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How To Achieve Sufficient Levels Of The Antioxidant Glutathione For Cellular Health
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If combating free radicals and oxidative stress were a sport, glutathione would be the reigning champion across all divisions.* Often referred to as the "master antioxidant," glutathione has garnered a reputation for its free-radical-neutralizing activities that help support everything from immune, digestive, and brain function to detoxification and longevity.*
But as vast and beneficial as glutathione is for overall oxidative balance, it can be surprisingly difficult to maintain sufficient levels of the antioxidant.*
What is glutathione?
Glutathione1 is a tripeptide made of three amino acids: glutamine, glycine, and cysteine. The sulfuric organic compounds that make up glutathione create a sticky effect that helps the antioxidant capture unwanted molecules (e.g., free radicals and toxins) so they can be removed from the body.*
A vital function that bolsters glutathione's fight against oxidative stress, these antioxidant actions help modulate redox homeostasis2 (aka redox balance), which is the healthy equilibrium between oxidized versus reduced compounds, like the generation and elimination of reactive oxygen species (ROS).*
While some ROS are needed for normal, healthy physiological function, an imbalanced ratio between antioxidants and free radicals can lead to various health concerns throughout the body. Antioxidants help us maintain redox balance, and glutathione is the leader of the pack.*
How the "master antioxidant" earned its title
According to Lise Alschuler, N.D., FABNO, professor of clinical medicine at the University of Arizona, glutathione is the most prevalent and important cellular antioxidant. "Glutathione supports the redox potential within a cell, facilitating the cell's ability to quench oxidative stress and reset its antioxidative capacities,"* she explains.
In addition to glutathione's direct antioxidant properties, it also recycles vitamins C and E, which are powerful antioxidants in their own right.* No matter which toxins are thrown its way, glutathione has a knack for orchestrating its team of antioxidant players to ensure unwanted molecules are taken care of and oxidative balance is ultimately restored.*
Considering glutathione is found in every cell in the body, it's no secret that its free-radical-fighting capabilities are utilized universally.* However, the highest concentrations of glutathione are found in the liver and kidneys3, suggesting the antioxidant is a key player in helping these organs' elimination process and removal of toxins from the body.*
Natural detoxification processes and pathways buffer us from daily biological and environmental stressors, and glutathione's role in the detoxification of various compounds (including mercury and certain persistent organic pollutants, notes Alschuler) is evident.*
In terms of whole-body well-being, healthy metabolic detoxification has positive outcomes for everything from immune function to longevity. Glutathione has certainly earned its "master" title, wouldn't you agree?
How to maintain healthy glutathione levels
While glutathione is an endogenous antioxidant (meaning it can be made in the body assuming its amino acid constituents are present), maintaining sufficient body compartment stores can be challenging under certain circumstances. A host of factors like poor diet, stress, pollution, toxins, and even aging deplete glutathione levels4, causing a ripple effect affecting our whole-body health.
If you recall, glutathione has not only direct antioxidant properties but is also responsible for recycling antioxidants like vitamins C and E.* When glutathione levels are low, it drastically limits the body's capacity for neutralizing free radicals and inherently skews redox balance5.
Luckily, there are a few ways we can support our glutathione production and maintain sufficient stores of the master antioxidant.
Adopt a glutathione-supporting diet
While glutathione is found in some foods, dietary sources are poorly absorbed by the body and do very little to improve glutathione status. That said, there are a number of nutrients you can eat to help support glutathione's production, retention, and regeneration.
"Glutathione requires nutritional building blocks, specifically three amino acids: cysteine, glycine, and glutamine. Therefore, ensuring healthy quality protein intake is essential," explains functional-medicine-trained clinician Deanna Minich, Ph.D., CNS, FACN, IFMCP.
"Overall, selecting a dietary pattern that emphasizes lean protein sources, cruciferous vegetables, polyphenol-rich fruits and vegetables, herbs and spices, green tea, and foods rich in omega-3 fatty acids (such as fish) would encourage healthy glutathione levels for most individuals," Minich adds.
In addition to a well-balanced diet, some vitamins and minerals are especially important in promoting glutathione synthesis and replenishment:
- Sulfur: This essential mineral is a critical component of glutathione synthesis. Garlic, onions, and cruciferous vegetables6 such as broccoli, cauliflower, Brussels sprouts7, kale, and cabbage are all rich sources of sulfur.
- Vitamin C: Similar to glutathione, vitamin C supports redox balance by restoring other antioxidants like glutathione8 and vitamin E (and acts as a potent antioxidant in its own right).* Some vitamin-C-rich foods include guava, red bell peppers, kiwi, and citrus fruits like lemons, limes, oranges, and grapefruit.
- Selenium: Another essential mineral, selenium supports glutathione-related enzymes by increasing their expression and activity.* Some selenium-rich foods include beef, chicken, brown rice, and Brazil nuts.
While a healthy diet supports glutathione production and activity, it isn't a foolproof approach. "People who have gene variants that incline them to low glutathione and/or those who have high toxin loads may need additional supplemental support,"* Minich notes.
Increase absorption with supplements
For a long time, scientists did not believe oral glutathione supplements were effective at increasing glutathione levels due to low bioavailability (and thus, bioefficacy). mbg's vice president of scientific affairs Ashley Jordan Ferira, Ph.D., RDN, shares that "glutathione's smear campaign really took off, but it was categorically wrong. Well-designed research just needed to play catchup."
Indeed, a groundbreaking 2015 clinical study from the European Journal of Nutrition9 demonstrated that a specific form of oral glutathione supplement called Setria® can increase both blood levels and body compartment stores of glutathione when taken daily.* As Ferira explains, "This clinical trial proves that key forms of glutathione are not only bioavailable but efficacious in positively impacting glutathione status in the body. These are hugely important findings."*
"The methods of testing and specific knowledge of glutathione have increased over the years, making some of the older studies showing that glutathione was not absorbed controversial and almost obsolete," explains Danielle Citrolo, PharmD, VP of scientific & regulatory affairs at Kyowa Hakko USA (the innovator and manufacturer of Setria®).
Citrolo goes on to say that glutathione is a very unstable molecule that is rapidly removed from the blood and tissues, so it must be replenished daily. With Setria® glutathione, oral glutathione stores are improved thanks to proper absorption in the intestinal lining.*
"Older studies did not take into account the fact that multiple dosing may be required, as well as particular handling of the samples taken to test the glutathione levels," Citrolo explains.
Taking a supplement with 250 milligrams of Setria® glutathione—a clinically efficacious dose thanks to the current science—every day (like mbg's daily detox+) is a great way to promote sufficient glutathione levels and increase overall antioxidant activity in the body.*
In addition to taking bioavailable glutathione, there are a few other key bioactives and botanicals that support glutathione production and replenishment.
For example, supplements that include cysteine (e.g., whey protein powder) or direct precursors to cysteine (particularly, N-acetyl-L-cysteine, aka NAC10) can help promote glutathione production.* According to Alschuler, these targeted ingredients are especially helpful in increasing overall glutathione levels because cysteine is the rate-limiting amino acid (i.e., the slowest nutritional building block) in glutathione synthesis.*
When it comes to herbal bioactives, milk thistle contains a powerful free-radical scavenger phytonutrient compound called silymarin11 that has been shown to modulate glutathione-metabolizing enzymes12 and promote healthy redox balance.* Additionally, milk thistle supports the detoxification process by bolstering healthy liver function and protecting liver cells from toxins.*
Exercise regularly
Adding physical activity to your weekly routine helps all areas of health, including antioxidant activity.
In a 2014 clinical study13 from Free Radical Biology and Medicine, glutathione levels were shown to be higher among older adults who exercised regularly throughout their lives. While participating in physical activity at all ages is important, this study indicates that exercise is an effective way to counteract naturally depleting glutathione levels as we age.
According to a study from the Journal of Integrative and Complementary Medicine, yoga is particularly beneficial14 for increasing glutathione levels. Healthy, young adults who practiced yoga for 90 minutes at least once a week had remarkably higher levels of glutathione compared to the control group. (If you're new to yoga, check out our beginner's guide here.)
While yoga is fantastic for physical and mental health, any form of movement (even gardening!) can help reduce oxidative stress and bolster whole-body health.
The takeaway
Glutathione is an all-star antioxidant that fights against free radicals to promote redox balance and whole-body health.* While it can be a challenge to maintain sufficient glutathione levels, there are habits that can help. From vitamin-C-rich foods to supplementation, small steps add up and will pay dividends in benefits to your immune function and longevity.
In addition to a nutrient-dense diet and regular exercise, a comprehensive, 360-degree targeted supplement (like mindbodygreen's daily detox+, which features Setria® glutathione as the hero, plus major supporting actors vitamin C, NAC, milk thistle, and selenium), is an easy way to support glutathione production, replenishment, and retention to get after free radicals and combat environmental stressors daily.*
14 Sources
- https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC2696075/
- https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC2932530/
- https://academic.oup.com/jn/article/134/3/489/4688681?login=false
- https://pubmed.ncbi.nlm.nih.gov/25271248/
- https://pubmed.ncbi.nlm.nih.gov/19558212/
- https://pubmed.ncbi.nlm.nih.gov/17617661/
- https://pubmed.ncbi.nlm.nih.gov/8200071/
- https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC4596346/
- https://pubmed.ncbi.nlm.nih.gov/24791752/
- https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC4540061/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4665566/
- https://pubmed.ncbi.nlm.nih.gov/20600218/
- https://www.sciencedirect.com/science/article/abs/pii/S089158491400224X?via%3Dihub
- https://pubmed.ncbi.nlm.nih.gov/26181573/
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