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Review
. 2017 Oct 25;9(11):1165.
doi: 10.3390/nu9111165.

Precision Nutrition and Omega-3 Polyunsaturated Fatty Acids: A Case for Personalized Supplementation Approaches for the Prevention and Management of Human Diseases

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Free PMC article
Review

Precision Nutrition and Omega-3 Polyunsaturated Fatty Acids: A Case for Personalized Supplementation Approaches for the Prevention and Management of Human Diseases

Floyd H Chilton et al. Nutrients. .
Free PMC article

Abstract

Background: Dietary essential omega-6 (n-6) and omega-3 (n-3) 18 carbon (18C-) polyunsaturated fatty acids (PUFA), linoleic acid (LA) and α-linolenic acid (ALA), can be converted (utilizing desaturase and elongase enzymes encoded by FADS and ELOVL genes) to biologically-active long chain (LC; >20)-PUFAs by numerous cells and tissues. These n-6 and n-3 LC-PUFAs and their metabolites (ex, eicosanoids and endocannabinoids) play critical signaling and structural roles in almost all physiologic and pathophysiologic processes.

Methods: This review summarizes: (1) the biosynthesis, metabolism and roles of LC-PUFAs; (2) the potential impact of rapidly altering the intake of dietary LA and ALA; (3) the genetics and evolution of LC-PUFA biosynthesis; (4) Gene-diet interactions that may lead to excess levels of n-6 LC-PUFAs and deficiencies of n-3 LC-PUFAs; and (5) opportunities for precision nutrition approaches to personalize n-3 LC-PUFA supplementation for individuals and populations.

Conclusions: The rapid nature of transitions in 18C-PUFA exposure together with the genetic variation in the LC-PUFA biosynthetic pathway found in different populations make mal-adaptations a likely outcome of our current nutritional environment. Understanding this genetic variation in the context of 18C-PUFA dietary exposure should enable the development of individualized n-3 LC-PUFA supplementation regimens to prevent and manage human disease.

Keywords: arachidonic acid; eicosanoids; endocannabinoids; fatty acid desaturase genes; gene-diet interaction; human disease; inflammation; omega-3 fatty acids; polyunsaturated fatty acids.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Polyunsaturated fatty acid biosynthesis. n-3 and n-6 LC-PUFA are synthesized from dietary intake of essential fatty acids ALA and LA, respectively, through a series of enzymatic desaturation (FADS2 and FADS1) and elongation (ELOVL2 and ELOVL5) steps. This pathway gives rise to primary n-3 LC-PUFAs and n-6 LC-PUFAs such as EPA, DPA, DHA and ARA. These LC-PUFAs (as free fatty acids or complex lipids) and their metabolites impact a wide ranges of physiologic and pathophysiologic processes. Abbreviations: FADS1/2, fatty acid desaturase 1/2; ELOVL 2/5, fatty acid elongase 2/5; ALA, α-linolenic acid; SDA, stearidonic acid; EtSA, eicosatetraenoic acid; EPA, eicosapentaenoic acid; DPA, docosapentaenoic acid; DHA, docosahexaenoic acid; LA, linoleic acid; GLA, γ-linolenic acid; DGLA, dihomo-γ-linolenic acid; ARA, arachidonic acid; ADA, adrenic acid; PG, prostaglandin; TX, thromboxane; LT, leukotriene; HEPE, hydroxyeicosapentaenoic acid; HETrE, hydroxyeicosatrienoic acid, HETE, hydroxyeicosatetraenoic acid; DiHETE, dihydroxyeicosatetraenoic acid; EET, epoxyeicosatetraenoic acid; 2AG, 2-arachidonoylglycerol; AEA, arachidonoyl ethanolamide/anandamide.
Figure 2
Figure 2
Genetic variation near the FADS gene cluster. (A) A expanded depiction of the FADS gene cluster on chromosome 11 illustrates the genomic location (build hg19) of: genes in this region (shown in dark blue, from RefSeq), the FADS cluster haplotype region and single nucleotide polymorphisms (SNPs) (region highlighted in light blue with SNPs shown as black vertical bars), and three individual SNPs identified as the most significantly associated genetic variants genome-wide with LC-PUFA levels (rs174537, rs174547, and rs174548); (B) The observed percentage of derived vs. ancestral FADS cluster haplotype varies by ethnicity.
Figure 3
Figure 3
Anatomy of gene-diet interactions leading to n-6 LC-PUFA excesses and n-3 LC-PUFA deficiencies. Dietary intake of n-3 and n-6 18C-PUFAs, ALA and LA, respectively, interact with FADS or ELOVL genetic and epigenetic variation (that impacts FADS or ELOVL expression or resultant activity) to determine circulating and cellular levels of n-3 and n-6 LC-PUFAs. These interactions can result in an unhealthy balance of LC-PUFAs, with excess levels of n-6 LC-PUFAs or deficiencies of n-3 LC-PUFAs.
Figure 4
Figure 4
Serum Levels of ARA and DHA in African Americans (AfAm) and European Americans (EuAm). Both n-6 and n-3 LC-PUFAs (arachidonic acid, ARA; and docosahexaenoic acid, DHA) are elevated in serum from AfAm relative to EuAm from the same clinical diabetes study cohort [106].

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