*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.”
Raising Glutathione
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.
Pennee Hundley
https://www.nanoceuticalsolutions.com/product/1-bottle-nanosized-sublingual-glutathione/
This is a great Glutathione supplement that I have found that REALLY WORKS!
Christina S
Lots of great information in the article but no recommendation to a supplement that may have all the required components. What is the best supplment for MFHTR?
Thomas
How can you increase Glutathione without increasing CBS 699T Gene?
Matthew
I think we have to be very careful in taking antioxidant supplements, especially NAC and vitamin E. Yes, they scavenge reactive oxygen species and downregulate oxidative stress but, equally, they inhibit basal and macro autophagy – vitamin E also seems to increase mTOR. Autophagy is dysfunctional in many diseases and is crucial in maintaining cell health. That’s where polyphenols are more attractive as certain one’s have been noted to promote autophagy without significantly elevating ROS.
Having thought about this, it seems that a balance between ROS scavenging and autophagy needs to be struck. At times when ROS is excessive things like NAC can work quickly to brings everything in to check but long-term use on a daily basis doesn’t strike me as very advisable. Indeed, use every so often seems more prudent to mop up ROS.
Trevor
Is there a good resource to find a good MTHFR specialist in different areas? I’m in Salt Lake City Utah and don’t know where to start?
Is there any specific testing your recommend?
Andrea Post author
Hi Trevor – Dr Lynch maintains a database of doctors who have been through his training program https://seekinghealth.org/physician-directory/
The doctor will recommend appropriate tests as we are all different
Jodi Parker
Hello,
I’m looking to supplement with Glutathione as my levels are quite low. Is Liposomal Glutathione still considered the best form to take orally or is Acetyl Glutathione better? I’m seeing a lot of articles suggestion that Acetyl is a more stable oral form, but I’m not sure how accurate any of the information is since I can’t find anything published more recently than 2014. I just want to be sure I’m getting the product most beneficial in helping to solve that issue. Any idea what a good starting off point is in terms of how much to take?
Thank you!
Jessica
I have had four c-sections in the past five years, two all requiring strong antibiotics. I started having health issues after the second surgery. It’s all adding up now. I live in Northwest Arkansas and would love recommendations of any doctors within a days driving that anyone could suggest for these issues. Being floxxed, MTHFR, glutathione deficient, etc.
Andrea Post author
Amber W
Hi Jessica,
I’m in the Nashville area, and I love Jackie Warner at Thrive Health and Wellness in Nolensville, TN. She is a nurse practitioner, but she worked super hard to get to the bottom of my autoimmune and hormone issues. She also takes insurance.
Amber W
Hi Jessica,
I’m in the Nashville area, and I love Jackie Warner at Thrive Health and Wellness in Nolensville, TN. She is a nurse practitioner, but she worked super hard to get to the bottom of my autoimmune and hormone issues. She also takes insurance.
Joey Szekeres
I have had awesome results taking NAC on the higher dose side. It’s a wonderful supplement that has made me feel great and will take it from time to time.
Jenn
I might add that the geneticists say my liver can not utlize glutathione but my skin can
Bat Sheva Sida
Hi Jenn, I also found out that high iron levels can also affect glutathione levels.
Jenn
I wish you would cover missing gene glutathione.. i have absent glutathione gene from both parents.. I know about taking the precursers from my genetic report; NAC , L / S – Glutathione , glycine , garlic, onions, hot peppers, etc etc..
Also have MTHFR gene mutation
Joy
I had genetic testing that reveals that I am completely missing the genetics to produce glutathione. My naturopath has me on oral glutathione. I struggle with a myriad of health problems despite being young and maintaining a meticulously healthy lifestyle. Should someone like me even bother trying to build up production of glutathione if I am missing the genetics to produce it?
Dina Drovetto
Joy, any chance you took a fluoroquinolone drug in the past; Cipro levaquin avelox?? I was also in perfect health and was destroyed by cipro.
Cindy
I was on repeated doses of Cipro and Levaquin and it was shortly after that that my health nosedived and I developed inflamed tendons, fatigue and pain. Twenty years later and I still have these problems.
Kathy
I have a question on this – I recently took L-glutithione for about a week using the coffee enema route since I know if can’t be absorbed easily by mouth. I was trying to detox over break because I get such migraines from it. I started developing tremendous muscle aches, fatigue and depression – I still have these symptoms but somewhat less. I stopped the L- glutithione and that seemed to help, and I just started taking low doses of methyl B12 and Methyl folate. I’m a bit lost on what has happened to me and what to do about it.
Andrea Post author
It could be a detox reaction, Kathy but I couldn’t say for certain…
Margaret
Wow! So much to learn!
Both my husband I are compound heterozygous and we are on this learning journey together.
Thank you.
Peter
I read something about glutathione, and don’t understand why?
“THINGS TO AVOID
Glutathione and glutathione precursors such as NAC and glutamine, undenatured whey. The glutathione induces immediate active b12 deficiencies, apparently by converting active methylb12 to inactive glutathionylb12 and rapidly excreting it.”
here is the original link:http://forums.phoenixrising.me/index.php?threads/b-12-the-hidden-story.142/
Andrea Post author
Thanks for sharing, Peter. The only thing I can really add here is that, despite their being the gold standard for many years in raising glutathione levels, NAC and whey protein are NOT the most effective ways to do this. And NAC presents its own side effects. It is also the wrong form of cysteine.
It seems impossible to me that glutathione itself would cause a person to be B12 deficient as glutathione is made naturally in the body with or without our interventions. I don’t see any facts being linked to in this person’s post so it is hard to understand if he is confused or repeating incorrect information.
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Jenn Moran
Thank you so much for this blog. I came across it while researching about methylation. I found out through test ran by my ND that I am not a methylater and my body is also very sensitive to gluten. I have been having a lot of issues the last year and not feeling “normal” or myself. I turned 27 last month and within the last year it I have been working out and eating cleaner than ever yet I still seem to have a lot of things going on that just doesn’t add up. Your website is helping me in my own person journey and research and also questions to ask my doctor and suggestions on test that I may need done. A BIG THANK YOU! Bless you!!
Andrea Post author
I am so happy to be able to help you, Jenn =) You’re very welcome – happy you are figuring things out! Be well, Andrea
Lindy
Our doctor explained to us that methylated B vitamins, especially B12 will help the body make glutathione to help the liver with detoxing. My child did take a liver detox product for a couple months that had some extra glutathione, but right now he also takes SAM-e and is only supposed to take NAC if re-exposed to toxins. Just a comment about the whey protein — watch out. Most whey protein is LOADED with hidden MSG. Un-denatured whey protein is better. You can also try RAW vegetable protein at health food stores. As you may know, MSG, aspartame and other excitotoxins (20+ different food additives) cause damage to nerve cells and kill brain cells. And just because something is “organic” doesn’t mean it doesn’t have MSG. You have to learn all the different names for MSG, since food companies try to hide it.
Andrea Post author
Yes, getting the methylation pathway functioning optimally will assist in normal cellular function. The issue with glutathione is that even those people with normal methylation genes become deficient in it as they age. This is due to the cumulative sleep deficit, poor eating habits, stress and environmental toxins. It can be very difficult to get the nutrients that we need from food alone. Cysteine, for example, is very difficult to come by, yet so important to glutathione production. Then you have the chronic inflammation that increases oxidants in our bodies – this is triggered by processed foods, too much meat, gut issues, toxins, etc.
Thanks for sharing the information on whey protein…whey protein and NAC are actually quite outdated methods of raising glutathione. You need way more of these substances to raise it efficiently than most people are able to tolerate. I hear quite a few doctors still touting the benefits of NAC for raising glutathione and I wish they had better information. That was the gold standard 10 years ago but not anymore. So many people can’t tolerate it anyway (including me).
I am aware of the MSG issue – thanks for raising awareness on it! So damaging, especially for children…
Kristie
Thank you so much for your answer! Here is a VERY 🙂 condensed version of my story. I have struggled with not feeling my best for many years. First birth control made me feel bad. I went to dr’s and never found any answers.Fast forward to 3 years ago, I felt terrible alot. I started researching. I suspected thyroid first. Then I realized I had adrenal issues. I started suspecting mercury. I worked with a dr. and after I was on a supplement program for quite a while and felt some better I had my mercury fillings safely removed with a specialized dentist. I have continued to improve and know that I definitely saw improvement after the fillings were gone. I still had some lingering symptoms. One of the worst was feeling bad if I pushed myself. That makes vacation kind of tough. Recently, I started with a new doctor. I was grateful for all that my previous dr. had done. I knew I needed some insight on some specific things however (including methylation). She found I had low homocysteine, and said I probably should hold off on my b12 shots prescribed by my other doctor. And maybe change the forms of my b vitamins to non methylated forms. Also, one of my liver enzymes was high. They have gone up and down over the years. I was originally told I had PCOS because of cyst on my ovaries. But my latest bloodwork showed awesome numbers for glucose, triglycerides etc. Both of my dr’s suspected lyme’s because of testing. So, I recently started a protocol of samento and banderol. I felt worse and am waiting for a little now to see if I feel any better. I need to see alot of improvement to know that I need to keep doing that. But I have wondered if figuring out methylation would help me. I am already on a high quality b vitamin and a good multi mineral. I wonder if testing would change anything.
Kristie
I am just beginning to learn about this. This phrase in your article caught my eye: “My husband and I, having addressed all of our MTHFR issues with supplementation and toxin removal last year” Could you explain or point me to some posts that shows what your testing showed and how it helped you decide what suppplements to take (or other therapies). And how you accomplished toxin removal. Also, I would love to know what improvements you have seen specifically. Thank you!!
Andrea Post author
Hi Kristie, Thanks so much for your email! It’s really impossible to say what supplements you should take based on the issues I experienced. You can read back through my diary posts to get an overview of what I’ve experienced personally. Everyone is so unique. Have you done any SNP testing yet or are you just starting out doing some research? The things that led me to MTHFR were high RBC folate and elevated homocysteine when I had a ton of bloodwork done at the start of my investigations last year. But since then there has been a lot of testing…you’ll see everything from cellular stress to thyroid to virus to adrenal testing in the posts.
I highly suggest you find a practitioner to work with, especially if you aren’t feeling well. Even though I started with a protocol myself because it took me awhile to find the right doctor, the best practitioners will tell you that MTHFR (or any other) “protocols” are bogus. You want bioindividualized medicine – something catered specifically to you and your needs. The more I research and study (even introductory university courses) the more I’m drawing connections and seeing just how many things can affect us. The cornerstone to good health is your immune system. You want to know if you’re experiencing inflammation or having issues with your gut. You want to know if your hormones are balanced. You want to know whether you have anything sinister like Lyme disease or a virus that keeps knocking you down. You want to get away from taking over the counter or prescription drugs unnecessarily for every little thing (I’m not saying that you do that – I’m speaking to the collective you here). And you want to know what vitamins, minerals and other nutrients you are deficient in so you can target supplementation. There is no easy fix and sometimes it can take a long time to get better – just depends on where you are now and where you want to go. I found I had to go outside our insurance for a lot of things and that’s never fun. And yes, some money does get wasted along the way. That’s part of the process if you don’t find the right practitioner right off the bat, unfortunately.
It’s apt that your comment landed on this post because those are the kinds of things that can deplete glutathione and also the kinds of things that increasing glutathione can assist your body in clearing. For me personally, I started off with general fatigue, infertility issues, undertreated hypothyroidism, inflammation and elevated homocysteine – but I never felt sick until I took almost a year’s worth of synthetic vitamins like folic acid trying to get pregnant. In six months I turned everything around and now only have one major outstanding issue, which I’ve covered in my February 11 post.
I hope that’s answered your questions a little bit. If not I think you’ll find a lot of information in the posts I linked to. The “Health Conditions” section covers a lot also – lots of research and this entire blog links out to peer-reviewed studies and articles written by medical professionals since I am a journalist and not a doctor. I hope you find something here that helps you =) The resources page links out to a lot of good info also.
Good luck with your own health journey and if you have any specific questions, I’d like to invite you to the brand new forums. I’m trying to move all health-related discussions over there so we can all share and benefit from each others’ knowledge. I certainly don’t know it all! All the best, Andrea