Glycine is the simplest amino acid (the aminoacetic acid, with the chemical formula NH2-CH2-COOH) — it is the smallest and most abundant of the amino acids in the human body, and it is one of the three amino acids that constitute the glutathione tripeptide (the other two are cysteine and glutamate). The glycine is not just a structural component of the glutathione — it is the rate-limiting component of the glutathione synthesis, because the concentration of the glycine in the cells is the lowest of the three glutathione precursors and therefore it is the determinant of the maximum rate of the glutathione synthesis. The glutathione synthesis occurs in two steps: first, the glutamate and the cysteine are combined by the gamma-glutamyl cysteine ligase (GCL) to form the gamma-glutamyl cysteine, and second, the glycine is added to the gamma-glutamyl cysteine by the glutathione synthetase (GS) to form the glutathione. The rate of this second step is determined by the glycine concentration, and in most cells the glycine concentration is the limiting factor for the glutathione synthesis — which means that increasing the glycine availability (through the diet or the supplementation) can increase the glutathione levels even when the cysteine and the glutamate levels are adequate. Without adequate glycine and glutathione synthesis, the cells are vulnerable to the oxidative stress, the detoxification is impaired, and the ageing accelerates — the hallmark of the glycine deficiency and of the low glutathione states. The typical dietary glycine intake from the collagen-rich foods (bone broth, chicken skin, pork skin, beef) and from the gelatin is 2-5g daily, and the therapeutic doses for the glutathione support are 3-10g of the glycine supplement daily — making the glycine supplementation one of the most evidence-based interventions for the restoration of the glutathione levels and for the protection against the oxidative stress and the toxins.
Glycine and the Detoxification
Glycine is essential for the detoxification of the xenobiotics (foreign compounds such as the drugs, the environmental toxins, and the food additives) and of the endogenous toxins (such as the bilirubin, the bile acids, and the reactive carbonyl species) through the glycine conjugation pathway. The glycine conjugation (also called the hippuric acid formation) is the process by which the activated foreign compounds (the CoA esters of the foreign acids) are conjugated with the glycine in the liver, to form the hippuric acid derivatives that are excreted in the urine. This glycine conjugation pathway is one of the most important detoxification pathways in the liver — it is responsible for the detoxification of the salicylates (aspirin), the benzoates (food preservatives), the cinnamates ( cinnamon), the indoles (from the gut microbiota), and many other foreign compounds. The glycine conjugation capacity declines with age and in people with the liver disease — and this decline is associated with the increased susceptibility to the environmental toxins and to the drug side effects. By supplementing with the glycine, the glycine conjugation capacity is restored, and the liver’s ability to detoxify the foreign compounds is improved — which is one of the primary mechanisms of the glycine’s hepatoprotective and anti-ageing effects.
The clinical importance of the glycine for the glutathione synthesis and for the detoxification is underscored by the observation that the glycine supplementation increases the glutathione levels and improves the metabolic health in humans. A study in 8 healthy older adults found that the glycine supplementation at 3g daily for 2 weeks increased the glutathione levels in the blood mononuclear cells (by 25-35%) and improved the insulin sensitivity (by 10-15%, as measured by the HOMA-IR) — demonstrating the potent glutathione-boosting and metabolic effects of the glycine in humans. Another study found that the glycine supplementation improved the sleep quality and reduced the inflammation (by 15-20%, as measured by the CRP and the IL-6) — which are the hallmarks of the anti-ageing and the metabolic health effects of the glycine.
Practical Application
For general glycine supplementation for the glutathione support and for the detoxification, the evidence-based approach is to supplement with 3-10g of glycine daily (as the pure glycine powder, which is the most affordable and the most bioavailable form). The glycine should be taken before the bedtime (to align with the circadian pattern of the glutathione synthesis, which peaks during the sleep and during the fasting state), and it can be taken with the NAC (at 600-1800mg daily) and with the alpha-lipoic acid (at 300-600mg daily) for the maximum glutathione-boosting effect. The glycine is generally well-tolerated with no significant adverse effects at doses up to 30g daily, and it is one of the safest amino acids (because it is not neurotoxic like the glutamate, and it does not have the excitotoxic effects that are associated with the other amino acids). For comprehensive glutathione and longevity support, glycine pairs well with the NAC (which provides the cysteine for the glutathione synthesis), with the selenium (which is a cofactor for the glutathione peroxidase), with the vitamin D (which regulates the glutathione levels through the transcription of the glutathione-related genes), and with the sleep (which is one of the most important natural stimulators of the glutathione synthesis and of the cellular repair processes).
Leave a Reply