Tailored vitamin D regimens offer significant cardiac benefit

Adults with heart disease who had a previous heart attack and took vitamin D doses tailored to reach optimal blood levels reduced their risk of another heart attack by more than half compared to those who did not have their vitamin D blood levels optimized, according to a preliminary study to be presented at the American Heart Association's Scientific Sessions 2025. The meeting, Nov. 7-10, in New Orleans, is a premier global exchange of the latest scientific advancements, research and evidence-based clinical practice updates in cardiovascular science.

Previous studies found low vitamin D levels are linked to worse heart health. The TARGET-D randomized clinical trial included adults with heart disease who also had a previous heart attack to determine whether achieving optimal vitamin D blood levels could prevent future heart attacks, strokes, heart failure hospitalizations or deaths. More than 85% of participants began the study with vitamin D levels in their blood below 40 ng/mL, a level many experts believe is insufficient for optimal health. Unlike earlier vitamin D randomized trials that used standard doses, the TARGET-D trial personalized the doses based on the results of each participant's blood test.

"Previous clinical trial research on vitamin D tested the potential impact of the same vitamin D dose for all participants without checking their blood levels first," said Heidi T. May, Ph.D., M.S.P.H., FAHA, principal investigator of TARGET-D and an epidemiologist and professor of research at Intermountain Health in Salt Lake City, Utah.

We took a different approach. We checked each participant's vitamin D levels at enrollment and throughout the study, and we adjusted their dose as needed to bring and maintain them in a range of 40-80 ng/mL."

Heidi T. May, Intermountain Health in Salt Lake City

Participants in the TARGET-D study were randomized to two groups: The standard of care group did not receive management of their vitamin D levels, and the treatment group received tailored vitamin D supplementation, with doses adjusted every three months until their vitamin D blood levels were above 40 ng/mL. Once the vitamin D level was above 40 ng/mL, levels were checked annually and doses adjusted if levels dropped below that target.

Researchers monitored both vitamin D and calcium levels for the participants in the treatment group throughout the study to prevent vitamin D toxicity. Doses were reduced or stopped if vitamin D levels rose above 80 ng/mL. Excessive vitamin D can lead to hypercalcemia (higher-than-normal levels of calcium in the blood), kidney failure and abnormal heart rhythm.

The study's key findings include:

• People who received personalized dosing of vitamin D supplements to achieve vitamin D levels greater than 40 ng/mL for nearly four years had a 52% lower risk of heart attack compared to participants whose vitamin D levels were not managed.
• More than 85% of participants had vitamin D levels below 40 ng/mL when they enrolled in the study.
• Nearly 52% of participants in the treatment group required more than 5,000 IU of vitamin D each day to reach the target blood levels of greater than 40 ng/mL. This dose is more than six times the FDA-recommended daily intake of 800 IU.

The study primarily focused on whether or not optimal levels of vitamin D could help reduce the risk of serious events like heart attack, heart failure, stroke or death among adults with heart disease. Researchers found that tailored vitamin D doses did not significantly reduce the primary outcome of death, heart failure hospitalization or stroke; however, supplementation appeared to be beneficial for preventing heart attack specifically.

May says that these results could improve patient care by focusing on blood tests for vitamin D levels and tailoring doses. "We encourage people with heart disease to discuss vitamin D blood testing and targeted dosing with their health care professionals to meet their individual needs," she added.

May and her study colleagues emphasized that more clinical trials are needed to determine whether targeted treatment with vitamin D could help prevent heart disease, before a first cardiac event.

Before adding or changing a vitamin regimen, the American Heart Association encourages people with heart disease to consult their cardiologist.

The study had several limitations. Only adults with a diagnosis of heart disease were included, so the results may not apply to people without heart disease. In addition, the smaller number of participants means a more complete analysis of other conditions and outcomes was not possible. In addition, most participants were from the same racial group, with approximately 90% self-identifying as white, so additional research is needed to determine whether the results apply to people of all backgrounds.

Study details, background and design:

• The study enrolled 630 adults with acute coronary syndrome treated at Intermountain Medical Center in Utah from April 2017 to May 2023, with an average follow-up of 4.2 years.
• Participants were an average age of 63 years old, 78% were men, and 48% had a previous heart attack.
• Participants were randomly assigned to one of two groups: The treatment group received targeted vitamin D supplementation to achieve optimal levels, with ongoing dose adjustments every three months based on blood testing to reach and maintain vitamin D levels above 40 ng/mL but not over 80 ng/mL. There was no vitamin D monitoring or dose-tailoring for patients in the standard care group.
• About 52% of study participants in the treatment group with vitamin D levels below 40 ng/mL began taking 5,000 IU daily as their starting dose.
• A total of 107 major cardiac events, including heart attack, heart failure hospitalization, stroke or death, occurred during the study period (15.7% occurred in the treatment group, and 18.4% occurred in the standard care group).