Supplements that improve Vitamin D genes

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VitaminDWiki - Genetics chart, *are not seen by Vitamin D test 

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Perplexity AI June 2025

Compound	CYP2R1	CYP27A1	CYP27B1	CYP24A1	VDBP	VDR
Glutathione	↑ expression (hepatocytes) 4	↑ expression (restored) 1	↑ expression (liver/kidney) 1 3	↓ expression (hepatocytes/kidney) 1 3	↑ expression 1 4	↑ expression & transcriptional activity 1 3 5
Resveratrol	Mixed: ↑ mRNA in HUH-7	Mixed: ↑ mRNA but ↓ protein in HEK-293	Mixed: ↑ mRNA in HEK-293; ↑ protein in MCF7	↑ mRNA & protein in HEK-293	N/A	Activates transcription & enhances VDR-RXR dimerization
Quercetin	Mixed: ↑ mRNA but ↓ protein in HEK-293	Mixed: ↑ mRNA but ↓ protein in HEK-293	Mixed: ↑ mRNA in HUH-7; no protein change	↑ protein in HEK-293	N/A	Low-affinity ligand; activates transcription
Omega-3	N/A	N/A	↑ expression in liver (with cholecalciferol)	↓ expression in kidney & liver	N/A	Binds with low affinity; activates VDR-RXR
Magnesium	↑ activity (cofactor role)	N/A	Essential for enzyme function	↓ activity (cofactor role)	N/A	Upregulates VDR expression in parathyroid glands
Zinc	N/A	N/A	N/A	Inhibits CYP24A1 in SW480 cells	N/A	Supports VDR zinc finger structure
Curcumin	N/A	N/A	N/A	Induces CYP24A1 in Caco-2	N/A	Binds & activates VDR; upregulates expression
Berberine	N/A	N/A	N/A	N/A	N/A	Enhances VDR activity (N-terminal region)
Butyrate	N/A	N/A	↑ mRNA in gingival fibroblasts	N/A	N/A	Upregulates VDR expression; synergizes with 1,25D
Metformin	N/A	N/A	↑ expression (synergistic with vitamin D₃)	N/A	N/A	Upregulates VDR in kidney cells

Glutathione details

1. Multi-enzyme regulation: Upregulates CYP2R1 (25-hydroxylase) 4, CYP27A1 (mitochondrial hydroxylase) 1, and CYP27B1 (1α-hydroxylase) 1 3 while suppressing CYP24A1 (catabolic enzyme) 1 3.
2. VDBP enhancement: Increases both mRNA and protein expression of vitamin D binding protein in hepatocytes 1 4, extending 25(OH)D half-life.
3. VDR synergy: Restores VDR expression in glutathione-deficient renal cells 3 and amplifies VDR-mediated transcriptional responses through AP-1 signaling 5.
4. Oxidative stress link: Glutathione deficiency causes reciprocal dysregulation - ↓ CYP27B1/VDR and ↑ CYP24A1 1 3, creating vitamin D resistance.

Citations

1. https://pmc.ncbi.nlm.nih.gov/articles/PMC6208166/
2. https://www.grassrootshealth.net/blog/vitamin-d-glutathione-nac-important-relationships-pay-attention/
3. https://pubmed.ncbi.nlm.nih.gov/30578920/
4. https://mdanderson.elsevierpure.com/en/publications/l-cysteine-supplementation-upregulates-glutathione-gsh-and-vitami
5. https://www.mdpi.com/1422-0067/25/4/2284
6. https://www.nature.com/articles/s41420-024-01912-9
7. https://www.mdpi.com/2073-4409/12/2/335
8. https://pubmed.ncbi.nlm.nih.gov/31616013/
9. https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fj.202201400R
10. https://www.ncbi.nlm.nih.gov/gene/1591

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Earlier Perplexity detailed report

  Perplexity PDF

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See also VitaminDWiki

• Note: poor response to Vitamin D test, not poor response of vitamin D getting to cells_
  • Response to Vitamin D – 25% high, 24% low (ignores other than genes) – July 2024
  • Response to Vitamin D - many studies
• Many genes can restrict Vitamin D from getting to the cells – Aug 2023
• Review of 11 Vitamin D genes – Nov 2017
• Glutathione master antioxidant, improves many vitamin D genes, about 20 cents per day
• Resveratrol
  • Resveratrol - liposomal may be best form to increase cellular Vitamin D - Feb 2023
  • COVID-19 Cytokine storms attenuated by Vitamin D, Omega-3, Mg, Resveratrol, etc – April 2021
  • Resveratrol fights Parkinson, Alzheimers, Diabetes, Cardiovascular, ALS, Stroke, etc.– Nov 2018
  • Bone Mineral Density increased by Resveratrol (which activates the Vitamin D Receptor) – RCT Nov 2020
  • Resveratrol treats Multiple Sclerosis and other autoimmune diseases – many studies
  • Resveratrol Efficacy improvements – special issue 2017
• Vitamin D Receptor
  • Vitamin D Receptor deactivated by some health problems - many studies
  • VDR category is associated with these 49 other VitaminDWiki categories as of 2024
    • Genetics 74, Binding Protein 46, Virus 33, CYP27B1 32, Pregnancy 24, Breathing 24, Diabetes 23, Cancer 22, Infant-Child 21, Cancer - Breast 19, Autoimmune 18, Resveratrol 18, Cognitive 16, Obesity 16, Osteoporosis 13, Cancer - Colon 13, Gut 13, Immunity 12, Parkinson 11, Cancer - Other 11, Seniors 10, Rheumatoid Arthritis 10, Cancer - Skin 10, Multiple Sclerosis 10, Hypertension 9, Vision 8, Tuberculosis 8, Skin 7, Thyroid 7, Skin - Dark 7, Cancer - Prostate 7, Back pain 7, Fertility and sperm 6, Dental 6, Women 6, Cancer - Ovarian 6, Bone - Health 6, Sports 6, Cardiovascular 6, Lupus 6, Cancer - after diagnosis 5, UV 5, Liver 5, Intervention 4, Autism 4, Deficiency 4, Books & videos 4, Mortality 4, Stroke 4, Middle East 4, Kidney 4, Cancer - Lung 4, Cancer - Bladder 4
• Vitamin D Binding Protein
  • No response to vitamin D 7X more likely if poor CYP24A1 or VDBP genes - Feb 2023
  • Autism has a 2.5 X higher risk of being severe if poor Vitamin D Binding gene – Nov 2024
  • No response to Vitamin D was 11 X more likely to have if poor Binding gene – Sept 2022
  • T1 Diabetes 6.5 X more likely in South African Blacks if poor Vitamin D Binding Protein – July 2022
  • Multiple Sclerosis 2.8 X more likely if poor Vitamin D Binding Protein – May 2022
• CYP27B1
  • COVID maximum downregulation of Vitamin D receptor and CYP27B1 resulted in death - Feb 2024
  • Miscarriage (Recurrent Spontaneous) associated with poor CYP27B1 gene - Jan 2024
  • Every Parkinson’s brain had a gene modification that limited how much vitamin D was available (CYP27B1) – Feb 2022
• CYP24A1 gene and Vitamin D - many studies
  • Suppression of CYP24A1 gene got more Vitamin D to cells to fight Breast Cancer – March 2023
  • No response to vitamin D 7X more likely if poor CYP24A1 or VDBP genes - Feb 2023
  • Suicide attempts by males 3.7 X more likely if poor Vitamin D gene (CYP24A1) – Oct 2021
  • Hypertension 2X more likely if poor CYP24A1 vitamin D gene (China) – Jan 2020
• CYP34A4
  • Colon Cancer protects itself by changing the VDR and CYP3A4 genes – Dec 2022
  • Ivermectin decreases CYP3A4
• CYP2R1 detected by Vitamin D test
  • Autoimmune diseases and poor Vitamin D genes – GC, CYP2R1, CYP27B1, and VDR – April 2024
  • COVID-19 5X worse if poor Vitamin D gene (CYP2R1) – June 2021
  • Activation (methylation) of CYP2R1 and CYP24A1 predict response to dose of vitamin D – Oct 2013