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Linoleic Acid Study: Inflammatory Response is Gene Dependent

The effects of linoleic acid on the human body are largely dependent on genes, a new study from the University of Eastern Finland shows, published in the American Journal of Clinical Nutrition. Researchers found that people carrying different variants of the FADS1 gene had a different inflammatory response and different changes in their fasting glucose levels when supplementing their diet by linoleic acid rich sunflower oil. This was the first time these associations were studied in humans.

According to Postdoctoral Researcher Maria Lankinen from the University of Eastern Finland, the findings warrant speculation on whether the recommended intake of linoleic acid – and possibly other fatty acids, too – should be tailored to match a person’s genes. “However, further research is needed before we can make any recommendations based on genes,” Postdoctoral Researcher Lankinen says.

The FADS1 gene regulates the body’s fatty acid metabolism and also plays a role in glucose metabolism. A person’s diet, in turn, has a major impact on the concentrations of different fatty acids in the body. Linoleic acid is found in plant-based oils, nuts and seeds, and it is the most common polyunsaturated omega 6 fatty acid.

A high intake and high levels of linoleic acid in the blood have been associated with a reduced risk of type 2 diabetes and cardiovascular disease. On the other hand, however, the metabolites of linoleic acid can mediate inflammation, which is why a high intake of linoleic acid is regarded as a plausible factor contributing to low-grade inflammatory state. According to the newly published study, these contradictory observations could be explained by genetic differences.

The study explored whether point mutations in rs174550 of the FADS1 gene modify the effects of linoleic acid on serum fatty acid composition and on fasting glucose, insulin and CRP levels. These were analyzed in more than 1,300 middle-aged men participating in the METSIM (Metabolic Syndrome in Men) Study. In addition, 60 men participated in the FADSDIET intervention for carriers of two different gene variants. Over the course of four weeks, they supplemented their daily diet by 30-50 ml of linoleic acid rich sunflower oil. Selecting the participants on the basis of their genes makes this a unique research setting, which provides information on the interactions of diet with genes.

Results/ In the FADSDIET trial, the plasma linoleic (LA) proportion increased in both genotype groups in response to an LA-enriched diet.

  • Responses in concentrations of serum hsCRP and plasma fasting glucose and the proportion of arachidonic acid (20:4n–6) in plasma phospholipids and cholesteryl esters differed between genotype groups (interaction of diet × genotype, P < 0.05).
  • In TT homozygous subjects, plasma eicosanoid concentrations correlated with the arachidonic acid proportion in plasma and with hsCRP (r = 0.4–0.7, P < 0.05), whereas in the CC genotype there were no correlations.

The findings indicate that the effects of linoleic acid on the human body are largely dependent on which variant of the FADS1 gene a person is carrying. This has an effect on, for example, how effectively a linoleic acid supplement can lower fasting glucose levels. Moreover, depending on the gene variant, increased intake of linoleic acid can make a person’s CRP levels go either up or down. The FADS1 gene variant also had an effect on the levels of inflammation mediators, which are created from the metabolites of linoleic acid and other omega 6 fatty acids.

Conclusion/ The findings show that the FADS1 genotype modifies metabolic responses to dietary LA. The emerging concept that personalized dietary counseling should be modified by the FADS1 genotype needs to be tested in larger randomized trials.

Source: Maria A Lankinen, Alexander Fauland, Bun-ichi Shimizu, Jyrki Ågren, Craig E Wheelock, Markku Laakso, Ursula Schwab, Jussi Pihlajamäki. Inflammatory response to dietary linoleic acid depends on FADS1 genotype. The American Journal of Clinical Nutrition, 2019; DOI: 10.1093/ajcn/nqy287


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