| 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.
Time-Scale Flag (TSF): P / R / G
Clinical trial data suggest vitamin D supplementation effects may be attenuated in individuals with obesity, potentially due to pharmacokinetic and inflammatory differences.
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| The Warburg effect (aerobic glycolysis) is a metabolic phenotype where many cancer cells use high glycolytic flux and lactate production even when oxygen is available. Tumors often contain hypoxic regions that further drive glycolysis, but Warburg metabolism can also occur under normoxic conditions (“pseudo-hypoxia”) via oncogenic signaling and metabolic rewiring. Hypoxia-inducible factor 1 alpha (HIF-1α) is one important driver in hypoxic tumor regions. HIF-1α upregulates glycolytic genes (e.g., GLUT1, HK2, LDHA) and promotes reduced mitochondrial pyruvate oxidation in part through induction of PDK (which inhibits PDH), shifting carbon toward lactate. Warburg effect (GLUT1, LDHA, HK2, and PKM2).Classic HIF-Warburg axis: PDK1 and MCT4 (SLC16A3) (pyruvate gate + lactate export). Here are some of the key pathways and potential targets: Note: use database Filter to find inhibitors: Ex pick target HIF1α, and effect direction ↓ 1.Glycolysis Inhibitors:(2-DG, 3-BP) - HK2 Inhibitors: such as 2-deoxyglucose, can reduce glycolysis -PFK1 Inhibitors: such as PFK-158, can reduce glycolysis -PFKFB Inhibitors: - PKM2 Inhibitors: (Shikonin) -Can reduce glycolysis - LDH Inhibitors: (Gossypol, FX11) -Reducing the conversion of pyruvate to lactate. -Inhibiting the production of ATP and NADH. - GLUT1 Inhibitors: (phloretin, WZB117) -A key transporter involved in glucose uptake. -GLUT3 Inhibitors: - PDK1 Inhibitors: (dichloroacetate) - A key enzyme involved in the regulation of glycolysis. PDK inhibitors (e.g., DCA) activate PDH and shift pyruvate into TCA/OXPHOS, reducing lactate pressure. 2.Pentose phosphate pathway: - G6PD Inhibitors: can reduce the pentose phosphate pathway 3.Hypoxia-inducible factor 1 alpha (HIF1α) pathway: - HIF1α inhibitors: (PX-478,Shikonin) -Reduce expression of glycolytic genes and inhibit cancer cell growth. 4.AMP-activated protein kinase (AMPK) pathway: -AMPK activators: (metformin,AICAR,berberine) -Can increase AMPK activity and inhibit cancer cell growth. 5.mTOR pathway: - mTOR inhibitors:(rapamycin,everolimus) -Can reduce mTOR activity and inhibit cancer cell growth. Warburg Targeting Matrix (Cancer Metabolism)
Time-Scale Flag (TSF): P / R / G
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| 2367- | VitD3, | Vitamin D activates FBP1 to block the Warburg effect and modulate blast metabolism in acute myeloid leukemia |
| - | in-vivo, | AML, | NA |
| 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 |
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#:947 State#:% Dir#:1
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