In a groundbreaking preliminary study to be unveiled at the American Heart Association’s Scientific Sessions 2025, researchers present compelling evidence that personalized vitamin D supplementation could dramatically reduce the risk of recurrent heart attacks among adults already diagnosed with heart disease. This study, known as TARGET-D, breaks new ground by individualizing vitamin D doses based on blood levels rather than administering uniform doses as has been done in prior trials. The findings suggest that tailoring vitamin D intake to achieve optimal circulating levels may be a crucial strategy in cardiovascular risk mitigation, potentially halving the incidence of subsequent myocardial infarctions.
Vitamin D, a secosteroid hormone primarily synthesized in the skin via sunlight exposure, has garnered interest in cardiovascular research due to its pleiotropic effects on inflammation, endothelial function, and myocardial health. While epidemiologic data have long linked low vitamin D concentration with adverse cardiovascular outcomes, intervention studies have yielded inconsistent results. A key limitation of earlier randomized controlled trials was their “one-size-fits-all” dosing design, which failed to account for individual variability in baseline vitamin D status and responsiveness. TARGET-D addresses these shortcomings by imposing a rigorous monitoring protocol that adjusts supplementation every three months, aiming to maintain serum 25-hydroxyvitamin D [25(OH)D] levels within a tightly controlled therapeutic window of 40 to 80 ng/mL.
The clinical trial enrolled 630 adults with diagnosed acute coronary syndrome at Intermountain Medical Center in Utah over a six-year period, with an average follow-up of just over four years. The cohort was primarily male (78%) with a mean age of 63, and nearly half had a history of prior myocardial infarction. Importantly, more than 85% of participants initially had suboptimal vitamin D levels below 40 ng/mL, underscoring widespread insufficiency in this cardiovascularly vulnerable population. Participants were randomized into two groups: one received standard care without vitamin D level management, while the treatment arm underwent serial blood testing and personalized dosing to surpass the 40 ng/mL threshold safely, avoiding toxicity by capping at 80 ng/mL.
Remarkably, the treatment group demonstrated a 52% reduction in the risk of recurrent heart attacks compared to controls, marking one of the most significant effect sizes reported in recent vitamin D cardiovascular research. This pronounced risk reduction did not extend to other serious cardiovascular endpoints such as heart failure hospitalization, stroke, or all-cause mortality, which remained statistically unaffected. These nuanced results suggest that vitamin D’s cardioprotective role may be selectively potent in modulating mechanisms underlying atherothrombosis and myocardial ischemia-reperfusion injury, rather than broader heart failure pathology or cerebrovascular events.
The doses required to achieve these optimal serum levels were often substantially higher than currently recommended dietary allowances. Over half of the participants receiving supplementation needed daily doses exceeding 5,000 IU, a figure that surpasses the FDA’s advised intake by more than sixfold. Such supraphysiological dosing was safely administered under strict surveillance to prevent adverse effects like hypercalcemia and nephrotoxicity. This finding raises pressing questions about the adequacy of standard vitamin D dosing guidelines, particularly in populations with cardiovascular disease and low baseline stores.
Mechanistically, vitamin D influences cardiovascular health through multiple pathways. It regulates the renin-angiotensin-aldosterone system (RAAS), modulates inflammatory cytokine production, and enhances endothelial nitric oxide synthase (eNOS) activity, promoting vasodilation. Deficiency correlates with upregulated pro-inflammatory markers and vascular calcification, both contributing to atherosclerotic plaque progression and instability. Thus, optimizing vitamin D status might confer plaque stabilization and decreased thrombogenicity, translating clinically into fewer infarctions.
The personalized approach of TARGET-D underscores the importance of routine clinical measurement of 25(OH)D levels rather than empirical dosing. By dynamically adjusting vitamin D supplementation based on serial biomarker feedback, clinicians can tailor interventions more precisely to physiologic needs, minimizing under- or overdosing risks. This methodology challenges the prevailing paradigm wherein fixed-dose supplementation is standard, advocating for precision medicine tactics in cardiovascular preventive care.
Nevertheless, the study is not without limitations. The predominantly Caucasian demographic, comprising approximately 90% of subjects, restricts the generalizability of results to more ethnically diverse populations. Additionally, the relatively modest sample size and event count constrain statistical power for some secondary endpoints. Further investigations involving larger, multiethnic cohorts and focusing on primary prevention settings are needed to validate and expand upon these findings.
The implications of the TARGET-D trial extend beyond cardiology into public health and nutrition policy. Widespread vitamin D insufficiency and the growing burden of coronary artery disease globally emphasize the potential for simple, cost-effective interventions to reduce morbidity. However, the safety of high-dose vitamin D supplementation must remain a clinical priority, necessitating rigorous monitoring to avert complications associated with hypervitaminosis D.
Leading epidemiologist and principal investigator Dr. Heidi T. May of Intermountain Health advocates for a shift towards biomarker-driven vitamin D therapy in heart disease management. “Our results suggest that targeting vitamin D supplementation based on blood levels can significantly diminish the risk of subsequent heart attacks. This approach demands a personalized, vigilant clinical protocol that diverges from the traditional fixed-dose model,” she remarked.
Until these preliminary findings are corroborated by larger, peer-reviewed trials, clinicians should exercise caution. The American Heart Association emphasizes consultation with healthcare providers before initiating or modifying vitamin D regimens, especially given the variable responses and potential adverse effects documented with high-dose supplementation. Nonetheless, the promising TARGET-D data pave the way for innovative cardiovascular prevention strategies centered on nutrient optimization.
Ultimately, the study heralds a paradigm shift in the integration of nutritional biomarkers into cardiovascular care, demonstrating that individualized vitamin D optimization may serve as a vital adjunct in reducing ischemic heart disease risk. As the medical community awaits further confirmation, these data present a hopeful avenue to improve outcomes in a population at enduring risk of recurrent cardiac events.
Subject of Research: Personalized Vitamin D Supplementation and Cardiovascular Outcomes in Adults with Heart Disease
Article Title: Tailored Vitamin D Dosing Halves Risk of Recurrent Heart Attack in Adults with Heart Disease: Insights from the TARGET-D Trial
News Publication Date: November 9, 2025
Web References:
- American Heart Association Scientific Sessions 2025: https://professional.heart.org/en/meetings/scientific-sessions
- TARGET-D Abstract: https://eppro02.ativ.me/appinfo.php?page=Session&project=AHA25&id=4382525&server=eppro02.ativ.me
- Heart Attack Information: https://www.heart.org/en/health-topics/heart-attack
Keywords: Cardiovascular disorders, Coronary artery disease, Heart disease, Vitamins, Vitamin D
