Vitamin D dose response is underestimated by Endocrine Society's Clinical Practice Guideline
Endocr Connect 2013 EC-13-0008
Malachi J McKenna mjmckenn at iol.ie and Barbara F Murray
M McKenna, St. Michael's Hospital, Dun Laoghaire, Ireland
B Murray, St. Michael's Hospital, Dun Laoghaire, Ireland
Objective: The recommended daily intakes of vitamin D according to the recent Clinical Practice Guideline (CPG) of the Endocrine Society are 3-to-5-fold higher than the Institute of Medicine (IOM) report. We speculated that these differences could be explained by different mathematical approaches to the vitamin D dose response.
Methods: Studies were selected if the daily dose was <=2000 International Units (IU)/d, the duration exceeded 3 months, and 25-hydroxyvitamin D (25OHD) concentrations were measured at baseline and post-therapy. The rate constant was estimated according to the CPG approach.
The achieved 25OHD result was estimated according to:
- (1) the regression equation approach of the IOM;
- (2) the regression approach of the Vitamin D Supplementation in Older Subjects (VIDOS) study; and
- (3) the CPG approach using a rate constant of 2.5 (CPG2.5)
- and a rate constant of 5.0 (CPG5.0).
The difference between the expected and observed 25OHD result was expressed as a percentage of observed, and analysed for significance against a value of 0% for the four groups.
Results: Forty-one studies were analysed. The mean (CI) rate constant was 5.3(4.4-6.2) nmol/L /100 IU/d, on average 2-fold higher than the CPG rate constant. The mean (CI) for the difference between the expected and observed expressed as a percentage of observed were:
- (1) IOM, -7(-16,+2)% (t=1.64, p=0.110);
- (2) VIDOS, +2(-8,+12)% (t=0.40, p=0.69);
- (3) CPG2.5, -21(-27,-15)% (t=7.2, p<0.0001); and
- (4) CPG5.0 +3(-4,+10)% (t=0.91, p=0.366).
Conclusion: The CPG "rule of thumb" should be doubled to 5.0 nmol/L (2.0 ng/ml)/100 IU/d, adopting a more risk-averse position.
Received 9 February 2013; Received in final form 10 March 2013; Accepted 12 March 2013; Accepted Preprint first posted online on 12 March 2013
PDF is attached at the bottom of this page
Note: This is for vitamin D dose levels of < 2000 IU
See also VitaminDWiki
- Vitamin D Recommendations around the world - IU and ng
- Endocrine Society recommend higher vitamin D levels – June 2011
- Every 400 IU increase of vitamin D3 increases serum level about 8 ng– Systematic Review Aug 2012 which = this study
- 200 IU needed to increase vitamin D levels by 1 ng (not 100 IU) – summary of 25 studies – Feb 2014
- Vitamin D response: 800 IU: 20 ng, 3200 IU: 45 ng – RCT March 2012 less than 2X at higher dose levels
- Dose response equation square root of IU
- Overview Vitamin D Dose-Response which has the following graph, which show that linear response ratio which varies with the dose size