Daily supplements may improve cardiometabolic health

• According to a new meta-study, an average supplemental dose of 3,320 IU of vitamin D per day is associated with reduced blood pressure, total cholesterol, hemoglobin A1C, and fasting blood insulin and glucose.
• The finding comes from a new meta-study of 99 randomized, controlled trials from around the world investigating the benefits of vitamin D for cardiometabolic health.
• The meta-study attempts to explain and distill findings of sometimes inconsistent studies regarding vitamin D.

A new, comprehensive review of existing, often conflicting, research on the benefits of vitamin D supplementation extracts a fresh view of its value in maintaining cardiometabolic health.

The authors of the meta-study found that taking a median dose of 3,320 International Units (IU) of vitamin D per day, or around 83 micrograms, was associated with several significant cardiometabolic benefits.

These benefits included reductions in systolic and diastolic blood pressure, overall cholesterol, hemoglobin A1C—a marker of type 2 diabetes—and fasting blood glucose and insulin.

The researchers from China and the United States examined the details of 99 randomized, controlled trials (RCTs) published until March 26, 2024. The trials involved 17,656 participants and were conducted among widely varying populations in various global locations.

A key component of the meta-study was a cataloging of differences between the RCTs that might explain their varying conclusions. Once those differences were understood, the authors of the meta-study could re-analyze and compare the RTCs’ data in a more balanced, apples-to-apples manner.

The resulting findings were less hampered by conflicts, and a few special cases relating to specific populations emerged.

The researchers found vitamin D supplementation provided the greatest benefit to non-Westerners, people with lower levels of circulating vitamin D in their blood, people with a BMI of under 30, and people ages 50 and older.

Simin Liu, MD, ScD, professor of epidemiology, surgery, and medicine at Brown University, Providence, RI, and corresponding author of the meta-study, described some ways in which the RCTs differed from each other that caused them to arrive at different conclusions.

“Several main sources of heterogeneity in earlier studies that led to conflicting findings relating supplementation to cardiometabolic risk factors included ethnocultural background, age, body weight, and study participants’ circulating 25[OH]D levels at enrollment,” he said.

Jayne Morgan, MD, cardiologist and the Executive Director of Health and Community Education at the Piedmont Healthcare Corporation in Atlanta, GA, who was not involved in the meta-study, noted another reason the medical community is not as confident regarding vitamin D as one might hope.

“While there are a plethora of studies demonstrating a link between taking vitamin D and a lower risk of heart disease, there is still a lack of a direct cause and effect. Further, although low serum vitamin D levels are associated with increased cardiovascular risk, it remains unclear whether this is a cause or contributing factor to heart disease, or rather a consequence of heart disease.”
— Jayne Morgan, MD

Still, “Here is where the data is leaning but [there is] nothing definitive yet regarding cardiovascular endpoints. So while there is not the standard of evidence-based data here, it certainly reaches the metric of evidence-informed,” Morgan said.

“Further, there are benefits on bone health, muscle function, and reduced inflammation. It’s possible positive effects on both hypertension, diabetes, and lipids are worth watching as well,” she added.

“Non-Westerners have relatively lower circulating vitamin D levels, and thus have a higher likelihood of benefiting from vitamin D supplementation,” Liu said. The same is true of people whose BMI is less than 30 kg·^m−2.

“Similarly, serum vitamin D levels tend to decrease with age, which may explain the more significant cardiometabolic improving effect observed with vitamin D supplementation in people aged 50 and older,” he added.

Morgan said all of this “seems to indicate that the ‘catch up’ could be a critical piece of the puzzle.”

“Meaning, those without low levels of vitamin D to start, and who only enhanced their levels, had less of an effect and moved the needle less than those who ‘covered more ground’ in raising their [vitamin D] blood levels because they started so low,” she explained.

Liu said that even with the positive associations seen for 3,320 IU of vitamin D per day for many people the ethnographic differences observed in the meta-study suggest, “There is certainly truth to the saying ‘One size does not fit all.’’”

“Achieving optimal levels of vitamin D for cardiometabolic health would require careful assessment of each person’s ethnocultural background and biological features to implement personalized intervention strategies,” Liu said.

He noted that, according to the meta-study’s findings, people with obesity and low 25[OH]D levels would likely need higher vitamin D doses and for longer durations.

“We may need to test for higher vitamin D doses with longer intervention durations to see if cardiometabolic health outcomes in diverse populations differ in the variables identified in our study: ethnocultural background, age, body weight, and study participants’ circulating 25[OH]D levels at enrollment,” Liu said.