Oral glutathione’s protective effects on fasting-induced intestinal atrophy

Glutathione (GSH) homeostasis is critical for health maintenance and disease prevention. Glutathione depletion has been shown to lead to increased oxidative stress, ageing and an increased risk of chronic disease [1].

Fasting and other malnutrition states are known to cause GSH depletion. Sources of GSH within intestinal mucosa include biliary secretions and dietary intake from foods such as fruit, vegetables and meat [2,3,4]. Additional GSH is located intracellularly, possessing a fundamental role in antioxidant protection [9].

Decreased GSH levels during fasting have been shown to cause small intestinal mucosal atrophy, in part due to the increased permeability of tight junctions. This in turn can lead to bacterial endotoxins leaking into the bloodstream [5.6]. Fasting has also been shown to increase reactive oxygen species (ROS) production in intestinal mucosa. This may lead to the further loss of intestinal mucosal structure and function when the conditions of inflammation, injury or shock are present [7,8].

A 2017 study by Uchida et al. examined the use of oral GSH supplementation in intestinal mucosal recovery [9]. Intestinal mucosal height was found to be significantly reduced in fasted rats resulting in significant intestinal atrophy. However, oral GSH supplementation reversed jejunal mucosal damage with significantly greater improvement noted in the high GSH supplemented group compared to the low dosed group. Furthermore, oral GSH supplementation lead to decreased ROS in the jejunal mucosa, thus cell proliferation was enhanced. Although outcomes are yet to be translated into human studies, preliminary results suggest oral GSH administration during fasting may provide mucosal regeneration potential [9].

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[4] Takahashi, I., Kern, M., Dodds, W., Hogan, W., Layman, R., Ammon, H. (1990). Fasting and postprandial hepatic bile flow in unanesthetized opossums. Am J Physiol, 259, G745-G752.

[5] Ziegler, T. (1996). Molecular mechanisms of intestinal injury, repair, and growth. In: Takala, J., Rombeau, J. (1996). Gut Dysfunction in Critical Illness. New York, Springer-Verlag, 25-52.

[6] Shaw, D., Gohil, K., Basson, M. (2012). Intestinal mucosal atrophy and adaptation. World J Gastroenterol, 18, 6357-6375.

[7] Darmon, N., Pélissier, M., Heyman, M., Albrecht, R., Desjeux, J. (1993). Oxidative stress may contribute to the intestinal dysfunction of weanling rats fed a low protein diet. J Nutr, 123, 1068-1075.

[8] Jonas, C., Farrell, C., Scully, S., Eli, A., Estívariz, C., Gu, L., Jones, D., Ziegler, T. (2000). Enteral nutrition and keratinocyte growth factor regulate expression of glutathione-related enzyme messenger RNAs in rat intestine. JPEN J Parenter Enteral Nutr, 24, 67-75.

[9] Uchida, H., Nakajima, Y., Ohtake, K., Ito, J., Morita, M., Kamimura, A., Kobayashi, J. (2017). Protective effects of oral glutathione on fasting-induced intestinal atrophy through oxidative stress. World Journal of Gastroenterology, 23 (36), 6650-6664.