Hydroxyvitamin d 25
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The Role of Serum 25-Hydroxyvitamin D in Health Outcomes
Cardiovascular Disease and 25-Hydroxyvitamin D
Inverse Association with Cardiovascular Events and Mortality
Research has consistently shown an inverse relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and cardiovascular disease (CVD) outcomes. A meta-analysis of 34 studies involving 180,667 participants found that each 10 ng/mL increase in 25(OH)D was associated with a 10% reduction in total CVD events and a 12% reduction in CVD mortality1. Another study involving 10,170 individuals from the Danish general population reported that lower 25(OH)D levels were linked to a higher risk of ischemic heart disease, myocardial infarction, and early death5.
Cancer Risk and 25-Hydroxyvitamin D
Mixed Evidence on Cancer Incidence and Mortality
The relationship between 25(OH)D levels and cancer risk is complex and varies by cancer type. A systematic review of Mendelian randomization studies found no significant associations between genetically predicted 25(OH)D levels and the risk of total cancer or specific cancers such as breast, prostate, colorectal, and lung cancers2. However, a pooled analysis of two randomized trials and a prospective cohort study indicated that higher 25(OH)D concentrations (≥60 ng/mL) were associated with a significantly lower risk of breast cancer3. Additionally, a meta-analysis of prospective cohort studies suggested that higher 25(OH)D levels were inversely associated with cancer mortality, although the evidence for cancer incidence was less conclusive9.
Dyslipidemia and 25-Hydroxyvitamin D
Reduction in Dyslipidemia Risk
Higher serum 25(OH)D levels have been linked to improved lipid profiles. A systematic review and meta-analysis of 57 observational studies found that higher 25(OH)D levels were associated with a significant reduction in the odds of hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C), and overall dyslipidemia4. However, no significant association was found between 25(OH)D levels and high low-density lipoprotein cholesterol (LDL-C) or hypercholesterolemia.
Diabetes and 25-Hydroxyvitamin D
Inverse Association with Type 2 Diabetes
Epidemiological evidence suggests an inverse relationship between 25(OH)D levels and the risk of type 2 diabetes. A meta-analysis that included data from the European Prospective Investigation into Cancer (EPIC)-Norfolk study found that higher baseline 25(OH)D levels were associated with a lower risk of developing type 2 diabetes10. The combined relative risk of type 2 diabetes was significantly lower in individuals with the highest quartile of 25(OH)D compared to those in the lowest quartile.
Mortality and 25-Hydroxyvitamin D
All-Cause Mortality
Low 25(OH)D levels have been associated with increased all-cause mortality. An individual participant data meta-analysis of 26,916 individuals from a European consortium found that lower 25(OH)D concentrations were linked to a higher risk of all-cause mortality, with no significant increased risk observed at high 25(OH)D levels up to 125 nmol/L7.
Conclusion
The evidence suggests that higher serum 25-hydroxyvitamin D levels are beneficial for reducing the risk of cardiovascular events, certain types of cancer, dyslipidemia, type 2 diabetes, and all-cause mortality. However, the associations vary by health outcome and further research, including randomized controlled trials, is needed to establish causality and optimal 25(OH)D levels for different populations.
Sources and full results
Most relevant research papers on this topic
Serum 25-hydroxyvitamin D and the risk of cardiovascular disease: dose-response meta-analysis of prospective studies.
Higher serum 25(OH)D levels are associated with a reduced risk of total cardiovascular disease events and mortality.
Meta-Analysis
Very Rigorous Journal
Highly CitedSerum 25-Hydroxyvitamin D and Cancer Risk: A Systematic Review of Mendelian Randomization Studies
Higher serum 25-hydroxyvitamin D levels do not significantly lower the risk of cancer incidence or mortality in European-ancestry populations.
Systematic ReviewBreast cancer risk markedly lower with serum 25-hydroxyvitamin D concentrations ≥60 vs <20 ng/ml (150 vs 50 nmol/L): Pooled analysis of two randomized trials and a prospective cohort
Higher 25(OH)D concentrations are associated with a dose-response decrease in breast cancer risk, with concentrations 60 ng/ml being most protective.
Meta-Analysis
Rigorous JournalHighly CitedSerum 25-hydroxyvitamin D levels and dyslipidemia: a systematic review and dose-response meta-analysis of epidemiologic studies.
Higher serum 25-hydroxyvitamin D levels are associated with significant reductions in the odds of hypertriglyceridemia, low HDL-C, and dyslipidemia in a dose-response trend.
Meta-Analysis25-Hydroxyvitamin D Levels and Risk of Ischemic Heart Disease, Myocardial Infarction, and Early Death: Population-Based Study and Meta-Analyses of 18 and 17 Studies
Decreasing plasma 25-hydroxyvitamin D levels are associated with an increased risk of ischemic heart disease, myocardial infarction, and early death.
Meta-AnalysisHighly CitedSerum 25-hydroxyvitamin D levels and survival in colorectal and breast cancer patients: systematic review and meta-analysis of prospective cohort studies.
Higher 25(OH)D levels (>75nmol/L) are associated with significantly reduced mortality in colorectal and breast cancer patients.
Meta-AnalysisVery Rigorous JournalHighly CitedVitamin D and mortality: Individual participant data meta-analysis of standardized 25-hydroxyvitamin D in 26916 individuals from a European consortium
Low vitamin D levels are associated with an increased risk of all-cause mortality, suggesting that treatment of vitamin D deficiency may prevent premature deaths.
Meta-AnalysisRigorous JournalHighly CitedFeeding supplemental 25-hydroxyvitamin D3 increases serum mineral concentrations and alters mammary immunity of lactating dairy cows.
Feeding supplemental 25-hydroxyvitamin D3 increases serum mineral concentrations and alters mammary immunity in lactating dairy cows, leading to less severe mastitis responses.
RCTRigorous Journal25-Hydroxyvitamin D and Total Cancer Incidence and Mortality: A Meta-Analysis of Prospective Cohort Studies
A higher 25-hydroxyvitamin D concentration is associated with a lower risk of cancer incidence and cancer mortality.
Meta-AnalysisVery Rigorous JournalCirculating 25-hydroxyvitamin D concentration and the risk of type 2 diabetes: results from the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort and updated meta-analysis of prospective studies
Higher circulating 25-hydroxyvitamin D levels are associated with a lower risk of developing type 2 diabetes.
Meta-AnalysisRigorous JournalHighly Cited