Effects of nicotinic acid on fatty acid kinetics, fuel selection, and pathways of glucose production in women

Chronic nicotinic acid (NA) ingestion effectively lowers lipid levels, but adverse effects on glucose metabolism have been reported. Our goal was to i nvestigate acute and chronic effects of NA on lipolysis and glucose metabol ism in women. Healthy normolipidemic volunteers (n = 5) were studied twice; four-day hospital stays were separated by 1 mo, during which time subjects took increasing doses of NA to 2 g/day (500 mg, 4 times). In the second st udy, 500 mg of NA was given at 0800. Rates of appearance (Ra) of free fatty acid (FFA), glycerol, and glucose were determined by isotope dilution (of [1,2,3,4-C-13(4)]-palmitate, [2-C-13(1)]glycerol, and [U-C-13(6)]glucose). Mass isotopomer distribution analysis was used to measure gluconeogenesis a nd glycogenolysis. Fasting FFA concentrations ([FFA]), Ra FFA, and Ra glyce rol were nonsignificantly elevated after 1 mo. Acute NA induced a significa nt reduction followed by a rebound overshoot of [FFA], Ra FFA, and Ra glyce rol. Whole body fat oxidation fell initially and then increased back to bas al levels; endogenous glucose production (EGP) increased in parallel with c arbohydrate oxidation and then returned to basal values. The increased EGP was due entirely to increased glycogenolysis, not gluconeogenesis. We concl ude that chronic effects of NA on FFA metabolism are complex (acute suppres sion followed by overshoot of Ra FFA and [FFA] on top of a trend toward bas al elevations), that responses after NA are consistent with operation of a glucose-fatty acid cycle in peripheral tissues, and that secondary effects on EGP were through changes in glycogenolysis, not gluconeogenesis.