Glutathione and related biochemicals

By Cat, Feb 2019

Glutathione is a small peptide comprised of three amino acids: glycine, cysteine and glutamine, with a big impact on the health of our bodies. It is a major antioxidant present in every cell, and the primary detox agent in the liver.

“Coined ‘The Mother of All Antioxidants’ by Mark Hyman, MD, glutathione is one of the hottest topics in both natural health and medical circles today.” (1A) Although our bodies are capable of creating glutathione as needed, an alarming rate of people are deficient because of depletion from modern issues; read on for more.

Other, related biochemicals discussed in this article are: lipoid acid, glutamine, glycine, and N-acetyl cysteine (NAC). 

See also: 1. Natural Health and Healing Topics Menu; 2. Diet & Health Menu

Glutathione

Modern issues responsible for glutathione deficiency in many people (from Dr. Axe (1a)):

• Pre-mature aging
• Infections
• Chronic stress
• Injuries
• Environmental toxins
• So-called “health foods”
• Genetically modified foods (GMOs)
• Artificial sweeteners
• Overuse of antibiotics
• And radiation therapy that is all too easily given to cancer patients today

Glutathione provides the following health benefits:

• Plays a crucial role in immune function;
• Promotes T-cell function, which is critical for a strong immune system;
• Helps prevent drug resistance;
• Protects from environmental toxins;
• Discourages cancer progression.

Its functions in the body include (but not limited to):

• Conjugates (“links together”) with drugs to make them more digestible;
• Is a cofactor (“helper molecule”) for some important enzymes including glutathione peroxidase (which protects you from oxidative damage);
• Is involved in protein disulfide bond rearrangement (which is critical for the biogenesis of one-third of all human proteins);
• Reduces peroxides (natural bleaching agents that are harmful to the body);
• Participates in leukotriene production (vital component for inflammatory and hypersensitivity reactions);
• Helps the liver detoxify fat before bile is emitted, which takes stress off of the gallbladder;
• Helps detoxify methylglyoxal, a toxin produced as a by-product of metabolism;
• Cancer apoptosis (“programmed cell death”).

Glutathione cofactors

(from Immune Health Science: (2b)):

• Vitamin C – as an antioxidant it assists glutathione in this function and has been shown scientifically to raise glutathione levels short term; it is recycled by glutathione from its oxidized state back to its active state, thus strengthening antioxidant defenses; vitamin C also recycles vitamin E and alpha lipoic acid.
• Vitamin E – as an antioxidant it also assists glutathione in eliminating free radicals much like vitamin C; it is also required for the proper functioning of glutathione enzymes; it recycles vitamin C and alpha lipoic acid.
• B vitamins – vitamins B1 and B2 maintain glutathione and its enzymes in their active forms; vitamin B2 participates in the formation of a glutathione molecule; vitamin B6 influences glutathione synthesis indirectly as it is important for the proper functioning of amino acids including GSH precursors; vitamin B6 increases the amount of magnesium (a vital cofactor) that can enter cells; folate (B9) pushes cysteine towards glutathione production rather than homocysteine production; folate and vitamin B12 work together in amino acid metabolism and protein synthesis. You can read more about the link (2c). 
• Selenium – part of the enzyme glutathione peroxidase (GPx). Glutathione peroxidases, also known as selenoproteins, are a family of antioxidant enzymes that speed up the reaction between glutathione and free radicals.
• Magnesium – required for the proper functioning of the enzyme gamma glutamyl transpeptidase (GGT) involved in the synthesis of glutathione.
• Zinc – zinc deficiency reduces glutathione levels, especially in red blood cells. However, zinc levels above normal have pro-oxidant properties and reduce glutathione too.
• Alpha lipoic acid – There are two forms of lipoic acid: R- and S- lipoic acid. The R-form is far more biologically active in the body (primarily as an antioxidant and free-radical scavenger) than the S-form. The R- form is an antioxidant and free-radicals scavenger produced by the body.  See below for more. 

The Top 9 foods/supplements to boost glutathione levels

The following are cited by Dr. Axe (1A):

1. Milk thistle [I take this as part of my Liver-Support tincture from Swan Valley Herbs];
2. Whey protein [I use Bob’s Red Mill whey protein in my morning smoothie. I have food sensitivity to other brans because they dry the whey with high heat; Bob’s Red Mill uses low-heat processing);
3. High-sulfur foods (my favs are broccoli, kale, cauliflower and other members of the cruciferous family of vegetables];
4. NAC supplement [I still have a food sensitivity to this sulfur-containing supplement, so instead rely on foods high in cysteine];
5. Alpha lipoid acid (ALA) supplement [I’m currently taking NOW’s Alphasorb-C supplement, as it has low level of ALA, so that I can gradually increase the dose to avoid the return of a food sensitivity];
6. Methylation nutrients: B6 (pyridine), B9 (folate as methyl-folate), B12 (cobalamin as methyl-cobalamins) and B7 (Biotin).  [I currently get these from my whole food multi]. NOTE: it’s especially important to take the methyl versions of folate and cobalamin if your body has trouble with methylation – see MTHFR gene and Methylation topic.
7. Selenium – this is an essential mineral, but it’s very important that you take it in chelated form (bonded by an amino acid, peptide or protein, rather than in salt form). Selenium methionine is one good supplement form; or selenium-yeast. Do not take it as “sodium selenite,” as this salt form is a toxic heavy metal. [I get this from my whole food multi.]
8. Vitamins C and E. [I get vitamin C from fruits in my morning smoothie, and also in my Alphasorb-C supplement. I take a Gamma-E mixed tocopherol/tocotrienol supplement, which provides all forms of this vitamin.]
9. Raw liver from pastured, grass-fed beef. [Because it is hard for me to find grass-fed beef liver where I live, I add desiccated liver powder from grass-fed Argentine beef to my morning smoothie.]

Related biochemicals

Alpha Lipoic Acid

The following is from Immune Health Science (2a)  unless noted otherwise.

As mentioned above, the R- and S- forms are produced from chemical manufacture of alpha-lipoic acid supplements in a 50/50 ratio. That means a 100 mg alpha-lipoic acid supplement is providing 50 mg of the biologically active R form. R-lipoic acid is also available in supplements (without S-lipoic acid) (6).

Alpha lipoic acid is a powerful antioxidant produced by every cell in the body, and is a cofactor of glutathione production. It has been scientifically proven to enhance and maintain glutathione levels by stimulating enzymes involved in the synthesis of glutathione. It is vital in the cycle of returning glutathione from its oxidized form back to its reduced (active) form, thus increasing glutathione levels by recycling it.

It also: 

• Recycles other antioxidants, such as glutathione cofactors vitamin C and vitamin E, and also co-enzyme Q10, from their oxidized state back to their reduced (active) state. Alpha lipoic acid is recycled itself by glutathione, vitamin C and vitamin E as all these molecules work together synergistically.
• Helps increase the cellular uptake of cysteine, the crucial building block of glutathione.
• Binds with excess copper, iron, lead and cadmium preventing these metals’ accumulation and the resulting oxidative damage, thus reducing the work load of glutathione in heavy metal removal.
• Binds tightly with toxic mercury, even in the brain and the nervous system, thus neutralizing this metal’s toxicity and assisting glutathione in this task. Important note: if you suffer from significant heavy metal toxicity, do not take alpha-lipoic acid without consulting a doctor who is knowledgeable about heavy metal detoxification and under whose expert supervision you should detoxify.

Small amounts of alpha lipoic acid are found in foods: red meat, organ meats (especially liver), broccoli, spinach, potatoes, brewer’s yeast, and to a smaller degree – tomatoes, peas and Brussels sprouts, but the amounts are not sufficient to help with health conditions. Instead, the best source is NAC supplements.

The most common recommended dosage is 100-250 mg a day (50 – 125 mg of R-lipoic acid); higher doses have been used for specific problems. Please consult your doctor before increasing your daily dose.

Glutamine

Glutamine is one of the amino acids that comprise glutathione. It is not to be mistaken as glutamate or MSG (mono-sodium glutamate). It is the most abundant amino acid in the blood. One of the best dietary sources is dairy proteins (casein and whey), but it is hard to get enough from food alone. The following “proven glutathione benefits” are from Dr Axe (Note: I’ve changed their order slightly):

1. Improves gastrointestinal health
2. Helps leaky gut and ulcers
3. Improves IBS and diarrhea
4. Boosts brain health
5. Promotes muscle growth and decreases muscle wasting
6. Improves athletic performance and recovery from endurance exercise
7. Burns fat and improves diabetes

Dr Axe recommends consuming 3 servings from the following list or glutamine-rich foods daily, to improve your glutamine levels:

1. Bone broth (or stock)
2. Grass-fed beef
3. Spirulina
4. Chinese cabbage
5. Cottage cheese
6. Asparagus
7. Broccoli rabe
8. Wild-caught fish (cod and salmon)
9. Venison
10. Turkey

Glycine:

Glycine is another amino acid present in glutathione, and is the smallest of the amino acids. It is made by the body, and is also abundant in some foods, especially bones (as in stocks and bone broth) and skin. It has benefits for the entire body; here are just a few; I’ve put the “key ways it supports the body” in bold text (from Dr. Axe (1b))

• helping build lean muscle mass
• preventing scaropenia (muscle loss, muscle wasting or deterioration)
• playing a role in the production of human growth hormone
• boosting mental performance and memory
• helping prevent strokes and seizures
• protecting skin from signs of aging or cellular mutations
• protecting collagen in joints and reducing joint pain
• improving flexibility and range of motion
• stabilizing blood sugar and lowering risk for type 2 diabetes
• improving sleep quality
• lowering inflammation and free radical damage by increasing glutathione production
• reducing risk for certain types of cancer
• building the lining of the gastrointestinal tract
• producing bile salts and digestive enzymes
• helping reduce allergic and autoimmune reactions
• boosting energy levels and fighting fatigue
• helping produce red blood cells
• fighting the effects of stress and anxiety
• helping control symptoms of seizures, schizophrenia and mental disorders

Glycine is also useful in ridding the pesticide glyphosate from the body (see my article How to detox glyphosate (Roundup) from your body for details.

Cysteine and NAC (N-Acetyl Cysteine):

Cysteine is the other amino acid present in glutathione. It is available in most high-protein foods, and also in the cruciferous (cabbage family) of vegetables. Our bodies can also make cysteine from another amino acid, methionine. If you have deficiency of methionine or if your methionine/glycine ratio is out of balance, you may not be getting enough cysteine. (see Chris Masterjohn’s site: Balancing Methionine and Glycine in Foods: The Data Base for more). 

N-acetyl cysteine (NAC) is a supplemental source of cysteine, acting as a precursor to glutathione (GSH). It has recently been proven highly efficient at treating neuro-cognitive issues like addiction, compulsive behaviors, schizophrenia and bipolar disorder. Dr. Axe recommends taking 200–500 mg daily (1).

• Food sources of cysteine (from Livestrong (3) and My Food Data (4) include all meats, dairy (such as ricotta cheese, cottage cheese, yogurt) and eggs. Plant sources: grains such as granola and oat flakes. Vegetables like broccoli, red pepper and onion are significant sources of cysteine; other plant sources include bananas, garlic, soy beans, linseed and wheat germ. From _ “sunflower seeds, other nuts/seeds, whole grains such as wheat, kamut, oat, barley; wild rice, quinoa, millet, bulgur”
• Regarding NAC supplements (3): “Consult your medical-care provider before taking NAC supplements. Too much cysteine or methionine can cause health problems, as well. A 2009 study by Temple University found that diets high in methionine can contribute to the development of Alzheimer ’s disease in mice. According to the University of Maryland Medical Center, NAC may also raise another amino acid associated with heart disease. Possible side effects of NAC can occur at any dose and include nausea, vomiting, and diarrhea. Oral administration of NAC may cause a severe allergic reaction that swells the soft tissue below the skin of the face, lips and eyes and can develop to a life-threatening condition.”

I have a strong food sensitivity to NAC (and other sulfur-containing nutrients); thankfully, taking myo-inositol supplement has helped with other sulfur-containing nutrients such as alpha lipoid acid, but I still have a problem with NAC.

References:

1. Dr. Axe articles:
   1. Top 9 Foods & Supplements to Boost Glutathione
   2. Glycine: The muscle building, brain boosting amino acid that benefits the entire body
2. Immune Health Science:  NOTE: you may get an error message for these links. In that case, search”immune health science” followed by the text of the title.  The article should be at the top of the list.
   1. Alpha Lipoic Acid Benefits – Immune Health Science;
   2. Glutathione Cofactors; 
   3. vitamin B12 deficiency and its effect on immune health 
3. livestrong.com/article/531520-food-sources-of-n-acetyl-cysteine/
4. myfooddata.com/articles/high-cysteine-foods.php
5. Huff Post, LIFE, article by Mark Hyman M.D.: Glutathione, The Mother of All Antioxidants (huffpost.com/entry/glutathione-the-mother-of_n_530494)
6. Life Extension on R-lipoic acid: from lifeextension.com/vitamins-supplements/Item28539/R-lipoic-Acid