On-line Vitamin D response simulation – July 2021

Personalise vitamin D 3 using physiologically based pharmacokinetic modelling
CPT Pharmacometrics Syst Pharmacol. 2021 May 7. doi: 10.1002/psp4.12640
Zhonghui Huang 1, Tao You 1
 Download the PDF from VitaminDWiki

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Model response for 20 ng 4,000 IU

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Model response for 20 ng 2,000 IU

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Model 1.0

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Model development

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Observed data used to make the model

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Observed Increases used to make the model

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Observed single day dose-response

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Plasma concentration of Vitamin D3 metabolite 25-hydroxyvitamin D3 (25(OH)D3 ) is variable among individuals. The objective of this study is to establish an accurate model for 25(OH)D3 pharmacokinetics (PK) to support selection of a suitable dose regimen for an individual. We collated Vitamin D3 and 25(OH)D3 plasma PK data from reported clinical trials and developed a physiologically based pharmacokinetic (PBPK) model to appropriately recapitulate training data. Model predictions were then qualified with 25(OH)D3 plasma PK under vitamin D3 and 25(OH)D3 dose regimens distinct from training data. From data exploration, we observed the increase in plasma 25(OH)D3 after repeated dosing was negatively correlated with 25(OH)D3 baseline levels.

Our final model included a first-order vitamin D3 absorption, a first-order vitamin D3 metabolism and a nonlinear 25(OH)D3 elimination function. This structure explained the apparent paradox.

Remarkably, the model accurately predicted plasma 25(OH)D3 following repeated dosing up to 1250μg/d in the test set. It also made sensible predictions for large single Vitamin D3 doses up to 50000μg in the test set.

Model predicts 10μg/d regimen may be ineffective for achieving sufficiency (plasma 25(OH)D3 ≥ 75nmol/L) for a severely deficient individual (baseline 25(OH)D3 = 10nmol/L), and it might take the same person over 200 days to reach sufficiency at 20μg/d dose. We propose to personalise vitamin D3 supplementation protocol with this PBPK model. It would require measuring 25(OH)D3 baseline levels, which is not routinely performed under the current UK public health advice.

Observed response charts from previous studies

10,000 IU of Vitamin D for 7 years with no excessive Calcium in 4,800 patients – Dec 2018
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Response to Vitamin D: summary chart of 8 studies – March 2013
Response - 8 studies bit.ly/16TuWp5

Same dose of vitamin D for everyone is virtually impossible - Dec 2015
Dose/response from 36 studies
Dose Response Dec 2015 (VDW# 7156)
97% will have a response above the dashed lower line

Huge variation in response to vitamin D supplementation – personal vitamin D response index – Dec 2016
Figure 2A daily dose of 3,200 IU
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See also in VitaminDWiki

VitaminDWiki suggestions of possible refinements to version 1.0

Model 1.0 includes data from response by groups (not individuals) to daily dosing
Refinements that would likely decrease the response

  • weight,
  • obesity,
  • genes,
  • poor gut,
  • Poor liver, Poor kidney
  • Age (seniors have less bio-availability)

Refinements that might increase the response

  • other forms of vitamin D (topical, gut-friendly, etc)
  • co-factors (Mg, etc)

Other refinements of interest

  • other dosing intervals (weekly, 2 per month, monthly)
  • loading dose
  • loading dose followed by maintenance dosing

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Minimum that ce be simulated is daily for 1 week
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VitaminDWiki page titles containing "RESPONSE"

Items found: 171
Title Modified
Response to vitamin D dose, overview of 25 studies - Feb 2014 02 Aug, 2014
Similar response to Vitamin D supplements by senior white and black women – Feb 2013 08 May, 2014
U-shaped response to vitamin D – possible causes 24 Apr, 2014
Response to high dose vitamin D is limited by vitamin A - July 2013 13 Apr, 2014
Hypothesis: Low vitamin D is responsible for many recent increases in health problems 01 Jan, 2014
Hypothesis: Magnesium accounts for some of the variation in vitamin D response – Oct 2013 16 Nov, 2013
40 percent less likely to get adequate vitamin D response if have certain genes – Jan 2013 10 Sep, 2013
Increased D levels responsible for Dead Sea therapy – May 2011 16 Aug, 2013
Response to vitamin D related to DBP and CYP2RI genes – Aug 2013 10 Aug, 2013
Response to Vitamin D3 varied with rs4588, D2 less response than D3 and did not change – April 2013 13 Jul, 2013
Higher BMI decreased response to 700 IU vitamin D – RCT 2008 26 Feb, 2013
Difference in Fok gene reduced response to vitamin D by 35 percent – Nov 2012 17 Nov, 2012
Response by Masterjohn on vitamin A thwarting vitamin D – Mar 2010 26 Oct, 2012
Is Vitamin D Supplementation Responsible for the Allergy Pandemic – May 2012 27 Jun, 2012
Metabolites and genes may predict responses to Calcium and Vitamin D – Jan 2011 24 Jun, 2012
40 ng response plateau to 2000 to 4,000 IU of vitamin D – June 2012 19 Jun, 2012
More response to 1100 IU vitamin D in cold season or less BMI – May 2012 15 May, 2012
Miss Ohio Teen USA on responsible tanning 29 Sep, 2010
Genetics Determines Vitamin D Response 19 Aug, 2010
Hormesis: response to dose may not be linear 16 Jun, 2010
Would be nice to capture and share vitamin D dose /response / benefit information 24 May, 2010
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