A recent review in the Journal of the American College of Cardiology highlights the contrasting findings between observational studies, which have reported a strong association between vitamin D deficiency and cardiovascular disease (CVD), and the lack of response in vitamin D supplementation trials.
The inverse correlation between blood levels of vitamin D and many elements of CVD has been established in Europeans as well as Caucasian and Afro-Caribbean Americans.
Studies showed an “inverse relationship between 25-OH D levels and the prevalence of hypertension, insulin resistance, frank type 2 diabetes mellitus (DM), and dyslipidemia,” wrote co-authors Ibhar Al Mheid and Arshed Quyyumi from Emory University School of Medicine in Atlanta.
Research has also identified possible mechanisms explaining how vitamin D may reduce inflammation, lower blood pressure and improve the condition of the linings of arteries.
However, most randomised controlled trials (RCTs) using vitamin D supplementation show insignificant or no benefit. In this review, the researchers suggest possible reasons for the apparent lack of reduction in CVD related events.
Low dosage
The largest vitamin D RCT to date, the Women’s Health Initiative (WHI) trial, supplemented vitamin D at 400 IU/day (together with 1 gram/ day of calcium).
The researchers suggest “the low dose of vitamin D, as well as inclusion of women already taking calcium and vitamin D at doses up to those of the trial’s treatment dosage,” as being possible factors for the absence of reduced CVD events.
Pre-existing CVD
Most RCTs involving vitamin D were designed to investigate benefits to bone health in elderly patients many of whom “had established CVD or risk factors,” the researchers noted.
In tertiary prevention studies, patients often had advanced kidney failure, or pulmonary diseases, further limiting conclusions on vitamin D’s ability to reduce coronary events.
Small trial size
The researchers explained “any beneficial or protective effects of vitamin D therapy will likely be evident only in clinical trials recruiting at least thousands of patients, particularly for hard endpoints such as cardiovascular mortality.”
Many trials have simply been too small to identify a meaningful effect.
Cause or effect?
The authors speculated that a reverse cause-effect mechanism might explain vitamin D’s apparent ineffectiveness.
They proposed, “Ambulatory subjects with normal outdoor exercise activities are likely to have higher vitamin D levels (from increased sunlight exposure) and lower likelihood of CVD.”
Therefore, “although the strong association between vitamin D deficiency and incident CVD implies a cause-and-effect relationship, this is complicated by the possibility that low 25-OH D levels may be a result of CVDs, rather than the cause of disease.”
2018: a VITAL year
Results are eagerly awaited from the ongoing VITAL (VITamin D and Omega-3 triAL) RCT involving 25,000 healthy middle-aged US adults. The trial will examine whether vitamin D supplementation (2000 IU/day), either with or without omega-3 fatty acids, reduces the incidence of CVD events (including stroke).
Findings should be available in 2018. The authors of this review hope this will aid resolution of vitamin D’s controversial role in heart disease.
Source: Journal of the American College of Cardiology
Volume 70, Issue 1, pages 89-100 doi: 10.1016/j.jacc.2017.05.031
“Vitamin D and Cardiovascular Disease Controversy Unresolved”