Interpreting Clinical Trials With Omega-3 Supplements in the Context of Ancestry and Genetic Variation.
AuthorChilton, Floyd H
O'Connor, Timothy D
Johnstone, Laurel M
Schembre, Susan M
Tsai, Michael Y
Rich, Stephen S
Bridgewater, Susan J
Mathias, Rasika A
JournalFrontiers in Nutrition
PublisherFrontiers Media S.A.
MetadataShow full item record
AbstractHuman diets in developed countries such as the US have changed dramatically over the past 75 years, leading to increased obesity, inflammation, and cardiometabolic dysfunction. Evidence over the past decade indicates that the interaction of genetic variation with changes in the intake of 18-carbon essential dietary omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA), linoleic acid (LA) and α-linolenic acid (ALA), respectively, has impacted numerous molecular and clinical phenotypes. Interactions are particularly relevant with the FADS1 and FADS2 genes, which encode key fatty acid desaturases in the pathway that converts LA and ALA to their long chain (≥20 carbons), highly unsaturated fatty acid (HUFA) counterparts. These gene by nutrient interactions affect the levels and balance of n-6 and n-3 HUFA that in turn are converted to a wide array of lipids with signaling roles, including eicosanoids, docosanoids, other oxylipins and endocannabinoids. With few exceptions, n-6 HUFA are precursors of pro-inflammatory/pro-thrombotic signaling lipids, and n-3 HUFA are generally anti-inflammatory/anti-thrombotic. We and others have demonstrated that African ancestry populations have much higher frequencies (vs. European-, Asian- or indigenous Americas-ancestry populations) of a FADS "derived" haplotype that is associated with the efficient conversion of high levels of dietary n-6 PUFA to pro-inflammatory n-6 HUFA. By contrast, an "ancestral" haplotype, carrying alleles associated with a limited capacity to synthesize HUFA, which can lead to n-3 HUFA deficiency, is found at high frequency in certain Hispanic populations and is nearly fixed in several indigenous populations from the Americas. Based on these observations, a focused secondary subgroup analysis of the VITAL n-3 HUFA supplementation trial stratifying the data based on self-reported ancestry revealed that African Americans may benefit from n-3 HUFA supplementation, and both ancestry and FADS variability should be factored into future clinical trials design.
Rights/TermsCopyright © 2022 Chilton, Manichaikul, Yang, O'Connor, Johnstone, Blomquist, Schembre, Sergeant, Zec, Tsai, Rich, Bridgewater, Mathias and Hallmark.
fatty acid desaturase
omega-3 deficiency syndrome
polyunsaturated fatty acid
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/18136
- Precision Nutrition and Omega-3 Polyunsaturated Fatty Acids: A Case for Personalized Supplementation Approaches for the Prevention and Management of Human Diseases.
- Authors: Chilton FH, Dutta R, Reynolds LM, Sergeant S, Mathias RA, Seeds MC
- Issue date: 2017 Oct 25
- Omega-3 Supplementation and Heart Disease: A Population-Based Diet by Gene Analysis of Clinical Trial Outcomes.
- Authors: Fernandez ML, Blomquist SA, Hallmark B, Chilton FH
- Issue date: 2021 Jun 23
- Genetic Variation, Diet, Inflammation, and the Risk for COVID-19.
- Authors: Simopoulos AP
- Issue date: 2021
- Differences in erythrocyte phospholipid membrane long-chain polyunsaturated fatty acids and the prevalence of fatty acid desaturase genotype among African Americans and European Americans.
- Authors: Rifkin SB, Shrubsole MJ, Cai Q, Smalley WE, Ness RM, Swift LL, Milne G, Zheng W, Murff HJ
- Issue date: 2021 Jan
- Erythrocyte polyunsaturated fatty acid composition is associated with depression and FADS genotype in Caucasians.
- Authors: Cribb L, Murphy J, Froud A, Oliver G, Bousman CA, Ng CH, Sarris J
- Issue date: 2018 Oct