Landmark Antioxidant Study Shows Oral Glutathione Is Bioavailable, May Benefit Immune Health


This new study may quell controversy over whether oral supplementation with the antioxidant glutathione works.

A new study may quell controversy over whether oral supplementation with the antioxidant glutathione works. While the few human clinical studies performed on glutathione so far have shown less-than-impressive results, this first-ever long-term study indicates that oral supplementation with glutathione does in fact significantly increase the body’s own glutathione levels.

Often called the “master antioxidant,” glutathione is a tripeptide present in nearly all body cells and is a critical regulator of oxidative stress and immune function. In the body, glutathione protects cells against oxidative stress, plays a role in detoxification of toxins and carcinogens, helps regulate protein function, and helps maintain immune function. Low glutathione levels are associated with increased risk of diseases like cancer, cardiovascular disease, arthritis, and diabetes.

While animal and in vitro studies have demonstrated bioavailability from glutathione supplementation, previous small-scale oral-supplementation human studies did not and led to arguments over whether oral glutathione supplementation has any benefit for humans. One of those earlier human studies may have been too short in duration to show effects, argue the researchers of the new glutathione study published in the May issue of the European Journal of Nutrition (EJN). The aforementioned seven-subject study showed no significant effects on plasma glutathione levels during a 4.5-hour period, but the EJN study authors wrote that “the rapid turnover of [glutathione] in human plasma would likely make it difficult to detect an increase in plasma after a single oral dose.”

“It is well known in the science community that glutathione is one of the primary protective molecules in the body; however, whether or not glutathione levels could be supplemented by oral glutathione administration has been hotly debated and clinical data has been lacking,” said the EJN study’s lead author John P. Richie, Jr., PhD, professor of public health sciences and pharmacology at Penn State University School of Medicine.

The 6-month ENJ study is the first long-term study on oral glutathione supplementation. It was a randomized, double-blind, placebo-controlled trial on 54 adults. Subjects were given placebo or a high (1000 mg/day) or low (250 mg/day) oral dose of Kyowa Hakko USA’s (New York City) Setria glutathione supplement.

At baseline and at 1, 3, and 6 months, researchers measured glutathione levels in the blood, erythrocytes, plasma, lymphocytes, and exfoliated buccal mucosal cells. For both the low- and high-dose groups, glutathione levels in the blood increased after 1,3, and 6 months compared to placebo. In the high-dose group, at six months, glutathione levels increased up to 35% in erythrocytes, plasma, and lymphocytes and 260% in buccal cells. In the low-dose group, glutathione levels increased 17% and 29% in blood and erythrocytes, respectively. Both groups also showed a reduction in oxidative stress as indicated by decreases in the oxidized glutathione: reduced glutathione ratio in whole blood after six months.

Most increases were dose and time dependent, and glutathione stores returned to baseline levels after a one-month washout period, indicating that ongoing supplementation may be crucial when it comes to glutathione.

This study also indicates oral glutathione supplementation’s benefits for immune health. After three months of the study, the high-dose glutathione subjects had a twofold increase in natural killer cell cytotoxicity, compared to placebo. “Overall, the present findings provide a basis for conducting larger studies focusing on immune function,” the researchers said.

“Increasing [glutathione] represents a potentially important approach to counteract disorders associated with glutathione depletion, enhance detoxification capacity, and protect against disease. Oral [glutathione] supplementation represents one such strategy for enhancing tissue [glutathione] levels,” they wrote.


Jennifer Grebow
Nutritional Outlook magazine



Richie JP Jr et al., “Randomized controlled trial of oral glutathione supplementation on body stores of glutathione,” European Journal of Nutrition, published online head of print May 5, 2014. 

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