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Glutathione - The Genetic Connection

There is a genetic connection to low GSH levels. A gene designated GSTM1 (glutathione S-transferase Mu 1) is a human glutathione S-transferase (GST) enzyme thought to play a role in the biotransformation of pollutants, drugs, toxins, all generally known as xenobiotics.

GSTM1 is one of the family of glutathione S-transferases, which allow GSH to interact with harmful organic hydroperoxides to neutralize and excrete them from the body.

There is strong evidence linking chronic fatigue syndrome and GSTM1 dysfunction. It is possible that the effectiveness of GSH supplementation in those with chronic fatigue syndrome may be in part dependent upon their genetic status with reference to the GSTM1 gene. It is also possible to possess a mutant genetic makeup (GSTM1-0/0) that does not allow for the production of GSH.

It has been estimated that 40-60% of the population may have two copies (one from each parent) of the same mutant form of the GSTM1 gene, lacking that gene's normal function. The health outlook for chronic fatigue patients with GSTM1-0/0 is worse than for those who do not possess that genetic make-up.

If someone is in that population without an active GSTM1 gene, they may need to compensate by eating more broccoli or by eating “super broccoli” that has higher levels of the active plant chemical sulforaphane. Consuming larger portions of broccoli or super broccoli makes it possible to retain greater amounts of sulforaphane not to mention other vitamins and minerals.

Considering that most of us have no idea what type of GSTM1 gene we carry nor do we know how much broccoli is enough, eating broccoli and other cruciferous vegetables as part of a healthy lifestyle is highly recommended.

If someone can't handle all that broccoli, then consider broccoli sprouts in salads or on sandwiches. They are higher in sufloraphane anyway.

Genetics aside, as Dr. Hyman stated, as we age our levels of glutathione steadily decline.

This correlates with his observations that the lowest GSH levels are seen in the oldest, sickest, hospitalized patients and the highest levels in the younger, healthier individuals. The charts shown above and to the right illustrate this quite well.

The good news is that supplementation with a GSH accelerator product GSH levels are restored across all groups, both the healthy and catastrophically ill.


The Methylation Cycle

Methylation
refers to the attachment or substitution of a methyl hydrocarbon group on various molecules through the interaction of appropriate enzymes.

It's called methylation because the hydrocarbon in question is methane and in human biochemistry, a hydrogen atom gets replaced with the methyl group.

Dr. Van Konynenburg, PhD., an independent researcher in glutathione and the methylation cycle for many years, believes that the fundamental biochemical issue in a large subset of chronic fatigue syndrome (CFS) patients is that the methylation cycle is blocked. The main goal of this treatment approach is to remove this block and restore the methylation cycle.

He also believes that GSH depletion is directly responsible for many of the features of CFS, but that it is usually not possible to normalize the GSH levels on a permanent basis by direct supplementation of glutathione building blocks.

Rather, the methylation cycle block must be corrected first to break the cycle that is holding down the glutathione levels. In addition to this, about one-third of CFS patients, because of particular genetic mutations described in the previous paragraph, cannot tolerate supplementation with GSH or other substances intended to help them directly build GSH.

In biological systems, methylation is enabled by enzymes and is extremely important in several areas. Methylation can be involved in modification of heavy metals, regulation of gene expression, regulation of protein function, and RNA metabolism. Methylation of heavy metals can also occur outside of biological systems.

Thus, if the process is blocked and unable to occur, we will have problems in a lot more areas than chronic fatigue.

For a very comprehensive article on the methylation cycle including a list of supplements to take to get the cycle kick-started once it has stalled, go to Dr. Myhill's site, "CFS-The Methylation Cycle-Updated May 2009".

Clinical Trials
The 70,000 to 80,000 papers submitted on glutathione are backed up by numerous clinical studies. There is no doubt about the importance and function of GSH on one’s health. So we can safely talk about the benefits of glutathione all day without worry.

What we cannot do, is promote a specific GSH support product with cure or healing claims unless it has been through the FDA's New Drug Application process and been approved for use with a specific health condition.

Suffice it to say that there are literally hundreds of trials that have been conducted or are being conducted now. The link to "Psych Drug Truth" shows a page from an intensely interesting and informative website dealing with psychotropic drugs, among other things, and how glutathione works to detoxify the body of such poisons.

This linked page deals with GSH and, what is interesting about it, is that it contains probably 200 or so links to Glutathione related PubMed articles detailing many of the aforementioned clinical trials

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