Abstract
Scope: We investigated the FADS1 rs174550 genotype interaction with dietary intakes of high linoleic acid (LA) and high alpha‐linolenic acid (ALA) on the response of fatty acid composition of plasma phospholipids (PLs), and markers of low‐grade inflammation and glucose‐insulin homeostasis. Methods and Results: One‐hundred thirty homozygotes men for FADS1 rs174550 SNP (TT and CC genotypes) were randomized to an 8‐week intervention with either LA‐ or ALA‐enriched diet (13 E% PUFA). The source of LA and ALA were 30–50 ml of sunflower oil (SFO, 62–63 % LA) and Camelina sativa oil (CSO, 30–35 % ALA), respectively. In the SFO arm, there was a significant genotype x diet interaction for the proportion of arachidonic acid in plasma phospholipids (p<0.001), disposition index (DI30) (p = 0.039), and for serum high‐sensitive c‐reactive protein (hs‐CRP, p = 0.029) after excluding the participants with hs‐CRP concentration of >10 mg/l and users of statins or anti‐inflammatory therapy. In the CSO arm, there were significant genotype x diet interactions for n‐3 polyunsaturated fatty acids, but not for the clinical characteristics. Conclusions: The FADS1 genotype modifies the response to high PUFA diets, especially to high‐LA diet. These findings suggest that approaches considering FADS variation might be useful in personalized dietary counseling.
Key Points
Proportions of PUFAs in plasma lipids and erythrocyte membranes are used as biomarkers of dietary intake of PUFAs, but fatty acid (FA) composition is also partly determined by genetic variants of the FA desaturase (FADS) gene cluster in chromosome11. Human FADS1 and FADS2 genes encode delta-5- and delta-6-desaturases (respectively), which catalyze key steps in the n-3 and n-6 lipid biosynthesis pathways. The frequencies of FADS cluster variants differ among global populations [12-15], which indicates the need for personalized and population-based approaches considering FADS genetic variation when investigating the effects of PUFA rich foods or supplements. In the current FADSDIET2 study, we aimed to investigate the interaction between FADS1 rs174550 genotypes and high dietary intakes of LA and ALA on the response of fatty acid composition of plasma PLs, and glucose-insulin homeostasis in more detail by performing an oral glucose tolerance test (OGTT). The current study, investigated both n-3 and n-6 PUFAs and included an n-6 arm with a LA enriched diet and an n-3 arm with an ALA enriched diet. Furthermore, the study replicated previous findings regarding the FADS1 rs174550 genotypes x high-LA diet interaction effects on low-grade inflammation estimated by hs-CRP.
In this randomized controlled clinical trial, genotype x diet interactions modifying proportions of circulating PUFAs in response to an 8-week high-LA SFO and high ALA CSO diets in participants with different FADS1 rs174550 genotypes (TT or CC) were found. It is well known that this genotype modifies proportions of PUFAs in plasma lipids in cross-sectional studies. The response to high-PUFA diets was modified by the genotype. That is worth of noting in future clinical trials investigating the health effects of plant- based sources of dietary PUFAs or supplements. Furthermore, a significant genotype x diet interaction for DI30, an estimate measure of β-cell function adjusted for insulin sensitivity, which has shown to be predictive for development of diabetes was found.
In the CSO arm, EPA and DPA plasma proportions were significantly increased only in the carriers of the TT genotype. These results are in line with earlier findings showing lower plasma proportions of EPA after a diet enriched in flaxseed oil on minor allele homozygotes for FADS1 and FADS2. Significant changes in PUFA pattern in this study might be related to low baseline dietary LA:ALA ratio of our participants. At baseline, the dietary intakes of LA and ALA were around 10 and 2.5 grams per day, respectively, resulting in a LA:ALA ratio of 4:1, which is low compared with the ratio e.g. in the U.S., where LA:ALA ratios of > 10:1 have been reported.
The study clearly confirms that genotype x diet interaction exists in the context of PUFA metabolism. Since circulating PUFAs have been strongly associated with e.g. risk of cardiovascular diseases and T2D this interaction might be important to consider when searching for the most optimal prevention strategies for the burden of these diseases. Besides of proportions of circulating PUFAs, the effect of genotype was reflected in serum hs-CRP and insulin secretion on 8-week SFO diet.