Tuesday, September 8, 2015

Abundant Energy Summit: Dr. Myhill speaks about the role of mitochondrial function in ME/CFS

This article first appeared on ProHealth.

Following (scroll down) is a transcript from the Abundant Energy Summit’s interview with Dr. Sarah Myhill.

The Summit was held from August 24 - 31, 2015 and featured a number of speakers.

Dr. Myhill is a physician who specializes in ME and other complex illnesses. Her approach is considered "alternative," that is, it draws upon nutritional strategies, hands-on therapies, and supplementation with micronutrients, rather than relying exclusively on pharmaceuticals.

Much like Dr. Cheney, Dr. Myhill believes that mitochondrial dysfunction lies at the heart of ME/CFS. The mitochondria are the power houses of cells. Their job is to form adenosine triphosphate (ATP), the molecule that generates the energy needed for all functions - breathing, digesting, thinking, walking ... everything. When the mitochondria are inhibited from doing their job, less ATP is produced, and, as a consequence, your ability to maintain physical and mental function is reduced. (Skeletal muscle is especially affected, as the mitochondria in muscle cells are less efficient that those in organs. Typically, people with mitochondrial disease find it difficult to walk.)

ATP is composed of three parts: 1) adenine, a purine nucleobase, 2) ribose, a sugar, and 3) three phosphates connected by high energy bonds. When one of those bonds is broken by an enzyme, 7,200 calories are released. That's a lot of energy. And we need all of it. In order to simply lie in bed and breathe, an adult uses roughly 10 million ATP molecules per second.

If your mitochondria are impaired in any way, even a tiny bit, your body will find it difficult to perform even the most basic functions. You will find it difficult to digest your food (the production of stomach acid requires an enormous amount of ATP), your heart will suffer from diastolic dysfunction, which also requires a large amount of ATP, you will be unable to think clearly, you will experience muscle weakness, particularly in the legs, and you will be exhausted after the slightest effort. The more your mitochondria are impaired, the more exhausted you will be, and the less it will take to send you to bed.

Dr. Myhill's site is a goldmine of information. On it, you will find everything from alcohol intolerance to valacyclovir. I encourage you to take a look.

Niki Gratrix: Hi everyone this is Niki Gratrix and welcome to another episode of the Abundant Energy Summit. I have the pleasure today of introducing Dr. Sarah Myhill.

Dr. Myhill worked with the NHS for 20 years before entering into private practice. She was the Honorary Secretary for the British Society for Allergy and Nutritional Medicine for 17 years, and has worked with over 5,000 patients with fatigue.

She believes the central mechanism is mitochondrial dysfunction. She is the author, with colleagues, of three scientific studies in the International Journal of Clinical and Experimental Medicine showing that the level of mitochondrial dysfunction correlates with the degree of fatigue. She is also the author of the book, It’s Mitochondria Not Hypochondria.

Q: You have a car analogy in your book. Please explain that.

Myhill: Let’s start from the beginning. The first and most important thing to grasp about Chronic Fatigue Syndrome is that it is not a diagnosis, it is a clinical picture that may have many causes. It is my job as a physician to find the causes. The second important thing to grasp is that we have symptoms for a very good reason. Symptoms protect us from ourselves. If we didn’t experience fatigue we’d work all day and all night. And we’d be dead in eleven days, because nobody has survived eleven days without sleep.

The symptom of fatigue can arise for many reasons that have to do with delivery systems and energy expenditure - how we spend and create our energy. We always have to keep ourselves where our energy demands don’t exceed our energy delivery. We need to pay attention to both sides of the equation: energy demands vs energy delivery.

The body is just another machine, like a car. Like any machine it needs the right fuel in the tank. That fuel has everything to do with diet and gut function.

How do we burn our fuel to create energy? Mitochondria are essential for creating energy from fuel. They are the little engines that exist in every cell in the body, and in every cell in every living organism. Without mitochondria we wouldn’t have life as we know it.

What mitochondria do is they take fuel from the bloodstream derived from carbohydrates, fats, and proteins (in the form of acetate groups) and burn them in the presence of oxygen to produce ATP. Think of ATP as a molecule with which you can do any function in the body.

The thyroid gland is also terribly important. It determines how the fast those mitochondria go, like an accelerator pedal in a car. We have to be careful about how we spend our energy. Spend it too fast and we wouldn’t have survived a harsh winter.

What allows us to gear up energy spending is the adrenal gland, which I think of as the gear box in a car. Adrenaline is the short-term immediate hormone for energy delivery; cortisol is the intermediary and DHEA is for long-term energy delivery. Those hormones allow us to adjust energy demand to energy delivery very closely.

Of course, all cars have to be serviced regularly. We service our bodies during sleep. Every single living thing, even bacteria, need a time in which metabolic processes shut down to allow healing and repair to take place.

Those are the central, important aspects.

Q: You talk about how the immune system takes up a huge amount of energy.

Myhill: That’s on the other side of the equation, where we look at how energy is spent in the body. An astonishing amount of energy – two-thirds of all energy we generate – just goes into staying alive: basic metabolic rate, heart function, lung function, gut function, liver function, brain function. All those things demand energy. The rest we should spend physically, or mentally, in terms of mental exercise.

I think of the immune system as a brain that isn’t contained within the skull, but is spread throughout the body. It’s intelligent, it’s decision-making. It’s highly active, and it’s highly demanding of energy. It likes to run on fat, and so on. But when the immune system is activated it uses up a massive amount of energy.

How do I know that? If a normal person gets flu, they get instant ME. They’re bed-bound for a week or two until their immune system switches off and they get well again. When their immune system is activated because of infection, that’s normal, desirable, and essential to dealing with an infectious threat.

But if the immune system is activated because of allergy, that’s what I call useless inflammation. The body is spending immunological energy on something that is not a threat. That kicks an immunological hole in our energy bucket.

Q: Let’s focus a little more on the mitochondria. Would you please expand on the production of ATP?

Myhill: When ATP is being efficiently recycled, ATP forms ADP. Then it goes back into the mitochondria where it again forms ATP. That is an extraordinary efficient cycle. In fact, when we are functioning at our maximum potential, a molecule of ATP can be recycled back through our mitochondria every ten seconds. If there was no such recycling, then we would burn more than our body’s weight of ATP every day.

We run into problems when energy demand exceeds energy delivery. The body has some emergency mechanisms. Let’s say I have to run for my life, all these energy systems would be employed. One of them is to switch into anaerobic metabolism that produces lactic acid. We all know about that. It’s the lactic acid burn that slows athletes down and stops them, and stops ME patients as well.

Another mechanism is when two molecules of ADP combine to form one molecule of ATP and one of AMP. The ATP can be quickly recycled, but the AMP is recycled very slowly. So suddenly, you’re pulling the plug on your supply of ATP. It’s all draining out of your system. That is what I suspect causes the delayed fatigue in ME.

Interestingly, another paper has come out recently, where they tried to reproduce that idea in a computer using low rates of metabolism and putting in all the variables. And they came up with the same conclusion.

Q: What are some of the causes of mitochondrial underfunction?

Myhill: Broadly speaking, there are two important causes. The mitochondria can be deficient in raw materials – magnesium, CoQ10, acetyl-l-carnitine, vitamin B3, and D-ribose. Those are the 5 things we see that mean the mitochondrial are deficient. We measure these things when we do mitochondrial tests.

Or, mitochondria can be going slow because they are blocked by something. Blocking factors can include environmental toxins, energy delivery blockers, heavy metals, and fermenting gut products.

You can block mitochondria by stacking things on top of the mitochondrial membrane. It’s no good making ATP if you can’t get the ATP out of the mitochondria and into the cell where it’s needed. Mitochondrial membranes are made up of proteins that act like a little shuttle that takes ATP out of the mitochondria and then brings ADP back into the mitochondria where it is turned into ATP. There are lots of things that can block that shuttle. We can do tests to determine what those blocking factors are.

As an aside, I got interested in ME when I started seeing farmers with sheep dip flu. They had been poisoned by organophosphates. Organophosphates inhibit oxidative phosphorylation. That is how they block the mitochondia’s ability to make ATP.

Broadly speaking those blockers fall into two groups: they can be toxins from the outside world, such as pesticides and heavy metals, or they can be products from within the body. I suspect a major source of those is products from the fermenting gut.

Q: And inflammatory processes lead back to the gut.

Myhill: Mitochondria are important, but I spend as much time with my patients talking about diet, and talking about gut function. So many problems start with the gut.

Q: Mitochondrial malfunction explains the illness brilliantly, but it’s not the cause, it’s the effect.

Myhill: The whole thing is circular. We all come into this area with different theories, but we all end up offering similar patterns of treatment – diet, detoxing regime, nutritional supplements, correcting hormones, and so on. But mitochondria are central players.

Q: Diet, pacing, micronutrients and sleep are your four foundational things. Do you want to expand a little on that, especially pacing?

Myhill: It’s back to square one. Fatigue is a mechanism that protects us from ourselves. If someone is experiencing fatigue because they are overdoing, they are constantly stressing their mitochondria and their energy supply and they are constantly going into anaerobic metabolism and producing lactic acid.

Let’s talk about anaerobic metabolism. Normally, mitochondria function on oxygen. When you burn a molecule of sugar in the presence of oxygen, you’ll produce about 26 molecules of ATP. But when you stress your mitochondria and switch to anaerobic metabolism, burning a molecule of sugar only produces two molecules of ATP. If you do this on a regular basis you get a buildup of lactic acid.

To convert that lactic acid back to pyruvic acetate takes six molecules of ATP. What that means is if you overdo things it takes an awfully long time to get back to square one. The point of pacing is to avoid getting into anaerobic metabolism. So, pacing is crucially important. People will get better if they pace. If they don’t pace, eventually there is tissue damage and inflammation sets in, which kicks another hole in the energy bucket.

Q: You have a basic protocol for micronutrients, what is that?

Myhill: Although I began by seeing patients with ME, I have come to the conclusion that no matter what a patient comes to me for, there is a basic package of treatment that we should all be doing. In terms of diet, this consists of a “stone age diet”: meat, fish and eggs, nuts and seeds, lots of veggies, and low-fructose fruits, such as berries.

Number two is sleep. Most people are sleep deprived. If you need an alarm clock to wake up in the morning you are sleep deprived.

The third thing I talk about is micronutrients. Because modern farming depletes the soil of minerals, we should all be taking a basic package of micronutrients – vitamins, minerals, and amino acids.

Q: Talking further about the Stone Age Diet, are you recommending a grain-free diet?

Myhill: Grains are too toxic for humans to consume. So, remove all gluten completely. The fermenting gut is a very big problem.

The upper gut should be a near-sterile carnivorous digesting gut to deal with meat and fat. The lower gut, which is teeming with bacteria, digests vegetable fiber. So, the lower gut is a fermenting gut. If we overwhelm our liver with sugar, for example, we switch into the fermenting gut and have all the problems of metabolic syndrome.

What I am saying is that a modest amount of carbohydrate is fine if you’ve got perfect digestion. But my ME patients don’t have perfect digestion. So, carbohydrates are a major risk factor for chronic fatigue syndrome.

I consider being vegetarian a major risk factor for chronic fatigue syndrome for two reasons. Vegetarian foods tend to be high GI, that is, grains and fruits. They are also high in the major antigens: dairy, gluten, and yeast.

Q: Would you talk a little about B12 and magnesium?

Myhill: Magnesium is centrally important for mitochondrial function. In fact, 40% of all the energy that comes out of mitochondria simply maintains the ion pumps that kick calcium out of cells and drag magnesium in. If the mitochondria are going slow, they can’t kick the calcium out, which is toxic within cells, and they can’t drag the magnesium in. So they don’t have the magnesium they need to make the mitochondria even work. There is a vicious cycle here. If you can’t get the magnesium in, the mitochondria won’t work, and if the mitochondria can’t work, you don’t get the magnesium in.

The reason magnesium injections are so helpful is that you are spiking the level of magnesium in the blood for a short period of time. All of a sudden it’s much easier to drag the magnesium into the cells. The mitochondria then start working again properly. Magnesium injections kick start the mitochondrial engine.

With B12 I think there may be a similar mechanism going. The thing about B12 is that it is very poorly absorbed. Even people with the best gut function will only absorb 1% of the B12 that they are taking. Only about another 1% actually gets into the brain, where it is very important for cognitive function.

The point about B12 is that if you inject it, you spike the levels in the blood, and you get the B12 into the brain. I’m only hypothesizing, because so many of my ME patients find their brain function and their mood is so greatly improved with B12 injections. B12 is performance enhancing in athletes, and even in horses. Trainers give horses B12 injections, and they go faster. That means their mitochondria are working better. And, B12 injections are an incredibly safe thing to do.

Q: Are you having much luck with transdermal forms?

Myhill: Transdermal forms of B12 are better than oral forms. They get about 6% absorption. But again, it’s not as good as the injection because you don’t spike blood levels.

Q: You mentioned the mitochondrial cocktail?

Myhill: When we do tests, we tailor treatments to individuals because we measure CoQ10, carnitine, B12, magnesium, and ATP. But if you can’t access those tests, you can do no harm by taking those supplements.

I have yet to find an ME patient with normal levels of CoQ10. These days I tend to use ubiquinol, which gets much better blood levels. 200 mg of ubiquinol will correct all my patients.

Q: Diet and environment need to be under control for any of this to work.

Myhill: That’s very important. We are living in an age in which we are being overwhelmed with toxins. A supplement I routinely prescribe for my ME patients is glutathione, which is essential for getting rid of heavy metals and is a potent antioxidant. With 250 mg a day of glutathione you can do no harm.

Another interesting facet of mitochondria is that they determine aging. We age at the rate that our mitochondria age.

Q: There have to be different approaches for different people. Some may need thyroid support, some adrenal support.

Myhill: I always say that getting people well from chronic fatigue syndrome or ME is like a jigsaw puzzle. You’ve got to have all the pieces in place at the same time. You can’t try one thing, and when it doesn’t work, you try another. You’ve got to start with the foundation stones of pacing, diet, supplements, sleep. Then you build on that with the mitochondrial stuff, thyroid stuff, adrenal stuff, gut fermentation stuff. You can do a lot of this yourself with simple nutritional therapy. It’s very doable.

Q: What about tests?

Myhill: The tests we use are all documented research tests. We apply them clinically. The problem with new, innovative tests is that they are hideously expensive. But don’t wait for the tests to come out to start to get better. Put the basic package in place as well as you possibly can. It’s all about tipping points.

I say to my patients, all we have to do is get you 51% better and your body will do the rest.

You can find out more about Dr. Myhill at DrMyhill.co.uk

Wednesday, August 26, 2015

An Open Letter from Researchers to Senator Mikulski: Patients suffering from ME/CFS deserve funding

The woeful state of funding for ME/CFS is so dire that two HHS-funded initiatives, the IOM and the P2P, have taken pains to point it out.

The IOM committee stated that “Remarkably little funding has been made available” to study this disease, and “More research is essential.” The P2P, a report sponsored by the NIH, came to the same conclusion.

Limited knowledge and research funding creates an additional burden for patients and health care providers. 
There are few disease-specific clinical trials; a disconnect on ways patients, clinicians, and researchers define meaningful outcomes; a lack of well- 4 controlled, multifaceted studies using large, diverse samples; and limited public and private research dollars directed at ME/CFS. 
Current research has neglected many of the biological factors underlying ME/CFS onset and progression. 
Overall, there has been a failure to implement what we already know for ME/CFS patients while the disease steals their health and well-being. Scientifically rigorous research is needed to improve this situation... Innovative biomedical research is urgently needed to identify risk and therapeutic targets.
In spite of this urgent need - stated in unequivocal terms by reports sponsored by HHS - the NIH has repeatedly denied funding to researchers who have a solid track record. Ron Glaser, President of the PsychoNeuroImmunology Research Society (PNIRS) and recognized as one of the world's most cited authors in his field, was turned down. Nancy Klimas, whose Gulf War research was funded, has been repeatedly rejected. Ian Lipkin, the world's foremost virus hunter, was rejected, as was Ron Davis, who was named among the top 7 of "Today's Greatest Inventors" in 2013 and is winner of numerous prestigious prizes.  

Nobody in their right mind could claim that these researchers did not know how to conduct meritorious research when they submitted their proposals. Yet, at the most recent CFSAC meeting Cheryl Kitt, Deputy Director of the Center for Scientific Review at NIH, claimed that there aren’t many people interested in researching ME/CFS and that the NIH hasn’t received applications of sufficient quality.

In answer to that specious claim, some of the top researchers in the field have written an open letter to Senator Mikulski (D- Maryland). Mikulski is chair of the Senate Appropriations Committee.

Read more about the push for increased NIH funding in this excellent article:

Lobbyists seek new funds for chronic fatigue syndrome research


August 17, 2015

Dear Senator Mikulski,

We the undersigned scientists are writing to express our interest and enthusiasm for researching myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a common and disabling illness long ignored by our nation’s health agencies.

Many of us have had a very difficult time securing adequate funding. Others have been unable to determine even how to apply for funding, as no institute within the NIH has responsibility for researching ME/CFS. The NIH has responded to requests for increased funding by stating that few researchers are interested in studying the illness.

On the contrary there are Nobel Laureates, several members of the National Academy of Sciences, biochemists, biophysicists, geneticists, immunologists, neuroscientists, experts in public health and infectious disease, epidemiologists, and physicians eager and ready to study this disease, were adequate funding made available. The undersigned are just some of those researchers.

We have so much to learn and large studies are needed to understand how to help patients regain their health. With societal costs in the tens of billions of dollars each year, an infusion of government funding could quickly repay that investment.

Currently, ME/CFS is massively underfunded compared to other diseases of similar severity and number of patients. The NIH allocates just $5 million per year to study this illness, which affects between 836,000 and 2.5 million Americans. Patients suffering from ME/CFS deserve funding proportional to and commensurate with other diseases with similar patient populations. The Institute of Medicine, a special HHS advisory committee, and a recent NIH­-appointed expert panel all agree: It is imperative to increase research funding for ME/CFS.

If invited to apply for NIH funding via a new Request for Applications (RFA), we would eagerly submit grant proposals.

Linda Tannenbaum, Executive Director, Open Medicine Foundation

Scientific Advisory Board:

Ronald W. Davis, Professor of Biochemistry and Genetics, Stanford University School of Medicine, Member of the National Academy of Sciences

Paul Berg, Nobel Laureate in Chemistry, Professor emeritus of Stanford University

Mario R. Capecchi, Nobel Laureate in the Physiology or Medicine category, Professor of Human Genetics at University of Utah School of Medicine, Member of the National Academy of Sciences

Mark M. Davis, Professor of Microbiology and Immunology at Stanford University School of Medicine, Director of Stanford Institute for Immunity, Transplantation and Infection, Member of the National Academy of Sciences

H. Craig Heller, Professor of Biology at Stanford University

Andreas M. Kogelnik, Physician­, Scientist, Founder and Director of the Open Medicine Institute

Baldomero M. Olivera, Biology Professor at the University of Utah, Member of the National Academy of Sciences

Ronald G. Tompkins, Professor of Surgery at the Harvard Medical School, Chief of Trauma, Burns and Surgical Care Service at the Massachusetts General Hospital, Chief of Staff at the Shriners Hospitals for Children in Boston

James D. Watson, Nobel Laureate in Physiology or Medicine, Chancellor of Cold Spring Harbor Laboratories, Member of the National Academy of Sciences

Wenzhong Xiao, Assistant Professor of Bioinformatics at Harvard Medical School, Director of the Inflammation & Metabolism Computational Center at Massachusetts General Hospital

Susan Levine, MD Researcher and Clinician, Private Practice New York, New York Visiting Fellow, Cornell University Ithaca, New York

Peter C. Rowe, MD, Professor of Pediatrics, Director, Pediatric Chronic Fatigue Clinic, Johns Hopkins Children’s Center, Maryland

Alan R. Light, PhD, Professor, Department of Anesthesiology and Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, Utah

Kathleen C. Light, PhD, Researcher, Professor, Department of Anesthesiology, University of Utah School of Medicine, Salt Lake City, Utah

Zaher Nahle, Phd, MPA, Vice President for Research and Scientific Programs, Solve ME/CFS Initiative, California

Leonard A. Jason, PhD Professor of Psychology DePaul University Chicago, Illinois

Derek Enlander, MD, MRCS, LRCP Attending Physician Mount Sinai Medical Center, New York ME CFS Center, Mount Sinai School of Medicine New York, New York

David L. Kaufman, MD, Medical Director, Open Medicine Institute, California

Staci Stevens, MA, Exercise Physiologist, Founder of Workwell Foundation, California

Jared Stevens, BS, Clinical Coordinator, Workwell Foundation, California

Dorothy Hudig, PhD, Professor of Immunology, Department of Microbiology and Immunology,
University of Nevada School of Medicine Reno, NV

Patrick O. McGowan, PhD, Assistant Professor, University of Toronto Scarborough Centre for Environmental Epigenetics and Development (CEED) Department of Biological Sciences Cell
and Systems Biology, Psychology, Physiology Toronto ON

Marcie Zinn, PhD, Neuroscientist, DePaul University Chicago, Illinois

Mark Zinn, Co Founder, NeuroCognitive Research Institute, Dublin, CA

Jarred Younger, PhD, Associate Professor, Departments of Psychology, Anesthesiology, and Rheumatology, University of Alabama at Birmingham

David Maughan, PhD, Professor of Molecular Physiology & Biophysics, Emeritus, University of Vermont School of Medicine Burlington, VT

Wednesday, August 19, 2015

ME Action Calls for Funding Equality

In light of the recent CDC funding cut for ME/CFS, ME Action's call for equal funding is both timely and urgent.

Along with Mass CFIDS Association Board members, I am meeting with Elizabeth Warren's staff on Thursday. I urge all of you in the target states (see below) to contact your representatives.

These meetings can be done by phone, and by several people simultaneously.

There are two messages: Increase funding commensurate with impact of the illness, and move ME/CFS from the Office of Research on Women's Health (which gets no funding), to the National Institute of Neurological Disorders and Stroke.

This is a representative democracy. Let's get represented!
#MEAction recently launched as an online platform to help anyone become an advocate.
Now we are announcing our own advocacy action: A quick-strike lobbying campaign to spur the US Congress to vastly increase research funding for ME/CFS at the National Institutes of Health.
We launched this effort to capitalize on the 21st Century Cures Act, which would give the NIH an extra $8.75 billion over five years. The House of Representatives passed the bill earlier this summer, and the Senate is now considering the bill. Currently, the NIH allocates just $5 million per year of its $31.3 billion budget to study ME/CFS.

This moment is crucial – key senators on the HELP committee can add provisions to the bill before they vote.


To that end, we have retained a well-connected consultant who previously worked for the Senate Finance Committee and helped pass key provisions of the Affordable Care Act. This consultant is now meeting with important Senate staffers, and patient advocates are calling into those meetings to present our two-point “ask”:
  • NIH will establish authority for researching ME/CFS within the National Institute of Neurological Disorders and Stroke (NINDS).
  • NINDS will establish an intramural and extramural ME/CFS program, funded at levels comparable to illnesses with similar patient numbers and economic cost to society.
Getting this language written into law would be a major victory for ME/CFS patients and allies. Our early experience suggests that key Senate staffers are open to this message. There’s a lot of work still to be done, and the outcome is uncertain. But one thing is certain: We will make progress by repeatedly sending this consistent message to Congress.
You can download our “one-pager” that we are using to present our case here.


We still need help from patient advocates willing and able to call into 30-minute meetings on Capitol Hill from the following states and Congressional districts:
  • Alaska (all)
  • Kansas (all)
  • Kentucky (all)
  • Louisiana (all)
  • Michigan (Midland, Saginaw Township, Mount Pleasant, Owosso, Thomas Township, Bridgeport Township, Big Rapids and Alma)
  • New Jersey (New Brunswick, Perth Amboy, Sayreville, Piscataway and Asbury Park)
  • Wyoming (all)
If you live in any of those locations and would like to join the effort, please sign up here.
No matter where you live, sign the US funding equality petition and help us take the petition to the streets.


In the coming weeks, we will be enlisting the entire community’s help to speak to Congress in one, loud voice through a coordinated campaign. In the meantime, we need your help to make this endeavor a success. The huge lobbying efforts for Alzheimer disease, Parkinson disease, and other major diseases spend millions of dollars each year trying to reach Congress.
Please donate today. Consider making it a recurring donation. Your contribution, no matter how small, will help us bring the future here faster.


Monday, August 10, 2015

Ampligen to Be Supplied Throughout Europe As Well As Turkey

Hemispherx Biopharma's agreement to supply Ampligen to ME/CFS patients in Europe could not have come at a better time.

 recent paper by a group of downstate New York psychiatrists made headlines when it proposed that fibromyalgia and CFS (among others) should be placed on the spectrum of anxiety disorders.

The agreement to use an immune modifier to treat ME/CFS underscores the position stated in the IOM report that this is not a psychogenic disease, much less an anxiety disorder.


Hemispherx Enters Into an Agreement With myTomorrows for an Early Access Program for Rintatolimod in Europe

Press Release: PHILADELPHIA, Aug. 10, 2015 (GLOBE NEWSWIRE) -- Hemispherx Biopharma, Inc. (NYSE MKT: HEB) (the "Company" or "Hemispherx"), reported today that it has executed an agreement with Impatients, N.V., a Netherlands based company doing business as myTomorrows, for the commencement and management of an Early Access Program (EAP) in all of Europe and Turkey.

myTomorrows, as Hemispherx' exclusive service provider in Europe and Turkey, will perform EAP activities in Europe and Turkey to include the supply of rintatolimod for the treatment of Chronic Fatigue Syndrome (CFS) to patients with an unmet medical need.

Govert Shouten, Ph.D, Co-Founder & CBO at myTomorrows, said "Rintatolimod for CFS fits perfectly with the raison d'être of myTomorrows. CFS affects as many people in Europe as in the US and there is no drug approved anywhere specifically for CFS. In clinical trials rintatolimod has shown promising results for certain CFS patients particularly those most severely affected.

As we do with other life-threatening and debilitating diseases such as cancer, MS, and depression, myTomorrows will set up and roll out the early access programs needed to help these patients.

Thomas K. Equels, Executive Vice Chairman and CFO of Hemispherx said "We are very pleased to be collaborating with myTomorrows to provide rintatolimod under these unique Early Access Programs. Not only will this collaboration create the possibility for physicians to use rintatolimod under certain circumstances, myTomorrows will collaborate with these physicians to capture data on patients treated and such data may add to our other efforts to gain full regulatory approval in Europe, Latin America, Australia, New Zealand as well as the U.S. and elsewhere."

myTomorrows was founded by physicians and experts from the pharmaceutical industry who want to facilitate early access to developmental drugs for patients with high unmet needs. Ronald Brus, M.D., was the former CEO of Crucell, a vaccine company acquired by Johnson & Johnson for $2.4 billion in 2011. Govert Shouten was previously Vice President, Business Development at Crucell.

About Rintatolimod

Rintatolimod is a member of a new class of specifically-configured ribonucleic acid (RNA) compounds targeted as potential treatment of diseases with immunologic defects and/or viral causation.

About myTomorrows

myTomorrows provides patients that are excluded from clinical trials access to drugs in development. They focus on disease areas with unmet needs; oncology, neurology, psychiatry and rare diseases. myTomorrows identifies the latest developments in drugs and facilitates requests for access to these drugs in development. Their physicians and bio-medical specialists identify the latest drug developments from across the globe. Physicians and pharmacists can register online and request information about the drugs myTomorrows provides access to. In most countries health authorities must grant permission for treatment with a non-registered drug. myTomorrows facilitates requests for permission for physicians and pharmacists.

About Hemispherx Biopharma

Hemispherx Biopharma, Inc. is an advanced specialty pharmaceutical company engaged in the manufacture and clinical development of new drug entities for treatment of seriously debilitating disorders especially life-threatening viruses. Hemispherx's flagship products include Alferon N Injection® and the experimental therapeutics rintatolimod and alpha interferon LDO. Rintatolimod is an experimental RNA nucleic acid being developed for globally important debilitating diseases and disorders of the immune system, including Chronic Fatigue Syndrome. Hemispherx's platform technology includes components for potential treatment of various severely debilitating and life threatening diseases including cancers.

Disclosure Notice

The information in this press release is intended solely for the United States and includes certain "forward-looking" statements including without limitation statements about additional steps which the FDA may require and Hemispherx may take in continuing to seek commercial approval of rintatolimod for the treatment of Chronic Fatigue Syndrome in the United States and abroad. The final results of these and other ongoing activities could vary materially from Hemispherx's expectations and could adversely affect the chances for approval of the rintatolimod in the United States and other countries. Any failure to satisfy the FDA regulatory requirements or the requirements of other countries could significantly delay, or preclude outright, approval of rintatolimod in the United States and other countries including Australia and New Zealand.

Information contained in this news release, other than historical information, should be considered forward-looking and is subject to various risk factors and uncertainties. For instance, the strategies and operations of Hemispherx involve risk of competition, changing market conditions, changes in laws and regulations affecting these industries and numerous other factors discussed in this release and in the Company's filings with the Securities and Exchange Commission. The final results of these efforts could vary materially from Hemispherx's expectations. No evidence has suggested that rintatolimod will ever be commercially approved for the new potential treatment indications, including, but not limited, to the treatment of CFS.

Forward-Looking Statements

To the extent that statements in this press release are not strictly historical, all such statements are forward-looking, and are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Words such as "intends," "plans," and similar expressions are intended to identify forward-looking statements. The inclusion of forward-looking statements should not be regarded as a representation by Hemispherx that any of its plans will be achieved. These forward-looking statements are neither promises nor guarantees of future performance, and are subject to a variety of risks and uncertainties, many of which are beyond Hemispherx's control, which could cause actual results to differ materially from those contemplated in these forward-looking statements. Examples of such risks and uncertainties include those set forth in the Disclosure Notice, above, as well as the risks described in Hemispherx's filings with the Securities and Exchange Commission, including the most recent reports on Forms 10-K, 10-Q and 8-K. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Hemispherx undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise revise or update this release to reflect events or circumstances after the date hereof. No evidence is suggested that rintatolimod will ever be commercially approved for the CFS treatment indications mentioned in this release into USA or other countries.

Friday, August 7, 2015

Federal Government Slashes ME/CFS Funding to Zero

In an almost incomprehensible move, funding for ME/CFS has been eliminated entirely from the 2016 CDC budget. Both the IOM and the P2P reports - initiatives funded by the Federal government - stressed the woeful underfunding of ME/CFS and called for more research. Yet, the Federal government has responded by cutting funding completely.

Please take a moment to copy and paste the sample email below. Send it to:

Laura_friedel@appro.senate.gov;Chol_pak@appro.senate.gov; Alex_Keenan@appro.senate.gov; Lisa_bernhardt@appro.senate.gov

If you live in Massachusetts please fill out the contact form for Elizabeth Warren. You can find it here:

Send her this note:

Subject: Please restore CDC funding for Chronic Fatigue Syndrome

I understand that the Senate Appropriations Committee has recommended that funding for the CDC’s programs for Chronic Fatigue Syndrome be terminated as of 2016.

I am a patient with Chronic Fatigue Syndrome (CFS), also known as Myalgic Encephalomyelitis or ME/CFS. The Institute of Medicine has just issued a major report on this “serious, chronic, complex, multisystem disease” citing the devastation on the lives of the 836,000 to 2.5 million Americans who suffer from this debilitating disease, the $20 billion annual cost to society, and the enormous need for more research which can lead to better treatments and a cure. We need MORE money for research, medical education, and information for patients and their families, NOT a termination of support.

I urge you to reinstate the $5.4 million funding for the CDC/CFS programs immediately.

Reprinted from the Solve ME/CFS Initiative Website

Reinstate Federal Research Funding for ME/CFS

Please act now! The $5.4 million in CDC funding for ME/CFS has been stricken from the Senate’s version of the 2016 federal budget. As you can see from the graphic below, ME/CFS was the only disease to be reduced to $0.

You have an opportunity to directly impact federal funding for ME/CFS by sending an email to the four key staff members who serve the Senators on this budget committee:

Laura_friedel@appro.senate.gov;Chol_pak@appro.senate.gov; Alex_Keenan@appro.senate.gov; Lisa_bernhardt@appro.senate.gov
Please take a moment to send them an email asking that the funds be reinstated immediately. We have posted a draft letter here for you to use. Feel free to revise as it suits you but note that time is of the essence. We need to have the emails sent within the next week to have any chance at reversing this decision and preserving our much-needed funding.

Dear Senator:

I am writing to urge you to reinstate the $5.4 million for Chronic Fatigue Syndrome funding. This is included in the CDC budget under Emerging and Zoonotic Infectious Diseases, on Page 59 of the Senate Budget.

I understand that the $5.4 million in funding submitted by the Centers for Disease Control for Chronic Fatigue Syndrome has been stricken from the 2016 appropriations bill by the Senate Appropriations Committee. This is an appalling act of inhumanity, and I urge you to reinstate the $5.4 million amount into the 2016 budget without delay.

As you may be aware, the prestigious Institute of Medicine of the National Academies published a landmark report on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome on Feb. 10 of this year. The IOM committee unequivocally and scientifically established that Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome is a physiological, not psychological, illness. The IOM stated firmly that Myalgic Encephalomyelitis/Chronic Fatigue Syndrome is “a serious, chronic, complex, multisystem disease... In its most severe form, this disease can consume the lives of those whom it afflicts.”

The IOM committee further established that between 836,000 and 2.5 million Americans suffer from this devastating disease, which carries with it an economic burden of $17 to $24 billion to our country annually.

I am one of those Americans who has had their life and livelihood stolen by this illness, which renders 25 percent of us house- or bed-bound at some point. While the vast majority of us are not well enough to march on Capitol Hill to demand equitable funding from our government, rest assured we are still able to vote.

As a member of the Senate Subcommittee, I urge you to reinstate this $5.4 million CDC funding immediately. You have an opportunity to be on the right side of history.

Email address
USPS address

Friday, July 31, 2015

August Deadlines and Opportunities for Advocacy

Reprinted with the kind permission of Jennie Spotila and Occupy CFS

By Jennie Spotila

There are a number of opportunities for ME/CFS advocacy right now – all of which you can do on your own from home! Here are the details:

CFS Advisory Committee Public Comment: The Federal Register notice for the August 18-19th meeting has been published.
  • Registration to attend in person is different this time! You must download a form on the CFSAC website (although it’s not available yet) and email it to CFSACmtg@hhs.gov. Registration for attendance closes August 13th.
  • Public comment registration is required to comment in person or by phone. Request a slot by emailing CFSACmtg@hhs.gov. Comments are limited to three minutes in length, and registration closes August 10th.
  • Written public comment can be submitted, whether you have a speaking slot or not. Comments should be no longer than 5 single spaced pages using 12pt font, and should be in MS Word format. Email your comments to CFSACmtg@hhs.gov by August 13th for inclusion in the public record.
NIH Strategic Plan: Public comment is due August 16th. I‘ve posted details about the plan and my own comments.

Key States Targeted for NIH Funding Petition: MEAction is looking for advocates in twenty-two key states to participate in targeted advocacy with Congress. Even if you don’t live in one of those states, you can still sign the petition.

More advocacy actions will be launched in the near future, so stay tuned HERE.

Monday, June 29, 2015

Study Finds SEID Case Definition Captures Patients With Depression, MS, Lupus

The IOM study - a million dollars down the drain
Leonard Jason has done it again. He has applied the scientific method and come up with something that makes sense.

The IOM has, according to Jason, devised an unworkable case definition. This failure is due to lack of scientific method (coming up with a hypothesis, testing it against evidence, revising the hypothesis, and testing it again to see if it describes all known data and has predictive value).

HHS has a poor track record when it comes to epidemics of new illnesses. They not only came up with an unworkable case definition (and a ridiculous name) for ME a couple of decades ago, they ignored AIDS, are currently ignoring Lyme disease, and have consistently put the interests of the medical/industrial complex ahead of anything that resembles public health.

SEID and the definition that accompanies it are merely one more drop in the ocean of bureaucratic collusion that typifies HHS.

It takes people like Leonard Jason and his colleagues to demonstrate just how negligent HHS has been.

"Empirical methods," he says, "could have been employed to test the proposed classification system, and the committee members might have benefited from testing out their proposed model with an actual data set." This is a gentle way of saying, "you pulled this definition out of your left ear, and it doesn't work."

Here are all the ways it doesn't work, according to the report below:

1) In the first study (60 people) the definition for SEID captured 100% of the people with ME/CFS, but it also captured 33% of patients with MS, and a staggering 47% of patients with lupus.

2) In the second study (45 people), SEID captured 27% of patients with major depression.

3) In the third study (213 people), 75% of the patients who met the Fukuda criteria also met the criteria for SEID. But 44% of those who did not meet the Fukuda criteria were also diagnosed with SEID, and 47% of the patients who had fatigue from other causes - drug and alcohol related causes, psychiatric illnesses, anorexia, chronic diseases - also met the definition for SEID.

4) Using those statistics, and comparing them to the prevalence rate established by the Fukuda definition, Jason's team came up with a prevalence rate that was 2.8 times higher than the current rate. That means if the CDC currently calculates a prevalence of 1 million people with ME/CFS in the US, the estimate would be increased to 2.8 million. And the overwhelming majority of those patients would have other diseases.

Aside from the inability of the new definition to accurately identify a distinct patient population, Jason points out that this definition will ultimately make treatment research impossible: "If individuals with primary affective disorder are misdiagnosed with SEID and provided cognitive behavioral treatment, they will more likely have positive outcomes, and this may create more difficulties in understanding the effects of these interventions for those who have ME."

Jason has called for an "open and inclusive process where all parties, including key gatekeepers, including the patients, scientists, clinicians and government officials, are involved in the decision making process." However, given the abysmal lack of faith shown by HHS, it might be best to leave that department out of any decision making process that involves sick people.

Cited post: The IOM Report: The Good, The Bad, and the Absolutely Hideous


Unintended Consequences of not Specifying Exclusionary Illnesses for Systemic Exertion Intolerance Disease

By Leonard A. Jason *, Madison Sunnquist, Bobby Kot, and Abigail Brown

Center for Community Research, DePaul University, Chicago, IL 60614, USA (see end of article for contact information)


The Institute of Medicine recently proposed a new case definition for chronic fatigue syndrome (CFS), as well as a new name, Systemic Exertion Intolerance Disease (SEID). Contrary to the Fukuda et al.’s CFS case definition, there are few exclusionary illnesses specified for this new SEID case definition. The current study explored this decision regarding exclusionary illnesses using the SEID criteria with four distinct data sets involving patients who had been identified as having CFS, as well as healthy controls, community controls, and other illness groups. The findings indicate that many individuals from major depressive disorder illness groups as well as other medical illnesses were categorized as having SEID. The past CFS Fukuda et al. prevalence rate in a community based sample of 0.42 increased by 2.8 times with the new SEID criteria. The consequences for this broadening of the case definition are discussed.

Keywords: Myalgic Encephalomyelitis; chronic fatigue syndrome; systemic exertion intolerance disease; case definitions

1. Introduction

The Institute of Medicine (IOM) [1] recently proposed a new case definition, which was intended to replace the Fukuda et al. [2] chronic fatigue syndrome (CFS) criteria, the most widely used case definition for the past twenty years. The Fukuda et al. criteria [2] require four symptoms out of a possible eight, but it is possible that some individuals who meet these diagnostic criteria do not have core symptoms of the illness, such as post-exertional malaise. With the Fukuda et al. case definition [2], there are about a million people estimated to have this illness in the US [3]. In reaction to limitations in the Fukuda et al. case definition [2], the Canadian Clinical Criteria Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS) [4] was developed, and it specified core symptoms, including post-exertional malaise, impairment of memory and concentration, unrefreshing sleep, arthralgia and/or myalgia; and several autonomic, neuroendocrine, and immune manifestations. Still later, the International Consensus Criteria for Myalgic Encephalomyelitis (ME-ICC) criteria [5] were developed, and these criteria specified eight symptoms within four domains: Post-Exertional Neuroimmune Exhaustion; Neurological Impairments; Immune, Gastro-intestinal, and Genitourinary Impairments; and Energy Production/Transportation Impairments. Others have tried to develop more empiric-based methods [6]. Each of these case definitions excluded a variety of medical or psychiatric illnesses that might be the cause of the symptoms.

Recently, the IOM [1] issued a report that proposed a new name (Systemic Exertion Intolerance Disease, SEID) and case definition that included the following four symptoms: substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social or personal activities; post-exertional malaise; unrefreshing sleep; and at least one of the two following symptoms: cognitive impairment or orthostatic intolerance. Whereas the Fukuda et al. [2] CFS criteria, the ME/CFS Canadian criteria [4], and the ME-ICC criteria [5] excluded other medical and psychiatric conditions that might have produced the fatigue, the new SEID criteria [1] had a different position regarding exclusionary conditions. The IOM [1] (p. 186) document defining SEID stated: “Over the years, case definitions of ME/CFS have differed significantly in their classification of exclusionary conditions and comorbidities. As a result, a number of disorders, such as morbid obesity and an array of psychiatric disorders, are listed as exclusionary in one definition and as comorbid in another, despite the lack of scientific evidence that being affected by such disorders precludes having ME/CFS. Indeed, it has become increasingly clear that many patients with ME/CFS have other disorders as well…Some of these other disorders may develop as part of the spectrum of ME/CFS or in response to the burdens of this disorder.” In addition, within the IOM [1] (p. 185) SEID document, it states that a detailed history and comprehensive physical examination should be used “to determine a differential diagnosis and, where clinically indicated, to exclude other disorders that could cause the patient’s symptoms, as well as to identify any comorbid conditions”. More details on exclusions are provided within the IOM’s SEID Report Guide for Clinicians [7] (p. 4), where it states: “The presence of other illnesses should not preclude patients from receiving a diagnosis of ME/CFS (SEID) except in the unlikely event that all symptoms can be accounted for by these other illnesses.” The word “unlikely” conveys the impression that most other illnesses would be considered comorbid and not exclusionary as they probably would not account for the unique SEID symptoms.

The problem for diagnosticians in interpreting these guidelines is that the core IOM symptoms are not unique to SEID, as other illnesses have comparable symptoms (e.g., cancer, Hashimoto’s, lupus, chronic heart failure, multiple sclerosis, etc.). Thus, according to the above IOM guidelines, if these illnesses account for the SEID symptoms, then it is another illness and not SEID. Therefore, many illnesses are now considered a comorbid condition with SEID. However, trying to determine whether an illness is exclusionary vs. comorbid is a challenging diagnostic task. The IOM [1] (p. 187) provides the following example that illustrates this complexity: “The committee recognizes that diagnosis and treatment of comorbid conditions is necessary when caring for patients. For example, a patient with ME/CFS with a prominent history of snoring and sleep apnea may have polysomnography diagnostic of sleep apnea. Treatment with continuous positive airway pressure could improve the patient’s overall condition but not resolve all the symptoms of ME/CFS, signifying that in this individual, obstructive sleep apnea is a comorbid condition rather than the cause of the patient’s ME/CFS symptoms.” This suggests that if treatment resolved all the SEID symptoms, then the patient had another illness (in the case above, obstructive sleep apnea); however, if the treatment does not resolve the issues, than the condition is comorbid with SEID. In other words, the ability to determine if an illness is exclusionary rests on its successful treatment, and clearly, many chronic illnesses do not have treatments that cure or alleviate all symptoms.

In addition, Ze-dog [8] pointed out that this new SEID definition lacks exclusion criteria, and as a consequence, it is easier for a person with a primary psychiatric diagnosis to be labeled as having SEID. Verrillo [9] also commented on these exclusionary SEID ambiguities, and then suggested that because major depression is not exclusionary, patients with a primary psychiatric disorder might be included in the SEID classification. These publications were only commentaries and did not provide data, so it is still unclear whether the SEID case definition [1] could inappropriately include cases of purely affective disorders, such as Major Depressive Disorder (MDD). It is also unclear whether SEID is more common within other autoimmune illnesses such as MS and Lupus. The present study evaluated whether the SEID case definition distinguished between persons with MDD, and other illnesses, using archival data that were available. We used data from four distinct studies, each with different case ascertainment methods, so we could begin to determine how the new SEID criteria might affect a variety of samples representing tertiary care settings, community based settings, as well as more patient self-diagnosed samples. We hypothesized that individuals with a number of formerly exclusionary illnesses would meet the SEID case definition, thus possibly increasing the prevalence rate of this illness.

2. Methods

2.1. Study 1

2.1.1. Procedure

In the first study, a CFS screening questionnaire had a combination of existing and new measures including: (1) several demographic related items; (2) The Fatigue Scale [10]; and (3) a list of symptoms associated with CFS. Interviewees were asked a series of questions that assessed whether or not they had a number of symptoms commonly experienced by people with CFS. The symptoms needed to be experienced for 6 or more months. The questions were asked by interviewers (for more details of this study, see [11]).

2.1.2. Participants

A total of 60 individuals (15 with CFS, 15 Controls, 15 with Multiple Sclerosis (MS), and 15 with Lupus) were recruited from the greater Chicago area for the present study. Fifteen of the participants were diagnosed by a physician in Chicago with experience in diagnosing and treating CFS. Each of these participants met the Fukuda et al. [2] definition of CFS. To be diagnosed with the CFS Fukuda et al. [2] criteria, participants had to experience persistent or relapsing fatigue for a period of six or more months concurrent with at least four of eight somatic symptoms that do not predate the fatigue. These symptoms are: sore throat, lymph node pain, muscle pain, joint pain, post-exertional malaise, headaches of a new or different type, memory and concentration difficulties, and unrefreshing sleep. Participants also needed to experience substantial reductions in occupational, educational or personal activities as a result of the illness and must not have any exclusionary medical or psychiatric illnesses.

Fifteen healthy control participants had not been diagnosed with CFS or any other illness that could cause significant fatigue. These participants had also been seen by a physician, and no illnesses that could cause fatigue were found (e.g., unresolved cases of hepatitis C virus infection, untreated hypothyroidism).

In addition, fifteen participants with a diagnosis of Multiple Sclerosis (MS) were recruited from self-help groups in the Chicago area. Each of these participants met Poser et al.’s [12] criteria for definite MS. Participants with other chronic medical conditions in addition to MS were excluded. Finally, fifteen participants with a diagnosis of Systemic Lupus Erythematosus (SLE) were recruited from self-help groups in the Chicago area. The participants with Lupus had to meet the SLE criteria as defined by the American Rheumatology Association [13]. There were no significant differences between groups with respect to race, age, education, marital status, and occupation. However, there were significantly fewer women in the healthy control group as compared to the other groups, and significantly more people were on disability in the CFS and MS group compared to the healthy control group.

2.1.3. SEID Diagnosis

To meet the SEID criteria [1] within this sample, a patient needed to have 6 or more months of illness. To meet the substantial reduction from previous levels of functioning criteria, a patient would have needed to have 6 or more months of substantial reduction in functioning. To meet the post-exertional malaise criteria, a patient would need to have indicated presence of at least 1 of our two post-exertional malaise symptoms: sickness/fatigue for >24 h after exercising or experiencing high levels of fatigue after everyday activity. To meet the unrefreshing sleep criteria, a patient would need to indicate unrefreshed sleep that is more frequent than their pre-illness levels. In order to meet the cognitive impairment criteria, a patient would need at least one of the following cognitive items: difficulty concentrating, difficulty finding the right word to say, difficulty with memory, or difficulty remembering things. Due to a lack of items that tapped into orthostatic intolerance criteria, patients would instead need to meet the cognitive impairment criteria to qualify for the SEID criteria. In another study, we found the option to have orthostatic intolerance instead of cognitive impairment typically enabled only approximately 2% more participants to meet SEID criteria [14].

2.1.4. Results

As indicated in Table 1, 100% (n = 15) of those in the CFS group met the SEID criteria, whereas 47% (n = 7) in the Lupus group, 33% (n = 5) in the MS group, and 0% in the control group met the SEID criteria. In an effort to compare this new SEID case definition to the older Fukuda et al. [2] criteria, we computed the sensitivity and specificity. The SEID criteria evidenced a sensitivity of 1.0 (indicating that 100% of participants with CFS were correctly identified by the SEID criteria) and a specificity of 0.73 (indicating that 27% of participants without CFS were classified as meeting the SEID criteria).

Table 1. CFS, MS, Lupus, and Control Sample n = 60.

Diagnosis                                         Percent Who Qualify for SEID

CFS (n = 15)                                    100% (n = 15)
MS (n = 15)                                      33% (n = 5)
Lupus (n = 15)                                  47% (n = 7)
Control (n = 15)                                  0% (n = 0)

2.2. Study 2

2.2.1. Procedure

In the second study, participants were screened by a trained interviewer to determine if they met the inclusion and exclusion criteria for CFS, MDD, or healthy controls (for more details, see [15]). As part of this screening process, all participants were administered the SCID-IV [16] to assess for psychiatric conditions. Participants who met criteria for participation were asked to complete a battery of questionnaires that measured demographics, social, emotional, and physical functioning, activity level, depression, and a comprehensive list of physical, cognitive, and emotional symptoms. Participants were asked to provide data for fatigue and the 8 diagnostic symptoms specified by the Fukuda et al. [2] case definition. They were asked to report if each symptom had been present for 6 months or longer, began before the onset of their fatigue or health problems, how often it was experienced, and rated the intensity of each symptom on the same scale of 0 to 100. A prior study by King and Jason [17] found that the CFS group against the MDD and control group had significant differences for the following items rated on severity: 4 symptoms in the fatigue/weakness group (fatigue, post-exertional malaise, muscle weakness, need to nap each day), 3 symptoms in the neuropsychological category (frequently losing train of thought, difficulty finding the right word, confusion/disorientation), 4 symptoms in the infectious category (sore throat, tender lymph nodes, hot and cold spells, feeling chilled/shivery), 3 symptoms in the rheumatologic category (muscle pain, pain in multiple joints without swelling, night sweats), 1 symptom in the cardiopulmonary category (shortness of breath), 1 symptom in the neurological category (blurred vision) and unrefreshing sleep. Therefore, these items were also used in the present study.

The Structured Clinical Interview for the DSM-IV (SCID) is a valid and reliable semi-structured interview guide that closely resembles a traditional psychiatric interview [16]. The SCID is designed to identify current, past, and lifetime (chronic or recurring, current and past) diagnoses for a majority of DSM-IV, Axis I psychiatric disorders. The SCID is commonly administered during a single session lasting 45 min to an hour. Diagnostic decisions generated by the SCID are based on all possible sources of historical, symptomatic, and behavioral information. The SCID begins with a semi-structured interview portion designed to yield a tentative diagnosis. The tentative diagnosis is then systematically assessed during the structured portion of the interview through the use of embedded questions that conform to the exact, Axis I criteria set forth by the DSM-IV.

The SF-36 is 36-item instrument that is comprised of multi-item scales that assess physical functioning, role limitations, social functioning, bodily pain, general mental health, vitality, and general health perceptions. Higher scores indicate better health, lower disability, or less impact of health on functioning.

Reliability and validity studies have demonstrated that the 36-item version of the SF-36 has high reliability and validity in a wide variety of patient populations [18].

2.2.2. Participants

A total of 45 individuals (15 with CFS, 15 with MDD, and 15 healthy controls) were recruited from the greater Chicago area [15]. Fifteen participants with CFS were solicited to participate in the present study. Participants were drawn from two sources, a local CFS support group in Chicago and previous research studies conducted at DePaul University. Participants were required to have been diagnosed with CFS, using Fukuda et al.’s [2] diagnostic criteria, by a Board-certified physician and were required to have a current (active) case of CFS. All participants had been seen by their physician in the past year. Individuals who reported having uncontrolled or untreated medical illnesses (e.g., untreated anemia) were excluded.

All participants were screened with the SCID-IV to ensure that they did not have any exclusionary psychiatric illnesses as stipulated by the Fukuda et al. [2] case definition.

Fifteen participants with a diagnosis of MDD were solicited from a local chapter of the National Depressive and Manic Depressive support group in Chicago. Participants were required to have been diagnosed with major depression by a licensed psychologist or psychiatrist. All participants were screened with the SCID-IV to ensure that they met criteria for a current (active) case of major depression and did not have any other current psychiatric illnesses. Individuals who had other current psychiatric conditions in addition to major depression were excluded. Individuals who reported having uncontrolled or untreated medical illnesses (e.g., anemia, diabetes) were also excluded. In the MDD group, all 15 (100%) participants met DSM-IV diagnostic criteria for MDD. None of the participants in the MDD group met criteria for MDD with catatonic, melancholic, psychotic, or atypical features. Participants in the MDD group did not meet criteria for any other Axis I disorders.

Finally, fifteen healthy control participants were solicited from the greater Chicago area. Individuals who did not have any medical illnesses or who did not have any uncontrolled or untreated illnesses (e.g., anemia, diabetes) were allowed to participate. All participants were screened with the SCID-IV to ensure that they did not have any current psychiatric illnesses. Individuals with current psychiatric conditions were excluded. Sociodemographic data were compared across the three groups, and there were no significant differences with respect to gender, race, age, SES, education, marital status, occupation, work status, and additional roles [15].

2.2.3. SEID Diagnosis

To meet the SEID criteria [1] within this sample, a patient would need to have 6 or more months of fatigue. Because the SEID criteria do not indicate how to assess substantial reductions, we used criteria that has been published in prior studies with specified cut off points [6,14]. To meet substantial reduction from previous levels of functioning criteria, a patient needed to meet 2 of the following 3 SF-36 criteria: role physical <50, social functioning <62.5, or vitality <35. To meet the post-exertional malaise criteria, a patient needed to have 6 or more months of post-exertional malaise. To meet the unrefreshing sleep criteria, a patient needed to have 6 or more months of unrefreshing sleep. To meet the SEID criteria, the individual needed to have either a cognitive impairment or orthostatic intolerance symptom. In order to meet the cognitive impairment criteria, a patient would need at least one of the following cognitive items: impaired memory present for 6 months or longer, slowness of thought, absent mindedness or forgetfulness, or difficulty focusing. To meet the orthostatic intolerance criteria, a patient would need presence of at least one of the following items: dizziness, wobbling feet when getting up.

2.2.4. Results

As indicated in Table 2, 93% (n = 14) of those in the CFS group, 27% (n = 4) in the MDD group, and 0% in the control group met SEID criteria. In an effort to compare this new SEID case definition to the older Fukuda et al. [2] criteria, we computed the sensitivity and specificity. These criteria resulted in a sensitivity of 0.93 and a specificity of 0.86.

Table 2. CFS vs. MDD Database n = 45.

Diagnosis                              Percent Who Qualify for SEID

CFS (n = 15)                         93% (n = 14)

MDD (n = 15)                       27% (n = 4)

Control (n = 15)                     0% (n = 0)

2.3. Study 3

2.3.1. Procedure

The data were derived from a larger community-based study of CFS that was carried out in three stages [3]. Stage 1 entailed a cross-sectional screening telephone survey of a random sample of 28,673 households, with 18,675 adults completing the screening interview (65.1% completion rate). Of these participants, 780 (4.2%) of the respondents had six or more months of fatigue. Stage 2 involved a structured psychiatric interview for a sample of those respondents from Stage 1 who screened positive for a CFS-like syndrome based on the Fukuda et al. [2] criteria, as well as a screen negative control sample.

In Stage 3, a physician conducted a detailed medical examination to rule out exclusionary medical conditions. All patients underwent detailed reviews of their medical history and a thorough physical and neurological examination to detect evidence of diffuse adenopathy, hepatosplenomegaly, synovitis, neuropathy, myopathy, cardiac or pulmonary dysfunction. All had routine blood tests performed including complete blood count, chemistry screen (including glucose, electrolytes, calcium, magnesium, liver function tests and renal function tests), sedimentation rate, rheumatoid factor, Antinuclear Antibody, triiodothyronine, thyroxine, thyroid-stimulating hormone, Creatine phosphokinase, human immunodeficiency virus, hepatitis screen, B12, red blood cell folate and serum carnitine determinations. All patients had a urinalysis performed.

2.3.2. Participants

According to the Phase 1 screen, of the 18,675 interviewees, 16,453 (88%) had no prolonged or chronic fatigue, 1435 (7.7%) had prolonged fatigue, and 780 (4.2%) had chronic fatigue (seven cases refused to answer the fatigue questions). Among those 780 respondents with chronic fatigue, at Phase 1; 304 had ICF-like illness (e.g., not enough minor symptoms to be eligible for a CFS diagnosis), 68 had a CF-explained-like condition, and 408 had CFS-like profiles. All 408 members of the CFS-like group were invited to participate in Phase 2. Of this group of 408 individuals with CFS-like symptoms, the physician review team reviewed data on 166 individuals, who provided data during the Phase 2 evaluation.

There were 47 individuals who were evaluated in a control group, and these individuals screened negative for CFS-like illness during Phase 1.

A team of four physicians and a psychiatrist were responsible for making a final diagnosis with two physicians independently rating each file using the current U.S. case definition of CFS [2]. Where physicians disagreed, a third physician rater was used [3]. Table 3 shows the number of cases in the control group (Control), individuals who were diagnosed with CFS using the Fukuda et al. [2] case definition (CFS), Idiopathic chronic fatigue (ICF, individuals who did not meet all the Fukuda criteria), and chronic fatigue explained (CF, i.e., melancholic depression, bipolar disorders, anorexia nervosa/bulimia nervosa, psychotic disorders, drug or alcohol related disorders, or medical explanations for their fatigue).

Table 3. Community Epidemiology database n = 213.

Diagnosis                             Percent Who Qualify for SEID

CFS (n = 32)                       75% (n = 24)

ICF (n = 45)                        44% (n = 20)

CF (n = 89)                          47% (n = 42)

Control (n = 47)                      6% (n = 3)

2.3.3. SEID Diagnosis

To meet the SEID criteria [1] within this data set, a patient would need to have one of the following indications of 6 or more months of fatigue: fatigue for 6 or more months or fatigue present for more than 50% of the time for a minimum of 6 consecutive months. To meet substantial reduction from previous levels of functioning criteria, a patient needed to meet 2 of the following 3 criteria: role physical <50, social functioning <62.5, or vitality <35. To meet the post-exertional malaise criteria, a patient needed to report the occurrence of one of the following symptoms: prolonged generalized fatigue or malaise following previously tolerable levels of exercise, feeling generally worse than usual or fatigued for 24 h or more after exercise, or exercise brings on my fatigue. To meet the unrefreshing sleep criteria, a patient needed one of the following symptoms: after a night of sleep do you feel rested, after a night of sleep does your fatigue go away temporarily, needing to nap daily, problems falling/staying asleep. To meet the SEID criteria, the individual needed to meet either the cognitive impairment or orthostatic intolerance symptom. In order to meet the cognitive impairment criteria, a patient would need presence of at least one of the following cognitive items: forget recent conversations and events, confusion or distortion in familiar places, inability to concentrate, difficulty retaining information, only able to focus on one thing at a time, or new trouble with math. To meet the orthostatic intolerance criteria, a patient would need presence of at least one of the following items: sharp shooting pains in chest, rapid heartbeat, feeling unsteady on feet, often feeling dizzy, feeling weak or dizzy right after standing up.

2.3.4. Estimating SEID Prevalence

Prevalence, which is the number to be estimated, is represented by P (p). The total number of respondents screened in Phase 1 (18,668) is N (Nt). The proportion of screened positives (408/18,668 = 0.0219) is PI (π), and the proportion of screened negatives (18,260/18,668 = 0.9781) is 1 − PI (1 − π). The proportion of screened positives evaluated in Phase 2 who were diagnosed with SEID (Number of cases with SEID/166) is L1 (λ1), and the proportion of screened negatives evaluated in Phase 2 who were diagnosed with SEID (0/47 = 0.0) is L2 (λ2).

2.3.5. Results

As indicated in Table 3, 75% (n = 24) of those in the CFS group met the SEID criteria, whereas 47% (n = 42) for the CF group, 44% (n = 20) for the ICF group, and 6% (n = 3) for the controls. Within the Chronic Fatigue explained by medical or psychiatric illness (CF), of those 19 with Melancholic Depression, 47% (n = 9) met the SEID criteria. In addition, for those with a medical reason for their fatigue, 48% (n = 16) met SEID criteria. In an effort to compare this new SEID case definition to the older Fukuda et al. [2] criteria, we computed the sensitivity and specificity. In this sample, the SEID criteria had a sensitivity of 0.75 and a specificity of 0.64.

This data set had been previously used to estimate the prevalence of CFS [3], which was 0.42. With the new number of SEID cases, we recalculated the prevalence rate, using methods described elsewhere [19].

This information was then used in the following formula to obtain the estimate of the prevalence [P = L1 × PI + L2 × (1 − PI) = L1 × 0.0219 + 0.0 × 0.9781]. The SEID Prevalence rate = L1 × PI + L2 × (1 − PI) = (89/166) × 0.0219 + 0.0 × 0.9781 = 0.0117. As the prior CFS Fukuda et al. [2] prevalence rate was 0.0042, the new SEID prevalence rate was 2.8 (0.0117/0.0042) times greater.

2.4. Study 4

2.4.1. Procedure

We solicited participants with a diagnosis of MDD and CFS to participate in this study [20]. We administered to all participants the CDC Symptom Inventory, which assesses information about the presence, frequency, and intensity of 19 fatigue related symptoms during the past one month [21]. All eight of the critical Fukuda et al. [2] symptoms were included as well as 11 other symptoms (e.g., diarrhea, fever, sleeping problems, nausea, etc.). For each of the eight Fukuda et al. [2] symptoms, participants were asked to report the frequency (1 = a little of the time, 2 = some of the time, 3 = most of the time, 4 = all of the time) and severity (the ratings were transformed to the following scale: 0.08 = very mild, 1.6 = mild, 2.4 = moderate, 3.2 = severe, 4 = very severe). The frequency and severity scores were multiplied for each of the eight critical Fukuda et al. [2] symptoms and were then summed, in order to determine whether a person met the Fukuda et al. [2] criteria, as operationalized by Reeves et al. [22].

2.4.2. Participants

We recruited 64 individuals, 27 with CFS and 37 with MDD. We obtained our sample of participants with CFS from two sources, local CFS support groups in Chicago and a previous research study conducted at DePaul University. To be included in the study, participants were required to have been diagnosed with CFS, using the Fukuda et al. [2] diagnostic criteria, by a certified physician and were required to currently meet CFS criteria using the Fukuda et al. criteria. We excluded individuals who had other current psychiatric conditions in addition to major depression or who reported having untreated medical illnesses (e.g., diabetes, anemia).

For the MDD group, we found participants from three sources, local chapters of the Depression and Bipolar Support Alliance group in Chicago; Craigslist—a free local classifieds ad forum that is community moderated; and online depression support groups. To be included in the study, all participants were required to have been diagnosed with a MDD by a licensed psychologist or psychiatrist. We excluded individuals who had other current psychiatric conditions in addition to a MDD (e.g., bipolar, schizophrenia) or who reported having untreated medical illnesses were also excluded. We carefully screened participants to ensure that participants from the MDD group did not have CFS as defined by the Fukuda et al. [2] criteria.

2.4.3. SEID Diagnosis

To meet the SEID criteria [1] within this sample, a patient needed to have 6 or more months of illness. To meet substantial reduction from previous levels of functioning criteria, a patient needed to meet 2 of the following 3 criteria: role physical <50, social functioning <62.5, or vitality <35. To meet the post-exertional malaise criteria, a patient would need to have a frequency of at least some of the time and severity score of at least moderate to indicate prolonged levels of malaise following previously tolerated exercise. To meet the unrefreshing sleep criteria, patients would have to have indicated at least 1 of the unrefreshing sleep symptoms: Unrefreshing sleep in the past month, unrefreshing sleep present 6 months or longer, or trouble sleeping through falling or staying asleep. In order to meet the cognitive impairment criteria, a patient would need to have a frequency of at least some of the time and severity score of at least moderate to indicate impaired concentration. Due to a lack of items that tapped into orthostatic intolerance criteria, patients would instead need to meet the cognitive impairment criteria to qualify for this measure. In a prior study by Jason, Sunnquist, Kot, Brown, Newton et al. [14], when using the option to have orthostatic intolerance instead of cognitive impairment, only an additional 2% of participants meet the SEID criteria [14].

2.4.4. Results

As indicated in Table 4, 81% (n = 22) of those in the CFS group met the SEID criteria, whereas 24% (n = 9) of those in the MDD group met SEID criteria. In an effort to compare this new SEID case definition to the older Fukuda et al. [2] criteria, we computed the sensitivity and specificity. The SEID criteria resulted in a sensitivity of 0.81 and a specificity of 0.76.

Table 4. CFS vs. MDD Database n = 64.

Diagnosis                              Percent Who Qualify for SEID

CFS (n = 27)                        81% (n = 22)

MDD (n = 37)                      24% (n = 9)

3. Discussion and Conclusions

Tables 1–4 indicate that the SEID criteria will probably select few individuals from healthy control samples, and although a few controls were identified as meeting SEID in Table 3, that control sample included a large group of individuals from the community, many of whom did have varying levels of fatigue and other problems. In addition, it appears that the SEID criteria do identify most of those who met the Fukuda criteria, as evidenced by the generally high sensitivity statistics; however, rates tend to be lower in Table 3, which is a community rather than tertiary sample, where symptom rates tend to be lower. Most importantly, the SEID criteria do tend to identify high rates of those with other medical illnesses, as indicated in Tables 1 and 4 and the low specificity levels, and therefore many individuals with autoimmune and other health illnesses that had been exclusionary with prior case studies will now be comorbidity. In addition, as indicated in Tables 2 and 4, many individuals with a purely affective disorder will now be also classified as having SEID.

Rates of SEID could increase due to the reduction of many exclusionary criteria. Based on study 3, using the Jason et al. [3] community-based epidemiologic study, 32 individuals had been classified as meeting the Fukuda et al. [2] criteria, for a prevalence rate of 0.42, but we estimate that 89 from this sample would now meet the SEID criteria, for a prevalence rate of 1.17, thus, the SEID prevalence rate would be 2.8 times as great. Of course, if our samples had only included those who had been selected patients had met the Fukuda et al. [2] criteria, as occurred in a recently published study [14], then those with many medical and psychiatric illnesses would have already been excluded, so in a study comprised of just those meeting the Fukuda et al. [2] criteria, the rates of those meeting the SEID criteria would be much more comparable to those meeting the CFS Fukuda criteria [14].

The current study suggests that the core SEID symptoms are not unique to SEID, as some patients with other illnesses, such as those evaluated in this study, have comparable symptoms. As a consequence, some patients with illnesses that had previously been exclusionary under past case definitions such as Fukuda et al. [2] will now be comorbid, possibly leading to an expanded number of individuals meeting SEID criteria. Even though the SEID criteria are for a clinical case definition [1], rather than a research case definition, it is likely that it will be used for research by investigators, as a similar process occurred with the clinical Fukuda et al. [2] CFS criteria. If there are ambiguities with case definitions, like what has occurred with the Fukuda et al. [2] CFS criteria, there will be difficulties in replicating findings across different laboratories, estimating the prevalence of the illness, consistently identifying biomarkers, and determining which treatments help patients. To develop or validate a reliable case definition, we need to both provide operationally explicit inclusionary and exclusionary criteria as well as develop a consensus within the scientific community for the case definition.

The current study suggests that some patients with MDD, who also have chronic fatigue, sleep disturbances, and poor concentration, will be misdiagnosed as having SEID. MDD can occur for anyone with a serious medical illness. Some patients might have been depressed prior to becoming ill with SEID, and probably others as a reaction to this illness [23]. However, patients with CFS have symptoms including night sweats, sore throats, and swollen lymph nodes, that are not commonly found in depression, and illness onset with CFS is often sudden, occurring over a few hours or days, whereas primary depression generally shows a more gradual onset [24,25]. Hawk, Jason, and Torres-Harding [15] were 100% successful in differentiating patients with CFS and MDD using the following variables: percent of time fatigue was reported, post-exertional malaise severity, unrefreshing sleep severity, confusion/disorientation severity, shortness of breath severity, and self-reproach.

Mood disorders are the most prevalent psychiatric disorders after anxiety disorders: for major depressive episode, the one-month prevalence is 2.2%, and lifetime prevalence is 5.8% [26]. The erroneous inclusion of people with primary psychiatric conditions in SEID samples would have detrimental consequences for the interpretation of epidemiologic, etiologic, and treatment efficacy findings for people with this illness. This is what occurred with another CFS case definition developed by the CDC [22]. Jason et al. [19] found that 38% of those with a diagnosis of a MDD were misclassified as having CFS using the CDC empirical case definition of Reeves et al. [22]. Fortunately, few adopted the Reeves et al. [22] empiric case definition, but the IOM [1] has considerably more prestige and influence, so their proposed SEID case definition criteria could ultimately have more far reaching effects. In study 3, 47% of those with Melancholic Depression met SEID criteria, whereas rates of MDD meeting SEID criteria in studies 2 and 4 were 27% and 24%, respectively. If individuals with primary affective disorder are misdiagnosed with SEID and provided cognitive behavioral treatment, they will more likely have positive outcomes, and this may create more difficulties in understanding the effects of these interventions for those who have ME (Myalgic Encephalomyelitis). Price, Mitchell, Tidy and Hunot [27] reviewed 15 studies of CBT with a total of 1043 participants with CFS. At treatment’s end, the CBT group showed more clinical improvement in contrast to those in usual care, but changes were not maintained at a one- to seven-month follow-up when including patients who had dropped out.

There are additional aspects of the IOM [1] case definition that have problems, besides exclusionary criteria. For example, it is unfortunate that there was a lack of a recommendation for a mental health evaluation, or a structured clinical interview, especially as some of these symptoms can overlap with primary affective or mood disorders. The SEID criteria require a patient to have either cognitive impairment or orthostatic illness, but orthostatic intolerance does not evidence prevalence rates as high as the other proposed core symptoms, whereas cognitive impairment does have higher prevalence rates [28]. Also, factor analytic studies do not support this system of a choice of cognitive impairment vs. orthostatic intolerance [29].

We believe this report did not adequately deal with the issue of whether distinct categories or continuous measures best capture patient differences, as there well might be different groupings of patients, with some having different features or more severity.

Finally, empirical methods could have been employed to test the proposed classification system, and the committee members might have benefited from testing out their proposed model with an actual data set, as has recently been done [14].

There are a number of limitations in the present study. As we used archival data sets, some of the questions that have been proposed to define SEID were not available. Clearly, the current study needs to be replicated with questions that are now proposed [7], however, our questionnaires were able to assess that vast majority of issues and domains within SEID. In addition, several of our samples were relatively small, so larger studies are needed. Furthermore, we were only able to identify data sets representing a few illnesses, and more illnesses need to be investigated to assess whether some patients with these diagnoses might be included within the SEID classification system. It should be noted that samples recruited from patient organizations or that do not have an independent physician work up and diagnosis might be less reliable. The new SEID [1] criteria suggest frequency and severity ratings, many of which were not available from the data sets reported in the current study, so it is possible that some occurrence ratings selected less impaired individuals and inflated the number of patients meeting SEID criteria.

Finally, none of the studies included a two-day exercise challenge, and such a test would be a better approach for documenting post-exertional malaise. However, such a test might exclude some of the individuals from a SEID diagnosis, and given that the SEID is a clinical criteria, most medical practitioners will not have access to this expensive two-day exercise test in the diagnostic process.

The recent IOM report [1] is being widely discussed among academics and the patient community [30]. There is a need to also consider how these recommendations will affect patients in other countries, given the prestige associated with an IOM report. The present study suggests that there might be a number of illnesses that had been exclusionary, which now might now be considered comorbid. This is a complex diagnostic decision, and there probably is a need for clearer rules regarding whether a person has an exclusionary or comorbid illness. Ultimately, we need investigations to help point to implications of using these new criteria, and ultimately, we need an open and inclusive process where all parties, including key gatekeepers including the patients, scientists, clinicians and government officials, are involved in the decision making process.

Author Contributions

All authors contributed to the conceptualization of the study, the data analysis, and the writing of this article.

Conflicts of Interest: The authors declare no conflicts of interest.


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© 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).

Contact information:

Center for Community Research, DePaul University, Chicago, IL 60614, USA; E-Mails: MSUNNQUI@depaul.edu (M.S.); BKOT@depaul.edu (B.K.); ABROWN57@depaul.edu (A.B.)

* Author to whom correspondence should be addressed; E-Mail: LJASON@depaul.edu;

Tel.: +1-773-325-2018; Fax: +1-773-325-4923.

Academic Editor: Andreas Kjaer

Received: 25 March 2015 / Accepted: 16 June 2015 / Published: 23 June 2015

Diagnostics 2015, 5, 272-286; doi:10.3390/diagnostics5020272

ISSN 2075-4418

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