Heart and vitamin D: reduces heart attack risk and future complications

Initial editorial note: this article was previously published and has been updated according to scientific and divulgative criteria. The text is for informational purposes only and does not replace medical advice.

IN BRIEF

• Vitamin D deficiency is often associated with an increased cardiovascular risk in observational studies, but evidence from supplementation trials is conflicting.
• Plausible cellular mechanisms include vitamin D receptors in the heart and blood vessels and a possible anti-fibrotic effect on cardiac tissue.
• Large randomized trials have not shown clear protection from vitamin supplementation for the primary prevention of cardiovascular events.
• In patients with heart failure or documented deficiency, some evidence indicates possible benefits on parameters of cardiac function, but clinical data on long-term outcomes remain limited.
• Interpret with caution: difference between observational association and causal evidence; the decision on testing and supplementation should be personalized by a physician.

Abstract: what does science say?

Definition and context

Vitamin D is a fat-soluble substance that the body obtains from food and from skin synthesis induced by UV rays. Commonly measured serum values are those of 25-hydroxyvitamin D (25[OH]D). "Deficiency" or "insufficiency" refers to concentrations below the limits established by guidelines, which may vary depending on local recommendations and age group.

What available evidence shows

Numerous observational studies describe a relationship between low levels of 25(OH)D and an increased risk of cardiovascular events (heart attack, heart failure, mortality). However, experimental evidence obtained with supplementation is heterogeneous: large trials and meta-analyses have not, to date, provided robust evidence of a reduction in cardiovascular events in the general population when supplementation is administered regardless of baseline levels.

Dependence on dose, frequency, and context

The effect of vitamin D seems to depend on the context: an impact is more likely when there is a documented deficiency compared to populations with normal levels. The formula (cholecalciferol vs ergocalciferol), dose (low daily doses vs high intermittent doses), and duration of the intervention also influence the results. Therefore, the generalization of results across studies is limited.

Scientific evidence: observations, mechanisms, and trials

Epidemiological studies have shown that low levels of 25(OH)D are associated with an increased risk of cardiovascular events in the general population, suggesting a relevant link between vitamin status and heart health. [1]

From a biological perspective, vitamin D receptors (VDR) exist in cardiomyocytes and vascular cells, and cellular and animal studies indicate that the active metabolite of vitamin D can modulate inflammatory processes, fibrotic response, and endothelial function: in vitro, 1,25-dihydroxyvitamin D3 inhibited the activation of cardiac fibroblast cells induced by TGFβ1, a mechanism that explains the possible limitation of scarring after myocardial damage. [6]

Despite these plausible biological bases, randomized clinical trials have so far yielded conflicting results. The VITAL study, one of the largest primary prevention trials with vitamin D, did not show a significant reduction in cardiovascular events in the general population randomized to supplementation. [2] A large meta-analysis of randomized trials found no benefit of supplementation on the reduction of overall cardiovascular events. [3]

Conversely, in selected subgroups—for example, patients with heart failure and documented vitamin D deficiency—some smaller controlled studies have reported improvements in echocardiographic parameters and cardiac remodeling after high-dose supplementation, suggesting potentially relevant clinical effects in specific contexts but not yet definitively demonstrated in terms of major clinical events. [7]

Finally, even well-conducted studies in severely critical populations have yielded neutral outcomes on mortality or short-term clinical outcomes after administration of high doses of vitamin D, emphasizing that merely correcting serum levels does not always guarantee an immediate clinical benefit. [8]

What it means in practice

For professionals and the public, a correct reading of the evidence requires distinguishing between two main points. First, the presence of an observational correlation between low vitamin D levels and cardiovascular disease does not equate to proof of causality; factors such as physical activity, nutritional status, and chronic disease can confound the association. Second, generalized supplementation to prevent heart attack in the population without documented deficiency is not supported by solid evidence.

In practical terms: measuring 25(OH)D levels may be indicated when there are clinical reasons (symptoms, risk factors, associated conditions) or in the presence of groups at risk of deficiency (e.g., very limited sun exposure, malabsorption). When deficiency is documented, correction with supplementation according to established clinical recommendations may be justified primarily for metabolic-skeletal reasons and, potentially, have favorable effects on cardioprotection in specific subgroups—but it remains necessary to rely on a physician for dosages and monitoring. [3]

Key points to remember

• Vitamin D deficiency is associated, in observations, with an increased cardiovascular risk, but this association does not prove causality.
• Plausible biological mechanisms (VDR receptors, inflammatory modulation, and anti-fibrotic effect) offer a possible explanation but are not sufficient to establish a generalized clinical benefit.
• Large trials and meta-analyses have not confirmed a clear protective effect of supplementation for the primary prevention of heart attack in the general population.
• In patients with documented deficiency or heart failure, some studies indicate possible improvements in cardiac parameters; the relevance to major clinical outcomes remains uncertain.
• Deciding on testing and supplementation must be a personalized medical act, with assessment of risk, baseline levels, and benefit/risk ratio.

Limitations of the evidence

Difference between observational studies and causal evidence

Observational studies are useful for identifying associations and generating hypotheses, but they can be influenced by unmeasured confounders: for example, people who engage in more outdoor activity tend to have higher vitamin D levels and also better cardiovascular health for other reasons. To demonstrate causality, randomized clinical trials with clearly defined endpoints are needed; such trials, when available, do not always confirm observational signals. [1]

Methodological limitations and variability among studies

Trials exist in many variants: different dosages, formulations, regimens (daily vs bolus), and populations (deficient vs non-deficient). Furthermore, in many studies, cardiovascular events were not the primary endpoint, so the design is not optimal for answering the specific question about cardiac prevention. Combined meta-analyses can mask heterogeneity and especially the possible benefit in deficient subgroups. [3] [4]

Editorial conclusion

Research on vitamin D and cardiovascular health has produced consistent results in describing an observational association and plausible biological mechanisms. However, the clinical translation of this knowledge remains partial: evidence from randomized trials and meta-analyses does not currently support routine supplementation for the prevention of heart attack in the general population. At the same time, in subjects with documented deficiency and in certain clinical contexts (e.g., heart failure), there are signals of possible benefit that warrant further targeted studies of sufficient size to evaluate relevant clinical outcomes. Diagnostic and therapeutic choices must remain personalized and shared with a physician, based on assessment of serum levels, individual risk factors, and potential drug interactions.

Editorial note

Article originally published in the past and updated according to scientific and divulgative criteria to reflect recent literature. The purpose is informative; it does not replace medical consultation. For individual decisions on tests or supplementation, consult your doctor.

SCIENTIFIC RESEARCH

1. Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation. 2008;117(4):503–11. https://doi.org/10.1161/CIRCULATIONAHA.107.706127
2. Manson JE, Cook NR, Lee I‑M, Christen W, Bassuk SS, Mora S, et al.; VITAL Research Group. Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. N Engl J Med. 2019;380(1):33–44. https://doi.org/10.1056/NEJMoa1809944
3. Barbarawi M, Kheiri B, Zayed Y, Barbarawi O, Dhillon H, Swaid B, et al. Vitamin D Supplementation and Cardiovascular Disease Risks in More Than 83 000 Individuals in 21 Randomized Clinical Trials: A Meta‑analysis. JAMA Cardiol. 2019;4(8):765–76. https://doi.org/10.1001/jamacardio.2019.1870
4. Petrelli F, Luciani A, Rivera‑Carrasco E, et al. Vitamin D Supplementation and Its Impact on Mortality and Cardiovascular Outcomes: Systematic Review and Meta‑Analysis of 80 Randomized Clinical Trials. Nutrients. 2023;15(8):1810. https://doi.org/10.3390/nu15081810
5. Milazzo V, Cosentino N, Trombara F, Marenzi G. Vitamin D and cardiovascular diseases: From physiology to pathophysiology and outcomes. Biomedicines. 2024;12(4):768. https://doi.org/10.3390/biomedicines12040768
6. McManus B, Baird C, et al. 1,25‑Dihydroxyvitamin D3 Inhibits TGFβ1‑Mediated Primary Human Cardiac Myofibroblast Activation. PLoS One. 2015;10(6):e0128655. https://doi.org/10.1371/journal.pone.0128655
7. Witte KK, Byrom R, Gierula J, et al. Effects of Vitamin D on Cardiac Function in Patients With Chronic Heart Failure: The VINDICATE Study. J Am Coll Cardiol. 2016;67(22):2593–603. https://doi.org/10.1016/j.jacc.2016.03.508
8. Ginde AA, Brower RG, Caterino JM, et al.; NHLBI PETAL Clinical Trials Network. Early High‑Dose Vitamin D3 for Critically Ill, Vitamin D‑Deficient Patients. N Engl J Med. 2020;382:2525–36. https://doi.org/10.1056/NEJMoa1911124