Compartmental analysis of plasma and liver n-3 essential fatty acids in alcohol-dependent men during withdrawal

Abstract

The mechanism by which chronic ethanol consumption reduces concentrations of long chain polyunsaturated (LCP) fatty acids (FA) in tissues of humans was investigated in alcohol-dependent (AD) men during early withdrawal and to a well-matched control group by fitting the concentration-time curves of d5-labeled n-3 FA from plasma and liver, which originated from an oral dose of d5-linolenic acid (d5-18:3n-3) ethyl ester to a compartmental model. Blood sampled over 168 h and a liver specimen obtained 96 h after isotope administration were analyzed for d5-18:3n-3, d5-20:5n-3, d5-22:5n-3, and d5-22:6n-3. Plasma 20:5n-3 and 22:5n-3 were lower in AD subjects, compared with controls (20:5n-3: -50%, 22:5n-3: -34%). Increased amounts of d5-18:3n-3 were directed toward synthesis of d5-20:5n-3 in AD subjects (P < .05). However, this effect was offset by larger amounts of 20:5n-3 lost from plasma (control: 2.0 vs. AD: 4.2 mg d−1). In livers of AD subjects, more d5-18:3n-3 and d5-22:5n-3 were utilized for synthesis of d5-20:5n-3 (+200%) and d5-22:6n-3 (+210%), respectively, than was predicted from plasma kinetics. Although, the potential to utilize linolenic acid for synthesis of LCP FA was greater in AD subjects compared with controls, heightened disappearance rates of 20:5n-3 reduced overall plasma concentrations of several endogenous n-3 LCP FA.

Keywords

• ethanol
• α-linolenic acid
• docosahexaenoic acid
• isotope tracer
• compartmental modeling
• d5-fatty acids