Database Query Results : Vitamin D3, ,

VitD3, Vitamin D3: Click to Expand ⟱
Features: Promote calcium and phosphorus absorption
Vitamin D3 (Cholecalciferol)
- Major VITAL study stated Vit D did not reduce invasive cancer, but Secondary Analysis stated reduces the incidence of metastatic cancer at diagnosis.
- Amount needed may depend on your BMI.
- Vitamin D deficiency, as determined by serum 25(OH)D concentrations of less than 30 ng/mL,
- Target achieving 80 ng/mL
- Vitamin D may modulate oxidative stress markers. (ROS)
- Nrf2 plays a key role in protecting cells against oxidative stress; this is modulated by vitamin D
- Vitamin D has antioxidant and anti-inflammatory regulatory effects; whether supplementation alters response to specific chemotherapy regimens remains context-dependent and not firmly established. - excess Vit D can raise calcium and cause harm
Vitamin D deficiency is generally defined as serum 25(OH)D <20 ng/mL (50 nmol/L), though some guidelines consider ≥30 ng/mL sufficient.
- One recommendation is to get your level up to around 125 ng/ml (however not supported by consensus clinical trial evidence).
- Chemo depletes Vitamin D levels so 10,000 IUs daily? – ask your doctor first. Typical maintenance dosing for most adults is 800–2000 IU/day; higher doses may be used short-term under medical supervision when correcting deficiency.

After correction of vitamin D deficiency through loading doses of oral vitamin D (or safe sun exposure), adequate maintenance doses of vitamin D3 are needed. This can be achieved in approximately 90% of the adult population with vitamin D supplementation between 1000 to 4000 IU/day, 10,000 IU twice a week, or 50,000 IU twice a month [10,125]. On a population basis, such doses would allow approximately 97% of people to maintain their serum 25(OH)D concentrations above 30 ng/mL [19,126]. Others, such as persons with obesity, those with gastrointestinal disorders, and during pregnancy and lactation, are likely to require doses of 6,000 IU/day.

Vitamin D, particularly its active form 1,25-dihydroxyvitamin D (calcitriol), exerts multiple biological effects that may influence cancer development and progression.
Calcitriol has been reported to induce cell cycle arrest (often at the G0/G1 phase) and promote pro-apoptotic mechanisms in various cancer cell types.

Inhibition of Angiogenesis:
Some studies indicate that vitamin D can reduce the expression of pro-angiogenic factors, thereby potentially limiting the blood supply to tumors, which is necessary for tumor growth and metastasis.

Effects on the Wnt/β-catenin Pathway:
The Wnt/β-catenin signaling pathway, often dysregulated in several cancers (for example, colorectal cancer), may be modulated by vitamin D.
Calcitriol has been shown in some models to inhibit β-catenin signaling, which is associated with decreased cell proliferation and tumor progression.
Vitamin D may interact with other signaling pathways, including the PI3K/AKT/mTOR pathway, which is involved in cell survival and proliferation.

Rank Pathway / Axis Cancer / Tumor Context Normal Tissue Context TSF Primary Effect Notes / Interpretation
1 VDR nuclear signaling (calcitriol → VDR/RXR → gene regulation) Differentiation ↑; proliferative drive ↓ (reported) Homeostatic gene regulation across many tissues R, G Transcriptional reprogramming Core biology is hormone-like gene regulation; many downstream “anti-cancer” effects are VDR-mediated and context-dependent.
2 Cell-cycle braking (p21/p27; Cyclin/CDK tone) Cell-cycle arrest ↑ (reported) ↔ / growth control support G Cytostasis Often described as downstream of VDR transcriptional programs; strength varies widely by tumor type and VDR expression.
3 Apoptosis / differentiation programs Apoptosis ↑ and/or differentiation ↑ (reported) ↔ G Phenotype shift Observed in many preclinical models; not a universal direct cytotoxin signature.
4 Immune modulation (innate/adaptive tone) Anti-inflammatory immune tone ↑ (context); microenvironment effects (reported) Immune regulation support R, G Immunomodulation Vitamin D signaling is active in both innate and adaptive immunity; effects depend on baseline status and context.
5 NF-κB / inflammatory transcription (downstream) Inflammatory programs ↓ (reported) Inflammation tone ↓ (context) R, G Anti-inflammatory signaling Commonly reported as a downstream correlate of VDR signaling and immune shifts; avoid presenting as a primary “direct inhibitor.”
6 Wnt/β-catenin & EMT/invasion programs (reported) EMT / invasion pressure ↓ (reported; model-dependent) ↔ G Anti-invasive phenotype Frequently discussed in colorectal and other models; keep “reported/model-dependent.”
7 Angiogenesis signaling (VEGF outputs; reported) Angiogenic outputs ↓ (reported) ↔ G Anti-angiogenic support Usually a later phenotype-level outcome tied to inflammatory and differentiation programs.
8 Systemic endocrine axis: calcium/phosphate homeostasis Hypercalcemia risk if excessive (therapy-limiting for analogs) Bone/mineral homeostasis (core physiologic role) R, G Endocrine regulation Key reason active vitamin D analogs in oncology are constrained: dose-limiting hypercalcemia.
9 Clinical oncology evidence (population-level) Incidence: generally no clear reduction; Mortality: some meta-analyses show modest reduction — — Translation constraint RCT meta-analyses often find reduced cancer mortality without clear reduction in total cancer incidence; results vary by trial design, baseline status, and dosing pattern.
10 Safety / monitoring constraints (hypercalcemia; interactions) — Excess vitamin D can cause high calcium; risk increases with high-dose supplements and certain conditions/meds — Clinical risk management Upper limits and avoiding unnecessary high-dose regimens matter; routine testing is not recommended for most healthy people without indications.

Time-Scale Flag (TSF): P / R / G

  • P: 0–30 min (rapid signaling is limited; most effects are not truly “instant”)
  • R: 30 min–3 hr (early transcription/signaling shifts begin)
  • G: >3 hr (gene-regulatory adaptation and phenotype outcomes)


Clinical trial data suggest vitamin D supplementation effects may be attenuated in individuals with obesity, potentially due to pharmacokinetic and inflammatory differences.
Domain Normal BMI (<25) Overweight (25–29.9) Obesity (≥30) Interpretation / Notes
Baseline 25(OH)D Levels Higher on average Moderately lower Significantly lower (volume dilution + sequestration) Vitamin D is fat-soluble; adipose tissue can sequester vitamin D, lowering circulating 25(OH)D.
Response to Supplementation Greater increase per IU Blunted increase Markedly blunted increase Obese individuals often require higher doses to achieve the same serum 25(OH)D level.
VDR Expression / Signaling Baseline signaling intact Possible mild attenuation Evidence of altered vitamin D signaling (context-dependent) Obesity-associated inflammation and metabolic dysregulation may influence VDR activity.
Systemic Inflammation Lower baseline inflammatory tone Elevated Chronically elevated Obesity increases IL-6, TNF-α, CRP; this may blunt anti-inflammatory effects of vitamin D.
Cancer Incidence (VITAL Trial) No overall reduction in invasive cancer No significant reduction No significant reduction Primary endpoint showed no reduction across BMI groups.
Advanced / Metastatic Cancer Signal (Secondary Analyses) Stronger reduction signal in normal BMI Weaker effect No clear benefit observed Secondary analyses suggested benefit mainly in non-obese participants; interpretation remains debated.
Mortality Signal (Meta-analyses) Modest reduction reported Less consistent Attenuated or absent Some pooled analyses show reduced cancer mortality, with stronger signals in non-obese individuals.
Dose Considerations 800–2000 IU/day often sufficient May require higher maintenance dose Higher supervised dosing sometimes required Guidelines emphasize individualized dosing based on measured 25(OH)D and clinical context.
Hypercalcemia Risk Low at standard doses Low–moderate (dose dependent) Still present at high doses Risk relates to absolute dose and duration, not BMI alone.


Scientific Papers found: Click to Expand⟱
4624- Bor,  VitD3,    Boron as a Medicinal Ingredient in Oral Natural Health Products
- Review, Pca, NA
*Half-Life↝, *eff↑, PSA↓, TumVol↓, IGF-1↓, *memory↓, *motorD↓,
1496- SFN,  VitD3,    Association between histone deacetylase activity and vitamin D-dependent gene expressions in relation to sulforaphane in human colorectal cancer cells
- in-vitro, CRC, Caco-2
eff↑, VDR↑, CYP11A1↓, HDAC↓,
4616- VitA,RetA,  VitC,  VitD3,  VitE,  Rad  Vitamins and Radioprotective Effect: A Review
- Review, NA, NA
*radioP↑, *ROS↓,
4067- VitB12,  VitB6,  VitD3,    Plants, Plants, and More Plants: Plant-Derived Nutrients and Their Protective Roles in Cognitive Function, Alzheimer's Disease, and Other Dementias
- Review, AD, NA
*cognitive↑,
4050- VitB12,  VitD3,  VitE,    Nutrient intake, nutritional status, and cognitive function with aging
- Review, AD, NA
neuroP↑,
4055- VitB6,  VitD3,    Vitamin B6 and vitamin D deficiency co-occurrence in geriatric memory patients
- Study, AD, NA
*Risk↓, *cognitive↑,
4077- VitB6,  FA,  VitB12,  VitD3,  VitE  Vitamin Supplementation as an Adjuvant Treatment for Alzheimer’s Disease
- Review, AD, NA
*antiOx↑, *cognitive↑, *homoC↓, *Risk↓, *Risk↓, *Risk↓, *other↝, *Dose↝, *Risk↓, *Risk↓,
4086- VitD3,    The beneficial role of vitamin D in Alzheimer's disease
- Review, AD, NA
*Mood↑, *cognitive↑, *eff↑,
1223- VitD3,    Vitamin D3 Treatment Influences PGE2 and TGFβ in Normal and Increased Breast Cancer Risk Women
- Trial, NA, NA
*TGF-β↑, *PGE2↓,
4618- VitD3,    Vitamin D sensitizes cervical cancer to radiation-induced apoptosis by inhibiting autophagy through degradation of Ambra1
- in-vivo, Cerv, NA
Risk↓, RadioS↑, Apoptosis↑, EMT↝,
4617- VitD3,    Vitamin D3 and its Potential to Ameliorate Chemical and Radiation-Induced Skin Injury During Cancer Therapy
- Case Report, NA, NA
radioP↑,
1313- VitD3,  MEL,    The effects of melatonin and vitamin D3 on the gene expression of BCl-2 and BAX in MCF-7 breast cancer cell line
- in-vitro, BC, MCF-7
BAX↑, Bcl-2↓, Bax:Bcl2↑, eff↑,
4350- VitD3,    Vitamin D: Evidence-Based Health Benefits and Recommendations for Population Guidelines
- Review, Var, NA - Review, AD, NA
Risk↓, angioG↓, TumMeta↓, AntiCan↑, *cognitive↑, *Mood↑,
4320- VitD3,    Unraveling the molecular mechanisms of vitamin deficiency in Alzheimer's disease pathophysiology
- Review, AD, NA
*Calcium↝, *cognitive↑, *Aβ↓, *Inflam↓, *Risk↓, *other↝,
4187- VitD3,    Protective effects of vitamin D on neurophysiologic alterations in brain aging: role of brain-derived neurotrophic factor (BDNF)
- in-vivo, NA, NA
*BDNF↑, *MDA↓, *Casp3↓,
4186- VitD3,    The Association of Vitamin D, Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF), and Glial Cell-Derived Neurotrophic Factor (GDNF) with Development in Children
- Study, NA, NA
*BDNF∅,
4185- VitD3,    Effects of vitamin D supplementation on neuroplasticity in older adults: a double-blinded, placebo-controlled randomised trial
- Study, NA, NA
*other↑, *BDNF∅,
4184- VitD3,    Neuroplasticity-related effects of vitamin D relevant to its neuroprotective effects: A narrative review
- Review, NA, NA
*BDNF↑, *cognitive↑,
4183- VitD3,  Ex,    Combined Exercise and Vitamin D on Brain-Derived Neurotrophic Factor
- Review, NA, NA
*BDNF↑, *Inflam↓, *other↝,
4182- VitD3,    The association between vitamin D and BDNF on cognition in older adults in Southern Brazil
- Study, AD, NA
*cognitive↑, *BDNF↑,
1741- VitD3,    Vitamin D Deficiency: Effects on Oxidative Stress, Epigenetics, Gene Regulation, and Aging
- Review, Var, NA
*Inflam↓, *antiOx↑, *eff↑, *ROS↓, *NRF2↑, *GPx↑, *Dose↝, Dose↑,
1738- VitD3,    VITAL study: an incomplete picture?
- Trial, Var, NA
AntiCan↑, *BioAv↓, Dose↑,
1739- VitD3,    Effect of Vitamin D3 Supplements on Development of Advanced Cancer
- Trial, Var, NA
AntiCan↑, Dose↝, Risk↓, TumCP↓, Inflam↓, eff∅,
115- VitD3,    Vitamin D3 Inhibits Hedgehog Signaling and Proliferation in Murine Basal Cell Carcinomas
- in-vivo, RCC, NA - in-vivo, BCC, NA
HH↓, GLI2↓, Shh↓, Gli1↓, Ki-67↓, TumCP↓,
1740- VitD3,    Vitamin D and Cancer: An Historical Overview of the Epidemiology and Mechanisms
- Review, Var, NA
Risk↓, eff↑, eff↑, Risk↓, Risk↓, ChemoSen↑, RadioS↑, Cyt‑c↑, Casp3↑, Casp9↑, hTERT/TERT↓, eff↑, E-cadherin↑, CLDN2↑, ZO-1↑, Snail↓, Zeb1↓, Vim↓, VEGF↓, NK cell↑, Risk↓, eff↑,
3921- VitD3,  RES,    Vitamin D Combined with Resveratrol Prevents Cognitive Decline in SAMP8 Mice
- in-vivo, AD, NA
*cognitive↑, *Aβ↓, *BACE↓, *p‑tau↓, *p‑CREB↑, *p‑NF-kB↓, *neuroP↑,
2369- VitD3,    Long Non-coding RNA MEG3 Activated by Vitamin D Suppresses Glycolysis in Colorectal Cancer via Promoting c-Myc Degradation
- in-vitro, CRC, DLD1 - in-vitro, CRC, RKO
MEG3↑, Glycolysis↓, lactateProd↓, LDHA↓, PKM2↓, HK2↓,
2368- VitD3,    Vitamin D3 supplementation shapes the composition of gut microbiota and improves some obesity parameters induced by high-fat diet in mice
- in-vivo, Obesity, NA
*Weight↓, *TNF-α↓, *IL1β↓, LPS↓, *ZO-1↑, *GutMicro↑,
2367- VitD3,    Vitamin D activates FBP1 to block the Warburg effect and modulate blast metabolism in acute myeloid leukemia
- in-vivo, AML, NA
FBP1↑, Warburg↓, Glycolysis↓, lactateProd↓,
2366- VitD3,    Vitamin D3 decreases glycolysis and invasiveness, and increases cellular stiffness in breast cancer cells
- in-vitro, BC, MCF-7
Glycolysis↓, tumCV↓, Apoptosis↑, mTOR↓, AMPK↑, EMT↓, E-cadherin↑, F-actin↑, Vim↓,
2365- VitD3,    Vitamin D Affects the Warburg Effect and Stemness Maintenance of Non- Small-Cell Lung Cancer Cells by Regulating the PI3K/AKT/mTOR Signaling Pathway
- in-vitro, Lung, A549 - in-vitro, Lung, H1975 - in-vivo, NA, NA
Glycolysis↓, Warburg↓, GLUT1↓, LDHA↓, HK2↓, PKM2↓, OCT4↓, SOX2↓, Nanog↓, PI3K↓, Akt↓, mTOR↓,
2171- VitD3,    Vitamin D and the Immune System
- Analysis, Nor, NA
eff↑, Dose↝, eff↝, eff↑, eff↑,

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 32

Pathway results for Effect on Cancer / Diseased Cells:


Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   FBP1↑, 1,   Glycolysis↓, 4,   HK2↓, 2,   lactateProd↓, 2,   LDHA↓, 2,   PKM2↓, 2,   Warburg↓, 2,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↑, 2,   BAX↑, 1,   Bax:Bcl2↑, 1,   Bcl-2↓, 1,   Casp3↑, 1,   Casp9↑, 1,   Cyt‑c↑, 1,   hTERT/TERT↓, 1,   MEG3↑, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 1,   EMT↝, 1,   Gli1↓, 1,   HDAC↓, 1,   HH↓, 1,   IGF-1↓, 1,   mTOR↓, 2,   Nanog↓, 1,   OCT4↓, 1,   PI3K↓, 1,   Shh↓, 1,   SOX2↓, 1,   VDR↑, 1,  

Migration ⓘ

CLDN2↑, 1,   E-cadherin↑, 2,   F-actin↑, 1,   GLI2↓, 1,   Ki-67↓, 1,   Snail↓, 1,   TumCP↓, 2,   TumMeta↓, 1,   Vim↓, 2,   Zeb1↓, 1,   ZO-1↑, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   VEGF↓, 1,  

Barriers & Transport ⓘ

GLUT1↓, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,   LPS↓, 1,   NK cell↑, 1,   PSA↓, 1,  

Hormonal & Nuclear Receptors ⓘ

CYP11A1↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   Dose↑, 2,   Dose↝, 2,   eff↑, 9,   eff↝, 1,   eff∅, 1,   RadioS↑, 2,  

Clinical Biomarkers ⓘ

hTERT/TERT↓, 1,   Ki-67↓, 1,   PSA↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 3,   neuroP↑, 1,   radioP↑, 1,   Risk↓, 7,   TumVol↓, 1,  
Total Targets: 66

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   GPx↑, 1,   MDA↓, 1,   NRF2↑, 1,   ROS↓, 2,  

Core Metabolism/Glycolysis ⓘ

p‑CREB↑, 1,   homoC↓, 1,  

Cell Death ⓘ

Casp3↓, 1,  

Transcription & Epigenetics ⓘ

other↑, 1,   other↝, 3,  

Migration ⓘ

TGF-β↑, 1,   ZO-1↑, 1,  

Immune & Inflammatory Signaling ⓘ

IL1β↓, 1,   Inflam↓, 3,   p‑NF-kB↓, 1,   PGE2↓, 1,   TNF-α↓, 1,  

Synaptic & Neurotransmission ⓘ

BDNF↑, 4,   BDNF∅, 2,   p‑tau↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 2,   BACE↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   Dose↝, 2,   eff↑, 3,   Half-Life↝, 1,  

Clinical Biomarkers ⓘ

Calcium↝, 1,   GutMicro↑, 1,  

Functional Outcomes ⓘ

cognitive↑, 9,   memory↓, 1,   Mood↑, 2,   motorD↓, 1,   neuroP↑, 1,   radioP↑, 1,   Risk↓, 7,   Weight↓, 1,  
Total Targets: 36

Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:167  Target#:%  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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