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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
Enter parameters then click on SiMULATE.
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VitaminDWiki page titles containing "RESPONSE"

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Created by admin. Last Modification: Sunday October 24, 2021 11:34:38 GMT-0000 by admin. (Version 46)

Attached files

ID Name Comment Uploaded Size Downloads
16478 single dose months.jpg admin 24 Oct, 2021 30.85 Kb 385
16477 Single dose days.jpg admin 24 Oct, 2021 39.78 Kb 381
16476 PK model_compressed.pdf admin 24 Oct, 2021 477.10 Kb 257
15569 Simulation.jpg admin 08 May, 2021 76.00 Kb 499
15565 Mdoel response 20 ng 2,000 IU on then off.jpg admin 07 May, 2021 24.99 Kb 675
15564 model response 20 ng, 4,0000 IU.jpg admin 07 May, 2021 24.33 Kb 706
15563 Response vs baseline.jpg admin 07 May, 2021 32.81 Kb 662
15562 1 year responses.jpg admin 07 May, 2021 54.78 Kb 640
15561 model development.jpg admin 07 May, 2021 59.73 Kb 685
15560 Model.jpg admin 07 May, 2021 53.02 Kb 649