Higher milk intake has been associated with a lower stroke risk, but not with risk of CHD. Residual confounding or reverse causation cannot be excluded. Therefore, we estimated the causal association of milk consumption with stroke and CHD risk through instrumental variable (IV) and gene-outcome analyses. IV analysis included 29 328 participants (4611 stroke; 9828 CHD) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD (eight European countries) and European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) case-cohort studies. rs4988235, a lactase persistence (LP) SNP which enables digestion of lactose in adulthood was used as genetic instrument. Intake of milk was first regressed on rs4988235 in a linear regression model. Next, associations of genetically predicted milk consumption with stroke and CHD were estimated using Prentice-weighted Cox regression. Gene-outcome analysis included 777 024 participants (50 804 cases) from MEGASTROKE (including EPIC-CVD), UK Biobank and EPIC-NL for stroke, and 483 966 participants (61 612 cases) from CARDIoGRAM, UK Biobank, EPIC-CVD and EPIC-NL for CHD. In IV analyses, each additional LP allele was associated with a higher intake of milk in EPIC-CVD (β = 13·7 g/d; 95 % CI 8·4, 19·1) and EPIC-NL (36·8 g/d; 95 % CI 20·0, 53·5). Genetically predicted milk intake was not associated with stroke (HR per 25 g/d 1·05; 95 % CI 0·94, 1·16) or CHD (1·02; 95 % CI 0·96, 1·08). In gene-outcome analyses, there was no association of rs4988235 with risk of stroke (OR 1·02; 95 % CI 0·99, 1·05) or CHD (OR 0·99; 95 % CI 0·95, 1·03). Current Mendelian randomisation analysis does not provide evidence for a causal inverse relationship between milk consumption and stroke or CHD risk.

Rapid selection of a genetic variant that confers continuous life-long lactase production in Europeans (LCT-13910 C/T) has been attributed to the advantages of acquiring nutrients from consuming milk without the disadvantages of lactose malabsorption. Individuals with this genetic lactase persistence (LP) variant generally consume more milk and have been shown to have higher levels of serum vitamin D. Vitamin D is the principal regulator of Ca absorption and its synthesis in skin is dependent on UVB exposure. The primary aim of the present study was to compare serum vitamin D concentrations with LP variant and to control for UVB exposure. Data from over 100 000 individuals living in Norway, a country with low UVB exposure, was retrospectively retrieved for comparison of genetic LP variant, serum 25-hydroxyvitamin D (25(OH)D) concentration and the time of year when serum samples were taken. For comparison, a similar analysis was performed with a natural dairy micronutrient, namely vitamin B12. It was found that individuals with the genetic LP variant had considerably higher levels of serum 25(OH)D (P < 2 × 10−16, Cohen's d = 0·73) but lower levels of vitamin B12 (P < 2 × 10−16, Cohen's d = 0·11), compared with genetic lactase non-persistent individuals, even when controlled for seasonality, age and sex. The difference in serum 25(OH)D levels did not diminish in summer months, showing the role of vitamin D in LP variant selection in areas of low UVB irradiation. LP variant selection advantage through acquiring another dairy micronutrient, vitamin B12, was not observed.

This study examines if lactase non-persistent (LNP) children and adolescents differ from those who are lactase persistent (LP) as regards milk avoidance and Ca intake. We also studied potential differences in anthropometric features related to obesity, and examined if milk avoidance is associated with lactase-persistence status. Additionally, we aimed to determine if heterozygous subjects showed an intermediary phenotype as regards Ca intake. Furthermore, we tested if LP and LNP influence vitamin D intake. The European Youth Heart Study is an ongoing international, multi-centre cohort study primarily designed to address CVD risk factors. Children (n 298, mean age 9·6 years) and adolescents (n 386, mean age 15·6 years) belonging to the Swedish part of the European Youth Heart Study were genotyped for the LCT-13910 C > T polymorphism. Mendelian randomisation was used. Milk avoidance was significantly more common in LNP adolescents (OR 3·2; 95% CI 1·5, 7·3). LP subjects had higher milk consumption (P < 0·001). Accordingly, energy consumption derived from milk and Ca intake was lower in LNP (P < 0·05 and P < 0·001, respectively). Heterozygous subjects did not show an intermediary phenotype concerning milk consumption. LP or LNP status did not affect vitamin D intake or anthropometric variables. LNP in children and adolescents is associated with reduced intake of milk and some milk-product-related nutritional components, in particular Ca. This reduced intake did not affect the studied anthropometric variables, indicators of body fat or estimated vitamin D intake. However, independently of genotype, age and sex, daily vitamin D intake was below the recommended intakes. Milk avoidance among adolescents but not children was associated with LNP.