Written By: Kevin Cann
A conversation I had with Dr. Terry Wahls the other day made me want to revisit one of my past articles and add to it. In this article, http://robbwolf.com/2013/03/13/understanding-combating-oxidative-stress-huntingtons-disease/ , I explained the importance of intracellular glutathione in combatting oxidative damage. I also made the recommendation of N-Acetyl-Cysteine to aid in the production of the powerful antioxidant. Dr. Wahls said this to me “When I used supplements – I slowed my decline, when I designed my food supply to get those same nutrients – my strength began to return. Print that and put up where you work – stare it every day. The supplement studies are best used to guide how we create the food plans.” Keeping that statement in mind I will address foods that can aid in glutathione synthesis.
The first step in producing glutathione is catalyzed by gamma-glutamylcystein synthase. This enzyme binds cysteine to the gamma carbon of glutamate which forms gamma-glutamylcystein. The next step involved uses glutathione synthase to combine a glycine to gamma-glutamylcystein. All of this requires ATP for energy and requires nutrients to be completed and maintained. The end result of this chemical reaction is glutathione.
Copper and zinc balance is an important aspect in maintaining glutathione levels. Glutathione may play a role in removing excess copper (http://www.jbc.org/content/264/10/5598.full.pdf ). Foods such as grains, nuts, seeds, beans, and chocolate tend to be high in copper. A diet that is high in these foods can indirectly lower intracellular glutathione levels by increasing plasma copper levels. Meat increases copper, but is balanced by the increase in zinc. Birth control pills and some IUDs also contain copper. A zinc deficiency may lower glutathione levels all on its own (http://jn.nutrition.org/content/111/6/1098.full.pdf ).
The proper ratio of copper to zinc is .7:1. The majority of people with an imbalance in these two important minerals typically have excess copper and deficient zinc. Imbalances can lead to hyperactivity, severe PMS, autism, depression, and ADHD. Making sure we have these two minerals in the proper balance is key to maintaining glutathione levels.
Magnesium is also an important mineral in terms of glutathione synthesis. In a study done on rats, magnesium deficient rats showed lower levels of intracellular glutathione (http://jn.nutrition.org/content/112/3/488.full.pdf ). This is potentially due to magnesium’s role in ATP production, as ATP is the main source of energy for glutathione synthesis.
Vitamin B6, vitamin B12, and folate are also important for maintaining glutathione levels, as well as exercise. The research has shown that all of these factors can decrease homocysteine levels and increase glutathione levels independently (http://www.ncbi.nlm.nih.gov/pubmed/22261439 ). Vitamin C has also been shown to raise red blood cell glutathione in healthy adults (http://ajcn.nutrition.org/content/58/1/103.short ). Vitamin E is important as well, as it protects the two enzymes responsible for glutathione production (http://www.ncbi.nlm.nih.gov/pubmed/12959415 ). Vitamin D also can increase glutathione levels and protect us from neurodegeneration (http://www.ncbi.nlm.nih.gov/pubmed/11893522 ). So what is this all telling us?
This tells us that there are a lot of factors that go into our total health. No one supplement can save us from the perils of aging and cure all disease. There are instances where supplementation is absolutely necessary in conjunction with a healthy diet and lifestyle.
In my article, Understanding and Combatting Oxidative Damage in Huntington’s Disease, I discussed the use of N-Acetyl-Cysteine (NAC) to help maintain glutathione levels. Getting back to Dr. Wahls quote, supplements slowed her decline, but it was the natural foods that allowed her to regain her strength. The brassica food family may be one of note when attempting to combat illnesses that are associated with increased oxidative damage. Along with the NAC supplementation, people with disorders such as Huntington’s Disease want to consume ample amounts of vegetables in the brassica family. They contain all the nutrients mentioned above for glutathione synthesis. Of course supplementation and eating lots of broccoli is not enough on its own. Adequate vitamin D levels are necessary, proper circadian rhythm, and the ability to manage one’s stress appropriately. On top of all that, we need proper digestive function to extract the nutrients from the food.
Our body is one large and continuous chemical reaction. It requires all different types and adequate amounts of nutrients to fuel these reactions. Supplementation is great to fix deficiencies and give some added support. However, the keys to our health rely on nutrient dense foods as well as other lifestyle factors.
Found an interesting paper the other day – homocysteine represents the potential sulfur pool, it can be remethylated to SAMe (AdoMet) for methylation reactions, or converted to cysteine, glutathione, taurine, sulfate via trans-sulfation.
Glucose and insulin decreases trans-sulfation, increases methylation.
http://www.ncbi.nlm.nih.gov/pubmed/19088160
Insulin increased cellular homocysteine production primarily by its inhibition of transsulfuration. When cells were exposed to elevated insulin and glucose, homocysteine remethylation was enhanced, which consequently increased intracellular adoMet concentrations by inducing adoMet synthase activity. Elevated glucose further enhanced DNA methyltransferase activity that subsequently led to increased global DNA methylation.
This, if it applies generally, makes carbohydrate restriction a strategy for replenishing glutathione and taurine.
I’ve noticed that when I’m in ketosis I can taste sulfur after meals. This would explain it.
It is a chicken and egg situation? http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3017313/ Were these people predisposed to this or not? Either way get some sleep, get some sun, eat nutrient dense foods, and manage your stress for favorable gene expression!
Some sun, very important to make you feel good and happy 🙂 – Used to live in the UK and it effected me big time due not seeing and feeling the sun much.
I’d eat some of these veggies everyday, but I’m a bit worried about androgen and thyroid antagonism. Hell, they are antiestrogenic too!
Any thoughts on overdoing the brassicas? As a male, I’d like to maximize androgens and T3. I guess lowering e2 would tell the body to ramp up testosterone, so maybe brassica is more of a balancer?
Another reminder that looking at the science is not enough, we must look for tangible results, too.
I’ve been using intracellular glutathione to try to fight oxidative damage for a while now.
http://youtu.be/LDJjqY4H3Cc?t=39m27s
Chris Masterjohn + this article = win
Very helpful article. I have a patient right now – a 19 year old male college student who is a 3-season track athlete at a D1 school. He came to me because he has fatigue, running times have gone up from high school, and he can’t keep weight on despite eating enough and frequently. Per a nutrient analysis, he has low B12, high copper to zinc levels, and low glutathione status, along with poor insulin-glucose control. wondering if celiac disease is underlying and/or pernicious anemia, as he eats a good amount of animal foods. In any case, he had been taking lots (190 mg/day) of iron with no improvement in his fatigue. No CBC has been done, so don’t know what his H&H are, and no iron labs available either. Wondering if he might be iron toxic and that could lower glutatione? I am hoping that sublingual B12 supplementation will help his glutathione levels. You think it would be good to add a liposomal glutathione supplement?
When supplementing Glutathione through a pill or capsule (orally) make sure to look for an Acetyl Glutathione, this is a far more bioavailable form of Glutathione that is far more effective in increasing cellular glutathione levels. Also precursors such as N-Acetyl Cysteine are beneficial to take alongside an Acetyl Glutathione supplement to promote endogenous creation of glutathione as well as recycling it efficiently.
Why do you recommend Acetyl over Liposomal Glutathione?? All of my reading indicates that the latter is the most bioavailable form of oral glutathione. We researched all options including suppositories made of Acetyl and determined Liposomal was the way to go. We are buying it and it is expensive but we are considering making our own and would value your insight. Thank you.
Excellent article, thanks for sharing all this amazing information. I never knew about the proper ratio of copper to zinc, I guess I’ve been taking way to much zinc. By the way, I can only recommend Robb’s book The Paleo Solution: The Original Human Diet (click the shop link above), it’s packed with great information and really useful!
Thanks for sharing.