KNOW HOW: Good Design for Your Vitamin D Trial

Dr. med. Raimund von Helden, Verbraucherberatung VitaminDelta, 57368 Lennestadt referring to Grant WB et al.


1) Fragestellung


citation of William Grant et al.: (1)

  • Many health benefits are attributed to vitamin D, ...
  • with those findings supported mostly by observational outcome studies of relationships to serum 25-hydroxyvitamin D [25(OH)D].
  • However, many randomized controlled trials (RCTs) aiming to confirm those findings have failed,
  • ...perhaps because serum 25(OH)D is an index of UVB exposure
  • and non-vitamin D mechanisms or because disease reduces serum 25(OH)D content.


  • But the most likely reason for that failure is inappropriate design, conduct, analysis, and interpretation of RCTs.
  • Most RCTs used principles designed to test pharmaceutical drugs;
  • that design incorporates the assumptions that the RCT is the sole source of the agent
  • and that dose-response relationships are linear.
  • However, neither assumption is true for vitamin D, since
  • neither vitamin D dose-responses or health outcome serum 25(OH)D concentration relationships are linear-
  • larger changes being induced with low rather than high baseline 25(OH)D values.

2) Methode


3) Ergebnisse

Grant WB et al:
Here, we propose a hybrid observational approach to vitamin D RCT design,
based primarily on serum 25(OH)D concentration,
requiring an understanding of serum 25(OH)D concentration-health outcome relationships,
  1. measuring baseline 25(OH)D values,
  2. recruiting non-replete subjects,
  3. measuring serum 25(OH)D during the trial
  4. for adjustment of supplemental doses for achievement of pretrial selection of
  5. target 25(OH)D values,
  6. and analyzing health outcomes in relation to those target values
  7.  rather than solely to vitamin D dosages.

4) Folgerungen

✅ get the baseline Vitamin D level - before intake
✅ get Calcium, alk Phosph, Kreatinine, Magnesium serum levels
✅ use the including target, setup and maintainance for each subject
✅ get a second Vitamin D level - in the end 

Try to display yout data with a scatter plot as shown in this example:
"The best display for significance is... a scatter plot, because the level counts, not the group!"
  • x-axis with Vitamin D level
  • y-axis with your parameter of clinical items
  • most transparent display of your data & variation
  • regression-curve shows the correlation
The biggest advantage however is this:
  • Some subjects will rise their Vitamin D level by intake, others will not. 
  • Sunshine can make a big diffence: 10.000 to 20.000 Units every day in addition.
  • However this additional Vitamin D from sunshine does not harm this kind of scatter plot.
  • The display sets the focus on the resulting vitamin D level, but not the Vitamin D intake.


Grant WB, Boucher BJ, Bhattoa HP, Lahore H.
Why vitamin D clinical trials should be based on 25-hydroxyvitamin D concentrations.
J Steroid Biochem Mol Biol. 2018 Mar;177:266-269. doi: 10.1016/j.jsbmb.2017.08.009.
Epub 2017 Aug 24. PubMed PMID: 28842142.

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