Optomizing Glutathione for Health and Human Performance
Many of us, me included, have thought of ways to improve our health in this New Year. Perhaps you have kicked off a new fitness regime or have started a new diet plan. As we begin the journey to better health, I want to bring attention to a molecule called glutathione and its implications for health and human performance.
Glutathione is one of the most powerful antioxidants responsible for maintaining cellular health. It is found in all cells, but is highly concentrated in the brain and liver. Glutathione is a chief biomarker of cellular redox status (electron allocation), meaning it can accept electrons from free radical species. Less glutathione increases the cell’s vulnerability to oxidative damage, and consequently increases the risk for disease.1 It is good that our body naturally produces glutathione , however many have less than optimal glutathione levels due to stress, infection (HIV and Hepatitis C), poor diet, lack of sleep, and exposure to toxins and xenobiotics (statins, hormonal contraceptives, analgesics).
Deficiencies in glutathione leave the body vulnerable to toxins and inflammation—making the body weak and robbing one of high performance. Worst of all, low glutathione levels are linked to diseases including: autism1, atherosclerosis, coronary artery disease2, Alzheimer’s disease3, Crohn’s disease4, leukemia5, inflammatory bowel disease6, celiac disease7, osteoarthritis8 and chronic fatigue syndrome9.
Despite differing in biochemical pathways, these diseases are facilitated by high levels of oxidative stress. Oxidative stress is an imbalance between free radicals and antioxidant defenses and is a primary cause of cellular damage leading to disease.10 Throughout a life span, one is constantly exposed to free radicals through strenuous work, environmental toxin exposure, diet, and autoimmune disorder. Even something as essential as oxygen can be toxic under certain conditions, and this phenomenon is called the oxygen paradox.11
There is good news however. We can take an active role in preventing disease by increasing our antioxidant capacity. Antioxidants protect the cell from free radicals by accepting their unpaired electrons, thereby quenching the free radical’s reactivity. Reducing free radicals protects the cell from oxidative damage and, ultimately, facilitates disease prevention. A large body of literature supports the notion that dietary antioxidants play an important role in preventing many human diseases.11
Glutathione is called the “master antioxidant” by some and for good reason. As antioxidant, its primary functions include:
Glutathione has many other responsibilities in addition to antioxidant function, including metabolism and cellular regulation, which will not be included here. For comprehensive reviews see sources 12 and 13.
By quenching free radicals, glutathione facilitates a decrease in oxidative stress at the cellular level. At the organismal levels, the effects are manifest as: increased energy, better sleep quality exercise recovery, and blood circulation15, mental clarity, less inflammation, and slower aging. Additionally, glutathione recycles other antioxidants and antioxidant enzymes including vitamin C, E, lipoic acid, CoQ10, super oxide dismutase, and catalase.11
So how do we optimize our glutathione levels?
The most obvious way to increase glutathione is through direct supplementation. However taking an oral supplement is ineffective, as it denatures in the stomach before it has pharmacological effects. Intravenous glutathione is an option, however I would consult your physician before taking further action. Another option for direct supplementation is liposomal glutathione, that is, glutathione encapsulated in tiny fat cells. I have no idea if this actually works, but I am willing to give it a try.
Other practical ways to optimize your glutathione levels include:
A German study demonstrated increased glutathione levels and related biomarkers in the blood of swimmers who swam at least once per week in ice-cold water for 5-10 minutes. I plan on testing this in the future.
Glutathione is synthesized from its precursor amino acids cysteine, glutamic acid, and glycine and undenatured whey has these glutathione precursors. I supplement Proserum Grass-Fed Whey Protein Concentrate as it is the cleanest sourced protein I could find on the market. Also, I stir my protein into solution using warm water. I do not blend as doing so breaks-up the protein reducing its quality.
Cysteine is the limiting amino acid in glutathione synthesis, thus increasing its precursor stimulates cysteine uptake by the cells and increases intracellular glutathione production.12 N-acetylcysteine is a stable and effective source to supplement glutathione synthesis.11 I have started supplementing 200mg daily with lunch.
Although it is one of three building blocks for glutathione synthesis, glutamate is actually broken down in the small intestine, thus supplementing the amino acid is ineffective for those looking to increase their glutathione levels. However, the amino acid glutamine is hydrolyzed to glutamate by the enzyme glutaminase, and the ketone alapha-ketoglutarate produces glutamine from branched chain amino acids— readily supplying glutaminase ingredients to produce glutamate and, ultimately, glutathione.11
The amino acid glycine can be directly supplemented, and has been shown to increase glutathione concentration in the liver cells of protein-deficient mice.11
Methionine is another amino acid one can supplement, as it is not synthesized by the body and can only be supplied through diet. This amino acid reacts with the enzyme gamma-glutamylcysteine synthase in liver cells to produce cysteine.12
Doing so gives the body another way to produce cysteine for glutathione production, as this antioxidant reduces the amino acid cystine to cysteine.17 In the past I have taken 200mg supplements with lunch.
Dietary selenium supports glutathione peroxidase which is an important enzyme for recycling glutathione.17A dietary deficiency of selenium has been shown to decrease tissue glutathione peroxidase activity by 90% leading to peroxidative damage and mitochondrial dysfunction.11 One can increase their selenium by simply supplementing 100mcg with a meal (I haven’t taken this supplement before so I cannot speak to its effects) or eat foods rich in selenium such as grass-fed beef and wild-caught oysters.
A deficiency in dietary magnesium reduces glutathione reductase, another enzyme responsible for recycling glutathione. Magnesium is a cofactor for two pentose-cycle enzymes that catalyze the production of Nicotinamide adenine dinucleotide phosphate (NADPH) and its oxidized form NADP+. 12 The oxidation NADPH gives a proton to glutathione reductase so it can help recycle glutathione. In short, magnesium facilitates the recycling of glutathione. Supplement 600 to 800mg per day of magnesium malate, citrate, or aspartate, but be careful as too much can lead to diarrhea. The best time to take magnesium is in the evening since it confers relaxing effects.
Mineral elements like sulfur are available to us exclusively through dietary protein, yet only 2 of the 20 amino acids normally present in protein contain sulfur, and these include cysteine and methionine. Proteins contain between 3 and 6% sulfur amino acids and as stated earlier, cysteine is the limiting amino acid in glutathione synthesis and methionine facilitates cysteine production, neither of which are stored in the body.18 Thus we can increase our glutathione supply by eating food rich with these proteins. These include grass-fed beef, pork, lamb, or chicken. Wild caught and low mercury sea food is another good choice— salmon, king crab, and shrimp to name a few. Other sources include: soft-boiled eggs (so the protein and fats don’t go rancid from overheating), onions, garlic, broccoli, and red pepper.
Glutathione is one of the most powerful antioxidants that can improve our health and performance by helping our bodies run better, giving us more energy, decreasing inflammation from oxidative stress, and ultimately reducing our risk for disease.
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Optomizing Glutathione for Health and Human Performance