Tag: alternative treatments

“Maureen’s Story”: Diagnosing a Case of Mold Toxicity

Reprinted with the kind permission of ProHealth: 9/14/11

Dr. Neil Nathan, a specialist in treatment of complex medical illnesses, practices with Gordan Medical Associates near Mendocino, CA.

This information is excerpted with kind permission from his book On Hope and Healing for Those Who Have Fallen Through the Medical Cracks ©2010 Neil Nathan, MD, all rights reserved. These excerpts provide a general introduction to biotoxicity as one cause of unexplained illness; but a detailed discussion of biotoxicity’s many agents, symptoms, diagnosis, and treatment can be found in the book.

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Mold and Biotoxicity: There’s a Fungus Among Us

When it comes to understanding the different components of chronic illness, the concept of toxicity has received a good deal of recent attention. With the publication of Dr. Richie Shoemaker’s brilliant book, Mold Warriors, we now have some new tools to both evaluate and treat toxicity in its different forms.

It is fairly obvious that a microbe (bacteria, virus, fungus, parasite, or other infective agent) makes us sick by infecting us, and it is equally clear that treating these disease-causing microbes will make us better. But what is just becoming clear to us is that not only do these microbes make us sick by causing an infection, but some of these microbes can, in the process of being killed by our immune system, release toxins into our bodies that make us even sicker. Because these toxins are made by microbes, which are living biological systems, we call them biotoxins.

For most, the immune system recognizes these toxins and uses its defense mechanisms to destroy them. Unfortunately, about 25% of people are genetically unable to make an antibody to these toxins, and these patients may get progressively sicker as the toxins accumulate within their bodies.

What specific microbes are we talking about? The most common offenders are molds, especially the black mold Stachybotrys, but several other mold species such as Cladosporium and Fusarium can play a role in toxin formation. Harmful toxins can also be produced by certain viruses, especially those in the Herpes family, such as Epstein-Barr virus, which is the agent of mononucleosis; Cytomegalovirus; and Human Herpes Virus 6 (HHV-6), which is the agent of roseola infection.

A new and particularly toxic strain of HHV-6 has recently been discovered and has now been linked to chronic fatigue [ME/CFS] and fibromyalgia. Lyme bacteria can also produce these toxins, as can infections with the mycoplasmas, which are infective particles between viruses and bacteria in size. The atypical pneumonias (walking pneumonia) and Gulf War syndrome are examples of these infective agents.

Symptoms

So what are the symptoms of biotoxicity? Patients with this problem may experience a surprisingly wide range of symptoms related to many different organ systems. These symptoms sound a lot like fibromyalgia or chronic fatigue or depression. In children, it might appear like ADHD.

Diagnosis

The first order of business is to even consider the diagnosis.

Treatment

Several treatments for biotoxicity are currently in use. Dr. Shoemaker provides a combination of medications based on his testing. In its simplest form, this consists of using “Cholestyramine” the binding resin cholestyramine (trade name, Questran) or its cousin, Welchol.

Maureen’s Story

Maureen was a 28-year-old woman whom I saw for the first time in March of 2006. Her symptoms had begun three years previously, when she was working in a building with a very leaky roof.

She had also experienced several traumatic events at the same time, including a difficult divorce, which complicated both our evaluation and her perceptions about what may have triggered her illness.

In August of 2005, Maureen began to violently throw up on a daily basis, and this went on for months. She saw multiple physicians, including several gastrointestinal specialists, and underwent extensive testing, which showed no obvious cause for her symptoms.

She was diagnosed by various physicians as having bipolar disorder, irritable bowel syndrome, and hypochondriasis (meaning it was all in her head or psychosomatic).

Since her initial exposure to the mold, Maureen had gained 35 pounds and had developed sensitivities to all sorts of chemicals and perfumes (which we call multiple chemical sensitivities). This is actually a common event following untreated biotoxin exposure.

She continued to experience daily nausea and vomiting, regular headaches, and an inability to think clearly. She described her poor decision making in very simple terms: It’s like I’m inept.

She also reported blurred vision and bouts of chest tightness with wheezing.

When Maureen came to me, she had just lost her job of 14 years, at which she had been previously quite competent, and she was trying to live a normal life and raise her three children.

But she could hardly function.

Her energy level was very low, and she reported difficulty staying asleep and waking up unrefreshed each morning. She described joint pains in her neck, shoulder, and upper back, and she displayed the classical irritable bowel symptoms of gas bloating, distention and diarrhea alternating with constipation.

When I tested her vision with the Functional Acuity Contrast Test (FACT),a test of ability to detect contrasts that can indicate poor retinal function and has been closely related to biotoxicity], the results strongly suggested biotoxin exposure.

Her DHEA test was a little low, as was her progesterone level. I started her on natural progesterone cream, ¼ tsp daily, applied to her skin. I also put her on a small dose of DHEA.

And we started cholestyramine in the form of Questran Light, one scoop mixed with water three times daily, which is the best immediate treatment for mold toxicity.

When Maureen returned in April, just six weeks later, she reported that she was already 80% better. Her energy was markedly improved despite the fact that she was still living in her home, which had obvious mold exposure.

She had a new job, was successfully working again, but noticed that when she missed even a single day of her Questran, she became lethargic again.

She planned to remediate her home to clean up the mold, and she was thrilled that she had her life back; she was no longer plagued by nausea, vomiting, chest pain, and joint pain.

She was so impressed with her improvement in just a short period of time, that she bought a copy of Mold Warriors to give to her family physician, who had essentially told her she was a hypochondriac.

Her physician refused to even look at the book or to take Maureen’s story seriously.

It has been my experience that most of our mold-toxic patients have had a similar experience to Maureen’s. Their symptoms are usually misunderstood as representing psychological imbalances, particularly depression, but they do not respond well to antidepressant and anti-anxiety medications. That should be the tip-off that we need to look deeper for a cause of these symptoms.

Recalling that only 25% of patients are genetically unable to make the antibodies they need to these toxins, these patients may live in a home with others who have no symptoms or work in a mold-laden environment where others are not sick.

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* Neil Nathan, MD, is perhaps best known to ProHealth readers for his recent trial of “A simplified Methylation Protocol for Treatment of ME/CFS and Fibromyalgia,” conducted in collaboration with Drs. Amy Yasko, Rich Van Konynenburg, and Jacob Teitelbaum.

Note: This information has not been reviewed by the FDA. It is general information and is not meant to take the place of a physician’s attention or to prevent, diagnose, treat or cure any illness, condition or disease. It is very important that you make no change in your healthcare plan or health support regimen without researching and discussing it in collaboration with your professional healthcare team.

Natural Strategies for Stopping a Common Energy Drain in ME/CFS and Fibromyalgia

By Jacob Teitelbaum, MD

www.ProHealth.com • October 12, 2011

Dr. Teitelbaum, a well-known fatigue and pain specialist who contracted CFS as a medical student, has researched ME/CFS/FM patients’ nutritional and therapeutic needs for more than 20 years. This article is reproduced with kind permission* from his educational web site at https://www.vitality101.com/

Reprinted with the kind permission of ProHealth: 10/12/11

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Treating Low Blood Volume & Decreased Heart Function in CFS & FM

In this important article we will discuss a critical but usually overlooked part of treating Chronic Fatigue Syndrome and fibromyalgia effectively. It can be relatively easy to treat, but is not very glamorous, and is therefore often forgotten.

We will focus on research by Dr. Barry Hurwitz and a team of University of Miami researchers, including Dr. Nancy Klimas, who is wonderful and one of my favorite people in the CFS community… Their [2009] study shows that patients with CFS have:

1. A lower blood volume (basically are dehydrated).

2. Fewer red blood cells to carry oxygen and nutrients (basically anemia, despite normal blood tests).

The study also discusses that although the heart may be smaller in CFS and beats less efficiently, this is likely caused by the dehydration and low blood volume, as opposed to primarily being a heart problem. (More on the details later.)

The good news is that all of these issues can be effectively treated and optimized naturally – which can leave you feeling much better!

THE BOTTOM LINE FIRST

There are several key things that you can do to treat the low blood volume and low blood cell levels that will leave you feeling better:

1. Treat the Dehydration.

Despite your increased thirst and drinking a lot (“like a fish”), most of you are still dehydrated because you’re urinating even more. This occurs for several reasons, including underactive adrenal function and a decrease in antidiuretic hormone (“anti-peeing hormone”), both of which are routinely present in CFS because of the hypothalamic dysfunction (“blowing a fuse”) that we often discuss….

Quick Fixes:

a. Drink more water! Instead of counting glasses of water (an annoying way to spend the rest of your life), check your mouth and lips to see if they are dry. If they are, drink!

b. Eat more salt. Unless you have high blood pressure or heart failure, you need more salt than most people. In fact, many studies have shown that the more salt people eat the longer they live [see sidebar at end of article, “High Salt Intake is Associated with BETTER Health”], and for most people the need to avoid salt has been a problematic medical myth (see six dangerous “Medical Myths“). Use an iodized salt or better yet sea salts… Enjoy salty foods as well.

c. Improve adrenal function. This is discussed at more length in “The Adrenal Gland, and Symptoms of Adrenal Insufficiency,” but a simple way to do this is with an excellent product called Adrenal Stress End.

d. Saline IVs. Clinical experience has also shown that salt water (saline) IVs can be very helpful. The effects are transient though, unless other nutrients are added  – e.g., the Myers’ Cocktails [which are IV vitamin and mineral therapies first conceived in the 1970s by the late John Myers, MD, at Johns Hopkins] administered at holistic physicians’ offices [such as] the Fibromyalgia and Fatigue Centers.

2. Increase Your Body’s Production of Red Blood Cells.

Although treating the infections and hormonal problems we discuss overall in the SHINE Protocol will do this (addressing possible problems with Sleep, Hormones, Infection, Nutrition, and Exercise), below are key things that will help.

a. Treat for low iron – even if your blood tests are normal but modestly low. The best blood test is called a “ferritin” level. Your doctor will say it is normal if it is over 12, but research has shown(2) that in people with chronic fatigue, iron supplementation increased energy dramatically in people with a ferritin under 50 (see Iron Helps Fatigue – Even with Normal Iron Levels and No Anemia) who were not anemic. If the ferritin blood test is under 50, or the iron percent saturation blood test is under 25%, take 1-2 tablets of iron (29 mg with vitamin C) each afternoon or evening on an empty stomach for 4-6 months.

b. Treat for low testosterone and low thyroid levels – despite the normal blood tests. Both of these, especially the testosterone (use only the safe and natural bioidentical forms), increase red blood cell production.

3. Improve Your Heart Function

Though the study discussed in this article notes that the low blood volume and anemia are key, other studies and clinical experience show that nutrients that improve heart function also improve energy in CFS patients. These include:

a. Ribose (Corvalen) 5 gm (1 scoop) 3x day for 3 weeks, then twice a day.

b. Acetyl L-carnitine 500 mg 2x day. [See for example “Long-chain acylcarnitine deficiency in patients with Chronic Fatigue Syndrome,” Journal of Internal Medicine, Jul 2011].

c. The Energy Revitalization System vitamin powder (contains 50 nutrients including B vitamins and magnesium).

d. Coenzyme Q10 at 200 mg daily.

Give the above treatments 6-12 weeks to see the effect. But by one month, most of you will be feeling a lot better with these treatments. In addition, if you have not already done so, do the free Symptom Analysis Program to tailor an overall treatment protocol to your case. Although you do not need to have your blood tests results, if they are available the program will also analyze the more important tests.

WHAT THE UNIVERSITY OF MIAMI STUDY SHOWS

The study(1) looked at 146 people with chronic fatigue syndrome, 30 of whom were very severely affected. It compared them to healthy controls and then factored in how active or sedentary the people were.

People with CFS showed 25% lower heart contractility, so they pumped much less blood.

They then did specialized testing which showed what the person’s total blood volume was and also whether they had enough red blood cells, both of which have been shown to be low in the majority of those with severe CFS.

As all of the above problems have been shown to be common in CFS, the study explored whether there was predominantly a heart problem or whether all of these findings could be explained by dehydration and having too few red blood cells. I would note that, normally, having too few red blood cells would be called being anemic.

Unfortunately, the standard blood tests for anemia compare the amount of blood cells relative to the blood volume. As both are low, the blood count tests come back as normal despite CFS patients in reality being functionally very anemic.

As the study authors note, “The elevated prevalence of low red blood cell volume suggests that the CFS subjects may have an anemia type that goes undetected by standard hematologic evaluations.”

In other words, people with CFS are likely to be anemic despite normal testing (being 6% to 13% lower than optimal, depending on the severity of their CFS).

The role of decreased heart function in CFS has been a major focus of work by Dr. Paul Cheney, MD, PhD, a chronic fatigue syndrome expert who is intimately familiar with the effects of heart problems, as he needed a heart transplant himself. He theorizes (and I am markedly oversimplifying his theory) that heart function decreases as an adaptation to not being able to properly handle the oxygen needed to make energy in CFS.

Chronic disease in general can trigger dehydration and low red blood cell volume, so there are many possible reasons for these occurring in CFS. Deconditioning can also then decrease heart function.

This study was associated with another study looking at whether injections of a prescription blood cell stimulating hormone called
“erythropoietin” would be helpful in CFS, which would naturally lead to some focus towards interpreting the results as being associated with a deficiency of blood cells as opposed to a heart problem. The benefits of erythropoietin treatment were modest relative to the cost and hassle, though, and I think the researchers’ bias is fairly modest.

The authors conclude, “Given these findings, it may be prudent in the clinical setting to perform a direct examination of blood volume status in CFS patients and consider treatment for those with abnormal levels. A blood volume deficit may:

• Impact adversely oxygen delivery and nutrient supply,

• Impair hemodynamic regulation (e.g., blood pressure and heart function),

• And contribute to the exacerbation of fatigue and other CFS symptomatology.”

As their earlier study showed minimal benefit from only increasing the amount of red blood cells using erythropoietin, it again shows the need to use an overall treatment approach to treat all the problems present in CFS.

These include raising red blood cell mass and treating the dehydration, but also treating the underlying infections, adrenal under activity, and other problems that are at the root of these problems.

As we know that most people with CFS will have the dehydration and “anemia despite normal blood testing,” I do not think it is worth the cost of doing these expensive nuclear scans, but instead recommend the simple treatments discussed in the summary above, which we know are helpful in CFS. (Again, these are part of the SHINE Protocol.)

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SIDEBAR: High Salt Intake is Associated with BETTER Health
Re: “Sodium Intake & Mortality Follow-Up in the Third National Health and Nutrition Examination Survey – NHANES III.”

This study is a fascinating one. It is based on the NHANES data base, which is one of the most respected (if not the most respected) nutritional data bases in the country. What the study showed is the opposite of what we have been led to believe medically.

It showed that the lower the salt intake, the HIGHER the risk of death. Put differently, our advice to people to avoid salt is more likely to be harmful than helpful!

On the other hand, though there was no significant evidence that salt was harmful, the evidence for a low salt diet being harmful was modest, so if people want to avoid salt it probably won’t hurt them too much.

The possibility of a low salt diet being harmful was also likely affected by more people in the low salt diet group having high blood pressure, so it may have been the underlying high blood pressure which caused their higher death risk (i.e., people with high blood pressure were told by their doctors to be on low salt diets, and this could be a “confounding variable” that makes people misinterpret the data. The low salt didn’t kill them, but rather it was their earlier high blood pressure).

Bottom line – Enjoy yourself! Eat the amount of salt that your body wants and don’t worry about it (if you don’t have high blood pressure or heart failure).

The Abstract:
“Sodium Intake and Mortality Follow-Up in the Third National Health and Nutrition Examination Survey – NHANES III.” (The full text article is here – https://pmc.ncbi.nlm.nih.gov/articles/PMC2518033/)

Background: Sodium restriction is commonly recommended as a measure to lower blood pressure and thus reduce cardiovascular disease (CVD) and all cause mortality. However, some studies have observed higher mortality associated with lower sodium intake.

Objective: To test the hypothesis that lower sodium is associated with subsequent higher cardiovascular disease (CVD) and all cause mortality in the Third National Health and Nutrition Examination Survey (NHANES III).

Design: Observational cohort study of mortality subsequent to a baseline survey.

Participants: Representative sample (n=8,699) of non-institutionalized US adults age 30 and older, without history of CVD events, recruited between 1988-1994.

Measurements and Main Results: Dietary sodium and calorie intakes estimated from a single baseline 24-h dietary recall. Vital status and cause of death were obtained from the National Death Index through the year 2000.

Hazard ratio (HR) for CVD mortality of lowest to highest quartile of sodium, adjusted for calories and other CVD risk factors, in a Cox model, was 1.80 (95% CI 1.05, 3.08, p=0.03). [Note: an HR of 1.0 would represent no difference; so a ratio of 1.80 would indicate that individuals in the lowest sodium intake quartile were 80% more likely on average to die of a cardiovascular event than those in the highest sodium intake group.]

Non-significant trends of an inverse association of continuous sodium (per 1,000 mg) intake with CVD and all-cause mortality were observed with a 99% CI of 0.73, 1.06 (p=0.07) and 0.86, 1.04 (p=0.11), respectively, while trends for a direct association were not observed.

Conclusion: Observed associations of lower sodium with higher mortality [all causes] were modest and mostly not statistically significant. However, these findings also suggest that for the general US adult population, higher sodium is unlikely to be independently associated with higher CVD or all-cause mortality.

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1. Low Blood Volume and Red Blood Cell Mass Study, Abstract: “Chronic fatigue syndrome: Illness severity, sedentary lifestyle, blood volume and evidence of diminished cardiac function,” Barry E. Hurwitz, Nancy G. Klimas, et al. Behavioral Medicine Research Center, University of Miami, Florida. Clinical Science (Lond), Oct 19, 2009.

2. Reference for Iron Study: “Iron supplementation for unexplained fatigue in non-anaemic women: Double blind randomised placebo controlled trial,” F Verdon, et al. BMJ, May 2003.

* Copyright © 2011 by The Annapolis Chronic Fatigue and Fibromyalgia Research Center for Effective CFS/FMS Therapies. All rights reserved.

Disclaimer: These statements have not been evaluated by the FDA. This information and the supplements discussed are not intended to diagnose, prevent, treat or cure any illness, condition or disease. It is very important that you make no change in your healthcare plan or health support regimen without researching and discussing it in collaboration with your professional healthcare team.

The Pall Protocol for Treating CFS/ME

Dr. Martin Pall’s NO/ONOO– (“No! Oh, no!”) hypothesis is probably the most comprehensive explanation of cellular dysregulation in CFS and other oxidative stress illnesses. His model proposes that the chronic stage of CFS is driven by a vicious cycle of oxidative stress, in which the basic mechanisms that are meant to control pathogens don’t turn off. The result is oxidants run amok, creating havoc in the cell’s energy cycles, and increasing inflammation.

The protocol described here was originally put together by Dr. Pall and by Dr. Grace Ziem. It is based on antioxidant treatments which break the vicious cycle of oxidative stress as well as other agents that act to lower other parts of the cycle, such as lowering inflammatory responses, improving mitochondrial function and lowering excessive NMDA activity. However, taking large quantities of single antioxidants can actually increase oxidative stress. Once antioxidants such as tocopherols (vitamin E), vitamin C, and flavonoids react with free radicals, these antioxidants are themselves converted into free radicals. Other antioxidants are then needed to neutralize those newly formed free radicals. Therefore, a wide variety of antioxidants is optimal.

PLEASE NOTE: Dr. Pall emphasizes that he is a Ph.D., not an M.D., and none of these therapies should be viewed as medical advice.

Below is a list of Dr. Pall’s therapies. More detailed information follows.

  1. Nebulized reduced glutathione
  2. Nebulized inhaled hydroxocobalamin
  3. Mixed natural tocopherols
  4. Buffered C
  5. Magnesium, as malate
  6. Four flavonoids: gingko, cranberry extract, silymarin and bilberry
  7. Selenium, as selenium-grown yeast
  8. CoQ10
  9. Folic acid
  10. Carotenoids including lycopene, lutein and B carotene
  11. Alpha lipoic acid
  12. Zinc (modest dose), manganese (low dose), copper (low dose)
  13. Vitamin B6, as pyridoxal phosphate
  14. Riboflavin 5′-phosphate
  15. Betaine (trimethylglycine)
  16. Acetyl-carnitine
  17. Taurine

Detailed antioxidant protocol:

Vitamin C. Pall suggests 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 nitric oxide synthase (NOS) uncoupling, and high doses of vitamin C can be useful in scavenging peroxynitrite (ONOO–), the most central element in his NO/ONOO– cycle hypothesis.

CoQ10. CoQ10 has been used in a number of diseases to improve mitochondrial function. It scavenges free radicals, protects against loss of mitochondrial respiratory function, increases energy metabolism, and down regulates NMDA activity. Take early in the day.

Magnesium. This mineral lowers NMDA activity, reducing excitotoxicity. Dr. Pall believes that “magnesium is one of the most promising agents for treatment of multisystem diseases, but, like other such agents, it produces modest responses and may best be used in a complex, combination therapy.”

Selenium. Selenium is considered an antioxidant because certain proteins that contain selenium have antioxidant properties. Selenium occurs in glutathione peroxidases, enzymes that eliminate peroxide in cells. Selenium is also essential in making T3, the most active form of thyroid hormone. The best form of selenium is selenomethionine, which is a selenium-grown yeast. (For those who are yeast-sensitive, there are non-yeast forms.)

Carotenoids. These are plant pigments which are quite active in scavenging free radicals. Lycopene is more active than beta-carotene as a peroxynitrite scavenger. Lutein and zeaxanthin, two carotenoids, may also have special roles as antioxidants because of the way they insert into biological membranes.

Flavonoids. Anthocyanidins, which are found in purple plants, lower inflammatory activity, act as potent chain-breaking antioxidants, and regenerate other chain-breaking antioxidants after they have been converted to free radicals. Flavonoids also act as chelators for free iron, protecting cells from oxidative damage. Many flavonoids are soluble in both water and lipids. Flavonoids from green tea, citrus, grape seed extract, gingko, soy, olive, hawthorn, blueberry, and purple rice are effective antioxidants. Silymarin scavenges peroxynitrite, and increases the synthesis of SOD (superoxide dismutase), which makes it especially important. Flavonoids are rapidly absorbed in foods, and are quickly excreted through the kidneys, so they need to be eaten (or taken) throughout the day.

Acetyl-L-carnitine. Carnitine transports fatty acids into mitochondria, and is therefore essential for providing cellular energy. Acetyl-L-carnitine is more effective than L-carnitine because most oral L-carnitine ends up being excreted by the kidneys before it can be transported through the blood-brain barrier. Acetyl-L-carnitine is transported more efficiently. Recently, it has been shown that acetyl-L-carnitine lowers excessive NMDA activity and this may well be more important than the effects on mitochondrial function for lowering the NO/ONOO– cycle.

Reductive Stress Agents. Reductive stress causes oxidative stress. Methyl groups – SAMe, betaine, and carnitine – act as protective agents. Dr. Pall’s preference for a methylated compound is betaine (TMG.) It is cheaper and more stable than SAMe.

Hydroxocobalamin form of B12. B12 is a potent nitric oxide scavenger, but it is difficult to absorb. Oral absorption of B12 is limited by intrinsic factor. [Independent of intrinsic factor, the absorption rate of B12 is less than 1% of the total amount ingested.] Hydroxocobalamin taken as a nasal spray or injection is more effective.

Folate (folic acid). Reduced folate decreases uncoupling of NOS activity. Reduced folate in the form of 5-methyltetrahydrofolate (5-MTHF) is a potent scavenger of peroxynitrite and may well turn out to be among the most useful agents for lowering the NO/ONOO– cycle. Optimal dosage may well vary among different individuals but, in general, it should be taken along with quite a bit of vitamin C (at least 500 mg and preferably perhaps twice this amount). The reaction between peroxynitrite and 5-MTHF is important not only because it can be used to lower peroxynitrite levels. It is also important because in NO/ONOO– diseases, elevated peroxynitrite will act to lower the levels of 5-MTHF, lowering methylation cycle activity, and will also act to lower all reduced folates in the body. In this way, lowered methylation activity may be caused by the NO/ONOO– cycle.

B6, as P5P. B6 minimizes neurotoxicity. The best form is pyridoxine phosphate (P5P).

Riboflavin. Riboflavin is important for the production of reduced glutathione. It is also useful in the treatment of migraine.

Alpha Lipoic Acid (ALA) scavenges free radicals. As an added benefit, it can regenerate other antioxidants by reducing oxidized and free radical forms of glutathione, tocopherols, vitamin C and flavonoids. It can maintain glutathione pools by turning oxidized glutathione into its active form, reduced glutathione. ALA can cross the blood-brain barrier, making it an effective tool for reducing damage due to oxidative stress in the brain.

Zinc, Manganese and Copper. These minerals are components of superoxide dismutases (SOD), the enzymes that convert the oxidant superoxide into hydrogen peroxide and oxygen. Zinc, copper and manganese deficiencies can produce oxidative stress, part of which may be due to the lowered ability to produce SODs. Doses of these metals can be tricky. Excessive levels of copper and manganese can themselves produce oxidative stress. Excessive zinc lowers copper levels. Dr. Pall suggests “modest levels.”

Taurine is an unusual amino acid, because it is an antioxidant as well as a neurotransmitter. Taurine acts to stimulate the synthesis of GABA, and is transported easily across the blood-brain barrier, allowing it to work in the brain. Taurine stimulates several inhibitory receptors, leading to lowered NMDA activity. It also acts to lower intracellular calcium levels, thus lowering NO synthesis.

Long-chain omega-3 fatty acids. Polyunsaturated fatty acids (PUFAs) are more susceptible to lipid peroxidation than are other fatty acids, and consequently they tend to be depleted whenever there is oxidative stress. Fish oil, borage oil and flaxseed oil are sources of long-chain omega-3 fatty acids.

Curcumin, honokiol (from magnolia), cat’s claw, vinpocetine and feverfew all reduce inflammation by lowering NF-kappaB activity, as do a number of conventional pharmaceuticals.

Vitamin E should not be taken as synthetic alpha-tocopherol, which is the most commonly taken form, Pall argues. Rather, it should be taken as relatively high doses of gamma-tocopherol and tocotrienols with modest amounts of natural alpha-tocopherol. These other forms of vitamin E have important functions, such as lowering inflammation, scavenging an important breakdown product of peroxynitrite, lowering excessive NMDA activity and improving mitochondrial function, all important for lowering NO/ONOO– cycle diseases.

Algal supplements. Both chlorella and blue-green algae are rich in antioxidants. Blue-green algae contain phycocyanin, which is a potent free radical scavenger.

FURTHER READING:

Pall, Martin. Explaining “Unexplained Illnesses”: Disease Paradigm for Chronic Fatigue Syndrome, Multiple Chemical Sensitivity, Fibromyalgia, Post-Traumatic Stress Disorder, Gulf War Syndrome and Others. New York: Harrington Park Press, trade division of Haworth Press, Inc. 2007.

This book is technical, but well worth reading. Dr. Pall has made a remarkable contribution to the study of “unexplained illnesses.”

“How Can We Cure NO/ONOO– Cycle Diseases: Approaches to Curing Chronic Fatigue Syndrome/Myalgic Encephalomyelitis, Fibromyalgia, Multiple Chemical Sensitivity, Gulf War Syndrome and Possibly Many Others.” Martin Pall. Townsend Letter. Feb/March 2010.

Excellent paper by Martin Pall on agents that lower parts of the NO/ONOO? cycle. Contains detailed information on protocols and potential therapeutic agents. 

Martin Pall – MEPedia’s comprehensive page on Dr. Pall includes publications, talks, interviews, papers, and more.

Antioxidant Suggestions from Dr. Martin Pall, Ph.D.  Tables of supplements recommended by Dr. Pall, along with mechanisms and comments.

Micronutrition as a Therapeutic Strategy for Mitochondrial Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: A Narrative Review

Abstract:

Fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are chronic multisystem disorders characterized by persistent fatigue, pain, cognitive dysfunction, sleep disturbances, and reduced quality of life. Increasing evidence implicates mitochondrial dysfunction, oxidative and nitrosative stress, immune dysregulation, and altered redox and nicotinamide adenine dinucleotide (NAD+) metabolism as interconnected mechanisms contributing to fatigue, although the strength of evidence varies across these pathways. Micronutrients are essential components of mitochondrial bioenergetics, antioxidant defense, and immune-metabolic regulation.

This narrative review critically examines the mechanistic and clinical evidence supporting mitochondrial-oriented micronutritional interventions in fibromyalgia and ME/CFS, including NAD+ precursors, B-complex vitamins, magnesium, coenzyme Q10, alpha-lipoic acid, GlyNAC, L-carnitine, pyrroloquinoline quinone, taurine, and creatine. Mechanistic plausibility is distinguished from clinical efficacy, as disease-specific randomized controlled evidence remains limited for several interventions. We further discuss biomarkers, metabolic phenotyping, and precision nutrition within a systems-based micronutrition framework.

Finally, we present the rationale for a future randomized, double-blind, placebo-controlled trial in fibromyalgia patients with clinically significant fatigue, which is planned for 2027, subject to ethics approval and prospective registration, as a strategy for future clinical validation.

Source: Abanades S, Fernández I, Capdevila N, Cardona F. Micronutrition as a Therapeutic Strategy for Mitochondrial Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: A Narrative Review. Nutrients. 2026 Aug 19;18(16):2702. doi: 10.3390/nu18162702. PMID: 42654282. https://www.mdpi.com/2072-6643/18/16/2702 (Full text)

Targeting Bioenergetic, Redox and Prostaglandin Pathways in Long COVID-Associated Post-Exertional Malaise and Brain Fog: A Nutraceutical Translational Hypothesis

Abstract:

Post-exertional malaise (PEM) and cognitive dysfunction (hereafter “cognitive dysfunction”, including the patient-reported syndrome often described as “brain fog”) are among the most disabling features of Long COVID; yet, approved disease-modifying treatments remain lacking. Emerging evidence implicates interacting disturbances in mitochondrial bioenergetics, redox regulation and neurovascular inflammation, although much of the supporting evidence remains indirect and derives from acute COVID-19, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), primary mitochondrial disease, inflammatory biology and mechanistic pharmacology rather than from direct Long COVID intervention trials.

This hypothesis-generating narrative review develops a mechanism-based translational framework: that a pathway-targeted nutraceutical programme may modulate selected elements of these three axes, subject to prior demonstration of formulation quality, pharmacokinetic feasibility, target engagement and safety. Candidate modules comprise coenzyme Q10 and alpha-lipoic acid for bioenergetic/redox support; selenium, sulforaphane and resveratrol for Nrf2-thioredoxin-related redox regulation; and Boswellia serrata, luteolin and eicosapentaenoic acid for putative prostaglandin/resolution-pathway modulation. Sonlicromanol provides a conceptual mechanistic precedent for combined redox and prostaglandin-directed pharmacology, but it is not considered pharmacologically equivalent to an eight-agent nutraceutical combination.

We summarise the mechanistic rationale, distinguish direct from indirect evidence, define qualitative evidence-grading criteria, outline safety and interaction considerations, and propose a staged translational research programme. This framework is intended to generate falsifiable hypotheses for future Long COVID studies, not to imply established clinical efficacy.

Source: Praet SFE. Targeting Bioenergetic, Redox and Prostaglandin Pathways in Long COVID-Associated Post-Exertional Malaise and Brain Fog: A Nutraceutical Translational Hypothesis. Nutrients. 2026 Aug 13;18(16):2650. doi: 10.3390/nu18162650. PMID: 42654231. https://www.mdpi.com/2072-6643/18/16/2650 (Full text)

REenergizeME: intermittent hypoxia-hyperoxia treatment for myalgic encephalomyelitis/chronic fatigue syndrome-protocol for a randomised, placebo-controlled trial

Abstract:

Introduction: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, disabling condition characterised by post-exertional malaise (PEM), autonomic dysfunction and markedly reduced quality of life. Its prevalence has increased following the COVID-19 pandemic, yet no effective disease-modifying treatments are available and underlying mechanisms remain unclear. Evidence implicates immune-metabolic dysregulation, impaired energy metabolism, vascular dysfunction and altered oxygen handling. Intermittent hypoxia-hyperoxia treatment (IHHT) is a non-pharmacological intervention proposed to induce adaptive physiological and cellular responses via hypoxia- and redox-sensitive pathways. This trial evaluates the clinical efficacy of IHHT in ME/CFS and explores associated mechanisms.

Methods and analysis: This randomised, placebo-controlled, participant- and assessor-blinded clinical trial will enrol 104 female patients aged 20-59 years who meet the International Consensus Criteria for ME/CFS along with a healthy control group for mechanistic comparisons. Participants will be randomised 1:1 to IHHT or placebo following baseline assessments. The intervention will be delivered over 8 weeks. The primary endpoint is change in quality of life measured by the vitality domain of the Short Form-36 Health Survey. Secondary endpoints include PEM severity, fatigue severity, cognitive severity, functional capacity and autonomic symptoms assessed using validated patient-reported outcome measures and objective tests. Exploratory endpoints include pain phenotyping, autonomic, sudomotor and neurophysiological assessments, tissue oxygenation by near-infrared spectroscopy, peripheral small-fibre nerve assessments using corneal confocal microscopy and skin biopsy and immune-metabolic and oxidative stress biomarkers. Assessments will be conducted at baseline; post-treatment; and at 3, 6 and 12 months follow-up.

Ethics and dissemination: The trial is conducted in accordance with the Declaration of Helsinki and International Council for Harmonisation – Good Clinical Practice guidelines and was approved by the Danish Scientific Ethical Committees (De Videnskabsetiske Medicinske Komitéer, VMK; approval no. 2500959). Written informed consent will be obtained from all participants. Results will be disseminated through peer-reviewed publications and scientific conferences.

Trial registration number: ClinicalTrials.gov Identifier: NCT07317401.

Source: Nochi M, Kristensen SK, Mehrani N, Guerreiro I, Nørholm IMD, Chandra S, Olufsen M, Gudbergsen LR, Brinth LS, Stokholm R, Karlsson P, Tankisi H, Mehlsen J, Foldager CB, Olsen RKJ. REenergizeME: intermittent hypoxia-hyperoxia treatment for myalgic encephalomyelitis/chronic fatigue syndrome-protocol for a randomised, placebo-controlled trial. BMJ Open. 2026 Aug 14;16(8):e117729. doi: 10.1136/bmjopen-2026-117729. PMID: 42601095. https://bmjopen.bmj.com/content/16/8/e117729 (Full text)

Exploring the mechanisms of acupuncture in improving cognitive function in post-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome: study protocol for a randomized controlled trial using multimodal MRI

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a common sequela following COVID-19. Although cognitive dysfunction is one of the most debilitating symptoms in ME/CFS, effective therapies are limited. Acupuncture is an important complementary and alternative therapy for ME/CFS and has been shown to have positive effects on cognitive dysfunction in other diseases. However, the effect and mechanism of acupuncture in treating cognitive dysfunction in post-COVID-19 ME/CFS(PCME/CFS) remain unclear. In this study, we designed a randomized controlled trial to evaluate the efficacy of acupuncture treatment in improving cognitive function in PCME/CFS and to investigate the neural mechanisms of acupuncture using multimodal magnetic resonance imaging (MRI) techniques.

Methods: A total of 129 patients and 30 healthy controls (HCs) will be enrolled. The 129 patients with PCME/CFS will be randomly assigned in a 1:1:1 ratio to a verum acupuncture (VA), sham acupuncture (SA), or a waitlist control group. Participants in the VA and SA groups will receive three sessions of treatment per week for 8 weeks, while patients in the waitlist control group will be treated after the 8-week waiting period. The primary outcome is the change in the Symbol Digit Modalities Test (SDMT) score from baseline to week 8. The secondary outcome measures include changes from baseline to endpoint (week 8) in cognitive performance as assessed by the Digit Span Test (DST), Trail Making Test (TMT), Rey Auditory Verbal Learning Test (RAVLT), Rey-Osterrieth complex figure test (RCFT), Stroop Color and Word Test (SCWT), phonemic fluency test, category fluency test, action fluency test, and 30-item Boston Naming Test (BNT-30). In addition, changes in hippocampal metabolites and resting-state functional connectivity(RSFC) will be examined using 1H-magnetic resonance spectroscopy(1H-MRS) and functional MRI (fMRI), respectively. Moreover, the Multidimensional Fatigue Inventory (MFI-20), Pittsburgh Sleep Quality Index (PSQI), Generalized Anxiety Disorder 7-item scale (GAD-7), 24-item Hamilton Depression Scale (HAMD-24), and 36-Item Short Form Survey (SF-36) will also be assessed at baseline and week 8.

Discussion: The results of this study will provide preliminary evidence regarding the efficacy of acupuncture therapy in improving cognitive function in PCME/CFS and will explore whether acupuncture improves cognitive function in this disease by modulating metabolism and RSFC in the hippocampus.

Clinical trial registration: www.clinicaltrials.gov, identifier: NCT07357688.

Source: Luo T, Luo Y, Huang L, Jin H, An Y, Huang J, Luo K, Guo Y, Wang D, Liu D, Wu X. Exploring the mechanisms of acupuncture in improving cognitive function in post-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome: study protocol for a randomized controlled trial using multimodal MRI. Front Neurol. 2026 Jun 3;17:1793397. doi: 10.3389/fneur.2026.1793397. PMID: 42383026; PMCID: PMC13318089. https://pmc.ncbi.nlm.nih.gov/articles/PMC13318089/ (Full text)

Hyperbaric oxygen therapy improves clinical symptoms and functional capacity and modulates thalamic connectivity in ME/CFS: a prospective cohort study

Abstract:

Background: Hyperbaric oxygen therapy (HBOT) has been proposed as a treatment for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but evidence remains limited. This study evaluated its clinical effectiveness and feasibility, as well as associated functional brain changes.

Methods: Thirty patients with ME/CFS (mean age 42.3 ± 11.7 years; 7 males, 23 females) received 40 HBOT sessions. Clinical outcomes were assessed at baseline, during treatment, and four weeks post-treatment. The primary outcome was change in the physical functioning subscale of the Short Form-36 Health Survey (SF-36 PF). Secondary outcomes included severity of core symptoms assessed via questionnaires, exercise capacity, handgrip strength, cognitive performance, orthostatic intolerance, and brain magnetic resonance imaging (MRI; volumetry and functional connectivity [FC]). Thirty age- and sex-matched healthy controls (mean age 42.3 ± 11.3 years; 7 males, 23 females) were included for MRI comparison.

Results: SF-36 PF significantly improved during HBOT compared with baseline (g = 0.71, p = 0.006). SF-36 pain (p = 0.002, g = 0.79) and Chalder Fatigue Scale also showed clinically meaningful reductions (p < 0.001, g = -0.87). Exercise capacity (g = 0.66), muscle strength (g = 0.40), and information processing speed (g = 0.52) improved significantly after treatment (all p < 0.05). Treatment adherence was high and tolerability was favorable, with no major adverse events reported. Functional MRI analyses revealed increased thalamic FC in ME/CFS patients compared to healthy controls in bilateral sensorimotor (p < 0.001, t = 5.65, FDR-corrected) and visuo-occipital regions (p < 0.001, t = 5.40, FDR-corrected) at baseline. Following HBOT, thalamic hyperconnectivity shifted toward patterns observed in healthy controls. Responders, defined as a ≥ 10 points increase in SF-36 PF, showed greater reductions in thalamic hyperconnectivity than non-responders (p < 0.001, t = -4.34 to -5.18, FDR-corrected).

Conclusions: HBOT was well tolerated and associated with significant improvements in physical functioning, fatigue, pain, and cognitive performance in ME/CFS. The post-treatment shift in thalamocortical connectivity toward healthy control patterns and its association with clinical response support the hypothesis that functional thalamic dysregulation contributes to ME/CFS pathophysiology and may be modulated by HBOT. This provides a network-level rationale for controlled trials to confirm therapeutic efficacy.

Trial registration: ClinicalTrials.gov NCT06118138. Registered 01 November 2023 – Retrospectively registered, https://clinicaltrials.gov/study/NCT06118138?cond=ME%2FCFSamp;term=HBOTamp;rank=1.

Source: Kim L, Cammà G, Peters CK, Mantwill M, Müller O, Leprêtre N, Heindrich C, Rust R, Krill M, Hartung TJ, Reeß LG, Krohn S, Heymann CV, Wittke K, Finke C, Scheibenbogen C. Hyperbaric oxygen therapy improves clinical symptoms and functional capacity and modulates thalamic connectivity in ME/CFS: a prospective cohort study. J Transl Med. 2026 Jun 5. doi: 10.1186/s12967-026-08324-6. Epub ahead of print. PMID: 42249466. https://link.springer.com/article/10.1186/s12967-026-08324-6 (Full study available as PDF file)

Molecular hydrogen as a treatment for ME/CFS: a mini-review of clinical evidence and mechanistic rationale

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem illness characterized by profound fatigue, post-exertional malaise, cognitive impairment, and autonomic dysfunction, yet it currently lacks FDA-approved treatments. Molecular hydrogen (H2), administered primarily as hydrogen-rich water (HRW), has emerged as a potential therapeutic candidate due to its selective antioxidant effects, anti-inflammatory activity, and support of mitochondrial and cellular homeostasis. These mechanisms align with several biological abnormalities implicated in ME/CFS, including oxidative stress, chronic inflammation, and impaired energy metabolism. This narrative mini-review summarizes mechanistic evidence relevant to ME/CFS and evaluates three developmental clinical studies of HRW in this population.

Although early trials are small and methodologically limited, moderate-dose HRW consumed over extended durations has demonstrated feasibility and preliminary benefits in reducing fatigue and improving physical function, with generally mild side effects. Overlapping findings in Long COVID further suggest potential applicability across related post-viral fatigue conditions. Key limitations include small sample sizes, reliance on self-report outcomes, and the absence of objective biomarkers.

Future research should prioritize larger, rigorously controlled trials incorporating remote biometric and biochemical assessments to clarify mechanisms of action and identify responsive subgroups. Overall, molecular hydrogen represents a promising, low-burden adjunctive therapy warranting further investigation in ME/CFS.

Source:Friedberg F and LeBaron TW (2026) Molecular hydrogen as a treatment for ME/CFS: a mini-review of clinical evidence and mechanistic rationale. Front. Med. 13:1760210. doi: 10.3389/fmed.2026.1760210 https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2026.1760210/full (Full text)

Vitamin D in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome After COVID-19 or Vaccination: A Randomized Controlled Trial

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) can develop as post-vaccination syndrome (PVS) or Post-Acute Sequelae of SARS-CoV-2 infection (PASC). In our prior retrospective study, most patients with PVS who developed ME/CFS had vitamin D insufficiency or deficiency. We evaluated the efficacy of vitamin D replacement therapy guidance for ME/CFS symptom improvement in patients with vitamin D insufficiency or deficiency.

Methods: This open-label randomized controlled trial enrolled 91 participants with ME/CFS as PVS or PASC and serum 25(OH) vitamin D < 30 ng/mL across five clinical sites. Participants were randomized 1:1 to intervention (active vitamin D preparation plus vitamin D replacement therapy guidance: 25 μg daily supplementation, dietary counseling, sun exposure, and exercise) or control (active vitamin D preparation alone) for 12 weeks. The primary endpoint was the change in ME/CFS symptom count from screening to Week 12.

Results: Mean symptom change was -6.7 in the intervention group versus -1.2 in the control group (between-group difference -5.6; 95% CI: -7.2, -3.9; p < 0.001). Serum 25(OH) vitamin D improved from 18.6 to 27.1 ng/mL in the intervention group, while the control group showed a decreasing trend (between-group difference 10.2 ng/mL; 95% CI: 7.9, 12.5). Achievement of <8 symptoms (i.e., no longer meeting ME/CFS diagnostic criteria) was significantly higher in the intervention group, with 16 participants achieving this threshold compared to 1 in the control group (p < 0.001). Subgroup analyses showed consistent benefit in both PVS (n = 56) and PASC (n = 29) cohorts.

Conclusions: Vitamin D replacement therapy guidance significantly reduced ME/CFS symptoms along with improvement of serum 25(OH) vitamin D levels in patients with vitamin D insufficiency or deficiency who developed ME/CFS as PVS or PASC.

Source: Kodama S, Nakata M, Konishi N, Yoshino M, Fujisawa A, Naganuma M, Kobayashi Y, Hirai Y, Kitagawa A, Miyokawa M, Mishima R, Teramukai S, Fukushima M. Vitamin D in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome After COVID-19 or Vaccination: A Randomized Controlled Trial. Nutrients. 2026 Feb 3;18(3):521. doi: 10.3390/nu18030521. PMID: 41683343. https://www.mdpi.com/2072-6643/18/3/521 (Full text)