While polyunsaturated fatty acids (PUFAs) are widely considered to be among the “good” dietary fats, clear evidence of their health benefits in humans is surprisingly limited.  One of the likely causes of this ambiguity is the complexity of PUFA metabolism in the context of overall diet in humans. In a recent article, members of the Voruganti laboratory and their colleagues review how genetic variation (polymorphisms) can affect PUFA metabolism and cause different outcomes with respect to cardiovascular disease risk, type 2 diabetes, and fatty liver. Such variation is often not accounted for when interpreting clinical trials and this can lead to mixed or unclear results.

One example of how genetic variation affects potential efficacy of PUFAs is found with the fatty acid desaturase (FADS) gene cluster. Polymorphisms in these genes impact PUFA metabolism; interestingly, there is a strong correlation between specific polymorphisms and race/ethnicity that may reflect the effects of ancestral diet on the evolution of individuals’ metabolism. Similar results have been seen for other FADS-associated genes. One consequence of these differences is that the racial makeup of the study population can impact the results, in some cases leading to conflicting assessments when comparing studies based on different populations.

Another complicating factor is that even among “good” fats, some PUFAs (the so-called w-3 PUFAs) are thought to be better than others (the w-6 PUFAs), at least with respect to their anti-inflammatory properties. This applies to both the individual amount of each PUFA and to the relative amount (i.e., w-3:w-6 ratio) in the diet, with these ideal amounts also subject to the genetic differences noted above.

Overall, the authors stress that proper design and interpretation of clinical trials is crucial to unequivocally demonstrating health properties and establishing ideal dosages of PUFAs. This entails carefully accounting for study participants’ race/ethnicity, genetics, and dietary habits, especially when comparing results across multiple studies.

Panda C, Varadharaj S, Voruganti VS (2022). PUFA, genotypes and risk for cardiovascular disease. Prostaglandins Leukot Essent Fatty Acids, 176:102377.

Posted April 4, 2022