The randomised controlled trial, by researchers in Riyadh, Saudi Arabia, enlisted 269 subjects between 18 and 60, 41% males and 59% females, who were not taking vitamin D supplements, consuming more than one serving of milk per day, or getting more than 10 hours per week of exposure to the sun.
The researchers split the participants into a number of different supplementation protocols, providing them vitamin D2 daily, vitamin D3 daily, a daily D2/D3 combination, D2 or D3 fortnightly, D2 or D3 every four weeks, or a daily placebo, for 140 days, all in the form of standardized oral capsules.
All participants except those in the placebo group received a total vitamin D dose of 250,000 IU over the 140 day study period, not counting any missed doses. Doses ranged from 2,000 IU for daily protocols to 50,000 IU for four-weekly protocols.
Researchers drew blood before the start of the protocols, every day for the first four days, then at day seven, day 14, and every two weeks after that.
Daily D less effective
While all the active supplementation regimens raised blood serum 25(OH)D levels, the study found the two-weekly D3 protocol, followed by the 4-weekly D3 protocol and the daily D2, were the best at raising blood serum levels across the full length of the study period.
The study, published in the journal BMC Endocrine Disorders, also showed that participants receiving only D2 showed decreases in their levels of D3, as shown in previous studies, and that this was linked to the resulting overall level of 25(OH)D, rather than levels of D2 consumed.
“It may be that there is a regulatory mechanism that increases the disposal of 25(OH)D in response to increases in its level and that it has been observed with D2 treatment mainly because study participants commonly don’t have measurable 25(OH)D2 levels,” the researchers wrote in their study.
“Since there was essentially no change in 25(OH)D3 level in the group that received combination of 1000 IU D2 and 1000 IU D3, it appears that, in a setting similar to our study (baseline 25(OH)D level around 40 nmol/L and average dose of 1800 IU daily), an amount of 25(OH)D that can be produced by 1000 IU intake is disposed daily. If such a mechanism really exists it can be exploited in defining normal 25(OH)D levels,” they added.
Genetic link to lower uptake
When pooling data with two other trials, the researchers noted subjects with particular gene variants linked to low baseline 25(OH)D blood serum levels also showed the smallest increases.
“Thus in some subjects, low baseline 25(OH)D level may reflect a genetic potential rather than lifestyle influence and may be associated with lower rather than higher increment in 25(OH)D level,” they wrote.
Female subjects in the study showed 22% higher vitamin D uptake rates than men after 140 days, with the researchers saying their results suggested around 49% better bioavailability of both D2 and D3 in women.
They noted D binding proteins are higher in women than men, as well as women on oral contraceptives, premenopausal women, and postmenopausal women on hormone therapy, suggesting a link with oestrogen.
“The observed sex differences may be related to higher D binding protein and faster 25-hydroxyaltion in females; although a sex difference in D absorption rate cannot be excluded. It is also possible that higher body fat and lower baseline 25(OH)D levels in females may play a role,” they noted.
The researchers also noted body mass index was a significant predictor for D2 levels, but not D3, and only during the first four weeks of treatment. But they said the link between BMI and the response to vitamin D supplementation was not clear.
Source: BMC Endocrine Disorders
Published online ahead of print, doi: 10.1186/s12902-017-0163-9
“Differential effects of vitamin D2 and D3 supplements on 25-hydroxyvitamin D level are dose, sex, and time dependent: a randomized controlled trial”
Authors: Hammami, M.M.; Yusuf, A.