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A new randomized clinical trial from Intermountain Health suggests that a personalized strategy for vitamin D3 supplementation after a heart attack can cut the risk of a second heart attack by roughly 50%. The trial tested a "target-to-treat" approach—measuring blood levels and adjusting doses to reach a defined target—rather than giving the same supplement dose to every patient.
Why this study matters now
Cardiovascular disease remains the leading cause of death worldwide, and preventing repeat events in people who have survived an initial heart attack is a top clinical priority. At the same time, vitamin D deficiency is common: surveys estimate that roughly half to two-thirds of people globally have suboptimal vitamin D levels. Lifestyle changes, reduced sun exposure, and skin cancer prevention have made many populations more reliant on dietary supplements or fortified foods to maintain serum vitamin D.
Previous observational research linked low vitamin D with poorer heart outcomes, but randomized trials using fixed supplement doses generally failed to show clear cardiovascular benefits. Intermountain Health’s new trial, presented at the 2025 American Heart Association Scientific Sessions in New Orleans, asked a different question: what if we set a blood-level goal and tailored supplementation so each patient reached it?
How the TARGET-D trial worked
The TARGET-D randomized controlled trial enrolled 630 patients who had suffered a heart attack within one month before enrollment. Recruitment ran from April 2017 through May 2023, and participants were followed through March 2025 for major cardiovascular events.
Two study arms
- Usual care arm: no study-led vitamin D management; clinicians could follow their standard practices.
- Targeted treatment arm: researchers measured serum vitamin D and adjusted vitamin D3 doses to achieve a goal of greater than 40 ng/mL (nanograms per milliliter) of 25-hydroxyvitamin D, the standard lab marker.
At baseline, 85% of enrolled heart attack patients had vitamin D levels below 40 ng/mL. More than half of the patients in the targeted arm required an initial dose of 5,000 international units (IU) of vitamin D3—well above the common blanket recommendations of 600–800 IU for adults—followed by scheduled checks and dose adjustments. Patients who were not yet at target were rechecked every three months; once a target level was achieved they moved to annual monitoring.
What the trial found
Across the full cohort, 107 patients experienced a major adverse cardiac event (MACE), defined broadly as a repeat heart attack, hospitalization for heart failure, stroke, or death. The study did not show a statistically significant difference between groups for overall MACE. However, when researchers examined specific outcomes, the risk of a follow-up heart attack was reduced by approximately 50% in the group that received targeted vitamin D management.
Importantly, investigators reported no increase in adverse events linked to higher vitamin D dosing when levels were monitored and adjusted. That safety signal—alongside the sizeable reduction in recurrent heart attacks—suggests the benefit is worth further investigation but stops short of immediately changing clinical guidelines.
Scientific context and limitations
WHY might a target-based strategy work when fixed-dose trials failed? One plausible explanation is interindividual variability in how people absorb and metabolize vitamin D. Fixed doses produce a wide range of blood concentrations, leaving many people either undertreated or, rarely, overexposed. A "treat-to-target" model ensures patients actually reach the serum levels thought to be protective, here defined pragmatically as >40 ng/mL.
Limitations of the TARGET-D trial include its sample size and event counts: the study was large for a specialized interventional trial but not powered to robustly test many secondary endpoints. The overall MACE outcome was neutral, and the heart-attack-specific benefit—while compelling—requires replication in a larger, multicenter trial to confirm causality and rule out chance findings.
Other considerations: vitamin D metabolism interacts with kidney function, medications, and genetic differences in vitamin D binding proteins. The trial protocol’s annual and quarterly checks are more intensive than routine care in many settings, so implementing this approach would need practical workflows and clear cost-benefit assessment.
What this means for patients and clinicians
For patients who have had a heart attack, this study suggests a potential low-cost, low-risk add-on strategy: measure serum 25-hydroxyvitamin D and consider individualized supplementation aimed at achieving a target range. It is not a license for high-dose self-prescribing; unsupervised megadoses can carry risks. Instead, the takeaway is that monitoring and personalization are key.
Clinicians should await larger confirmatory trials before routine adoption, but they may increasingly consider vitamin D status as one modifiable factor in comprehensive secondary prevention plans that already include antiplatelet therapy, statins, blood pressure control, smoking cessation, and cardiac rehabilitation.
Expert Insight
"The most interesting aspect is the shift from 'one-size-fits-all' dosing toward a precision approach," says Dr. Anna Ruiz, a cardiologist and clinical trialist. "If replicated, targeted vitamin D could become a simple, evidence-based tool alongside established therapies to reduce the burden of recurrent heart attacks. The next decade should focus on who benefits most, how to monitor efficiently, and cost-effectiveness in real-world clinics."
Intermountain Health investigators have called for larger, multicenter trials to validate these findings and to explore whether target-based vitamin D management can reduce other cardiovascular outcomes beyond repeat myocardial infarction.
Source: scitechdaily
Comments
DaNix
Is this even true? fixed dose trials failed before, maybe subgroup effect. Also what about kidney patients, drug interactions? not convinced yet.
bioNix
wow 50% fewer repeat heart attacks? if true this is massive. But 40 ng/mL target, frequent checks, who pays for all that? still hopeful tho
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