Background:
Laboratory studies suggest that ω3 and ω6 polyunsaturated fatty acids (PUFA) may have divergent effects on the development of obesity. Epidemiologic studies comparing the associations for ω3 and ω6 PUFA are limited.
Objective:
We prospectively examined whether the baseline proportions of ω3 and ω6 PUFAs on erythrocyte membranes were associated with the risk of becoming overweight and changes in body weight in the Women’s Health Study (WHS).
Methods:
We identified WHS participants in a previous nested case-control study of hypertension who reported a body mass index (BMI) <25 kg/m
2
at baseline. Baseline fatty acid (FA) composition of erythrocyte membranes was measured as biomarkers of dietary FA intake using gas chromatography. Women who subsequently reported a BMI ≥25 kg/m
2
during follow-up were defined as becoming overweight. Body weight change was calculated as the difference in reported body weight from baseline to annual follow-up questionnaires.
Results:
Among 534 women with baseline BMI <25 kg/m
2
, 186 became overweight during an average of 10 years of follow-up. After initial adjustment for age, race, randomized treatment, the hazard ratios (HR) and 95% confidence interval (95% CI) for becoming overweight across increasing quartiles of erythrocyte PUFA were 1.00, 0.77 (0.49-1.21), 1.12 (0.75-1.67), and 1.19 (0.79-1.77) for
cis
ω6 PUFA (p, trend: 0.31), 1.00, 0.90 (0.61-1.31), 0.76 (0.51-1.13), 0.71 (0.45-1.10) for
cis
ω3 PUFA (p, trend: 0.09), and 1.00, 1.37 (0.84-2.22), 1.57 (1.01-2.43), and 1.58 (1.01-2.46) for ω6 to ω3 PUFA ratio (p, trend: 0.046). Additional adjustment for lifestyle and dietary factors did not substantially attenuate these associations, with HR (95% CI) of 1.00, 1.26 (0.76-2.08), 1.44 (0.91-2.28), and 1.56 (0.97-2.51) across increasing quartiles of ω6 to ω3 PUFA ratio (p, trend: 0.064). Analysis of longitudinal change in body weight showed similar associations. After multivariable adjustment, the mean±standard error of weight gain over an average of 10 years of follow-up across increasing quartiles of erythrocyte PUFA were 2.34±0.49, 1.92±0.53, 2.86±0.54, and 3.10±0.53 kg for
cis
ω6 PUFA (p, trend: 0.04), 2.97±0.52, 2.60±0.53, 2.74±0.53, 2.16±0.51 kg for
cis
ω3 PUFA (p, trend: 0.095), and 2.13±0.51, 2.65±0.54, 2.77±0.53, 2.98±0.52 kg for ω6 to ω3 PUFA ratio (p, trend: 0.05).
trans
PUFA 18:2 was not associated with the risk of becoming overweight or longitudinal weight gain. Analyses of joint categories of ω3 and ω6 PUFA did not show significant interaction
.
Conclusion:
In this prospective study, we found suggestive evidence that the proportion of
cis
ω6 PUFA on erythrocyte membrane was positively associated, and
cis
ω3 PUFA inversely associated, with the risk of becoming overweight and weight gain in initially normal-weight women.