BACKGROUND: The consumption of monounsaturated trans fatty acids (TFAs) increases the risk of cardiovascular disease (CVD). Putative differences between the effects of TFAs from industrially produced and natural sources on CVD risk markers were not previously investigated in healthy subjects. OBJECTIVE: We aimed to compare the effects of TFAs from industrially produced and natural sources on HDL and LDL cholesterol, lipoprotein particle size and distribution, apolipoproteins, and other lipids in healthy subjects. DESIGN: In a randomized, double-blind, controlled, crossover design, 46 healthy subjects (22 men and 24 women) consumed food items containing TFAs (11-12 g/d, representing approximately 5% of daily energy) from the 2 sources. RESULTS: Forty subjects (19 men and 21 women) completed the study. Compared with TFAs from industrially produced sources, TFAs from natural sources significantly (P = 0.012) increased HDL cholesterol in women but not in men. Significant (P = 0.001) increases in LDL-cholesterol concentrations were observed in women, but not in men, after the consumption of TFAs from natural sources. Apolipoprotein (apo)B and apoA1 concentrations confirmed the changes observed in LDL and HDL cholesterol. Analysis of lipoprotein subclass showed that only large HDL and LDL concentrations were modified by TFAs from natural sources but not by those from industrially produced sources. CONCLUSIONS: This study shows that TFAs from industrially produced and from natural sources have different effects on CVD risk factors in women. The HDL cholesterol-lowering property of TFAs seems to be specific to industrial sources. However, it is difficult in the present study to draw a conclusion about the effect of TFAs from either source on absolute CVD risk in these normolipidemic subjects. The mechanism underlying the observed sex- and isomer-specific effects warrants further investigation. AD - Institut National de Recherche Agronomique and Food Science, UMR1019, Clermont-Ferrand, France.