Abstract
Intake of the plant-derived omega-3 fatty acid alpha-linolenic acid (ALA) has been associated with anti-atherosclerotic properties. However, information on the association between ALA intake and development of peripheral artery disease (PAD) is lacking. In this follow-up study, we investigated the association between dietary intake of ALA and the rate of PAD among middle-aged Danish men and women enrolled into the Danish Diet, Cancer and Health cohort between 1993 and 1997. Incident PAD cases were identified through the Danish National Patient Register. Intake of ALA was assessed using a validated food frequency questionnaire. Statistical analyses were performed using Cox proportional hazard regression allowing for separate baseline hazards among sexes and adjusted for established risk factors for PAD. During a median of 13.6 years of follow-up, we identified 950 valid cases of PAD with complete information on covariates. The median energy-adjusted ALA intake within the cohort was 1.76 g/d (95% central range: 0.94-3.28). In multivariable analyses, we found no statistically significant association between intake of ALA and the rate of PAD (P = 0.339). Also, no statistically significant associations were observed in analyses including additional adjustment for co-morbidities and in sex-specific analyses. In supplemental analyses with additional adjustment for potential dietary risk factors, we found a weak inverse association to PAD with ALA intake above the median, but the association was not statistically significant (P = 0.314). In conclusion, dietary intake of ALA was not consistently associated with decreased risk of PAD.
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Key Points
The majority of previous follow-up studies investigating the association between ALA intake and the risk of atherosclerotic cardiovascular disease have focused on coronary heart disease (CHD). Some cohort studies have reported inverse associations between ALA intake and CHD risk, but the results have not been consistent. The objective of this study was to investigate the association between intake of ALA and the risk of peripheral artery disease (PAD).
In this large follow-up study, indications of a weak inverse U-shaped association between ALA intake and the rate of PAD in analyses including adjustment for established risk factors and indications of a weak inverse association between ALA intake and the rate of PAD above the median intake in analyses including adjustment for established risk factors and dietary risk factors were found. However, none of these associations were statistically significant. Given the relatively weak and statistically non-significant associations observed, this study suggests that dietary intake of ALA is not appreciably associated with the risk of PAD within this population of middle-aged Danish men and women. It should be stressed that this study did not investigate the potential effect of a Mediterranean diet on PAD risk, but the results may indicate that the possible protective effect provided by the Mediterranean dietary pattern on PAD and major cardiovascular events is unlikely to be ascribed to ALA intake.
This study had some limitations. Participants were followed by linkage with nationwide registries with very limited loss to follow-up, which limits the potential of selection bias. Information on ALA intake was obtained using a self-administered FFQ and measurement error is inevitable, but because of the temporality in a follow-up study, exposure measurement error probably occurred at random, which generally leads to an underestimation of the true association and loss of statistical power. The FFQ used in this study was not specifically developed to assess ALA intake. Further, information on diet was only available at baseline and changes in dietary habits during follow-up may have occurred. Thus, repeated dietary measurements would have been preferable to limit random measurement error and to capture potential changes in dietary habits over time.
Previous studies have suggested that high intakes of the major n-6 PUFA linoleic acid and LC n-3 PUFAs may lower the conversion efficiency of ALA into LC n-3 PUFAs due to inhibition on shared enzymes. The median intake of LC n-3 PUFAs in this cohort was 0.7 g/d, which was higher than in cohort studies reporting inverse associations between ALA intake and CHD and this may be of importance for because a large study has suggested that ALA may reduce CHD risk in particular when intake of LC n-3 is low. Further well-powered studies investigating the role of genetics and intake of LC n-3 and n-6 PUFAs on the association between ALA and the risk of atherosclerotic cardiovascular disease are warranted.