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Serum Acetate:Propionate Ratio Is Related to Serum Cholesterol in Men but Not Women^1,2,

Thomas M. S. Wolever^*,,3, Judlyn Fernandes^* and A. Venketeshwer Rao^*

^* Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada M5S 3E2 Clinical Nutrition and Risk Factor Modification Centre, and Division of Endocrinology and Metabolism, St. Michael's Hospital, Toronto, Ontario, Canada M5C 2T2

Acetic and propionic acids, produced by colonic fermentation of unabsorbed carbohydrates, may influence systemic lipid metabolism. To determine whether the ratio of the concentrations of acetate to propionate in peripheral serum of fasting humans was related to serum cholesterol, we studied 62 men [age 45 ± 17 y (mean ± SD), range 19–74 y; body mass index 25.0 ± 2.8 kg/m²] and 69 women [43 ± 18 y, (range, 18–77 y); body mass index 23.0 ± 3.1 kg/m²] with normal serum lipid concentrations. The concentrations of serum acetate, propionate and buty-rate (means ± SD) were similar in men (98 ± 33, 3.8 ± 1.5 and 2.3 ± 1.5 µmol/L, respectively) and women (92 ± 38, 3.9 ± 1.9 and 2.3 ± 1.6 µmol/L). There were significant positive relationships between the serum acetate:propionate ratio and total cholesterol (r = 0.466, P = 0.0002) and LDL cholesterol (r = 0.384, P = 0.0023) in men, but in women the relationships were not significant (R = 0.174, P = 0.15 and r = 0.135, P = 0.27, respectively). The relationships in men remained significant after adjustment for age and body mass index. These data support the hypothesis that, at least in men, colonic short-chain fatty acids influence systemic lipid metabolism. The relationships among the factors influencing colonic short-chain fatty acid production, the enterohepatic circulation of endogenous estrogens, dietary phytoestrogens and blood lipids in women, however, need further clarification.

KEY WORDS: • humans • short-chain fatty acids • colonic fermentation • cholesterol

¹ Supported by the Natural Sciences and Engineering Research Council of Canada.

² The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

³ To whom correspondence should be addressed.

Manuscript received 30 November 1995. Revision accepted 11 July 1996.