Good News for Wine Lovers

Epidemiological studies and controlled trials on alcohol consumption invariably show a U shaped mortality curve where abstinence is associated with higher mortality and increasing alcohol consumption improves health until mortality begins to rise again with high alcohol consumption. As well as all-cause mortality there is a greater reduction of cardiovascular mortality that apparently exceeds the protection afforded by taking statins. While the toxic effects of excess alcohol on brain and liver cells have been known for some time the biological mechanisms behind the protective effect of moderate alcohol consumption include increased high-density lipoprotein cholesterol, decreased platelet aggregation and blood coagulation factors, and beneficial effects on endothelial function and inflammation. These beneficial effects of alcohol are likely due to the rapid increase in the short chain fatty acid, acetate in the blood stream soon after alcohol consumption.

Since the discovery of receptors for short chain fatty acids in 2003 there has been a huge interest in their important signaling functions and understanding of the relationship of gut microbiota and health, particularly inflammation. The main source of short chain fatty acids is bacterial fermentation of fibre but alcohol is another important source of acetate which in some circumstances can be greater than the amount generated from fibre fermentation (6). After consumption alcohol is quickly absorbed and metabolized to acetate increasing blood levels up to 20 fold. Acetate is an energy source for most organs including brain cells and it is also a signaling molecule as an agonist of free fatty acid receptor 2 (FFAR2) expressed widely on cells of the immune system, blood vessels and fat cells. Widespread beneficial effects of Short Chain Fatty Acids are listed below:

· SCFAs reduce inflammation and regulate adipokine secretion in adipose tissue increasing leptin and decreasing the pro-inflammatory resistin.

· SCFAs have anti-inflammatory effects in colitis, arthritis and asthma

· SCFA induce T regulatory cells important in controlling intestinal barrier functions and immunity

· Acetate via acetylation effects protein function and gene expression. Increased acetate levels stimulate mitochondrial function and has been linked to delaying the aging process.

· SCFA’s control Glucagon Like Peptide 1 release from intestinal L cells. GLP1 slows gastric emptying, lowers glucose levels, and reduces food consumption. GLP1 is an important regulator of glucose metabolism and also suppresses appetite.

· GLP1 has been recently shown to stimulate apolipoprotein A-I gene expression in hepatocytes in culture with important implications for increasing plasma HDL and protection against cardiovascular disease.

· GLP1 prevents the accumulation of monocytes and macrophages in arterial wall and suppresses proinflammatory cytokine expression in macrophages.

· SCFAs stimulate secretion of anorexic hormone PYY from intestinal L cells.

· SCFAs also inhibit the secretion of the orexigenic hormone ghrelin.

· SCFAs reduce endothelial cell expression of leukocyte adhesion molecules VCAM and ICAM which are important in the development of cardio-vascular diseases.

Summary

Acetate and other short chain fatty acids activate specific receptors that are widely expressed throughout body tissue importantly on immune cells and adipose tissue and suppress inflammation while the FFAR2 receptors in intestinal cells produce additional signaling molecules GLP1 and PYY which suppress appetite, increase HDL and contribute to further anti-inflammatory and metabolic regulatory functions. Pharmaceutical companies see a multibillion dollar business in producing drugs which mimic GLP1. Better results without side effects are achievable with a high fibre diet and a couple of glasses of wine.