Randomized controlled trial of oral glutathione supplementation on body stores of glutathione
Richie JP Jr1, Nichenametla S, Neidig W, Calcagnotto A, Haley JS, Schell TD, Muscat JE.
1Department of Public Health Sciences, Penn State Cancer Institute, H069, Penn State University College of Medicine, 500 University Drive, Hershey, PA, 17033, USA.
Eur J Nutr. March 2015, Volume 54, Issue 2, pp 251-263
Glutathione (GSH), the most abundant endogenous antioxidant, is a critical regulator of oxidative stress and immune function. While oralGSH has been shown to be bioavailable in laboratory animal models, its efficacy in humans has not been established. Our objective was to determine the long-term effectiveness of oral GSH supplementation on body stores of GSH in healthy adults.
A 6-month randomized, double-blinded, placebo-controlled trial of oral GSH (250 or 1,000 mg/day) on GSH levels in blood, erythrocytes, plasma, lymphocytes and exfoliated buccal mucosal cells was conducted in 54 non-smoking adults. Secondary outcomes on a subset of subjects included a battery of immune markers.
GSH levels in blood increased after 1, 3 and 6 months versus baseline at both doses. At 6 months, mean GSH levels increased 30-35 % in erythrocytes, plasma and lymphocytes and 260 % in buccal cells in the high-dose group (P < 0.05). GSH levels increased 17 and 29 % in blood and erythrocytes, respectively, in the low-dose group (P < 0.05). In most cases, the increases were dose and time dependent, and levels returned to baseline after a 1-month washout period. A reduction in oxidative stress in both GSH dose groups was indicated by decreases in the oxidized to reduced glutathione ratio in whole blood after 6 months. Natural killer cytotoxicity increased >twofold in the high-dose group versus placebo (P < 0.05) at 3 months.
These findings show, for the first time, that daily consumption of GSH supplements was effective at increasing body compartment stores of GSH.
Combined L-citrulline and glutathione supplementation increases the concentration of markers indicative of nitric oxide synthesis.
McKinley-Barnard S, Andre T, Morita M2, Willoughby DS. J Int Soc Sports Nutr.2015 Jun 10;12:27. doi: 10.1186/s12970-015-0086-7. eCollection 2015.
Combining L-citrulline with GSH augments increases in nitrite and NOx levels during in vitro and in vivo conditions.
1 Andersen HR. Age and Aging. 1998; 27:643-648.
2 Lang CA, et al. J Lab Clin Med. 2002 Dec; 140(6):380-1.
3 Ashfaq S et al. J Am Coll Cardiol. 2006 Mar 7;47(5):1005-11.
4 Richie JP et al. Nutr Cancer. 2008;60(4):474-82.
5 Flagg EW et al. Am J Epidemiol. 1994;139(5):453-65.
6 Cohen SM et al. Br J Ophthalmol. 1994 Oct;78(10):791-94.
7 Coral K et al. Eye. 2006 Feb;20(2):203-7.
8 Jonas CR et al. Free Radic Biol Med. 2002;33:1499-506.
9 Julius M et al. J Clin Epidemiol. 1994;47(9):1021-26.
10 Blanco RA et al. Diurnal variation in glutathione and cysteine redox states in human plasma. Am J Clin Nutr. 2007 Oct;86(4):1016-23.of chronically enhancing the body's stores."