The study, reported in Clinical Nutrition, looked at self-reported adverse events from a four-year randomised controlled trial in which more than 5,000 people were given either a high-dose vitamin D3 supplement or a placebo every month.
While long-term intake of vitamin D at low levels is known to be safe, the international team many behind the study noted that in recent years a number of clinical trials and research programmes have backed the effectiveness of high-dose vitamin D supplementation in a number of situations.
However, ‘relatively little’ is known about the long-term safety of high-dose vitamin D supplementation, said the team – led by senior author Professor Robert Scragg from the University of Auckland.
“The safety of long-term high-dose vitamin D supplementation is unclear,” the team wrote – noting that concerns regarding long-term effects were raised by two trials with annual dosing of more 300,000 IU, given for three or more years, which suggested an increased risk of falls and fractures compared to placebo.
“However, other trials with lower bolus doses have not found an increased risk of falls and fractures in vitamin D supplemented participants, while additional trials have found promising health outcomes from large and long-term doses of vitamin D supplementation,” said the team.
To test the safety of a monthly high-dose of vitamin D3 supplement – taken for up to 4 years – Scragg and his colleagues performed a randomised, double blind, placebo-controlled trial of 5108 adults aged 50–84 years old.
Participants were randomly assigned to receive monthly doses of 100,000 IU vitamin D3 or placebo, for a average follow-up of 3.3 years (range 2.5–4.2 years).
A blind coded monthly questionnaire – including an open-ended question about any adverse events they attributed to the study capsules – was used to analyse safety and adverse event occurrence.
In total, the team noted that 419 (16.5%) of participants taking vitamin D and 399 (15.8%) taking placebo reported more than 1 adverse event.
“Despite a slightly higher incidence of recurrent adverse events in vitamin D arm, the incidence rate ratio (1.17) was not significantly higher in vitamin D,” said Scragg and colleagues – who noted that all results were adjusted for age, sex, and ethnicity.
As a result, they concluded that monthly supplementation of 100,000 IU vitamin D3 for a average of 3.3 years did not affect participant-reported adverse events.
Further evidence needed?
The team suggested that the findings of the current trial are ‘in agreement’ with a recent systematic review and meta-analysis, which included 19,389 participants and found that the number of participants with any adverse event was not different between vitamin D and placebo arms.
However, they also noted that further evidence to support or refute the findings should soon come from large trials with similar doses, which are wither underway or have recently finished.
“Publication of their safety results in the next few years should shed further light on the safety of monthly (and even less frequent) bolus dosing of vitamin D supplements,” said.
Source: Clinical Nutrition
Published online ahead of print, doi: 10.1016/j.clnu.2018.07.034
“Monthly high-dose vitamin D3 supplementation and self-reported adverse events in a 4-year randomized controlled trial”
Authors: Zarintaj Malihi, et al