Odd-chain fatty acids as a biomarker for dietary fiber intake: a novel pathway for endogenous production from propionate1,2

Background: The risk of type 2 diabetes is inversely correlated with plasma concentrations of odd-chain fatty acids [OCFAs; pentadecanoic acid (15:0) and heptadecanoic acid (17:0)], which are considered as biomarkers for dairy fat intake in humans. However, rodent studies suggest that OCFAs are synthesized endogenously from gut-derived propionate. Propionate increases with dietary fiber consumption and has been shown to improve insulin sensitivity. Objective: We hypothesized that OCFAs are produced in humans from dietary fibers by a novel endogenous pathway. Design: In a randomized, double-blind crossover study, 16 healthy individuals were supplemented with cellulose (30 g/d), inulin (30 g/d), or propionate (6 g/d) for 7 d. In addition, human hepatoma cells were incubated with different propionate concentrations. OCFAs were determined in plasma phospholipids and hepatoma cells by gas chromatography. Results: Cellulose did not affect plasma OCFA levels, whereas inulin and propionate increased pentadecanoic acid by ∼17% (P < 0.05) and 13% (P = 0.05), respectively. The effect on heptadecanoic acid was even more pronounced, because it was elevated in almost all participants by inulin (11%; P < 0.01) and propionate (13%; P < 0.001). Furthermore, cell culture experiments showed a positive association between propionate and OCFA levels (R2 = 0.99, P < 0.0001), whereas palmitate (16:0) was negatively correlated (R2 = 0.83, P = 0.004). Conclusions: Our data show that gut-derived propionate is used for the hepatic synthesis of OCFAs in humans. The association of OCFAs with a decreased risk of type 2 diabetes may therefore also relate to dietary fiber intake and not only dairy fat. This trial was registered at www.germanctr.de as DRKS00010121.