Biomarkers of dairy fat intake, incident cardiovascular disease, and all-cause mortality: A cohort study, systematic review, and meta-analysis

Background We aimed to investigate the association of serum pentadecanoic acid (15:0), a biomarker of dairy fat intake, with incident cardiovascular disease (CVD) and all-cause mortality in a Swedish cohort study. We also systematically reviewed studies of the association of dairy fat biomarkers (circulating or adipose tissue levels of 15:0, heptadecanoic acid [17:0], and trans-palmitoleic acid [t16:1n-7]) with CVD outcomes or all-cause mortality. Methods and findings We measured 15:0 in serum cholesterol esters at baseline in 4,150 Swedish adults (51% female, median age 60.5 years). During a median follow-up of 16.6 years, 578 incident CVD events and 676 deaths were identified using Swedish registers. In multivariable-adjusted models, higher 15:0 was associated with lower incident CVD risk in a linear dose-response manner (hazard ratio 0.75 per interquintile range; 95% confidence interval 0.61, 0.93, P = 0.009) and nonlinearly with all-cause mortality (P for nonlinearity = 0.03), with a nadir of mortality risk around median 15:0. In meta-analyses including our Swedish cohort and 17 cohort, case-cohort, or nested case-control studies, higher 15:0 and 17:0 but not t16:1n-7 were inversely associated with total CVD, with the relative risk of highest versus lowest tertile being 0.88 (0.78, 0.99), 0.86 (0.79, 0.93), and 1.01 (0.91, 1.12), respectively. Dairy fat biomarkers were not associated with all-cause mortality in meta-analyses, although there were <= 3 studies for each biomarker. Study limitations include the inability of the biomarkers to distinguish different types of dairy foods and that most studies in the meta-analyses (including our novel cohort study) only assessed biomarkers at baseline, which may increase the risk of misclassification of exposure levels. Conclusions In a meta-analysis of 18 observational studies including our new cohort study, higher levels of 15:0 and 17:0 were associated with lower CVD risk. Our findings support the need for clinical and experimental studies to elucidate the causality of these relationships and relevant biological mechanisms. Author summary Why was this study done? Many dietary guidelines recommend limiting dairy fat consumption in order to lower saturated fat intake and cardiovascular disease (CVD) risk. However, increasing evidence suggests that the health impact of dairy foods is more dependent on the type (e.g., cheese, yoghurt, milk, and butter) rather than the fat content, which has raised doubts if avoidance of dairy fats is beneficial for cardiovascular health. Dairy foods are a major source of nutrients, and their consumption is increasing worldwide; thus, it is important to advance our understanding of the impact of dairy fat on CVD risk. What did the researchers do and find? We measured dairy fat consumption using an objective biomarker, serum pentadecanoic acid (15:0), in 4,150 Swedish 60-year-olds and collected information about CVD events and deaths during a median follow-up of 16.6 years. When we accounted for known risk factors including demographics, lifestyle, and disease prevalence, the CVD risk was lowest for those with high levels of the dairy fat biomarker 15:0, while those with biomarker levels around the median had the lowest risk of all-cause mortality. We also conducted a systematic review and meta-analysis, and the combined evidence from 18 studies also showed higher levels of 2 dairy fat biomarkers (15:0 and heptadecanoic acid 17:0) were linked with lower risk of CVD, but not with all-cause mortality. What do these findings mean? The findings from our study using fatty acid biomarkers suggest that higher intake of dairy fat were associated with lower CVD risk in diverse populations including Sweden (a country with high dairy intake), though more trials are needed to understand if and how dairy foods protect cardiovascular health.

Automated summary

Serum pentadecanoic acid (15:0) levels were inversely associated with incident cardiovascular disease risk in a linear dose-response manner and nonlinearly with all-cause mortality, with a nadir of mortality risk around median 15:0 levels. Meta-analyses showed that higher levels of 15:0 and 17:0 were associated with lower risk of total cardiovascular disease, supporting the need for further research on dairy fat intake and cardiovascular health.