Glutathione

Glutathione is one of the primary antioxidant and toxin conjugation systems in our bodies (Pizzorno 2014). Antioxidation is necessary within our bodies primarily due to our utilisation of oxygen as a final reactant in our energy-producing metabolism. Glutathione hereby acts as a shield against so-termed reactive oxygen species, which arise naturally in our energy-metabolism.

Glutathione mainly has two forms, as which it occurs in our bodies: a reduced form and an oxidised form. The reduced form can be used to shield our cellular structures against oxidative damage, whilst the oxidised form can't. Oxidation itself can further glycation, which is a topic I will talk on in a future post.

Furthermore, glutathione is used to conjugate and thus neutralise the negative effect of aldehydes and other reactive oxygen species, which arise from utilising carbohydrates as an energy and carbon source (Farrera and Galligan 2022).

We synthesise glutathione from cysteine, glycine, and glutamate. None of these amino acids are considered essential (see prior post on protein), but we need a reaction equivalent of sulfur to synthesise cysteine from other amino acids. This reaction equivalent of sulfur can only be ingested in the form of cysteine or methionine – the two sulfur-containing amino acids. Methionine we find in abundance in all animal products, cysteine in eggs and cereals (Day et al. 2022).

Blood glutathione is depleted in individuals upon carbohydrate feeding (Istfan et al. 2021), which would indicate that using cereals, which exhibit a high load of carbohydrates are a subpar source for reaction equivalents of sulfur, when considering our glutathione supply.

Keep in mind, that a decrease in blood glutathione concentration doesn't necessitate a parallel drop in intracellular glutathione concentrations, it is however made highly likely by the fact, that ketogenic feeding of rats (so, the inverse of carbohydrate feeding) showed significant increases in mitochondrial reduced glutathione, whereby mitochondria are intracellular structures, thus giving us a clue about intracellular glutathione levels (Jarret et al. 2008).

It would thus seem, that the best way to keep our main antioxidant reservoir – reduced glutathione – intact is to eliminate carbohydrates from our diets and increase supply of reaction equivalents of sulfur by the ingestion of animal protein, where such reaction equivalents are highly abundant.

Dai, Z., Zheng, W., and Locasale, J.W. (2022). Amino acid variability, tradeoffs and optimality in human diet. Nature Communications 13, 6683. 10.1038/s41467-022-34486-0.

Farrera, D.O., and Galligan, J.J. (2022). The Human Glyoxalase Gene Family in Health and Disease. Chemical Research in Toxicology 35, 1766-1776. 10.1021/acs.chemrestox.2c00182.

Istfan, N., Hasson, B., Apovian, C., Meshulam, T., Yu, L., Anderson, W., and Corkey, B.E. (2021). Acute carbohydrate overfeeding: a redox model of insulin action and its impact on metabolic dysfunction in humans. Am J Physiol Endocrinol Metab 321, E636-e651. 10.1152/ajpendo.00094.2021.

Jarrett, S.G., Milder, J.B., Liang, L.-P., and Patel, M. (2008). The ketogenic diet increases mitochondrial glutathione levels. Journal of Neurochemistry 106, 1044-1051. 10.1111/j.1471-4159.2008.05460.x.

Pizzorno, J. (2014). Glutathione! Integr Med (Encinitas) 13, 8-12.