Effectiveness of Vitamin D Supplements Affected by Multiple Factors

A new study suggests that factors such as gender, type of vitamin D, dosing schedule and BMI may influence the impact of your vitamin D supplements.

Vitamin D is an important nutrient that our bodies require in relatively large doses to maintain bone, nerve and organ health, as well as cognitive functioning. However, studies have shown that a large proportion of the world’s population is deficient in vitamin D – more than two-thirds in the US and Europe, and even higher percentages in other parts of the world.

Vitamin D comes in two primary forms: vitamin D2 (ergocalciferol), produced by plants, particularly mushrooms; and vitamin D3 (cholecalciferol), produced in humans through exposure to sunlight, and available from foods such as fish oils and egg yolk.

Given the widespread problem of vitamin D deficiency, vitamin D supplementation has become increasingly common, both as an additive in food sources like milk and cereals, and through pills, capsules, or drops.

However, controversy persists as to which type of D vitamin – D2 or D3 – is most effective in supplement form. Past research has provided inconsistent data on this point, potentially because absorption of supplements may be influenced by a range of factors including pre-existing vitamin D levels, body mass index (BMI), gender and frequency of supplementation, among other things.

A recent study published in BMC Endocrine Disorders examined the relationship between different vitamin D supplement regimes and levels of 25-hydroxy D, which is the best indicator of vitamin D status in the body.

The study involved 279 adults randomly assigned to receive vitamin D supplements according to varying regimens for a period of 140 days:

• Three groups of participants received daily doses of either D2, D3, or D2 and D3 combined;
• Two groups received either D2 or D3 in a bolus administered every two weeks;
• Two groups received either D2 or D3 in a bolus administered every four weeks;
• One additional group received placebos.

Doses were adjusted so that all participants (other than placebo) received the same total amount of vitamin D over the 140-day period of the trial, regardless of which group they were assigned to. Both researchers and participants were blinded to which participants were assigned to which vitamin D regimen.

The study produced a number of interesting results, including the following:

• Overall, participants receiving the 2-weekly bolus of vitamin D3 showed the greatest increase in 25-hydroxy D levels, followed by the 4-weekly vitamin D3 group, and the daily vitamin D2 group.
• During the first weeks of the trial, the 4-weekly regimens and 2-weekly regimens, respectively, were superior to all daily regimens.
• Vitamin D3 showed consistently higher effects than D2 for those participants on the 2-weekly and 4-weekly regimens. However, the vitamin D2 daily regimen was consistently more effective than the D3 daily regimen.
• Looking at vitamin D2 alone, participants receiving daily doses showed significantly higher 25-hydroxy D levels compared to participants in the 2-weekly and 4-weekly groups. The situation was reversed for vitamin D3, participants receiving daily doses showed lower 25-hydroxy D levels than those receiving the 2-weekly and 4-weekly bolus.
• The increase in 25-hydroxy D levels was inversely related to the baseline level, suggesting a threshold mechanism that may reduce the impact of supplementation on those with higher starting vitamin D levels.
• BMI was predictive of responsiveness to vitamin D2 supplementation but not vitamin D3; in addition, the correlation only applied during the first 4 weeks of the study regime. Past research had suggested that higher BMI was associated with less response to vitamin D supplements. However, this study’s results indicate a more complex relationship, depending in addition on the type of D vitamin administered, and the timing of the assessment.
• Women showed higher increases in D3, D2, and 25-hydroxy D levels than men, suggesting gender plays a role in the responsiveness to supplementation.
• Vitamin D treatment was associated with significant increases in urinary calcium and creatinine levels but not in the calcium/creatinine ratio.
• 25-hydroxy D levels increased in all groups receiving supplementation regardless of regimen, and increased significantly over placebo (6 nmol/L across all treatment groups compared with 3.3 nmol/L in the placebo group).

Authors of the study consider these results to show that effectiveness of vitamin D2 and D3 supplements may depend on a more complex array of factors than previously understood, including dosing schedule, gender, BMI, type of vitamin D, and total vitamin D levels. Overall, however, the results appear to confirm that vitamin D supplementation, whatever the form, does increase25-hydroxy D levels in the body.

Written By: Linda Jensen