Vitamin D3 vs. D2: Which Form Research Favors

Stand in the supplement aisle of any pharmacy from Portland to Presque Isle in January and you will find two kinds of vitamin D on the shelf. One bottle says D3. Another says D2. They cost about the same, they look about the same, and most shoppers grab whichever is cheaper or closer to eye level. The research says the choice matters more than the price tag, and it matters most right here, in a state where the winter sun is too weak to help.

Two letters, two different molecules

Vitamin D shows up in supplements as one of two compounds. D2 is ergocalciferol. D3 is cholecalciferol. According to the NIH Office of Dietary Supplements, the two forms differ chemically only in their side-chain structures, but they come from different places. D2 is made from plant and fungal sources, the classic example being mushrooms exposed to ultraviolet light, and it is the form often used to fortify foods. D3 is the version your own skin produces when sunlight hits it, and the kind found in fatty fish, egg yolks, and fish liver oils.

So far that sounds like a coin flip. It isn’t.

The head-to-head evidence

When researchers pool the trials, D3 comes out ahead. A 2021 systematic review and meta-analysis in Nutrients looked at 22 studies covering 1,277 people, split almost evenly between the two forms. D3 raised total blood vitamin D (the marker labs call 25-hydroxyvitamin D) by about 15.7 nmol/L more than D2 did. The same analysis found D3 did a better job suppressing parathyroid hormone, a signal tied to how the body manages bone turnover, and the authors concluded D3 was more effective regardless of the participants’ demographics, the dose, or how it was delivered.

If you want the picture without the decimal points: same vitamin, same dose, and one form simply moves the needle more.

The gap grows with big doses

How much more depends on how you take it. The 2021 review found the D3 advantage was widest with a single large dose and narrower with small daily doses. Take it daily and the difference was roughly 9.6 nmol/L. Take one big bolus and it jumped to about 25 nmol/L.

The most striking version of this comes from an older, tightly controlled study. In 2004, Armas, Hollis, and Heaney gave 20 healthy men a single 50,000 IU dose of either D2 or D3 and tracked their blood for 28 days. By that measure, D3 was about 9.5 times more potent at sustaining vitamin D levels. The D2 group’s numbers shot up and then crashed back to baseline within two weeks. The D3 group kept climbing. That is the kind of result that explains why so many clinicians quietly switched their recommendations.

A separate 2023 meta-analysis focused only on daily dosing and still found D2 fell short, raising total blood levels roughly 40 percent less than D3 across a dozen comparisons.

The catch researchers noticed

Here is the part that surprises people. Taking D2 does not just work less well. It can actually drag down the D3 portion of the vitamin D already in your blood. That 2023 analysis reported that D2 supplementation raised the D2 fraction (no surprise) while lowering the D3 fraction, and the effect was stronger in people who started with higher levels. You are adding one form and subtracting another at the same time.

Body weight changes the math, too. In people at a healthy weight, D3 was the clear winner. In people with overweight or obesity, the two forms performed about the same, and the researchers called body mass index the strongest factor shaping how anyone responded. So the D3 edge is real, but it is not identical for every body.

What this means for a Maine winter shelf

Latitude is why any of this matters here. Maine sits between roughly 43 and 47 degrees north (Portland is about 43.6). A classic 1988 study by Webb, Kline, and Holick measured what happens to skin at these latitudes in winter and found that sunlight in Boston, which sits just south of us, produced no usable vitamin D in skin from November through February. Go farther north and that dead window stretches even longer. The authors named the phenomenon the “vitamin D winter.”

That gap isn’t theoretical for Mainers. A longitudinal study of healthy 9- to 11-year-old girls in Maine, measured every September and March, found their average blood vitamin D dropped 28 percent over the winter, and nearly half showed insufficiency at some point. For four or five months a year, what you eat and what you swallow is doing the work the sun does the rest of the year.

None of this is a prescription. Health authorities set the general adult recommended intake at 600 IU a day, rising to 800 IU after age 71, with an upper limit of 4,000 IU a day for anyone nine and older, and those targets apply no matter which form you pick. The form question is narrower than the dose question. It is simply this: if you have already decided to take vitamin D through a northern winter, the evidence points toward the form your skin would have made anyway.

D3 also holds up better in the bottle. Researchers writing in Nutrition Bulletin in 2017 noted that D2 is less stable in storage and breaks down more easily, which is part of why D3 is the form generally favored for supplements and fortified foods. Reading the rest of the label is its own skill, and our guide to how to read a supplement label covers third-party testing seals and the fine print worth checking. For the deeper question of dose and delivery, see our look at choosing a vitamin D3 supplement, and for the full regional picture, our guide to vitamin D in northern New England.

Two letters. One is the form your body recognizes from a July afternoon on the coast. In February, that turns out to be the one worth grabbing.

Sources

• NIH Office of Dietary Supplements. Vitamin D – Health Professional Fact Sheet. 2024. https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/
• Balachandar R, et al. Relative Efficacy of Vitamin D2 and Vitamin D3 in Improving Vitamin D Status: Systematic Review and Meta-Analysis. Nutrients (PMC, NIH/NLM). 2021. https://pmc.ncbi.nlm.nih.gov/articles/PMC8538717/
• Comparison of the Effect of Daily Vitamin D2 and Vitamin D3 Supplementation on Serum 25-Hydroxyvitamin D Concentration and Importance of Body Mass Index: A Systematic Review and Meta-Analysis. Advances in Nutrition (PMC, NIH/NLM). 2023. https://pmc.ncbi.nlm.nih.gov/articles/PMC10831883/
• Armas LAG, Hollis BW, Heaney RP. Vitamin D2 is much less effective than vitamin D3 in humans. Journal of Clinical Endocrinology & Metabolism (PubMed). 2004. https://pubmed.ncbi.nlm.nih.gov/15531486/
• Webb AR, Kline L, Holick MF. Influence of season and latitude on the cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston and Edmonton will not promote vitamin D3 synthesis in human skin. Journal of Clinical Endocrinology & Metabolism (PubMed). 1988. https://pubmed.ncbi.nlm.nih.gov/2839537/
• Sullivan SS, et al. Adolescent girls in Maine are at risk for vitamin D insufficiency. Journal of the American Dietetic Association (PubMed). 2005. https://pubmed.ncbi.nlm.nih.gov/15942551/
• Tripkovic L, Wilson LR, Lanham-New SA. Vitamin D2 vs. vitamin D3: They are not one and the same. Nutrition Bulletin (Wiley). 2017. https://onlinelibrary.wiley.com/doi/abs/10.1111/nbu.12293

This article is for informational purposes only and does not constitute medical advice. Consult a qualified healthcare provider before making any health decisions.