J Infect Dis. 2008 Jul;61(4):279-85.
http://www.ncbi.nlm.nih.gov/pubmed/18653969 (Abstract)
QUERCETIN
BACKGROUND. Quercetin, a flavonol, is
chiefly used to treat asthma and allergies. Quercetin has properties
similar to that of the antihistamine disodium cromoglycate (found in
Gastrocrom and Nasalcrom). It can inhibit mast cell production and
block histamine release, two functions that together can curb many
allergic responses. In its antioxidant function, quercetin decreases
the synthesis of pro-inflammatory leukotrienes, and inhibits free
radical production and lipid peroxidation.
Quercetin is reported to help relieve
muscle pain, particularly along the upper back and shoulders. It is
commonly found in many food sources: green tea, apples, red onions,
red grapes, citrus fruits, tomato, broccoli, leafy green vegetables,
cranberries and raspberries, among others.
USES IN CFS/ME: An interesting study
conducted in 2009 by Davis et al found that quercetin increased the
genesis of mitochondria in mice, significantly improving exercise
tolerance. The reason this study is important is that it was done in
vivo. (Most studies on antioxidants are performed in test tubes.) As
exercise intolerance is the hallmark symptom of CFS/ME, quercetin may
play an important role in improving physical stamina among people
with CFS/ME.
PROTOCOL. Because it is so poorly
absorbed, quercetin needs to be taken with bromelain, an enzyme found
in pineapple. Dr. James Balch, author of Prescription for Nutritional
Healing, recommends 1000 to 2000 mg one to three times a day to
prevent or lessen the severity of asthma attacks and allergies.
CFS/ME patients are advised to start with much smaller doses,
200-1200 mg a day.
PROS AND CONS. Quercetin is the most
widely used bioflavonoid among patients with CFS/ME. A number of
allergy-prone patients with CFS/ME have noted that allergy symptoms
subside with quercetin. For patients with many allergies, this may
provide overall improvement because allergy symptoms can cause
systemic problems. Some patients with interstitial cystitis have
noted an improvement in symptoms after taking quercetin. The primary
side effect is that high doses may cause diarrhea.
AVAILABILITY AND COST. Quercetin (with
bromelain) is available from health food stores and online vitamin
catalogs. A three-month supply may cost as little as $8. ProHealth
markets a 100-tablet bottle of a quercetin-bromelain combination
(also containing vitamin C and magnesium) for about $15.
FURTHER READING
Davis JM, Murphy EA, Carmichael MD,
Davis B. “Quercetin increases brain and muscle mitochondrial
biogenesis and exercise tolerance.” Am J Physiol Regul Integr Comp
Physiol. 2009 Apr;296(4):R1071-7.
http://www.ncbi.nlm.nih.gov/pubmed/19211721 (Abstract)
Park HH, Lee S, Son HY, Park SB, Kim
MS, Choi EJ, Singh TS, Ha JH, Lee MG, Kim JE, Hyun MC, Kwon TK, Kim
YH, Kim SH. “Flavonoids inhibit histamine release and expression of
proinflammatory cytokines in mast cells.” Arch Pharm Res. 2008
Oct;31(10):1303-11. http://www.ncbi.nlm.nih.gov/pubmed/18958421
(Abstract)
Pearce FL, Befus AD, Bienenstock J.
“Mucosal mast cells. III. Effect of quercetin and other flavonoids
on antigen-induced histamine secretion from rat intestinal mast
cells.” J Allergy Clin Immunol. 1984 Jun;73(6):819-23.
http://www.ncbi.nlm.nih.gov/pubmed/6202731 (Abstract)
Shaik YB, Castellani ML, Perrella A,
Conti F, Salini V, Tete S, Madhappan B, Vecchiet J, De Lutiis
MA,Caraffa A, Cerulli G. “Role of quercetin (a natural herbal
compound) in allergy and inflammation.” J Biol Regul Homeost
Agents. 2006 Jul-Dec;20(3-4):47-52.
http://www.ncbi.nlm.nih.gov/pubmed/18187018 (Abstract)
BUTYRIC ACID (BUTYRATE)
DESCRIPTION. Butyrates (butanoic, or
butyric acid) are short-chain saturated fatty acids found naturally
in the human intestine and in butter fat.
BACKGROUND. Short-chain fatty acids
(volatile fatty acids) are produced in the colon as natural
by-products of the bacterial fermentation of fiber. These fatty acids
provide an energy source for the mucosal cells of the lining of the
colon, enabling them to check the proliferation and establishment of
pathogens (such as salmonella and Candida) and allowing greater
absorption of magnesium and vitamin K. Deficiency of these fatty
acids results in malabsorption, diarrhea, and, over the long term,
colitis.
Of the three fatty acids found in all
mammals – butyrate, acetate, and propionate – butyrate is the
preferred energy substrate. It stimulates the normal proliferation of
mucous cells, enabling greater efficiency of all colonic functions.
Butyrates have been used successfully to treat Candida overgrowth
(yeast infection), cancer, ulcerative colitis, and nonspecific
inflammatory conditions of the colon. It is one of the treatments
recommended for leaky gut and for alleviating food sensitivities.
USES IN CFS/ME. A significant number of
people with CFS/ME suffer from gastrointestinal problems. According
to Dr. Cheney, 90% of his CFS/ME patients have small intestinal
bacterial overgrowth (SIBO), a condition in which bacteria from the
large intestine migrate into the small intestines, interfering with
fat and carbohydrate metabolism and causing a spate of GI symptoms.
Rao et al found that 50% of CFS/ME patients meet the criteria for
irritable bowel syndrome (IBS), a gut motility disorder. Butyrates,
because they provide a substrate for beneficial intestinal flora, can
be used in conjunction with probiotics to help restore gut mucosa
damaged by SIBO as well as maintaining gut motility.
Although butyrates are primarily
recommended for treating digestive disorders, it may also have a
positive effect on some neurological problems associated with CFS/ME.
Dr. Cheney proposes that an imbalance in the actions of the
neuroexcitatory chemical NMDA (N-methyl-D-aspartate) and the
neuroinhibitor GABA (gamma amino butyric acid) may lead to many of
the troubling neurological symptoms experienced by patients with
CFS/ME (insomnia, intolerance of sensory stimuli, seizure-like
activity, pain) (CFIDS Chronicle, Spring 1995).
For many patients, down regulation of
the NMDA receptors, accomplished with small doses of Klonopin
(clonazepam), magnesium, Nimotop (nimodipine), melatonin, or calcium
channel blockers, leads to general improvement of all symptoms.
Butyrate, because it forms a component of GABA, may also rectify some
of this neurochemical imbalance by increasing the amount of
neuroinhibitory action in the brain.
PROTOCOL. Butyrate is usually taken
orally. The suggested dose is one or two capsules with each meal. It
smells awful, so you may want to store it in the refrigerator.
PROS AND CONS. Butyrate is inexpensive,
safe, and does not require a prescription.
AVAILABILITY AND COST. ButyrEn tablets,
marketed by Allergy Research Group, are hypoallergenic, containing no
yeast, wheat, corn, soy, dairy products, or artificial colors or
resins. The tablets are buffered with calcium and magnesium. ButyrEn
is available from online distributors and some specialized vitamin
stores. One bottle of 100 capsules costs as little $9 on amazon.
PureFormulas markets a 90-capsule bottle of Cal-Mag Butyrate made by
Ecological Formulas for $10.50. Shipping is free.
FURTHER READING
Life Extension is a bit pricier than
other suppliers, but their website contains a very thorough
description of the mechanisms of butyric acid.
http://www.lifeextensionvitamins.com/bualregr.html
RESEARCH
Rao, A Venket, Alison C Bested, Tracey
M Beaulne, Martin A Katzman, Christina Iorio, John M Berardi and Alan
C Logan. “A randomized, double-blind, placebo-controlled pilot
study of a probiotic in emotional symptoms of chronic fatigue
syndrome.” Gut Pathogens 2009, 1:6.
http://www.gutpathogens.com/content/1/1/6
CHOLINE
DEFINITION. Choline is an amine (a
nitrogen-containing compound) similar in function to B vitamins.
BACKGROUND. Choline is an essential
nutrient, which means it cannot be synthesized by the body and must
be obtained through food sources. Foods high in choline include egg
yolk, liver, fatty meats, nuts and brown rice.
Choline performs three vital biological
functions: 1) It is an important component of phosphatidylcholine,
which forms cell walls and supports cellular function; 2) Choline
serves as a precursor to acetylcholine, the neurotransmitter
responsible for memory formation and muscle movement; 3) Choline is
an important methyl donor, supporting the methylation cycle through
its metabolite, trimethylglycine (betaine).
A deficiency in choline can lead to
liver damage (“fatty liver”) and a reduction in kidney function.
Lack of choline in the diet can also cause infertility, growth
impairment, bone abnormalities, and hypertension. Because choline
plays such an important role in nervous system development, a
deficiency in early life can lead to neurological deficits. Vegans
and athletes are particularly prone to choline deficiency.
USES IN CFS/ME. Because choline serves
as a marker for certain types of brain damage, it is one of the
compounds that is measured in magnetic resonance (MR) spectroscopy.
For example, high amounts of choline accompanied by low amounts of
creatine and N-acetyl aspartate (NAA) are indicative of stroke
(cerebral ischemia and hypoxia). MR spectroscopy can also be used to
monitor changes in tumors, stroke, epilepsy, metabolic disorders,
infections, and neurodegenerative diseases.
In 2004 Chaudhuri and Behan used MR
spectroscopy to assess brain chemistry in CFS/ME patients. They found
that in CFS/ME patients, choline levels in the occipital cortex and
basal ganglia were raised, but NAA and creatine were normal. The
researchers concluded that in the absence of NAA and with no
structural abnormalities, the increase in choline was probably due to
increased phospholipase activity (the enzyme that breaks down the
phospholipids that make up cell walls) rather than to inflammation.
They theorized that viral activity could possibly contribute to the
increased choline, as many viruses increase the activity of
phospholipase.
While Chaudhuri and Behan concluded
that inflammation in the brain was not indicated by their test
results, further research indicates otherwise. Martin Pall has
suggested that activation of NMDA receptors (due to oxidative stress)
provides the missing inflammatory pathway that Chaudhuri and Behan
were unable to identify. In fact, an increase in choline can be an
early signal of an inflammatory process, even in the absence of NAA.
The mechanism which induces release of choline was identified by
Gasull et al as an inhibition of phosphatidylcholine synthesis rather
than phospholipase degradation. The researchers found that the
increase in extracellular choline was induced by NMDA receptor
activation, which ties in with Martin Pall's theory. In addition,
Gasull's group found that early choline release was directly related
to excitotoxic cell death caused by glutamine.
PROTOCOL. Given the important role of
choline in neuronal protection from oxidative stress, as well as the
fact that it is a component of acetylcholine, choline comprises a
valuable addition to any CFS/ME treatment plan. Dr. Cheney recommends
taking 50 mg of choline bitartrate a day. Dr. Teitelbaum recommends
the same dose, accompanied by vitamin C.
High doses (10 to 16 grams/day) of
choline are not recommended. Side effects from excessive intake of
choline have been associated with a fishy body odor, vomiting,
salivation, and increased sweating. (The fishy body odor results from
excretion of trimethylamine, a metabolite of choline.) Taking large
doses of choline in the form of phosphatidylcholine (lecithin) does
not generally result in fishy body odor. However, lecithin is not
usually well-tolerated by CFS/ME patients.
AVAILABILITY AND COST. Choline
bitartrate supplements are not widely available, so most people
decide to purchase lecithin powder, which is inexpensive and easy to
find. PureFormulas.com markets a bottle of 100 choline bitartrate
capsules (235 mg) for roughly $10. Purebulk.com sells a 100-gram
container of choline bitartrate powder for $4.25. The powder may be a
more viable option for most people as it allows for titration. Many B
vitamin formulations contain choline, so check labels. It may be
worthwhile to purchase a good-quality B-complex supplement that
includes choline, as this will give you the proper balance of B
vitamins as well.
FURTHER READING
This Oregon University site provides
excellent information about choline.
http://lpi.oregonstate.edu/infocenter/othernuts/choline/
“What are Choline and Inositol?”
(Good overview):
http://www.livestrong.com/article/326852-what-are-choline-inositol/
“Choline on the Brain? A Guide to
Choline in Chronic Fatigue Syndrome.” Cort Johnson. Aug, 2005.
http://aboutmecfs.org.violet.arvixe.com/Rsrch/CholineBrain.aspx
Ray Sahelian's sensible advise on
choline: http://www.raysahelian.com/cdp.html
“Fundamentals of MR Spectroscopy.”
John R. Hesselink. (A nice summary of MR spectroscopy.)
http://spinwarp.ucsd.edu/neuroweb/Text/mrs-TXT.htm
RESEARCH
Chaudhuri, A., P.O. Behan. “In vivo
magnetic resonance spectroscopy in chronic fatigue syndrome.”
Prostaglandins, Leukotrienes and Essential Fatty Acids 71 (2004)
181–183.
http://www.cfids-cab.org/cfs-inform/MitochondrialATP/chaudhuri.behan04.pdf
Chaudhuri A, Condon BR, Gow JW, Brennan
D, Hadley DM. “Proton magnetic resonance spectroscopy of basal
ganglia in chronic fatigue syndrome.” Neuroreport. 2003 Feb
10;14(2):225-8.
http://www.cfids-cab.org/cfs-inform/Brainscans/chaudhuri.etal03.pdf
Cohen BM, Renshaw PF, Stoll AL, Wurtman
RJ, Yurgelun-Todd D, Babb SM. “Decreased brain choline uptake in
older adults. An in vivo proton magnetic resonance spectroscopy
study.” JAMA. 1995 Sep 20;274(11):902-7.
http://www.nutrasal.com/library/pdfs/21.pdf
Doležal, Vladimír, Stanislav Tuček.
“Activation of muscarinic receptors stimulates the release of
choline from brain slices.” Biochem Biophys Res Commun. 1984 May
16;120(3):1002-7. http://www.ncbi.nlm.nih.gov/pubmed/6732780
(Abstract)
Gasull, Teresa, Nuria
DeGregorio-Rocasolano, Agustin Zapata and Ramon Trullas. “Choline
Release and Inhibition of Phosphatidylcholine Synthesis Precede
Excitotoxic Neuronal Death but Not Neurotoxicity Induced by Serum
Deprivation.” First Published on March 28, 2000. The Journal of
Biological Chemistry, 275,18350-18357.
http://www.jbc.org/content/275/24/18350.full
COQ10 (UBIQUINONE, UBIQUINOL)
DESCRIPTION. CoQ10 (ubiquinone) is a
fat-soluble coenzyme found in the mitochondria of most mammal cells.
BACKGROUND. CoQ10 was first discovered
by R.A. Morton, a biochemist who gave it the name ubiquinone after
its ubiquitous presence in nearly all living things. "Co"
stands for coenzyme (a vitamin-like substance), "Q" for
quinone (the group of organic chemicals to which CoQ belongs), and
"10" for the number of isoprene units that characterize the
particular coenzyme found in animal cells.
CoQ10 is vital for electron transport,
the intracellular function that ultimately provides the energy
necessary to sustain life. CoQ10 is also a powerful antioxidant and
is important in immune system function. The Japanese have
successfully used CoQ10 to treat gum disease, heart disease, and high
blood pressure, and to enhance the effectiveness of the immune
system. Research performed in Japan and elsewhere indicates that
CoQ10 can be of benefit in treating allergies (owing to its ability
to block the effects of histamine), asthma, candidiasis, obesity,
diabetes, mental function diseases such as Alzheimer's disease, and
can slow the aging process (CoQ10 levels decline with age).
High amounts of CoQ10 occur naturally
in fatty saltwater fish, especially mackerel, salmon, and sardines.
USES IN CFS/ME. CoQ10 is one of the
most frequently used supplements for the treatment of CFS/ME-related
fatigue because of its importance in the production of adenosine
triphosphate (ATP), the cellular source of energy. In addition to
reducing fatigue, CoQ10 may alleviate muscle weakness and pain. It is
also one of the few supplements that seems to reduce cognitive
dysfunction. Its role as a free radical scavenger may lead to
improvement in immune responses in patients with CFS/ME. Although its
effects as a natural antihistamine have not yet been specifically
explored in CFS/ME, patients with allergies may benefit from CoQ10.
There is also evidence that CoQ10 is
deficient in CFS/ME patients. In 2009 Maes et al measured plasma
CoQ10 in 58 CFS/ME patients. Compared to normal controls, the CFS/ME
group had values significantly below the lowest recorded levels of
the control group. Patients with very low levels of CoQ10 suffered
significantly more from concentration and memory disturbances. The
researchers concluded that lowered levels of CoQ10 play a role in the
pathophysiology of ME/CFS and that “symptoms, such as fatigue, and
autonomic and neurocognitive symptoms may be caused by CoQ10
depletion.” Their results suggested that patients with CFS/ME would
benefit from CoQ10 supplementation in order to normalize the low
CoQ10 syndrome.
PROTOCOL. Nearly all CFS/ME physicians
recommend supplementation with CoQ10. CoQ10 can be taken in a single
dose or divided into two doses taken at different times during the
day. There is evidence that dividing the dose is more effective than
taking it all at once. The normal recommended dose is between 30 and
200 mg/day. Dr. Lapp and Dr. Klimas recommend 120 mg a day.
Sublingual CoQ10, reputedly more effective against cognitive
dysfunction, may be taken at higher doses. Oral CoQ10, although
primarily absorbed by the digestive tract and liver, is also
effective for some patients. The oral dosage varies, but is usually
25 to 50 mg/day. It may take up to eight weeks to see effects from
oral CoQ10. Because CoQ10 is fat-soluble, it should be taken with a
meal that contains some kind of fat or oil.
PROS. Taken at lower doses, CoQ10 is a
supplement with very few side effects. Patients report improvements
in energy, stamina, light-headedness, and syncope (fainting). Dr.
Lapp reports that half of his patients see improvement after taking
CoQ10. A significant number of patients, particularly those with
fibromyalgia, find that CoQ10 increases their energy over the course
of the day.
CONS. Some patients report that CoQ10,
while giving them an initial energy boost, also increases insomnia
and causes jitters. Some people report, paradoxically, that CoQ10
produces exhaustion, although this effect may be more common in the
acutely ill than in those with stable symptoms. CoQ10 lowers blood
sugar levels, which may be problematic for patients with
hypoglycemia. High doses can cause flu-like symptoms.
AVAILABILITY AND COST. CoQ10 can be
purchased at most health food stores and from online distributors.
There is a mind-boggling array of CoQ10 products. High-grade brands
are preferred. (CoQ10 deteriorates rapidly when exposed to heat and
light.) Because CoQ10 is fat-soluble, it should be purchased as a
softgel (not capsule), preferably with a natural preservative (such
as vitamin E).
Sublingual CoQ10 can be purchased from
online sources without a prescription. Intensive Nutrition, Inc.
markets a sustained-release sublingual CoQ10 for $25 (80 mg, 30
count). Source Naturals sells sublingual CoQ10 for $14 (30 mg, 120
count).
CoQ10 is also available by prescription
as a gel. Unlike other forms of CoQ10, the gel is water soluble, and
bypasses the GI tract completely. The gel is more easily absorbed
that oral forms, so less CoQ10 needs to be taken. CoQ10 gel has been
given orphan status by the FDA for treating mitochondrial
dysfunction. (Orphan status means that a drug has been approved for
the treatment of rare disorders.)
A more easily absorbed form of CoQ10,
ubiquinol, is currently being marketed in the U.S. CoQ10 is converted
in the body to ubiquinol, which is the active form of the enzyme, and
therefore, more potent. Not only is ubiquinol more easily absorbed,
it is longer acting than ubiquinone. Ubiquinol can be purchased from
health food stores and online distributors. Vitacost sells a wide
variety of ubiquinol products, ranging in cost from $8 to $74. (Read
the labels carefully to confirm that the product contains pure
ubiquinol.) Olympian Labs sells a bottle of 60 ubiquinol softgels (50
mg) with relatively few additives for $27.62.
Oral CoQ10 is not usually covered by
insurance, as it is classed as a supplement.
FURTHER READING
Excellent summary of CoQ10 in CFS/ME:
http://phoenixrising.me/?page_id=4759
An interesting and useful site
containing a discussion of ubiquinol, a comparison of ubiquinol to
CoQ10, links and research: http://ubiquinol.org/what-is-ubiquinol
Website of the International CoQ10
Association: http://www.icqa.org/ICQA/home.html
Ray Sahelian's informative site.
Effects of CoQ10, studies and FAQs.
http://www.raysahelian.com/coq10.html
Compounding pharmacies that make CoQ10
troches: http://www.mitoaction.org/blog/coq-10-update
Information on CoQ10 gel:
http://www.epic4health.com/noname.html
PATIENT REVIEWS
Patient reviews of CoQ10:
http://www.revolutionhealth.com/drugs-treatments/rating/coenzyme-q10-coq10-for-chronic-fatigue-syndrome-cfs-cfids-me?sort=recent
RESEARCH
Maes M, Mihaylova I, Kubera M,
Uytterhoeven M, Vrydags N, Bosmans E. “Coenzyme Q10 deficiency in
myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is
related to fatigue, autonomic and neurocognitive symptoms and is
another risk factor explaining the early mortality in ME/CFS due to
cardiovascular disorder.” Neuro Endocrinol Lett. 2009;30(4):470-6.
http://www.ncbi.nlm.nih.gov/pubmed/20010505 (Abstract)
D-RIBOSE
DESCRIPTION. D-Ribose is a
water-soluble simple sugar that is an important component of nucleic
acids, vitamin B2, and various coenzymes.
BACKGROUND. Ribose was first identified
in 1891 by Emil Fischer, a German chemist and recipient of the Nobel
Prize in Chemistry. Fischer's primary work concerned sugars and the
identification of their various functions. Ribose is an extremely
important sugar in that it comprises the backbone of RNA, one of the
three major macromolecules essential to all forms of life. Ribose is
also a component of ATP, NADH and several other compounds that
control the metabolism of carbohydrates, proteins, and fat.
USES IN CFS/ME. Mitochondrial defects
that lead to low production of ATP, the principal source of cellular
energy, have been thoroughly documented in people with CFS/ME. Low
levels of ATP are responsible for the hallmark symptoms of CFS/ME,
exercise intolerance and fatigue. However, direct supplementation
with ATP seems to have no effect on either fatigue or stamina. This
is due to the fact that ATP has a molecular weight of more than 500,
which means that it is nearly impossible to absorb. Therefore, the
mitochondrial defects leading to low ATP production must be addressed
at a lower level in the metabolic chain.
The body makes ATP through the Krebs
cycle, in which various enzymes convert citric acid into ATP. These
enzymes are often deficient in people with CFS/ME, resulting in a
lower production of ATP. The body can also make ATP from glucose, but
the process involves first converting glucose into lactic acid, which
then accumulates in the muscles, causing the familiar “burn” of
over-exertion. This is also a longer and less efficient process than
the Krebs cycle. D-Ribose cuts the time required to produce ATP
because the body can quickly convert D-Ribose into ATP without
converting it first into lactic acid.
In a 2006 pilot study, Teitelbaum et al
found that in 36 CFS/FM patients, 66% experienced improvement in
energy, pain, sleep, mental clarity and overall well-being after
treatment with D-Ribose. The average improvement in energy was 45%,
while the global improvement was 30%. The researchers concluded that
D-Ribose “significantly reduced symptoms in patients suffering from
fibromyalgia and chronic fatigue syndrome.”
Apart from its uses in CFS/ME, D-Ribose
is among the most popular nutritional supplements to have been
recently patented. In 2010, Bioenergy Inc, the company which markets
Corvalen (the brand recommended by Dr. Teitelbaum), achieved its
highest revenue earnings in the history of the company.
PROTOCOL. The serving size recommended
by Jarrow is 2 grams (½ tsp/one scoop) up to three times a day. Dr.
Teitelbaum recommends 5000 mg (5 grams) of D-Ribose three times a day
for two to three weeks, then twice a day. Dr. Myhill also recommends
15 grams a day. Interestingly, she notes that the effects of D-Ribose
can be enhanced by caffeine. She notes that D-Ribose has a short
half-life, which is why it must be taken in small doses throughout
the day. D-Ribose should be taken with food.
While initial doses of 15 grams are
recommended by Drs. Teitelbaum and Myhill, it should be remembered
that many CFS/ME patients are sensitive to supplements. Dr. Cheney
has observed that fully one-third of his patients cannot tolerate
D-Ribose. To test for sensitivities, an initial small dose (1 to 2
grams a day) is recommended.
PROS. D-Ribose appears to be generally
well tolerated by people with CFS/ME. Patients usually notice
improvement in energy levels within two or three days, although one
patient commented that “within an hour, it was like a super thick
fog bank had dissipated.” D-Ribose works particularly well with
brain fog, daytime sleepiness and hypersomnia.
CONS. Some patients report that
D-Ribose makes them sleepy, and that it saps them of energy. Those
who take high doses (15 grams a day) have reported diarrhea, nausea,
and headache. Because D-Ribose is derived from corn, those with corn
allergies may not be able to tolerate this supplement. Although
D-Ribose does not have the same properties as table sugar, it can be
converted back to glucose, which may have an adverse effect on
patients with Candida, as well as those with blood sugar problems.
D-Ribose supplementation is not advised for diabetics. Nor is it
recommended for those with gout, as it causes an increase in uric
acid levels (which are usually low in people with CFS/ME).
AVAILABILITY AND COST. D-Ribose is
widely available in health food stores and from online suppliers.
Costs range from $10 to $75, depending on the brand. Corvalen, the
brand Dr. Teitelbaum prefers, sells for roughly $30 for a 280-gram
container (56 servings, or roughly an 18-day supply at three scoops a
day). Vitacost markets a 100-gram bottle made by Jarrow for about $10
(45 scoops).
FURTHER READING
Dr. Teitelbaum addresses questions
about D-Ribose:
http://www.endfatigue.com/web-newsletters/Newsletter_3_questions_d-ribose.html
Dr. Teitelbaum explains the functions
and benefits of D-Ribose.
http://www.endfatigue.com/health_articles_d-e/D-ribose-powerful_body_energizer.html
Teitelbaum JE, JA St. Cyr, C Johnson.
“The Use of D-Ribose in Chronic Fatigue Syndrome and Fibromyalgia:
A Pilot Study” J Alternative and Complementary
Medicine2006;12(9):857-862.
http://www.fibroandfatigue.com/files/d-ribose.pdf
Dr. Lapp's list of supplements,
including D-Ribose:
http://www.prohealth.com/library/showarticle.cfm?libid=16109
Myhill, Sarah, Norman E. Booth, and
John McLaren-Howard. “Chronic fatigue syndrome and mitochondrial
dysfunction.” Int J Clin Exp Med.2009;2(1): 1–16.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680051/
(This is a very long paper. You may
want to jump to the following site.)
A summary of the information in the
previous paper:
http://www.drmyhill.co.uk/wiki/CFS_-_The_Central_Cause:_Mitochondrial_Failure
Creatine and D-Ribose studies:
http://www.vrp.com/energizers/mitochondrial-restoration-part-iii-d-ribose-and-creatine-increase-mitochondrial-energy-production
A patient's encouraging report of her
experiences with D-Ribose.
http://www.healingwell.com/community/default.aspx?f=15&m=1253136
DIGESTIVE ENZYMES
DESCRIPTION. Gastrointestinal enzymes
are secreted in the GI tract for the purpose of breaking down large
food molecules into smaller molecules that are more easily absorbed.
BACKGROUND. Digestive enzymes are
secreted in the mouth by salivary glands, in the stomach, in the
pancreas and throughout the small intestine. Enzymes are classed into
groups according to their function: proteases split proteins into
amino acids, lipases split fat into fatty acids and glycerol,
carbohydrases split sugars and carbohydrates into glucose, and
nucleases split nucleic acids into nucleotides, which form RNA and
DNA. Nucleotides also potentiate the production of ATP.
The mouth is where the digestive
process is initiated. Enzymes which are released by salivary glands
include lingual lipase, to start the digestion of fats; and amylase,
which starts the conversion of carbohydrates into glucose; as well as
immune system chemicals such as IgA to battle bacterial toxins, and
R-factor which helps with the absorption of B12.
The main enzyme produced in the stomach
is pepsin, which breaks down proteins. There are a number of other
gastric secretions in the stomach which aid the process of breaking
down food, the most important of which are hydrochloric acid (HCl ),
which activates pepsin and destroys bacteria; intrinsic factor, which
aids in the absorption of B12 by protecting it from HCl ; and
gastrin, the hormone which stimulates the stomach lining to produce
HCl and intrinsic factor.
The pancreas produces trypsin, which
further breaks down proteins into amino acids; pancreatic lipase,
which breaks down fats; pancreatic amylase, which further breaks down
carbohydrates into glucose; protease, for breaking down proteins; and
several nucleases.
The small intestines, among many other
chemicals, produce sucrase, to break down sugars; lactase, to break
down lactose in milk; and maltase, which breaks maltose down into
glucose.
USES IN CFS/ME. Given the broad range
of GI disturbances in CFS/ME patients, as well as the importance of
the GI tract in maintaining both nutritional health and immune system
functioning, digestive enzymes can play a critical role in treatment.
Dr. Cheney believes enzyme supplementation is essential for all
CFS/ME patients.
PROTOCOL. Dr. Cheney recommends one or
two tablets of Ultrazyme (made by Douglas Labs). Ultrazyme provides a
broad spectrum of enzymes, including lipase, amylase, protease, ox
bile extract, cellulase, pepsin and L-lysine. Dr. Myhill recommends
Polyzyme Forte, a broad-spectrum enzyme supplement made by BioCare
(available the U.K.). Enzymes are sensitive to temperature extremes.
They should be taken with warm water or food. Enzymes are activated
by moisture, so make sure you keep the tablets dry.
PROS. Many patients swear by enzymes,
claiming that they help eradicate digestion problems as well as many
food sensitivities.
CONS. Enzymes can be hard on the
stomach. For those who are prone to reflux, or heartburn, enzymes may
exacerbate these problems. Stomach problems can be mitigated by
taking enzymes with food (rather than on an empty stomach).
AVAILABILITY AND COST. Enzymatic
supplements are readily available at any health food store and from
online suppliers. A 60-tablet bottle of Ultrazyme (Douglas Labs)
sells for around $15 on amazon.com. Enzymatic supplements can also be
purchased in powder form. Plant-based enzymes, which are not degraded
by stomach acid, should always be purchased.
FURTHER READING
Dr. Cheney discusses gut dysbiosis and
CFS/ME symptoms:
http://www.cheneyclinic.com/gut-dysbiosis-modulates-significant-cfs-symptoms/247
Dr. Cheney discusses Betaine HCl and
the function of enzymes. (Written by Carol Sieverling)
http://www.prohealth.com/library/showarticle.cfm?libid=8037
Lots of articles about enzymes:
http://www.enzymestuff.com/
DHEA
NOTE: Not all CFS/ME patients have low
levels of DHEA. Before embarking on a course of DHEA, make sure to
have your DHEA level tested.
DEFINITION. DHEA
(dehydroepiandrosterone) is a naturally occurring adrenal hormone.
BACKGROUND. DHEA, a hormone produced in
the adrenal cortex, generates the sex hormones estrogen and
testosterone. It is the most common hormone in the blood and is found
in greatest concentrations in the brain. Perhaps because DHEA levels
decrease with age, it has been called "the fountain of youth."
A substantial body of research has provided evidence that DHEA may
help the elderly by strengthening bones and muscles, decreasing joint
pain, and improving sleep and mood. In addition to influencing
hormone production, DHEA has several effects on immune system
function, not the least of which is the regulation of lymphokine
production.
A study conducted in 1993 by
researchers at the University of Tennessee showed that DHEA decreases
the amount of circulating interleukin-6 (a potent bone resorber and
pro-inflammatory cytokine) and enhances the function of natural
killer cells. Another study conducted in 1998 confirmed an inverse
correlation between DHEA levels and IL-6 (as DHEA drops, IL-6
increases). DHEA has also been used to treat osteoporosis. A
twelve-month study conducted in Canada confirmed that in
post-menopausal women the application of DHEA in the form of 10%
cream stimulated bone formation.
USES IN CFS/ME. Inspired by mounting
evidence of adrenal cortical hypofunction in CFS/ME, clinicians have
tested for blood levels of DHEA in CFS/ME patients. Some have
discovered lower than normal levels. Based on these results, low
doses of DHEA have been administered in hopes of raising immune
function and normalizing the metabolic and endocrine disturbances
that commonly accompany CFS/ME. It is believed that DHEA could also
act as an antiviral agent because testosterone, a DHEA derivative,
has demonstrable antiviral effects.
PROTOCOL. The usual dosage of DHEA is
25 to 100 mg/day, although a number of clinicians report good results
with smaller doses. Dr. Majid Ali states that he frequently
prescribes DHEA in doses of 50 mg taken on alternating days for up to
several months. In contrast, Dr. James McCoy found that smaller doses
(10 mg or less) are equally, if not more, effective than larger doses
(CFIDS Chronicle, Fall 1993). He recommended starting at one tenth
the normal dose to minimize the chance of negative reactions. Many
patients with CFS/ME confirm that smaller doses (10 mg) work well for
them.
PROS. Patients with CFS/ME have
reported weight loss, increased energy, improved cognitive function,
and better immune system responses with DHEA.
CONS. A number of patients have
reported heart palpitations, jitters, and altered mental and
emotional states. Female patients have experienced hair loss and
acne. Dr. Paul Cheney points out that DHEA is often most beneficial
in mild CFS/ME. He notes that even in cases where DHEA deficiency can
be documented, administration of this hormone has caused severe
relapse in some of his more profoundly ill patients (CFIDS Chronicle,
Spring 1995).
Researchers have noted side effects in
older women given standard doses of DHEA (25-200 mg a day), including
acne and hirsutism (facial hair growth). DHEA also lowers cortisol,
an anti-inflammatory adrenal hormone responsible for raising blood
sugar levels. It is important to remember that even though DHEA is a
natural substance, it is still a powerful hormone. Hormones, because
they are released directly into the bloodstream, produce profound
metabolic effects, not all of which are intended. Like other steroid
or hormone treatments, DHEA is not without some risk and must be
approached with caution.
AVAILABILITY AND COST. DHEA can be
purchased online and at most health food stores. It is inexpensive.
Vitacost sells many brands for less than $10. Mexican wild yam
products containing diosgenin should be avoided, as the body cannot
convert diosgenin to DHEA.
Although DHEA is sold as a supplement
in the U.S., it cannot be purchased in the U.K. and Canada without a
prescription. South Dakota and Missouri prohibit the sale of DHEA.
Those under the age of 18 cannot purchase DHEA without a
prescription. Most bottles of DHEA contain the warning: “Not for
women under the age of 35.”
One of the natural precursors to DHEA,
pregnenolone, may be less risky than DHEA. Patients report increased
energy, enhanced mental clarity, and general improvement after taking
pregnenolone. The dosage is 10 mg every other day in patients younger
than 50 years, and 20 mg every other day in patients over 50 years
old. Pregnenolone can be purchased from online suppliers at roughly
the same cost as DHEA. Pregnenolone carries the same warnings as
DHEA.
FURTHER READING
Very thorough overview of DHEA. Many
studies are cited.
http://www.tidesoflife.com/dhea__basic_information.htm
Dr. Cheney on DHEA and other
supplements (1995). http://www.immunesupport.com/news/95sum003.htm
Good article on the effects of DHEA on
aging: http://www.anti-agingmd.com/dhea.html
PATIENT REVIEWS
CFS/ME patient reviews of DHEA:
http://www.revolutionhealth.com/drugs-treatments/rating/dehydroepiandrosterone-for-chronic-fatigue-syndrome-cfs-cfids-me
RESEARCH
Casson PR, Andersen RN, Herrod HG,
Stentz FB, Straughn AB, Abraham GE, Buster JE. “Oral
dehydroepiandrosterone in physiologic doses modulate immune function
in postmenopausal women.” Am J Obstet Gynecol. 1993
Dec;169(6):1536-9. http://www.ncbi.nlm.nih.gov/pubmed/8267058
(Abstract)
Labrie F, Diamond P, Cusan L, Gomez JL, Bélanger A, Candas B.
"Effect of 12-Month Dehydroepiandrosterone Replacement Therapy
on Bone, Vagina, and Endometrium in Postmenopausal Women." J
Clin Endocrinol Metab. 1997 Oct;82(10):3498-505.
http://jcem.endojournals.org/content/82/10/3498.short (Abstract)
ESSENTIAL FATTY ACIDS
Fish Oil, Flaxseed Oil, Evening
Primrose Oil, Borage Seed Oil
DESCRIPTION. Essential fatty acids are
fats (lipids) that are important in a number of physiological
processes. They cannot be produced by the body and therefore must be
obtained through dietary sources.
BACKGROUND. The two most important
types of essential fatty acids are omega-3 and omega-6. Omega-3 fatty
acids – alpha linolenic acid (ALA), docosahexanoic acid (DHA), and
eicosapentaenoic (EPA) – are found in fish oil (especially cold
water fish) and flaxseed oil. Omega-6 fatty acids (linoleic acid, LA)
are found in many plant oils, including evening primrose oil, borage
oil, and black currant oil.
Essential fatty acids are vital to a
number of physiological processes, such as regulating cholesterol
levels, keeping the skin moist and supple, and producing
prostaglandins (hormone-like substances that affect a variety of body
functions). Essential fatty acids are also indispensable in
maintaining the structure and function of cell membranes. Most
important, essential fatty acids, particularly those found in fish
oil, can act as immune system modulators, enhancing immune system
activity where needed, and inhibiting it when there is an upregulated
immune response.
Several factors can affect fatty acid
metabolism. Poor diet, stress, diabetes, excessive alcohol intake,
radiation, and viral infections can disrupt the metabolism of
essential fatty acids, making it difficult for the body to produce
fatty acid metabolites in sufficient quantities. In such cases,
supplementation may be necessary to prevent deficiency states.
Supplementation with essential fatty acids has improved such diverse
conditions as premenstrual syndrome (PMS), heart disease, rheumatoid
arthritis, multiple sclerosis, hyperactivity in children, depression
and mononucleosis.
USES IN CFS/ME. In 1987 Dr. Peter
Behan, a professor of Clinical Neurology in Glasgow, Scotland, found
that patients with CFS/ME have a disorder in fatty acid metabolism.
Dr. Behan surmised that the disorder was the result of chronic viral
infection much like mononucleosis, a prolonged illness that also
produces abnormal serum fatty acid concentration. He conducted a
double-blind trial using a fatty acid supplement (Efamol) containing
both omega-3 and omega-6 fatty acids (Acta Neurologica Scandinavica,
1990). After 16 weeks of treatment, an astounding 85% of patients
showed marked improvement, primarily in the areas of fatigue,
dizziness, headaches, depression, and muscle pain.
In 1994, Gray and Martinovic
hypothesized that the chronic immune system activation found in
CFS/ME patients results in hyporesponsiveness of essential fatty acid
metabolites, which produces a state in which even minor stressors can
disturb homeostasis. They tested their hypothesis by administering
dietary essential fatty acids to a group of CFS/ME patients. After
three months, 90% of the patients treated showed signs of
improvement.
While the results of Behan's and Gray's
studies were encouraging, not all studies have confirmed that the
administration of EFAs significantly improves CFS/ME symptoms. It
wasn't until specific EFAs were tested that some light was shed on
the effects of EFA supplementation in CFS/ME.
In 2003 Liu et al measured specific
EFAs in the red blood cells of CFS/ME patients. The researchers found
that both DHA and ARA (arachidonic acid) levels were low, indicating
a state of oxidative stress. The authors concluded that because
ratios of EFAs are essential in maintaining signal transduction, the
disruption in EFA ratios might induce an impairment in both
circulation and immune system function. The authors stated that
recurrent sore throat, tender lymph nodes, muscle aches, arthralgia,
and headaches might be due to disruption in EFA signaling.
Puri's 2004 study of eicosapentaenoic
acid (EPA) showed that it was the omega-3 fatty acids that produced
the greatest improvement in CFS/ME symptoms. Four patients with
chronic, intractable CFS/ME were treated with high doses (approx 1500
mg a day) of an over-the-counter high eicosapentaenoic acid fatty
acid supplement (Equazen, Ltd., London). All four patients showed
improvement in symptoms within 12 weeks of treatment. They reported a
lessening of “brain fog,” and an overall sense of well-being. The
same patients when treated with a placebo did not note a similar
improvement. While the cohort was small, the findings of this study
were significant.
On the heels of this study, in 2005
Maes et al studied the ratios of fatty acids in CFS/ME patients. The
researchers measured omega-6 and omega-3 fatty acid ratios in 22
CFS/ME patients and 12 controls. They found that CFS/ME patients,
regardless of age or gender, had significantly higher levels of
linoleic acid and arachidonic acid (omega-6) than controls. Both
linoleic acid and arachidonic acid are implicated in the production
of pro-inflammatory cytokines. They speculated that the low levels of
circulating zinc found in CFS/ME patients (indicating an inflammatory
response) might be due to the depletion of omega-3 fatty acids. The
authors further hypothesized that the defects in T cell activation
found in CFS/ME might also be attributed to a deficit in omega-3
fatty acids.
AVAILABILITY AND COST. EFAs are
available at any health food store and through online suppliers. Many
companies sell combinations of different EFAs for maximum effect.
Because these are oils which are highly prone to rancidity, it is
worth the price to buy a high quality product.
FURTHER READING
“The ABCs of EFAs.” CFIDS
Chronicle, Summer 2008.
http://www.cfids.org/cfidslink/2009/040107.pdf
Good summary of essential fatty acids,
their function, and their role as a treatment for CFS/ME.
RESEARCH
Gray JB, AM
Martinovic. “Eicosanoids and essential fatty acid modulation in
chronic disease and the chronic fatigue syndrome.” Medical
Hypotheses; Vol 43, Issue 1, July 1994, Pages 31-42
http://www.ncbi.nlm.nih.gov/pubmed/7968718 (Abstract)
Liu, Zhandong, Dexin Wang, Qiming Xue,
Jun Chen, Yongjie Li, Xiaoli Bai, and Liwen Chang. “Determination
of Fatty Acid Levels in Erythrocyte Membranes of Patients with
Chronic Fatigue Syndrome.” Nutritional Neuroscience, Volume 6
Number 6 (December 2003), pp. 389–392.
http://www.cfids-cab.org/cfs-inform/Hypotheses/liu.etal03.pdf
Maes, Michael, Ivana Mihaylova and
Jean-Claude Leunis. “In chronic fatigue syndrome, the decreased
levels of omega-3 poly-unsaturated fatty acids are related to lowered
serum zinc defects and defects in T cell activation.”
Neuroendocrinology Letters; No 6, December, Vol 26, 2005.
http://www.nel.edu/26-2005_6_pdf/NEL260605A22_Maes.pdf
Ninjs, Jo, and Kenny De Meirleir.
“Letter to the Editor: Oxidative Stress Might Reduce Essential
Fatty Acids in Erythrocyte Membranes of Chronic Fatigue Syndrome
Patients.” Nutritional Neuroscience, Volume 7 Number 4 (August
2004), pp. 251–253
http://cfids-cab.org/cfs-inform/Hypotheses/nijs.demeirleir04.pdf
Puri BK. “The use of eicosapentaenoic
acid in the treatment of chronic fatigue syndrome.” Prostaglandins
Leukot Essent Fatty Acids. 2004 Apr;70(4):399-401.
http://www.cfids-cab.org/cfs-inform/CFStreatment/puri04.pdf
FISH OILS
DESCRIPTION. The oil derived from
deep-sea fish (sardines, mackerel, salmon, and herring) is the
richest source of omega-3 fatty acids (DHA and EPA). Four ounces of
salmon can contain as much as 3600 mg of omega-3 fatty acids. Fish
oil capsules have been particularly helpful in treating fibromyalgia,
often providing immediate relief from pain. Fish oil is so effective
that some physicians suggest it in place of Advil (ibuprofen) for
pain from inflammation. Because of its anti-inflammatory properties,
fish oil can also be used to treat arthritis and colitis.
AVAILABILITY AND COST. High-quality
brands of fish oils are available from Kyolic and Cardiovascular
Research Ltd. Plain cod liver oil is not recommended because the
amount needed to provide sufficient fatty acids might lead to an
overdose of vitamin A. Fish oils can range in price from $5 to $15
for a month's supply, depending on the brand, and can be purchased in
health food stores or through online vitamin catalogs. The usual dose
is one to four capsules a day.
For those who experience stomach upset
with fish oil, the enteric-coated version, Fisol (made by Nature's
Way), may be preferred. The enteric coating allows the capsules to
pass through the stomach, dissolving only once they reach the
intestines. One capsule of Fisol provides 500 mg of omega-3 fatty
acids. Vitacost sells a 180-capsule bottle of Fisol for $16.
PATIENT REVIEWS
CFS/ME patient reviews of fish oil:
http://www.revolutionhealth.com/drugs-treatments/rating/fish-oil-omega-3-epa-dha-fatty-acids-for-chronic-fatigue-syndrome-cfs-cfids-me
FLAXSEED OIL
DESCRIPTION. Flaxseed (linseed) is a
good plant source of omega-3 fatty acids. It is also high in
magnesium and zinc, two important factors in fatty acid metabolism,
as well as B complex vitamins, protein, and potassium. Flaxseed oil
is low in saturated fat and calories and contains no cholesterol. It
has a delicious nutty flavor and can be added to salad dressings or
sprinkled over vegetables.
Flaxseed is high in alpha-linoleic acid
(ALA), which the body converts to eicosapentaenoic acid (EPA) and
docosahexaenoic acid (DHA), the two fatty acids found in fish oils.
Some clinicians prefer flaxseed oil to fish oil because it is lower
on the food chain and thus contains fewer fat-soluble contaminants.
Fish oils, as opposed to vegetable oils, also contain large
quantitites of vitamin A, which can be toxic in excessive amounts.
AVAILABILITY AND COST. Flaxseed oil can
be purchased in health food stores and is inexpensive. NOW markets a
24-ounce bottle of organic flaxseed oil for $9. Flaxseed oil must be
stored in the refrigerator to avoid rancidity. It should not be used
for cooking. Gelcaps are also available.
PATIENT REVIEWS
CFS/ME patient ratings for flaxseed
oil:
http://www.revolutionhealth.com/drugs-treatments/rating/flax-seed-oil-omega-3-alpha-linolenic-acid-for-chronic-fatigue-syndrome-cfs-cfids-me
EVENING PRIMROSE OIL
DESCRIPTION. Evening primrose oil is
one of the most popular and perhaps most effective of the omega-6
essential fatty acids. It comes from the evening primrose
(Oenothera), a lovely yellow flower that grows wild along roadsides.
The seeds contain large amounts of GLA (gamma-linoleic acid), a
linoleic acid metabolite. Unlike other omega-6 fatty acids, GLA does
not lead to increased production of pro-inflammatory cytokines, but
has an anti-inflammatory effect. Evening primrose oil has been used
to help alleviate the symptoms of premenstrual syndrome (PMS),
menstrual cramps, and arthritis, often with dramatic results. It may
even lessen the symptoms of endometriosis.
PROS AND CONS. Patients with CFS/ME
have reported increased energy, improvements in skin disorders
(eczema, acne, dry skin), and decreased mood swings. Side effects,
although uncommon, include headache, nausea, mild intestinal
discomfort, and, rarely, weight gain.
AVAILABILITY AND COST. Evening primrose
oil capsules are relatively inexpensive. A bottle of 60 softgels can
be purchased for under $10 from online distributors.
PATIENT REVIEWS
CFS/ME patient ratings of evening
primrose oil:
http://www.revolutionhealth.com/drugs-treatments/rating/vitamin-c-ascorbic-acid-for-chronic-fatigue-syndrome-cfs-cfids-me
BORAGE SEED OIL
DESCRIPTION. Borage seed oil, made from
the borage plant, contains the highest GLA content of any currently
available seed oil, up to four times more than the GLA content of
evening primrose oil. Patients who have gained little benefit from or
cannot tolerate evening primrose oil because of food sensitivities
often take borage oil with good results. The recommended dose is
lower than for evening primrose oil, only one to three capsules a
day. As with all EFAs, it is best to purchase products that are high
quality. Pureformulas.com markets a bottle of 30 softgels made by
Allergy Research Group for $14.
FOS (Fructooligosaccharides)
DESCRIPTION. FOS
(Fructooligosaccharides) are natural sugars derived from fruits and
vegetables.
BACKGROUND. FOS is produced from the
degradation of inulin, or polyfructose. It is roughly half as sweet
as sugar. FOS has achieved popularity as a “prebiotic,” something
that provides a necessary substrate for lower intestinal flora,
particularly bifidobacteria. FOS also helps increase the absorption
of calcium and magnesium.
USES IN CFS/ME. FOS is primarily used
in conjunction with probiotics to aid in the promotion of friendly
gut bacteria.
Opinions about FOS are mixed in the
CFS/ME community. Dr. Cheney, for example, is not a fan of FOS. In a
1999 talk about CFS/ME patients with leaky gut, he likened FOS to
“throwing fertilizer on a patch of weeds.” By this, he is
referring to the fact that FOS, like other prebiotics, will nourish
harmful bacteria as well as friendly bacteria. In the presence of a
bacterial infection in the gut or SIBO (small intestine bacterial
overgrowth), prebiotics such as FOS will only make the condition
worse. Dr. Myhill, on the other hand, recommends supplementation for
FOS to help replenish friendly flora.
PROTOCOL. The normal dose is ¼ to 1
teaspoon of powder, taken 2 -3 times daily, in divided doses, with or
between meals. FOS is sweet, so it can be used in place of sugar.
PROS AND CONS. There is not much
patient feedback on FOS. In small amounts it does not cause side
effects. If too much is taken, it can cause gas. Because FOS provides
a substrate for all bacteria, it should not be taken in the presence
of intestinal bacterial infections (such as C diff or SIBO).
AVAILABILITY AND COST. FOS is available
at health food stores and from online distributors. It can be
purchased in capsules, tablets, or in a powder. Most health care
practitioners recommend the powder, as it can be more easily
titrated. PureFormulas.com markets a 100-gram container of FOS made
by Pure Encapsulations for about $14. (At 1 teaspoon a day, a
100-gram container will last a month.) There are many probiotic/FOS
combinations on the market.
GABA
DESCRIPTION. GABA (gamma aminobutyric
acid) is the chief neuroinhibitory neurotransmitter in mammals. While
GABA is commonly referred to as an amino acid, it is not incorporated
into proteins.
BACKGROUND. Although GABA was first
synthesized in the 19th century, it wasn't until 1950 that it was
first discovered to be a central component of the nervous system of
mammals. GABA is synthesized in the brain from glutamate, a
neuroexcitatory neurotransmitter, through the enzyme L-glutamic acid
decarboxylase in conjunction with the active form of vitamin B6.
GABA's main function in the brain is to balance neuroexcitatory
neurotransmitters by preventing nerves from excessive firing. There
are many pharmaceuticals that act on GABA receptors, including
anti-anxiety medications, anti-seizure medications, and pain
medications. Valerian, skullcap, kava and L-theanine are supplements
that act on GABA receptors.
USES IN CFS/ME. GABA has not been
widely investigated in CFS/ME patients. Kowalski et al proposed that
decreased activity of the enzymes which produce GABA may be the cause
of several disorders, including CFS/ME. However, Murrough et al did
not find any significant decrease in GABA itself among CFS/ME
patients. In contradiction to Murrough's findings, McGregor et al
found decreased beta-alanine (a GABA analogue) in CFS/ME patients,
correlating with symptoms. However, Theodorsson et al found that
while there was abnormal excretion of beta-alanine in CFS/ME
patients, it did not correlate with symptoms.
Notwithstanding this collection of contradictory evidence, it has long been proposed that people with CFS/ME suffer from neuroexcitatory states corresponding to an upregulated immune system.
Notwithstanding this collection of contradictory evidence, it has long been proposed that people with CFS/ME suffer from neuroexcitatory states corresponding to an upregulated immune system.
Some CFS/ME doctors recommend GABA for
their patients who experience anxiety and/or insomnia. Because GABA
does not easily cross the blood-brain barrier, most physicians prefer
to use pharmaceutical analogues such as Neurontin.
PROTOCOL. Dr. Rosenbaum recommends
500-1500 mg of GABA to his patients with insomnia.
PROS AND CONS. Given its inability to
cross the blood-brain barrier, there is some doubt as to whether
taking GABA supplements has any effect at all on the nervous system.
But putting scientific skepticism aside, some patients report that it
makes them jittery the day after using it for insomnia, which means
it has some ability to affect the brain.
AVAILABILITY AND COST. GABA is sold in
health food stores and from online suppliers. It is relatively
inexpensive, and is available in pill, sublingual and powder form.
The sublingual form is supposed to provide the greatest calming
effect.
RESEARCH
Hannestad U, Theodorsson E, Evengård
B. “Beta-Alanine and gamma-aminobutyric acid in chronic fatigue
syndrome.” Clinica Chimica Acta. 2007 Feb;376(1-2):23-9.
http://www.cfids-cab.org/cfs-inform/Hypotheses/hannestad.etal.06.txt
Kowalski A, Rebas E, Zylińska L.
[Gamma-aminobutyric acid--metabolism and its disorders].Postepy
Biochem. 2007;53(4):356-60.
http://www.ncbi.nlm.nih.gov/pubmed/19024900 (Abstract)
McGregor NR, Dunstan RH, Zerbes M, Butt
HL, Roberts TK, Klineberg IJ. “Preliminary determination of a
molecular basis of chronic fatigue syndrome.” Biochem Mol Med. 1996
Apr;57(2):73-80. http://www.ncbi.nlm.nih.gov/pubmed/8733884
(Abstract)
Murrough JW, Mao X, Collins KA, Kelly
C, Andrade G, Nestadt P, Levine SM, Mathew SJ, Shungu DC. “Increased
ventricular lactate in chronic fatigue syndrome measured by 1H MRS
imaging at 3.0 T. II: comparison with major depressive disorder.”
NMR Biomed. 2010 Jul;23(6):643-50.
http://www.ncbi.nlm.nih.gov/pubmed/20661876 (Abstract)
GALANTAMINE
DESCRIPTION. Galantamine is a selective
acetylcholinesterase inhibitor.
BACKGROUND. Galantamine has been used
for decades in Eastern Europe for various central nervous system
disorders, including post-polio paralysis and myasthenia gravis. It
was originally derived from the Galanthus Caucasicus (Caucasian
snowdrop), whose nodding white blooms are among the first to appear
in the spring. Recently, a synthetic compound, galantamine
hydrobromide (brand name: Razadyne), was approved by the FDA as a
treatment for Alzheimer's disease. Because galantamine increases
acetylcholine, it has also been used to block the effects of nerve
gas and organophosphate pesticides, which operate by blocking
acetylcholine.
Chemically, galantamine reduces the
action of acetylcholinesterase (AchE), the enzyme that breaks down
acetylcholine. Galantamine also modulates nicotinic cholinergic
receptors, which acts to increase the release of acetylcholine.
USES IN CFS/ME. The first study to test
galantamine as a treatment for CFS/ME was conducted in 1996 by a team
composed of Dr. Ernir Snorrason, Dr. Arni Geirsson and Dr. Kari
Stefansson. Their hypothesis was that a dysfunction of the
cholinergic system lay at the heart of CFS/ME. The researchers tested
their hypothesis by administering galantamine hydrobromide to 39
CFS/ME patients.
The results were impressive; 43%
reported an 50% improvement in fatigue, pain and sleep. The authors
noted that the improvement was stable, and that none of the patients
who had reported 50% improvement relapsed after the cessation of the
trial. Most dramatic was the improvement in sleep. More than 60% of
the patients who finished the study reported a 70% improvement of
sleep disturbances.
Given the striking results of this
study, it is puzzling that there was so little follow-up. In 2009
Turan et al investigated the effects of galantamine on stress
hormones in a group of CFS/ME patients. The study found that
DHEAS/cortisol ratios normalized with galantamine treatment. But,
while the findings confirmed a cholinergic deficit in CFS/ME, there
have been no further treatment studies.
PROTOCOL. There is no protocol for
galantamine. The Snorasson group used several different doses, but
even at the lowest dose (5 mg) several patients developed severe
nausea. High doses caused hallucinations, sweating, diarrhea,
vomiting and confusion. Even though the side effects passed,
Snorasson's group recommended starting with very low doses and close
monitoring by a physician. They also recommended taking galantamine
several hours before bed so as to reduce the risk of nightmares.
Galantamine should be taken with choline.
AVAILABILITY AND COST. Galantamine is
in the unusual class of medications that are both prescription drugs
and supplements. (Even more confusing, nobody seems to know if there
is a difference between the two.)
Galanta Mind, a blend of 4 mg
galantamine hydrobromide, choline and B6 made by Life Enhancement, is
available from such diverse sources as amazon.com, iHerb, and Sears.
A 90-capsule bottle costs between $40 and $57, depending on the
supplier. The manufacturer cautions that galantamine is for adults
only. Instructions on the bottle read: “Start with one capsule each
morning with breakfast for the first week. Add a second capsule with
lunch, starting the second week. If desired, add another capsule to
the breakfast serving the third week. Then, if desired, add another
capsule to the lunch serving the fourth week, for a total of four
capsules per day. If sensitivity occurs, reduce the amount used. If
sensitivity continues, stop taking this supplement.”
FURTHER READING
“If Only Galantamine Could Talk.”
Great summary of galantamine's fascinating history as well as its
medicinal properties:
http://www.life-enhancement.com/article_template.asp?ID=973
“Can Galantamine Help Chronic
Fatigue?” Article on acetylcholine deficiency in CFS/ME patients.
http://www.life-enhancement.com/article_template.asp?id=2224
Ray Sahelian discusses galantamine:
http://www.raysahelian.com/galantamine.html
RESEARCH
Snorrason E, Geirsson A, Stefansson K.
“Trial of a selective acetylcholinesterase inhibitor, galanthamine
hydrobromide, in the treatment of chronic fatigue syndrome.”
Journal of Chronic Fatigue Syndrome 1996; 2(2/3): 35-54.
http://www.hfme.org/researchmisc.htm (Scroll down for abstract.)
Spence VA, Khan F, Kennedy G, Abbot NC,
Belch JJF. “Acetylcholine mediated vasodilatation in the
microcirculation of patients with chronic fatigue syndrome: a short
review.”
http://www.meresearch.org.uk/research/reviews/ach_review.html
Turan T, Izgi HB, Ozsoy S, Tanrıverdi
F, Basturk M, Asdemir A, Beşirli A, Esel E, Sofuoglu S. “The
effects of galantamine hydrobromide treatment on
dehydroepiandrosterone sulfate and cortisol levels in patients with
chronic fatigue syndrome.” Psychiatry Investig. 2009
Sep;6(3):204-10. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2796068/
GLUCOSAMINE SULFATE
DESCRIPTION. Glucosamine sulfate is a
mucopolysaccharide made up of the sugar glucose and the amino acid
glutamine. It is the synthetic form of glucosamine, a naturally
occurring amino acid compound found in the joints.
BACKGROUND. Glucosamine sulfate has
been used for many years in Europe, Asia, and the Philippines to
treat osteoarthritis. It appears to stimulate the synthesis of
connective tissue and cartilage by aiding in the production of
glucosaminoglycans and proteoglycans, the key building blocks of
cartilage. Because glucosamine is also one of the main components of
the synovial fluids that cushion joints and surrounding tissues, it
has been used to treat degenerative joint diseases. It also may have
anti-inflammatory properties, thereby lessening the need for
anti-inflammatory pain medications.
USES IN CFS/ME. It is difficult to
determine how useful glucosamine may be for people with CFS/ME. Its
mode of action indicates that, in theory, it may be of benefit to
patients with joint pain, fibromyalgia, or interstitial cystitis.
PROTOCOL. Dr. Jason Theodasakis, author
of The Arthritis Cure, suggests taking glucosamine sulfate with
chondroitin, another mucopolysaccharide, for maximum benefits. His
daily dosage recommendations are based on patient weight:
• Less than 120 pounds: 1000 mg
glucosamine sulfate plus 800 mg chondroitin
• 120 to 200 pounds: 1500 mg
glucosamine sulfate plus 1200 mg chondroitin
• 200 pounds or more: 2000 mg
glucosamine sulfate plus 1600 mg chondroitin
Other health care providers believe
glucosamine sulfate is effective alone, although some recommend the
addition of bromelain, an enzyme derived from pineapple, to help
maximize its effects. Standard adult dosage as indicated by the
manufacturer is one or two tablets three times a day. Health effects
should be noticed within six to eight weeks. If no benefits are
apparent by then, glucosamine sulfate should be discontinued.
PROS AND CONS. Glucosamine sulfate is
generally considered safe and is well tolerated by most patients.
However, some may be allergic to its source (usually crustacean
shells). Patients taking blood thinners should consult with their
physician before taking glucosamine sulfate because many of the
mucopolysaccharides inhibit platelet formation.
AVAILABILITY AND COST. Glucosamine
sulfate is available from health food stores and online distributors.
A bottle of 120-tablets or capsules usually costs between $12 and
$15. Glucosamine sulfate is also available in liquid form.
FURTHER READING
Results of a comprehensive multi-center
investigation of glucosamine chondroitin.
http://nccam.nih.gov/research/results/gait/qa.htm
GLUTATHIONE
DESCRIPTION. Glutathione is a
tripeptide composed of glycine, cysteine, and glutamic acid.
BACKGROUND. Glutathione is found in
high concentrations in every tissue in the body. It is one of the
three most powerful antioxidants and detoxification agents in the
body, protecting tissues against damage from oxygen radicals such as
hydrogen peroxide and superoxide. It also helps reduce injury caused
by radiation, chemotherapy, heavy metals (mercury), and drugs
(including cigarettes and alcohol). NAC (N-acetyl-L-cysteine), a
precurser to glutathione, is an antidote to acetaminophen poisoning
and helps deter the toxic effects of naphthalene, benzene, and
anthracine. Low glutathione levels are associated with cataracts and
muscle wasting diseases.
USES IN CFS/ME. A relationship between
glutathione, muscle fatigue, low natural killer (NK) cell activity
and CFS/ME was first proposed in 1997 by Droge and Holm, two
scientists researching HIV in Heidelberg, Germany. Notably, Droge and
Holm suggested cysteine supplementation as an adjunct to antiviral
therapies to correct low glutathione. Expanding on their idea in
1999, two researchers at McGill University proposed that competition
for glutathione between the immune system and skeletal muscles might
be the cause of fatigue, muscle weakness, and pain in CFS/ME
patients. More recently, Shungu et al found that glutathione levels
were low in the cerebrospinal fluid of CFS/ME patients.
Dr. Patricia Salvato of Houston, Texas,
reported in the CFIDS Chronicle (Jan/Feb 1998) that she had treated
276 CFS/ME patients with glutathione injections. Eighty-two percent
of her patients experienced improvement in fatigue, 71 % reported
improvement in memory and concentration, and 62% reported reduced
pain. Natural killer cell function was also measured, with 187 people
showing a two-fold increase. Some patients received the therapy for
as long as 16 months. The only adverse side effects observed were
palpitations in a few patients and a slight rash or itching around
the site of injection.
Dr. Paul Cheney, who at one time stated
that glutathione deficiency was universal among CFS/ME patients, has
noted a striking improvement in his patients' symptoms, especially
headache, within days of initiating glutathione treatment.
PROTOCOL. Because oral glutathione is
poorly absorbed in the gut, Dr. Cheney recommends reduced glutathione
(CFIDS Chronicle, Spring 1995). Initial doses are high, from 150 to
425 mg three times a day. After a short time, doses can be reduced to
75 to 150 mg three times a day and maintained at those levels.
Glutathione can also be administered IV.
AVAILABILITY AND COST. There is no way
of knowing how much, in any, glutathione is absorbed by mouth, so
injectable forms are preferred. (These require a doctor.) Alternative
forms of glutathione (suppositories and troches) may have greater
absorption rates. A pack of 30 Zetpil glutathione suppositories are
available through Forrest Health for $99. Glutathione troches are
available through compounding pharmacies.
In part because glutathione is so
difficult to administer effectively, a synthetic glutathione
peroxidase mimic, ebselen, has been developed. Initial studies
demonstrated that ebselen was effective in protecting against
chemotherapy-induced hearing loss, renal injury and in recovery from
stroke (if administered within 24 hours). Ebselen protects against
manganese toxicity, inhibits Candida overgrowth, and performs a host
of antioxidant activities. Ebselen has been licensed in the U.K. for
treatment of ischemic stroke. It has not yet been approved by the
FDA.
FURTHER READING
Rich Van Konynenburg's excellent review
of glutathione, including protocols, dosages, suppliers.
http://aboutmecfs.org.violet.arvixe.com/Trt/TrtGlutathioneBuild.aspx
Another excellent discussion by Rich
Van Konynenburg proposing glutathione depletion as a cause of CFS/ME:
http://www.prohealth.com/me-cfs/blog/boardDetail.cfm?id=1287095
A list of articles about glutathione
written by Rich Van Konynenburg.
http://forums.phoenixrising.me/showthread.php?12927-Documents-by-Rich-Van-Konynenburg
An interesting, if somewhat convoluted,
discussion of glutathione and its role in CFS/ME.
http://user.xmission.com/~total/temple/Soapbox/Articles/glutathione.html
Ray Sahelian discusses glutathione's
role in various disease processes. Some good research citations.
http://www.raysahelian.com/glutathione.html
Glutathione suppositories:
http://www.forresthealth.com/reduced-glutathione-suppositories-30-count.html
RESEARCH
Bounous G, Molson J. “Competition for
glutathione precursors between the immune system and the skeletal
muscle: pathogenesis of chronic fatigue syndrome.” Med Hypotheses
1999 Oct;53(4):347-9. http://www.ncbi.nlm.nih.gov/pubmed/10608272
(Abstract)
Droge W, and Holm E. “Role of
cysteine and glutathione in HIV infection and other diseases
associated with muscle wasting and immunological dysfunction.”
FASEB J. (1997) 11:1077-1089.
http://www.fasebj.org/content/11/13/1077
Maes M, Mihaylova I, Kubera M,
Uytterhoeven M, Vrydags N, Bosmans E. “Lower whole blood
glutathione peroxidase (GPX) activity in depression, but not in
myalgic encephalomyelitis / chronic fatigue syndrome: another pathway
that may be associated with coronary artery disease and
neuroprogression in depression.” Neuro Endocrinol Lett.
2011;32(2):133-40. http://www.ncbi.nlm.nih.gov/pubmed/21552194
(Abstract)
Nakamura, Yoshimasa, Qing Feng, Takeshi Kumagai, Koji Torikai, Hajime
Ohigashi, Toshihiko Osawa, Noriko Noguchi, Etsuo Niki, and Koji
Uchida. “Ebselen, a Glutathione Peroxidase Mimetic Seleno-organic
Compound, as a Multifunctional Antioxidant: Implication for
Inflammation-Associated Carcinogensis.” The Journal of Biological
Chemistry, January 25, 2002, 277, 2687-2694.
http://www.jbc.org/content/277/4/2687 (Abstract)
Shungu DC, Weiduschat N, Murrough JW,
Mao X, Pillemer S, Dyke JP, Medow MS, Natelson BH, Stewart JM, Mathew
SJ. “Increased ventricular lactate in chronic fatigue syndrome.
III. Relationships to cortical glutathione and clinical symptoms
implicate oxidative stress in disorder pathophysiology.” NMR
Biomed. 2012 Jan 27. http://www.ncbi.nlm.nih.gov/pubmed/22281935
(Abstract)
HERBS
Aloe vera, Astragalus, Chamomile,
Echinacea, Garlic, Ginger, Gingko, Ginseng, Goldenseal, Gotu kola,
Kava, Licorice, Lomatium, Milk Thistle, St. John's Wort, Uva ursi,
Valerian
DESCRIPTION. Medicinal herbs are plants
taken orally as teas or tinctures, or applied topically as poultices
in order to heal the body.
BACKGROUND. Plants have always been
used as remedies, which makes herbal treatment the earliest form of
medicine. (The earliest human graves contain remnants of medicinal
flowers.) Even animals eat certain plants when they become ill.
Throughout the ages, people have used herbal remedies for an
assortment of problems and, until the nineteenth century, herbs were
the treatment of choice for most common ailments. Herbs have such a
long history they are regarded as folk remedies. The contemporary
medical world, as a consequence, has largely excluded them from
scientific investigations, with the exception of the Chinese, who
take herbs quite seriously. The government of China has funded a
considerable amount research to study the chemical components,
action, and efficacy of a number of herbs.
USES IN CFS/ME. A large number of
patients with CFS/ME symptoms use herbs regularly, either as herbal
substitutes for pharmaceuticals or as adjuncts to other therapies.
Although many find that a particular herb is helpful for a specific
symptom, most report that herbs have limited value in treating CFS/ME
over the long term. It should be noted, however, that patients who
have tried Chinese herbs (usually on the recommendation of an
acupuncturist) generally report a higher rate of success.
PROTOCOL. Although herbalists recommend
blending herbs for maximum effect, patients with CFS/ME frequently
have had poor responses to multiple-herb blends (with the notable
exception of Chinese herbs). For CFS/ME symptoms, herbs are best
taken singly in teas or tinctures. Teas are prepared according to the
part of the plant used. One teaspoon of herb leaves is steeped in two
cups of boiling water for 15 or 20 minutes or ½ teaspoon of herb
root or bark is boiled in two cups of water. One to two cups of tea
per day can be taken for up to two weeks. After that, the herb loses
its potency. Tinctures are usually purchased from health food stores.
Because they are quite strong, tinctures are usually taken a few
drops at a time in water. For chronic symptoms, teas are advised.
Short-term problems (flu, toothache, etc.) are best treated with
tinctures.
Note: Most tinctures are prepared in an
alcohol medium. People with CFS/ME are advised to "flash off"
the alcohol by adding the tincture to scalding hot water.
PROS AND CONS. Herbs are inexpensive,
safe, and readily available. However, it is always best to purchase
them from a health food or specialty store. Culinary herbs from the
grocery store are usually treated with chemical preservatives, seldom
organic, and have little medicinal worth. The advantage of herbs for
many people with drug and chemical sensitivities is that they can
produce the desired therapeutic effects without as many side effects.
This is not to say that negative reactions are not possible. People
with bladder problems (interstitial cystitis), gastrointestinal
symptoms, or migraine headaches may find that many herbs produce the
same side effects as pharmaceuticals.
In general, patients with CFS/ME should
avoid herbs classified as stimulants (ephedra, lomatium, and
ginseng), because these can overtax the adrenal glands. Ephedra (ma
huang), used to treat bronchial infections, is a powerful stimulant
and can cause high blood pressure, palpitations, and even stroke.
Ginseng and lomatium, although not as strong as ephedra, can produce
similar reactions in the severely ill. Echinacea, because it is an
immune system stimulant, might best be avoided by those with
upregulated immune systems.
Some herbs such as goldenseal and St.
John's Wort must be used with caution. St. John's Wort acts like a
monoamine oxidase inhibitor (MAOI) and must be treated with the same
care as the drug. (The newsletter of the Center for Specialized
Immunology reported a serious reaction in a patient who took St.
John's Wort concomitantly with an antidepressant.)
Chapparal and comfrey have caused liver
problems in some people who took too high a dose. However, there are
many other herbs that can provide temporary, safe relief from
numerous CFS/ME symptoms. Those interested in pursuing herbal
remedies should read about herbs before embarking on an herbal
therapy program or should consult with an herbalist.
FURTHER READING
Dr. Teitelbaum's herb recommendations
for CFS/ME patients. http://www.immunesupport.com/news/99spr012.htm
Nicely organized site about herbs.
Herbs are listed alphabetically for easy access.
http://www.herbwisdom.com/
BOOK
Castleman, Michael. The Healing Herbs.
Emmaus, Pa.: Rodale Press, 1991
This is a well-organized introduction
to herbs and their uses.
ALOE VERA
Aloe vera is a succulent plant
originating in Africa. Because it exudes a mucousy substance when
cut, it has a long history as a topical treatment for minor burns.
More recently, aloe juice has been promoted as an immune enhancer and
as a treatment for cancer. Though research has not been able to
substantiate these claims, aloe vera juice is recommended for people
with a variety of immune system ailments.
While some people with CFS/ME have
taken aloe and been pleased with the results, there are more negative
than positive reviews. Although it is touted as a cure for IBS, aloe
vera can cause diarrhea and intestinal irritation even in very small
amounts.
FURTHER READING
General information about aloe vera:
http://www.herbwisdom.com/herb-aloe-vera.html
CFS/ME patient reviews of aloe vera:
http://www.revolutionhealth.com/drugs-treatments/rating/aloe-vera-aloe-barbadensis-for-chronic-fatigue-syndrome-cfs-cfids-me
ASTRAGALUS
Astragalus (Astragalus membranaceous)
root has been popularized as an immune system modulator. It reputedly
enhances immune system function when it is deficient and down
regulates it when overactive. It is also thought to increase energy,
stamina, and well-being and supports adrenal gland function. Some use
it as a digestive aid. The effects of astragalus are not dramatic in
most people, but some CFS/ME patients have noted increased energy
after taking tincture of astragalus.
Recent research has shown that
astragalus has measurable medicinal properties. A 2011 study by Cheng
et al showed that astragalus may serve as a natural
cholesterol-lowering agent. Astragalus has also been shown to enhance
both humoral and cellular immune response (Th1 and Th2).
FURTHER READING
General information about astragalus
http://www.immunesupport.com/news/98spr007.htm
More general information about
astragalus: http://www.herbwisdom.com/herb-astragalus.html
RESEARCH
Cheng Y, Tang K, Wu S, Liu L, Qiang C,
Lin X, Liu B. “Astragalus Polysaccharides Lowers Plasma Cholesterol
through Mechanisms Distinct from Statins.” PLoS ONE.
2011;6(11):e27437. http://www.ncbi.nlm.nih.gov/pubmed/22110652
(Abstract)
Du X, Chen X, Zhao B, Lv Y, Zhang H,
Liu H, Chen Z, Chen Y, Zeng X. “Astragalus polysaccharides enhance
the humoral and cellular immune responses of hepatitis B surface
antigen vaccination through inhibiting the expression of transforming
growth factor β and the frequency of regulatory T cells.” FEMS
Immunol Med Microbiol. 2011 Nov;63(2):228-35
http://www.ncbi.nlm.nih.gov/pubmed/22077226
CHAMOMILE
Chamomile (Matricaria chamomila [German
chamomile]; Anthemis nobilis [Roman chamomile]) is a member of the
daisy family. It is currently one of the most popular herbs in the
United States and is widely used as an herb tea, in shampoos and
soaps, and in skin-care products. Chamomile has been known as a
sedative and antifever medicine since ancient times and was used by
Greek and Roman physicians to treat a variety of ailments.
Contemporary herbalists recommend
chamomile to treat digestive problems and ulcers, to prevent the
spread of infections, and to reduce inflammation. Because chamomile
is an antispasmodic, it has also been used to lessen the severity of
menstrual cramps. Perhaps the most interesting effect of this herb is
its ability to stimulate the immune system. British researchers
discovered that chamomile increases macrophages and B lymphocytes.
USES IN CFS/ME. Patients with CFS/ME
have chamomile tea before bedtime to help with insomnia and to
alleviate gastrointestinal symptoms. Simply inhaling the steam is
enough to produce a calming effect. (The sedative effects of the tea
may be due to apigenin, a flavonoid that binds to benzodiazepine
receptors.) In general, the herb is well tolerated. Chamomile tea
should not be boiled because boiling makes the tea bitter. Those
allergic to ragweed should avoid this herb.
FURTHER READING
General information about chamomile:
http://www.herbwisdom.com/herb-chamomile.html
ECHINACEA
The roots of the purple coneflower
(Echinacea angustifolia, E. purpura) were used by Plains Indians as a
cure for all kinds of infections. Although it has been relied on as a
topical wound healer since Colonial times, echinacea's antibiotic
properties have largely been unexplored until recently. Research
conducted in Germany in the 1950s through the 1980s revealed that
echinacea has broad antibiotic properties, much like penicillin, due
to a substance (echinacein) that counteracts cell-penetrating
enzymes. In this manner, echinacea works to strengthen individual
cell defenses.
Echinacea also acts as an immune system
stimulant. Echinacea boosts the macrophage's ability to destroy
germs. It possesses antifungal as well as antibacterial properties.
As an antiviral agent, echinacea has been used effectively to treat
influenza and the common cold as well as to check herpesvirus
infections.
USES IN CFS/ME. People with CFS/ME
often use echinacea at the first sign of a cold or flu to help lessen
the severity of the illness, and some even report lessening of all
symptoms after using this herb. Echinacea tinctures are more
effective than pills or capsules. An alcohol-free tincture should be
used, however, because alcohol dramatically lessens the potency of
this herb. Dry echinacea root can be purchased in health food stores
and boiled to make a tea.
PROTOCOL. Dr. Teitelbaum recommends 300
to 325 mg taken three times a day. He recommends that patients take a
break from echinacea for one week each month, or it will stop
working. He suggests echinacea may also improve adrenal function.
Other practitioners recommend starting at lower doses (200 mg).
Alcohol-free tinctures can be taken at 15 to 20 drops a day.
Dr. Cheney is not a fan of echinacea.
He believes that the immune-activating properties of the herb may
pose problems for CFS/ME patients with upregulated immune systems.
FURTHER READING
General information about echinacea:
http://www.herbwisdom.com/herb-echinacea.html
CFS/ME patient reviews of echinacea:
http://www.revolutionhealth.com/drugs-treatments/rating/echinacea-echinacea-spp-for-chronic-fatigue-syndrome-cfs-cfids-me
RESEARCH
See DM, Broumand N, Sahl L, Tilles JG.
“In vitro effects of echinacea and ginseng on natural killer and
antibody-dependent cell cytotoxicity in healthy subjects and chronic
fatigue syndrome or acquired immunodeficiency syndrome patients.”
Immunopharmacology 1997 Jan;35(3):229-35.
http://www.ncbi.nlm.nih.gov/pubmed/9043936 (Abstract)
GARLIC
Garlic (Allium sativum) has a long
history as a medicinal plant. The earliest medicinal description of
garlic dates from 3000 BC. Garlic was even found in the tomb of King
Tut. It has been used to treat headache, insect bites, menstrual
disorders, intestinal worms, tumors, and heart disease. Garlic is a
powerful antibiotic and antiprotozoan agent. It kills intestinal
parasites, destroys the bacterium that causes tuberculosis, and can
be used against various fungi, including Candida albicans. Daily
ingestion of as little as half a clove of garlic can lower
cholesterol. Garlic also lowers blood pressure, which means it may
have a negative effect on people with hypotension. Some people with
CFS/ME tend to be sensitive to garlic in both its raw and cooked
forms. Enteric, deodorized garlic pills can reduce intestinal upset.
A commonly recommended brand of deodorized garlic in capsules,
Kyolic, is widely available from health food stores.
FURTHER READING
General information about garlic:
http://www.herbwisdom.com/herb-garlic.html
CFS/ME patient reviews of garlic:
http://www.revolutionhealth.com/drugs-treatments/rating/garlic-allium-sativum-for-chronic-fatigue-syndrome-cfs-cfids-me
GINGER
Ginger (Zingiber officinale) was used
by the ancient Greeks as a digestive aid. It is still used as an
antidote for motion sickness, nausea, and numerous digestive
disturbances. It soothes smooth muscles, making it useful for
alleviating menstrual cramps, as well. Ginger can be taken in capsule
form or boiled to make tea. Ginger root is available from grocery or
health food stores. Ginger powder, however, as found in the spice
section of a grocery store, should not be used as a medication
because it is usually irradiated. Excessive amounts may cause mild
headache. Some people with CFS/ME find ginger difficult to tolerate.
USES IN CFS/ME. Dr. Teitelbaum is a
ginger enthusiast. He recommends it for relief of muscle and joint
pain, nausea, migraines, motion sickness, and for raising blood
pressure (for those with hypotension). The most common use among
people with CFS/ME is for nausea, a symptom which can be utterly
debilitating if unchecked.
PROTOCOL. Ginger is a food, so it can
be taken on an as-needed basis. It can be purchased as a whole root,
grated and added to food, or boiled to make a tea. For those with
less tolerance for ginger's strong flavor, candied ginger may be
eaten (or simply held under the tongue) as an alternative. Dry
encapsulations are also available, although these tend to be less
effective.
PROS AND CONS. A small amount of ginger
goes a long way. CFS/ME patients find it especially effective for
nausea and dizziness. It has an almost immediate effect. Dry ginger
capsules may cause heartburn.
AVAILABILITY AND COST. Fresh ginger and
candied ginger are available in health food stores, supermarkets and
Asian specialty markets. Dried, encapsulated ginger can be purchased
at health food stores and from online distributors. A 180-capsule
bottle of Nature's Way dry ginger costs about $5 from Vitacost.
FURTHER READING
CFS/ME patient reviews of ginger:
http://www.revolutionhealth.com/drugs-treatments/rating/ginger-zingiber-officinale-for-chronic-fatigue-syndrome-cfs-cfids-me
GINGKO
Gingko (Gingko biloba) is the oldest
species of tree on the planet. The Chinese have used its leaves for
over 5000 years as an elixir to promote longevity. Studies have shown
that gingko, by increasing blood flow to the brain, helps reduce the
risk of stroke. It can also dramatically improve memory and reaction
time. The neuroprotective effects of gingko are well documented.
There is some evidence that gingko modulates serotonin and dopamine,
and may have antidepressant-like effects. Gingko also acts as a
potent antioxidant, reducing oxidative stress by simultaneously
scavenging peroxynitrite, nitric oxide and superoxide. In Europe,
gingko is used as a conventional drug for treating short-term memory
loss, headache, tinnitus, anxiety, vertigo, and depression.
USES IN CFS/ME. Alan Logan and Cathy
Wong, in their comprehensive assessment of non-drug treatments for
CFS/ME, state that because ginkgo has specific effects on cerebral
blood flow, it may be useful for CFS symptoms related to
hypoperfusion in the brain. Many CFS/ME doctors have recommended
gingko to their patients, including Dr. Cheney and Dr. Teitelbaum.
PROTOCOL. For maximum effectiveness,
gingko biloba should be taken as an extract (not a tea). Extracts are
available in either pill or liquid form. In pill form, Dr. Teitelbaum
recommends a 50:1 extract standardized to have 24% Glycosides (this
will be indicated on the label). A 60-mg capsule can be taken once a
day. The standard dose of liquid extract is 20 drops, up to three
times a day. It may take up to six weeks to take effect.
PROS. For some people, gingko has been
a “lifesaver,” allowing them to process information again. Many
CFS/ME patients have reported that gingko helps cognitive function,
memory, and “brain fog.” Some report a decrease in migraines and
headache, as well as increased circulation to the legs.
CONS. Although gingko is usually well
tolerated, some patients with CFS/ME have reported increased fatigue.
Excessive doses can cause irritability, restlessness, nausea, and
diarrhea. Gingko has mild blood thinning properties, which means it
cannot be taken in conjunction with pharmaceutical blood thinners
(e.g., Coumadin).
FURTHER READING
General information about gingko:
http://www.herbwisdom.com/herb-ginkgo-biloba.html
More general information about gingko:
http://www.altnature.com/gallery/Ginkgo_Biloba.htm
CFS/ME patient reviews of gingko:
http://www.revolutionhealth.com/drugs-treatments/rating/ginkgo-ginkgo-biloba-for-chronic-fatigue-syndrome-cfs-cfids-me
Logan, Alan C., and Cathy Wong.
“Chronic Fatigue Syndrome: Oxidative Stress and Dietary
Modifications.”
http://www.thorne.com/altmedrev/.fulltext/6/5/450.pdf
RESEARCH
Bastianetto S, Ramassamy C, Doré S,
Christen Y, Poirier J, Quirion R. “The Ginkgo biloba extract (EGb
761) protects hippocampal neurons against cell death induced by
beta-amyloid.” Eur J Neurosci. 2000 Jun;12(6):1882-90.
http://www.ncbi.nlm.nih.gov/pubmed/10886329 (Abstract)
Diamond BJ, Shiflett SC, Feiwel N,
Matheis RJ, Noskin O, Richards JA, Schoenberger NE. “Ginkgo biloba
extract: mechanisms and clinical indications.” Arch Phys Med
Rehabil. 2000 May;81(5):668-78.
http://www.ncbi.nlm.nih.gov/pubmed/10807109 (Abstract)
Ihl R., Bachinskaya N., Tribanek M.,
Hoerr R. and Napryeyenko O. for the GOTADAY Study Group. “Efficacy
and Tolerability of a Once Daily Formulation of Ginkgo biloba Extract
EGb 761® in Alzheimer's disease and Vascular Dementia: Results from
a Randomised Controlled Trial.” Pharmacopsychiatry. 2011 Nov 15.
http://www.ncbi.nlm.nih.gov/pubmed/22086747 (Abstract)
Rojas P, Serrano-García N,
Medina-Campos ON, Pedraza-Chaverri J, Ogren SO, Rojas C.
“Antidepressant-like effect of a Ginkgo biloba extract (EGb761) in
the mouse forced swimming test: role of oxidative stress.”
Neurochem Int. 2011 Oct;59(5):628-36.
http://www.ncbi.nlm.nih.gov/pubmed/21672588 (Abstract)
Woelk H, Arnoldt KH, Kieser M, Hoerr R.
“Ginkgo biloba special extract EGb 761 in generalized anxiety
disorder and adjustment disorder with anxious mood: a randomized,
double-blind, placebo-controlled trial.” J Psychiatr Res. 2007
Sep;41(6):472-80. http://www.ncbi.nlm.nih.gov/pubmed/16808927
(Abstract)
GINSENG
Ginseng (Panax schinseng,aka Chinese or
Korean ginseng) is an ancient tonic and stimulant. It has been shown
to possess anti-inflammatory, anti-diabetic, and antioxidant
properties. Ginseng is frequently described as an “adaptogen,”
which means it can have normalizing metabolic effects, especially
when homeostasis is disrupted. Although it possesses enormous
therapeutic potential for common ailments, ginseng is usually not
recommended to patients with severe CFS/ME. Ginseng stimulates the
adrenal glands and can increase production of interferon. Because
most patients with CFS/ME have excessive interferon production as
well as endocrine abnormalities, panax ginseng may increase symptoms.
Siberian ginseng (Eleutherococcus
senticoccus), although it belongs to a different genus, has similar
medicinal qualities to panax ginseng. (Though interestingly, Siberian
ginseng appears to have the opposite effect of reducing inflammatory
responses.) Siberian ginseng, marketed as Eleutherococcus Senticosus,
is less expensive than panax ginseng and is often found in herbal
ginseng formulations. (Check the label if you are looking for pure
panax ginseng.)
Ginseng should not be used with
estrogens or corticosteroids because of possible additive effects. It
may affect the blood glucose levels of patients with diabetes
mellitus.
RESEARCH
Gaffney BT, Hügel HM, Rich PA. “Panax
ginseng and Eleutherococcus senticosus may exaggerate an already
existing biphasic response to stress via inhibition of enzymes which
limit the binding of stress hormones to their receptors.” Med
Hypotheses. 2001 May;56(5):567-72.
http://www.ncbi.nlm.nih.gov/pubmed/11388770 (Abstract)
Jung CH, Jung H, Shin YC, Park JH, Jun
CY, Kim HM, Yim HS, Shin MG, Bae HS, Kim SH, Ko SG. “Eleutherococcus
senticosus extract attenuates LPS-induced iNOS expression through the
inhibition of Akt and JNK pathways in murine macrophage.” J
Ethnopharmacol. 2007 Aug 15;113(1):183-7.
http://www.ncbi.nlm.nih.gov/pubmed/17644291 (Abstract)
See DM, Broumand N, Sahl L, Tilles JG.
“In vitro effects of echinacea and ginseng on natural killer and
antibody-dependent cell cytotoxicity in healthy subjects and chronic
fatigue syndrome or acquired immunodeficiency syndrome patients.”
Immunopharmacology. 1997 Jan;35(3):229-35.
http://www.ncbi.nlm.nih.gov/pubmed/9043936 (Abstract)
GOLDENSEAL
Goldenseal (Hydrastis canadensis) is a
North American herb known best for its antibiotic properties.
Berberine, a substance found in goldenseal, kills many of the
bacteria that cause diarrhea, as well as the protozoa that cause
amoebic dysentery and giardiasis. It has been used against cholera
bacteria and as a treatment for throat, sinus, and topical bacterial
infections. Research has shown that goldenseal is also effective
against some viral infections. People with CFS/ME generally use
goldenseal to treat sinusitis and canker sores. It should be used
with caution, however. Excessive or lengthy (more than 10 days)
treatment can lead to neurological disturbances and gastrointestinal
upset. The safest way to take goldenseal is externally as a poultice
or paste spread directly over the sinuses or other affected area.
Goldenseal should not be used during pregnancy because it stimulates
uterine contractions.
RESEARCH
Cecil CE, Davis JM, Cech NB, Laster SM.
“Inhibition of H1N1 influenza A virus growth and induction of
inflammatory mediators by the isoquinoline alkaloid berberine and
extracts of goldenseal (Hydrastis canadensis).” Int
Immunopharmacol. 2011 Nov;11(11):1706-14.
http://www.ncbi.nlm.nih.gov/pubmed/21683808 (Abstract)
GOTU KOLA
Gotu kola (Centella asiatica;
Hydrocotyle asiatica), also known as sheep rot, Indian pennywort,
marsh penny, and water pennywort, was originally used in Sri Lanka as
a promoter of longevity. It is a member of the Umbelliferae family,
which also includes carrots, parsley, dill, and fennel. Despite the
similarity in name, gotu kola is not related to the stimulant kola.
In small amounts, gotu kola is taken as a tonic, and in larger
amounts as a sedative. Gotu kola traditionally has been used in the
treatment of leprosy, but it is also noted for its ability to promote
blood circulation. Gotu kola has been used to increase memory and
mental function by increasing circulation to the brain.
FURTHER READING
Shinomol G K, Muralidhara, Bharath M M.
“Exploring the Role of "Brahmi" (Bocopa monnieri and
Centella asiatica) in Brain Function and Therapy.” Recent Pat
Endocr Metab Immune Drug Discov 2011 Jan;5 1:33-49.
http://www.ncbi.nlm.nih.gov/pubmed/22074576 (Abstract)
KAVA
Kava, or kava-kava (Piper methysticum)
is a plant native to the Pacific. Traditionally, it has been used in
the South Pacific in drinks. The roots of the plants have a sedative
effect, making it a popular treatment for anxiety.
There has been a considerable amount of
controversy surrounding the medicinal use of kava in recent years. In
2001, researchers discovered an apparent link to kava and liver
toxicity which led European, British and Canadian authorities to ban
kava sales in 2002. However, further research indicated that the
toxic compounds were located in the stem peelings and leaves, which
are parts of the plant not traditionally consumed. (Only the roots
are used in Pacific cultures.) A study published in 2003 by Whitton
et al found that modern extraction methods, using acetone or ethanol,
were responsible for kava toxicity.
Kava is used primarily as a sleep aid
and as an anxiolytic. In 1997 Volz et al found that an extract of
kava was just as efficacious as benzodiazepines or antidepressants in
reducing anxiety, and with none of the side effects. There is also
some evidence that kava may be useful in treating ADD, which might
help reduce the need for stimulant medications in children.
PROTOCOL. The recommended dose of kava
extract for insomnia is 70 – 200 mg taken an hour before bedtime.
For daytime anxiety, 70 mg may be taken one to three times a day.
Kava is not sedating when taken at moderate doses. To avoid stomach
upset, it's best to take kava with a little food.
RESEARCH
Sarris J, Kean J, Schweitzer I, Lake J.
“Complementary medicines (herbal and nutritional products) in the
treatment of Attention Deficit Hyperactivity Disorder (ADHD): a
systematic review of the evidence.” Complement Ther Med. 2011
Aug;19(4):216-27. http://www.ncbi.nlm.nih.gov/pubmed/21827936
(Abstract)
Teschke R, Sarris J, Schweitzer I.
“Kava hepatotoxicity in traditional and modern use: The presumed
Pacific kava paradox hypothesis revisited.” Br J Clin Pharmacol.
2011 Jul 29. http://www.ncbi.nlm.nih.gov/pubmed/21801196 (Abstract)
Volz HP, Kieser M. “Kava-kava extract WS 1490 versus placebo in
anxiety disorders--a randomized placebo-controlled 25-week outpatient
trial.” Pharmacopsychiatry 1997 Jan;30(1):1-5.
http://www.ncbi.nlm.nih.gov/pubmed/9065962 (Abstract)
Whitton, Peter A., Andrew Lau, Alicia
Salisbur, Julie Whitehousec, Christine S. Evans. “Kava lactones and
the kava-kava controversy.” Phytochemistry, Volume 64, Issue 3,
October 2003, Pages 673-679.
http://www.sciencedirect.com/science/article/pii/S0031942203003819
LICORICE
Licorice (Glycyrrhiza glabra) has long
been known as one of nature's most potent healing herbs. It is a
popular ingredient in many Chinese herbal remedies and has been used
to treat cough, sore throat, ulcers, arthritis, herpes infections,
and hepatitis. When combined with other herbs, licorice can increase
their effectiveness.
USES IN CFS/ME. In CFS/ME, licorice is
reputed to alleviate symptoms associated with adrenal insufficiency
(intolerance to heat, cold, noise, and other stimuli, low blood
pressure, faintness). Because the action of licorice's main active
chemical, glycyrretinic acid (GA), resembles that of the adrenal
hormone aldosterone, licorice helps the body retain salt (and water)
and ultimately may help raise blood volume and pressure. Because low
blood pressure is a problem for many patients with CFS/ME, licorice
could prove beneficial, especially for those who are sensitive to the
drugs normally recommended to correct low blood pressure. In
addition, licorice raises serum cortisol levels (often low in CFS/ME
patients) and stimulates natural killer cell activity.
PROTOCOL. Dr. Riccardo Baschetti has
used licorice for patients with low or low-normal plasma levels of
cortisol. He claimed that dramatic improvement in CFS/ME symptoms
could be seen after taking licorice for just three days (New Zealand
Medical Journal, 1995). Baschetti recommends 2.5 gm of licorice root
a day, in extract or capsules dissolved in milk. (Milk enhances the
aldosterone-like effects of the licorice.)
Dr. Peter D'Adamo, a naturopath who
also uses licorice to treat symptoms of CFS/ME, suggests taking ¼
teaspoon (2 gm) of solid licorice extract one to three times a day.
He recommends his patients take 500 mg of the amino acid methionine
and 99 mg of potassium supplement three times a day along with the
licorice to counteract any potassium and sodium imbalances.
A number of physicians have recommended
licorice for NMH (neurally mediated hypotension). NMH is a common
problem for patients with CFS/ME, affecting up to 90% of the CFS/ME
population. Many people with CFS/ME are sensitive to Florinef, the
medication normally prescribed for NMH. Dr. Calkins, a member of the
team at Johns Hopkins Medical Center that performed the initial
investigations on NMH in adolescents, stated that "medicinal
licorice is a good alternative for those sensitive to Florinef."
Dr. Cheney also endorses licorice for
treating NMH. Dr. Cheney has found that Florinef forces potassium
depletion, which further depresses the HPA
(hypothalamus-pituitary-adrenal) axis in CFS/ME patients. Licorice
can accomplish the same results as Florinef, without the side
effects. He recommends two licorice root tablets with glycerizzin two
times a day. Dr. Cheney adds the caution, “Blood pressure must be
monitored when taking licorice root!”
For optimal effect, licorice should be
taken in the morning. (Cortisol levels in the body reach their peak
at about 8AM.) It is important to note that licorice candies produced
in the U.S. do not use licorice, but anise, as a flavoring. Doctors
caution their patients to use pure licorice, not DGL. DGL
(de-glycyrrhizinated licorice ), a form of licorice in which
glycyrrhizin has been removed. Glycyrrhizin is removed in DGL to
prevent hypertension, however, it is the ingredient in licorice that
treats NMH.
PROS AND CONS. Patients who have taken
licorice report increased energy levels and improvement in symptoms
of hypoglycemia, though some have noticed that its effectiveness
wanes after a few months. Because of its steroid-like qualities, and
due to its ability to help retain sodium, it is important to monitor
licorice intake. Too much licorice, especially without potassium
supplementation, can cause serious side effects. If high blood
pressure, headaches, lethargy, and water retention develop, the
dosage should be decreased immediately. Patients taking drugs that
could interact with licorice, such as heart medications, MAOIs, or
diuretics, should consult with their physician before embarking on a
licorice protocol.
AVAILABILITY AND COST. Solid licorice
extract is marketed by Allergy Research Group. A 4-oz container (½
tsp = 3 grams) sells for $24 through PureFormulas.com (online).
Douglas Labs sells a 60-capsule bottle of pure licorice (500 mg) for
$16 (also through PureFormulas.com).
FURTHER READING
Good article on licorice:
http://drholly.typepad.com/licorice/
Excellent summary of licorice as a
treatment for CFS/ME: http://www.encognitive.com/node/15023
General information on licorice root:
http://www.herbwisdom.com/herb-licorice-root.html
Ray Sahelian on licorice:
http://www.raysahelian.com/licorice.html
Baschetti, R. “Chronic fatigue
syndrome and liquorice” N Z Med J. 1995 Apr 26;108(998):156-7.
LOMATIUM
Lomatium is a North American herb
reputed to have antiviral properties. It has been used to treat
influenza, colds, and diseases such as measles. A number of patients
who have tried lomatia extract have felt overstimulated. Some have
experienced malaise, insomnia, and jitteriness after as little as one
drop. Reports from the late 1980s stated that some CFS/ME patients
have developed severe allergic reactions while taking this herb.
FURTHER READING
Literally everything you need to know
about lomatium: http://www.naturalpedia.com/Lomatium.html
MILK THISTLE/SILYMARIN
Milk thistle (Silybum marianum), also
referred to as silymarin, appears to have a remarkable effect on the
liver. There is a great deal of research showing that active
ingredient in silymarin, silybin, stimulates liver cells to
regenerate and is effective in treating jaundice, hepatitis C, and
cirrhosis. Silymarin increases the amount of liver glutathione, a
tripeptide that activates liver enzymes. As a consequence, milk
thistle helps protect the liver from toxins, including poisonous
mushrooms, and various petrochemicals. In addition, silymarin has
powerful antioxidant, anti-inflammatory, anti-cancer and
cardioprotective properties. It also helps synthesize superoxide
dismutase (SOD), an enzyme that increases mitochondrial function and
can prevent oxidative stress both within and outside cell walls.
USES IN CFS/ME. Dr. Cheney has proposed
that many people with CFS/ME have reduced liver function, and even
subclinical hepatitis. For CFS/ME patients with mild liver
dysfunction, milk thistle may provide some relief.
PROTOCOL. Milk thistle is poorly
absorbed, so 150-300 mg a day is needed for basic liver support. Dr.
Cheney recommends 150 mg silymarin/milk thistle taken twice a day.
Siliphos, a more bioavailable form of silymarin, may be taken at
lower doses. Some studies show that a silymarin-phosphatidylcholine
complex may be absorbed more easily than regular standardized milk
thistle. Phosphatidylcholine, a key element in cell membranes, helps
silymarin attach easily to cell membranes, which may help in keeping
toxins from getting inside liver cells.
PROS AND CONS. While milk thistle is
generally well tolerated, common side effects are itching,
indigestion and headache. Some patients have reported nausea and poor
appetite on higher doses. People with allergies to plants in the
aster family: daisies, artichokes, ragweed, chrysanthemums,
marigolds, chamomile, yarrow, kiwi, and common thistle may also be
allergic to milk thistle.
AVAILABILITY AND COST. Milk thistle, in
liquid or capsule form, can be purchased at any health food store and
through online vitamin suppliers. Standardized milk thistle extracts
yielding 80% of the active ingredient in silymarin, silybin, are
recommended. Jarrow, Metabolic Maintenance, Pure Encapsulations, and
Douglas Labs all market standardized milk thistle. Prices range from
$13 to $30 for a 100-capsule bottle. Siliphos is available from
Vitacost and PureFormulas.com for roughly the same price.
FURTHER READING
Detailed information on silymarin:
http://www.salamresearch.com/html/milk_thistle_product.html
Ray Sahelian on milk thistle. Includes
dosage, research and medical uses.
http://www.raysahelian.com/silymarin.html
RESEARCH
Chen IS, Chen YC, Chou CH, Chuang RF,
Sheen LY, Chiu CH. “Hepatoprotection of silymarin against
thioacetamide-induced chronic liver fibrosis.” J Sci Food Agric.
2011 Nov 18. http://www.ncbi.nlm.nih.gov/pubmed/22102319 (Abstract)
Kalantari H, Shahshahan Z, Hejazi SM,
Ghafghazi T, Sebghatolahi V. “Effects of silybum marianum on
patients with chronic hepatitis C.” J Res Med Sci. 2011
Mar;16(3):287-90. http://www.ncbi.nlm.nih.gov/pubmed/22091246
(Abstract)
Rašković, A.; Stilinović, N.;
Kolarović, J.; Vasović, V.; Vukmirović, S.; Mikov, M. “The
protective effects of silymarin against doxorubicin-induced
cardiotoxicity and hepatotoxicity in rats.” Molecules. 2011 Oct
12;16(10):8601-13. http://www.mdpi.com/1420-3049/16/10/8601
ST. JOHN'S WORT
St. John's Wort (Hypericum perforatum),
a plant with anti-inflammatory, antiseptic and mood lifting
properties, has been documented as a remedy for roughly two thousand
years. Currently, it is a well-established treatment for depression.
In Germany, St. John's Wort is widely prescribed for children and
teens with depression as a safe alternative to antidepressants. The
Cochrane Collaboration, an organization that reviews trials of health
care treatments, found that in 29 studies with over 5,400 depressed
patients St. John's Wort fared better than placebo.
Like most herbs, St. John's Wort has
the potential to treat a variety of health problems. In 2011
Mozaffari et al found that St. John's Wort was useful for treating
IBS (irritable bowel syndrome), a bowel motility condition for which
antidepressants are sometimes prescribed. Studies have shown that St.
John's Wort increases mitochondrial function, reduces inflammation,
and inhibits nerve firing in epilepsy.
PROS AND CONS. St. John's Wort is
generally well tolerated. However, it cannot be taken in conjunction
with other antidepressants. Like any pharmaceutical antidepressant,
it cannot be taken within two weeks of treatment with MAOIs. St.
John's Wort decreases the effectiveness of many drugs, including
benzodiazepines, oral contraceptives, beta blockers, statins,
antiretrovirals, and theophylline.
FURTHER READING
Good general information about St.
John's Wort: http://www.herbwisdom.com/herb-st-johns-wort.html
Cochrane Collaboration's summary of
research on St. John's Wort for depression.
http://summaries.cochrane.org/CD000448/st.-johns-wort-for-treating-depression.
A CFS/ME patient's review of St. John's
Wort:
http://www.revolutionhealth.com/drugs-treatments/rating/st-johns-wort-hypericum-perforatum-for-chronic-fatigue-syndrome-cfs-cfids-me
RESEARCH
Huang N, Rizshsky L, Hauck C, Nikolau
BJ, Murphy PA, Birt DF. “Identification of anti-inflammatory
constituents in Hypericum perforatum and Hypericum gentianoides
extracts using RAW 264.7 mouse macrophages.” Phytochemistry. 2011
Nov;72(16):2015-23. http://www.ncbi.nlm.nih.gov/pubmed/21855951
(Abstract)
Mozaffari S, Esmaily H, Rahimi R,
Baeeri M, Sanei Y, Asadi-Shahmirzadi A, Salehi-Surmaghi MH, Abdollahi
M. “Effects of Hypericum perforatum extract on rat irritable bowel
syndrome.” Pharmacogn Mag. 2011 Jul;7(27):213-23.
http://www.ncbi.nlm.nih.gov/pubmed/21969792 (Abstract)
Wang Y, Zhang Y, He J, Zhang H, Xiao L,
Nazarali A, Zhang Z, Zhang D, Tan Q, Kong J, Li XM. “Hyperforin
promotes mitochondrial function and development of oligodendrocytes.”
J Neurochem. 2011 Nov;119(3):555-68.
http://www.ncbi.nlm.nih.gov/pubmed/21848657 (Abstract)
Woelk H. “Comparison of St John's
wort and imipramine for treating depression: randomised controlled
trial.” BMJ. 2000 Sep 2;321(7260):536-9.
http://www.ncbi.nlm.nih.gov/pubmed/10968813 (Abstract)
UVA URSI
A member of the Ericaceae family, uva
ursi (Arctostaphylos uva-ursi) has been used for more than 100 years
as a urinary tract antiseptic. Once in the urinary tract, the
chemical (arbutin) found in uva ursi is transformed into an
antiseptic agent, hydroquinone. This herb also contains diuretic
chemicals (ursolic acid) and astringents. However, uva ursi is
effective against urinary tract infections only if the urine is
alkaline; therefore, citrus fruits (including tomatoes), vitamin C,
and acidic foods should be avoided immediately before and after
taking it.
Uva ursi is also used as an
anti-Candida treatment and as an anti-bacterial.
PROS AND CONS. Some patients have
reported “die-off” reactions from taking uva ursi.
VALERIAN
Valerian (Valeriana officionalis) has
long been used as a tranquilizer, and for treating epilepsy,
nervousness, anxiety, insomnia, headache, and intestinal cramps.
During World War I, it was routinely taken to relieve the
"overwrought nerves" brought on by artillery bombardment.
Valerian is used extensively in Germany, where it is the active
ingredient in more than 100 over-the-counter sleep aids. The active
ingredients in valerian are chemicals known as valepotriates, which
are found in highest concentrations in the roots of the plant.
CFS/ME physicians recommend valerian
primarily as a sleep aid. It can be taken as a tea or in capsule
form, but because of its odor, capsules are usually preferred.
Valerian should be taken with a little milk or food to prevent
stomach upset. Valerian is often combined with other herbal sleep
aids, such as passionflower, hops, and skullcap.
FURTHER READING
Good summary of the uses of valerian:
http://www.herbwisdom.com/herb-valerian.html
Several CFS/ME doctors discuss remedies
for insomnia, including valerian.
http://www.prohealth.com/library/showarticle.cfm?libid=8563
RESEARCH
Dimpfel W, Suter A. “Sleep improving
effects of a single dose administration of a valerian/hops fluid
extract - a double blind, randomized, placebo-controlled sleep-EEG
study in a parallel design using electrohypnograms.” Eur J Med Res.
2008 May 26;13(5):200-4. http://www.ncbi.nlm.nih.gov/pubmed/18559301
(Abstract)
Leathwood PD, Chauffard F, Heck E,
Munoz-Box R. “Aqueous extract of valerian root (Valeriana
officinalis L.) improves sleep quality in man.” Pharmacol Biochem
Behav. 1982 Jul;17(1):65-71.
http://www.ncbi.nlm.nih.gov/pubmed/7122669 (Abstract)
Taavoni S, Ekbatani N, Kashaniyan M,
Haghani H. “Effect of valerian on sleep quality in postmenopausal
women: a randomized placebo-controlled clinical trial.” Menopause.
2011 Sep;18(9):951-5. http://www.ncbi.nlm.nih.gov/pubmed/21775910
(Abstract)
HISTAME
DESCRIPTION. Histame is a dietary
supplement containing the enzyme, diamine oxidase (DAO).
BACKGROUND. Diamine oxidase (also known
as histaminase) is an enzyme found in large concentrations in the
intestinal lining (mucosa) of all mammals. Its function is to break
down histamine. Unlike antihistamines, Histame does not block
histamine receptors, but acts directly on histamine itself.
In a study published in 1980, Luk et al
found that after inducing damage to the intestines of rats, the
amount of diamine oxidase was an accurate marker of intestinal
integrity. The lower the amount of diamine oxidase, the greater the
degree of damage. The researchers concluded that diamine oxidase was
unique among intestinal mucosal enzymes in its ability to predict
intestinal integrity.
In 2007 Maintz and Novak observed that
people with low amounts of DAO can develop food sensitivities which
symptomatically mimic food allergies (flushing, hypotension,
diarrhea, headache, tachycardia, and itching). Although their
symptoms match those of true allergies, these individuals do not test
positive for IgE-mediated allergies. Low levels of circulating DAO
prevent the breakdown of histamine in their intestines, causing
allergic-type reactions, particularly to histamine-rich foods. Foods
that are rich in histamine include all fermented and aged foods:
cheese, alcohol, sauerkraut, canned fish (tuna, sardines), pizza,
processed meats, as well as many fruits and chocolate. Nearly 100
drugs have been found to cause a decrease in DAO activity, including
doxycycline, MAO inhibitors, cimetidine (Tagamet), and Verapamil (a
calcium-channel blocker). DAO requires copper and Vitamins B2 and B6.
USES IN CFS/ME. Histamine intolerance
is characteristic of CFS/ME patients. Aside from new allergies, many
CFS/ME patients develop food sensitivities, as well as conditions
such as migraines, rosacea and interstitial cystitis, which are
provoked by tyrosine-rich foods. (Tyrosine is converted to tyramine,
which is closely related to histamine.) Histame has been recommended
by Dr. Kenny De Meirleir as part of treating gut dysbiosis in CFS/ME
patients.
PROTOCOL. The makers of Histame
recommend taking one or two tablets within 15 minutes of consuming
histamine-rich food. The capsules can be opened and the contents
swallowed, if preferred.
AVAILABILITY. Histame can be purchased
from a number of online sources. Prices range from $20-$40 for a
bottle of 30 capsules.
FURTHER READING
Histame website: http://histame.com/
Patient thread on Histame:
http://forums.phoenixrising.me/showthread.php?11967-90-cured-from-bed-bound-with-Histrelief-Histame-Daosin
Patient thread on histamine
intolerance:
http://forums.phoenixrising.me/archive/index.php/t-1804.html
Comprehensive list of histamine-rich
foods: http://histame.com/histamine-rich-foods-substances
An interesting study about histamine
fish poisoning: http://www.allergyclinic.co.nz/guides/63.html
RESEARCH
Luk, G
D, T M Bayless, and S B Baylin Diamine oxidase (histaminase). “A
circulating marker for rat intestinal mucosal maturation and
integrity.” J Clin Invest. 1980 July; 66(1): 66–70.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC371506/
Maintz, Laura and Natalija Novak.
“Histamine and histamine intolerance.” American Journal of
Clinical Nutrition, Vol. 85, No. 5, 1185-1196, May 2007
http://www.ajcn.org/content/85/5/1185.full
In-depth medical study examining the
effects of histamine on the gut, histamine intolerance, and the
correlation of DAO levels with food intolerance.
INOSINE/ISOPRINOSINE
DESCRIPTION. Inosine is a purine
ribonucleoside (a nitrogen-containing compound combined with
D-ribose). Isoprinosine (brand: Imunovir) is its pharmaceutical
equivalent (now largely replaced by inosine).
BACKGROUND. Inosine is a naturally
occurring chemical in the body which leads to the production of uric
acid, a potent free radical scavenger. As a basic component of cells,
uric acid is involved in a number of physiological processes
including carbohydrate metabolism, insulin regulation, and protein
synthesis. Uric acid levels are low in all inflammatory diseases,
including CFS/ME. Pharmaceutical forms of inosine (inosine pranobex,
or isoprinosine) have been used as immune system modulators.
Currently, inosine is being investigated as a possible treatment for
Parkinson's disease.
As a supplement, inosine is primarily
used to enhance athletic performance. Manufacturers claim that
because inosine is a precursor to adenosine, it facilitates the
production of ATP (adenosine triphosphate). As a consequence, inosine
should theoretically increase energy and endurance. Although there
does not appear to be any research to substantiate these claims,
inosine is included in many sports supplements.
USES IN CFS/ME. Both Dr. Kenny De
Meirleir and Dr. Cheney have largely replaced isoprinosine with
inosine in their treatment protocols, under the assumption that the
two are equivalent. Inosine, like its pharmaceutical counterpart, is
supposed to modulate the immune system and act as an antiviral.
However, inosine does not appear to possess the same antiviral
properties as isoprinosine. The main function of inosine is as an
antioxidant, which is linked to its ability to raise uric acid levels
in the blood.
Dr. Klimas still uses isoprinosine
(Imunovir) with her patients. The protocol is to alternate taking 3
and 6 pills daily, with weekends off, for three months. Over the next
three months no Imunovir is taken. The physician decides how often to
repeat this course of medication based on immune markers (as
determined by blood tests).
PROTOCOL. The standard dosage of
inosine is 500 mg three times a day for five days a week (allowing
for weekend “drug holidays”). As always, CFS/ME patients are
advised to start with low doses.
PROS AND CONS. Paradoxically, inosine
seems to help with joint pain (gout is caused by an excess of uric
acid, which is raised by inosine) and, to some degree, with energy.
Although inosine functions as an antioxidant, the process of
converting it to uric acid produces superoxide, a potent oxidant.
Some patients report that inosine works fine for a while and then
stops having an effect. Patients who were previously able to tolerate
isoprinosine have reported headaches and insomnia while taking
inosine.
AVAILABILITY AND COST. Inosine is a
supplement, which means it can be purchased without a prescription at
health food stores and from online distributors. Source Naturals
markets a 120-tablet bottle of inosine (500 mg) for roughly $20.
Imunovir is currently registered outside the United States for the
treatment of acute and chronic viral infections, including herpes and
measles. It can be obtained in Canada.
FURTHER READING
Basic information on isoprinosine,
including sources. http://www.anapsid.org/cnd/drugs/isoprinosine.html
Manufacturer's description of Imunovir:
http://www.rivexpharma.com/products_imunovir.html
CFS/ME patient thread discussing
isoprinosine and inosine:
http://www.prohealth.com/me-cfs/blog/boardDetail.cfm?id=1396515
INOSITOL
DESCRIPTION. Inositol is a carbocyclic
polyol (a sugar alcohol) which forms an essential component of cell
membranes.
BACKGROUND. Inositol, like choline, is
an important component of phospholipids, the fatty substances which
surround all cells in the body. Also like choline, inositol helps
with the transportation of fats, and prevents their accumulation in
any one site (e.g., the liver). Because it is a key component of the
myelin sheaths that surround nerves in the central nervous system,
inositol performs a crucial role in maintaining the integrity of the
nervous system.
Inositol also plays an important role
in energy metabolism; its metabolites regulate bone mass and mediate
amino acid signaling, acting as a “second messenger” for cell
receptors. Inositol phosphates are important for a number of cellular
functions, including cell growth, apoptosis (programmed cell death),
cell migration, and cell differentiation. Inositol is found in the
brain and nerves, muscles, bones, reproductive organs, stomach,
kidney, spleen, liver and heart.
Because inositol is a second messenger
of serotonin, it has been successfully used to treat several
psychiatric conditions. (Second messengers are molecules that relay
signals from neurotransmitters into the cell.) Medical uses of
inositol include treatment of obsessive-compulsive disorder (OCD),
anxiety, and depression. Inositol is also used for insomnia.
Inositol is produced in the gut in
limited quantities by bacterial flora. Dietary sources include calf
liver, cantaloupe, beans, dried beans, lentils, milk, nuts, oats,
pork, rice, veal, wheat germ and whole-grain products.
PROTOCOL. Dr. Myhill recommends
500-2,000 mgs for low GABA activity. Dr. Teitelbaum recommends a
slightly lower dose, 500-1,000 mgs a day. Maija Haavisto reports that
500 – 750 mg taken at bedtime improves insomnia.
PROS AND CONS. Inositol is safe and
inexpensive. Some people report that they wake up at night with it.
(This may be due to its SSRI-like effects.)
AVAILABILITY AND COST. Pure inositol
(also known as myoinositol) can be purchased in powder form.
PureFormulas.com markets a 250-gram container made by Pure
Encapsulations for $35 (at 500 mg a day, this will last approximately
a year and five months). Inositol frequently comes combined with
choline. Twinlabs, NOW, Solgar and Source Naturals all market
inositol/choline combinations (500 mg) at less than $10 a bottle.
Inositol often is included in B complex supplements.
FURTHER READING
Ray Sahelian's informative page on
inositol: http://www.raysahelian.com/inositol.html
Links to useful articles about
inositol: http://www.livestrong.com/inositol/
A nice summary of the functions of
inositol in the body: http://www.diagnose-me.com/treat/T47006.html
Treatment of obsessive-compulsive
disorder, panic attacks, and depression with inositol.
http://www.comprehensivepsychiatricresources.com/item.php?item_id=221&category_id=48
Maija Haavisto's excellent summary of
treatments she has tried. Scroll down for inositol, or read them all:
http://www.fiikus.net/?cfssupplements
Very interesting and informative
patient thread about the use of inositol in OCD and its relationship
with histamine:
http://www.stuckinadoorway.org/forums/archive/index.php?t-10476.html
RESEARCH
Gianfranco C, Vittorio U, Silvia B,
Francesco D. “Myo-inositol in the treatment of premenstrual
dysphoric disorder.” Hum Psychopharmacol. 2011 Oct;26(7):526-30.
http://www.ncbi.nlm.nih.gov/pubmed/22031267 (Abstract)
MALIC ACID
DESCRIPTION. Malic acid, an
intermediate in the Krebs cycle, aids in the production of adenosine
triphosphate (ATP).
BACKGROUND. Malic acid is found
primarily in apples and pears, as well as other fruits. It is used
primarily as a flavor enhancer and to lend tartness to food products.
Malic acid helps in the breakdown and utilization of fats and glucose
in muscle tissue, even in low oxygen conditions, and plays an
important role in the production of ATP.
USES IN CFS/ME. Because of the
prominent role malic acid plays in the energy-producing Krebs cycle,
a deficiency can lead to inadequate breakdown of glucose in muscle
tissue, with resulting buildup of lactic acid and other toxins.
Increased amounts of malic acid should relieve many of the symptoms
associated with tissue acidosis (spasms, cramps, and burning pain). A
number of CFS/ME physicians recommend malic acid combined with
magnesium to treat fibromyalgia symptoms. Dr. Guy Abraham, Dr. J. E.
Michalek, Dr. Jorge Flechas, and Dr. I. Jon Russell observed
improvement in pain among CFS/ME patients taking Super Malic, a
combination of 200 mg of malic acid and 50 mg of magnesium (Journal
of Rheumatology, 1995). The researchers noted that low doses of Super
Malic were not effective, and recommended six tablets a day for two
months.
PROTOCOL. As with other supplements,
physicians recommend starting with the lowest dose, one tablet daily
taken with food and water, to check for possible sensitivities. The
dosage can be increased gradually to between 6 and 12 tablets daily,
depending on tolerance. If gastrointestinal problems develop, the
dosage should be decreased. Although results may be experienced
within a few days, most physicians recommend a trial of several
months.
PROS. As a dietary supplement, malic
acid is relatively risk free. People with CFS/ME report increased
energy, less muscle pain and more stamina. One patient reported a
complete cessation of leg spasms, allowing her to rest better.
Surprisingly, a patient with kidney stones reported that they
decreased after taking malic acid for ten days.
CONS. Some patients report nausea and
stomach cramps (on 400 mg a day). Others find malic acid to be too
stimulating, resulting in insomnia. The stimulating effects can be
reduced by combining malic acid with magnesium.
AVAILABILITY AND COST. Malic acid is
available from most health food and vitamin stores. Malic acid
supplements are inexpensive. PureFormulas.com sells a bottle of 90
capsules (600 mg) made by Ecological Formulas for $12. Super Malic
has been discontinued. However, various combinations of magnesium and
malic acid are still available. Allergy Research Group markets a
120-tablet bottle of Magnesium Malate Forte (124 mg magnesium, 500 mg
malic acid, with 10 mg B2) for roughly $20 (through
PureFormulas.com).
FURTHER READING
Patient thread on malic acid:
http://www.chronicfatiguetreatments.com/forums/vitamins-for-chronic-fatigue-f7/topic593.html
RESEARCH
Russell IJ, Michalek JE, Flechas JD,
Abraham GE. Treatment of fibromyalgia syndrome with Super Malic: a
randomized, double blind, placebo controlled, crossover pilot study.”
J Rheumatol. 1995 May;22(5):953-8.
http://www.ncbi.nlm.nih.gov/pubmed/8587088 (Abstract)
MELATONIN
DESCRIPTION. Melatonin is a hormone
produced by the pineal gland.
BACKGROUND. Melatonin is a naturally
occurring hormone produced in the pineal gland, the brain's "master
gland." It is derived from serotonin, one of the brain's most
important neurotransmitters. Serotonin, a neurochemical derived from
the amino acid tryptophan, is converted by enzymes sensitive to the
diurnal cycle of darkness and light into melatonin. Melatonin,
because it is produced in the part of the brain that regulates
diurnal rhythms, is essential for maintaining normal sleep patterns.
Large amounts of melatonin are produced in children, which is one
reason why young people sleep so much. As we age, melatonin levels
decrease, making it more difficult for the elderly to sleep through
the night.
Disruption of both melatonin and
serotonin production has been implicated in seasonal affective
disorder, the treatment of which involves increasing melatonin levels
through exposure to full-spectrum light early in the day. Low
melatonin and serotonin levels have also been implicated as
contributing factors to depression. Currently, physicians are
exploring the use of melatonin as an anti-aging factor. It is
possible that supplementation with melatonin in the elderly may help
correct the disturbed sleep, poor immune response, and diminished
capacity for tissue repair typical of the aging process.
Melatonin may also help correct
insomnia in the young. Studies released by the Massachusetts
Institute of Technology showed that it took less than half the time
for volunteers given melatonin to fall asleep than those given a
placebo. Subjects given melatonin also tended to sleep about twice as
long as those given placebo and woke without the “hangover”
normally associated with sleeping pills. The results of this study
are encouraging to those with sleep disorders. However, the
effectiveness of melatonin depends on a number of other factors.
Benita Middleton and her colleagues at
the University of Surrey tested the effect of melatonin in
conjunction with body temperature. They discovered that in subjects
whose body temperature rose later in the day, melatonin had a
negative effect on sleep, producing extremely fragmented sleeping and
waking patterns. Although melatonin is produced in the pineal gland,
it is regulated by a part of the hypothalamus, the suprachiasmatic
nucleus, which acts as the body's “clock” by tracking the length
of the day. The hypothalamus also controls body temperature, so it is
not surprising that the body's internal clock is linked to core
temperature. Middleton concluded that while melatonin plays an
important role in circadian sleep cycles, the effects are highly
individualized.
Melatonin also regulates the “gut
clock.” About 400 times more melatonin is produced in the gut than
in the brain. The reason for this vast production of melatonin is
that digestion is regulated by circadian rhythms. Bile flow increases
at night, as do other digestive secretions. Melatonin functions not
only to set the circadian rhythms of the digestive system, but to
harmonize them with immune and endocrine functions. When these
rhythms are disrupted, digestive disturbances result.
It is known that people with severe
insomnia are prone to irritable bowel syndrome (IBS), peptic ulcers,
fatty liver, GERD, and dyspepsia. In an interesting study of the use
of melatonin for treating IBS conducted by Lu et al in 2005, 88% of
the patients reported significant improvement of their GI symptoms
after 8 weeks of treatment with melatonin over placebo. Oddly enough,
the patients experienced no difference in sleep between melatonin and
placebo.
USES IN CFS/ME. Sleep disturbance is
one of the primary symptoms of CFS/ME. Many patients experience
persistent insomnia throughout the illness. Even after a full night's
rest, patients with CFS/ME awaken tired. Many clinicians believe that
treating the CFS/ME sleep disorder is of primary importance because
it reduces the severity of many other symptoms. However, owing to the
prevalence of drug and chemical sensitivities in the CFS/ME
population, it is not always easy to find a safe, effective means of
obtaining a good night's rest. Melatonin may offer an alternative.
In 2006 van Heukelom et al explored the
use of melatonin on CFS/ME patients with Dim Light Melatonin Onset
(DLMO) later than 11:30 PM. DLMO is when the body begins its own
production of melatonin. In healthy people, it occurs roughly two
hours before bedtime, provided the light is dim. Van Huekelom's group
found that in people with CFS/ME the delayed onset of DLMO was
rectified by administration of 5 mg of melatonin five hours before
DLMO. After three months, fatigue, energy, and concentration were
significantly improved. The researchers concluded that melatonin was
an effective therapy for those CFS/ME patients with significantly
delayed sleep onset.
Although many CFS/ME physicians use
melatonin, there is no clear evidence from the literature that
melatonin levels are actually deficient in CFS/ME patients. In a
study of 13 adolescents with CFS/ME, Knook et al found that melatonin
levels were actually higher in the CFS/ME group than in controls.
There is a possible explanation for why
some CFS/ME patients might be high in melatonin. Researchers have
found that melatonin increases the release of cytokines, immune
system chemicals that act as messengers to initiate various immune
responses. In 1997 Garcia-Maurino et al found that melatonin
increased the production of IL-2, IL-6 and gamma interferon,
enhancing the effectiveness of Th1 (cellular) immunity (the type of
immune function that combats viruses).
A previous study by Ben-Nathan et al
found that injecting virus-infected mice with melatonin significantly
reduced mortality rates. The implication for at least some people
with CFS/ME is that the excess melatonin might be a response to
reactivated viruses, providing a hormonal route to immune activation.
In light of melatonin's role in enhancing cellular immunity, which is
deficient in people with CFS/ME, this is an area which warrants
further investigation, especially given the strong association
between mono and CFS in teens.
PROTOCOL. Dr. Lapp uses melatonin with
patients who have “phase shifted.” That is, they can't fall
asleep until 1 or 2AM, and then sleep all day (indicating that the
body's “clock” needs to be reset). He recommends starting with as
little as 0.1 mg taken a half-hour before bedtime and increasing the
dose until the desired effect is achieved. He also has observed that
synthetic (not from animal sources) and sublingual forms of melatonin
are safest and most effective (MEssenger, 1997). Dr. Lapp does not
recommend melatonin for children younger than the late teens.
While product labels usually recommend
one to two tablets (3 to 6 mg) taken before bedtime, studies at the
Massachusetts Institute of Technology indicate 0.3 mg daily is
sufficient to raise blood levels to normal. MIT researcher, Dr.
Richard Wurtman, claims that serious side effects can be produced by
taking standard doses, which can raise blood levels to more than 10
times the norm. Dr. Teitelbaum also agrees that the standard dose of
3 mg is too high. He recommends taking no more than 0.5 mg.
PROS. A number of CFS/ME patients have
reported that melatonin has given them their best night's sleep in
years. Melatonin works quickly. For people who become insomniacs
while taking beta blockers, melatonin supplementation may provide
considerable relief. (Beta blockers can deplete the body of
melatonin.)
CONS. Melatonin can lose its
effectiveness over time. After working beautifully for a few weeks or
months, it can suddenly stop providing the desired results. Some
people report paradoxical reactions, such as feeling more awake or
experiencing partial or light sleep states. The reason melatonin
works for some but not for others may have to do with individual
biorhythms (see above). It is possible that patients with CFS/ME
whose temperatures rise in the evening due to immune activation may
not respond well to melatonin treatment.
Excessive doses of melatonin can cause
jitters and headaches. Female patients may experience hormonal
disturbances (early onset of periods). Interactions with
antidepressant drugs such as Prozac, Elavil, or Zoloft and the pain
medication, Ultram, have been reported. People taking antidepressants
should discuss the risks and benefits of melatonin with their
physicians. Preexisting depression as well as orthostatic intolerance
may be worsened by melatonin.
AVAILABILITY AND COST. Although it is a
hormone, melatonin is currently considered a nutritional supplement.
Consequently, it can be purchased over the counter from most health
food stores and vitamin catalogs. A 100-tablet bottle of melatonin
(3mg) can cost less than $5. Those who wish to start with lower doses
should order the liquid.
FURTHER READING
“Sleep and Snake Oil.” Rachel
Preiser. Discover Magazine. March 1997.
http://discovermagazine.com/1997/mar/sleepandsnakeoil1082
Cort Johnson's informative page about
melatonin in CFS/ME.
http://aboutmecfs.org.violet.arvixe.com/Trt/TrtMelatonin.aspx
Dr. Lapp on melatonin and other sleep
medications.
http://www.prohealth.com/library/showarticle.cfm?libid=8563
Melatonin safety assessment by the Mayo
Clinic.
http://www.mayoclinic.com/health/melatonin/NS_patient-melatonin/DSECTION=safety
CFS/ME patient forum on melatonin:
http://forums.phoenixrising.me/archive/index.php/t-12516.html?s=8dd572918a1b8e25a023bda45d398c90
RESEARCH
Ben-Nathan D, Maestroni GJ, Lustig S,
Conti A. “Protective effects of melatonin in mice infected with
encephalitis viruses.” Arch Virol. 1995;140(2):223-30.
http://www.ncbi.nlm.nih.gov/pubmed/7710351 (Abstract)
Carrillo-Vico A, Guerrero JM, Lardone
PJ, Reiter RJ. “A review of the multiple actions of melatonin on
the immune system.” Endocrine. 2005 Jul;27(2):189-200.
http://www.ncbi.nlm.nih.gov/pubmed/16217132 (Abstract)
Garcia-Maurino S, MG Gonzalez-Haba, JR
Calvo, M Rafii-El-Idrissi, V Sanchez- Margalet, R Goberna and JM
Guerrero. “Melatonin enhances IL-2, IL-6, and IFN-gamma production
by human circulating CD4+ cells: a possible nuclear receptor-mediated
mechanism involving T helper type 1 lymphocytes and monocytes.” The
Journal of Immunology, Vol 159, Issue 2 574-581, 1997.
http://www.jimmunol.org/content/159/2/574.abstract (Abstract)
Guerrero JM, Reiter RJ.
“Melatonin-immune system relationships.” Curr Top Med Chem. 2002
Feb;2(2):167-79. http://www.ncbi.nlm.nih.gov/pubmed/11899099
(Abstract)
Knook L, Kavelaars A, Sinnema G, Kuis
W, Heijnen CJ. “High nocturnal melatonin in adolescents with
chronic fatigue syndrome.” J Clin Endocrinol Metab. 2000
Oct;85(10):3690-2. http://www.ncbi.nlm.nih.gov/pubmed/11061525
(Abstract)
Konturek PC, Brzozowski T, Konturek SJ.
“Gut clock: implication of circadian rhythms in the
gastrointestinal tract.” J Physiol Pharmacol. 2011
Apr;62(2):139-50. http://www.ncbi.nlm.nih.gov/pubmed/21673361
(Abstract)
http://www.jpp.krakow.pl/journal/archive/04_11/pdf/139_04_11_article.pdf
(Full text)
Lu WZ, Gwee KA, Moochalla S, Ho KY.
“Melatonin improves bowel symptoms in female patients with
irritable bowel syndrome: a double-blind placebo-controlled study.”
Aliment Pharmacol Ther. 2005; 22: 927-934.
http://www.ncbi.nlm.nih.gov/pubmed/16268966 (Abstract)
Smits M G, Van Rooy R, Nagtegaal J E.
“Influence of Melatonin on Quality of Life in Patients with Chronic
Fatigue and Late Melatonin Onset.” J Chronic Fatigue Syndrome.
2002;10(3/4):25-32. 29.
http://www.cfids-cab.org/cfs-inform/Melatonin/smits.etal02.pdf
van Heukelom RO, Prins JB, Smits MG,
Bleijenberg G. “Influence of melatonin on fatigue severity in
patients with chronic fatigue syndrome and late melatonin secretion.”
Eur J Neurol. 2006 Jan;13(1):55-60.
http://www.ncbi.nlm.nih.gov/pubmed/16420393 (Abstract)
Williams G, Waterhouse J, Mugarza J,
Minors D, Hayden K. “Therapy of circadian rhythm disorders in
chronic fatigue syndrome: no symptomatic improvement with melatonin
or phototherapy.” Eur J Clin Invest. 2002 Nov;32(11):831-7.
http://www.ncbi.nlm.nih.gov/pubmed/12423324 (Abstract)
MINERALS
Calcium, Magnesium, Selenium, Colloidal
Silver, Zinc
CALCIUM
BACKGROUND. Calcium is the most
abundant mineral in the human body. A 150-pound adult's body contains
about three pounds of calcium, 99% of which is found in the skeletal
bones. The small portion of calcium found in soft tissues and body
fluids is essential for maintaining a number of important biochemical
functions, including regular heartbeat and transmission of nerve
impulses. Calcium also prevents muscle cramps and is vital for the
formation of healthy teeth and strong bones.
There are two main forms of calcium:
inorganic and organic. The inorganic forms (sulfate, carbonate, and
phosphate) are poorly absorbed. The organic forms (citrate, lactate,
gluconate, orotate, aspartate, ascorbate and various chelates) are
better absorbed. Once calcium is metabolized through the action of
stomach acid, it passes into the small intestine where the ionized
(liquified) calcium is absorbed into the bloodstream. Ionized calcium
is the most important physiological component of calcium. In fact,
because calcium is so easily bound to other compounds, blood
measurements of total calcium are useless for determining the amount
of calcium actually available in the body. Only ionized calcium gives
an accurate picture as to how much calcium is actually available to
maintain physiological functions.
USES IN CFS/ME. CFS/ME patients often
take calcium at night to alleviate insomnia. It is also useful for
treating muscle spasms. Those ingesting high amounts of protein or
phosphorus may want to supplement their intake of dietary calcium
because both protein and phosphorus increase calcium excretion from
the body. Good natural sources of calcium are dairy products and
green leafy vegetables.
PROTOCOL. Dr. Lapp recommends 1,000 mg
to 1,500 mg daily. Calcium intake should not exceed 2500 mg a day.
Calcium cannot be properly absorbed and assimilated unless vitamin D
and trace minerals are present (chromium, boron, copper, iron,
manganese, phosphorus, silicon, strontium, and zinc). It is important
to supplement with these trace minerals while taking calcium, because
calcium competes with other minerals for absorption in the
intestines. It is also important to supplement with magnesium.
(Magnesium prevents plaque buildup from unabsorbed calcium.)
Liquid ionic calcium is more easily
absorbed and utilized than other forms of calcium. For example, only
10% of either calcium carbonate (Tums) or calcium citrate is
absorbed. This means you get 100 mg of usable calcium for every 1,000
mg consumed. (You'd have to eat over 30 Tums to get 1000 mg of
calcium.) Calcium lactate, found in milk, fares a little better at
33%. In contrast, calcium aspartate is 85% absorbed and calcium
orotate is 90-95% absorbed. Ionic calcium is nearly 100% absorbed.
CFS/ME patients taking verapamil (a
calcium channel blocker) to treat cognitive dysfunction need to be
aware that calcium supplements may interfere with the effects of this
medication. People with a history of kidney disease or kidney stones
should not take calcium supplements, because the additional calcium
may exacerbate the condition.
PROS AND CONS. Calcium is inexpensive
and generally well tolerated. Calcium supplements can interfere with
the absorption of both iron and zinc (but not magnesium), so if you
are supplementing with either of these minerals, be sure to take them
at least two hours after (or before) taking calcium.
AVAILABILITY AND COST. There is a wide
variety of calcium supplements available at supermarkets, drug
stores, health food stores, and from online distributors. Mineral
Life sells an 8-oz bottle of liquid ionic calcium for $20 (60-day
supply). Pure Essence markets Ionic Fizz (a blend of ionic trace
minerals and vitamins) for $16 through Vitacost. Advanced Research
markets a 100-tablet bottle of calcium orotate combined with
magnesium for about $20 (through amazon.com). Advanced Research also
markets a 100-tablet bottle of calcium aspartate for the very
affordable price of $7.
FURTHER READING
Good
overview of calcium, including rates of absorption for different
calcium compounds.
http://www.uswellnessmeats.com/Calcium_Myth_and_Facts.pdf
Brief interview with Dr. Spreen about
the different forms of calcium and their bioavailability.
http://www.alkalizeforhealth.net/Lcalcium.htm
Ionic calcium supplier:
http://www.mineralifeonline.com/pd-calcium-8oz-60-day-supply.cfm
“When
Is It Appropriate to Order an Ionized Calcium?” Laura M. Calvi and
David A. Bushinsky. JASN July 1, 2008 vol. 19 no. 71257-1260.
http://jasn.asnjournals.org/content/19/7/1257.full
Good medical article about the
importance of measuring ionic calcium in the bloodstream.
MAGNESIUM
BACKGROUND. Magnesium is one of the six
major minerals classified as essential for the functioning of the
human body. The average human body contains about 25 grams of
magnesium salts, about half of which is stored in the bones and
one-fourth in muscle. Only about 2% circulates freely in the blood.
The rest is located within the cells. Blood levels of magnesium are
controlled by the kidneys.
Magnesium is necessary for relaying
nervous system impulses and for normal metabolism of calcium and
potassium. Much like a vitamin, magnesium functions as a coenzyme,
aiding in enzyme systems, storage and release of energy generated
from carbohydrates, and synthesis of proteins and DNA. Magnesium
deficiency can result in anorexia, nausea, learning disabilities,
personality changes, weakness, exhaustion, and muscle pain.
According to the USDA, a staggering 68%
of Americans do not consume the daily recommended intake for
magnesium. In a forward-looking article written in 1990, Kubena et al
outlined the effects of chronic marginal intakes of magnesium,
including “abnormalities in reproduction, growth, and development
and disorders of neuromuscular, cardiovascular, renal, and immune
function.” In addition, the authors pointed out that problems
related to the use of pharmacological agents or trace metals, such as
aluminum (which has been implicated in the development of Alzheimer's
disease), may be worsened with a low intake of magnesium.
Dr. Pall has speculated that, given the likelihood that people with CFS/ME are marginally deficient in magnesium before falling ill, magnesium deficiency may contribute to the pathogenesis of the illness.
Dr. Pall has speculated that, given the likelihood that people with CFS/ME are marginally deficient in magnesium before falling ill, magnesium deficiency may contribute to the pathogenesis of the illness.
USES IN CFS/ME. Magnesium is an
indispensable supplement for people with CFS/ME. Nearly every CFS/ME
physician includes either injectable or oral magnesium as part of
their protocol. In early 1991, I.M. Cox, M.J. Campbell, and D. Dowson
published a preliminary study on magnesium levels in CFS/ME patients
(Lancet, 1991). All 22 patients studied had reduced levels of serum
magnesium.
They followed up their findings with a
randomized clinical study in which 15 of the patients received
intramuscular injections of magnesium sulfate every week for six
weeks and 17 received a placebo. Of the 15 patients receiving
magnesium, 12 reported improvement in symptoms. Although subsequent
studies have not confirmed low serum levels of magnesium to be
universal among CFS/ME patients, magnesium is still the most
frequently recommended mineral supplement for patients with CFS/ME.
In his book, Explaining “Unexplained
Illnesses,” Dr. Martin Pall presents a compelling argument
implicating oxidative stress in the etiology of CFS/ME. An important
part of the ongoing oxidative stress typical of multisystem illnesses
like CFS/ME, FM and Gulf War Syndrome is the chronic excitability of
NMDA receptors, which results in a hyperactive nervous system (along
with cell damage, inflammation, and lowered production of ATP).
Magnesium is one of the principal inhibitors of NMDA activity, which
makes it a valuable treatment for any illness involving chronic
oxidative stress.
Dr. Myhill believes that low magnesium
levels in CFS/ME patients is a symptom of mitochondrial failure. When
mitochondria fail, calcium leaks into cells and magnesium leaks out.
According to Dr. Myhill, this leakage explains why it is useless to
test serum levels of magnesium. As she puts it, “Serum levels are
maintained at the expense of intracellular levels. If serum levels
change this causes heart irregularities and so the body maintains
serum levels at all cost. It will drain magnesium from inside cells
and indeed from bone in order to achieve this.” Dr. Myhill's
explanation not only accounts for why serum levels of magnesium are
inconsistent in CFS/ME, but why magnesium supplementation is
effective.
PROTOCOL. Magnesium can be administered
orally or by injection. Because oral magnesium is difficult to
absorb, the forms most frequently recommended are magnesium citrate
and magnesium glycinate. Magnesium citrate will dissolve in water,
which makes it more bioavailable than most other forms of magnesium.
However, Dr. Cheney has observed that magnesium glycinate causes the
least intestinal upset and is the most easily absorbed. The usual
recommended dosage is 200 to 400 mg/day taken with food, although
CFS/ME patients are cautioned to start with a smaller dose and
increase it gradually. Intramuscular injections of 1 cc of magnesium
sulfate (50%) or magnesium chloride can be administered once or twice
a week. Because of magnesium's effect on heart function, the first
injection should be performed in a physician's office.
PROS AND CONS. Most people who take
magnesium, whether oral or injected, report increased stamina and
energy. Many include better sleep as an additional benefit (most
likely due to magnesium's muscle-relaxing effects). The main drawback
of injected magnesium is that the injections are painful. The
simultaneous administration of vitamin B12 or lidocaine helps relieve
the pain of the injection. Because magnesium is a cathartic, high
doses can cause diarrhea. In patients prone to gastrointestinal
upset, a low dose is normally recommended.
AVAILABILITY AND COST. Oral magnesium
is readily available from health food stores, online vitamin
suppliers, and most drugstores. It is inexpensive. A bottle of 120
tablets of either magnesium glycinate or magnesium citrate (400 mg)
costs $12 from Vitacost. Topical magnesium creams are also available.
PureFormulas.com markets a 4-ounce jar of magnesium cream made by
Kirkman for $16. (Or you can make your own cream using Epsom salts.)
Magnesium can be purchased as a powder and mixed into a beverage for
easier assimilation. Magnesium sulfate injections usually cost $16 to
$20 per injection.
FURTHER READING
Excellent summary of magnesium's
effects on the body from the Linus Pauling Institute.
http://lpi.oregonstate.edu/infocenter/minerals/magnesium/
Dr. Myhill discusses magnesium
deficiency and treatment in CFS/ME patients.
http://www.drmyhill.co.uk/wiki/Magnesium_-_treating_a_deficiency
USDA statistics on nutrient consumption
by state and nationally.
http://www.ars.usda.gov/Services/docs.htm?docid=11197
“Review and Hypothesis: Might
Patients with the Chronic Fatigue Syndrome Have Latent Tetany of
Magnesium Deficiency.” Mildred Seelig, MD, MPH
http://www.mgwater.com/clmd.shtml
RESEARCH
Cox IM, Campbell MJ, Dowson D. “Red
blood cell magnesium and chronic fatigue syndrome.” Lancet. 1991
Mar 30;337(8744):757-60. http://www.ncbi.nlm.nih.gov/pubmed/1672392
(Abstract)
Kubena KS, Durlach J. “Historical
review of the effects of marginal intake of magnesium in chronic
experimental magnesium deficiency.” Magnes Res.1990
Sep;3(3):219-26. http://www.ncbi.nlm.nih.gov/pubmed/2132753
(Abstract)
Lindberg JS, Zobitz MM, Poindexter JR,
Pak CY. “Magnesium bioavailability from magnesium citrate and
magnesium oxide.” J Am Coll Nutr. 1990 Feb;9(1):48-55.
http://www.ncbi.nlm.nih.gov/pubmed/2407766 (Abstract)
Manuel y Keenoy, B, Moorkens, G,
Vertommen, J, Noe, M, Neve, J, and De Leeuw, I. “Magnesium status
and parameters of the oxidant-antioxidant balance in patients with
chronic fatigue: effects of supplementation with magnesium.” J Am
Coll Nutr. 2000 Jun;19(3):374-82.
http://www.ncbi.nlm.nih.gov/pubmed/10872900 (Abstract)
Seelig, Mildred MD, MPH. “Review and
Hypothesis: Might Patients with the Chronic Fatigue Syndrome Have
Latent Tetany of Magnesium Deficiency.” Journal of Chronic Fatigue
Syndrome, Vol. 4(2) 1998 http://www.mgwater.com/clmd.shtml
SELENIUM
BACKGROUND. Selenium is a trace mineral
found in the soil, and in foods such as lobster, tuna, shrimp,
oysters, fish, brown rice, garlic, whole grains, sesame seeds, and
mushrooms. Although it is needed in only small amounts, selenium
performs an important role in kidney, spleen, pancreas and liver
function, as well as in reproduction. In men, about half of the
body's selenium is concentrated in the testes. Selenium forms a
component of glutathione peroxidase, the body's most prolific
antioxidant. Deficiencies in selenium can lead to infertility,
arthritis, hypothyroidism (selenium is essential for making T3), loss
of energy, immune system deficiency, and, in children, cardiac
problems.
Apart from its many metabolic
functions, selenium performs an important role in the functioning of
the immune system. In a 1994 study performed at New York University,
subjects who received a 200 mcg daily supplement of selenium for
eight weeks showed an enhanced immune response to foreign antigens,
including an increase natural killer cell activity. Research also
indicates that selenium up-regulates IL-2 and increases activation of
T helper cells. Selenium supplementation may also down regulate
abnormally high levels of the inflammatory cytokines IL-8 and TNF
alpha.
It is because of selenium's dual
function as an antioxidant and as an immune system enhancer that
attention has recently been drawn to its possible role in the
creation of “superbugs,” such as the Ebola virus. In the
mid-1990s two researchers, Melinda Beck, a virologist at the
University of North Carolina, and Orville Levander, a nutritional
chemist with the USDA, set about to investigate the effects of
selenium deficiencies on mice infected with Coxsackie virus. They
discovered that not only did the mice develop virally induced heart
disease, but that the virus itself had mutated into a more virulent
strain.
Subsequent studies by Beck and
colleagues confirmed that a host deficient in selenium not only has a
poor immune response, but also can influence the genetic makeup of
the virus, producing a more deadly strain. In an enormously
understated conclusion, the authors stated that “this latter
finding markedly changes our concept of host-pathogen interactions
and creates a new paradigm for the study of such phenomena.” For
those who have suffered for decades from the long-term effects of
viral infections, the implications of this study are ominous.
USES IN CFS/ME. In CFS/ME, selenium is
used primarily as an antioxidant. Selenium helps form glutathione
peroxidases (which eliminate peroxide oxidants in the cell), as well
as acting as a peroxynitrite scavenger. Both of these properties make
selenium an important adjunct in antioxidant therapy. Selenium's role
in thyroid hormone production also make it an essential supplement
for people suffering from borderline hypothyroidism (a common finding
in CFS/ME, due to disturbances in the endocrine system). Selenium has
been identified as a mood enhancer as well.
In an interesting study of the
psychological impact of selenium, Benton observed that “the
metabolism of selenium by the brain differs from other organs in that
at times of deficiency the brain retains selenium to a greater
extent.” Benton proposed that this preference indicates that
selenium is important in psychological function, particularly mood.
In his article, Benton cites five studies that have associated low
selenium intake with poorer mood. These studies seem to bear out
independent reports from CFS/ME patients who have successfully taken
selenium in place of antidepressants.
PROTOCOL. Dr. Pall recommends selenium
methionine as the best form of selenium. Unless there is a verified
selenium deficiency, low doses are recommended (50 mcg).
PROS AND CONS. Selenium is toxic at
high levels, and overdoses can cause numerous symptoms: hair loss,
tooth decay, brittle nails, nausea, vomiting, poor appetite, metallic
taste in the mouth, loss of feeling in the hands and feet, and
changes in skin pigmentation. (A garlic smell on the breath is an
indication of excessive selenium intake.) Selenium is often produced
as a yeast, which is problematic for people with Candida overgrowth
and mold allergies, so check the label carefully.
AVAILABILITY AND COST. Selenium is
widely available at health food stores and from online suppliers.
PureFormulas.com markets a bottle of yeast-free seleno-methionine
capsules (200 mcg) made by Douglas Labs for $26.40 (250 capsules).
Capsules can be divided for a lower dose.
FURTHER READING
Detailed information about selenium
from the Linus Pauling Institute.
http://lpi.oregonstate.edu/infocenter/minerals/selenium/
“Is Selenium Deficiency Behind Ebola,
AIDS and Other Deadly Infections?”
http://infonom.com.ar/task/html/selenium_deficiency_behind_tod.html
RESEARCH
Beck, Melinda A., Heather K. Nelson,
Qing Shi, Peter Van Dael, Eduardo J. Schiffrin, Stephanie Blum, Denis
Barclay, and Orville A. Levande. “Selenium deficiency increases
the pathology of an influenza virus infection.” FASEB J. 2001
Jun;15(8):1481-3. http://www.fasebj.org/content/15/8/1481.full.pdf
Beck MA, Levander OA, Handy J.
“Selenium deficiency and viral infection.” J Nutr. 2003 May;133(5
Suppl 1):1463S-7S. http://www.ncbi.nlm.nih.gov/pubmed/12730444
(Abstract)
Beck MA, Handy J, Levander OA. “Host
nutritional status: the neglected virulence factor.” Trends
Microbiol. 2004 Sep;12(9):417-23.
http://www.ncbi.nlm.nih.gov/pubmed/15337163 (Abstract)
Benton D. “Selenium intake, mood and
other aspects of psychological functioning.” Nutr Neurosci. 2002
Dec;5(6):363-74. http://www.ncbi.nlm.nih.gov/pubmed/12509066
(Abstract)
Kiremidjian-Schumacher L, Roy M, Wishe
HI, Cohen MW, Stotzky G. “Supplementation with selenium and human
immune cell functions. II. Effect on cytotoxic lymphocytes and
natural killer cells.” Biol Trace Elem Res. 1994
Apr-May;41(1-2):115-27. http://www.ncbi.nlm.nih.gov/pubmed/7946899
(Abstract)
COLLOIDAL SILVER
NOTE: Some of the colloidal minerals
distributed by multilevel marketers contain arsenic and lead, which
are toxic even in small doses. Caution should be exercised. Read
labels carefully!
DESCRIPTION. Colloidal silver solution
is composed of ultrafine, non-soluble particles of silver suspended
in a liquid medium such as water.
BACKGROUND. Colloidal silver has long
been used as a germicide. In the early twentieth century, colloidal
silver was used in place of antibiotics. Silver was used orally,
intravenously, and intramuscularly (as an injection), as a throat
gargle, and in eyedrops. Colloidal silver has been used to treat such
varied maladies as tonsillitis, cystitis, ringworm, and dysentery.
Over the course of this century, antibiotics have replaced silver as
drugs of choice, although silver nitrate is still used to prevent eye
infection in newborn infants.
USES IN CFS/ME. Some patients with
CFS/ME report that colloidal silver helps control recurring
infections, particularly in the mouth. Research has shown that
colloidal silver may be of benefit in treating oral infections,
sinusitis, sore throat, and canker sores.
PROTOCOL. Dosage varies, depending on
the concentration of the product used.
PROS AND CONS. It appears that low
doses of silver are fairly safe. However, argyria (grayish skin
discoloration) may develop when excessive doses of silver are
ingested. Because most studies evaluating the antimicrobial
properties of silver are not conducted on people, patients are
cautioned to exercise judgment before choosing silver over a
medication whose mode of action and recommended dosage are better
known.
AVAILABILITY AND COST. Colloidal silver
may be purchased from most health food stores and online
distributors. It costs $12 to $25 for a 4-oz bottle, depending on the
brand. Some companies make a spray colloidal silver for oral use.
Stick to reputable brands such as Source Naturals when purchasing.
RESEARCH
Damiani V, Di Carlo M, Grappasonni G,
Di Domenico R, Dominici P. “Efficacy of a new medical device based
on colloidal silver and carbossimetyl beta glucan in treatment of
upper airways disease in children.” Minerva Peditr. 2011
Oct;63(5):347-54. http://www.ncbi.nlm.nih.gov/pubmed/21946445
(Abstract)
Eby DM, Luckarift HR, Johnson GR.
“Hybrid antimicrobial enzyme and silver nanoparticle coatings for
medical instruments.” ACS Appl Mater Interfaces. 2009
Jul;1(7):1553-60. http://www.ncbi.nlm.nih.gov/pubmed/20355960
(Abstract)
Khan SS, Mukherjee A, Chandrasekaran N.
“Studies on interaction of colloidal silver nanoparticles (SNPs)
with five different bacterial species.” Colloids Surf B
Biointerfaces. 2011 Oct 1;87(1):129-38.
http://www.ncbi.nlm.nih.gov/pubmed/21640562 (Abstract)
Lansdown AB. “Silver in health care:
antimicrobial effects and safety in use.” Curr Probl Dermatol.
2006;33:17-34. http://www.ncbi.nlm.nih.gov/pubmed/16766878 (Abstract)
Monteiro DR, Gorup LF, Silva S, Negri
M, de Camargo ER, Oliveira R, Barbosa DB, Henriques M. “Silver
colloidal nanoparticles: antifungal effect against adhered cells and
biofilms of Candida albicans and Candida glabrata.” Biofouling.
2011 Aug;27(7):711-9. http://www.ncbi.nlm.nih.gov/pubmed/2175619 2
(Abstract)
ZINC
BACKGROUND. Zinc is a remarkably
versatile mineral. It plays an important role in the more than 70
enzyme systems that regulate most metabolic processes. It stimulates
digestion, aids in extracting stores of vitamin A from the liver,
helps maintain the mucous lining of the mouth, throat, stomach, and
intestines, is vital for the normal growth of hair, skin, and nails,
controls sexual maturation and fertility (zinc deficiency in men can
lead to infertility), and aids in the healing of wounds. Zinc is
necessary for the utilization of vitamin B6, a vitamin which is
crucial for nervous system function. It also helps improve immune
responses, although excessive intake of zinc (more than 50 mg) can
suppress immune function. (High doses of zinc also deplete copper.)
USES IN CFS/ME. Many CFS/ME patients
take zinc to help relieve sore throat and other viral symptoms. In a
2005 study published by Maes et al, 33 CFS/ME patients were examined
for serum zinc deficiencies. The researchers found that serum levels
of zinc were lower in CFS/ME patients than in controls. In addition,
low serum zinc status was related to signs of inflammation and
defects in early T cell activation pathways. Since zinc is a strong
antioxidant, the results of this study support the findings that CFS
is accompanied by increased oxidative stress. The researchers
concluded that “the results of these reports suggest that some
patients with CFS should be treated with specific antioxidants,
including zinc supplements.”
PROTOCOL. The recommended daily
allowance for zinc is 15 mg. The most bioavailable form is high-zinc
yeast. This is a form of yeast that has a high zinc content.
Unfortunately, it is not available in the U.S. (Lalmin Zn, a
high-zinc yeast supplement using Saccharomyces cerevisiae, is
produced in Denmark.) Zinc picolinate is well-absorbed, as is zinc
citrate. Zinc carnosine, a combination of zinc and the amino acid
carnosine, is reported to be well absorbed, as well as providing
support for the mucosal lining of the stomach and gut.
AVAILABILITY AND COST. Zinc is
available from health food stores, vitamin catalogs, and some
drugstores. As with other mineral supplements, it is not expensive. A
100-tablet bottle of zinc picolinate (25 mg) made by Country Life
costs less than $5 on Vitacost. Zinc should be taken with food to
avoid stomach upset. Zinc is found naturally in pumpkin seeds, liver,
egg yolks, and seafood (especially oysters).
FURTHER READING
Essential reading about zinc:
http://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/
Article discussing zinc bound in yeast:
http://www.nutraingredients.com/Research/Zinc-bound-in-yeast-promotes-superior-bioavailability-claims-study
Interesting study of high-zinc yeast in
rats: http://www.beta-glucan-info.com/pdf/Zinc_Bioavailability.pdf
RESEARCH
Maes, Michael, Ivana Mihaylova, Marcel
De Ruyter. “Lower serum zinc in Chronic Fatigue Syndrome (CFS):
Relationships to immune dysfunctions and relevance for the oxidative
stress status in CFS.” Journal of Affective Disorders. 2006
Feb;90(2-3):141-7.
http://cfids-cab.org/cfs-inform/Hypotheses/maes.etal05.pdf
Mahmood A , A J FitzGerald, T
Marchbank, E Ntatsaki, D Murray, S Ghosh, and R J Playford. “Zinc
carnosine, a health food supplement that stabilises small bowel
integrity and stimulates gut repair processes.” Gut. 2007 February;
56(2): 168–175.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1856764/
MONOLAURIN
DESCRIPTION. Monolaurin is a mono-ester
formed from glycerol and lauric acid.
BACKGROUND. Monolaurin is a fatty acid
found in human breast milk. Lauric acid, a closely related compound,
is found in coconuts. It has broad anti-microbial properties. In in
vitro studies, monolaurin was able to destroy several strains of
bacteria. H. Pylori is particularly susceptible – which may be why
coconut water is traditionally used as a treatment for dyspepsia in
tropical countries.
Other in vitro studies have shown that
monolaurin can kill viruses by destroying their lipid membrane.
(Laurates are commonly found in soap.) Some of the viruses
inactivated by these lipids are measles, herpes simplex, hepatitis C,
and cytomegalovirus (CMV). A number of fungi, yeasts, and protozoa
are also inactivated or killed by monolaurin. These include ringworm,
Candida albicans, and the protozoan parasite Giardia lamblia. Among
the many benefits of monolaurin is the fact that it can destroy
harmful bacteria without affecting beneficial intestinal flora.
USES IN CFS/ME. Monolaurin is an
antiviral, antifungal and anti-Candida treatment. It is used as a
safe alternative to pharmaceutical antivirals and antifungals, which
often have harmful side effects.
PROTOCOL. Physicians advise starting
with very low doses (¼ scoop of Lauricidin) to prevent Herxheimer,
or “die-off,” reactions. The makers of Lauricidin recommend
starting with one pellet a day (approx 30 mg) in order to avoid
Herxheimer reactions. Do not chew the pellets. (They taste like
soap.) Monolaurin capsules can be taken with greater frequency. Dr.
Teitelbaum recommends taking 9 capsules (300 mg) once a day on an
empty stomach for 1 week, followed by 6 capsules once a day for 20
days. He recommends taking lysine 1500 mg twice a day while on
monolaurin.
PROS AND CONS. Patients report that
monolaurin helps ward off colds and flus. One patient wrote that at
high doses (500 mg) it helped shingles. However, most patients report
that monolaurin will cause “die off” (Herxheimer-like) reactions.
Some fibromyalgia patients have reported an increase of pain on even
very low doses of Lauricidin. Other side effects include acid reflux
and a general “sick” feeling.
AVAILABILITY AND COST. Patients
recommend purchasing pure monolaurin (Lauricidin). An 8-oz container
of Lauricidin pellets can be purchased for around $30 on amazon.com.
Ecological Formulas markets two monolaurin combinations (one with
magnesium, and one with lysine) for roughly $13 for a 90-capsule
bottle (through PureFormulas.com online).
FURTHER READING
A Review of Monolaurin and Lauric Acid.
Shari Lieberman and Harry Preuss.
http://www.easihealth.co.za/wordpress/wp-content/uploads/downloads/2011/02/trials/Monolaurin.pdf
Patient thread on monolaurin:
http://www.prohealth.com/me-cfs/blog/boardDetail.cfm?id=428991
Manufacturer's information on
Lauricidin: http://lauricidin.com/tech_data/
RESEARCH
Preuss HG, Echard B, Enig M, Brook I,
Elliott TB. “Minimum inhibitory concentrations of herbal essential
oils and monolaurin for gram-positive and gram-negative bacteria.”
Mol Cell Biochem. 2005
Apr;272(1-2):29-34.http://www.ncbi.nlm.nih.gov/pubmed/16010969
(Abstract)
Zhang H, Wei H, Cui Y, Zhao G, Feng F.
“Antibacterial interactions of monolaurin with commonly used
antimicrobials and food components.” Journal of Food Science. 2009
Sep;74(7):M418-21. http://www.ncbi.nlm.nih.gov/pubmed/19895490
(Abstract)
MUSHROOM EXTRACTS
LEM (shiitake), Maitake, Cordyceps
Mushroom extracts have become
increasingly popular in recent years for their broad medicinal
properties. Research has shown that mushroom extracts have
anticancer, anti-diabetes, antibacterial, antifungal, and immune
stimulating properties. Although many varieties of mushroom extracts
are currently marketed for their medicinal effects, the two mushroom
extracts most widely used for CFS/ME are the shiitake (LEM) and
maitake.
In 2002 Dr. Peter R. Rothschild
conducted a 120-day study to observe therapeutic responses to RM-10
(a combination of 10 mushroom extracts) for the reduction of symptoms
in 33 CFS/ME patients. The researchers found that 60% of the
participants reported a reduction of symptoms by 40%, with 33%
totally asymptomatic by the end of the trial period. All participants
reported some degree of improvement. Dr. Rothschild stated, "We
had highly significant results with the multi-mushroom formula, brand
named RM-10 [TM]. For affected patients, there was a remarkable
percentage of remissions and a quite noticeable improvement in
symptomology overall.”
FURTHER READING
Good general information about mushroom
extracts. http://www.nammex.com/MedicinalMushroomBooks.html
Report on RM-10 mushroom extract
administered to CFS/ME patients.
http://findarticles.com/p/articles/mi_m0ISW/is_2002_August-Sept/ai_90794449/
Description of RM-10:
http://www.healthfoodemporium.com/garden-of-life/rm_10.html
SHIITAKE (LEM)
DESCRIPTION. LEM (Lentinus edodes
mycelium) is an extract made from the immature shiitake mushroom.
BACKGROUND. Although shiitake mushrooms
have long been used in the East for culinary purposes, they have
recently gained attention for their medicinal value. Numerous
studies, mostly conducted in Japan, have demonstrated that LEM
increases immune system function by stimulating production of
lymphocytes and macrophages, the immune system's defense against
bacteria, viruses, and tumor cells. LEM may also interfere with the
action of reverse transcriptase (an enzyme that aids in viral
replication) and block cell receptor sites of viruses. Owing to these
properties alone, LEM shows promise in treating cancer, diseases
related to immune system dysfunction, and viral infections.
USES IN CFS/ME. Most patients with
CFS/ME use LEM as a general treatment for lethargy, weakness, and
exhaustion, three primary symptoms of CFS/ME. A number have reported
improvement in stamina, energy, and strength, decreased diarrhea, and
increased white blood cell count after taking LEM.
PROTOCOL. Shiitake extract is usually
sold in liquid or tablet form. The suggested dose is 40 drops of
liquid, taken twice daily. Up to eight tablets may be taken a day. As
with other medications, patients with CFS/ME should start with
smaller doses and gradually increase to the full dose.
PROS AND CONS. LEM is one of the few
botanical products that affects CFS/ME as a whole. A number of
patients report general improvement and lessening of some of their
worst symptoms. LEM may provoke a severe allergic reaction in
patients with allergies to mushrooms, molds, and other fungi. Those
with recurring yeast infections, athlete's foot, or thrush should
probably delay trying LEM until these problems are resolved.
AVAILABILITY AND COST. Shiitake
extracts are widely available in health food stores and through
internet suppliers. Vitacost sells a 2-oz bottle of pure shiitake
extract made by Planetary Herbals for $12. Source Naturals markets a
bottle of 40 tablets for about $15.
FURTHER READING
“Mushroom Extracts: Exciting News for
Good Health.” Neenyah Ostrom's article on LEM and CFS/ME.
http://www.immunesupport.com/news/93fal003txt.htm
Sloan Kettering's very thorough review
of shiitake extract:
http://www.mskcc.org/cancer-care/herb/shiitake-mushroom
MAITAKE EXTRACT
BACKGROUND. The maitake (Grifola
frondosa) is a large mushroom that resembles Elizabethan neck
ruffles. It grows in clusters at the base of oak trees in Japan and
North America. Maitake mushrooms are used in Asian cuisine, and
because of their size (up to 50 pounds) are known as the “king”
of mushrooms. Maitake mushrooms are rich in nutrients, including B
vitamins, magnesium, potassium, and calcium.
In the late 1980s an active constituent
in maitake, a beta-glucan compound, was found to enhance immune
activity. Studies have shown that whole maitake also has the ability
to regulate blood sugar and blood pressure, as well as insulin,
lipids and cholesterol. Recent research has shown that maitake also
has antioxidant and anticancer properties.
USES IN CFS/ME. People with CFS/ME use
maitake extract as an immune system stimulator, particularly of NK
(natural killer) cells. (Low NK cell activity has been well
documented among CFS/ME patients.)
PROTOCOL: Maitake capsules should be
taken on an empty stomach. The standard dose for 300 mg capsules is
one to three capsules taken twice daily.
AVAILABILITY AND COST. Iherb.com
markets a full spectrum maitake extract made by Mushroom Science for
$24 for a bottle of 90 capsules.
FURTHER READING
Extensive list of many maitake
extracts: http://www.vitasprings.com/maitake.html
RESEARCH
Yeh JY, Hsieh LH, Wu KT, Tsai CF.
“Antioxidant properties and antioxidant compounds of various
extracts from the edible basidiomycete Grifola frondosa (Maitake).”
Molecules. 2011 Apr 15;16(4):3197-211.
http://www.ncbi.nlm.nih.gov/pubmed/21499220 (Abstract)
CORDYCEPS
BACKGROUND. Cordyceps is a fungus that
grows on the larvae of the caterpillar, Hepialus armoricanus
Oberthuer, found in China and Tibet. (Traditionally, the product
contains both the fungus and its caterpillar host.) Cordyceps has
been used in China to treat a wide range of conditions including
fatigue, sexual dysfunction, and coughs. It is an adaptogen and
immune stimulant.
Cordyceps has also been found to
increase red blood cells, and to stimulate the production of
testosterone (which is perhaps why it is used for sexual
dysfunction). Research conducted primarily in China has also found
cordyceps beneficial in increasing cellular oxygen absorption,
protecting the liver, enhancing the immune system (by increasing
natural killer cell activity), and improving shortness of breath and
fatigue in patients suffering from chronic heart failure.
PROS AND CONS. CFS/ME patients have
reported that cordyceps gives them a boost. It also reduces “air
hunger” and increases stamina.
MORE INFORMATION
Sloan-Kettering's page on cordyceps:
http://www.mskcc.org/cancer-care/herb/cordyceps
“Dr Oz: Chronic Fatigue Syndrome,
Cordyceps & D5 Ribose Sweetener.”
http://www.drozfans.com/dr-ozs-advice/dr-oz-chronic-fatigue-syndrome-cordyceps-d5-ribose-sweetener/
“Cordyceps Chinensis.” Everything
you could possibly want to know about Cordyceps.
http://mdidea.com/products/herbextract/cordyceps/data06.html
“Mushroom remedy 'makes you fit' A
Chinese mushroom improves the fitness of middle-aged and elderly
people, research suggests.”
http://news.bbc.co.uk/2/hi/health/3638543.stm
NAC (N-acetylcysteine )
DESCRIPTION. N-acetylcysteine (NAC) is
a derivative of cysteine, an amino acid.
BACKGROUND. NAC acts as an antioxidant,
and is a precursor to glutathione. Clinically, it has been used to
treat acetaminophen (paracetamol in Britain) overdose. It has also
been used to reduce the viscosity of mucus in pulmonary conditions
such as pneumonia, bronchitis, emphysema and tuberculosis. NAC is
commonly used in patients with renal impairment. It is being explored
as a possible treatment for both schizophrenia and bipolar disorder.
NAC's ability to counteract glutamate hyperactivity in the brain also
make it a good candidate for treating obsessive-compulsive disorder.
NAC is also a chelating agent for mercury, and can be used for
mercury toxicity.
USES IN CFS/ME. NAC can inhibit muscle
fatigue after exercise. Reid et al, in a 1994 study, showed that
pre-treatment with NAC improved performance of muscles during
exercise. They suggested that “oxidative stress plays a causal role
in the fatigue process” and that NAC “may be useful clinically.”
Research on NAC has shown that it is
effective in reducing depletion of glutathione. People with CFS/ME
are demonstrably low on glutathione. However, direct supplementation
with glutathione is problematic because glutathione is rapidly broken
down in the gut. Taking glutathione precursors, such as NAC, allows
the body to synthesize glutathione on its own.
PROTOCOL. Martin Pall has speculated
that because NAC rapidly releases cysteine, it may cause neural
excitotoxicity. He recommends using NAC at low doses.
PROS AND CONS. NAC is generally well
tolerated. However, in those who are sensitive to stimulants, it can
cause insomnia and headaches. NAC is contraindicated for people with
kidney stones.
AVAILABILITY AND COST. NAC is available
at health food stores and from online suppliers. It is inexpensive. A
60-capsule bottle of Carlson NAC (500 mg) costs about $8 (through
Vitacost).
FURTHER READING
Kelly GS. “Clinical applications of
N-acetylcysteine.” Altern Med Rev. 1998 Apr;3(2):114-27.
http://www.ncbi.nlm.nih.gov/pubmed/9577247 (Abstract)
Kerksicki, Chad and Darryn Willoughby.
“The Antioxidant Role of Glutathione and N-Acetyl-Cysteine
Supplements and Exercise-Induced Oxidative Stress.” Journal of the
International Society of Sports Nutrition 2005, 2:38-44.
http://www.jissn.com/content/2/2/38 (This is a review of research
into glutathione and NAC in exercise-induced muscle fatigue.)
Reid MB, Stokić DS, Koch SM, Khawli
FA, Leis AA. “N-acetylcysteine inhibits muscle fatigue in humans.”
J. Clin. Invest. 1994 Dec;94(6):2468-74.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC330079/
NADH (ENADA)
DESCRIPTION. NADH is the reduced form
of nicotinamide adenine dinucleotide (NAD), also called ubiquinone
reductase. It is found in all living cells.
BACKGROUND. NADH was first discovered
in the 1930s by an American scientist who observed that NADH played
an essential role in the energy production of cells. It was not until
more than 60 years had passed, however, that Dr. Georg Birkmayer, a
biomedical researcher from Vienna, Austria, developed a stable oral
form of NADH. Since then, a growing body of research has documented
that NADH not only acts as a driving force in the production of
cellular energy, but also is a potent antioxidant, is a key component
of DNA repair and cellular regeneration, and stimulates the
production of the neurotransmitters dopamine, noradrenaline, and
serotonin. Ongoing research in the United States and abroad may help
define the role of NADH in treating such degenerative neurological
conditions as Alzheimer's disease and Parkinson's disease.
USES IN CFS/ME. NADH may be of great
benefit in treating CFS/ME. When NAD is oxidized (NAD+) in the cell's
mitochondria, energy is released. This energy is preserved in the
form of adenosine triphosphate (ATP), a substance required by all
energy-absorbing processes in the body.
Researchers have proposed that NADH may
help correct the metabolic defect in CFS/ME that inhibits the
production of ATP. Because low ATP production means less energy,
clinicians believe NADH may alleviate CFS/ME-related exhaustion and
may also improve cognitive function. The three neurotransmitters
stimulated by NADH serve critical functions in the central nervous
system: dopamine is important for short-term memory; noradrenaline
contributes to alertness; and serotonin has a pronounced effect on
mood and regulates sleep.
In 1999 Forsyth et al conducted a trial
of NADH (as ENADA, a stable, bioavailable form of NADH) on 26 CFS/ME
patients. Thirty-six percent of the CFS/ME patients taking NADH
responded favorably, as opposed to 8% on placebo. No adverse effects
were noted. In a longer term, open-label phase of the study,
Birkmayer reports that “72% of the patients continued to report an
improvement of their symptoms after six months of taking 10 mg ENADA
daily. After approximately one year of taking ENADA the research
doctors are reporting up to 81 percent of the patients continue to
benefit from ENADA. These findings suggest that long-term ENADA
therapy can lead to continued improvements, especially in energy and
mental/ cognitive status.”
While these results looked promising,
there has been little follow-up on the initial trial with ENADA. Dr.
Myhill lists ENADA as one of the CFS treatments “not worth trying”
(along with graded exercise, CBT, and cold baths). As Dr. Myhill puts
it, “It is the old story - single interventions are highly unlikely
to result in worthwhile improvements because CFS is a complex problem
- it is the combined approach that gets the results.”
PROTOCOL. Although Forsyth et al used
10 mg a day, the suggested starting dosage of NADH is 5 mg/day,
(though some people report taking as much as 15 mg). The dosage is
dependent on weight. Heavier people will need a higher dose to see an
effect. NADH should be taken first thing in the morning on an empty
stomach (about 20 minutes before your first meal).
Dr. Lapp recommends NADH in combination
with acetyl-L-carnitine for his patients with severe “brain fog.”
He observes that it can take three to six months to produce a
response. Dr. Lapp recommends a dosage of 10 to 20 mg per day.
Patients note that sublingual NADH
tablets are more effective than oral forms.
PROS AND CONS. Some patients report
that NADH is moderately to mildly helpful, "making bad days
somewhat less bad and good days somewhat better" (CFIDS
Chronicle, Summer 1996). The majority of patients who take NADH note
that it helps with cognitive symptoms more than fatigue.
AVAILABILITY AND COST. NADH is
classified as a supplement and therefore does not require a
prescription. Source Naturals sells a 60-tablet bottle of reduced
Enada-NADH (5 mg) for $40 through Vitacost. PureFormulas.com sells a
30-tablet (10 mg) pack made by Physiologics for $38.50. Vitacost's
own brand of sublingual NADH (10 mg) costs $20 for a packet of 30
tablets. A 30-tablet box of 5 mg ENADA costs $22.25 through the
official ENADA website.
MORE INFORMATION
The official ENADA site, containing
product and brand information: http://www.enada.com/
FURTHER READING
Dr. Birkmayer's review of ENADA,
including summaries of trials, and recommended dosage.
http://www.encognitive.com/node/5059
Patient thread on NADH. Includes
references to several studies, responses and dosage.
http://forums.phoenixrising.me/archive/index.php/t-5096.html
RESEARCH
Forsyth LM, Preuss HG, MacDowell AL,
Chiazze L Jr, Birkmayer GD, Bellanti JA. “Therapeutic effects of
oral NADH on the symptoms of patients with chronic fatigue syndrome.”
Ann Allergy Asthma Immunol. 1999 Feb;82(2):185-91.
http://www.ncbi.nlm.nih.gov/pubmed/10071523 (Abstract)
PROBIOTICS
DESCRIPTION. Probiotic bacteria,
primarily Lactobacillus acidophilus and Bifidobacterium bifidus, aid
in many digestive processes and help maintain balance in the
intestines.
BACKGROUND. Digestive tract bacteria
(intestinal flora) have evolved within humans to aid in completing
the breakdown and absorption of many foods. Without the thousands of
"friendly" bacteria that inhabit the intestines,
malnutrition would develop no matter how much food was eaten. These
bacteria not only aid in digestion, but are responsible for
manufacturing many nutrients that are essential to survival, such as
the B vitamin complex. Some bacteria, such as bifidus, live in the
large intestine; others, such as acidophilus, live in the small
intestine.
As long as the intestinal flora are
working well, a minimum of digestive problems can be expected.
However, once the function of friendly flora is upset, harmful
bacteria can proliferate, causing bloating, stomach upset, poor
digestion, constipation, gas, and malabsorption problems. The most
common sources of flora upset are recurrent use of antibiotics, oral
contraceptives, aspirin, corticosteroids, poor diet, stress, and
Candida infections. In these cases, it may be necessary to use a
probiotic supplement to reestablish a healthy balance of intestinal
flora.
A number of studies have shown that
intestinal flora are effective for treating intestinal problems. In a
review of probiotic treatments for diarrhea, Guandalini found that
several strains of probiotics, including Lactobacillus GG,
Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium ssp,
Streptococcus ssp, and the yeast Saccharomyces boulardii, were
effective in combating diarrhea due to antibiotics, C. difficile and
viruses. Two strains, Lactobacillus GG and Saccharomyces boulardii
were particularly effective. Researchers have also found probiotics
helpful in treating irritable bowel syndrome and inflammatory bowel
disease, suggesting a possible link between these two conditions.
USES IN CFS/ME. Patients with
gastrointestinal symptoms or recurring yeast infections, or who
regularly take antibiotics, nonsteroidal anti-inflammatory drugs
(NSAIDs), oral contraceptives, or cortisone are advised to use a
probiotic supplement. Products that contain bifidus seem to help with
leaky gut.
Generally, people with CFS/ME appear to
suffer from a deficiency in friendly flora. According to a study by
Butt et al in Australia, the colonic bacterial population in CFS/ME
patients is deficient in Bifidobacterium and E. Coli. In contrast,
the lactic acid bacteria, Enterococcus, is significantly higher –
28.7% of the total aerobic flora in CFS/ME patients – than in the
healthy subjects (3-5%).
Remarkably, the researchers found that
specific changes in gastrointestinal flora were associated with
CFS/ME symptoms. A high enterococcal count positively correlated with
neurological and cognitive functions: nervousness, memory loss,
forgetfulness, confusion, and “mind going blank.” Similarly a
high aerobe/anaerobe ratio significantly correlated with poor colonic
functions, poor digestion, and malabsorption of the gastrointestinal
tract. The implications of this study are that the composition of
bacterial flora has a significant impact on both digestion and the
nervous system, and that in people with CFS/ME the two are linked.
In an interesting paper published in
2003, Logan et al proposed that probiotics might serve to enhance
immune function in people with CFS/ME. The authors pointed out that
people with CFS/ME have marked alterations in intestinal flora as
well as oxidative stress. They state that “lactic acid bacteria
(LAB) have the potential to influence the immune system in CFS
patients by supporting . . . cellular immunity and may decrease
allergies. In addition LAB are strong antioxidants, may improve EFA
status, can enhance absorption of micronutrients by protecting the
intestinal epithelial barrier.” The authors suggested that lactic
acid bacteria might have a therapeutic role in the treatment of
CFS/ME.
Probiotics may be useful for other
reasons as well. Due to disruptions in the balance of
neurotransmitters which are responsible for maintaining gut motility,
people with CFS/ME often have motility problems. When motility is
slowed, the bacteria from the large intestine can travel upward,
where they colonize the small intestines. This leads to a condition
known as SIBO (small intestinal bacterial overgrowth). Once
established in the small intestines, the bacteria interfere with the
breakdown of fats and carbohydrates. According to Dr. Cheney, a
significant percent of the CFS/ME population suffers from SIBO. The
standard treatment for SIBO is antibiotics, which, ironically, are
also the primary cause of SIBO. Many gastroenterologists recommend
treatment with probiotics, in particular Lactobacillus GG for SIBO in
order to restore beneficial flora after antibiotic treatment.
PROTOCOL. Probiotics are sold in
different forms. Each should be taken according to directions.
Enteric-coated tablets, for example, need to be taken only once a day
and can be taken with food, because the enteric coating protects the
bacteria from being destroyed by stomach acids. Patients with altered
intestinal flora as a result of taking antibiotics need to take a
probiotic supplement for a least two weeks after finishing the
treatment to repopulate the intestines. Single-strain varieties are
reported to be more effective than multiple strains.
PROS. Most patients with CFS/ME who
regularly take probiotics report easing of gastrointestinal symptoms
(especially gas and bloating) and overall improvement in digestion.
One of the main advantages of probiotics is that they can be taken
daily for months, or even years, without causing any adverse effects
or loss of benefits. They rarely cause side effects and are safe for
children.
CONS. Probiotics are not without risk.
There is some concern in the medical community about the safety of
probiotic supplements (which is why it is important to purchase
reputable brands). Probiotics should be used to caution in
individuals with an abnormal gastrointestinal mucosal barrier (leaky
gut), due to the risk of the bacteria penetrating the intestinal
wall. Some people with CFS/ME who have been diagnosed with SIBO
sometimes report experiencing flares and “brain fog” after taking
probiotics, especially if the initial infection has not been
eradicated.
AVAILABILITY AND COST. Many good brands
of probiotic supplements can be purchased from health food stores and
vitamin catalogs. Vitacost sells a package of 30 capsules of
Culturelle (Acidophilus GG) for $15. Vitacost sells a 50-capsule
bottle of Saccharomyces boulardii made by Allergy Research Group for
about the same price.
Acidophilus can also be found in foods
such as yogurt and kefir, although these are more effective at
maintaining intestinal balance once it has been corrected. Foods such
as miso and tofu can enhance bifidus growth, as can a number of
vegetables that provide intestinal substrate (fructo-oligosaccharides
(FOS) and inulin) in which the bacteria can flourish.
FURTHER READING
CFS/ME forum discussing some of the
risks of probiotics.
http://forums.phoenixrising.me/archive/index.php/t-8976.html
“Intestinal Flora.” Very good
website with research and specific information on intestinal flora.
http://www.probiotic.org/intestinal-flora.htm
"Probiotics in Clinical Practice:
An Update." Good general information about the clinical use of
probiotics: http://www.ecologyhealthcenter.net/node/839
“An Emerging Trend of High Dose
Probiotic Use in Clinical Practice- A Brief Survey.” October 2011.
http://www.pointinstitute.org/resources/Point+Inst.+High+Dose+Probiotics+Oct.+2011.pdf
Hibberd, Patricia L., Lisa E. Davidson.
“Safety of probiotics.”
http://chemistry-today.teknoscienze.com/pdf/HIBBERD%20AGRO4-08.pdf
Taylor C Wallace, Francisco Guarner, Karen Madsen, Michael D Cabana,
Glenn Gibson, Eric Hentges, Mary Ellen Sanders. “Human gut
microbiota and its relationship to health and disease.” Nutrition
Reviews, Volume 69, Issue 7, pages 392–403, July 2011.
http://onlinelibrary.wiley.com/doi/10.1111/j.1753-4887.2011.00402.x/full
RESEARCH
Butt H. L., Dunstan R. H., McGregor N.
R., Roberts T. K. “Bacterial colonosis in patients with persistent
fatigue.” Proceedings of the AHMF International Clinical and
Scientific Conference; 2001 Dec 1–2; Sydney, Australia.
http://www.ahmf.org/01access/01butt.html
Gibson GR, Beatty ER, Wang X, Cummings
JH. “Selective stimulation of bifidobacteria in the human colon by
oligofructose and inulin.” Gastroenterology. 1995
Apr;108(4):975-82. http://www.ncbi.nlm.nih.gov/pubmed/7698613
(Abstract)
Guandalini S. “Probiotics for
prevention and treatment of diarrhea.” J Clin Gastroenterol. 2011
Nov;45 Suppl:S149-53. http://www.ncbi.nlm.nih.gov/pubmed/21992955
(Abstract)
Logan, Alan C., A. Venket Rao, Dinaz
Irani. “Chronic fatigue syndrome: lactic acid bacteria may be of
therapeutic value.” Medical Hypotheses (2003) 60(6), 915–92.
http://www.cfids-cab.org/cfs-inform/Hypotheses/logan.etal03.pdf
Ku WH, Lau DCY, Huen KF. “Probiotics
Provoked D-lactic Acidosis in Short Bowel Syndrome: Case Report and
Literature Review.” HK J Paediatr (New Series) 2006;11:246-254.
http://hkjpaed.org/details.asp?id=577&show=1234
PIRACETAM (Nootropil, Lucetam)
DESCRIPTION. Piracetam is a derivative
of GABA (gamma-aminobutyricacid), the brain's primary neuroinhibitory
amino acid.
BACKGROUND. Piracetam is a nootropic,
or “smart drug.” It has been used for a wide range of
neurological impairments, including seizures, dementia, focal lesions
in the brain, and concussions. There is also evidence that it can
enhance cognitive performance among the healthy. In a study by Dimond
and Brouwers, administration of piracetam for 14 days improved verbal
memory in a group of college students. Piracetam appears to work not
just by acting on cholinergic receptors, but by decreasing the
viscosity of blood, which, in turn, enhances the delivery of oxygen
to the brain.
USES IN CFS/ME. Piracetam is used more
widely in Europe than in the U.S., where the FDA has determined that
because it is not a vitamin, mineral, amino acid, herb, botanical, or
other dietary substance, it is therefore not a supplement. Nor is it
approved as a drug, which puts piracetam in the odd category (along
with galantamine) of having no clinical status. As a consequence,
there has not been a great deal of research done on piracetam for
CFS/ME.
There is, however, a small but
significant body of research that seems to indicate that piracetam
would be appropriate for the treatment of cognitive impairment in
CFS/ME patients. In one such study, researchers in Brazil found that
piracetam protected the hippocampus (the part of the brain associated
with the formation of new memories) during alcohol withdrawal. It has
been widely noted that CFS/ME patients have difficulty forming new
memories, which is crucial to learning.
Of even greater interest to CFS/ME
patients is a study conducted in 2002 by Gabryel et al, in which
piracetam was shown to protect the brain against hypoxic injury. Not
only did the drug prevent cell damage, it stimulated mitochondrial
function, increasing intracellular ATP. Given the growing body of
evidence that people with CFS/ME not only experience lowered
oxygenation of brain tissues, but loss of brain matter, this finding
could point the way to effective treatment.
PROTOCOL. Dr. Teitelbaum recommends
1200 mg twice a day for 2 weeks, and then 2400 mg twice a day for 2
weeks to treat brain fog. He recommends that piracetam be taken with
hydergine, a dopamine-stimulating nootropic. CFS/ME patients may wish
to start with the recommended dosage, which is 400-800 mg a day.
Those with insomnia and sensitivities to stimulants should begin at
an even lower dose – 50 mg.
PROS AND CONS. There are very few
reported side effects, but large doses can cause headache,
restlessness and insomnia. Patients report good effects at very low
doses (50 mg a day). Effects are similar to caffeine – a feeling of
alertness, greater focus, and “being awake.”
AVAILABILITY AND COST. Piracetam is
available online. Amazon.com sells 60-capsule bottle of piracetam
(800 mg) for $23.42. This amounts to roughly $1 for 2 grams. If the
product works for you, bulk purchase is much less expensive.
FURTHER READING
“Living With Chronic Fatigue
Syndrome” blog entry on piracetam.
http://livingwithchronicfatiguesyndrome.wordpress.com/2011/04/04/piracetam-for-mecfs/
Patient experiences with piracetam
http://forums.phoenixrising.me/archive/index.php/t-9408.html
RESEARCH
Brandão F., M.M. Paula-Barbosa, A.
Cadete-Leite. “Piracetam impedes hippocampal neuronal loss during
withdrawal after chronic alcohol intake.” Alcohol, Volume 12, Issue
3, May–June 1995, 279–288.
http://www.ncbi.nlm.nih.gov/pubmed/7639963 (Abstract)
Dimond SJ, Brouwers EM. "Increase
in the power of human memory in normal man through the use of drugs."
Psychopharmacology. 1976 49 (3): 307–9.
https://www.ncbi.nlm.nih.gov/pubmed/826948 (Abstract)
Gabryel B, Adamek M, Pudełko A,
Małecki A, Trzeciak HI. "Piracetam and vinpocetine exert
cytoprotective activity and prevent apoptosis of astrocytes in vitro
in hypoxia and reoxygenation". Neurotoxicology 2002, 23 (1):
19–31. https://www.ncbi.nlm.nih.gov/pubmed/12164545
Waegemans T, Wilsher CR, Danniau A,
Ferris SH, Kurz A, Winblad B. "Clinical efficacy of piracetam in
cognitive impairment: a meta-analysis." Dementia and geriatric
cognitive disorders. (2002)13 (4): 217–24.
https://www.ncbi.nlm.nih.gov/pubmed/12006732 (Abstract)
Winblad, B. "Piracetam: a review
of pharmacological properties and clinical uses." CNS Drug
Reviews (2005)11 (2): 169–82. www.ncbi.nlm.nih.gov/pubmed/16007238
(Abstract)
ROYAL JELLY
DESCRIPTION. Royal jelly is a thick,
milky substance secreted by young nurse honeybees to nourish the
young larvae in a colony, especially the queen larvae.
BACKGROUND. Royal jelly is one of
nature's most potent foods. It is rich in B vitamins (especially
pantothenic acid), biotin, folic acid, and inositol. It also contains
vitamins A, C, D, and E, seven minerals, 18 amino acids, fatty acids,
enzymes and hormones, and is the only natural source of
acetylcholine, the neurotransmitter that aids in memory.
Health-enhancing properties attributed to royal jelly range from
reducing cholesterol levels to healing skin disorders.
In 2011 a group of researchers found
that royal jelly exerted a protective effect on the liver and kidneys
of rats which had been given cisplatin, a cytotoxic agent used for
chemotherapy. The beneficial effects of royal jelly were attributed
to a reduction of oxidative stress and apoptosis (cell death).
Oxidative stress and increased cell apoptosis are commonly found in
CFS/ME patients. Further research has indicated that royal jelly may
be effective in reducing inflammation.
USES IN CFS/ME. Although CFS/ME doctors
do not routinely prescribe royal jelly, it has been used by CFS/ME
patients for decades. Royal jelly is a natural source of
acetylcholine, a neurotransmitter some researchers believe is
deficient in CFS/ME, which may be why it is effective in reducing
muscle weakness some patients. Its anti-inflammatory properties make
it well suited to mitigating pain. Royal jelly also provides an
easily tolerated form of B vitamins. Many patients with CFS/ME who
need B vitamins cannot tolerate yeast-based vitamin B products.
Steve Wilkinson, author of Chronic
Fatigue Syndrome: A Natural Healing Guide, claims that royal jelly
can help provide increased stamina and energy, greater mental
alertness, and relief from muscle problems. He states that in his
case the improvement in muscle pain was "dramatic" after
just a few weeks of taking royal jelly.
In a pilot study conducted in England
with ME patients, approximately 40 of the participants noted an
improvement in energy and stamina. Twelve patients reported a
decrease in muscle and joint pain. Another forty noted a decrease in
depression. Eighty of the 109 participants said that royal jelly was
beneficial.
PROTOCOL. Y&S Eco Bee Farms
recommends taking ¼ teaspoon of royal jelly once or twice daily on
an empty stomach, followed by a small amount of chilled water. Royal
jelly can be taken for months. Some patients need two to three months
before its benefits can be felt. Pure royal jelly (not mixed with
honey) requires refrigeration because it spoils easily. Royal jelly
should not be mixed into or consumed with anything hot.
PROS. Royal jelly is a safe,
inexpensive supplement that provides some necessary nutrients, as
well as acting as immune modulator. As the only natural source of
acetylcholine (ACh), it is one of the safer treatments for the ACh
deficiency posited in CFS/ME patients.
CONS. Allergic reactions to royal jelly
are not unknown. Patients with a history of pollen allergies should
be cautious in using royal jelly. Patients with allergies should be
sure the royal jelly has not been mixed with other products (ginseng,
bee pollen, honey) to avoid possible allergic reactions to these
additives.
AVAILABILITY AND COST. Pure royal jelly
is available as a thick liquid or in capsules. Ebeehoney.com sells a
2 oz jar of pure royal jelly for $13. (Shipped with an ice pack.)
Because royal jelly loses its potency when improperly handled or
processed, it may be worthwhile to buy the purest form available. The
refrigerated section of health food stores usually contains the most
potent royal jelly products.
FURTHER READING
A pilot study of Irena Royal Jelly
conducted on 109 ME patients:
http://www.irenesteinrj.com/files/ME%20REPORT.pdf
Suppliers of Y&S pure royal jelly:
http://www.yahwehsaliveandwell.com/ysroyaljelly.html
Online site for purchasing pure royal
jelly: http://www.ebeehoney.com/royaljelly.html
RESEARCH
Harada S, Moriyama T, Tanaka A. [Two
cases of royal jelly allergy provoked the symptoms at the time of
their first intake]. Arerugi. 2011 Jun;60(6):708-13.
http://www.ncbi.nlm.nih.gov/pubmed/21709438 (Abstract)
Karadeniz A, Simsek N, Karakus E,
Yildirim S, Kara A, Can I, Kisa F, Emre H, Turkeli M. “Royal jelly
modulates oxidative stress and apoptosis in liver and kidneys of rats
treated with cisplatin.” Oxid Med Cell Longev. 2011;2011:981793.
http://www.ncbi.nlm.nih.gov/pubmed/21904651 (Abstract)
Kohno K, Okamoto I, Sano O, Arai N,
Iwaki K, Ikeda M, Kurimoto M. “Royal jelly inhibits the production
of proinflammatory cytokines by activated macrophages.” Biosci
Biotechnol Biochem. 2004 Jan;68(1):138-45.
http://www.ncbi.nlm.nih.gov/pubmed/14745176 (Abstract)
Yanagita M, Kojima Y, Mori K, Yamada S,
Murakami S. “Osteoinductive and anti-inflammatory effect of royal
jelly on periodontal ligament cells.” Biomedical Research.
2011;32(4):285-91. http://www.ncbi.nlm.nih.gov/pubmed/21878736
(Abstract)
SAMBUCOL
DESCRIPTION. Sambucol is an extract
made from the fruit of the European black elder tree (Sambucus nigra
L), a member of the Adoxaceae family.
BACKGROUND. Black elderberry berries
have long been used in Europe to make jams, jellies, soft drinks, and
aromatic wines. In addition to its pleasant taste, elderberry is
valued as a rich source of B vitamins and bioflavonoids, as well as
minerals such as calcium and phosphorus. Medicinal use of black
elderberry has been documented as early as the fifth century BC, when
the ancient Greeks described it as a remedy for colds, flu, and upper
respiratory tract infections. In the mid-1980s, researchers found
that two of the active ingredients in elderberry inhibited the
replication of the influenza virus by preventing the virus from
entering cells.
In a continuation of that research, in
1992 a group of Israeli scientists and physicians formulated a black
elderberry syrup that acted successfully against the influenza virus
in a laboratory setting. Soon afterward, a double-blind,
placebo-controlled study was conducted in patients with influenza in
southern Israel. The results of that study indicated that black
elderberry effectively reduced the duration and severity of influenza
infections. Flu symptoms (fever, cough, and muscle pain)
significantly improved in 20% of the patients within 24 hours,
compared with 8% of the control group. Within three days, more than
90% of the patients were symptom free, compared with six or more days
for the control group.
In 2011 a group of researchers from the
Institute of Medical Biology in Germany found that standardized
extract of elderberry inhibited viral replication of influenza A and
influenza B. They also found that the extract possessed antimicrobial
activity against both gram-positive and gram-negative bacteria in
liquid cultures. Another group of researchers in Austria found that a
fraction of elderberry produced broad anti-inflammatory effects and
supported “the traditional use of extracts and preparations of
Sambucus ebulus L., rich in ursolic acid, for the treatment of
chronically inflammatory processes.” Results of further studies
have also shown that elderberry extract can act against herpes virus
and Epstein-Barr virus.
USES IN CFS/ME. The fact that Sambucol
has such a wide range of antiviral effects may make it particularly
useful for the many patients with CFS/ME who have frequent colds and
flu. It may also be valuable for those who demonstrate reactivation
of Epstein-Barr virus and other latent viruses, the effects of which
can lead to many of the symptoms typical of CFS/ME. Many CFS/ME
patients taking Sambucol have noted overall improvement (Mass CFS/ME
Update, Fall 1995).
PROTOCOL. The recommended dosage of
Sambucol syrup is 4 tablespoons daily in adults and 1 tablespoon
daily in children younger than 12 years. Patients with CFS/ME should
probably start with a smaller dose to check for tolerance. Sambucol
should be taken on a full stomach. Dairy products should be avoided
for 30 minutes before and after to avoid stomach upset. The
manufacturers recommend refrigeration after opening.
PROS. Sambucol is an all-natural
product, which is an advantage for patients with chemical and drug
sensitivities. There are no reported side effects or
contraindications associated with its use. Those who have tried it
claim that it hastens recovery from flu and colds, and lessens
general malaise. Sambucol is also safe for children, which is good
news for parents of children with CFS/ME, because so few effective
pediatric medications are currently available.
CONS. Some patients report allergy-type
reactions (congestion, headache, dizziness) to elderberry. As fresh
elderberry leaves and bark are poisonous (but not the berries),
always purchase processed elderberry extracts with high flavonoid
content from a reputable company. Do not make your own tea.
AVAILABILITY AND COST. Sambucol is
currently marketed in the United States, Europe, Israel, and South
Africa through health food stores and drugstores. The liquid extract
contains glucose and honey for sweetening and raspberry extract to
enhance flavor. If a glucose-free product is desired, Sambucol is
available in lozenge form and as a liquid sweetened with sorbitol.
Vitacost sells 4 oz bottle of liquid Sambucol for between $10 and
$15. Lozenges in packs of thirty cost about $7. Prices at retail
outlets are generally considerably higher.
FURTHER READING
Complete information about the
composition, effects and clinical research of elderberry extract.
http://www.drugs.com/npp/elderberry.html
RESEARCH
Konlee, M. “A new triple combination
therapy.” Posit Health News. 1998 Fall;(No 17):12-4.
http://www.ncbi.nlm.nih.gov/pubmed/11366542 (Abstract)
Krawitz C, Mraheil MA, Stein M,
Imirzalioglu C, Domann E, Plechka S, Hain T. “Inhibitory activity
of a standardized elderberry liquid extract against
clinically-relevant human respiratory bacterial pathogens and
influenza A and B viruses.” BMC Complement Altern Med. 2011 Feb 25;
11:16. http://www.ncbi.nlm.nih.gov/pubmed/21352539 (Abstract)
Schwaiger S, Zeller I, Pölzelbauer P,
Frotschnig S, Laufer G, Messner B, Pieri V, Stuppner H, Bernhard D.
“Identification and pharmacological characterization of the
anti-inflammatory principal of the leaves of dwarf elder (Sambucus
ebulus L.).” J Ethnopharmacol. 2011 Jan 27;133(2):704-9.
http://www.ncbi.nlm.nih.gov/pubmed/21040770 (Abstract)
Zakay-Rones Z, E Thom, T Wollan, and L
Wadstein. “Randomized Study of the Efficacy of and Safety of Oral
Elderberry Extract in the Treatment of Influenza A and B Virus
Infections.” The Journal of International Medical Research. 2004;
32: 132-140. http://www.jimronline.net/content/full/2004/47/0445.pdf
SAMe
DESCRIPTION. SAMe (S-Adenosyl
methionine), is a primary methyl group donor that is involved in the
synthesis of neurotransmitters.
BACKGROUND. SAMe (pronounced “Sammy”)
was first discovered in Italy in 1952. It is a cornerstone in the
methylation cycle, which is the biochemical process through which
amino acids are transformed into neurotransmitters. (SAMe's
contribution of its methyl group (CH2) is what converts an amino acid
into a neurotransmitter.) It should not come as a surprise that SAMe
plays a key role in mood, nervous system regulation, and maintaining
energy levels, since all of these are regulated by neurotransmitters.
The first studies of SAMe's use in
depression were conducted in Italy in the 1970s. Because SAMe is a
primary methyl group donor, the authors concluded that depression
could be linked to the methylation cycle. Since that time, there have
been dozens of studies confirming the efficacy of SAMe in treating
depression.
USES IN CFS/ME: Rich Van Konynenburg
has proposed that in CFS/ME there is a partial block of the
methylation cycle. This would cause a depletion of ATP, as well as
reductions in neurotransmitters, detoxing agents such as glutathione,
and impairment of normal immune system function. Because SAMe is a
vital component of the methylation cycle, Dr. Myhill recommends it as
an all-round support.
PROTOCOL. SAMe should be taken on an
empty stomach. Low doses, ranging from 50 to 100 mg/day are
recommended. (Ray Sahelian advises taking half of a tablet, and
storing the rest for the next day.) Because SAMe can produce
insomnia, it is best taken in the morning. SAMe is highly unstable,
and should be stored in a cool, dry place to prevent deterioration.
SAMe should be taken with vitamin B6, B12 and folic acid as adjuncts.
PROS AND CONS. SAMe appears to have few
side effects. But as with any product that affects the central
nervous system (even indirectly), care should be exercised. While
most people feel an immediate improvement in mood and focus, some
sensitive individuals can experience side effects typical of
stimulants (jitters, insomnia, headache, anxiety). SAMe raises levels
of all neurotransmitters, so it is difficult to predict how any
individual person may respond.
AVAILABILITY AND COST. SAMe is
available in health food stores and from online suppliers. A package
of 20 foil-wrapped enteric-coated tablets (200 mg) costs $10 through
Vitacost.
SEE: Van Konynenburg/Yasko Methylation
Protocol
FURTHER READING
Ray Sahelian on SAMe:
http://www.raysahelian.com/sam-e.html
Dr. Myhill discusses the methylation
cycle: http://drmyhill.co.uk/wiki/CFS_-_The_Methylation_Cycle
RESEARCH
Kagan BL, Sultzer DL, Rosenlicht N,
Gerner RH. “Oral S-adenosylmethionine in depression: a randomized,
double-blind, placebo-controlled trial.” Am J Psychiatry. 1990
May;147(5):591-5. http://www.ncbi.nlm.nih.gov/pubmed/2183633
(Abstract)
Mischoulon, David and Maurizio Fava.
“Role of S-adenosyl-L-methionine in the treatment of depression: a
review of the evidence.” Am J Clin Nutr. 2002;76(suppl):1158S–61S.
http://www.ajcn.org/content/76/5/1158S.full.pdf
VITAMINS
Vitamin A, Beta-Carotene, Vitamin B12,
Vitamin B6, Vitamin B Complex, Vitamin C, Vitamin D, Vitamin E and
Tocotrienols
DESCRIPTION. Vitamins are organic
(carbon-containing) substances needed in tiny amounts to promote
biochemical reactions within living cells.
BACKGROUND. Vitamins, as independent
biochemical agents, were discovered around the turn of the century
when an English biochemist proposed that diseases such as rickets and
scurvy were most likely caused by a lack of "accessory food
factors" in the diet. After observing that these diseases could
be corrected by adding certain foods (whole rice, which is high in
vitamin B, to cure rickets; and oranges, an easy source of vitamin C,
to cure scurvy), scientists began to search for chemical compounds in
these foods that could produce such extensive changes in the body.
When these accessory food factors were finally isolated in food, the
name "vita-mine" was proposed (from the Latin vita,
necessary for life, and amine, a chemical substance containing
nitrogen). Later, when it was discovered that not all vitamins were
amines, the final "e" was dropped.
There are thirteen known vitamins, all
of which act as catalysts, or more specifically, coenzymes; that is,
they initiate or speed chemical reactions in cells while remaining
unchanged themselves. They accomplish their task mainly by combining
with a protein-containing apoenzyme (vitamins contain no protein) to
form a complete enzyme. The completed enzyme performs the role of
biochemical catalyst, enabling most of the body's vital cell
functions to occur in an orderly and efficient manner. Without
vitamins, many essential cell functions would cease, resulting in any
number of vitamin deficiency-related diseases and problems. Most
vitamins must be obtained from food because the body rarely
manufactures them in adequate amounts (vitamin K is the exception).
USES IN CFS/ME. Most CFS/ME physicians
and clinicians include vitamin supplementation as a part of a general
treatment protocol. The reasons vitamin supplementation is considered
such a central part of CFS/ME treatment are threefold.
First, the ill body consumes vitamins much faster than the healthy body. Patients, particularly those with long-term illnesses, need vitamins in amounts that exceed those which can be derived from food, especially when (as in CFS/ME) the illness causes certain metabolic defects.
First, the ill body consumes vitamins much faster than the healthy body. Patients, particularly those with long-term illnesses, need vitamins in amounts that exceed those which can be derived from food, especially when (as in CFS/ME) the illness causes certain metabolic defects.
Second, at least 50% of patients with
CFS/ME have absorption problems (leaky gut, low stomach acid
production, or other gastrointestinal difficulties). When food is
improperly digested, vitamins are not extracted efficiently,
necessitating some kind of supplementation.
Third, as has been pointed out by a
number of researchers, the particular nature of CFS/ME immune system
activation prevents some vitamins from working properly. The excess
cytokine production that blocks vitamin C function, for example, is
justification enough for supplementation.
The most frequently recommended vitamin
supplements are vitamin C and B12, but general wide-spectrum
supplements are also important. Benefits of vitamin supplementation
generally are not apparent for several weeks, but some undernourished
patients notice significant effects within a few hours. Many CFS/ME
patients report an overall improvement in vitality, energy level, and
stamina with vitamin supplementation. Few report any adverse effects
(and these are usually remedied by switching brands).
AVAILABILITY AND COST. Vitamins are
easily obtained from supermarkets, health food stores, pharmacies,
and online suppliers. Vitacost markets a good multi-vitamin/mineral
supplement made by Carlson for $8.50 (90 gelcaps).
Care should be taken to purchase
high-grade vitamins because the excessive heat and poor handling to
which low-grade vitamin products are exposed often cause fat-soluble
vitamins to become rancid and can considerably reduce the efficacy of
water-soluble vitamins. Excess filler also makes some cheaper
vitamins difficult to dissolve. (A good test for vitamin tablets is
to place one in a small glass of lemon juice. If it doesn't dissolve
in the lemon juice, it won't dissolve in your stomach.) With the
exception of vitamin E, synthetic vitamin preparations are as
effective as natural vitamins.
In addition to a wide-spectrum vitamin
supplement, many CFS/ME physicians recommend taking extra amounts of
specific vitamins for the purposes of providing added antioxidant
protection, for immune system enhancement, or to compensate for the
functional deficits common to the illness.
FURTHER READING
General information about vitamins (and
other) supplements for CFS/ME patients.
http://www.cfids.org/archives/2004/2004-1-article04.asp
VITAMIN A
DESCRIPTION. Vitamin A (retinol) plays
a variety of roles in human metabolism. It helps maintain the health
of the skin and all mucous linings of the body (stomach, intestines,
bladder, mouth, nose, throat, windpipe, and other air passages). It
is essential for vision. Vitamin A also increases resistance to
infections and is involved in the maintenance of the adrenal cortex,
where cortisol is formed.
USES IN CFS/ME. Vitamin A is primarily
used to help maintain mucous membranes, which are often compromised
in CFS/ME. Patients prone to intestinal, respiratory, or ear
infections also take vitamin A to boost immune system efficiency.
There have been attempts in the past to redefine vitamin A as an
"anti-infective agent." However, because its protective
capacity is limited to bacterial infections of the mucous membranes,
these have been abandoned.
The recommended daily allowance for
vitamin A is 5000 IU a day. Because vitamin A is fat soluble, it can
be stored in the liver, which means it can be taken less frequently
in larger doses. A physician or nutritionist should be consulted
before taking larger doses, however, to prevent possible overdosing.
Loss of appetite, irritability, widespread itching, headaches, and
mouth ulcers are all signs of vitamin A toxicity. People with low
thyroid function must take vitamin A supplements, as the thyroid is
responsible for converting beta-carotene into vitamin A.
AVAILABILITY AND COST. Vitamin A is
available from health food stores, many pharmacies, and some
supermarkets. The form of vitamin A most easily absorbed is
micellized A, a liquid suspension sold in health food stores. The
best natural sources of vitamin A are animal products (liver, whole
milk, butter, and cheese). Fish liver contains huge amounts of
vitamin A (200,000 to 1 million IU, depending on the type). Pregnant
women should not take more than 5000 IU of vitamin A, because higher
doses have been associated with birth defects.
BETA-CAROTENE
DESCRIPTION. Beta-carotene is the
precursor to vitamin A. When foods containing beta-carotene (yellow
or orange vegetables) are ingested, the liver converts the
beta-carotene to vitamin A. However, unlike vitamin A it cannot be
stored in the body and therefore entails far fewer risks of toxicity,
although its function remains largely the same. Like vitamin A,
beta-carotene strengthens mucous membranes. It also helps protect
against skin and lung cancer and improves the functioning of the
thymus gland (where T cells are produced). There is no recommended
daily allowance for beta-carotene, but people who take large amounts
often notice that certain areas of their skin, particularly the palms
and around the fingernails, turn yellowish orange. This condition is
called carotenemia and, while benign, is a sign that too much
beta-carotene is being consumed. Patients with diabetes or
hypothyroid conditions should avoid taking beta-carotene because they
cannot convert it to vitamin A.
USES IN CFS/ME. Beta-carotene is one of
the vitamins mentioned by clinicians as having particular value in
CFS/ME. Dr. Burke Cunha proposed that one of the chief benefits of
beta-carotene for CFS/ME patients lies in its ability to stimulate
the production of natural killer cells (CFIDS Chronicle, Fall 1993).
He found that among the majority of his patients who tested low in
natural killer cells, high doses of beta-carotene resulted in an
increase in the number of these cells. He also found less fatigue in
these patients. (Patients with normal numbers of natural killer cells
before therapy showed less improvement, however.)
Dr. Cunha postulated that by increasing
natural killer cell production, beta-carotene may serve as an
effective antiviral agent. He recommended a high dose (25,000 to
50,000 IU/day, depending on the patient's needs), but cautioned that
high doses of beta-carotene should not be taken for more than three
weeks to prevent carotenemia and vitamin A toxicity. Most clinicians
recommend a daily dose of 5000 to 10,000 IU in combination with other
antioxidants to prevent carotenemia.
FURTHER READING
Dr. Cunha on beta-carotene
supplementation for CFS/ME patients.
http://www.immunesupport.com/94wtr007.htm
CFS/ME patient ratings of
beta-carotene:
http://www.revolutionhealth.com/drugs-treatments/rating/beta-carotene-for-chronic-fatigue-syndrome-cfs-cfids-me
VITAMIN B12
DESCRIPTION. Vitamin B12 (cobalamin) is
a member of the B vitamin complex. It is naturally found in animal
products and is required for proper digestion, food absorption,
protein synthesis, metabolism of carbohydrates and fats, myelin
synthesis, nerve function, and activation of folic acid (used in the
formation of red blood cells). Its name is derived from cobalt, the
mineral to which this vitamin is bound. When cobalamin is ingested,
contact with stomach enzymes splits it apart, freeing it to join with
a special protein called "intrinsic factor," which is
secreted by the stomach lining. Only when vitamin B12 combines with
intrinsic factor – which converts the cobalamin into
methylcobalamin – can it be absorbed by the body. Because vitamin
B12 is highly unstable outside the body, cyanocobalamin, a synthetic
form of B12, is normally used in supplements. Oral vitamin B12 cannot
be absorbed in malabsorptive states such as pernicious anemia.
USES IN CFS/ME. Although the
traditional use for vitamin B12 injections has been limited to the
treatment of anemia, Dr. Charles Lapp and Dr. Paul Cheney have
observed that such injections are highly beneficial to their CFS/ME
patients, even in the absence of vitamin B12 deficiency or any sign
of anemia. They report that some 50% to 80% of their patients
demonstrate improved stamina and energy with vitamin B12 therapy
(CFIDS Chronicle, Fall 1993).
Dr. Cheney was first motivated to
include vitamin B12 in his general treatment plan after seeing
evidence that vitamin B12 injections had been helpful in a number of
nonanemic neuropsychiatric patients. These patients had demonstrated
some of the symptoms common to CFS/ME (paresthesia, sensory loss,
loss of coordination, and mood swings), all of which improved with
vitamin B12 injections. Dr. Cheney theorized that vitamin B12
injections work so well among CFS/ME patients because the elevated
rate of cytokine production in CFS/ME may be effectively blocking
vitamin B12 function in the body. In this case, massive amounts of
vitamin B12 would be needed to overcome the functional deficiency
brought about by excess cytokine production.
Vitamin B12 may also help correct the
red blood cell abnormalities in CFS/ME patients discovered by New
Zealand researcher Dr. Leslie O. Simpson (CFIDS Chronicle, Fall
1995). Dr. Simpson observed that hydroxocobalamin injections
corrected this defect by increasing production of disc-shaped cells.
About 50% of the patients in this group felt better with B12
injections.
Dr. Myhill, in her explanation of the
benefits of B12 in CFS/ME patients, observes that B12 is a powerful
free radical scavenger, particularly of nitric oxide. (People with
CFS/ME have high levels of nitric oxide.) In addition to mitigating
the harmful effects of nitric oxide, B12 also helps correct one of
the immune system abnormalities found in CFS/ME patients. According
to Dr. Cheney, CFS/ME patients experience a shift from Th1 (cellular)
to Th2 (humoral) immunity. In essence, the immune system is skewed in
favor of B cells (which search for pathogens in the bloodstream)
rather than searching for pathogens within cells. This imbalance
allows for the proliferation of viruses within cells. According to
Dr. Bell, vitamin B12 is one of the most effective means of
re-orienting the immune system back to Th1 (cellular) immunity.
PROTOCOL. The dosage Dr. Cheney
recommends is 2000 to 5000 ug/ml (in a 0.5 to 1.0 cc syringe)
administered subcutaneously or intramuscularly every two or three
days. Other physicians generally recommend 1000 to 2000 ug (1 to 2 cc
syringe) one to three times a week. Dr. Myhill starts with ½ mg (500
mcgms) daily by subcutaneous injection. Dr. Lapp says that to obtain
a “continuous and satisfactory level of improvement,” 3000 mcg of
cyanocobalamin every two to three days should be administered.
High doses of vitamin B12 must be
accompanied by a multivitamin that includes the entire vitamin B
complex to avoid B vitamin imbalances. This dosage can be tolerated
over long periods, although benefits can wane. In that case, a short
period without vitamin B12 injections (1 to 2 weeks) is usually
enough to reestablish its efficacy. Most physicians prefer
cyanocobalamin to hydroxocobalamin because it is the most stable form
of vitamin B12. However, some patients who cannot tolerate
cyanocobalamin prefer the more bioavailable, and longer acting,
hydroxocobalamin.
PROS. Most patients who take vitamin
B12 injections report favorable results. Common benefits include
increased energy, mental clarity, and stamina, usually lasting for
several days after a single administration. Because benefits may not
be felt for the first three to six weeks, a month's trial is
generally recommended.
CONS. Although vitamin B12 is fairly
innocuous, some patients report side effects. The most common side
effect is lassitude. Some patients also report local rashes, which
diminish when dosage is reduced, and various allergic reactions
(including diarrhea) to the preservatives used in the solution. To
avoid potential allergic reactions, a patch test should be performed
first. Administration of the first injection in a physician's office
is also recommended in highly allergic individuals.
AVAILABILITY AND COST. The most
effective form of B12 is injectable vitamin B12, available by
prescription. After injections, the most easily absorbed form of B12
is via nasal spray, also available by prescription. For those who do
not have a doctor willing to prescribe B12, there are both sublingual
and oral spray forms that are fairly well absorbed. (Don't waste your
money on oral tablets and capsules. They are very poorly absorbed.)
Perque markets activated sublingual hydroxocobalamin (2000 mcg) for
about $30 (100 lozenges). (Take one a day.) PureFormulas.com markets
B12 spray (with B6 and folic acid) made by NOW for $12.59.
FURTHER READING
Dr. Lapp's B12 recommendations:
http://www.cfids.org/archives/1999/1999-6-article03.asp
Dr. Myhill's excellent explanation of
why B12 works in CFS/ME patients.
http://www.drmyhill.co.uk/wiki/B12_-_rationale_for_using_vitamin_B12_in_CFS
B12 Basics – very detailed:
http://forums.phoenixrising.me/showthread.php?11522-Active-B12-Protocol-Basics/
Informative patient thread on the uses
of B12 for treating CFS/ME.
http://www.prohealth.com/fibromyalgia/blog/boardDetail.cfm?id=1318273
RESEARCH
van Asselt, D Z B, F W H M Merkus, F G
M Russel, and W H L Hoefnagels. “Nasal absorption of
hydroxocobalamin in healthy elderly adults.” Br J Clin Pharmacol.
1998 January; 45(1): 83–86.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1873990/
VITAMIN B6
DESCRIPTION. Vitamin B6 (pyridoxine,
pyridoxal, and pyridoxamine), is one of nature's busiest vitamins. It
is involved in more than one hundred essential chemical reactions in
the body, including making amino acids and neurotransmitters,
metabolizing energy, balancing hormones, and supporting the immune
system. High doses of B6 have been shown to decrease colorectal
cancer rates. Vitamin B6 is also used to prevent heart disease by
lowering cholesterol, to treat the nausea and vomiting associated
with morning sickness, and, because of its importance in nervous
system function, to treat various CNS conditions, including
depression, schizophrenia and ADD.
USES IN CFS/ME. A study published in
1999 by a group of British researchers found that CFS/ME patients had
reduced functional status of B vitamins, particularly B6. Because B6
is vital to so many neuroendocrine reactions, a deficiency can result
in impaired sleep (due to B6's role in converting glutamate to GABA),
hypoglycemia (due to the role of B6 in neoglucogenesis), and
neuropathy (damage to the peripheral nervous system). A classic sign
of vitamin B6 deficiency is skin eruptions resembling seborrheic
dermatitis, a common symptom in acute stages of CFS/ME. CFS/ME
patients have found that B6 is useful for treating pain, especially
carpal tunnel syndrome.
PROTOCOL. As high doses can cause
imbalances in other B vitamins, a low dose is recommended. The
minimum requirement is 1.5 mg. (The maximum dose is 100 mg.) The
active, and therefore most effective, form of B6 is pyridoxal
phosphate (also known as P5P). P5P is well tolerated and is easily
absorbed in oral form. High doses of B6 (200 mg) can cause symptoms
of nerve damage (loss of feeling in the legs, loss of balance). These
effects are reversible once the dosage is lowered. Supplementation
with zinc is advised if there is a deficiency of either B6 or zinc,
as B6 cannot be utilized without zinc.
FURTHER READING
The University of Maryland's
informative page on vitamin B6.
http://www.umm.edu/altmed/articles/vitamin-b6-000337.htm
RESEARCH
Heap LC, Peters TJ, Wessely S. “Vitamin
B status in patients with chronic fatigue syndrome.” J R Soc Med.
1999 Apr;92(4):183-5. http://www.ncbi.nlm.nih.gov/pubmed/10450194
(Abstract)
VITAMIN B COMPLEX
DESCRIPTION. Many patients with CFS/ME
benefit from taking a vitamin B complex formulation, either in
accompaniment to single B vitamins (to prevent imbalances) or alone.
CFS/ME patients have reported improvement in energy levels, symptoms
of premenstrual syndrome (PMS), mood, and sleep disorders after
taking vitamin B complex. Most vitamin B complex formulations include
vitamins B1 (thiamine), B2 (riboflavin), B3 (niacin), B5 (pantothenic
acid), B6 (pyridoxine, pyridoxal, and pyridoxamine), B7 (biotin), B9
(folic acid), and B12 (cobalamin). People with allergies, Candida
infection, or digestive symptoms should avoid yeast-based
formulations, which may be poorly tolerated.
AVAILABILITY AND COST. Nature's Life
and Source Naturals both sell a 100-capsule yeast-free bottle of B
complex for about $7 (available online). Vitacost sells its in-house
brand of yeast-free liquid vitamin B complex for $15 (will last three
months).
VITAMIN C
DESCRIPTION. Vitamin C (ascorbic acid)
is a water-soluble antioxidant found in most raw fruits and
vegetables. It serves a number of vital functions in the body,
including connective tissue repair (especially collagen), maintaining
healthy teeth and bones, promoting the synthesis of anti-inflammatory
hormones in the adrenal glands, helping to produce the
neurotransmitters serotonin and norepinephrine, healing wounds,
maintaining capillaries, healthy adrenal glands, and ovaries,
absorbing iron into the bloodstream, promoting efficient white blood
cells, and maintaining cholesterol balance. It is widely touted as a
preventive for the common cold, perhaps because vitamin C increases
the production of interferon, an antiviral cytokine.
Animal experiments have shown that
vitamin C has other immune system-enhancing effects as well,
increasing the body's ability to fight off bacterial infections and
promoting general immunity. Patients with allergies may want to take
special note of vitamin C's function as a natural antihistamine. A
research team led by the co-discoverer of vitamin C, Professor
Charles Glen King of Columbia University, demonstrated as early as
1940 that it can both prevent and moderate allergy symptoms. In
addition to its other beneficial properties, vitamin C is also a
natural chelator, helping to remove heavy metals and toxins from the
body.
Vitamin C is not stored in the body, as
are fat-soluble vitamins, and thus must be constantly replenished.
Smoking, drinking (alcohol), illness, and physical or emotional
stress all cause rapid depletion of vitamin C.
USES IN CFS/ME. Vitamin C is the most
widely used of all vitamins for CFS/ME patients, not just because of
its role as an antioxidant and free radical scavenger, but also
because of the numerous other vital functions it performs. Of
particular relevance to patients with CFS/ME is the role of vitamin C
in maintaining healthy capillaries. A number of researchers have
remarked on the poor circulation in patients with CFS/ME, resulting
in corollary illnesses such as Reynaud's phenomenon. Even more
critical in CFS/ME is reduced blood flow to the brain, which is
especially dependent on capillary action for its blood supply. This
function alone helps to place vitamin C at the forefront of any
vitamin therapy. However, its role in collagen formation and tissue
repair, its importance in immune system function, and its place as an
adrenal gland support do much to explain why it is one of the most
frequently recommended CFS/ME nutritional treatments.
PROTOCOL. Most nutritionists recommend
taking vitamin C to tolerance; that is, until the patient begins
experiencing diarrhea or burning urine. Considering the broad
spectrum of sensitivities among CFS/ME patients, tolerance can vary
considerably. CFS/ME clinicians generally recommend anywhere from
2000 – 6000 mg/day (taken in small divided doses) up to tolerance.
Dr. Martin Pall recommends doses on the
order of 500 to 1000 mg/day, taken several times per day. Vitamin C
can act to regenerate tetrahydrobiopterin (BH4) and, therefore, may
act to lower oxidative stress. High doses of vitamin C can be useful
in scavenging peroxynitrite (ONOO‾), the most central element in
his NO/ONOO‾ cycle hypothesis.
For those who are intolerant to vitamin
C, it is worthwhile to administer it topically. It is very easy to
make an ointment. Put a small amount of hand lotion into a small bowl
(only as much as you intend to use). Add 1/8 teaspoon of pure
ascorbic acid powder (about 500 mgs) to the lotion. Mix with your
finger and apply immediately to the skin. The mixture cannot be
stored, so be sure not to make too much. About 10% of the vitamin C
you use can be absorbed via this method. (Over a period of time, the
mixture will yellow your nails. This is because the vitamin C turns
yellow when exposed to moisture. The effect goes away when you stop
topical applications.)
PROS AND CONS. Vitamin C is
inexpensive, easy to take and usually well-tolerated. Patients report
that on low doses (500 – 1000 mg), they catch fewer colds. Some
CFS/ME patients are quite sensitive to vitamin C and can only
tolerate small amounts.
AVAILABILITY AND COST. Vitamin C is one
of the least expensive vitamins and is widely available at most
pharmacies, health food stores, online suppliers, and supermarkets.
Unfortunately, vitamin C is quite unstable. It degrades quickly when
exposed to light and heat, and has a short shelf life, which means
most commercial tablets and pills contain very little usable vitamin
C. In addition, Vitamin C degrades when exposed to moisture, which
means drinks with added vitamin C share the same drawbacks as
tablets.
The best form of Vitamin C is pure
vitamin C powder (ascorbic acid). Because it is a powder, it can be
titrated (taken in very small doses). Ascorbic acid is very sour, so
most people prefer mixing it with a bit of juice. Allergy Research
sells a 120-gm bottle of pure ascorbic acid powder for roughly $10
through Vitacost. At ½ teaspoon a day (2000 mg) a bottle will last
two months.
For those with gastrointestinal
symptoms, acid-free C powder may be more tolerable. Ascorbic acid can
be buffered with magnesium carbonate, calcium carbonate and/or
potassium carbonate to reduce acidity. Oral buffered vitamin C in
small doses is extremely safe, with virtually no side effects.
Intravenous (IV) drip is another form
of vitamin C therapy used in CFS/ME. Administering vitamin C directly
into the bloodstream not only increases the rate at which it is
absorbed but enhances its role as a chelating agent. A number of
health care practitioners use vitamin C as an essential component of
CFS/ME therapy.
Intravenous drip therapy should not be
administered daily and requires monitoring by a physician. The charge
for an intravenous drip is $70 to $125, depending on locale.
Insurance usually does not cover the cost.
FURTHER READING
Good overview of vitamin C supplements.
http://www.electroherbalism.com/Naturopathy/Therapies/Supplements/Vitamins/VitaminC/index.htm
Detailed overview of the Krebs cycle
and its role in CFS/ME.
http://www.nutritionreview.org/library/krebs.php
CFS/ME patient ratings of vitamin C:
http://www.revolutionhealth.com/drugs-treatments/rating/vitamin-c-ascorbic-acid-for-chronic-fatigue-syndrome-cfs-cfids-me
VITAMIN D
DESCRIPTION. Vitamin D is a unique
vitamin in that the body can synthesize it when exposed to sunlight.
There are two forms of vitamin D, ergocalciferol (D2) and
cholecalciferol (D3). The difference between the two forms is that D2
is derived from ergosterol (a chemical compound produced by
phytoplankton, invertebrates, and fungi) while D3 is produced by
ultraviolet light irradiation.
Vitamin D has come under increasing
scrutiny over the past few years due to its functions in bone
maintenance and immune system function. Physicians have known for
decades that cod liver oil is an effective treatment for rickets, a
childhood condition in which bones and teeth become soft. Ultimately,
it was discovered that rickets was caused by a deficiency of vitamin
D. As a consequence, vitamin D is added (actually, produced via
exposure to ultraviolet light) to all milk. Aside from rickets,
deficiencies in vitamin D have been linked to gingivitis,
inflammatory bowel disease, depression, fatigue, and heart disease.
Vitamin D is also recommended for women at risk for osteoporosis.
Vitamin D's role in the immune system
is no less important. One of its most important functions is to
activate T cells, in particular the T cells that identify and attack
invading pathogens. Without vitamin D, T cells remain dormant or
“naive.”
USES IN CFS/ME. In a 2009 study,
Berkovitz et al found that vitamin D levels were moderately to
severely low in CFS/ME patients as compared to the general
population. The researchers recommended vitamin D supplementation.
More recently, in 2011 a group of pediatric researchers at the Mayo
Clinic discovered that adolescents with CFS/ME and orthostatic
intolerance (OI) had low levels of both ferritin (a protein that
stores and releases iron) and vitamin D.
The question for some researchers is
whether low vitamin D levels are a cause of the illness or a result
of it. CFS/ME is characterized by a shift from Th1 (cellular) to Th2
(humoral) immunity. Basically, the immune system in a person with
CFS/ME spends too much effort identifying and attacking foreign
invaders (Th2) and too little effort focusing on pathogens within
cells (Th1). This allows for a proliferation of viruses that multiply
within cells. The argument is that Vitamin D, because it is crucial
for the production of macrophages (the immune system components that
“eat” extracellular pathogens), may become depleted as a result
of the shift to Th2.
PROTOCOL. In the presence of low serum
D levels, dosage is determined by the physician. For those who wish
to supplement, and who are getting adequate sun exposure, low doses
are advised (1000 – 2000 IU).
AVAILABILITY AND COST. Vitamin D is
inexpensive and widely available at any health food store,
supermarket, drug store and from online distributors. It is a
fat-soluble vitamin, so gelcaps or drops are more easily assimilated.
But, for those who are sensitive to gelcaps, there are dry forms of
vitamin D as well. (Although some form of oil or fat must be in the
intestines for proper absorption.) If you are already taking fish
oil, supplementation with vitamin D may not be necessary.
TESTING: There are two tests for
determining blood levels of vitamin D. The most commonly used test is
for 1,25 (OH)2 vitamin D (1,25 dihydroxy vitamin D). This test
measures a form of vitamin D that has a long half life (about three
weeks) and therefore will only give your doctor an overall picture of
your votamin . A more specific test, 25OH vitamin D (25-hydroxy
vitamin D ), will tell your doctor how much vitamin D is currently in
your bloodstream. Of the two tests, the second is more useful for
determining actual vitamin D levels.
FURTHER READING
List of articles concerning vitamin D
deficiency:
http://www.vitamindcouncil.org/about-vitamin-d/vitamin-d-deficiency/
CFS/ME patient reviews of vitamin D:
http://www.revolutionhealth.com/drugs-treatments/rating/vitamin-d-for-chronic-fatigue-syndrome-cfs-cfids-me
RESEARCH
Antiel RM, Caudill JS, Burkhardt BE,
Brands CK, Fischer PR. “Iron insufficiency and hypovitaminosis D in
adolescents with chronic fatigue and orthostatic intolerance.”
South Med J. 2011 Aug;104(8):609-11.
http://www.ncbi.nlm.nih.gov/pubmed/21886073 (Abstract)
Berkovitz S, Ambler G, Jenkins M,
Thurgood S. “Serum 25-hydroxy vitamin D levels in chronic fatigue
syndrome: a retrospective survey.” Int J Vitam Nutr Res. 2009
Jul;79(4):250-4. http://www.ncbi.nlm.nih.gov/pubmed/20209476
(Abstract)
VITAMIN E
DESCRIPTION. Vitamin E (tocopherol) is
a fat-soluble vitamin found in butterfat, meats, vegetable oils, and
particularly wheat germ oil, from which this vitamin was first
isolated in 1936. It is made up of four tocopherols (alpha, beta,
gamma, delta) and four tocotrienols (alpha, beta, gamma, delta). Like
other antioxidants, vitamin E serves to protect cell linings from
damage caused by oxidation. It helps to maintain red blood cell
membranes and other cell tissues (even the walls of the tiny
structures within cells), ensures normal muscle metabolism, and
protects essential unsaturated fatty acids and vitamin A from
destruction from oxidation. Vitamin E has protective activity against
methyl mercury toxicity and increases the activity of glutathione.
Zinc is needed to maintain proper levels of vitamin E in the blood;
thus, zinc deficiency can lead to low vitamin E levels.
USES IN CFS/ME. In a 2003 study
conducted in Italy, researchers found that CFS/ME patients exhibited
significantly lower antioxidants (vitamin E among others) in serum
samples as compared to controls. The CFS/ME group also had lower pain
thresholds than controls in all muscle sites tested. The researchers
correlated levels of vitamin E concentration to the degree of muscle
pain — the lower the vitamin E levels, the greater the pain. While
the researchers did not offer treatment suggestions, their findings
indicate that supplementation would be beneficial.
In 2009 Miwa and Fujita also found low
serum levels of vitamin E in CFS/ME patients. They concluded that the
reduction in vitamin E was due to oxidative stress. In a later study,
Miwa and Fujita found that low serum levels of vitamin E in CFS/ME
patients correlated with flares. They concluded that the “low level
of serum alpha-tocopherol was ameliorated during the remission phase
as compared with the exacerbation phase in the patients with chronic
fatigue syndrome, suggesting that increased oxidative stress may be
involved in the pathogenesis of chronic fatigue syndrome and might
also be directly related to the severity of the symptoms of chronic
fatigue syndrome.” This conclusion is very much in line with
research demonstrating oxidative stress in people with CFS/ME, and
leads to a specific course of supplementation. Vitamin E reduces
oxidative stress by mitigating the effects of lipid peroxidation.
Vitamin E can also reduce chronic inflammation by down-regulating the
NF-kappaB inflammatory pathway.
In keeping with these findings, and
numerous other studies linking oxidative stress to CFS/ME symptoms,
vitamin E is used chiefly for its properties as an antioxidant. Its
ability to strengthen cell walls and protect other vitamins and fats
from destruction makes it highly desirable as an adjunct to other
vitamin therapies.
PROTOCOL. Because it is fat-soluble,
only minimal amounts are needed to produce antioxidant benefits.
The optimal dosage, 200 IU of natural vitamin E (mixed tocopherols), taken daily with the largest meal is usually recommended for patients with CFS/ME. Vitamin E acts as a blood thinner, so do not take it with other blood thinners, or before surgery.
The optimal dosage, 200 IU of natural vitamin E (mixed tocopherols), taken daily with the largest meal is usually recommended for patients with CFS/ME. Vitamin E acts as a blood thinner, so do not take it with other blood thinners, or before surgery.
Recently, research has been focused on
tocotrienols, which are closely related to the tocopherols.
Tocotrienols, like tocopherols, are found in some vegetable oils,
wheat germ, barley, saw palmetto, and certain varieties of nuts and
grains. The reason for the high interest generated by tocotrienols is
that they have been shown to protect against brain cell damage and
cardiovascular disease, prevent cancer, reduce cholesterol and combat
oxidative stress to the skin produced by UV exposure. Dr. Pall has
pointed out that tocotrienols can penetrate tissues with saturated
fatty layers more efficiently than tocopherols, making tocotrienols,
particularly delta tocotrienols, powerful antioxidants.
AVAILABILITY AND COST. Vitamin E is
available at any drug store, health food store, and from online
suppliers. Look for a good brand of natural Vitamin E. Vitacost sells
natural vitamin E for between $8 and $17 a bottle. Delta tocotrienols
are available in health food stores and online through
PureFormulas.com and Vitacost for roughly $13 to $25 a bottle.
FURTHER READING
CFS/ME patient reviews of vitamin E:
http://www.revolutionhealth.com/drugs-treatments/rating/vitamin-e-for-chronic-fatigue-syndrome-cfs-cfids-me
RESEARCH
Kim S, Lee EH, Kim SH, Lee S, Lim SJ.
“Comparison of Three Tocopherol Analogs as an Inhibitor of
Production of Proinflammatory Mediators in Macrophages.” J
Pharmacol Sci. 2012 Feb 3.
http://www.ncbi.nlm.nih.gov/pubmed/22302019 (Abstract)
Miwa K, Fujita M. “Increased
oxidative stress suggested by low serum vitamin E concentrations in
patients with chronic fatigue syndrome.” Int J Cardiol. 2009 Aug
14;136(2):238-9. http://www.ncbi.nlm.nih.gov/pubmed/18684522
(Abstract)
Miwa K, Fujita M. “Fluctuation of
serum vitamin E (alpha-tocopherol) concentrations during exacerbation
and remission phases in patients with chronic fatigue syndrome.”
Heart Vessels. 2010 Jul;25(4):319-23.
http://www.ncbi.nlm.nih.gov/pubmed/20676841 (Abstract)
Rezk BM, Haenen GR, Van Der Vijgh WJ, Bast A. “The extraordinary
antioxidant activity of vitamin E phosphate.” Biochim Biophys Acta.
2004 Jul 5;1683(1-3):16-21.
http://www.ncbi.nlm.nih.gov/pubmed/15238215 (Abstract)
Vecchiet, Jacopo, Francesco Cipollone,
Katia Falasca , Andrea Mezzetti, Eligio Pizzigallo, Tonino
Bucciarelli, Silvana De Laurentis, Giannapia Affaitati, Domenico De
Cesare, Maria Adele Giamberardino. “Relationship between
musculoskeletal symptoms and blood markers of oxidative stress in
patients with chronic fatigue syndrome.” Neuroscience Letters,
Volume 335, Issue 3, January 2, 2003, Pages 151-154.
http://www.sciencedirect.com/science/article/pii/S0304394002010583
(Abstract)
Yam ML, Abdul Hafid SR, Cheng HM,
Nesaretnam K. “Tocotrienols suppress proinflammatory markers and
cyclooxygenase-2 expression in RAW264.7 macrophages.” Lipids. 2009
Sep;44(9):787-97. http://www.ncbi.nlm.nih.gov/pubmed/19655189
(Abstract)
WHEY PRODUCTS
Colostrom, Undenatured Whey, Probioplex
COLOSTRUM
DESCRIPTION. Colostrum is the first
milk produced by the mother in late pregnancy and just after birth.
BACKGROUND. Because babies are born
with immature digestive systems, colostrum delivers important
nutrients – proteins, vitamins, and sodium – in a concentrated
form. Colostrum also helps the newborn to clear excess bilirubin from
its system, which prevents jaundice. Most important, colostrum
contains antibodies, such as IgA, IgG, and IgM, three major
components of the immune system. Colostrum also contains cytokines,
interleukins, and tumor necrosis factor as well as a number of growth
factors. The antibodies in colostrum provide immunity, while growth
factors stimulate the development of the GI system, which together
provide the newborn with its first protection against pathogens.
USES IN CFS/ME. Gut problems (including
leaky gut, small intestine bacterial overgrowth (SIBO), irritable
bowel, and motility problems) are endemic in CFS/ME patients.
Colostrum may be beneficial for all these conditions. Many allergists
believe that colostrum helps food intolerance and allergies.
PROTOCOL. Dr. Teitelbaum recommends
three capsules of colostrum three times a day for six to nine months.
Then stop, or use the lowest dose needed for symptoms. If nausea or
indigestion occurs, lower the dose to a comfortable level for one or
two weeks until symptoms pass. Take first thing in the morning on an
empty stomach.
PROS AND CONS. Some patients report
increased energy after taking colostrum for a few weeks. As with
other milk-based products, however, many patients are sensitive to
colostrum.
AVAILABILITY AND COST. Colostrum is
available from health food stores and from online distributors.
Symbiotics sells a 60-capsule bottle of Colostrum Plus (950 mg) for
around $10 through Vitacost. Jarrow and Source Naturals also market
colostrum capsules for roughly the same price.
FURTHER READING
Colostrum and leaky gut:
http://www.carttonic.com/files/file_download.php?fi_id=684
RESEARCH
Hanson LA, Ahlstedt S, Andersson B,
Carlsson B, Fällström SP, Mellander L, Porras O, Söderström T,
Edén CS. “Protective factors in milk and the development of the
immune system.” Pediatrics. 1985 Jan;75(1 Pt 2):172-6.
http://www.ncbi.nlm.nih.gov/pubmed/3880886 (Abstract)
UNDENATURED WHEY
DESCRIPTION. Undenatured, or
non-denatured, whey is a form of whey (the liquid part of milk after
it has curdled) which has not been subjected to high temperatures.
BACKGROUND. Undenatured whey has been
used primarily for protein supplementation. It contains all the amino
acids in their natural unoxidized forms. Undenatured whey helps
control unfriendly bacteria in the gut, and supports the immune
system. The unoxidized cysteine is easily absorbed by the liver, and
can be used to make glutathione.
In 1991 Bounous and Gold found that
when mice were fed undenatured whey, their glutathione levels rose.
(These findings were confirmed by later studies by Pacheco et al.)
Further research has shown that undenatured whey's effect on
glutathione levels can ameliorate liver disease, asthma, and
diabetes.
USES IN CFS/ME. In CFS/ME patients,
undenatured whey has been used to increase glutathione levels in
patients who do not respond to direct glutathione supplementation.
Dr. Cheney found that in his patients, results with reduced
glutathione and with glutathione precursors (e.g., NAC) were
“modest.” He began using a weakly hydrolyzed whey protein and
noted positive results. This prompted Dr. Cheney to embark on a
six-month trial using ImmunoPro on a small subset of patients. At the
end of the study, the patients were tested for bacterial and viral
titers. He found that chlamydia pneumoniae, mycoplasma incognitus,
and mycoplasma penetrans were eradicated after six months. Dr. Cheney
did not find similar results with viral levels, but cautions that the
study was not large enough to draw conclusions.
PROTOCOL. Dr. Cheney's study patients
were given two packs a day (10 mg, or 1.75 tablespoon per pack) of
undenatured whey (ImmunoCal), but he reports that patients can take
more as results are dosage dependent. (The higher the dose, the
greater the effect.) Undenatured whey should be taken on an empty
stomach with a bit of water or milk (not juice).
PROS AND CONS. Those who respond to
undenatured whey report a marked increase in energy. Unfortunately, a
number of CFS/ME patients report “die-off” type reactions (sore
throats, swollen glands and flu-like symptoms) at even the smallest
doses. According to Richard Van Konynenburg, the lack of tolerance
could be due to a reaction to casein, or (and this is most likely) to
the fact that when glutathione is raised, it stimulates the immune
system. Immune system stimulation is often mistaken for “die-off.”
AVAILABILITY AND COST. ImmunoPro, the
brand Dr. Cheney currently recommends, can be purchased from online
distributors. Amazon.com markets a 10.6-oz (300 gm) container for
$33. At one scoop a day, the container will last for two months.
Swanson and ProHealth sell good quality undenatured whey for a
similar price.
FURTHER READING
Patient thread on nondenatured whey,
including an excellent explanation of how these products work by Rich
Van Konynenburg
http://forums.phoenixrising.me/showthread.php?9596-Whey-powder-any-CFS-issues-benefits
Information about whey and lactoferrin:
http://www.wellwisdom.com/pages/Whey-Facts.html
Dr. Cheney talks about whey protein and
glutathione
http://www.wellwisdom.com/pages/Whey-Facts.html#10tharticle
Carol Sieverling's article about whey,
Cheney and glutathione.
http://www.prohealth.com/library/showarticle.cfm?libid=8874
Detailed information on whey and
glutathione http://www.nutritionadvisor.com/glutathione.html
RESEARCH
Bounous G, Gold P. “The biological
activity of undenatured dietary whey proteins: role of glutathione.”
Clin Invest Med. 1991 Aug;14(4):296-309.
http://www.ncbi.nlm.nih.gov/pubmed/1782728 (Abstract)
Chitapanarux T, Tienboon P,
Pojchamarnwiputh S, Leelarungrayub D. “Open-labeled pilot study of
cysteine-rich whey protein isolate supplementation for nonalcoholic
steatohepatitis patients.” J Gastroenterol Hepatol. 2009
Jun;24(6):1045-50. http://www.ncbi.nlm.nih.gov/pubmed/19638084
(Abstract)
Pacheco MT, Sgarbieri VC. “Effect of
different hydrolysates of whey protein on hepatic glutathione content
in mice.” J Med Food. 2005 Fall;8(3):337-42.
http://www.ncbi.nlm.nih.gov/pubmed/16176144 (Abstract)
PROBIOPLEX
DESCRIPTION. Probioplex is a
whey-derived product that concentrates the active globulin (immune)
proteins in cow milk.
BACKGROUND. Probioplex is a source of
secretory IgA, the immunoglobulin found in mucosal secretions.
Secretory IgA is produced in the mucous lining of the intestines and
is essential both for maintaining the gut barrier and for "tagging"
unfriendly organisms in the gastrointestinal tract. It is used in the
treatment of leaky gut, ulcers, and damage to gut mucosa. Secondary
benefits include increased immune system efficiency, reduction of
yeast overgrowth, and control of enteric viral and bacterial
infections.
USES IN CFS/ME. Probioplex is
recommended for treating digestive tract problems, particularly leaky
gut, irritable bowel syndrome, gas, and food sensitivities. It may
serve as a substitute for L-glutamine for those who cannot tolerate
amino acids, as it performs a similar function. Probioplex also
stimulates the growth of helpful bacteria in the intestines, making
it a useful corollary treatment for Candida overgrowth, which is
common in CFS/ME. The secondary benefits of improving immune system
function are also highly relevant for patients with CFS/ME.
PROTOCOL. Probioplex is a powder that
can be mixed with water or juice. Nutritionists recommend ½ teaspoon
two to three times a day for 3 to 4 weeks. After that, the dosage
should be reduced to ¼ teaspoon once or twice a day and discontinued
when benefits are no longer noticeable. Reported benefits include
reduced abdominal pain due to gas, reduced bloating, relief of
constipation, reduced food reactivity, and improved sleep.
PROS AND CONS. Probioplex is safe, easy
to use, relatively inexpensive, and is available without
prescription. It resists digestion in the stomach and small intestine
and so may be taken with meals. However, because it is a whey
product, persons with milk allergies or sensitivities may not be able
to tolerate it. Probioplex also contains rice maltodextrin, which may
limit its value for those with rice allergies.
AVAILABILITY AND COST. Probioplex is
available from specialized vitamin stores and from online suppliers.
A 90-gm container (a one-month supply) costs about $30 from
PureFormulas.com.