The contribution of propionic acid to some physiological effects of dietary fibre

Abstract

Increased intake of dietary fibre (DF) is associated with several beneficial effects on carbohydrate and lipid metabolism, and possibly also on haemostasis. Various mechanisms have been proposed to explain these effect: Dietary fibre influences the secretion, digestion, absorption, and fermentation functions, as well as the morphologic structure of the gastrointestinal tract, and the transit ti me of food through the gut. This may lead to changes in blood nutrient dynamics and endocrine responses, which may influence cellular substrate availability and hormonal regulation of enzyme activities, with resultant changes in metabolism. Recently, questions have arisen about the physiological importance of short chain fatty acid metabolites of certain plant fibres. Some investigators have speculated that the short chain fatty acids (SCFAs) have metabolic effects that may explain some of the physiologic responses attributed to dietary fibre. To test the hypothesis ti at propionate, one of the SCFAs derived from the fermentation of DF and a-amylase resistant starch, contributes to the well-known effects of DF on carbohydrates and lipid metabolism (increased insulin sensitivity and decreased serum cholesterol), the diet of healthy human volunteers was supplemented with sodium propionate. The effect of dietary propionate on carbohydrate and lipid metabolism, as observed from changes in glucose tolerance, insulin response and serum lipid profiles after seven weeks, were compared with the known effects of fermentable DF on these variables. The study of the effects of propionate on metabolism in human subjects was, of necessity, confined to measurements of metabolites in blood. The literature survey indicated that the metabolism of the liver may be modified by propionate. Consequently, the contribution of propionate to the effects of DF on metabolism was investigated in animal models. The long- term effects of the soluble dietary fibre concentrate konjac-glucomannan (K-GM) and of sodium propionate on serum and liver lipids, glucose tolerance, serum insulin response and sensitivity, liver glycogen content, and plasma fibrinogen were compared in baboo s (Papio ursinus) fed a semi-synthetic Western diet (SSW-diet). The Zucker "fatly" rat was further used as an insulin resistant, hyperfibrinogenaemic model to compare the therapeutic effects of K-GM and sodium propionate; 1gainst a background SSW-diet. Resistant starch and ol11e r types of starch which escape digestion in the small intestine may quantitatively be more important as substrates for fermentation and propionate production than DF. The acute (short-term) effects or maize porridge with suspected varying amounts or digestible starch on blood glucose and serum insulin response in healthy volunteers were investigated to determine the physiological importance of resistant l starch. The results of the various studies, which aro~ discussed in detail in each separately presented study, and in chapter 9, show, inter alia, that: Supplementation of a Westernized diet with K-GM as well as propionate lower fasting circulating free fatty acid (FFA) levels significantly. This observation has far-reaching implications. It is known that high serum concentrations of FFA are associated with insensitivity to insulin and inhibition of cellular glucose uptake (' Randle effect'), increased plasma fibrinogen levels and also with atherosclerosis. Lower plasma fibrinogen concentrations were observed in experimental animals fed K-GM- or propionate-supplemented SSW-diets. Both supplements resulted in lower fasting serum insulin levels, as well as smaller glucose increments during glucose tolerance tests. These observations may indicate improved insulin sensitivity. An increase in insulin sensitivity may further explain the consistently higher percentage high-density lipoprotein cholesterol observed with both supplements in all the studies. In the animal models supplementation of a Westernised diet with K-GM as well as propionate lowered liver glycogen stores. The lower glycogen stores were associated with higher blood glucose levels in t11e animals fed propiona1e. These observations indicate that in addition to the documented effect of propionate on gluconeogenesis, propionate also stimulates glycogenolysis and glucose utilization in the fasting state. It seems as if lipolysis (mobilization of FFA) is inhibited at the same time. However, the raised blood glucose levels were not observed in humans. Liver cholesterol concentrations were significantly lower in baboons and Zucker rats fed the propionate and K-GM-supplemented SSW-diets than in animals fed the unsupplemented SSW-diet. This observation is supported by results reported in the literature, indicating inhibition of HMG-Co/\ reductase, a rate-limiting enzyme in cholesterol synthesis. Changes in the ratios of serum: liver cholesterol indicated that, in combination with inhibition of cholesterol synthesis, a shift in cholesterol from liver to serum occurred. Calculations to quantify tile contributim1 of propionate to the biochemical effects of DF in the various models, clearly revealed that the magnitude varies in different models because of species-differences and probably also as a result of an interaction with other specific effects of the DF in a particular model. The conclusion was reached that propionate contributes substantiall:1 to the ability of DF to increase insulin sensitivity and decrease liver cholesterol, circulating FFA and plasma fibrinogen concentrations. Hyperfibrinogenaemia, hype cholesterolemia, raised FFA levels and glucose- intolerance are risk factors for the pathogenesis of atherosclerosis. ·The results of this investigation reveal basic information on the mechanism of action of DF and also on the physiological importance of propionate, derived from bacterial fermentation of DF. A recommendation is made that subjects at risk for the development of degenerative Western diseases should increase their intake or fermentable dietary carbohydrate (substrates for propionate).