Prevention of covid-19 and other acute respiratory infections with cod liver oil supplementation, a low dose vitamin D supplement: quadruple blinded, randomised placebo controlled trial.

OBJECTIVE: To determine if daily supplementation with cod liver oil, a low dose vitamin D supplement, in winter, prevents SARS-CoV-2 infection, serious covid-19, or other acute respiratory infections in adults in Norway. DESIGN: Quadruple blinded, randomised placebo controlled trial. SETTING: Norway, 10 November 2020 to 2 June 2021. PARTICIPANTS: 34 601 adults (aged 18-75 years), not taking daily vitamin D supplements. INTERVENTION: 5 mL/day of cod liver oil (10 µg of vitamin D, n=17 278) or placebo (n=17 323) for up to six months. MAIN OUTCOME MEASURES: Four co-primary endpoints were predefined: the first was a positive SARS-CoV-2 test result determined by reverse transcriptase-quantitative polymerase chain reaction and the second was serious covid-19, defined as self-reported dyspnoea, admission to hospital, or death. Other acute respiratory infections were indicated by the third and fourth co-primary endpoints: a negative SARS-CoV-2 test result and self-reported symptoms. Side effects related to the supplementation were self-reported. The fallback method was used to handle multiple comparisons. RESULTS: Supplementation with cod liver oil was not associated with a reduced risk of any of the co-primary endpoints. Participants took the supplement (cod liver oil or placebo) for a median of 164 days, and 227 (1.31%) participants in the cod liver oil group and 228 (1.32%) participants in the placebo group had a positive SARS-CoV-2 test result (relative risk 1.00, multiple comparison adjusted confidence interval 0.82 to 1.22). Serious covid-19 was identified in 121 (0.70%) participants in the cod liver oil group and in 101 (0.58%) participants in the placebo group (1.20, 0.87 to 1.65). 8546 (49.46%) and 8565 (49.44%) participants in the cod liver oil and placebo groups, respectively, had ≥1 negative SARS-CoV-2 test results (1.00, 0.97 to 1.04). 3964 (22.94%) and 3834 (22.13%) participants in the cod liver oil and placebo groups, respectively, reported ≥1 acute respiratory infections (1.04, 0.97 to 1.11). Only low grade side effects were reported in the cod liver oil and placebo groups. CONCLUSION: Supplementation with cod liver oil in the winter did not reduce the incidence of SARS-CoV-2 infection, serious covid-19, or other acute respiratory infections compared with placebo. TRIAL REGISTRATION: ClinicalTrials.gov NCT04609423.

Coffee consumption and risk of breast cancer: A Mendelian randomization study.

BACKGROUND: Observational studies have reported either null or weak protective associations for coffee consumption and risk of breast cancer. METHODS: We conducted a two-sample Mendelian randomization (MR) analysis to evaluate the relationship between coffee consumption and breast cancer risk using 33 single-nucleotide polymorphisms (SNPs) associated with coffee consumption from a genome-wide association (GWA) study on 212,119 female UK Biobank participants of White British ancestry. Risk estimates for breast cancer were retrieved from publicly available GWA summary statistics from the Breast Cancer Association Consortium (BCAC) on 122,977 cases (of which 69,501 were estrogen receptor (ER)-positive, 21,468 ER-negative) and 105,974 controls of European ancestry. Random-effects inverse variance weighted (IVW) MR analyses were performed along with several sensitivity analyses to assess the impact of potential MR assumption violations. RESULTS: One cup per day increase in genetically predicted coffee consumption in women was not associated with risk of total (IVW random-effects; odds ratio (OR): 0.91, 95% confidence intervals (CI): 0.80-1.02, P: 0.12, P for instrument heterogeneity: 7.17e-13), ER-positive (OR = 0.90, 95% CI: 0.79-1.02, P: 0.09) and ER-negative breast cancer (OR: 0.88, 95% CI: 0.75-1.03, P: 0.12). Null associations were also found in the sensitivity analyses using MR-Egger (total breast cancer; OR: 1.00, 95% CI: 0.80-1.25), weighted median (OR: 0.97, 95% CI: 0.89-1.05) and weighted mode (OR: 1.00, CI: 0.93-1.07). CONCLUSIONS: The results of this large MR study do not support an association of genetically predicted coffee consumption on breast cancer risk, but we cannot rule out existence of a weak association.

Vitamin D intake, month the mammogram was taken and mammographic density in Norwegian women aged 50-69.

BACKGROUND: The role of vitamin D in breast cancer etiology is unclear. There is some, but inconsistent, evidence that vitamin D is associated with both breast cancer risk and mammographic density (MD). We evaluated the associations of MD with month the mammogram was taken, and with vitamin D intake, in a population of women from Norway--a country with limited sunlight exposure for a large part of the year. METHODS: 3114 women aged 50-69, who participated in the Norwegian Breast Cancer Screening Program (NBCSP) in 2004 or 2006/07, completed risk factor and food frequency (FFQ) questionnaires. Dietary and total (dietary plus supplements) vitamin D, calcium and energy intakes were estimated by the FFQ. Month when the mammogram was taken was recorded on the mammogram. Percent MD was assessed using a computer assisted method (Madena, University of Southern California) after digitization of the films. Linear regression models were used to investigate percent MD associations with month the mammogram was taken, and vitamin D and calcium intakes, adjusting for age, body mass index (BMI), study year, estrogen and progestin therapy (EPT), education, parity, calcium intakes and energy intakes. RESULTS: There was no statistical significant association between the month the mammogram was taken and percent MD. Overall, there was no association between percent MD and quartiles of total or dietary vitamin D intakes, or of calcium intake. However, analysis restricted to women aged <55 years revealed a suggestive inverse association between total vitamin D intake and percent MD (p for trend = 0.03). CONCLUSION: Overall, we found no strong evidence that month the mammogram was taken was associated with percent MD. We found no inverse association between vitamin D intake and percent MD overall, but observed a suggestive inverse association between dietary vitamin D and MD for women less than 55 years old.