Research into the role of vitamin D in preventing cardiovascular disease may be being hindered by generic dosing recommendations that fail to achieve optimal levels, warn US scientists.
They are calling for the recommendations to be personalised for different patients after their research found that some needed more than 10,000 IU/day (250 µg/day) to achieve optimal vitamin D levels.
In the US, the recommended dietary allowance (RDA) is 600 to 800 International Units (IU)/day (15-20 µg/day); in Europe, EFSA has set the dietary reference value (DRV) for vitamin D at 600 IU (15 µg/day).
Low levels of vitamin D have been shown to be associated with a higher risk of having a cardiac event, such as a heart attack or stroke. This has driven researchers to investigate whether the nutrient is effective in preventing cardiac events.
However, if patients in such trials are failing to reach optimal vitamin D levels, it could render the findings are inaccurate, the researchers, from Intermountain Health in Salt Lake City, explained.
“We’ve seen a series of studies that report an association between low vitamin D and poor heart outcomes, but also a few randomised clinical trials that do not report the same association,” said lead author and epidemiologist Heidi May, who presented the findings at the American Heart Association’s Scientific Sessions 2023 earlier this month.
“Our findings here show that just giving patients some vitamin D does not help them achieve optimal levels. If researchers are going to further look at vitamin D dosing as a possible way to improve heart health, patients need to be given the right doses to reach those ideal levels.”
Viet T Le, researcher and physician associate at Intermountain Health, added: “These findings show that without taking a tailored approach to evaluating and dosing with vitamin D, patients most likely will not see any results. We need to be far more intentional in how we’re treating patients with vitamin D beyond just telling them to take a vitamin pill.”
Target-D, a randomised clinical trial, was designed to evaluate whether achieving an optimal vitamin D level through personalised supplementation could reduce cardiovascular-related outcomes.
In the first analysis of the Target-D study, 632 patients were stratified into two groups. One group received a general recommendation to discuss vitamin D treatment with their doctor; the other, a targeted vitamin D treatment. The goal was to raise their 25-hydroxyvitamin D levels to more than 40 nanograms per ml (ng/ml).
Supplementation in the targeted treatment arm was based on a dosing algorithm. Participants returned at three-month intervals for assessment and dosing adjustment, until their levels reached above 40 ng/mL. Once that level had been achieved, they received no additional treatment and returned annually for reassessment.
Nearly 90% of participants required some level of vitamin D dosing. Of those, 86.5% required more than 2,000 IU daily, while 14.6% required more than 10,000 IU daily. Fewer than 65% achieved levels above 40 ng/mL at three months. Another 25% of patients required six months or longer of dosing titration.
“Other contemporary vitamin D studies may have underdosed study participants, which means their results may not be showing the true value of raising someone’s vitamin D levels,” said May.
In the second analysis of the Target-D study, the baseline characteristics of study participants are reviewed. Researchers found that baseline vitamin D levels were a median of 25 ng/mL; less than 20 ng/mL was considered deficient, and 20 to 30 ng/mL was insufficient.
Among those randomised to the treatment arm with a vitamin D level under 40, 58.5% of patients had a starting vitamin D dose of 5,000 IU — again, well over the RDA of 600 to 800 IU.
“If vitamin D can help prevent heart attacks, we want to know it, but our findings are showing that you can’t just tell someone to take a single low supplement dose, then set it and forget it,” said Le.
“We need to be more intentional in these trials in order to determine if there is a link between vitamin D supplementation and improved heart health, as well as how to dose it to help our patients if it does.”
