Glycine

Glycine is the smallest and simplest non-essential amino acid in humans, animals, and many mammals, generally synthesized from choline, serine, hydroxyproline, and threonine through interorgan metabolism primarily involving the kidneys and liver. ^[1] Although classed as non-essential, glycine is often not sufficiently synthesized under common feeding conditions, and endogenous synthesis can be inadequate for maximal collagen production. ^{[1] [2]} Glycine has indispensable roles in both excitatory and inhibitory neurotransmission, acting via N-methyl-D-aspartate type glutamate receptors and glycine receptors, respectively. ^[3]

Glycine acts as a precursor for several key low-molecular-weight metabolites, including creatine, glutathione, haem, purines, and porphyrins. ^[1] It exerts anti-inflammatory effects largely through modulating the expression of nuclear factor kappa B (NF-kB) in many cell types, decreasing pro-inflammatory cytokines and improving the insulin response. ^[4] Glycine residues occupy about one-third of the amino acid residues in collagen protein, so the supply of glycine can be a limiting factor for collagen synthesis. ^[5] Oral glycine before bedtime is associated with a decrease in core body temperature linked to increased cutaneous blood flow, a plausible mechanism for its effect on sleep since sleep onset involves a fall in core body temperature. ^[3]

A systematic review of glycine administration in adult humans found the nervous system demonstrated the most positive effects, with longer-term administration improving sleep in healthy populations and psychiatric symptoms in psychiatric populations. ^[6] In a meta-analysis of prospective metabolomics studies, glycine was inversely associated with the risk of developing type 2 diabetes. ^[7] A cross-ancestry Mendelian randomization meta-analysis integrating Chinese and European populations found evidence that genetically predicted glycine levels were associated with a lower risk of heart failure. ^[8] Dietary glycine increases healthy lifespan in model organisms and might decrease inflammation in humans, but larger long-term studies with more robust designs in healthy populations are warranted to examine whether it can prevent, delay, or reverse ageing. ^[6]

Dietary glycine supplementation at an appropriate dose has been reported to be effective in treating metabolic disorders in patients with cardiovascular diseases, several inflammatory diseases, obesity, cancers, and diabetes. ^[1] The evidence base for glycine as a pro-longevity molecule remains largely preclinical: glycine was found to boost longevity in genetically heterogeneous mice and extends lifespan in rats, with a leading proposed mechanism being that it mimics methionine restriction and activates autophagy via glycine N-methyltransferase. ^[9] As dietary glycine may be insufficiently synthesized endogenously, supplementation has been highlighted as important in avoiding the development of chronic inflammation. ^[4]