THE EFFECT OF DIETARY FIBRE ON HUMAN LIPID METABOLISM
Soluble fibre has been shown to lower serum cholesterol under experimental conditions. To date no survey has shown a relationship between soluble fibre and serum cholesterol. A survey was designed to establish if any relationship existed between the habitual intake of soluble fibre and serum cholesterol in 96 Saskatoon residents. Stepwise multiple regression analysis showed that soluble fibre was inversely related and responsible for 10% of the variation in serum total cholesterol (TC). TC, LDL-cholesterol (LDL-C), VLDL-cholesterol (VLDL-C) and triglycerides (TG) were directly related to Age, and HDL-C was inversely related to Age. Body Mass Index (BMI) was inversely related to HDL-C and directly related to VLDL-C and TG. The cholesterol lowering effect of soluble fibre may be mediated through propionate, a short chain fatty acid (SCFA) normally produced from the fermentation in the colon. Propionyl-CoA may compete with acetyl-CoA for binding sites on HMG-CoA synthase. Changes in serum glucagon have been reported when SCFA are infused rectally, and propionate is known to have a high affinity for carnitine. Increased glucagon secretion (which may inhibit cholesterol synthesis) has been reported as a response to decreased hepatic carnitine (CN) levels. To research one of possible mechanisms responsible for the cholesterol lowering of soluble fibre, a study was designed to determine if the SCFA propionate lowers serum cholesterol in human subjects, if acetate modifies the response, and to explore the mechanisms by which propionate, carnitine and glucagon interact. The study was carried out using 9 healthy male volunteers (initial TC > 5.5 mmol/L), who where fed a controlled low CN diet ( < 200 µmol/d) for 45 days (d). For 15-day periods subjects were on control (CTRL) or given by mouth 75 mmol propionate (PR) or 75 mmol propionate + 180 mmol acetate (PR+ACET). Treatment order was randomized. Faecal samples were collected throughout the study, and radiopaque faecal markers were given daily to ensure complete collection and measure intestinal transit time. 24 hour urine was collected on the last five days of each period during which the PABACHECK markers were taken (3xd). Urine samples were analyzed for para-amino benzoic acid (PABA) recovery to determine completeness of collection. On the last 2 days of each period fasting blood was taken. Statistical analysis was carried out by paired t-test with level of significance established at p <0.017 (Bonferroni correction for multiple comparisons). Faecal output (marker corrected faecal dry weight) decreased with propionate but no change was seen when acetate was added: CTRL 40.3 ±2.9 g/d (Mean±SEM); PR 36.3 ±2.6 g/d (p =0.001); PR +ACET 38.7 ±2.1 g/d. Neither total bile acids nor non-starch polysaccharide (NSP) excretion changed with either treatment. No ketones were found in any of the urine samples on either treatment and urinary urea nitrogen values were unchanged. Propionate significantly lowered serum total cholesterol when given alone, but when given together with acetate, no reduction was seen: CTRL 5.8 ±0.29 mmol/L; PR 5.5±0.30 mmol/L (p =0.005); PR + ACET 5.8 ±0.27 mmol/L. LDL-cholesterol was also significantly lowered by propionate with no change when acetate was added: CTRL 4.1 ±0.24 mmol/L; PR 3.8 ±0.29 mmol/L (p =0.013); PR + ACET 4.0 ±0.27 mmol/L. HDL-C, VLDL-C and TG were unchanged with both treatments. Serum SCFA showed no significant change with either treatment. Insulin was unchanged but glucagon increased with propionate, but not with added acetate: CTRL 93.8+2.7 pg/mL; PR 98.9±3.3 pg/mL (p=0.016); PR+ACET 98.3+4.2 pg/mL. Carnitine was measured in the plasma, urine and diet. No changes were found in plasma or urinary carnitines with either treatment. This study shows that propionate supplementation, clearly interferes with lipid metabolism in humans. Propionate reduced serum TC by 5%, and LDL-C by 7%. However until specific human liver enzymes can be studied in relation to these metabolic pathways, there is not enough evidence to indicate the mechanisms responsible. Both the increase in glucagon or competitive inhibition of acetyl-CoA in the synthesis of HMG-CoA could have been responsible for the lowering of serum cholesterol.
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