Human genetic variation in dietary fat metabolism and its implications for health & disease.
TOPICS DISCUSSED:
- Linoleic Acid Rise: Linoleic acid now comprises 6-8% or more of energy in Western diets.
- Metabolic Pathways: Omega-6 linoleic acid converts to arachidonic acid and pro-inflammatory oxylipins; omega-3 ALA converts via shared enzymes to EPA/DHA with anti-inflammatory effects.
- FADS Genetic Variants: Ancestry-linked haplotypes in the FADS cluster create large “pipe” size differences, altering fatty acid by up to 40% between ancestral and derived versions.
- Population Differences: African ancestry populations often have high-conversion “big pipe” genotypes; Indigenous American ancestry populations have low-conversion “small pipe” genotypes; European ancestry comes with a mix of both.
- Omega-3 Deficiency: High linoleic intake suppresses EPA production, especially in small-pipe populations, contributing to hypertriglyceridemia and fatty liver in Mexican cohorts.
- Clinical Evidence: Reanalysis of VITAL trial showed 83% reduction in myocardial infarction with omega-3 supplementation in African Americans; Mexican data link low EPA to unique diabetes forms.
- Methodological Issues: Compositional data (from GC-FID measurements) versus absolute concentration measurements can flip relationships between linoleic acid and key biomarkers.
ABOUT THE GUEST: Floyd Chilton PhD is Professor and Director of the Center for Precision Nutrition and Wellness at the University of Arizona. His research focuses on functional genomics, fatty acid metabolism, and precision nutrition, particularly how genetic ancestry influences responses to dietary fats.
RELATED EPISODE:
- M&M 291: Omega Polyunsaturated Fats & Inflammation | Philip Calder
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