Omega-3 fatty acids and risk of cardiovascular disease in Inuit: First prospective cohort study.

BACKGROUND AND AIMS: No prospective study have ever assessed if marine n-3 polyunsaturated fatty acids protect Inuit against cardiovascular disease as claimed. It is highly relevant as cardiovascular disease (CVD) incidence rates are rising concurrent with a westernization of diet. We aimed to assess the association between blood cell membrane phospholipid content of eicosapentaenoic acid and docosahexaenoic acid (EPA + DHA) on CVD risk in Inuit. METHODS: We used data from a cohort of adult Greenlanders with follow-up in national registers. The main outcome was fatal and non-fatal CVD incidence among participants without previous CVD. The continuous effect of EPA + DHA was calculated as incidence rate ratios (IRRs) using Poisson regression with age as time scale, adjusting for age, sex, genetic admixture, lifestyle and dietary risk factors. RESULTS: Out of 3095 eligible participants, 2924 were included. During a median follow-up of 9.7 years, 216 had their first CVD event (8.3 events/1000 person years). No association between EPA + DHA and CVD risk was seen, with IRR = 0.99 per percentage point EPA + DHA increase (95% CI: 0.95-1.03, p = 0.59). No association was seen with risk of ischemic heart disease (IHD) (IRR = 1.03, 95% CI: 0.97-1.09) and stroke (IRR = 0.98, 95% CI: 0.93-1.03) as separate outcomes or for intake of EPA and DHA. CONCLUSIONS: We can exclude that the CVD risk reduction is larger than 21% for individuals at the 75% EPA + DHA percentile compared to the 25% percentile. We need a larger sample size and/or longer follow-up to detect smaller effects and associations with IHD and/or stroke.

Genetic study of the Arctic CPT1A variant suggests that its effect on fatty acid levels is modulated by traditional Inuit diet.

Several recent studies have found signs of recent selection on the carnitine palmitoyl-transferase 1A (CPT1A) gene in the ancestors of Arctic populations likely as a result of their traditional diet. CPT1A is involved in fatty acid transportation and is known to affect circulating fatty acid profiles in Inuit as does the unique traditional diet rich in marine animals. We aimed to assess which fatty acids may have driven the selection of rs80356779, a c.1436C>T (p.(Pro479Leu)) variant in CPT1A, by analyzing a potential interaction between the variant and traditional Inuit diet. We included 3005 genome-wide genotyped individuals living in Greenland, who had blood cell membrane fatty acid levels measured. Consumption of 25 traditional food items was expressed as percentage of total energy intake. We tested for CPT1A × traditional diet interaction while taking relatedness and admixture into account. Increasing intakes of traditional diet was estimated to attenuate the effect of 479L on 20:3 omega-6 levels (p = 0.000399), but increase the effect of the variant on 22:5 omega-3 levels (p = 0.000963). The 479L effect on 22:5 omega-3 more than doubled in individuals with a high intake of traditional diet (90% percentile) compared with individuals with a low intake (10% percentile). Similar results were found when assessing interactions with marine foods. Our results suggest that the association between traditional diet and blood cell fatty acid composition is affected by the CPT1A genotype, or other variants in linkage disequilibrium, and support the hypothesis that omega-3 fatty acids may have been important for adaptation to the Arctic diet.