It has been known for decades that low-fat, high-carbohydrate diets can inc
rease plasma triglyceride levels, but the mechanism for this effect has bee
n uncertain. Recently, new isotopic and nonisotopic methods have been used
to determine in vivo whether low-fat, high-carbohydrate diets increase trig
lyceride levels by stimulating fatty acid synthesis. The results of a serie
s of studies in lean and obese weight-stable volunteers showed that very-lo
w-fat (10%), high-carbohydrate diets enriched in simple sugars increased th
e fraction of newly synthesized fatty acids, along with a proportionate inc
rease in the concentration of plasma triglyceride. Furthermore, the concent
ration of the saturated fatty acid, palmitate, increased and the concentrat
ion of the essential polyunsaturated fatty acid, linoleate, decreased In tr
iglyceride and VLDL triglyceride. The magnitude of the increase in triglyce
ride varied considerably among subjects, was unrelated to sex, body mass in
dex, or insulin levels, and was higher when fatty acid synthesis was consta
ntly elevated rather than having a diurnal variation. It was notable that m
inimal stimulation of fatty acid synthesis occurred with higher fat diets (
>30%) or with 10% fat diets enriched In complex carbohydrate. Public health
recommendations to reduce dietary fat must take into account the distinct
effects of different types of carbohydrate that may increase plasma triglyc
erides and fatty acid synthesis in a highly variable manner. The mediators
and health consequences of this dietary effect deserve further study.