Vitamin D and Cardiovascular Health - 2025

Vitamin D and Cardiovascular Health: A Narrative Review of Risk Reduction Evidence

Nutrients 2025,17,2102. https:// doi.org/10.3390/nu17132102

William B. Grant h* , Barbara J. Boucher 2©, Richard Z. Cheng :3,4©, Pawel Pludowski 5© and Sunil J. Wimalawansa 6

The role of vitamin D in reducing cardiovascular disease (CVD) risk remains debated despite growing evidence. Prospective observational studies consistently show that low serum 25-hydroxyvitamin D [25(OH)D] concentrations (below 40-50 nmol/L [16-20 ng/mL]) are associated with the highest risk of CVD incidence. In addition, a large prospective observational study found that serum 25(OH)D concentration was inversely correlated with CVD mortality rate to over 100 nmol/L.

Randomized controlled trials have not generally demonstrated benefit due to faulty study designs, such as enrolling participants with baseline 25(OH)D levels > 50 nmol/L. However, a major trial found that 60,000 IU/month of vitamin D3 supplementation reduced the risk of major cardiovascular events for participants with predicted 25(OH)D concentrations > 50 nmol/L or taking statins or CV drugs by ~13 to ~17%. In addition, vitamin D supplementation studies have found modest reductions in several CVD risk factors.

Other observational studies of vitamin D supplementation have reported reduced CVD risks (e.g., ischemic heart disease, hypertension, and myocardial infarction). Temporal ecological studies further support this relationship, revealing that CVD incidence rates are lowest in summer and CVD mortality rates are significantly higher in late winter—when 25(OH)D concentrations are lowest—compared to late summer. A previously reported analysis using eight of Hill's criteria for causality in a biological system further strengthens the biological plausibility of vitamin D's role in CVD risk reduction.

Its role in modulating inflammation and oxidative stress, improving endothelial function, and reducing several cardiometabolic risk factors supports its inclusion as part of a comprehensive, multi-modal approach to cardiovascular health.

Therefore, vitamin D should be considered an integral component in the prevention and management of CVD. Preferably, it should be used in combination with other nutritional supplements, a heart-healthy diet, and prescription medications to reduce the risk of CVD incidence.

People should consider vitamin D3 supplementation with at least 2000 IU/day (50 mcg/day) (more for those who are obese) when sun exposure is insufficient to maintain serum 25(OH)D concentrations above 75 nmol/L. To reduce CVD mortality rates, higher doses to achieve higher 25(OH)D concentrations might be warranted.

PDF

Summary by Perplexity AI Dec 2025

This comprehensive 2025 peer-reviewed article published in Nutrients examines the relationship between vitamin D and cardiovascular disease (CVD) risk, synthesizing evidence from multiple study types to evaluate causality.

Key Findings

The Vitamin D-CVD Association

The review establishes a consistent inverse relationship between low serum 25-hydroxyvitamin D [25(OH)D] concentrations and CVD risk. Prospective observational studies show that concentrations below 40–50 nmol/L (16–20 ng/mL) are associated with the highest CVD incidence risk, with even stronger associations for mortality rates extending to over 100 nmol/L. The effect on mortality is notably more pronounced than on incidence rates.[1]

Observational Evidence

Prospective cohort studies spanning 1990 to 2023 demonstrate consistent findings: relative risks for CVD mortality range from 1.39 to 5.33 when comparing low versus high vitamin D status, depending on baseline concentrations and participant age. A UK Biobank analysis of 37,079 CVD patients found that those with 25(OH)D >75 nmol/L had a 41% lower risk of CVD mortality compared to those with <25 nmol/L. Seasonal ecological studies reveal CVD mortality peaks in winter (when vitamin D is lowest) and reaches minimum levels in summer, supporting a direct relationship.[1]

Randomized Controlled Trial Findings

Traditional RCTs have largely failed to show vitamin D benefits, but the review identifies critical design flaws: most trials enrolled participants with already-sufficient baseline 25(OH)D levels (49–79 nmol/L) and used doses too low to normalize deficiency. However, the D-Health trial from Australia identified a significant breakthrough: among participants with predicted baseline 25(OH)D ≥50 nmol/L or taking statins or CV drugs, 60,000 IU/month vitamin D3 reduced major adverse cardiovascular events by approximately 13–17%. Reanalysis revealed independent beneficial effects for those on CV medications.[1]

CVD Risk Factor Improvements

Vitamin D supplementation studies document modest but consistent improvements in multiple CVD risk factors: reductions in systolic blood pressure, LDL cholesterol, triglycerides, fasting glucose, and glycated hemoglobin, with increases in HDL cholesterol. These improvements were most notable in participants with baseline vitamin D deficiency.[1]

Mechanistic Pathways

The article details eight major mechanisms by which vitamin D reduces CVD risk: suppressing renin secretion (lowering blood pressure), reducing inflammation, preventing arterial plaque instability, decreasing oxidative stress, improving endothelial function, reducing cardiac hypertrophy, preventing myocardial fibrosis, and improving metabolic syndrome parameters.[1]

Causality Assessment

Using Hill's criteria for biological causality, the review demonstrates that the vitamin D-CVD relationship satisfies nearly all criteria—strength of association, consistency, temporality, biological gradient, coherence, plausibility, and analog effects—except RCTs due to design limitations rather than lack of effect.[1]

Clinical Recommendations

The authors recommend vitamin D3 supplementation of at least 2000 IU/day (50 mcg/day) to maintain serum 25(OH)D above 75 nmol/L when sun exposure is insufficient, with higher doses (1.5–3 times baseline) for overweight or obese individuals. For reducing CVD mortality specifically, higher concentrations (100–125 nmol/L) achieved with 5000+ IU/day may be warranted.[1]

Important Perspective Shift

The review challenges the interpretation that negative RCT findings disprove vitamin D's role in CVD prevention. Instead, it argues that observational studies are more appropriate for evaluating micronutrients like vitamin D—which exist naturally in the body with broader dose-response curves—compared to pharmaceutical drugs with narrow therapeutic windows. The evidence strongly supports including vitamin D as an integral component of comprehensive CVD prevention strategies, ideally combined with other nutritional supplements, heart-healthy diet, and prescription medications.