Optimal DX Hot Topics: Glutathione Support

Glutathione, a tripeptide compound, is a key player in the body's battle against oxidative stress. It actively reduces oxidative stress, maintains redox balances, supports metabolic detoxification, and regulates the immune system.

Its production in the body depends on three conditionally essential amino acids: cysteine, glycine, and glutamic acid, with cysteine being the rate-limiting factor.

Production can be impaired by insufficient nutrient cofactors and genetic variations in the enzymes involved in the synthesis and regeneration of glutathione.

Glutathione insufficiency is not a condition to be taken lightly. It's associated with a range of health risks, including neurodegeneration, mitochondrial dysfunction, impaired detoxification, toxin accumulation, malignancy, and increased antioxidant need. The body's requirements for glutathione increase with oxidative stress, exposure to environmental contaminants, and greater toxic burden, making it crucial to maintain optimal levels.

Hepatic synthesis of glutathione and nutritional substrates, co-factors, and other nutrients that influence metabolism

5-Methyl-tetrahydrofolate (5MTHF), system alanine–serine–cysteine (ASC), cystathionine-β-synthase (CBS), cystathionine gamma-lyase (CGL), electrophile response element (EpRE), glutathione-S-transferase (GST), glutamate cysteine ligase (GCL), glutathione reductase (GRx), glutathione peroxidase (GPx), glutathione synthetase (GSx), hydrogen peroxide (H₂O₂), Nuclear factor erythroid factor-2-related factor 2 (Nrf2), S-adenosylmethionine (SAMe), S-adenosylhomocysteine (SAH), tetrahydrofolate (THF), thioredoxin reductase 1 (TRR1), water (H₂O), cystine/glutamate antiporter system (x_c⁻).

Insufficient levels of glutathione are not to be taken lightly. They are associated with several chronic conditions, including cognitive impairment, diabetes, hypertension, and neurodegenerative disorders. This underscores the importance of maintaining optimal glutathione levels for overall health.

Glutathione status can be assessed by measuring glutathione directly in blood or red blood cells and by monitoring levels of gamma-glutamyltransferase (GGT), the enzyme that regenerates extracellular reduced glutathione. GGT levels increase when glutathione needs increase.

Clinical conditions and diseases associated with glutathione

• Aging and related disorders
• Alzheimer’s disease
• Cancer
• Chronic liver disease
• Cognitive impairment
• Cystic fibrosis
• Diabetes, especially uncontrolled diabetes
• Human immunodeficiency virus (HIV)/ acquired immune deficiency syndrome (AIDS)
• Hypertension
• Infertility in both men and women
• Lupus
• Mental health disorders
• Multiple sclerosis
• Neurodegenerative disorders
• Parkinson’s disease

Nutrition support

Nutrients supporting glutathione production and blood levels include vitamin B2, B12, pantothenic acid, vitamin C, E, alpha-lipoic acid, and selenium. Fruits and vegetables fight oxidative stress and support glutathione status, especially citrus fruits and cruciferous vegetables.

Drinking 400 mL of conventional or organic grape juice significantly increased blood levels of glutathione, catalase, superoxide dismutase, glutathione peroxidase, and total antioxidant capacity within one to three hours of consumption.

Using rosemary, turmeric/curcumin, milk thistle, and Gingko bilioba may also positively impact glutathione status.

Consuming sulfur-rich foods containing preformed glutathione, N-acetylcysteine (NAC), and cysteine also support glutathione status. Whey protein is a significant source of cysteine and protein. Green foods, asparagus, avocado, cucumber, green beans, and spinach are especially supportive of glutathione status.

Sulfur-rich fruits and vegetables

Preparation tips for sulfur-rich vegetables

• Eat preferably raw or mildly steamed to preserve the integrity of sulfur compounds
• Refrain from freezing cruciferous vegetables, such as broccoli
• Add powdered mustard seeds during the heating process to increase sulforaphane content

Glutathione supplementation

Early speculation questioned whether supplemental preformed glutathione would translate into higher levels in the blood. However, randomized, double-blind, placebo-controlled studies demonstrated a significant dose-dependent increase in body stores of glutathione with 250 or 1,000 mg/day of preformed glutathione and a decrease in oxidative stress biomarkers.

Sublingual or liposomal forms of glutathione may be more bioavailable, favorably impacting systemic glutathione levels. Improvement in glutathione status is characterized by a decrease in the oxidized to reduced glutathione ratio and, conversely, an increase in the reduced to oxidized glutathione ratio.

A small study found that 500 or 1,000 mg/day of liposomal glutathione significantly increased plasma glutathione levels after two weeks of supplementation. Higher doses were more impactful in decreasing the oxidized to reduced glutathione ratio, decreasing biomarkers of oxidative stress, and improving immune function, lymphocyte proliferation, and natural killer cell activity.

Summary of nutrients and foods for support of glutathione levels

Optimal Takeaways

• Glutathione is formed from the conditionally essential amino acids glycine, glutamic acid, and cysteine, the rate-limiting compound.
• Glutathione production in the body also depends on several nutrient cofactors that should be consumed regularly.
• Optimize intake of fruits and vegetables, citrus and cruciferous foods, sulfur-containing foods, herbs, spices, green tea, omega-3 fatty acids, fish, and lean protein sources.
• Supplement with nutrient cofactors and preformed glutathione as needed.
• Monitor glutathione's blood and RBC levels and assess the oxidized to reduced glutathione ratio as needed.

Reference

Minich, Deanna M, and Benjamin I Brown. “A Review of Dietary (Phyto)Nutrients for Glutathione Support.” Nutrients vol. 11,9 2073. 3 Sep. 2019, doi:10.3390/nu11092073 This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/

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