Results from a massive meta-analysis of nutritional supplements published on July 8 cast more doubt on the value of testing for levels of vitamin D and supplementing accordingly for heart health, though study limitations leave questions open about potential benefits.
Vitamin D and a range of other supplements -- including vitamin B6, calcium, and folic acid -- "did not seem to have a significant effect on mortality or [cardiovascular disease] outcomes" in a review of 24 different supplements and dietary interventions in 105 meta-analyses, Dr. Safi Khan and colleagues reported in the Annals of Internal Medicine (July 8, 2019).
Vitamin D taken alone showed no resulting benefit or harm, while there was an increased risk for stroke when vitamin D was taken with calcium, according to the researchers. The analysis included randomized controlled data from two new trials: the Vitamin D and Omega-3 Trial (VITAL) and the Vitamin D Assessment Study (VIDA).
More fodder for testing debates
The findings provide support to those concerned about the overuse of vitamin D to improve cardiovascular health, among other conditions. Overtesting for vitamin D can be burdensome on smaller labs, draining resources from areas where testing could provide a real benefit, some pathologists have warned.
However, Khan, an internist at West Virginia University, and colleagues included a big caveat with their conclusions.
"Overall, these findings are limited by suboptimal quality of the evidence," they wrote. "This study can help those who create professional cardiovascular and dietary guidelines modify their recommendations, provide the evidence base for clinicians to discuss dietary supplements with their patients, and guide new studies to fulfill the evidence gap."
In an accompanying editorial titled "Dispense with supplements for improving heart outcomes," also published on July 8, Scripps Research's Dr. Amitabh Pandey and Dr. Eric Topol praised the "ambitious" nature of the meta-analysis, in that it included 277 trials in almost 1 million people.
They also flagged many limitations, however, including challenges with drawing conclusions based on studies done in disparate geographic locations. For example, folic acid was one of the few supplements associated with a benefit for cardiovascular outcomes. But that was largely driven by the inclusion of a large study done in China, "where a folate-rich diet is not routine," they noted.
In addition, the studies do not reflect interindividual variability, which has become evident recently through machine learning of large datasets, they wrote.
"Testing any diet or supplement in a broad population without acknowledging interindividual variability seems like a recipe for failure, especially because most trials are not randomized, are not of sufficient duration, or do not have enough hard outcome events," Pandey and Topol concluded. "Unfortunately, the current study leaves us with the same foggy conditions that we started with. Until these conditions clear, it would be reasonable to hold off on any supplement or diet modification in all guidelines and recommendations."
Topol: Tests are 'grossly overused'
What's the takeaway message for labs doing vitamin D testing? There are no data to support the common use of supplements and vitamins, and it follows that testing for levels of vitamin D or other vitamins has little basis, Topol, founder and director of the Scripps Research Translational Institute, told LabPulse.com by email.
"These tests are grossly overused, with limited utility in select patients," he said.
