Effects of diet, smoking and chronic alcohol misuse on plasma lipid profiles and n-6 essential fatty acid metabolism in males and females

Smoking and alcohol misuse are associated with reductions in long-chain polyunsaturated fatty acids (PUFA). We investigated plasma fatty acid (FA) profiles and in vivo n-6 PUFA metabolism in male and female participants who either smoked or did not smoke cigarettes. Participants followed self-selected (SS), fish-based (FB), and beef-based (BB) diets for three weeks each. Participants diagnosed with an alcohol use disorder (AUD) were included. Individuals received 2H5-18:2n-6 ethyl ester orally. Endogenous FA were analyzed using gas chromatography and the 2H5-n-6 PUFA by gas chromatography-mass spectrometry. The concentration-time curves for the 2H5-n-6 PUFA were fit to a compartmental model. RESULTS: Among non-smoking individuals, the FB diet elevated plasma 20:5n-3 and 22:6n-3 by 2.5-fold. This was not observed in smokers. Male smokers had higher plasma FA levels on both the SS and BB diets compared to non-smokers and heightened synthesis of 2H5-20:4n-6. In female smokers 2H5-20:4n-6 synthesis was suppressed on SS diets. In AUD males plasma n-3 PUFA were lower compared to smokers and both AUD males and females had diminished synthesis of 2H5-20:4n-6 compared to smokers. In smokers, turnover of plasma 20:4n-6 was lower relative to non-smokers. In AUD males, turnover of 18:2n-6 and 20:4n-6 were also lower compared to smokers. CONCLUSIONS: Smoking had a major impact on FA profiles in males but the effects on n-6 PUFA metabolism between males and females were diverse. The FB diet did not elevate plasma n-3 PUFA in smokers compared with non-smokers. In AUD participants synthesis of 2H5-20:4n-6 was impaired relative to smokers.