It has been suggested that vitamin D3 supplementation could be a potentially promising and safe approach to reduce risk of COVID-19 infections and deaths. Meta-analyses of randomised clinical trials (RCTs) have shown that vitamin D3 supplementation reduces the risk of acute respiratory tract infections.
In the current study, a team of researchers from Germany Cancer Research Center assessed the prevalence of vitamin D insufficiency and deficiency, and their association with mortality from respiratory diseases during 15 years of follow-up in a cohort of 9548 adults aged 50–75 years from Saarland, Germany.
They found that vitamin D insufficiency and deficiency (25-hydroxyvitamin D blood levels of 30–50 and <30 nmol/L, respectively) were found to be common (44% and 15%, respectively), and compared to those with sufficient status, participants with vitamin D insufficiency and deficiency had strongly increased respiratory mortality.
Overall, 41% (95% confidence interval: 20–58%) of respiratory disease mortality was statistically attributable to vitamin D insufficiency or deficiency.
The authors conclude that vitamin D insufficiency and deficiency are common and account for a large proportion of respiratory disease mortality in older adults, supporting the hypothesis that vitamin D3 supplementation could be helpful to limit the burden of the COVID-19 pandemic, particularly among women.
The report concludes: "In this large population-based cohort study from Saarland, Germany, the majority of participants aged 50–75 years at baseline had vitamin D insufficiency or deficiency, and these conditions were associated with increased mortality.
"In particular, mortality from respiratory diseases was increased by 2.1- and 3.0-fold in subjects with vitamin D insufficiency or deficiency, respectively, compared to participants with sufficient vitamin D status. Significant associations with respiratory disease mortality were seen among both women and men, but they were particularly strong for women.
"Overall, 41% of deaths from respiratory diseases were statistically attributable to vitamin D insufficiency or deficiency and could possibly be avoided by overcoming these conditions, assuming causality of the association."
However, the cause and effect relationship hasn't been proven in this study.
"The assumption of causality of vitamin D3 effects on mortality obviously requires most careful discussion," the report adds.
"Although we made the best attempts to adjust potential confounding factors, we cannot exclude the possibility of residual confounding by imperfect measurement of confounding variables, such as smoking or physical activity, or omission of unknown confounders.
"Interpretation of the evidence is further complicated by the fact that vitamin D deficiency could be considered both a consequence of poor health as well as a risk factor for increased vulnerability to acute disease and poor outcomes of chronic diseases among people with poor health.
"Our findings therefore require critical discussion in the light of additional criteria and evidence, such as biological mechanisms and plausibility, and, in particular, in the light of data from RCTs providing vitamin D3 supplementation."
The study is of note as no previous vitamin D3 supplementation RCTs have addressed mortality from respiratory disease as the primary endpoint, and no meta-analysis of results for this specific endpoint have been reported, which most likely reflects the relatively small share of deaths from respiratory diseases among all deaths.
The COVID-19 Debate
The authors add their voices to the ongoing debate around whether vitamin D supplementation should be utilised in order to limit the number of deaths caused by the COVID-19 pandemic.
"The Endocrine Society recommends 1500–2000 IU vitamin D3/day for adults of any age at high risk for vitamin D deficiency. The costs for such supplementation are in the order of 30€ per person per year, or even half that amount when sufficient vitamin D supply is ensured by carefully dosed sun exposure during the summer months.
"Along with expected savings from prevented respiratory and other diseases, this would make vitamin D3 Nutrients 2020, 12, 2488 11 of 12 supplementation a particularly cost-effective and most likely cost-saving measure, whose currently still widely neglected potential should receive increased attention in the debate on how to fight against the COVID-19 pandemic."
The ESTHER Study
This investigation was based on the ESTHER study (German name: Epidemiologische Studie der Verhütung, Früherkennung und optimierten Therapie chronischer Erkrankungen in der älteren Bevölkerung), an ongoing statewide cohort study from Saarland, Germany.
In this study, 9940 men and women, aged 50–75 years at baseline, were recruited by their general practitioners during a routine health check-up between 2000 and 2002. Blood samples were taken at baseline at the general practitioners’ offices. Information on socio-demographic and lifestyle characteristics and medical history were obtained by questionnaires from participants and their general practitioners.
Overall, 2363 (24.7%) study participants died during a median of 15.3 years of follow-up, of whom 815, 825 and 123 died from cardiovascular disease (CVD), cancer and respiratory disease, respectively.
Data revealed mortality from respiratory diseases was consistently highest among participants with vitamin D deficiency and consistently lowest among those with sufficient vitamin D levels throughout up to 16.5 years of follow-up.
Schöttker. B., et al
"Vitamin D Insufficiency and Deficiency and Mortality from Respiratory Diseases in a Cohort of Older Adults: Potential for Limiting the Death Toll during and beyond the COVID-19 Pandemic?"