Cross-sectional associations of smoking and alcohol intake with NMR-measured lipid and metabolic biomarkers in over 100,000 Mexican adults

Background Smoking and alcohol use increase disease risk through metabolic disruption, vascular damage, and chronic inflammation. Plasma-based nuclear magnetic resonance (NMR) metabolomics can profile lipoproteins, amino acids, and inflammatory biomarkers linked to lifestyle-related disease risk. Methods We examined cross-sectional associations of self-reported smoking and alcohol consumption with 138 NMR-measured metabolic biomarkers among Mexico City Prospective Study participants without chronic disease, not taking lipid-lowering medication, and with complete data. Confounder-adjusted associations were estimated before and after additional adjustment for other lifestyle characteristics and adiposity. Results Among 106,257 participants aged 35–84 years, 30,853 (29%) were current smokers and 72,868 (69%) were current alcohol drinkers. Compared with never smokers, individuals smoking ≥ 10 cigarettes per day had higher Apo-B/Apo-A1 ratio (0.21 SD), VLDL and LDL particles and lipids, and lower HDL measures, linoleic and omega-6 fatty acids, and branched-chain and aromatic amino acid levels. Higher alcohol intake showed mixed associations, including favourable HDL-related measures alongside pro-inflammatory and fatty acid alterations. Compared with occasional drinkers, individuals consuming > 210 g alcohol per week had higher SFA/FA ratio (0.49 SD), acetate (0.45 SD), and HDL measures, but lower linoleic acid/FA ratio (-0.49 SD), omega-6/FA ratio (-0.48 SD) and most amino acids. Both smoking and alcohol use were associated with higher levels of GlycA, a biomarker of chronic inflammation. While most smoking-biomarker associations were linear-shaped, some of the alcohol-related associations exhibited non-linear patterns. Associations remained broadly consistent after mutual adjustment for each other, and after further adjustment for physical activity, diet, and adiposity, and were broadly similar in men and in women, but somewhat stronger at younger than older age. Conclusions Smoking and alcohol consumption, even at moderate levels, are associated with widespread alterations in circulating metabolic biomarkers linked to cardiometabolic and inflammatory disease risk. Accounting for the confounding effects of these factors is required when investigating biomarker-disease associations.