*Updated 18 Feb 2016*
As I progress further and further into my reading and research on MTHFR and related conditions, glutathione (GSH) keeps popping up. Having reduced levels of glutathione is associated with many diseases and health conditions, including cancer, cystic fibrosis, Parkinson’s disease, Alzheimer’s disease, hypertension, atherosclerosis, emphysema, asthma, ME/chronic fatigue syndrome, fibromyalgia, autism, bipolar disorder and multiple sclerosis. In fact, if I hold up a list of diseases associated with reduced glutathione next to a list of diseases associated with MTHFR, they are almost identical.
This is not surprising considering the fact that the methylation pathway is crucial to glutathione production in the body. When it is said that people with MTHFR gene mutations are more susceptible to stress and toxins, it is this general decrease in glutathione among those with MTHFR that is being referred to. Everything related to GSH must be functioning optimally. A person needs to have enough GSH, along with the proper turnover rates and oxidation state. Otherwise the person is more susceptible to oxidative stress, which leads to disease. This is, of course, a vast simplification of the science involved (but you can get into that here if you’d like). The important thing to know is that this critical molecule is your body’s most powerful and abundant antioxidant and detoxifier. Your cells wouldn’t be able to survive without glutathione. And as we age, our GSH levels decline steadily and significantly, even if we feel healthy. People with chronic diseases have been found to have far lower levels of GSH than normal people.
Why Do I Need Glutathione?
- Glutathione is involved in many cellular processes, including cell differentiation, proliferation and apoptosis (death).
- The mitochondria in your cells make “free radicals” along with the energy they produce. If you’re deficient in GSH, your mitochondria are the first parts to be damaged. Unchecked free radicals also lead to degenerative diseases and aging.
- Glutathione is needed by the liver in order to carry out its detoxification processes. All those modern chemicals, toxins and medications put a huge burden on our livers and handling them depletes GSH stores. Your liver also needs GSH to make bile, which is essential for digestion and the breakdown of fats.
- Glutathione is essential for our immune system function, especially cell-mediated immunity. Infection, exercise and toxins all deplete glutathione and can trigger mitochondrial dysfunction. This explains why people with chronic infections may develop severe fatigue and other types of chronic health problems. GSH is essential for the production and responses of key immune system proteins like interleukin (IL)-2 and the activity of killer cells. GSH also reduces inflammation, which we’ve learned is a silent killer.
- It is essential to many other processes, including cellular redox homeostasis, oxygen transport, protection of DNA, amino acid transport, protection of B12 inside the cells and the removal of heavy metals.
Genetic Issues In Glutathione Depletion
The late Rich Van Konynenburg, Ph.D. was a proponent of the Glutathione—Methylation Cycle Block (GD-MCB) Hypothesis. While all of us are experiencing glutathione depletion as we age (beginning in our twenties), some people become more seriously ill than others earlier in life. Dr. Van Konynenburg’s hypothesis explains this as a combination of genetic predisposition and stressors, which can include “physical, biological, chemical, psychological/emotional” or a combination of these. Initially the stressors raise cortisol and epinephrine, depleting glutathione. This leads to toxin accumulation, vitamin B12 deficiency, a partial block of methionine synthase and then a dysregulation of sulfur metabolism. The sulfur metabolites drain into the transsulfuration pathway, are excreted and deplete methionine. Folate drains from the cells and this continues in a chronic vicious circle. This phenomenon has been observed not only in patients with chronic conditions like ME/CFS and fibromyalgia, but also in autistic patients.
Dr. Van Konynenburg observed the following symptoms and biomarkers in glutathione-deficient patients:
Oxidative stress, mitochondrial dysfunction and low ATP output, reduced cardiac output, toxin and heavy metal build-up, immune dysfunction, reactivation of herpes virus infections, thyroid problems, low cysteine-containing secretory proteins, high daily urine volumes, low natural killer and CD8 cells, high methylmalonate, partial methylation cycle blocks, fatigue, neuropathy, lowered synthesis of choline, creatine, carnitine, CoQ10, slow brain processing speed, high FIGLU in urine, low red and white blood cell counts, hair loss, poor digestion and absorption and other symptoms.
If you want to read more about this, please check out the linked presentation and article because I often see these symptoms described in online discussion groups. ME/CFS and fibromyalgia are related to many other chronic illnesses so just because you don’t think you have one of those conditions, or if you’re feeling a little off but you know something isn’t right, you could be on your way to developing one of the conditions described in this post. Remember, glutathione levels decline as we age and boosting them is an important way to protect your body and good health.
MTHFR is obviously an important gene to be aware of, not only for glutathione but for many other reasons discussed continually on this website. Some of the other genes associated with glutathione deficiency are GSS, GSTM1, GSTP1, GSTT1 and SOD. According to Dr. Paul Anderson of Anderson Medical Specialty Associates, people with mutations in these genes will “always need more precursor support.”
Personally I think glutathione depletion is to blame for much of the chronic illness that we are witnessing today. And you might say, well, the human body hasn’t changed? Why all of a sudden are we having so many problems? As Dr. David Katz said recently at the Future of Nutrition Conference, “there’s nothing wrong with human physiology, the problem is with our environment.” Most people are dealing with a lot of stress. We are bombarded with toxins and chemicals daily. More than 80,000 chemicals in the United States alone have never been fully tested to determine the effects they have on our health. Around 200 industrial chemicals and pollutants were found in the umbilical cord blood of babies born in US hospitals. This problem is only getting worse.
If you have MTHFR gene mutations, an important first step is to get your methylation pathway working properly (you’ll find information in the MTHFR section of the resources page of this site). According to Dr. Anderson, people who are very ill or healing will always need antioxidant support. Otherwise you will have “nitric oxide excess that blocks a lot of other pathways.” The sicker they are, the greater the required support such as intravenous (IV) and oral glutathione support.
You can get some glutathione from your diet but most of it is made by your body. As Dr. Jacob Teitelbaum explains, your body needs ATP and NADPH (which requires TPP) to make glutathione. These building blocks may be low in people who have illnesses like chronic fatigue and immune dysfunction. It becomes a vicious cycle as excessive glutathione depletion causes mitochondrial dysfunction, low triphosphate and ATP which leads to chemical toxicity and medication sensitivity.
Replacing glutathione is not as simple as taking a glutathione-containing supplement. Ideally you want your body to make its own glutathione. It’s essential to make sure that your method delivers the antioxidant efficiently to your cells.
- IV glutathione
- Glutathione/ATP injections
- N-acetyl cysteine (NAC)
- Whey protein
- Glutathione co-factors: selenium, B vitamins, alpha lipoic acids
- A specialized glutathione precursor supplement
- Foods containing glutathione and glutathione components
There is also a new form of liposomal glutathione in development.
Dr. Anderson adds that GSH requires selenium, magnesium, vitamins B2, B3, B5 and other basic cofactors. He likes alpha lipoic acid (200-300 mg twice daily for a while, assuming other cofactors are in place) and NAC. Dr. Mark Hyman recommends including vitamins C and E (all forms), milk thistle and regular exercise into the mix.
The level of glutathione support that you need will depend on your stage of illness and many other factors. If you need IV glutathione or injections, you’re going to be under the care of a health practitioner and usually dealing with an illness. Adding supplements like NAC or whey protein may work for some people, but many others can’t tolerate the sulfur. NAC used to put me to sleep when I took it and you need to take a large amount of it to see a noticeable benefit. The same goes for whey protein. Glutathione rich foods are a great natural option, but optimal absorption is key (and some of the foods have the sulfur issue again). You’ll also need to consume quite a bit of them.