Search Results (6)

Recent cohort studies indicate a potential role of the antioxidant α-tocopherol in reducing bone loss and risk of fractures, especially hip fractures. We performed a Mendelian randomization investigation of the associations of circulating α-tocopherol with estimated bone mineral density (eBMD) using heel ultrasound and fractures, identified from hospital records or by self-reports and excluding minor fractures. Circulating α-tocopherol was instrumented by three genetic variants associated with α-tocopherol levels at p < 5 × 10⁻⁸ in a genome-wide association meta-analysis of 7781 participants of European ancestry. Summary-level data for the genetic associations with eBMD in 426,824 individuals and with fracture (53,184 cases and 373,611 non-cases) were acquired from the UK Biobank. Two of the three genetic variants were strongly associated with eBMD. In inverse-variance weighted analysis, a genetically predicted one-standard-deviation increase of circulating α-tocopherol was associated with 0.07 (95% confidence interval, 0.05 to 0.09) g/cm² increase in BMD, which corresponds to a >10% higher BMD. Genetically predicted circulating α-tocopherol was not associated with odds of any fracture (odds ratio 0.97, 95% confidence interval, 0.91 to 1.05). In conclusion, our results strongly strengthen a causal link between increased circulating α-tocopherol and greater BMD. Both an intervention study in those with a low dietary intake of α-tocopherol is warranted and a Mendelian randomization study with fragility fractures as an outcome. Full article

Results from several studies show that only obese, unfit subjects, but not obese, fit subjects, are at higher mortality risk than are normal-weight fit subjects. The aim of the study was two-fold: (1) to examine the differences in C-reactive protein levels across different metabolic phenotypes (healthy and unhealthy) of weight status and (2) ascertain whether high levels of cardiorespiratory fitness (CRF) attenuate the association of C-reactive protein and metabolic phenotypes of weight status. This was a pooled study, which included data from three cross-sectional projects (1706 youth (921 girls) aged 12–18 years). We used a Shuttle run test to assess CRF. Adolescents were classified into six metabolic phenotypes (healthy and unhealthy) of weight status (non-overweight, overweight and obese), based on age- and sex-specific cutoff points for triglycerides, systolic blood pressure, HDL-cholesterol, glucose and body mass index. High-sensitivity assays were used to obtain the C-reactive protein as inflammatory biomarker. After adjustment for potential confounders (age, sex, pubertal stage and country), the analysis of covariance (ANCOVA) shows that C-reactive protein is directly associated with metabolic phenotypes of weight status. Subjects with obesity, regardless of their metabolic profile, had higher levels of C-reactive protein Z-score. In addition, (after adjustments for potential confounders) a two-way ANCOVA showed that high levels of CRF attenuated the associations of C-reactive protein levels in metabolic healthy non-overweight and in adolescents with obesity. In conclusion, higher CRF levels may attenuate the detrimental association between obesity and C-reactive protein independently of metabolic phenotype. Findings from this study are important for prevention, clinical practice on issues associated with adiposity and metabolic disorders. Full article

Mortality in relation to type of milk intake is unclear. We present mortality rates by intake of non-fermented milk fat content type and examine the degree of bias when other fat content types of non-fermented milk are kept in the reference category. For this purpose, we used a longitudinal cohort consisting of 61,433 women who had been administered food frequency questionnaires in 1987–1990 and in 1997, and analyzed time to death. Non-fermented milk consumption was divided into low ≤0.5%, medium 1.5%, or high fat 3%. For each specific type of milk, the first analysis (A) is restricted to those who consumed less than one serving per day of the other milk subtypes. In the second analysis (B), everyone is retained, i.e., leading to a reference category “contaminated” with other milk consumers. During follow-up, 22,391 women died. Highest (≥3 glasses/day) vs. lowest consumption category of milk (<1 glass/day) with 0.5% fat content was associated with a multivariable hazard ratio (HR) of 1.71 (95%CI 1.57–1.86) in analysis A, whereas the same comparison with a “contaminated” reference category in analysis B provided a HR of 1.34 (95%CI 1.24–1.45), p-value for homogeneity <0.0001. The corresponding HRs for 1.5% fat milk were: 1.82 (95%CI 1.63–2.04) and 1.38 (95%CI 1.25–1.51), and for 3% fat milk 1.95 (95%CI 1.77–2.15) and 1.40 (95%CI 1.29–1.52). HR for ≥3 glasses/day of total milk was 1.95 (95%CI 1.84–2.06). We observe a higher mortality in women with high milk consumption, irrespective of milk fat content. A “contaminated” reference group substantially attenuates the actual estimates. Full article

Whether vitamin D insufficiency is a contributing cause of depression remains unclear. We assessed whether serum 25-hydroxyvitamin D (S-25OHD) concentrations, the clinical marker of vitamin D status, were associated with major depression using Mendelian randomization. We used summary statistics data for six single-nucleotide polymorphisms significantly associated with S-25OHD concentrations in the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits (SUNLIGHT) consortium and the corresponding data for major depression (n = 59,851 cases and 113,154 controls) from the Psychiatric Genomics Consortium. Genetically predicted S-25OHD concentrations were not associated with major depression. The odds ratio per genetically predicted one standard deviation decrease in S-25OHD concentrations was 1.02 (95% confidence interval 0.97–1.08; p = 0.44). The results of this study indicate that genetically lowered S-25OHD concentrations are not associated with increased risk of developing major depression. Full article

We conducted Mendelian randomization analyses to investigate the associations of serum parathyroid hormone (S-PTH) and serum 25-hydroxyvitamin D (S-25OHD) concentrations with Alzheimer’s disease (AD). Five and seven single nucleotide polymorphisms associated with S-PTH and S-25OHD concentrations, respectively, were used as instrumental variables. Data for AD were acquired from the International Genomics of Alzheimer’s Project (17,008 AD cases and 37,154 controls). Genetically higher S-PTH concentrations were not associated with AD (odds ratio per standard deviation increase in S-PTH = 1.11; 95% CI 0.97–1.26; p = 0.12). In contrast, all seven 25OHD-increasing alleles were inversely associated with AD and two of the associations were statistically significant (p < 0.05). The odds ratio of AD per genetically-predicted one standard deviation increase in S-25OHD was 0.86 (95% CI 0.78–0.94; p = 0.002). This study provides evidence that vitamin D may play a role in AD but found no significant association between S-PTH and AD. Full article

Results from epidemiological studies of milk consumption and mortality are inconsistent. We conducted a systematic review and meta-analysis of prospective studies assessing the association of non-fermented and fermented milk consumption with mortality from all causes, cardiovascular disease, and cancer. PubMed was searched until August 2015. A two-stage, random-effects, dose-response meta-analysis was used to combine study-specific results. Heterogeneity among studies was assessed with the I² statistic. During follow-up periods ranging from 4.1 to 25 years, 70,743 deaths occurred among 367,505 participants. The range of non-fermented and fermented milk consumption and the shape of the associations between milk consumption and mortality differed considerably between studies. There was substantial heterogeneity among studies of non-fermented milk consumption in relation to mortality from all causes (12 studies; I² = 94%), cardiovascular disease (five studies; I² = 93%), and cancer (four studies; I² = 75%) as well as among studies of fermented milk consumption and all-cause mortality (seven studies; I² = 88%). Thus, estimating pooled hazard ratios was not appropriate. Heterogeneity among studies was observed in most subgroups defined by sex, country, and study quality. In conclusion, we observed no consistent association between milk consumption and all-cause or cause-specific mortality. Full article