Nutraceutical resources for diabetes prevention--an update.

There is considerable need for safe agents that can reduce risk for diabetes in at-risk subjects. Although certain drugs--including metformin, acarbose, and orlistat--have shown diabetes-preventive activity in large randomized studies, nutraceuticals have potential in this regard as well. Natural agents which slow carbohydrate absorption may mimic the protective effect of acarbose; these include: soluble fiber--most notably glucomannan; chlorogenic acid--likely responsible for reduction in diabetes risk associated with heavy coffee intake; and legume-derived alpha-amylase inhibitors. There does not appear to be a natural lipase inhibitor functionally equivalent to orlistat, although there are poorly documented claims for Cassia nomame extracts. Metformin's efficacy reflects activation of AMP-activated kinase; there is preliminary evidence that certain compounds in barley malt have similar activity, without the side effects associated with metformin. In supraphysiological concentrations, biotin directly activates soluble guanylate cyclase; this implies that, at some sufficient intake, biotin should exert effects on beta cells, the liver, and skeletal muscle that favor good glucose tolerance and maintenance of effective beta cell function. Good magnesium status is associated with reduced diabetes risk and superior insulin sensitivity in recent epidemiology; ample intakes of chromium picolinate appear to promote insulin sensitivity in many individuals and improve glycemic control in some diabetics; calcium/vitamin D may help preserve insulin sensitivity by preventing secondary hyperparathyroidism. Although conjugated linoleic acid--like thiazolidinediones, a PPAR-gamma agonist--has not aided insulin sensitivity in clinical trials, the natural rexinoid phytanic acid exerts thiazolidinedione-like effect in animals and cell cultures, and merits clinical examination. Other natural agents with the potential to treat and possibly prevent diabetes include extracts of bitter melon and of cinnamon. Nutraceuticals featuring meaningful doses of combinations of these agents would likely have substantial diabetes-preventive efficacy, and presumably could be marketed legally as aids to good glucose tolerance and insulin sensitivity.