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

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.

Genome-Wide Association Study for Serum Omega-3 and Omega-6 Polyunsaturated Fatty Acids: Exploratory Analysis of the Sex-Specific Effects and Dietary Modulation in Mediterranean Subjects with Metabolic Syndrome

“…These 2 families each encompass fatty acids with varying carbon chain length and degree of unsaturation. Supplemental Figure S1 shows PUFA biosynthesis, detailing the omega-6 and omega-3 pathways and the names of the main PUFA, as well as the elongation and the desaturation activities [1][2][3]. Briefly, the omega-6 PUFA linoleic acid (LA) and the omega-3 PUFA alpha-linolenic acid (ALA) from the diet are the key substrates that enter the pathways leading to the synthesis of the main long-chain PUFA.…”

“…Nonetheless, it has been claimed that the lack of conclusive evidence obtained in the meta-analyses may be due to several biases, including not only the poor quality of some of the meta-analyzed trials, but also other relevant factors such as the unmeasured role of genetic polymorphisms influencing the effect of dietary PUFA [1]. The potential role of FADS genetic polymorphism in determining the effects of dietary and pharmacological PUFA on several cardiovascular risk factors and outcomes, have been investigated by several studies [1,[60][61][62][63][64][65]. Among them, a post-hoc analysis from the OMEGA-REMODEL RCT, investigating the effect of high-dose of omega-3 PUFA post-acute myocardial infarction [65] reported that the FADS2 genotype can predict the beneficial effects of the omega-3.…”

Effects of Linoleic and Alpha‐Linolenic Ratios and Concentrations on In Vitro Endothelial Cell Responses

“…Direct supplementation of foods rich in LA and ALA is the efficient way to obtain LA/ALA ratio in body. The commonly oils are rich in LA and poor in ALA, such as soybean and corn oils . Blasbalg et al found that LA intake increased 158% from 2.79% to 7.21% of energy, and ALA intake increased 85% from 0.39% to 0.72% in 1909 and 1999, respectively.…”

Reasons Why Omega-3 Polyunsaturated Fatty Acids Produce Mixed Results in Alzheimer's Disease Prevention Studies

“…Preferably, surrogate AD biomarkers and disease mechanisms should be identified and shown to be altered after intervention with an appropriate omega-3 dose for the required time. There is a need for personalized AD intervention because of genetic dependence of omega-3 metabolism [3]. Non-invasive monitor of brain omega-3 contents using PET scans and other functional brain imaging modalities [6] are highly recommended approaches open for future investigation.…”

“…Serum levels of PUFAs are also controlled by the rate limiting enzyme, delta-6 desaturase. Desaturase haplotypes regulate omega fatty levels in different races [3]. Moreover, most Western diets are high in lipids and loaded with omega-6 PUFAs.…”