Loading...
 
Toggle Health Problems and D

Vitamin D response model – May 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


Model response for 20 ng 4,000 IU

Image

Model response for 20 ng 2,000 IU

Image

Model 1.0

Image

Model development

Image

Observed data used to make the model

Image

Observed Increases used to make the model

Image
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
Image

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
Image

Overview Vitamin D Dose-Response


VitaminDWiki observation

Model 1.0 includes single and daily dosing data and considers age, sex
Data appears to be based on average response of group - not individual responses
Perhaps future models might incude such variables as:

  • weight,
  • obesity,
  • genes,
  • other dosing intervals (weekly, 2 per month, monthly)
  • loading dose followed by maintenance doses
  • poor gut,
  • Poor liver, Poor kidney
  • other forms of vitamin D (topical, etc)
  • co-factors (Mg, etc)
  • indicate the response diffeences between poor and good responders

simulation can be run here
enter parameters then click on SiMULATE - example
Image


VitaminDWiki page titles containing "RESPONSE"

Items found: 127
Title Modified
Reasons for low response to vitamin D 22 Sep, 2021
Vitamin D injections should not be used if fast response is needed (COVID-19 in this case) 02 Sep, 2021
Vitamin D, C, A, and E, as well as Iron, Se, and Zinc each augment vaccine response – July 2021 20 Jul, 2021
Poor response to Asthma inhaler if poor Vitamin D Receptor – Dec 2019 01 Jul, 2021
Parathyroid response to Vitamin D among obese 27 Jun, 2021
Based on PTH response, obese adolescents may not need and much vitamin D as non-obese (12 ng vs 16.5 ng) – June 2021 12 Jun, 2021
Nanoemulsion forms improve nutrient response time and bioavailability - many studies 23 May, 2021
Poor response to vitamin D supplementation if poor level of B Vitamins (rats in this case) March 2021 22 May, 2021
Vitamin D response model – May 2021 07 May, 2021
Vaccine response improved by Vitamin D (Shingles in this case) – Jan 2021 06 May, 2021
Better response to shingles virus test after Vitamin D raised above 40 ng – Jan 2021 23 Apr, 2021
Stoss (bolus, loading) dose of vitamin D resulted in bigger response at 30 days (again) – RCT April 2021 21 Apr, 2021
Hemodialysis associated with very poor mRNA response (wonder if low vitamin D) – March 26, 2021 31 Mar, 2021
Response to vitamin D increased 30 percent with Magnesium - Nov 2018 07 Mar, 2021
Poor protein binding gene associated with poor Vitamin D response – RCT Nov 2019 02 Mar, 2021
Response to weekly Calcifediol in 4 months - RCT Aug 2022 03 Feb, 2021
Weekly response to semi-activated vitamin D slightly better than standard – RCT Nov 2019 21 Jan, 2021
Obese children had 2.2 X less response to a single dose of Vitamin D – Oct 2020 14 Oct, 2020
Response to 150,000 IU vitamin D once vs 5,000 IU daily – RCT May 2014 10 Jul, 2020
Those with Asthma or COPD had half the response to Vitamin D – March 2020 19 Mar, 2020
Response to Vitamin D increased if take Magnesium and Vitamin K2 – Grassroots March 2020 10 Mar, 2020
Response by obese to weekly 50,000 IU of Vitamin D – May 2018 12 Feb, 2020
Less response to 800 IU of Vitamin D by Africans than natives in Finland – RCT March 2018 25 Dec, 2019
Increased Vitamin D response if take cofactors, etc 05 Nov, 2019
Sublingual vitamin D gave similar response as oral for most, and better for some – RCT Sept 2019 17 Oct, 2019
Autistics have half of the response to Vitamin D (perhaps poor genes) – RCT Oct 2018 11 Oct, 2019
Poor ovarian response (poor IVF) associated with low vitamin D – Sept 2019 28 Sep, 2019
Poor CYP2R1 gene reduces blood response to Vitamin D supplementation – Aug 2019 20 Jul, 2019
Poor responses to UV and Vitamin D were correlated to just 4 poor genes – June 2019 19 Jul, 2019
Response to Vitamin D varied by 12 ng due to gene variants (CYP2R1) – Aug 2019 15 Jun, 2019
Single dose of Vitamin D as gummies resulted in higher blood response than hard tablets – May 2019 07 May, 2019
Sepsis reduced the Omega-3 response and half life – April 2019 14 Apr, 2019
Poor Vitamin D response 4X more likely if poor Vitamin D binding proteins - July 2019 09 Apr, 2019
25 minutes of daily sun provided less than half of the response as 500 IU of vitamin D (Korea) – RCT March 2019 26 Mar, 2019
Response to UV varies more with pigment genes and age than skin color – Jan 2019 24 Mar, 2019
Response to UV varies more with pigment genes and age than skin color – Feb 2019 24 Mar, 2019
Decreased response to vitamin D in white children having poor Vitamin D binding gene – Feb 2019 20 Mar, 2019
Monthly Vitamin D had a 20 percent better response than quarterly – small RCT April 2019 06 Mar, 2019
Vitamin D response time is 3-6 months, not much benefit in first 4 months – RCT July 2017 17 Feb, 2019
Poor Vitamin D binding had 30 percent less response to Vitamin D (50,000 IU weekly) – Feb 2019 04 Feb, 2019
7 ng less response by Multiple Sclerosis patients to 5,000 IU of vitamin D – Aug 2015 30 Dec, 2018
2 month response time to Vitamin D (Grassroots Health) 08 Dec, 2018
Vitamin D sprayed inside cheeks 2X more response (poor gut) – RCT Oct 2015 07 Dec, 2018
Response to Vitamin D varies with Vitamin D Binding Protein gene – RCT May 2018 06 Jun, 2018
Poor response to Osteoporosis medicine (risedronate) if vitamin D less than 16 ng – May 2018 09 May, 2018
No genetic response to 4,000 IU of Vitamin D (other studies disagree) – RCT April 2018 15 Apr, 2018
Vitamin D – individual responses to 100,000 IU – March 2017 11 Feb, 2018
Monthly vitamin D dosing had higher response than 3 per month – RCT Jan 2018 28 Jan, 2018
Multiple Sclerosis patients need more vitamin D to get same blood level response – Aug 2015 27 Jan, 2018
Vitamin D injection helped migrants a bit, but some had poor or even negative responses – Dec 2017 19 Jan, 2018
Vitamin D injection of 300,000 IU helped a bit, but many had a very small response – Dec 2017 19 Jan, 2018
Vitamin D injection of 600,000 IU (response by 10 individuals)– Sept 2017 29 Dec, 2017
10 reasons for poor response to Vitamin D (race, binding protein, etc.) – Nov 2017 24 Dec, 2017
Inflammation and immune responses to Vitamin D (perhaps need to measure active vitamin D) – July 2017 22 Nov, 2017
Low response to vitamin D for some people – genes are one of the causes – Nov 2014 22 Nov, 2017
Response to a large dose of vitamin D (80,000 IU) typically varied by 2 X – June 2016 14 Nov, 2017
Estrogen contraception pill doubled the response to 1,000 IU of vitamin D – RCT Sept 2017 04 Sep, 2017
Immune response was poor in mice and humans with low vitamin D and low vitamin A – May 2015 17 Aug, 2017
Vitamin D daily or weekly dosing resulted in similar response -RCT Jan 2016 20 Jul, 2017
Huge variation in response to vitamin D supplementation – personal vitamin D response index – Dec 2016 27 Jun, 2017
Vitamin D responses to as much as 15,000 IU per day – Feb 2017 20 Jun, 2017
Spray and oral forms of 3000 IU vitamin D provide similar long-term response – RCT Oct 2016 20 May, 2017
Overview Vitamin D Dose-Response 19 Apr, 2017
UVB 50 percent more response in obese than normal weight (other study disagrees) – Feb 2017 02 Mar, 2017
UVB 50 percent more response in obese than normal weight (yet response to Vitamin D is 50 percent less) – Feb 2017 28 Feb, 2017
Vitamin D injection lasts longer and has bigger response than weekly oral – Jan 2017 24 Dec, 2016
Graph of weekly response to monthly vitamin D supplementation – Aug 2015 17 Sep, 2016
RF from mobile phones reduced immune response in rats, unless they had vitamin D – Sept 2016 10 Sep, 2016
Burn patients have little vitamin D and uncertain response to supplementation – Dec 2014 04 Sep, 2016
Response to Vitamin D - Grassroots 01 Sep, 2016
Response to Vitamin D: summary chart of 8 studies – March 2013 01 Sep, 2016
Large variability in response to UV (more than response to oral Vitamin D) – March 2016 22 Jun, 2016
Large variability in response to UVB (similar to that of oral Vitamin D) – March 2016 22 Jun, 2016
Large variability in response of people to UVB (similar to that to oral Vitamin D) – March 2016 22 Jun, 2016
Dengue fever immune response and micronutrients (vitamins D, E, A, and Zinc, Iron, Chromium) – Nov 2015 11 Jun, 2016
Immune response to respiratory viruses – vitamin D connection – review May 2015 17 May, 2016
3X variation in response to dose of vitamin D – meta-analysis June 2012 24 Apr, 2016
PTH boosts immune response when vitamin D levels are low – May 2012 29 Mar, 2016
CYP2R1 and GC variations decrease vitamin D response – PHD thesis Nov 2015 18 Feb, 2016
Pigs have about 2X less variation in response to calcidiol as humans do to vitamin D – 2015 07 Dec, 2015
Vitamin D response reduced if taken with Calcium – meta-analysis Oct 2015 01 Dec, 2015
Response to Vitamin D supplementation – July 2015 25 Nov, 2015
How you might double your response to vitamin D 31 Oct, 2015
600,000 vitamin D loading doses – good response to both oral and muscular – Oct 2015 13 Oct, 2015
Different response by Vitamin D Receptor to Vitamin D vs Vit. D analogs – Sept 2015 24 Sep, 2015
If at high risk of vitamin D deficiency, get a higher response if take more Magnesium – Sept 2013 12 Sep, 2015
Response to 1000 IU of vitamin D varies by about 4 percent due to gene variants – RCT July 2014 09 Aug, 2015
More muscle response when have adequate vitamin D 27 Jul, 2015
Familial Mediterranean fever – poor response to colchicine if low vitamin D – June 2015 13 Jun, 2015
CYP2R1 gene probably responsible for low vitamin D response – RCT April 2014 02 Jun, 2015
Better response to Inflammatory Bowel Disease drug if more than 30 ng of vitamin D – March 2014 18 Apr, 2015
Vitamin D-binding protein controls T cell responses to vitamin D in the lab – Sept 2014 01 Apr, 2015
Low dose Vitamin D during pregnancy and infancy results in strange acute respiratory infection response – April 2015 24 Mar, 2015
Obese need 2X as much vitamin D to get the same response – June 2012 14 Mar, 2015
Is too much vitamin D bad (U-shaped response) – possible causes and cures 10 Mar, 2015
Response and adverse effects of 20,000 and 30,000 IU Vitamin D weekly - Feb 2015 09 Mar, 2015
24 ng lower response to Vitamin D due to obesity, low initial Vitamin D, and genetics – RCT Feb 2015 24 Feb, 2015
Genes are one of the reasons for low response to vitamin D – Nov 2014 24 Feb, 2015
Some people need more vitamin D to get the same response – perhaps due to genes – Nov 2014 24 Feb, 2015
Activation (methylation) of CYP2R1 and CYP24A1 predict response to dose of vitamin D – Oct 2013 24 Feb, 2015
Transdermal Magnesium Chloride spray - variable responses, removed toxic metals - 2010 21 Jan, 2015
Solutions if have poor response to conventional vitamin D 14 Dec, 2014
Immune System response of infants is associated with higher levels of vitamin D – RCT Nov 2014 08 Nov, 2014
How to predict response to a vitamin D dose – RCT April 2014 06 Nov, 2014
Not as much dark skin vitamin D response from single UV dose (no surprise) – Oct 2013 13 Aug, 2014
Dose response equations for Vitamin D 02 Aug, 2014
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

Created by admin. Last Modification: Saturday May 8, 2021 13:51:12 GMT-0000 by admin. (Version 30)

Attached files

ID Name Comment Uploaded Size Downloads
15569 Simulation.jpg admin 08 May, 2021 13:50 76.00 Kb 78
15566 pharmacokinetic modelling_compressed.pdf PDF 2021 admin 08 May, 2021 12:08 918.65 Kb 51
15565 Mdoel response 20 ng 2,000 IU on then off.jpg admin 07 May, 2021 21:44 24.99 Kb 213
15564 model response 20 ng, 4,0000 IU.jpg admin 07 May, 2021 21:43 24.33 Kb 246
15563 Response vs baseline.jpg admin 07 May, 2021 21:43 32.81 Kb 211
15562 1 year responses.jpg admin 07 May, 2021 21:42 54.78 Kb 203
15561 model development.jpg admin 07 May, 2021 21:42 59.73 Kb 223
15560 Model.jpg admin 07 May, 2021 21:42 53.02 Kb 211
See any problem with this page? Report it (FINALLY WORKS)