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Vitamin D - A master example of nutrigenomics – April 2023

Vitamin D - A master example of nutrigenomics

Redox Biology https://doi.org/10.1016/j.redox.2023.102695
Carsten Carlberg a b, Marianna Raczyk a, Natalia Zawrotna a

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Nutrigenomics attempts to characterize and integrate the relation between dietary molecules and gene expression on a genome-wide level. One of the biologically active nutritional compounds is vitamin D3, which activates via its metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) the nuclear receptor VDR (vitamin D receptor). Vitamin D3 can be synthesized endogenously in our skin, but since we spend long times indoors and often live at higher latitudes where for many winter months UV-B radiation is too low, it became a true vitamin.
The ligand-inducible transcription factor VDR is expressed in the majority of human tissues and cell types, where it modulates the epigenome at thousands of genomic sites. In a tissue-specific fashion this results in the up- and downregulation of primary vitamin D target genes, some of which are involved in attenuating oxidative stress.
Vitamin D affects a wide range of physiological functions including the control of metabolism, bone formation and immunity. In this review, we will discuss how the epigenome- and transcriptome-wide effects of 1,25(OH)2D3 and its receptor VDR serve as a master example in nutrigenomics. In this context, we will outline the basis of a mechanistic understanding for personalized nutrition with vitamin D3.
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  126. Seuter, S., Neme, A. & Carlberg, C. ETS transcription factor family member GABPA contributes to vitamin D receptor target gene regulation. J Steroid Biochem Mol Biol 177, 46-52, doi:10.1016/j.jsbmb.2017.08.006 (2018).
  127. Carlberg, C. Vitamin D and is target genes. Nutrients 14, doi:10.3390/nu14071354 (2022).
  128. Saccone, D., Asani, F. & Bornman, L. Regulation of the vitamin D receptor gene by environment, genetics and epigenetics. Gene 561, 171-180,
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  130. Pilon, C. et al. Methylation Status of Vitamin D Receptor Gene Promoter in Benign and Malignant Adrenal Tumors. Int J Endocrinol 2015, 375349, doi:10.1155/2015/375349 (2015).
  131. Chandel, N., Malhotra, A. & Singhal, P. C. Vitamin D receptor and epigenetics in HIV infection and drug abuse. Front Microbiol 6, 788, doi:10.3389/fmicb.2015.00788 (2015).
  132. Jiang, C. et al. The methylation state of VDR gene in pulmonary tuberculosis patients. J Thorac Dis 9, 4353-4357, doi:10.21037/jtd.2017.09.107 (2017).
  133. Hussain, M. Z. et al. Genetic and expression deregulation of immunoregulatory genes in rheumatoid arthritis. Mol Biol Rep 48, 5171-5180, doi:10.1007/s11033-021-06518- 3 (2021).
  134. Sun, J., Zhang, S., Liu, J. S., Gui, M. & Zhang, H. Expression of vitamin D receptor in renal tissue of lupus nephritis and its association with renal injury activity. Lupus 28, 290-294, doi:10.1177/0961203319826704 (2019).
  135. Matos, C. et al. Downregulation of the vitamin D receptor expression during acute gastrointestinal graft versus host disease is associated with poor outcome after allogeneic stem cell transplantation. Frontiers in immunology 13, 1028850, doi:10.3389/fimmu.2022.1028850 (2022).
  136. Neme, A., Seuter, S. & Carlberg, C. Vitamin D-dependent chromatin association of
  137. CTCF in human monocytes. Biochim Biophys Acta 1859, 1380-1388, doi:10.1016/j.bbagrm.2016.08.008 (2016).
  138. Dixon, J. R. et al. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485, 376-380, doi:10.1038/nature11082 (2012).
  139. Genomes Project, C. et al. An integrated map of genetic variation from 1,092 human genomes. Nature 491, 56-65, doi:10.1038/nature11632 (2012).
  140. Rieder, M. J. et al. Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. N Engl J Med 352, 2285-2293, doi:10.1056/NEJMoa044503 (2005).
  141. Carlberg, C. & Haq, A. The concept of the personal vitamin D response index. J Steroid Biochem Mol Biol 175, 12-17, doi:10.1016/j.jsbmb.2016.12.011 (2018).
  142. Carlberg, C. et al. Primary vitamin D target genes allow a categorization of possible benefits of vitamin D3 ^supplementation. PLoS ONE 8, e71042, doi:10.1371/journal.pone.0071042 (2013).
  143. Wilfinger, J. et al. Primary vitamin D receptor target genes as biomarkers for the vitamin D3 status in the hematopoietic system. J. Nutr. Biochem. 25, 875-884 (2014).
  144. Ryynanen, J. et al. Changes in vitamin D target gene expression in adipose tissue monitor the vitamin D response of human individuals. Mol Nutr Food Res 58, 20362045, doi:10.1002/mnfr.201400291 (2014).
  145. Saksa, N. et al. Dissecting high from low responders in a vitamin D3 intervention study. J Steroid Biochem Mol Biol 148, 275-282, doi:10.1016/jjsbmb.2014.11.012 (2015).
  146. Vukic, M. et al. Relevance of vitamin D receptor target genes for monitoring the vitamin D responsiveness of primary human cells. PLoS ONE 10, e0124339, doi:10.1371/journal.pone.0124339 (2015).
  147. Seuter, S. et al. Molecular evaluation of vitamin D responsiveness of healthy young adults. J Steroid Biochem Mol Biol 174, 314-321 (2017).
  148. Mangin, M., Sinha, R. & Fincher, K. Inflammation and vitamin D: the infection connection. Inflamm Res 63, 803-819, doi:10.1007/s00011-014-0755-z (2014).
  149. Salzer, J. et al. Vitamin D as a protective factor in multiple sclerosis. Neurology 79, 2140-2145, doi:10.1212/WNL.0b013e3182752ea8 (2012).
  150. Fleet, J. C., DeSmet, M., Johnson, R. & Li, Y. Vitamin D and cancer: a review of molecular mechanisms. Biochem J 441, 61-76, doi:10.1042/BJ20110744 (2012).
  151. Jiang, X. et al. Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels. Nature communications 9, 260, doi:10.1038/s41467-017-02662-2 (2018).
  152. Prabhu, A. V., Luu, W., Li, D., Sharpe, L. J. & Brown, A. J. DHCR7: a vital enzyme switch between cholesterol and vitamin D production. Prog Lipid Res 64, 138-151, doi:10.1016/j.plipres.2016.09.003 (2016).
  153. Hanel, A., Veldhuizen, C. & Carlberg, C. Gene-regulatory potential of 25-hydroxyvitamin D3 and D2. Front Nutr 9, 910601, doi:10.3389/fnut.2022.910601 (2022).
  154. Seuter, S., Pehkonen, P., Heikkinen, S. & Carlberg, C. Dynamics of 1a,25-dihydroxyvitamin D-dependent chromatin accessibility of early vitamin D receptor target genes. Biochim Biophys Acta 1829, 1266-1275, doi:10.1016/j.bbagrm.2013.10.003 (2013).
  155. Kreienkamp, R. et al. Vitamin D receptor signaling improves Hutchinson-Gilford progeria syndrome cellular phenotypes. Oncotarget, 30018-30031, doi:10.18632/oncotarget. 9065 (2016).
  156. Manson, J. E. et al. Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med 380, 33-44, doi:10.1056/NEJMoa1809944 (2019).
  157. Chen, Y., Michalak, M. & Agellon, L. B. Importance of nutrients and nutrient metabolism on human health. Yale J Biol Med 91, 95-103 (2018).
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  160. Neme, A. et al. In vivo transcriptome changes of human white blood cells in response to vitamin D. J Steroid Biochem Mol Biol 188, 71-76, doi:10.1016/jjsbmb.2018.11.019 (2019).
  161. Verstuyf, A., Carmeliet, G., Bouillon, R. & Mathieu, C. Vitamin D: a pleiotropic hormone. Kidney international 78, 140-145 (2010).
  162. Carlberg, C. The physiology of vitamin D-far more than calcium and bone. Front Physiol 5, 335, doi:10.3389/fphys.2014.00335 (2014).
See also by Carlberg in VitaminDWiki

6 of 6,980 results for nutrigenomics "vitamin d" in Google Scholar (Oct 2024)

  • Nongenomic Activities of Vitamin D - Dec 2022 FREE PDF
  • Using nutrigenomics to guide personalized nutrition supplementation for bolstering immune system - Jan 2023 c10.1007/s13755-022-00208-5|FREE PDF]
  • Nutrigenomics in Autoimmune Disease - 2024 Nutrigenomics in Autoimmune Disease - 2024 https://doi.org10.4018/979-8-3693-5528-2.ch01
  • Intervention Approaches in Studying the Response to Vitamin D3 Supplementation- Carlberg- July 2023 FREE PDF
  • Methylation of the Vitamin D Receptor Gene in Human Disorders - Dec 2023 FREE PDF
  • Vitamin D and Aging: Central Role of Immunocompetence- Carlberg - Jan 2024 FREE PDF

VitaminDWiki - Response to Vitamin D - many studies 149+

VitaminDWiki - Vitamin D Receptor activation can be increased in 14 ways

Resveratrol,  Omega-3,  Magnesium,  Zinc,   Quercetin,   non-daily Vit D,  Curcumin, intense exercise, Butyrate   Ginger,   Essential oils, etc  Note: The founder of VitaminDWiki uses 10 of the 14 known VDR activators

VitaminDWiki – The Vitamin D Receptor is associated with many health problems __

530 studies in Vitamin D Receptor category

Vitamin D tests cannot detect Vitamin D Receptor (VDR) problems
A poor VDR restricts Vitamin D from getting in the cells

See also: 48 studies in the Resveratrol category

It appears that 30% of the population have a poor VDR (40% of the Obese )
Several diseases protect themselves by deactivating the Vitamin D receptor. Example: Breast Cancer
- - - - - - - -
The Vitamin D Receptor is associated with many health problems

Health problems include: Autoimmune (19 studies), Breast Cancer (24 studies), Colon Cancer (13 studies), Cardiovascular (23 studies), Cognition (16 studies), Diabetes (24 studies), Hypertension (9 studies), Infant (22 studies), Lupus (6 studies), Metabolic Syndrome (4 studies), Mortality (4 studies), Multiple Sclerosis (14 studies), Obesity (17 studies), Pregnancy (24 studies), Rheumatoid Arthritis (10 studies), TB (8 studies), VIRUS (37 studies),   Click here for details
Some health problems, such as Breast Cancer, Diabetes, and COVID protect themselves by reducing VDR activation

55 health problems associated with poor VDR


A poor VDR is associated with the risk of 55 health problems  click here for details
The risk of 48 diseases at least double with poor VDR as of Jan 2023  click here for details
Some health problem, such as Breast Cancer reduce the VDR

VDR at-home test $29 - results not easily understood in 2016
There are hints that you may have inherited a poor VDR

How to increase VDR activation


Compensate for poor VDR by increasing one or more:

IncreasingIncreases
1) Vitamin D supplement  Sun
Ultraviolet -B		 Vitamin D in the blood
and thus in the cells
2) MagnesiumVitamin D in the blood
 AND in the cells
3) Omega-3 Vitamin D in the cells
4) Resveratrol Vitamin D Receptor
5) Intense exercise Vitamin D Receptor
6) Get prescription for VDR activator
   paricalcitol, maxacalcitol?		Vitamin D Receptor
7) Quercetin (flavonoid) Vitamin D Receptor
8) Zinc is in the VDRVitamin D Receptor
9) BoronVitamin D Receptor ?,
etc
10) Essential oils e.g. ginger, curcuminVitamin D Receptor
11) ProgesteroneVitamin D Receptor
12) Infrequent high concentration Vitamin D
Increases the concentration gradient		Vitamin D Receptor
13) Sulfroaphane and perhaps sulfurVitamin D Receptor
14) Butyrate especially gutVitamin D Receptor
15) BerberineVitamin D Receptor

Note: If you are not feeling enough benefit from Vitamin D, you might try increasing VDR activation. You might feel the benefit within days of adding one or more of the above

Far healthier and stronger at age 72 due to supplements Includes 6 supplements that help the VDR

VitaminDWiki – Vitamin D Receptor category:

530 studies in Vitamin D Receptor category

Vitamin D tests cannot detect Vitamin D Receptor (VDR) problems
A poor VDR restricts Vitamin D from getting in the cells

See also: 48 studies in the Resveratrol category

It appears that 30% of the population have a poor VDR (40% of the Obese )
Several diseases protect themselves by deactivating the Vitamin D receptor. Example: Breast Cancer
- - - - - - - -
The Vitamin D Receptor is associated with many health problems

Health problems include: Autoimmune (19 studies), Breast Cancer (24 studies), Colon Cancer (13 studies), Cardiovascular (23 studies), Cognition (16 studies), Diabetes (24 studies), Hypertension (9 studies), Infant (22 studies), Lupus (6 studies), Metabolic Syndrome (4 studies), Mortality (4 studies), Multiple Sclerosis (14 studies), Obesity (17 studies), Pregnancy (24 studies), Rheumatoid Arthritis (10 studies), TB (8 studies), VIRUS (37 studies),   Click here for details
Some health problems, such as Breast Cancer, Diabetes, and COVID protect themselves by reducing VDR activation

55 health problems associated with poor VDR


A poor VDR is associated with the risk of 55 health problems  click here for details
The risk of 48 diseases at least double with poor VDR as of Jan 2023  click here for details
Some health problem, such as Breast Cancer reduce the VDR

VDR at-home test $29 - results not easily understood in 2016
There are hints that you may have inherited a poor VDR

How to increase VDR activation


Compensate for poor VDR by increasing one or more:

IncreasingIncreases
1) Vitamin D supplement  Sun
Ultraviolet -B		 Vitamin D in the blood
and thus in the cells
2) MagnesiumVitamin D in the blood
 AND in the cells
3) Omega-3 Vitamin D in the cells
4) Resveratrol Vitamin D Receptor
5) Intense exercise Vitamin D Receptor
6) Get prescription for VDR activator
   paricalcitol, maxacalcitol?		Vitamin D Receptor
7) Quercetin (flavonoid) Vitamin D Receptor
8) Zinc is in the VDRVitamin D Receptor
9) BoronVitamin D Receptor ?,
etc
10) Essential oils e.g. ginger, curcuminVitamin D Receptor
11) ProgesteroneVitamin D Receptor
12) Infrequent high concentration Vitamin D
Increases the concentration gradient		Vitamin D Receptor
13) Sulfroaphane and perhaps sulfurVitamin D Receptor
14) Butyrate especially gutVitamin D Receptor
15) BerberineVitamin D Receptor

Note: If you are not feeling enough benefit from Vitamin D, you might try increasing VDR activation. You might feel the benefit within days of adding one or more of the above

Far healthier and stronger at age 72 due to supplements Includes 6 supplements that help the VDR

Increased risk of diseases if poor VDR

Increased risk associated with a poor Vitamin D Receptor
   Note: Some diseases reduce VDR activation
those with a * are known to decrease activation

Risk
increase		Health Problem
50Lyme Disease *
28Leprosy - another says 3X
15Chronic Heart Failure
15Temporary hair loss
14.7Childhood solid cancers
14Hand, Foot, and Mouth disease
13Sepsis
12COVID Death
11Metabolic Syndrome
9.6Chronic Periodontitis
   and smoke
8Juvenile Rheumatoid Arthritis
8.0Preterm birth
7.6Crohn's disease
7.5Respiratory Tract Infections
7.0Lung Cancer
5.8Low back pain in athletes
5 Respiratory Distress in preemies
5Ulcerative Colitis
5Coronary Artery Disease
5Asthma Child see also 1.3, 2.0 and 3.7
4.6Breast Cancer * 16.9 X another study
4.3Severe COVID in kids
4.1Vitiligo
4Liver Cirhosis
4Polycystic ovary syndrome
3.8Lupus
3.6 Pneumonia - children
3.3 Pre-term birth
3.1 Colon Cancer survival
3 Multiple Sclerosis
3Dengue
3 Waist size
3 Ischemic Stroke
3Alzheimer’s
9X in women
3Parkinson’s
3Gestational Diabetes
2.9Hand, Foot, Mouth Disease
2.8Osteoporosis & COPD
2.7Gastric Cancer
2.6Lupus in children
2.5 Lumbar Disc Degeneration
2.4Lung Cancer
2.3Cardio
2.3Autism
2.2Juvenile idiopathic arthritis
2.1Adolescent idiopathic scoliosis in Asians
2Obesity
2Diabetic Retinopathy
2Parkinson's
2 Wheezing/Asthma see also 5X
2 Melanoma   Non-melanoma Skin Cancers
2Myopia
2Preeclampsia
1.9Uterine Fibroids
1.9Early tooth decay
1.8Diabetic nephropathy
1.8Sleep Apnea
1.6Diabetes - Type I
1.6Prostate Cancer while black
1.5 Diabetes -Type II
1.5Gout
1.5Pertussis
1.5Obesity
1.4Graves Disease
1.4 Rheumatoid arthritis
1.3Hypertension
1.3Childhood asthma see also 5X
1.3Psoriasis in Caucasians
1.3Tuberculosis

VitaminDWiki – Genetics category contains

343 articles in the Genetics category

see also

Vitamin D blood test misses a lot
in Visio for 2023

  • Vitamin D from coming from tissues (vs blood) was speculated to be 50% in 2014, and by 2017 was speculated to be 90%
  • Note: Good blood test results (> 40 ng) does not mean that a good amount of Vitamin D actually gets to cells
  • A Vitamin D test in cells rather than blood was feasible (2017 personal communication)   Commercially available 2019
    • However, test results would vary in each tissue due to multiple genes
  • Good clues that Vitamin D is being restricted from getting to the cells
    1) A vitamin D-related health problem runs in the family
        especially if it is one of 51+ diseases related to Vitamin D Receptor
    2) Slightly increasing Vitamin D shows benefits (even if conventional Vitamin D test shows an increase)
    3) DNA and VDR tests - 120 to 200 dollars $100 to $250
    4) PTH bottoms out ( shows that parathyroid cells are getting Vitamin d)
       Genes are good, have enough Magnesium, etc.
    5) Back Pain
       probably want at least 2 clues before taking adding vitamin D, Omega-3, Magnesium, Resveratrol, etc
      • The founder of VitaminDWiki took action with clues #3&5
Vitamin D - A master example of nutrigenomics – April 2023        
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