Scientists have found that taking one type of vitamin D supplement appears to reduce the levels of another type that is more easily used by the body, and which could affect our immune system, reports New Scientist.
Our bodies create vitamin D when ultraviolet rays in sunlight convert a protein called 7-dehydrocholesterol in the skin into a type of vitamin D known as vitamin D3. When sunlight is sparse, some countries, for instance Britain, recommend people take supplements.
Two forms of these supplements are available: vitamin D3, or cholecalciferol – which normally comes from lanolin, the waxy substance on sheep’s wool – and vitamin D2, or ergocalciferol, which mainly comes from mushrooms. It was thought that it didn’t really matter which one you took.
But now, Emily Brown at the University of Surrey, UK, and her colleagues have performed a meta-analysis of 11 previously published, randomised-controlled trials on vitamin D supplements, with a total of 655 participants.
They found that taking vitamin D2 supplements can lead to a drop in the body’s concentration of vitamin D3. Why this happens, or if vitamin D3 supplements reduce vitamin D2 levels, isn’t entirely clear. Furthermore, in many of the studies, the vitamin D3 levels were lower in people taking vitamin D2 than they were in control groups not taking any vitamin D supplements.
“This is a previously unknown effect,” said Brown.
A 2022 study suggests vitamin D2 and D3 have overlapping but different roles in supporting immune function. Only vitamin D3 seems to stimulate the type-I interferon signalling system, for instance, which provides a first line of defence against bacteria and viruses.
Brown says the findings suggest vitamin D3 supplements may be more beneficial for most individuals than vitamin D2, but adds personal considerations need to be taken into account, such as wanting to avoid animal products.
They also don’t mean people should just stop taking vitamin D2, she said. “Your total vitamin D level will still be sufficient if you are taking vitamin D2 supplements, but you might find that it’s less effective and you might lose out on those additional functions regarding immune support.”
Ouliana Ziouzenkova at The Ohio State University points out studies have shown that among older people, the conversion of vitamin D3 to its active form called calcitriol can be less efficient, so D2 supplementation may be particularly beneficial in this population.
“In the absence of any evidence for negative effects, if someone who is vegan is deficient in vitamin D, opting for a D2 supplement over no supplement remains the prudent choice,” said Bernadette Moore at the University of Liverpool.
Plant-based vitamin D3 has started to become more accessible. For instance, a tomato has been gene-edited to produce vitamin D3, but trials are ongoing.
Team member Susan Lanham-New, also at the University of Surrey, hopes the research will remind people of the importance of vitamin D supplements. “There are many people in the United Kingdom and other areas of northern latitude who in winter get mild osteomalacia (known as rickets in children), caused by lack of vitamin D – which presents itself in lethargy, bone pain, muscle ache, susceptibility to infection, tiredness – and don’t realise,” she says.
Study details
Effect of vitamin d2 supplementation on 25-hydroxyvitamin d3 status: a systematic review and meta-analysis of randomised controlled trials open access
Emily Brown, Andrea Darling, Tracey Robertson, et al.
Published in Nutrition Reviews on 18 September 2025-
Abstract
Context
Researchers have identified differences in metabolic activity between vitamins D2 and D3. Moreover, it is suspected from randomised controlled trial data that vitamin D2 supplementation increases the metabolic clearance of 25-hydroxyvitamin D3 [25(OH)D3], but this effect has yet to be quantified.
Objective
This study sought to undertake a systematic review and meta-analysis of the effect of vitamin D2 supplementation on serum 25(OH)D3 concentrations.
Data Sources
PUBMED was searched for articles published from1 January 1975, to 1 February 2023. Of the 202 articles retrieved, 20 were included in this review, and of those, 11 were suitable for meta-analysis.
Data Extraction
Randomised controlled trials reporting either baseline and post-intervention serum 25(OH)D3 concentrations (nmol/L) or absolute changes in concentrations were included. Random-effects meta-analyses were calculated using Review Manager (version 5.3; The Cochrane Collaboration). Mean differences were reported with 95% CIs.
Data Analysis
In meta-analyses there was a reduction in serum 25(OH)D3 after vitamin D2 supplementation compared with control for end-of-trial between-groups data (random weighted mean difference [WMD] = −17.99 nmol/L; 95% CI, −25.86 to −10.12; P < .00001) and absolute change over the trial (random WMD = −9.25 nmol/L; 95% CI, −14.40 to −4.10; P = .0004).
Conclusions
Study participants who received vitamin D2 supplementation showed statistically significant reductions in serum 25(OH)D3 concentrations, compared to controls without supplementation. An inverse relationship between vitamin D2 and D3 concentrations has been proposed in the literature. A regulatory mechanism that increases the disposal rate of 25(OH)D after an increase in vitamin D concentrations could explain these results. However, further research is needed to establish whether vitamins D2 and D3 elicit different changes in overall vitamin D metabolism that might influence clinical advice to recommend vitamin D3 supplements over vitamin D2 supplements, where appropriate.
See more from MedicalBrief archives:
Vitamin D may slow cells’ ageing – Harvard study
Multivitamins don’t help you live longer – major US study
US study flags high vitamin D deficiency rates
Meta-analysis: No cardiovascular benefits to dietary supplements except vitamin B
Adverse effects of non-prescribed vitamins and supplements intake
Cancer mortality may drop by 12% with daily vitamin D – Germany study