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Oral glutathione supplementation has become very popular in the past decade.

Glutathione dietary supplements are known as L-glutathione, reduced glutathione or GSH. They come in pills, capsules, tablets, in powedered and liquid form, as sublingual drops or slow-melt tablets.glutathione (GSH) and its vital importance for proper detoxification, strong immune health, energy levels, endurance, muscle strength, anti-aging, master antioxidant role, and overall disease prevention.

People with various health concerns turn to glutathione pills, too, because they read in a health magazine or heard from TV gurus that raising glutathione would improve their condition.

Doctors who are aware of the benefits of elevated glutathione suggest glutathione supplementation to their patients, and/or prescribe NAC for them (while NAC is not glutathione, it is a pharmaceutical cysteine delivery system that raises GSH but can have some adverse side effects).

Oral glutathione supplementation is also very convenient – just take a pill once a day as you would do with a multivitamin. In our fast lives convenience is often as important as the end result of taking a supplement, if not more.

Our logic assumes that if a supplement is sold at all health food stores, pharmacies and online, and if it is advertised in mass media, it means the supplement must work well.

However, most people, including medical professionals, are not aware of the fact that glutathione pills may not be very helpful to the body. (Out of all the decades of research only one recent study showed an increase in blood GSH levels in healthy adults with oral supplementation. See the details below.)

Only very small amounts of pre-manufactured glutathione are able to enter bloodstream. Most of it is lost in the digestive tract and cannot effectively raise intracellular glutathione levels in the most important detoxification organs, such as liver, kidneys and lungs, because glutathione is a small protein molecule and gets digested.

p style="color: rgb(0, 0, 0); font-family: Verdana, Geneva, sans-serif; font-size: 13.008px; line-height: 16.9104px;"> It is very important to educate yourself to be able to make wise choices about how to raise glutathione effectively – that is why it is important to look at scientific research.

There still aren’t that many studies done using oral glutathione, especially on human subjects. The few studies that were performed so far are mostly the studies on mice or rats, some on healthy adults with no acute or chronic diseases, and a few on adults and children with certain serious diseases such as cystic fibrosis and autism.

Let’s examine what science has to say about usefulness of glutathione supplements.

ORAL GLUTATHIONE IN STUDIES ON MICE AND RATS

Some studies done on mice and rats show increased GSH in tissue, blood plasma and organs (liver, kidney, heart, lung, brain, small intestine and skin) after administration of oral glutathione.

However, there are several interesting observations:

• Mice that were not previously depleted of glutathione showed an increase in plasma glutathione only in lungs.
• Mice that showed significant increase in glutathione concentration were chemically pretreated for 5 days to deplete their glutathione levels. Still, glutathione rose in all organs except in the liver where it is most needed for detoxification.
• The effect of raised glutathione lasted 3 hours on average.
• All mice and rats received glutathione supplementation in doses much higher than the typical 500 mg dosage in human glutathione pills: 100mg/kg of weight for mice. If we do a comparison with human dosages for an average adult weighing 70 kg (approx. 154 lbs.) one 500 mg glutathione pill contains only 7.5 mg of glutathione per kg of weight.

So, to achieve similar results an adult will have to be severely glutathione deficient and take a minimum of 14 glutathione pills. To maintain the result of raised glutathione an adult will have to take this many pills several times a day.

Studies:

“Oral glutathione increases tissue glutathione in vivo”, Chemico-Biological Interactions, 1991;80(1):89-97.Aw TY, Wierzbicka G, Jones DP.

“Bioavailability of dietary glutathione: effect on plasma concentration”, The American Journal of Physiology, 1990 Oct; 259(4 Pt 1):G524-9.Hagen TM, Wierzbicka GT et al.

ORAL GLUTATHIONE IN STUDIES ON ADULTS AND CHILDREN WITH DISEASES

Research has proven that most known diseases are associated with low glutathione levels.In cases of acute and chronic conditions, and while undergoing harsh treatments, patients are severely glutathione deficient, and usually benefit even from slight elevation of GSH levels.

Research into the role of glutathione supplementation in disease is very limited. Studies that have been done so far are on autistic patients and patients with cystic fibrosis.

These studies indicate beneficial effect of oral GSH on raising Glutathione levels.But it is important to note that oral GSH was used in conjunction with either glutathione injections, or inhaled glutathione, or transdermal glutathione (skin patches). Thus, the beneficial result cannot be attributed solely to oral GSH.

One study examined the effects of oral glutathione in combination with inhaled glutathione on 13 cystic fibrosis patients 1-27 years old. Dosages ranged from 66 to148 mg/kg of weight a day in divided doses for the duration of 5.5 months. That translates into approximately 8 to 19 oral glutathione pills a day – again, the dosages were much higher than normal, and patients were monitored by medical personnel. At the end of this study it was concluded that “the use of a daily GSH regimen appears to be associated in CF patients with significant improvement in lung function and weight, and a significant decline in bacteria cultured in this uncontrolled study. These findings bear further clinical investigation in larger, randomized, controlled studies”.

The most recent 2015 placebo-controlledtrial with pediatric cystic fibrosis patients registered a significant improvement in growth rates, BMIand gut inflammation markers in a group of children who were administered oral glutathione at a dose of 65 mg/kg of body weight daily for 6 months.

Studies:

“Improvement in clinical markers in CF patients using a reduced glutathione regimen: an uncontrolled, observational study”, Journal of Cystic Fibrosis, September 2008; 7(5):433-6.Visca A, Bishop CT et al.

“A clinical trial of glutathione supplementation in autism spectrum disorders”, Medical Science Monitor, December 2011; 17(12):CR677-82.Kern JK, Geier DA, Adams JB et al.

"Oral reduced l-glutathione improves growth in pediatric cystic fibrosis patients: a randomized clinical trial", J Pediatr Gastroenterol Nutr. 2015 Jan Visca A, Bishop CT et al.

ORAL GLUTATHIONE IN STUDIES ON HEALTHY ADULTS

Research published before 2013 using healthy human subjects proves very poor bioavailability of oral and dietary glutathione:

1.“Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers”,Journal of Alternative and Complementary Medicine, September 2011; 17(9):827-33.Allen J, Bradley RD.

The effect of glutathione supplementation on biomarkers of systemic oxidative stress was examined in 40 healthy adult volunteers. This was a randomized, double-blind, placebo-controlled clinical trial. There were no differences in oxidative stress biomarkers between treatment groups before the study began. Then one group of volunteers were given 500 mg of oral GSH supplement twice daily for 4 weeks, another group received placebo. At the end of the study total reduced glutathione (GSH), oxidized glutathione (GSSG), and the ratio of GSH to GSSG (indicator of oxidative stress) were unchanged in both groups compared to the results obtained before supplementation.It was concluded that no significant changes were observed in biomarkers of oxidative stress, including glutathione status, in this clinical trial of oral glutathione supplementation in healthy adults.

2.“The systemic availability of oral glutathione”,European Journal of Clinical Pharmacology,1992; 43(6):667-9.Witschi A, Reddy S, et al.

Supplementation with glutathione pills was studied in 7 healthy volunteers. During 4.5 hours after the administration of glutathione in a massive dose of 3 g (3,000 mg) the concentrations of glutathione, cysteine, and glutamate in plasma did not increase significantly, suggesting that the systemic availability of glutathione is negligible in man.It was concluded that dietary glutathione is not a major determinant of circulating glutathione, and it is not possible to increase circulating glutathione to a clinically beneficial extent by the oral administration of a single dose of 3 g (3,000 mg) of glutathione.

3.“Dietary glutathione intake in humans and the relationship between intake and plasma total glutathione level”,Nutrition and Cancer, 1994;21(1):33-46.Flagg EW, Coates RJ, Eley JW et al.

This study investigated the associations between glutathione intake from food and plasma glutathione level (supplements were not used in this study). Concentrations of plasma total glutathione were measured in 69 white men and women before and after consumption of dietary GSH. Daily glutathione intake ranged from 13 to 109.9 mg (mean 34.8 mg).One of the observations was small negative correlations between dietary and plasma glutathione meaning that there is a possible decrease in blood GSN after ingestion of GSH containing foods.This negative correlation was higher in those with higher serum vitamin C levels indicating that high C levels may actually decrease Glutathione.It was concluded that factors regulating plasma Glutathione concentration are complex and not simply related to dietary glutathione intake.