Low dose vitamin D, calcium supplementation has little impact on adult subjects - RCT

Despite vitamin D deficiency being prevalent in the Middle East, few studies have tried to determine its health impact and what can be done to combat it.

As such, researchers from the United Arab Emirates University conducted an RCT to assess whether vitamin D3 and calcium, either alone or in combination, have significant health benefits on vitamin D-deficient adults.

Healthy but low on D?​

The researchers recruited 545 “apparently healthy community free-living”​ adults aged 18 and older in Al Ain, UAE for the RCT and randomly assigned them to receive tablets containing either 2000 IU of oral vitamin D3, 600 mg of calcium, a combination of the two, or a placebo daily for six months.

The study, conducted over a period of three years, focused on self-rated health and bone turnover markers as primary outcomes and measured participants’ 25(OH)D levels using their blood and urine samples.

Outcome measures were biochemical variables of metabolic risk factors, bone turnover (biochemical measures of bone metabolism) and muscle and general health. Of the 545 subjects, 277 completed a six-month follow-up after the trial had concluded.

The researchers found that 25(OH)D levels “marginally increased” in the two groups who had received vitamin D3 alone or combined with calcium, while a decline in 25(OH)D levels was seen in those who had received the calcium supplement alone or a placebo.

According to sub-group analysis, parathyroid hormone (PTH) concentration decreased and calcium-creatinine ratio increased significantly in those who had taken a combination of vitamin D and calcium, compared to those who had vitamin D or calcium alone, while an increase in both was seen in the placebo group.

However, at the six-month follow-up, there were “no statistically significant differences between the supplement and placebo groups” in body weight, BMI, blood pressure, body pains and general health.

Deficiency in benefits: Why?​

There were several possible reasons for the supplements’ lack of potential benefits in the RCT, including the large number of randomized subjects who did not attend the six-month follow-up. The researchers did note, however, that “baseline demographic and clinical characteristics were well-balanced across the groups who had follow-up data compared to those who did not come for the follow-up”.​

Additionally, 25(OH)D levels did not show the expected increase in relation to supplementation dosage and duration, though this was marginally better in those who reported consuming more than “120 (50th quartile) of prescribed trial medications”.​

Furthermore, 198 (70%) of the study’s subjects were overweight or obese, which were “reported to markedly decrease response to vitamin D supplementation”, ​possibly due to “greater volume of distribution and tightly bound vitamin D in fatty tissues”.​ According to recent research and some health professionals’ recommendations, obese individuals should receive two to three times more vitamin D than those of normal weight.

Still, adjustments for BMI, physical activity, sun exposure and a vitamin D- and calcium-rich diet did not show a “significant association with baseline vitamin D levels or response to supplements”.​

The researchers wrote there was an urgent need to study the impact of a higher dose, frequency and duration of vitamin D supplementation to “reach and sustain higher levels of 25(OH)D” ​and determine if vitamin D supplementation would have clinical benefits on a high-risk population.

They further acknowledged that research was required to test emerging evidence on how increased dietary intake or oral supplementation with calcium may mitigate the deleterious health effects of low vitamin D concentrations.

Finally, they stated that it was important to study the effects of a higher dose, frequency and duration of vitamin D supplementation, including more testing and adherence to the supplements to reach and sustain higher levels of 25(OH)D, especially in high-risk populations.

 ​

Source:​ BMC Musculoskeletal Disorders​

“A randomized, double-blind, placebo-controlled trial of vitamin D supplementation with or without calcium in community-dwelling vitamin D-deficient subjects​”

Authors:​ Salah Gariballa, et al.