Vascular protective properties of supplemental glycine

Supplemental glycine, via activation of glycine-gated chloride channels that are expressed on a number of types of cells, including Kupffer cells, macrophages, lymphocytes, platelets, cardiomyocytes and endothelial cells, has been found to exert anti-inflammatory, immunomodulatory, cytoprotective, platelet-stabilising and antiangiogenic effects in rodent studies that may be of clinical relevance.1–17 The plasma concentration of glycine in normally nourished individuals—around 200 µM—is near the K_m for activation of these channels, implying that the severalfold increases in plasma glycine achievable with practical supplementation can be expected to further activate these channels in vivo.18 ,19 The impact on membrane polarisation of such activation will hinge on the intracellular chloride content; cells which actively concentrate chloride against a gradient will be depolarised by channel activation, whereas other cells will experience hyperpolarisation. In cells that fail to concentrate chloride and that express voltage-activated calcium channels, glycine tends to suppress calcium influx; this effect is thought to mediate much of the protection afforded by glycine.1 The role of chloride channel activation in the mediation of glycine's physiological effects is commonly assessed by the concurrent application of the chloride channel inhibitor strychnine; if this abolishes glycine's effect, this effect is most likely mediated by chloride channels.

From the standpoint of vascular health, a recent report that glycine can stabilise platelets is of evident interest.7 When rats were fed diets containing 2.5–5% glycine, bleeding time approximately doubled, and the amplitude of platelet aggregation in whole blood triggered by ADP or collagen was halved. This effect was blocked by strychnine, and the investigators were able to confirm that platelets express glycine-gated chloride channels. They also demonstrated that human platelets likewise were glycine responsive and expressed such channels. Studies evaluating the interaction of glycine with aspirin or other pharmaceutical platelet-stabilising agents would clearly be appropriate, as …