Glutathione is the body’s main internal antioxidant, and is diminished in cases of oxidative stress, that is, when too many free radicals and other reactive oxygen and nitrogen species are generated for the body and the cell to detoxify successfully. As glutathione is used in these detoxifying reactions, it needs to be regenerated; but if diet is inadequate, or reactive oxygen species overpower the system, glutathione remains low in a vicious cycle that never allows the body to get out of oxidative stress. This is an unhealthy situation, one in which diabetics are particularly prone. However, there’s definitely something that can be done about this: improve the diet by adding more protein, especially cysteine-rich protein such as whey, and/or supplement the amino acids necessary to produce glutathione, those amino acids being cysteine and glycine. (Glutamine is also needed for synthesis of the tripeptide glutathione, but it is not an essential amino acid, i.e. not necessary – in most cases – in the diet.)
In the following paper, the researchers found diminished glutathione in diabetics. Glutathione Synthesis Is Diminished in Patients With Uncontrolled Diabetes and Restored by Dietary Supplementation With Cysteine and Glycine.
Sustained hyperglycemia is associated with low cellular levels of the antioxidant glutathione (GSH), which leads to tissue damage attributed to oxidative stress. We tested the hypothesis that diminished GSH in adult patients with uncontrolled type 2 diabetes is attributed to decreased synthesis and measured the effect of dietary supplementation with its precursors cysteine and glycine on GSH synthesis rate and oxidative stress.
RESEARCH DESIGN AND METHODS
We infused 12 diabetic patients and 12 nondiabetic control subjects with [2H2]-glycine to measure GSH synthesis. We also measured intracellular GSH concentrations, reactive oxygen metabolites, and lipid peroxides. Diabetic patients were restudied after 2 weeks of dietary supplementation with the GSH precursors cysteine and glycine.
Compared with control subjects, diabetic subjects had significantly higher fasting glucose (5.0 ± 0.1 vs. 10.7 ± 0.5 mmol/l; P < 0.001), lower erythrocyte concentrations of glycine (514.7 ± 33.1 vs. 403.2 ± 18.2 μmol/l; P < 0.01), and cysteine (25.2 ± 1.5 vs. 17.8 ± 1.5 μmol/l; P < 0.01); lower concentrations of GSH (6.75 ± 0.47 vs. 1.65 ± 0.16 μmol/g Hb; P < 0.001); diminished fractional (79.21 ± 5.75 vs. 44.86 ± 2.87%/day; P < 0.001) and absolute (5.26 ± 0.61 vs. 0.74 ± 0.10 μmol/g Hb/day; P < 0.001) GSH synthesis rates; and higher reactive oxygen metabolites (286 ± 10 vs. 403 ± 11 Carratelli units [UCarr]; P < 0.001) and lipid peroxides (2.6 ± 0.4 vs. 10.8 ± 1.2 pg/ml; P < 0.001). Following dietary supplementation in diabetic subjects, GSH synthesis and concentrations increased significantly and plasma oxidative stress and lipid peroxides decreased significantly.
Patients with uncontrolled type 2 diabetes have severely deficient synthesis of glutathione attributed to limited precursor availability. Dietary supplementation with GSH precursor amino acids can restore GSH synthesis and lower oxidative stress and oxidant damage in the face of persistent hyperglycemia.
Cysteine is the rate-limiting step in glutathione synthesis, and generally supplementation with it in the form of n-acetylcysteine should be enough to rebuild glutathione levels. Ideally, whey protein should be used instead (in my opinion), since it also supplies glycine as well as branched-chain amino acids, which are healthful and likely to be in short supply in cases of oxidative stress.
My speculation is that many cases of oxidative stress come about because many people are not eating enough protein. In these cases, the body cannot generate enough glutathione because the amino acids are needed elsewhere. (This occurs with glutathione competition.)
So, oxidative stress, whether in diabetes, chronic fatigue, depression, or other states of illness can be ameliorated with diet and supplements. These are central components in my book, Smash Chronic Fatigue.