Summary – Vitamin D and Cardiovascular Health (Grant et al., Nutrients 2025)

Our Newest Publication on Vit D and Cardiovascular Health

Overview
This is the latest publication from an international Vitamin D expert panel, including myself (Richard Z. Cheng, M.D., Ph.D.), alongside distinguished co-authors William B. Grant, B.J. Boucher, Pawel Pludowski, and Sunil J. Wimalawansa. The paper provides a comprehensive narrative review of the evidence linking vitamin D sufficiency to reduced cardiovascular disease (CVD) risk.

This article follows our earlier consensus paper:

Grant WB, Wimalawansa SJ, Pludowski P, Cheng RZ. Vitamin D: Evidence-Based Health Benefits and Recommendations for Population Guidelines. Nutrients. 2025 Jan 14;17(2):277. [PMID: 39861407; PMCID: PMC11767646]

That foundational work summarized the extensive evidence base for vitamin D across multiple health domains and proposed global population-level guidelines.

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Key Observational Findings

• Large-scale observational studies consistently show that serum 25(OH)D levels below 40–50 nmol/L are associated with increased risk of CVD and cardiovascular mortality.

• Seasonal, geographic, and ecological data corroborate these trends, with cardiovascular events peaking in winter and declining in summer when vitamin D levels are higher.

Mechanistic Insights
Vitamin D supports cardiovascular health through several biological mechanisms:

1. Suppression of the renin–angiotensin system, leading to lower blood pressure

2. Anti-inflammatory and antioxidant effects

3. Protection of endothelial function and plaque stabilization

4. Improved metabolic regulation, including insulin sensitivity and reduced myocardial fibrosis

RCTs and Intervention Data

• While many earlier RCTs reported null results, these were limited by methodological flaws: low dosing, short duration, and inclusion of already vitamin D–sufficient individuals.

• A recent trial using 60,000 IU/month vitamin D showed a 13–17% reduction in major cardiovascular events, particularly in participants with low baseline levels or those on existing CVD therapies.

• Additional intervention studies show modest improvements in blood pressure, lipid metabolism, and insulin resistance.

Causality – Hill’s Criteria
The evidence meets multiple criteria for causality as defined by Hill’s criteria, including strength, consistency, biological gradient, plausibility, and coherence.

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Clinical Implications and Commentary

• The paper recommends aiming for serum 25(OH)D levels ≥50 nmol/L (20 ng/mL), ideally 75–100 nmol/L (30–40 ng/mL).

• However, these dosing recommendations remain overly conservative given the totality of the scientific evidence—and also when applying common sense and logic, both of which are often lacking in today’s medical publishing and clinical practice, in my opinion.

As a clinician, I personally recommend higher doses of vitamin D—typically 5,000 IU/day or more—to safely and effectively maintain blood levels in the optimal range of 50–100 ng/mL (125–250 nmol/L). This is particularly important for individuals at high risk of deficiency or chronic disease.

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✅ Bottom Line

This review affirms that vitamin D plays a protective, likely causal role in cardiovascular health. Alongside our prior population guidelines paper, it strengthens the call for science-based, patient-centered vitamin D policies and a shift away from outdated, low-dose recommendations.