[The section below is Chapter 5 of my book, Chronic Fatigue Syndrome: A Treatment Guide, 2nd Edition. A young woman from Denmark requested that I post this chapter on my blog so she could have access to a translation.]

Disclaimer: I am not a medical professional. Nothing on this blog should be interpreted as medical advice.


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.”
  • 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.”
  • 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.”

Dowson, David, MD. “Nutrition Toxicity and ME/CFS.”


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.

Good summary of 5-HTP as a CFS/ME treatment:
Discussion of 5-HTP as a CFS/ME treatment:
Dr. Teitelbaum on 5-HTP and other natural sleep aids:
General information on 5-HTP:

CFS/ME patient reviews of 5-HTP:

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. (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. (Abstract)


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.

Benefits of AKG and its functions in the Krebs cycle:
A detailed description of Krebs cycle intermediaries, including AKG. Very technical.

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. (Abstract)


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.

This article questions the necessity of supplementing lipoic acid with biotin.

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

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. (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.


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.

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.

Dr. Michael Rosenberg's amino acid protocols for treating CFS/ME.

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.

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.

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. (Abstract)


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.)

Dr. Teitelbaum's carnitine protocol:

Benvenga S, Amato A, Calvani M, Trimarchi F. “Effects of carnitine on thyroid hormone action.” Ann NY Acad Sci. 2004 Nov;1033:158-67. (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. (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. (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. (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. (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. (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. (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. (Abstract)
Plioplys AV, Plioplys S. “Amantadine and L-carnitine treatment of Chronic Fatigue Syndrome.” Neuropsychobiology. 1997;35(1):16-23. (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. (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. (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. (Abstract)


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.

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.


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).

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. (Abstract)


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.)

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.

Very thorough discussion of the role of taurine:

El Idrissi A , Trenkner E. “Taurine as a modulator of excitatory and inhibitory neurotransmission.” Neurochem Res. 2004 Jan;29(1):189-97. (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.
Nakagawa K, Kuriyama K. “Effect of taurine on alteration in adrenal functions induced by stress.” Jap. J. Pharmacol. 1975 Dec;25(6):737-46. (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. (Abstract)


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.)

Dr. Myhill's excellent discussion of antioxidants:
Logan, Alan C. and Cathy Wong. “Chronic Fatigue Syndrome: Oxidative Stress and Dietary Modifications.” Altern Med Rev 2001;6 (5): 450-459.
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:
Dr. Cheney's talk on CFS/ME treatments, including antioxidants:

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. (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.
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. (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. (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. (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. (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 (Abstract)


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.

Dr. Sara Myhill's excellent discussion of hypochloridia:
Basic information about Betaine HCl:
A good explanation of the Heidelberg capsule test and hypochloridia.
Dr. Paul Cheney on dumping, hypochloridia, and Betaine HCl supplementation.


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.


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.

Sloan Kettering's review of the mechanisms of grape seed extract. Includes a list of studies.

Afaq F, Katiyar SK. “Polyphenols: Skin Photoprotection and Inhibition of Photocarcinogenesis.” Mini Rev Med Chem. 2011 Oct 28. (Abstract)
Lin, B. “Polyphenols and Neuroprotection against Ischemia and Neurodegeneration.” Mini Rev Med Chem. 2011 Oct 28 (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. (Abstract)


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.

Sloan Kettering's excellent summary of the mechanisms of pycnogenol. Contains a list of research studies:
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.
A thorough review of all research articles investigating pycnogenol.

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. (Abstract)


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.

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. (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. (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. (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. (Abstract)


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.

Life Extension is a bit pricier than other suppliers, but their website contains a very thorough description of the mechanisms of butyric acid.

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.


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. markets a bottle of 100 choline bitartrate capsules (235 mg) for roughly $10. 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.

This Oregon University site provides excellent information about choline.
“What are Choline and Inositol?” (Good overview):
“Choline on the Brain? A Guide to Choline in Chronic Fatigue Syndrome.” Cort Johnson. Aug, 2005.
Ray Sahelian's sensible advise on choline:
“Fundamentals of MR Spectroscopy.” John R. Hesselink. (A nice summary of MR spectroscopy.)

Chaudhuri, A., P.O. Behan. “In vivo magnetic resonance spectroscopy in chronic fatigue syndrome.” Prostaglandins, Leukotrienes and Essential Fatty Acids 71 (2004) 181–183.
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.
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.
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. (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.


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.

Excellent summary of CoQ10 in CFS/ME:
An interesting and useful site containing a discussion of ubiquinol, a comparison of ubiquinol to CoQ10, links and research:
Website of the International CoQ10 Association:
Ray Sahelian's informative site. Effects of CoQ10, studies and FAQs.
Compounding pharmacies that make CoQ10 troches:
Information on CoQ10 gel:

Patient reviews of CoQ10:

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. (Abstract)


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).

Dr. Teitelbaum addresses questions about D-Ribose:
Dr. Teitelbaum explains the functions and benefits of D-Ribose.
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.
Dr. Lapp's list of supplements, including D-Ribose:
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.
(This is a very long paper. You may want to jump to the following site.)
A summary of the information in the previous paper:
Creatine and D-Ribose studies:
A patient's encouraging report of her experiences with D-Ribose.


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 Enzymatic supplements can also be purchased in powder form. Plant-based enzymes, which are not degraded by stomach acid, should always be purchased.

Dr. Cheney discusses gut dysbiosis and CFS/ME symptoms:
Dr. Cheney discusses Betaine HCl and the function of enzymes. (Written by Carol Sieverling)
Lots of articles about enzymes:


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.

Very thorough overview of DHEA. Many studies are cited.
Dr. Cheney on DHEA and other supplements (1995).
Good article on the effects of DHEA on aging:

CFS/ME patient reviews of DHEA:

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. (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. (Abstract)


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.

“The ABCs of EFAs.” CFIDS Chronicle, Summer 2008.
Good summary of essential fatty acids, their function, and their role as a treatment for CFS/ME.

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 (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.
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.
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
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.


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.

CFS/ME patient reviews of fish 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.

CFS/ME patient ratings for flaxseed 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.

CFS/ME patient ratings of evening primrose 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. 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. 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.


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.
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.

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.
Kowalski A, Rebas E, Zylińska L. [Gamma-aminobutyric acid--metabolism and its disorders].Postepy Biochem. 2007;53(4):356-60. (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. (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. (Abstract)


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, 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.”

“If Only Galantamine Could Talk.” Great summary of galantamine's fascinating history as well as its medicinal properties:
“Can Galantamine Help Chronic Fatigue?” Article on acetylcholine deficiency in CFS/ME patients.
Ray Sahelian discusses galantamine:

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. (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.”
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.


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.

Results of a comprehensive multi-center investigation of glucosamine chondroitin.


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.

Rich Van Konynenburg's excellent review of glutathione, including protocols, dosages, suppliers.
Another excellent discussion by Rich Van Konynenburg proposing glutathione depletion as a cause of CFS/ME:
A list of articles about glutathione written by Rich Van Konynenburg.
An interesting, if somewhat convoluted, discussion of glutathione and its role in CFS/ME.
Ray Sahelian discusses glutathione's role in various disease processes. Some good research citations.
Glutathione suppositories:

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. (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.
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. (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. (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. (Abstract)


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.

Dr. Teitelbaum's herb recommendations for CFS/ME patients.
Nicely organized site about herbs. Herbs are listed alphabetically for easy access.

Castleman, Michael. The Healing Herbs. Emmaus, Pa.: Rodale Press, 1991
This is a well-organized introduction to herbs and their uses.

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.

General information about aloe vera:
CFS/ME patient reviews of aloe vera:

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).

General information about astragalus
More general information about astragalus:

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. (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

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.

General information about chamomile:

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.

General information about echinacea:
CFS/ME patient reviews of echinacea:

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. (Abstract)

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.

General information about garlic:
CFS/ME patient reviews of garlic:


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.

CFS/ME patient reviews of ginger:


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).

General information about gingko:
More general information about gingko:
CFS/ME patient reviews of gingko:
Logan, Alan C., and Cathy Wong. “Chronic Fatigue Syndrome: Oxidative Stress and Dietary Modifications.”

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. (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. (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. (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. (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. (Abstract)

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.

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. (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. (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. (Abstract)

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.

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. (Abstract)

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.

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. (Abstract)

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.

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. (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. (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. (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.

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 (online). Douglas Labs sells a 60-capsule bottle of pure licorice (500 mg) for $16 (also through

Good article on licorice:
Excellent summary of licorice as a treatment for CFS/ME:
General information on licorice root:
Ray Sahelian on licorice:
Baschetti, R. “Chronic fatigue syndrome and liquorice” N Z Med J. 1995 Apr 26;108(998):156-7.

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.

Literally everything you need to know about lomatium:

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 for roughly the same price.

Detailed information on silymarin:
Ray Sahelian on milk thistle. Includes dosage, research and medical uses.

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. (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. (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.


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.

Good general information about St. John's Wort:
Cochrane Collaboration's summary of research on St. John's Wort for depression.
A CFS/ME patient's review of St. John's Wort:

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. (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. (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. (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. (Abstract)

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 (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.

Good summary of the uses of valerian:
Several CFS/ME doctors discuss remedies for insomnia, including valerian.

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. (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. (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. (Abstract)


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.

Histame website:
Patient thread on Histame:
Patient thread on histamine intolerance:
Comprehensive list of histamine-rich foods:
An interesting study about histamine fish poisoning:

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.
Maintz, Laura and Natalija Novak. “Histamine and histamine intolerance.” American Journal of Clinical Nutrition, Vol. 85, No. 5, 1185-1196, May 2007
In-depth medical study examining the effects of histamine on the gut, histamine intolerance, and the correlation of DAO levels with food intolerance.


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.

Basic information on isoprinosine, including sources.
Manufacturer's description of Imunovir:
CFS/ME patient thread discussing isoprinosine and inosine:


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. 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.

Ray Sahelian's informative page on inositol:
Links to useful articles about inositol:
A nice summary of the functions of inositol in the body:
Treatment of obsessive-compulsive disorder, panic attacks, and depression with inositol.
Maija Haavisto's excellent summary of treatments she has tried. Scroll down for inositol, or read them all:
Very interesting and informative patient thread about the use of inositol in OCD and its relationship with histamine:

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. (Abstract)


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. 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

Patient thread on malic acid:

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. (Abstract)


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.

“Sleep and Snake Oil.” Rachel Preiser. Discover Magazine. March 1997.
Cort Johnson's informative page about melatonin in CFS/ME.
Dr. Lapp on melatonin and other sleep medications.
Melatonin safety assessment by the Mayo Clinic.
CFS/ME patient forum on melatonin:

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. (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. (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. (Abstract)
Guerrero JM, Reiter RJ. “Melatonin-immune system relationships.” Curr Top Med Chem. 2002 Feb;2(2):167-79. (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. (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. (Abstract) (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. (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.
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. (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. (Abstract)


Calcium, Magnesium, Selenium, Colloidal Silver, Zinc


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 Advanced Research also markets a 100-tablet bottle of calcium aspartate for the very affordable price of $7.

Good overview of calcium, including rates of absorption for different calcium compounds.
Brief interview with Dr. Spreen about the different forms of calcium and their bioavailability.
Ionic calcium supplier:
“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.
Good medical article about the importance of measuring ionic calcium in the bloodstream.


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.
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. 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.

Excellent summary of magnesium's effects on the body from the Linus Pauling Institute.
Dr. Myhill discusses magnesium deficiency and treatment in CFS/ME patients.
USDA statistics on nutrient consumption by state and nationally.
“Review and Hypothesis: Might Patients with the Chronic Fatigue Syndrome Have Latent Tetany of Magnesium Deficiency.” Mildred Seelig, MD, MPH

Cox IM, Campbell MJ, Dowson D. “Red blood cell magnesium and chronic fatigue syndrome.” Lancet. 1991 Mar 30;337(8744):757-60. (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. (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. (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. (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


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. 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.

Detailed information about selenium from the Linus Pauling Institute.
“Is Selenium Deficiency Behind Ebola, AIDS and Other Deadly Infections?”

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.
Beck MA, Levander OA, Handy J. “Selenium deficiency and viral infection.” J Nutr. 2003 May;133(5 Suppl 1):1463S-7S. (Abstract)
Beck MA, Handy J, Levander OA. “Host nutritional status: the neglected virulence factor.” Trends Microbiol. 2004 Sep;12(9):417-23. (Abstract)
Benton D. “Selenium intake, mood and other aspects of psychological functioning.” Nutr Neurosci. 2002 Dec;5(6):363-74. (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. (Abstract)


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.

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. (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. (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. (Abstract)
Lansdown AB. “Silver in health care: antimicrobial effects and safety in use.” Curr Probl Dermatol. 2006;33:17-34. (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. 2 (Abstract)


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).

Essential reading about zinc:
Article discussing zinc bound in yeast:
Interesting study of high-zinc yeast in rats:

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.
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.


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 Ecological Formulas markets two monolaurin combinations (one with magnesium, and one with lysine) for roughly $13 for a 90-capsule bottle (through online).

A Review of Monolaurin and Lauric Acid. Shari Lieberman and Harry Preuss.
Patient thread on monolaurin:
Manufacturer's information on Lauricidin:

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. (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. (Abstract)


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.”

Good general information about mushroom extracts.
Report on RM-10 mushroom extract administered to CFS/ME patients.
Description of RM-10:


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.

“Mushroom Extracts: Exciting News for Good Health.” Neenyah Ostrom's article on LEM and CFS/ME.
Sloan Kettering's very thorough review of shiitake 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. markets a full spectrum maitake extract made by Mushroom Science for $24 for a bottle of 90 capsules.

Extensive list of many maitake extracts:

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. (Abstract)


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.

Sloan-Kettering's page on cordyceps:
“Dr Oz: Chronic Fatigue Syndrome, Cordyceps & D5 Ribose Sweetener.”
“Cordyceps Chinensis.” Everything you could possibly want to know about Cordyceps.
“Mushroom remedy 'makes you fit' A Chinese mushroom improves the fitness of middle-aged and elderly people, research suggests.”

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).

Kelly GS. “Clinical applications of N-acetylcysteine.” Altern Med Rev. 1998 Apr;3(2):114-27. (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. (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.


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. 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.

The official ENADA site, containing product and brand information:

Dr. Birkmayer's review of ENADA, including summaries of trials, and recommended dosage.
Patient thread on NADH. Includes references to several studies, responses and dosage.

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. (Abstract)


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.

CFS/ME forum discussing some of the risks of probiotics.
“Intestinal Flora.” Very good website with research and specific information on intestinal flora.
"Probiotics in Clinical Practice: An Update." Good general information about the clinical use of probiotics:
“An Emerging Trend of High Dose Probiotic Use in Clinical Practice- A Brief Survey.” October 2011.
Hibberd, Patricia L., Lisa E. Davidson. “Safety of probiotics.”
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.

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.
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. (Abstract)
Guandalini S. “Probiotics for prevention and treatment of diarrhea.” J Clin Gastroenterol. 2011 Nov;45 Suppl:S149-53. (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.
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.

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. 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.

“Living With Chronic Fatigue Syndrome” blog entry on piracetam.
Patient experiences with piracetam

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. (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. (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.
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. (Abstract)
Winblad, B. "Piracetam: a review of pharmacological properties and clinical uses." CNS Drug Reviews (2005)11 (2): 169–82. (Abstract)


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. 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.

A pilot study of Irena Royal Jelly conducted on 109 ME patients:
Suppliers of Y&S pure royal jelly:
Online site for purchasing pure royal jelly:

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. (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. (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. (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. (Abstract)


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.

Complete information about the composition, effects and clinical research of elderberry extract.

Konlee, M. “A new triple combination therapy.” Posit Health News. 1998 Fall;(No 17):12-4. (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. (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. (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.


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

Ray Sahelian on SAMe:
Dr. Myhill discusses the methylation cycle:

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. (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.


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.

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.

General information about vitamins (and other) supplements for CFS/ME patients.


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.


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.

Dr. Cunha on beta-carotene supplementation for CFS/ME patients.
CFS/ME patient ratings of beta-carotene:


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.) markets B12 spray (with B6 and folic acid) made by NOW for $12.59.

Dr. Lapp's B12 recommendations:
Dr. Myhill's excellent explanation of why B12 works in CFS/ME patients.
B12 Basics – very detailed:
Informative patient thread on the uses of B12 for treating CFS/ME.

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.


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.

The University of Maryland's informative page on vitamin B6.

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. (Abstract)


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).


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.

Good overview of vitamin C supplements.
Detailed overview of the Krebs cycle and its role in CFS/ME.
CFS/ME patient ratings of vitamin C:


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.

List of articles concerning vitamin D deficiency:
CFS/ME patient reviews of vitamin D:

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. (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. (Abstract)


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.

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 and Vitacost for roughly $13 to $25 a bottle.

CFS/ME patient reviews of vitamin E:

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. (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. (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. (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. (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. (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. (Abstract)


Colostrom, Undenatured Whey, Probioplex


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.

Colostrum and leaky gut:

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. (Abstract)


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. 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.

Patient thread on nondenatured whey, including an excellent explanation of how these products work by Rich Van Konynenburg
Information about whey and lactoferrin:
Dr. Cheney talks about whey protein and glutathione
Carol Sieverling's article about whey, Cheney and glutathione.
Detailed information on whey and glutathione

Bounous G, Gold P. “The biological activity of undenatured dietary whey proteins: role of glutathione.” Clin Invest Med. 1991 Aug;14(4):296-309. (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. (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. (Abstract)


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

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