Dr. Michael F. Holick, Ph.D., M.D.
Dr. Michael F. Holick

Vitamin D2 vs. D3

Posted by mfholick on November 27, 2008 under Vitamin D | 12 Comments to Read

Vitamin D2 and Vitamin D3 Are They Equally Potent?

During the past several years, there have been two studies Trang et al, (Am J Clin Nutr 68:854-858, 1998); and Armas et al, (J Clin Endocrinol Metab 89:5387-91; 2004) that have raised questions about whether vitamin D2, which is found in some supplements, used in some fortified foods and is the pharmaceutical form of vitamin D that doctors prescribe for their patients, is as effective as vitamin D3 in maintaining a person’s vitamin D status, i.e., blood level of 25-hydroxyvitamin D.  Trang et al 1998 gave healthy adults 4,000 IU of vitamin D2 or 4,000 IU of vitamin D3 in alcohol for two weeks.   A comparison of the blood levels of 25-hydroxyvitamin D after two weeks revealed that there was approximately a 50% difference in the group receiving vitamin D3 (being approximately 50% higher) than the vitamin D2 group.  This implied that vitamin D3 was more effective than vitamin D2 in maintaining circulating blood levels of 25-hydroxyvitamin D.  Armas et al 2004 gave a single 50,000 IU dose of either vitamin D2 or 50,000 IU dose of vitamin D3 to healthy volunteers during the summer and observed that the group who received vitamin D2 had a more rapid drop in their circulating blood levels of 25-hydroxyvitamin D.  They also observed that the group that received vitamin D2 had a more rapid drop in their blood levels of 25-hydroxyvitamin D3 compared to the placebo group suggesting that vitamin D2 was not only less effective than vitamin D3 in maintaining circulating levels of 25-hydroxyvitamin D, but also that vitamin D2 increased the destruction of vitamin D3.

Based on these observations, physicians, health care professionals and patients have made an effort to find vitamin D supplements that contain vitamin D3.  However, in the United States, only vitamin D2 is available as a pharmaceutical preparation, and, thus, patients who are vitamin D deficient and treated by their physicians receive vitamin D2.  I treat vitamin D deficiency with 50,000 IU of vitamin D2 once a week for eight weeks.  To prevent vitamin D deficiency from recurring, I then put the patient on 50,000 IU of vitamin D2 every two weeks forever.  From my experience of over 100 patients on this regime for up to six years, their blood levels are sustained above 30 ng/ml which is considered to be the vitamin D sufficient range.  On average, the blood level was between 40-50 ng/ml.  Furthermore, an evaluation of their blood calcium, a measure of whether ingesting vitamin D2 at these levels, had caused any toxicity did not change.  Therefore, this regime was effective in maintaining my patients’ vitamin D status without causing any untoward toxicity.

To determine whether vitamin D2 was as effective as vitamin D3 in maintaining circulating blood levels of 25-hydroxyvitamin D, a study was conducted whereby healthy adults received either 1,000 IU of vitamin D2 or 1,000 IU of vitamin D3 in a capsule once a day in the winter for 11 weeks.  In addition, one group received a placebo capsule and one group received a capsule that contained 500 IU of vitamin D2 and 500 IU of vitamin D3 daily for 11 weeks.  Blood levels of both 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 were determined by state of the art method using liquid chromatography tandem mass spectroscopy.  Holick et al, (Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D, J Clin Endocrinol Metab  93:677-681, 2008;) reported that the blood levels of 25-hydroxvitamin D rose to the same degree in the healthy adults who took either 1,000 IU of vitamin D2 a day or 1,000 IU of vitamin D3 a day for 11 weeks.  The group that received vitamin D2 also had their blood level of 25-hydroxyvitamin D3 measured.  There was no significant drop in the blood level of 25-hydroxyvitamin D3.  To determine whether the mixture of vitamin D2 with vitamin D3 would alter the blood levels of 25-hydroxyvitamin D, the adults who received 500 units of vitamin D2 with 500 units of vitamin D3 also raised their total blood levels of 25-hydroxyvitamin D3 in an almost an identical manner as the adults who received 1,000 IU of vitamin D2 or 1,000 IU of vitamin D3 a day for 11 weeks.  The authors concluded that ingesting 1,000 IU of vitamin D2 or 1,000 IU of vitamin D3 a day during the winter (at a time when sun exposure had no influence on blood levels of 25-hydroxyvitamin D) that both vitamin D2 and vitamin D3 were equally effective in maintaining the blood levels of 25-hydroxyvitamin D.  Furthermore, vitamin D2 did not have a negative influence on serum levels of 25-hydroxyvitamin D3.  Adults who took 500 units of vitamin D2 with 500 units of vitamin D3 had similar increases in their blood levels of 25-hydroxyvitamin D suggesting that vitamin D2 taken with vitamin D3 does not have any negative influence on the metabolism of vitamin D3.  

The authors reviewed in their Conclusion several studies that had previously reported that vitamin D2 was as biologically effective as vitamin D3 in both pregnant women and in healthy adults.  This study confirms these observations and adds to the body of scientific literature demonstrating that at least when healthy adults take 1,000 IU of vitamin D2, they can be assured that it is as effective as taking 1,000 IU of vitamin D3.  

  • john stovall said,

    Since, as you pointed out, D-2 is only available via prescription, and D-3 is available OTC(D-3 Extreme from prohealth.com), wouldn’t it benefit your patients to purchase the latter preparation? I ask this because my wife seemed to get near immediate relief for her fibromyalgia with the D-2 50000 IU, and I am now planning to purchase the D-3 preperation for her. I would welcome any constructive comments.

  • Evelyne Tourigny said,

    I believe from my own experience that D2 is more effective on my fybromyalgia than D3. My blood level of D125 was very very high and my D25 was low. So, I suggest that your wife pass blood test of D125 and D25 before taking D3 just to be sure that her Dratio is at 0.95. Mine was at mor than 5. Also read about Batters syndrom and D ratio.

  • r.johnson said,

    mother at 90 years old put on your 50k iu program for deficiecy (rx). concerned over possible hypercalcemia and resultant effects it might have on her severe aortic stenosis. warranted? what can you send me to read before next doctors visit? thanks for your groundbreaking research!

  • To Much said,

    I take 4000 mg of Vit 43 a day. Took a blood test at Drs office and she said I needed more, she put me on 50,000units of D2 1.25mg, 1 capsule by mouth 2 times a week for 4 weeks. What is the difference and am I taking enough or do I need more?.

  • alfa1020 said,

    Vitamin D2 is not prescritpion only. I have just returned from England (April 2012)and whilst there, purchased from a supplement company 360 1000iu tablets through the mail. Next day delivery.

  • Candace said,

    I had a blood test that revealed that my Vitamin D level was 20 ng, and my Dr would like to see it at least up to 30 – 70 ng. I began taking 50,000 IU vitamin D2 once weekly for 8 weeks, then plan to switch to 1000 D3 daily for maintenance. From your statements above it looks like this may be a good plan for me. I was diagnosed 28 years ago with osteomalacia, but was led to believe that with proper diet and exercise I would not have to worry about Vitamin D deficiency in the future.

    I was diagnosed 13 years ago with severe fibromyalgia and vitamin D levels were never considered as a possible problem. I just changed doctors and this new doctor was surprised that my vitamin D levels have not been monitored through the years. I am just realizing how devestating vitamin D deficiencies can be to the body.

    Thank You for your information it is very helpful in understanding how to treat this disorder.


  • admin said,

    Dear alfa1020,
    Vitamin D2 is the only prescription form of Vitamin D in the United States. Most other countries in Europe, Asia as well as Australia mainly used vitamin D3 as a pharmaceutical. Vitamin D3 is readily available as a supplement in the United States.

  • admin said,

    Dear Candace,
    50,000 international units of vitamin D2 weekly should correct your vitamin D deficiency. However to maintain vitamin D deficiency I keep my patients on 50,000 international units of vitamin D once every 2 weeks. The alternative is to take 2000 international units vitamin D3 daily.

  • MZ said,

    I recently had my vitamin D levels drawn. My total is 37 and the D2 is <4. My doc says the levels are WNL.

    My joints hurt, I'm tired all the time, I'm unhappy (not normally), and I am moody.

    Any thoughts or suggestions?

    PS: my mothers vitamin D was recently at 9. Have there been any genetic links found?

  • admin said,

    Dear MZ,
    I agree with your physician. A level of 37 ng/mL is perfectly fine. The fact that your mother is very low at 9 ng/mL is consistent with the observations that diet provides very little vitamin D and that sensible sun exposure and a vitamin D supplement of 2000 IU vitamin D daily is required to maintain blood levels of 25-hydroxyvitamin D >30 ng/mL. Regarding your symptoms unfortunately they are not likely due to a deficiency in vitamin D.

  • nelson said,

    I recently had a vit D test and the results are D2<4.0, D3 39 and my total D 39. I have been taking a D3 2000IU daily. I am wondering, since I'm taking a daily supplement on my own and my total D is 39 (optimal around 50 from what I read on the net) should I be increasing my daily intake to 4000 IU's. I am on pravastatin for high chol. My current test indicate 148/ 37 HDL and 99LDL. Should I increase my intake?

  • admin said,

    Dear Nelson,
    39 ng/mL is fine. The Endocrine Society recommends a level of 40-60 ng/ML. I personally take 3000 IUs of vitamin D daily and my blood level is 50 ng/mL. Therefore it is reasonable if you want to increase your vitamin D intake to 3000 IUs daily.

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