Abstract
Glutathione is a tripeptide that plays a pivotal role in critical physiological processes resulting in effects relevant to diverse disease pathophysiology such as maintenance of redox balance, reduction of oxidative stress, enhancement of metabolic detoxification, and regulation of immune system function. The diverse roles of glutathione in physiology are relevant to a considerable body of evidence suggesting that glutathione status may be an important biomarker and treatment target in various chronic, age-related diseases. Yet, proper personalized balance in the individual is key as well as a better understanding of antioxidants and redox balance. Optimizing glutathione levels has been proposed as a strategy for health promotion and disease prevention, although clear, causal relationships between glutathione status and disease risk or treatment remain to be clarified. Nonetheless, human clinical research suggests that nutritional interventions, including amino acids, vitamins, minerals, phytochemicals, and foods can have important effects on circulating glutathione which may translate to clinical benefit. Importantly, genetic variation is a modifier of glutathione status and influences response to nutritional factors that impact glutathione levels. This narrative review explores clinical evidence for nutritional strategies that could be used to improve glutathione status.
Highlights
Glutathione is a tripeptide found in relatively high concentrations in many bodily tissues [1]
It is important to note that NAC has antioxidant properties in addition to being able to provide cysteine for glutathione synthesis. It is unclear if the effects of NAC on oxidative stress are due to these antioxidant properties or due to increased glutathione synthesis
Well-established reference ranges for Red blood cell (RBC) glutathione or GGT are lacking and likely confounded by intra-individual variation, it may be possible to monitor glutathione status using these biomarkers dynamically in a personalized way
Summary
Glutathione is a tripeptide (cysteine, glycine, and glutamic acid) found in relatively high concentrations in many bodily tissues [1] It plays a pivotal role in reducing oxidative stress, maintaining redox balance, enhancing metabolic detoxification, and regulating the immune system [1]. Homocysteine can gamma carbon bond of cystathionine, resulting in the release of cysteine which can be used by GCL either regenerate methionine or be directed to cysteine the trans-sulfuration pathway forming cystathionine via and GSx to form glutathione. There are some common single nucleotide polymorphisms (SNPs) that impact glutathione and associated processes and may subsequently influence disease risk These code for the enzyme glutathione S-transferase (GST), which conjugate the reduced glutathione to substrates during the detoxification process [34]. Having one or more of these polymorphisms is associated with an increased risk of certain diseases [37], especially when impacted by environmental triggers such as pollution, smoking, heavy metals, and other toxins
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