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Meta-analysis of RCTs compares efficacy of D2 vs D3 supplementation

Posted on: May 15, 2012   by  Kate Saley

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One of the most common questions we receive about vitamin D supplementation is whether to use D2 or D3. Generally, studies show that D3 is more potent and more efficacious, and it is also the “natural” form because it’s what your own body produces.

But let’s look at a recent meta-analysis to settle the potency debate.

Tripkovic L, Lambert H, Hart K, Smith CP, Bucca G, Penson S, Chope G, Hypponen E, Berry J, Vieth R, Lanham-New S. Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis. Am J Clin Nutr. May 2012.

Professor Tripkovic and colleagues at the University of Surrey reviewed 10 randomized controlled trials (RCTs) with a collective total of 1,016 participants ages 18-97. The studies included in the review encompassed a range of different dosages and administration methods:

  • Two of the studies administered a single bolus dose of varying quantities, one using alternate routes of administration (oral or intramuscular).
  • Six studies preferred daily supplementation with dosages ranging from 1,000 to 4,000 IU.
  • One study compared daily to monthly supplementation, 1,600 to 50,000 respectively, while another study supplemented 50,000 IU weekly.
  • The final study compared a single intramuscular injection of 300,000 IU of D2 to a single oral dose of 300,000 IU D3.

The researchers found:

  • In eight of the studies, regardless of the dose, frequency, or administration, concluded that cholecalciferol (D3) produced a significantly greater increase from baseline serum 25(OH)D levels compared with ergocalciferol (D2).
  • Two studies showed D2 and D3 were equally effective in raising serum 25(OH)D.

The authors also determined whether frequency of dosage had an effect on favoring of D2 or D3. Three out of the 4 studies which used bolus doses reported results which favored using vitamin D3 to raise serum levels most effectively. When focusing on the studies which used daily supplementation the results weren’t as strong, but a clear preference for cholecalciferol was present.

So the recommendation remains that D3 is preferable to D2 for better potency. If your doctor prescribes vitamin D from a pharmacy (usually Drisdol), ask them if you might be able to take alternative steps to ensure you receive vitamin D3 instead.

5 Responses to Meta-analysis of RCTs compares efficacy of D2 vs D3 supplementation

  1. texarc@gmail.com

    Please be aware that your pharmacist can order a 50,000iu D3 capsule from a distributor so you take it weekly, or it can be ordered directly from HiTech, for about $40.00 per 100 caps. That is the most cost effective way to get a 2 year supply! Just be cautious to NEVER, ever, exceed the daily limit of calcium (1000 to 1200 mg per day from ALL sources, counting also milk, yogurt,etc. as well as tablets) and do not take more than your blood level warrants. It is good to be aggressive about your blood level of 25(OH)D, but do so prudently and with information/intelligence! In other words, be sure to get tested!

  2. Brant Cebulla

    Thanks texarc. I believe pharmacies can get BioTech 50k IU capsules as well, no?

  3. bacullen@gmail.com

    “Two studies showed D2 and D3 were equally effective.” Equally effective at what?? It appears that the meta-analysis only looked at the ability to raise the circulating D2 or D3 concentration. Looking at the chemical structures of the 2 compounds it is likely that they would be absorbed by the body at similar rates.

    It is quite clear from the literature that D2, ergocalciferol, is NOT the chemical compound that ANY vertebrate should take (or be given) to replace a deficiency of D3, cholecalciferol, due to insufficient UVb exposure. D2 is a Medical Industry patent chemical, whereas D3 is real “vitamin” D.

    • Brant Cebulla

      bacullen, don’t lose sight that in the meta-analysis the authors point out that 8 studies found that D3 and D2 were not equally potent.

  4. texarc@gmail.com

    Sorry, Brant – just checked back on this thread. Pharmacies can indeed acquire the 50k iu D3 capsules from their distributor in order to use it anytime a doctor chooses to prescribe “vitamin d 50,000iu” – as I have done, all with complete accuracy and legality, and based on the science, definitely in my convictions a far better therapy than D2. Not quite as good as pure sun, but if a patient is not capable for whatever reason of obeying the “get sun regularly, just never burn” direction, then I feel Dr. Cannell has made a point – oral supplementation is prudent.
    The fascinating thing, is, those HiTech 50,000iu D3 capsules are OTC. Frankly, I have come to view many, many other “supplements”, like calcium and magnesium, or even common acetaminophen, as more likely to cause harm if overdose/misused, than say, D3 is.

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