Eur J Nutr. , 2019., Dec 12. doi: 10.1007/s00394-019-02159-2.

Adipose tissue content of alpha-linolenic acid and development of peripheral artery disease: a Danish case-cohort study.

Bork CS Lasota AN Lundbye-Christensen S et al.

Abstract

PURPOSE: The aim of this study was to investigate the association between adipose tissue content of the plant-derived n-3 fatty acid, alpha-linolenic acid, and the rate of incident peripheral artery disease (PAD). METHODS:  We conducted a case-cohort study nested within the Danish Diet, Cancer and Health cohort (n = 57,053), which was established between 1993 and 1997. Potential PAD cases were identified using linkage with The Danish National Patient Register and all potential cases were validated. Adipose tissue samples from the buttock were collected at baseline and fatty acid composition was determined in cases and in a random sample (n = 3500) from the cohort by gas chromatography. Statistical analyses were performed using weighted Cox regression allowing for different baseline hazards among sexes. RESULTS:  During a median of 13.5 years of follow-up, we identified 863 PAD cases with complete information. The median adipose tissue content of ALA in the sub-cohort (n = 3197) was 0.84% (interquartile range 0.73-0.94%) of total fatty acids. In multivariate analyses including adjustment for established risk factors, we observed a U-shaped association between ALA in adipose tissue and rate of PAD, but the association was not statistically significant (P = 0.131). Similar pattern of associations were observed between ALA content in adipose tissue and the rate of PAD among men and women. CONCLUSIONS: We found indications of a U-shaped association between adipose tissue content of ALA and the rate of PAD, but the association was not statistically significant.

 

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Key Points

Peripheral artery disease (PAD) is an atherosclerotic manifestation characterized by stenosis and occlusion of the arteries, which may compromise blood supply to the lower extremities. ALA may be available for energy production, metabolization into longer-chain more unsaturated n-3 PUFAs or incorporation into cells and tissues. The content of ALA in adipose tissue is considered the gold standard for long-term exposure to ALA intake and metabolism. The objective of this study was to investigate the association between adipose tissue content of ALA and the rate of PAD. It was hypothesized that adipose tissue content of ALA would be inversely associated with the rate of PAD.

An indication of a U-shaped association between adipose tissue content of ALA and the rate of PAD with the lowest rate observed close to the median content in adipose tissue, but the association was not statistically significant was found. A previous case-cohort study based on the Diet, Cancer and Health cohort found a statistically significant U-shaped association between adipose tissue content of ALA and the rate of ischemic stroke due to large artery atherosclerosis in analyses including 297 cases.

ALA may be influenced by several factors from intake to incorporation into adipose tissue including competition between PUFAs for metabolism and incorporation into adipose tissue and potential genetic differences in the shared enzymes responsible for PUFA synthesis. This study reported a modest correlation between estimated intake of ALA and its content in adipose tissue within the sub-cohort, which may be due to a combination of measurement error of estimated intakes on one side and metabolism of ALA on the other side. Few previous studies have investigated the associations between other biomarkers such as ALA content in plasma or blood cells and PAD, and results have been inconsistent. However, direct comparison of previous biomarker studies of ALA should be done with caution because differences in ALA content in human tissue may be largely influenced by differences in the underlying dietary pattern. In conclusion, a U-shaped pattern of association between adipose tissue content of ALA and the rate of incident PAD among Danish middle-aged men and women, was noted but the association was not statistically significant.