The following is from "Our molecular Nature - The Body's Motors, Machines and Messages":

Glutathione plays several essential roles in our protection. It is composed of three amino acids connected in tandem: glycine, cysteine, and in an unusual bond to its acidic group, glutamate. Glutathione is not built by the normal machinery of protein synthesis. The unusual bond to glutamate poses an impossible problem to a ribosome. Instead, it is constructed from its three component amino acids by two custom enzymes. The central cysteine is the key to the protection afforded by glutathione. Its sulfur atom scavenges destructive molecules like peroxides and free radicals, converting them to harmless compounds. In the liver, the enzyme glutathione S-transferase takes the sulfur from glutathione and attaches it to toxic molecules, making them more soluble and easier to eliminate, similarly to the oxygen added by cytochrome p450 enzymes. Glutathione also maintains our proteins in their proper form. Its sulfur atom reacts with unnatural sulfur-sulfur bonds in proteins, breaking them and allowing the proper pairings to form. This reactive sulfur also maintains the iron in hemoglobin (page 75) at the proper charge. Relatively high concentrations of glutathione, found throughout the body, are necessary for these functions. Cysteine by itself would probably serve as well, but free cysteine is quite reactive and would be toxic at this high level.

Glutathione plays a role in the detoxification of acetaminophen, a nonaspirin pain killer. Acetaminophen is broken down first by reaction with a cytochrome p450 enzyme, forming a highly toxic intermediate, then by addition of glutathione, forming a nontoxic product that is promptly excreted. In normal analgesic amounts, the drug is harmlessly cleared away in a few hours. However, if an overdose of acetaminophen is taken -- perhaps 30 grams for a normal adult -- the reserves of glutathione in the liver are depleted in this reaction. The highly reactive intermediates formed by cytochrome p450 then build up and react with other vital cellular components, causing extensive liver damage.
"Our molecular Nature - The Body's Motors, Machines and Messages" by David S. Goodsell, pg 118-119.

This next excerpt is from the SUMMARY OF A PRESENTATION BY PAUL CHENEY, M.D., Ph.D.

Mitochochondrial dysfunction, reducing ATP generation, is linked to glutathione deficiency by the Gibbs free energy equation. [The energy produced by metabolism of glucose is contained in the chemical bonds of adenosine triphosphate (ATP), which transfers it to where it can be used.] The Gibbs free energy equation says that the energy available to do work in the cell is equivalent to the glutathione concentration. [Glutathione is a peptide composed of three amino acids, cysteine, glutamate, and glycine. Like proteins, peptides are composed of amino acids, but peptides are smaller than proteins. In addition to its role in energy production, glutathione is the most abundant and most important anti-oxidant produced by the body and is a powerful detoxifier.] If there's a reduced energy available to do work, there will always be an equivalent reduction in glutathione.
(Note: The text between the square brackets [ ] was not part of the oral presentation given by Dr. Cheney. I assume that it was added by the transcriber for clarification purposes. I disagree with the transcriber's comment that glutathione has a role in energy production.)

My interpretation of the above is that glutathione production is either directly or indirectly affected by the production of ATP.

This is validated by the information on Glutathione - Synthesis at the "Virtual Free Radical School. The outline in this presentation describes, step-by-step, the processes involved in building glutathione. The two enzymes involved are both ATP-dependent. Therefore, a reduction in ATP could have a direct negative affect on the production of glutathione.

Since Dr. Cheney makes reference to the Gibbs free energy equation, which is affected by temperature, it may also be that a lower body temperature, due to reduced ATP production, may reduce the enzyme activation rate, reducing glutathione production.

Information on Gibbs free energy equation can be found on the webpage at:
How the Gibbs free energy equation may come into play with the the production of glutathione can be found at:
( This same article in html format can be found here. )

I was confused when Dr. Cheney suggested taking "isolated whey protein" products such as ImmuPlus to increase the production of glutathione. The presented information suggests that if ATP is increased then glutathione production would increase. Isolated whey proteins, from what I have found, do not influence production of ATP any more than other foods that a person may eat. The whey protein products are good sources for the amino acids that are necessary to build glutathione, but it was not brought out in the presentation that deficiencies of these particular amino acids were contributing factors for the low glutathione levels. Also, the amino acids needed to make glutathione are not "essential" amino acids, meaning that if the body does not get them from the foods that we eat, it can produce them from other resources.

Sweet dairy whey provides these same proteins, only at a lower concentration.

In a biochemistry textbook we find the following:

The reduced form of glutathione, a tripeptide with a free sulfhydryl group, serves as a sulfhydryl buffer that maintains the cysteine residues of hemoglobin and other red-cell proteins in the reduced state. The ratio of the reduced form of glutathione (GSH) to the oxidized form (GSSG) is normally about 500. The reduced form also plays a role in detoxification by reacting with hydrogen peroxide and organic peroxides.

Reduced glutathione appears to be essential for maintaining normal red-cell structure and for keeping hemoglobin in the ferrous state. Cells with a lowered level of reduced glutathione are more susceptible to hemolysis for reasons that are not yet understood.
"Biochemistry, 2nd edition" by Lubert Stryer, pg 344.

I wonder if this increased susceptibility to hemolysis, due to low glutathione levels, may be partly responsible for the low red blood cell mass in CFS/FMS that Drs. Bell and Streeten report.

The warning, indicating danger of liver damage from low glutathione in David Goodsell's book, is supported by information on the following webpages.

Silver Spring, Maryland, Sept. 19 (Bloomberg) -- Johnson & Johnson, the world's biggest seller of over-the-counter medicines, will change the U.S. labels for its Tylenol painkiller to emphasize that an overdose can cause liver damage.

Most taken Meds for Fibromyalgia
Do a word search for acetaminophen on this webpage to see which medications contain acetaminophen. Is your pain killer possibly contributing to low glutathione?

Acetaminophen is considered one of the safest analgesic drugs available, but the drug lacks an anti-inflammatory effect.

Given the information provided in David Goodsell's book, I do not think that acetaminophen should be taken by people with CFS/FMS. People with CFS/FMS are low in ATP and subsequently low in glutathione. If sufficient glutathione is not available to detoxify the toxic intermediates of acetominophen, liver damage may result. I provided the last link to show that this pain killer is still promoted as being safe. You cannot believe everything you read.

Researchers at Cornell University Medical Center found that an omega 3 rich diet revved up enzyme activity, including the important immune boosting, free radical fighter, glutathione S transferase. A range of omega 3 fatty acid research points to promising benefits of a diet high in fish oil for certain types of cancers.

The omega 3 and omega 6 fatty acids are polyunsaturated fatty acids that are an excellent source of healthy fat. The two key omega 3 fatty acids are EPA (Eicosapentaenoic Acid) and DHA (Docosahexaenoic Acid). These omega 3 fatty acids are found in fatty fish such as salmon, mackerel and sardines, and also in various plant foods such as soybeans, flaxseed and walnuts.

I suggest eating a serving of sardines, or other type of oily fish, once a week to maintain the benefits of that food in the article "Sardines and Herring".

If a person eats all the foods that have been found to increase the enzyme glutathione S-tranferase, it may be beneficial. But according to Dr. Cheney's presentation, a limiting factor in glutathione production is decreased ATP production. Glutathione S-transferase cannot perform its scavaging function without glutathione. Increasing the available ATP in the cell will probably have a greater affect in generating glutathione.

Raising the body temperature with FIR energy will mean that less ATP must be used to heat the body. While the body temperature is raised, more ATP will be available for other processes which require ATP. For example, the sodium potassium pump uses about 30% of the ATP that is manufactured in muscle cells. An even greater amount of ATP is used to power the sodium potassium pump in nerve cells.

I hope that this has helped some better understand the relationship of glutathione and ATP in CFS/FMS.

All the best,

I found the following website which suggests that a magnesium deficiency may also contribute to low glutathione levels. Researchers have shown that magnesium deficiency is very common in people with CFS-FMS. I thought that it would be beneficial to include in this article.

At is the following:

Findings help explain why low magnesium status is associated with many health disorders. Human volunteers at the Grand Forks Human Nutrition Research Center (GFHNRC), Grand Forks, North Dakota, were fed diets containing inadequate, marginal, and adequate amounts of magnesium over a 6 month period to ascertain whether a systemic neurogenic inflammatory response is of primary importance during magnesium deprivation. Magnesium deprivation resulted in elevated circulating substance P; changes in the release of other neurogenic peptides, including decreases in calcitonin generelated peptide and neuropeptide Y; and an apparent increase in oxidative stress as indicated by reduced circulating glutathione and increased extracellular superoxide dismutase. These findings may be the reason that numerous epidemiological findings and magnesium supplementation trials show that a low magnesium status is associated with numerous disorders including coronary heart disease, hypertension, migraine headaches, sleep disorders, mood disturbances, and osteoporosis.