Physicians' Academy for Cardiovascular Education

Causal association between milk intake and cardiometabolic risk factors

Evidence for a causal association between milk intake and cardiometabolic disease outcomes using a two-sample Mendelian Randomization analysis in up to 1,904,220 individuals

Literature - Vimaleswaran KS, Zhou A, Cavadino A, et al., - Int J Obes 2021; doi: 10.1038/s41366-021-00841-2

Introduction and methods

A causal association was found between greater dairy intake and higher body mass index, but not for CVD [1-3]. It is not clear whether consumption of milk and dairy products has a beneficial or adverse effect on risk of CVD [4].

In Mendelian randomization studies that examined the association between milk intake and diseases, the SNP rs4988235 upstream of the gene for the lactase enzyme has been used as a marker of milk intake [5-7]. The lactase enzyme plays a role in the digestion of milk sugar lactose and is encoded by the lactase (LCT) gene. The SNP rs4988235 affects the transcription of LCT and differences in this SNP result in phenotypes of lactase. The T allele was associated with lactase persistence and increase LCT gene promoter activity.

This Mendelian Randomization study investigated the association between milk consumption and CVD, T2DM and cardio-metabolic risk factors, including measures of adiposity, blood pressure, and markers of chronic inflammation, lipid and glucose metabolism.

The study included data of 417, 236 individuals from 3 large population-based studies (British Birth cohort, Health Retirement Study and UK Biobank). Information on milk intake was available from the British Birth cohort and the UK Biobank. SNP rs4988235 was genotyped in the 3 cohorts. Summary statistics data from several large consortia-based studies (GIANT, Global Lipids, MAGIC, ICBP, DIAGRAM, CARDIOGRAM, EPIC-InterAct (n=1,486,984) were also used for the meta-analysis.

Main results


A large-scale meta-analysis showed that the T allele of the LCT SNP rs49883235 indexing for greater milk intake was associated with CV-related risk factors, such as BMI, LDL-c and total cholesterol. Two-sample Mendelian randomization analysis confirmed the association between genetically instrumented greater milk intake and higher BMI, lower LDL-c, total cholesterol and HDL-c.

‘Large intervention trials are needed to establish the causal link between high milk consumption and cardio-metabolic phenotypes before changes in dairy consumption could be recommended for the prevention of cardiometabolic traits’, according to the authors.


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