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RCT: Dietary and supplemental D2 did not increase total vitamin D blood levels

Posted on: July 16, 2012   by  Rebecca Oshiro


A recent study published in The Journal of Nutrition found that D2 administered in supplemental form or as part of a meal containing mushrooms increased blood levels of D2 but simultaneously decreased blood levels of D3.

Stephensen CB, Zerofsky M, Burnett DJ, Lin YP, Hammock BD, Hall LM, McHugh T. Ergocalciferol from mushrooms or supplements consumed with a standard meal increases 25-hydroxyergocalciferol but decreases 25-hydroxycholecalciferol in the serum of healthy adults. J Nutr. 2012 Jul;142(7):1246-52. Epub 2012 May 23.

This double-blind, randomized feeding trial sought to determine if consuming UV-treated mushrooms is an efficacious way to raise blood levels of D2 and total vitamin D [25(OH)D]. 38 participants were divided into four groups:

  • placebo (non-irradiated mushrooms and a placebo capsule for a total of 34 IU D2)
  • M1 (mushrooms containing 352 IU D2 per serving plus a placebo capsule)
  • M2 (mushrooms containing 684 IU D2 per serving plus a placebo capsule)
  • a supplemental group that received a D2 capsule alongside non-irradiated mushrooms for a total of 1128 IU D2.

Each group received a lunch at the study site for six weeks that contained a serving of the mushroom they had been randomized to along with the corresponding capsule. They were provided with meals to take home for weekend lunches.

All the treatment groups experienced statistically significant elevations in D2 levels, but these gains were negated by an almost equal decrease in their D3 levels. Interestingly, the more vitamin D2 participants received, the more their D3 levels dropped. A significant negative association was calculated, such that for every .4 ng/mL increase in D2 levels, there was a .3 ng/mL decrease in D3 levels. At the end of the study, none of the treatment groups experienced statistically significant increases in total vitamin D [25(OH)D] status.

Similar studies conducted previously saw significant increases in total 25(OH)D status after D2 supplementation, but two key differences may explain this. Participants in the current study had higher baseline levels of total 25(OH)D ( >20 ng/mL) than other studies and presumably higher levels of D3 from sun exposure due to latitudinal and seasonal differences more favorable to vitamin D production.

The authors offered three possible explanations for the decreases seen in D3 levels as a result of D2 supplementation:

1.  The first is the possibility that increased intake of D2 accelerates the breakdown of D3 by increasing the activity of the 24-hydroxylase, the enzyme responsible for the catabolism of D3. However, compounds involved in this breakdown were measured in this study and there were no significant elevations, meaning that there wasn’t increased activity.

2.  Another possibility is that a negative reaction might occur between D2 and D3 in the liver, where increased D2 consumption could inhibit 25(OH)D production in general, so the body doesn’t more readily convert D3 into 25(OH)D.

3.  Lastly, there could be competition between D2 and D3 for absorption in the gut, although unlikely since most D3 would have been from skin production in this study.

In conclusion, previous studies have shown increases in total 25(OH)D in deficient participants receiving D2 rich mushrooms, but these results were not replicated in participants with higher baseline levels of 25(OH)D. The concurrent decrease in D3 levels seen with an increase of D2 levels was such that no significant rise in total vitamin D serum was seen in any of the treatment groups. Due to unresolved concerns regarding the ability of D2 supplementation to favorably impact 25(OH)D status, supplemental D3 is still recommended at this time.

8 Responses to RCT: Dietary and supplemental D2 did not increase total vitamin D blood levels

  1. John Cannell, MD

    Another possibilty is that the body preferential clears D3 over D2 because the body prefers to use D3.

    John Cannell, MD

    • Brant Cebulla

      John, the big thing in this study is that the more D2 someone took, the more D3 they cleared. What do you make of that? I would have guessed that the more vitamin D you take, the more you use and breakdown; but they measured 24-hydroxylase and found no evidence of increased activity here. Given such, why would D2 force you to clear D3?

  2. [email protected]

    The RCT referenced and 20 previous studies comparing D3 and D2 have all shown problems with D2. In 2011 Cochrane reported that D3, but not D2 reduced death rate. In 2003 it was decided that no primate should have D2. etc etc. Details and an excellent pair of graphs are at http://www.vitamindwiki.com/tiki-index.php?page_id=2138

  3. Rebecca Oshiro

    Thank you, Dr. Cannell! And Brant, I find that so confusing myself.

  4. Ian

    Is D2 stored effectively in adipose tissue? What is the rate of storage of D3 into adipose tissue?
    Could it be that the D3 is being preferentially stored, hence no elevated hydroxylase activity?

  5. Ian

    Does this one give a clue?
    Decreased bioavailability of vitamin D in obesity1,2,3 Jacobo Wortsman, Lois Y Matsuoka, Tai C Chen, Zhiren Lu, and Michael F Holick

    “It is possible that the subcutaneous fat, which is known to store vitamin D3, sequestered more of the cutaneous synthesized vitamin D3 in the obese than in the nonobese subjects because there was more fat available for this process. To determine whether the same phenomenon occurred when vitamin D was ingested orally, obese and nonobese subjects were challenged with an oral dose of 50000 IU vitamin D2. There was no relation between basal vitamin D2 concentrations and 25(OH)D. Peak blood concentrations of vitamin D2 were not significantly different between the obese and nonobese subjects. However, BMI was inversely correlated with peak blood vitamin D2 concentrations. Thus, the orally supplied vitamin D2 was more bioavailable, probably because after absorption into the lymphatic system and transfer into the bloodstream, it is also sequestered in the large pool of body fat. “

  6. Rebecca Oshiro

    Ian, I just finished reading a paper last night that challenges the idea of adipose tissue
    sequestering vitamin D. They suggest low vitamin D levels may actually be creating an environment that favors fat accumulation. Details soon! As for this study, the average BMIs of the control, supplement, M1 and M2 groups were 22.8, 24.5, 22.1 and 23.4 respectively. No one group had an average BMI that was even considered overweight, let alone obese.

  7. John Cannell, MD

    Good comments. I am not sure that giving someone 50,000 IU of D2 means their body starts utilizing more total vitamin D. Perhaps it just goes on utilizing D3 at the rate they did before and the D2 goes to muscle and fat (remember it is not just fat that stores it). If so, the 24 hydroxyalase would not be up regulated.

    I am leery of D2 and believe all D2 experiments will have to be repeated with human vitamin D.

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