The Methylation Cycle and the Production of Glutathione

The most important point of the methylation cycle is the production of glutathione (GSH). If GSH production is inhibited as it is with several types of genetic “glitches” then dysfunction and disease result.

 Methyl cycle defects (and low glutathione) leave you sensitive to environmental toxins, compromise your defense against microbial infection, and complicate proper reading of your remaining genes. Methyl cycle dysfunction explains why one individual is damaged by environmental toxins, while others living in the same environment are unaffected.

Glutathione is technically a tripeptide, which is a small protein, it is made up of only three amino acids. It is present naturally in every cell of the body, as well as in the blood, the bile and the fluid lining the lungs. The liver is normally the main producer of glutathione which plays many important roles in the body. Probably the best known are its protection against oxidative stress produced by oxidizing free radicals and other reactive oxygen species, its support for the immune system, and its role in removing a variety of toxic substances from the body.

When glutathione becomes somewhat depleted, as it does in many cases of CFS (Chronic Fatigue Syndrome), or ME (Myalgic encephalitis) its normal functions are simply not performed well. Many of the symptoms of CFS as well as observed abnormal results on specialized lab tests can be traced directly to glutathione depletion.

 Methylation “Glitches” can lead to Low Glutathione Symptoms:

• Fatigue due to oxidative stress and mitochondrial dysfunction and low ATP output (Pyruvate cannot run through Krebs cycle).
• Diastolic dysfunctions in the heart and resultant low cardiac output (heart palpations, fatigue, low heart rate)
• Buildup of toxins including heavy metals which damage many enzymes and block absorption. Which leads to further depletion of glutathione (vicious cycle).
• Immune dysfunction (inability to fight infections and autoimmune issues) from Natural Killer cell and CD8 cell cytotoxicity. This leads to chronic fatigue syndrome-reactivation of herpes family viral infections (Including EBV, HSV, etc).
• Autoimmune disease-Decreased cell mediated immune response and shift to TH2 immune response from TH1. Initially caused by the high cortisol output and later in the decreased HPA function and decreased glutathione in the CD4 T cells. Folate deficiency with low methylation decreases the B and T cell production.
• Joint pain and inflammation-Increased inflammation from pro-inflammatory cytokines reflects the ongoing activation of the dysfunctional immune response to pathogens and lack of control of inflammation from low cortisol.
• Digestive issues due to lack of ATP in parietal cells and low production of HCL. Low absorption of nutrients results along with gastric reflux and survival of yeasts and bacteria from food which results in dysbiosis. Lack of conversion of pepsinogen to pepsin (requires ATP). This all results in poor gastric signaling to the pancreas and gallbladder for release of digestive enzymes and bile. This also results in low absorption of B12 and further aggravates the problem. Low GSH leads to low volume of bile from the gallbladder.
• Food sensitivities and leaky gut: From low folate to repair the enterocytes that line the intestines and repair the damaged cells. Abnormal cortisol also decreases the secretory IgA levels which normally protect the gut lining. Increased levels of histamine lead to the release of zonulin which increases gaps in the cells of the intestines. The resultant food sensitivities result in further immune dysregulation.
• Thyroid problems (hypothyroidism, increased reverse T3, Hashimoto’s Thyroiditis) Glutathione normally protects the thyroid from damage due to hydrogen peroxide produced in the production of thyroid hormones. The immune system mounts an attack on these foreign proteins and creates the autoimmune response of Hashimoto’s. (GSH helps convert H2O2 to H2O along with Catalase)
• Low secretion and dysregulation of ACTH (adrenocorticotrophic hormone) This leads to low cortisol in the long run. The initial high stress period starts with high cortisol secretion then eventual exhaustion and low cortisol levels.
• Blunting of the HPA axis (pituitary-adrenal issues) due to continued high cortisol initially.
• Decreased ADH (Antidiuretic hormone) which leads to Diabetes Insipidis. Signs and symptoms include constant thirst and high urine volume. Eventually leading to low blood volume and increased fatigue.
• Excitotoxicity-glutamate cannot be broken down correctly into GABA. This results in neurological damage. (Symptoms include anxiety, nervousness, insomnia, diabetes)
• Low Dopamine-this can lead to depression, apathy, ADD, ADHD and addictive behavior.
• Disrepair of myelin-slow brain processing and possible MS, ALS. This also increases sensitivity to EMF’s. Myelin basic protein, phosphatidyl choline and choline plasmogen require methylation for repair. Lack of effective insulation causes the increased susceptibility to electromagnetic radiation damage.
• Neurotransmitter depletion-Resulting in depression, anxiety, bipolar disorder.