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Providing perspectives on recent research into vitamins and nutritionals

Possible Concentrations of an Essential Element in the Diet

The Future is Coming: Understanding Nutrient Requirements by Gender and Genetics

By Michael McBurney

Dietary Reference Intakes (DRIs) are based upon an Estimated Average Requirement (EAR) – the average daily nutrient intake to meet the requirements of half the individuals. Adjustments are made for life stage (age, pregnancy, lactation)because they influence requirements. Because gender affects nutrient requirements, DRIs are established separately for males and females. As genetic insights grow, expect current male and female DRIs to be delineated into appropriate subgroups.

Mammals convert the long-chain polyunsaturated (PUFA) omega-3 fatty acid α-linolenic acid (ALA) into longer-chain PUFAs such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Only ~4-6% of ALA is converted to EPA and DHA in adults. Childs and associates report a significant difference between men and women in ability to convert ALA to longer-chain omega-3 PUFA. Women had a significantly greater increase in plasma phospholipid EPA than males consuming the same high ALA diet. The study confirmed observations in men and women using stable isotopes. It is thought that estrogen may be regulating the proportion of ALA used for β-oxidation in women. Despite sex-specific effects on the proportion of ALA used for β-oxidation, Burdge and Calder emphasize the need for men and women to have adequate intakes of EPA and DHA to maintain optimal tissue function.

Nutrient requirements are assumed to be normally distributed but two different relationships are known to exist. There is a DRI, complete with EAR, Recommended Dietary Allowance (RDA), and Upper Limit (UL) for each sex. One for men. One for women. What if genetics further segregated nutrient requirements? There may be multiple phenotypes within each sex, each phenotype with a unique nutrient requirement.

Mozaffarian and colleagues report this may be the case using genome-wide associations (GWAS). They associated variations in single-nucleotide polymorphisms (SNPs) with circulating trans fatty acid concentrations in red blood cells and plasma phospholipids obtained from 8,013 individuals. Thirty-one SNPs were found to be statistically significant. Most significant was the FADS1/2 cluster regulating desaturase enzymes involved in the metabolism of n-3 and n-6 PUFA. However, the statistical relationship between FADS1/2 cluster and trans fatty acid concentrations was abolished when adjusted for circulating concentrations of arachidonic acid (ARA).

Genetically-based nutrient recommendations are not yet a reality. However, they will come. As scientists understand the impact of genetic polymorphisms, SNPs, on nutrient requirements and health, expect to see DRIs expand from two simple distributions (male and female) to multiple relationships within each gender (and life stage) describing specific genotype effects on nutrient intake requirements.

Main Citations

Childs CE, Kew S, Finnegan YE, Minihane AM, Leigh-Firzbank EC, Williams CM, Calder PC. Increased dietary alpha-linolenic acid has sex-specific effects upon eicosapentaenoic acid status in humans: re-examination of data from a randomized, placebo-controlled, parallel study. 2014 Nutr J doi: 10.1186/1475-2891-13-113

Mozaffarian D, Kabagambe EK, Johnson CO, Lemaitre RN, Manichaikul A, Sun Q, Foy M, Wang L, Wiener H, Irvin MR, Rich SS, Wu H, Jensen MK, Chasman DI, Chu AY, Fornage M, Steffen L, King IB, McKnight B, Psaty BM, Djousse L, Chen IY-D, Wu JHY, Siscovick DS, Ridker PM, Tsai MY, Rimm EB, Hu FB, Arnett DK. Genetic loci associated with circulating phospholipid trans fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium. 2014 Am J Clin Nutr doi: 10.3945/ajnc.114.094557

Other Citations

Gerster H. Can adults adequately convert alpha-linolenic acid (18:3n-3) to eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3)? 1998 Int J Vitamin Nutr Res 68(3):159-73

Burdge GC, Calder PC. Conversion of α-linolenic acid to longer-chain polyunsaturated fatty acids in human adults. 2005 Reprod Nutr Dev doi: 10.1051/rnd.2005047