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Cancer Metabolism might be fought by many things – such as vitamin D – Oct 2023

Cancer Metabolism as a Therapeutic Target and Review of Interventions

Nutrients 2023, 15, 4245. https://doi.org/10.3390/ nu15194245
Matthew T. J. Halma 1,2 , Jack A. Tuszynski3,4,5 and Paul E. Marik ^*
Department of Physics and Astronomy, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
EbMC Squared CIC, Bath BA2 4BL, UK
Department of Physics, University of Alberta, 11335 Saskatchewan Dr NW, Edmonton, AB T6G 2M9, Canada
Department of Data Science and Engineering, The Silesian University of Technology, 44-100 Gliwice, Poland
DIMEAS, Politecnico di Torino, Corso Duca degli Abruzzi 24, I-1029 Turin, Italy
Frontline COVID-19 Critical Care Alliance, Washington, DC 20036, USA * Correspondence: pmarik at flccc.net

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Cancer is amenable to low-cost treatments, given that it has a significant metabolic com­ponent, which can be affected through diet and lifestyle change at minimal cost. The Warburg hypothesis states that cancer cells have an altered cell metabolism towards anaerobic glycolysis. Given this metabolic reprogramming in cancer cells, it is possible to target cancers metabolically by depriving them of glucose. In addition to dietary and lifestyle modifications which work on tumors metabolically, there are a panoply of nutritional supplements and repurposed drugs associated with cancer prevention and better treatment outcomes. These interventions and their evidentiary basis are covered in the latter half of this review to guide future cancer treatment.

Recommended: Vitamin D (Extracted from PDF)

Vitamin D is synthesized in the human skin through the influence of UV B radiation and is then converted into the active form, 1,25-dihydroxyvitamin D3 (calcitriol), in the kidney [323-325]. 25-hydroxyvitamin D3 (25(OH)D3) is considered the best indicator of vitamin D status, with a level > 30 ng/mL considered normal, 20-30 ng/mL considered insufficient, and <20 ng/mL considered deficient [324-326]. Recent data suggest that a level > 50 ng/mL is desirable, and, ideally, targeting a level between 55 and 90 ng/mL is preferable [323,327-329]. Adequate vitamin D supplementation is important to achieve optimal levels in patients with low vitamin D levels, and using 50,000 IU D3 capsules in divided doses over a few days is recommended [323,328,329] (Supplementary Table S1).
Vitamin D plays a critical role in various physiological pathways, including energy metabolism, immunity, and cellular growth [330]. It has pleiotropic functions and regulates over 1200 genes within the human genome, with a significant role in the modulation of the immune system [323,331,332]. Observational and randomized controlled studies indicate that a low vitamin D status is associated with higher mortality from conditions like cancer and cardiovascular disease [333,334]. Vitamin D deficiency increases the risk of breast, colon, prostate, and other cancers, while supplemental vitamin D intake has an inverse relationship with cancer risk [324,335]. Higher latitudes are associated with increased risk of vitamin D deficiency and various cancers, with vitamin D supplementation likely playing a crucial role in cancer prevention [324,336]. Achieving a vitamin D level of 80 ng/mL may reduce cancer incidence rates by 70% [337].
Mechanism
Vitamin D exhibits diverse antineoplastic activity through various pathways. It binds to the vitamin D receptor and induces differentiation and apoptosis; it also inhibits cancer stem cells, proliferation, angiogenesis, and metastatic potential [338]. It promotes apoptosis of cancer cells, inhibits WNT-p catenin signaling, and has anti-inflammatory effects by downregulating nuclear factor-Kp and inhibiting cyclooxygenase expression [339-341]. Vitamin D also regulates cell cycle, growth factor pathways, and immune responses against tumor cells [337,342]. It triggers autophagic death, promotes cell differentiation, and exhibits anti-angiogenic effects [337,343,344]. These mechanisms collectively contribute to vitamin D's anticancer effects and may help reduce cancer incidence and mortality [336].
Clinical Evidence
Multiple studies indicate that a significant proportion of cancer patients are vitamin D-deficient (level < 20 ng/mL) and that higher plasma 25-hydroxyvitamin D levels are associated with improved survival in colorectal, breast, gastric, and lymphoma cancer patients [334,338,345-351]. Meta-analyses and clinical trials demonstrate that vitamin D supplementation may reduce cancer mortality and improve survival in cancer patients, especially when used in combination with chemotherapy [352-358]. SUNSHINE, a clinical trial on metastatic colorectal cancer patients, showed that “high-dose" vitamin D3 (aiming for a level of >50 ng/mL) combined with standard chemotherapy resulted in improved progression-free survival compared to standard-dose vitamin D3 [338]. Adequate vitamin D dosing aiming for a level between 55 and 90 ng/mL may have additional benefits in cancer patients [338]. Vitamin D supplementation is suggested to have additive or synergistic effects when combined with conventional chemotherapy [359,360].
Dosing Recommendation
Vitamin D supplementation is likely beneficial for most types of cancers, especially breast, colorectal, gastric, esophageal, lung, and prostate cancer, lymphomas, and melanoma. Due to the severe vitamin D deficiency observed in most cancer patients, a high loading dose of vitamin D is recommended, followed by dose titration aiming for a level of >50 ng/mL (target 55-90 ng/mL). Some types of cancer may require higher levels, up to 150 ng/mL, to halt growth and metastasis. Daily doses of 20,000 to 50,000 IU/day are suggested until the desired vitamin D level is reached. It is important to monitor vitamin D levels to ensure appropriate maintenance dosing, and daily dosing of vitamin D3 is preferred over large intermittent bolus dosing. Vitamin K2 (menaquinone (MK4/MK7)) and magnesium are recommended in conjunction with high vitamin D doses (>8000 IU/day). Measuring parathyroid levels and calcium levels can help titrate the vitamin D dose according to the Coimbra Protocol [65,66].
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39 Vitamin D references (of 520 references)
  • Wimalawansa, S.J. Physiological Basis for Using Vitamin D to Improve Health. Biomedicines 2023,11,1542. [CrossRef]
  • Holick, M.F. Vitamin D Deficiency. N. Engl. J. Med. 2002, 357, 266-281. [CrossRef]
  • Brandi, M.L. Indications on the use of Vitamin D and Vitamin D metabolites in clinical phenotypes. Clin. Cases Miner. Bone Metab. 2010, 7, 243-250.
  • Chapuy, M.C.; Preziosi, P.; Maamer, M.; Arnaud, S.; Galan, P.; Hercberg, S.; Meunier, PJ. Prevalence of Vitamin D Insufficiency in an Adult Normal Population. Osteoporos. lnt. 1997, 7, 439-443. [CrossRef]
  • Vieth, R. Why the optimal requirement for Vitamin D3 is probably much higher than what is officially recommended for adults. J. Steroid Biochem. Mol. Biol. 2004, 89-90, 575-579. [CrossRef]
  • Wimalawansa, S.J. Rapidly Increasing Serum 25(OH)D Boosts the Immune System, against Infections—Sepsis and COVID-19. Nutrients 2022,14, 2997. [CrossRef]
  • Wimalawansa, S.J. Effective and practical ways to overcome Vitamin D deficiency. J. Fam. Med. Community Health 2021, 8,1185.
  • Carlberg, C.; Velleuer, E. Vitamin D and the risk for cancer: A molecular analysis. Biochem. Pharmacol. 2022,196,114735. [CrossRef]
  • Baeke, F.; Takiishi, T.; Korf, H.; Gysemans, C.; Mathieu, C. Vitamin D: Modulator of the immune system. Curr. Opin. Pharmacol. 2010,10, 482-496. [CrossRef]
  • Bartley, J. Vitamin D: Emerging roles in infection and immunity. Expert Rev. Anti-lnfect. Ther. 2010, 8,1359-1369. [CrossRef] [PubMed]
  • Chowdhury, R.; Kunutsor, S.; Vitezova, A.; Oliver-Williams, C.; Chowdhury, S.; Kiefte-de-Jong, J.C.; Khan, H.; Baena, C.P.; Prabhakaran, D.; Hoshen, M.B. Vitamin D and risk of cause specific death: Systematic review and meta-analysis of observational cohort and randomised intervention studies. BMJ 2014, 348, g1903. [CrossRef] [PubMed]
  • Ng, K.; Venook, A.P.; Sato, K.; Yuan, C.; Hollis, B.W.; Niedzwiecki, D.; Ye, C.; Chang, I.W.; O'Neil, B.H.; Innocenti, F. Vitamin D status and survival of metastatic colorectal cancer patients: Results from CALGB/SWOG 80405 (Alliance). J. Clin. Oncol. 2015, 33, 3503. [CrossRef]
  • Hossain, S.; Beydoun, M.A.; Beydoun, H.A.; Chen, X.; Zonderman, A.B.; Wood, R.J. Vitamin D and breast cancer: A systematic review and meta-analysis of observational studies. Clin. Nutr. ESPEN 2019, 30,170-184. [CrossRef]
  • Zhang, Y.; Fang, F.; Tang, J.; Jia, L.; Feng, Y.; Xu, P.; Faramand, A. Association between Vitamin D supplementation and mortality: Systematic review and meta-analysis. BMJ 2019, 366, l4673. [CrossRef] [PubMed]
  • Muñoz, A.; Grant, W.B. Vitamin D and cancer: An historical overview of the epidemiology and mechanisms. Nutrients 2022, 14,1448. [CrossRef] [PubMed]
  • Ng, K.; Nimeiri, H.S.; McCleary, N.J.; Abrams, T.A.; Yurgelun, M.B.; Cleary, J.M.; Rubinson, D.A.; Schrag, D.; Miksad, R.; Bullock, A.J. Effect of high-dose vs standard-dose Vitamin D3 supplementation on progression-free survival among patients with advanced or metastatic colorectal cancer: The SUNSHINE randomized clinical trial. JAMA 2019, 321,1370-1379. [CrossRef]
  • Díaz, G.D.; Paraskeva, C.; Thomas, M.G.; Binderup, L.; Hague, A. Apoptosis is induced by the active metabolite of Vitamin D3 and its analogue EB1089 in colorectal adenoma and carcinoma cells: Possible implications for prevention and therapy. Cancer Res. 2000, 60, 2304-2312. [PubMed]
  • Feldman, D.; Krishnan, A.V.; Swami, S.; Giovannucci, E.; Feldman, B.J. The role of Vitamin D in reducing cancer risk and progression. Nat. Rev. Cancer 2014,14, 342-357. [CrossRef]
  • Mathieu, C.; Adorini, L. The coming of age of 1, 25-dihydroxyVitamin D3 analogs as immunomodulatory agents. Trends Mol. Med. 2002, 8,174-179. [CrossRef]
  • Yang, E.S.; Burnstein, K.L. Vitamin D inhibits G1 to S progression in LNCaP prostate cancer cells through p27Kip1 stabilization and Cdk2 mislocalization to the cytoplasm. J. Biol. Chem. 2003, 278, 46862-46868. [CrossRef]
  • Larriba, M.J.; García de Herreros, A.; Muñoz, A. Vitamin D and the epithelial to mesenchymal transition. Stem Cells lnt. 2016, 2016, 6213872. [CrossRef]
  • Bernardi, R.J.; Johnson, C.S.; Modzelewski, R.A.; Trump, D.L. Antiproliferative effects of 1a, 25-dihydroxyVitamin D3 and Vitamin D analogs on tumor-derived endothelial cells. Endocrinology 2002,143, 2508-2514. [CrossRef]
  • Ng, K.; Meyerhardt, J.A.; Wu, K.; Feskanich, D.; Hollis, B.W.; Giovannucci, E.L.; Fuchs, C.S. Circulating 25-hydroxyVitamin D levels and survival in patients with colorectal cancer. J. Clin. Oncol. 2008, 26, 2984-2991. [CrossRef]
  • Johansson, H.; Spadola, G.; Tosti, G.; Mandalà, M.; Minisini, A.M.; Queirolo, P.; Aristarco, V.; Baldini, F.; Cocorocchio, E.; Albertazzi, E. Vitamin D supplementation and disease-free survival in stage II melanoma: A randomized placebo controlled trial. Nutrients 2021,13,1931. [CrossRef] [PubMed]
  • Yuan, C.; Sato, K.; Hollis, B.W.; Zhang, S.; Niedzwiecki, D.; Ou, F.-S.; Chang, I.W.; O'Neil, B.H.; Innocenti, F.; Lenz, H.-J. Plasma 25-hydroxyVitamin D levels and survival in patients with advanced or metastatic colorectal cancer: Findings from CALGB/SWOG 80405 (Alliance). Clin. Cancer Res. 2019, 25,7497-7505. [CrossRef] [PubMed]
  • Mezawa, H.; Sugiura, T.; Watanabe, M.; Norizoe, C.; Takahashi, D.; Shimojima, A.; Tamez, S.; Tsutsumi, Y.; Yanaga, K.; Urashima, M. Serum Vitamin D levels and survival of patients with colorectal cancer: Post-hoc analysis of a prospective cohort study. BMC Cancer 2010,10, 347. [CrossRef] [PubMed]
  • Zgaga, L.; Theodoratou, E.; Farrington, S.M.; Din, F.V.; Ooi, L.Y.; Glodzik, D.; Johnston, S.; Tenesa, A.; Campbell, H.; Dunlop, M.G. Plasma Vitamin D concentration influences survival outcome after a diagnosis of colorectal cancer. J. Clin. Oncol. 2014, 32, 2430-2439. [CrossRef]
  • Toriola, A.T.; Nguyen, N.; Scheitler-Ring, K.; Colditz, G.A. Circulating 25-hydroxyVitamin D levels and prognosis among cancer patients: A systematic review. Cancer Epidemiol. Biomark. Prev. 2014, 23, 917-933. [CrossRef]
  • Tretli, S.; Schwartz, G.G.; Torjesen, P.A.; Robsahm, T.E. Serum levels of 25-hydroxyVitamin D and survival in Norwegian patients with cancer of breast, colon, lung, and lymphoma: A population-based study. Cancer Causes Control 2012, 23, 363-370. [CrossRef]
  • Chen, Q.-Y.; Kim, S.; Lee, B.; Jeong, G.; Lee, D.H.; Keum, N.; Manson, J.E.; Giovannucci, E.L. Post-diagnosis Vitamin D supplement use and survival among cancer patients: A meta-analysis. Nutrients 2022,14, 3418. [CrossRef]
  • Vaughan-Shaw, P.G.; Buijs, L.F.; Blackmur, J.P.; Theodoratou, E.; Zgaga, L.; Din, F.V.N.; Farrington, S.M.; Dunlop, M.G. The effect of Vitamin D supplementation on survival in patients with colorectal cancer: Systematic review and meta-analysis of randomised controlled trials. Br. J. Cancer 2020,123,1705-1712. [CrossRef]
  • Kuznia, S.; Zhu, A.; Akutsu, T.; Buring, J.E.; Camargo, C.A., Jr.; Cook, N.R.; Chen, L.-J.; Cheng, T.-Y.D.; Hantunen, S.; Lee, I.M. Efficacy of Vitamin D3 supplementation on cancer mortality: Systematic review and individual patient data meta-analysis of randomised controlled trials. Ageing Res. Rev. 2023, 87,101923. [CrossRef]
  • Wang, L.; Wang, C.; Wang, J.; Huang, X.; Cheng, Y. Longitudinal, observational study on associations between postoperative nutritional Vitamin D supplementation and clinical outcomes in esophageal cancer patients undergoing esophagectomy. Sci. Rep. 2016, 6, 38962. [CrossRef]
  • Madden, J.M.; Murphy, L.; Zgaga, L.; Bennett, K. De novo Vitamin D supplement use post-diagnosis is associated with breast cancer survival. Breast Cancer Res. Treat. 2018,172,179-190. [CrossRef] [PubMed]
  • Marshall, D.T.; Savage, S.J.; Garrett-Mayer, E.; Keane, T.E.; Hollis, B.W.; Horst, R.L.; Ambrose, L.H.; Kindy, M.S.; Gattoni-Celli, S. Vitamin D3 supplementation at 4000 international units per day for one year results in a decrease of positive cores at repeat biopsy in subjects with low-risk prostate cancer under active surveillance. J. Clin. Endocrinol. Metab. 2012, 97, 2315-2324. [CrossRef] [PubMed]
  • Wagner, D.; Trudel, D.; Van der Kwast, T.; Nonn, L.; Giangreco, A.A.; Li, D.; Dias, A.; Cardoza, M.; Laszlo, S.; Hersey, K. Randomized clinical trial of Vitamin D3 doses on prostatic Vitamin D metabolite levels and ki67 labeling in prostate cancer patients. J. Clin. Endocrinol. Metab. 2013, 98,1498-1507. [CrossRef] [PubMed]
  • Zeichner, S.B.; Koru-Sengul, T.; Shah, N.; Liu, Q.; Markward, N.J.; Montero, A.J.; Glück, S.; Silva, O.; Ahn, E.R. Improved clinical outcomes associated with Vitamin D supplementation during adjuvant chemotherapy in patients with HER2+ nonmetastatic breast cancer. Clin. Breast Cancer 2015,15, e1-e11. [CrossRef]
  • Amon, U.; Yaguboglu, R.; Ennis, M.; Holick, M.F.; Amon, J. Safety Data in Patients with Autoimmune Diseases during Treatment with High Doses of Vitamin D3 According to the "Coimbra Protocol". Nutrients 2022,14,1575. [CrossRef]
  • Finamor, D.C.; Sinigaglia-Coimbra, R.; Neves, L.C.M.; Gutierrez, M.; Silva, J.J.; Torres, L.D.; Surano, F.; Neto, D.J.; Novo, N.F.; Juliano, Y. A pilot study assessing the effect of prolonged administration of high daily doses of Vitamin D on the clinical course of vitiligo and psoriasis. Derm.-Endocrinol. 2013, 5, 222-234. [CrossRef]

VitaminDWiki – Cancer category contains:

87 Meta-analyses in VitaminDWiki with CANCER etc in the title

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5+ VitaminDWiki LOADING DOSE pages with CANCER etc in title

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726+ VitaminDWiki pages have both CANCER AND VITAMIN in the title

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Note: This does NOT include Leukemia, Lymphoma, Melanoma, etc.

600,000 Hits for (cancer metabolism) "vitamin d" in Google Scholar Oct 2023

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* Vitamin D and the risk for cancer: A molecular analysis - Feb 2022 https://doi.org/10.1016/j.bcp.2021.114735 FREE PDF
* New insights into molecules and pathways of cancer metabolism and therapeutic implications - Nov 2020 https://doi.org/10.1002/cac2.12112 FREE PDF
*Relationship Between Vitamin D Supplementation and Improvement in Body for Carcinogenesis: A Literature Review 2022 - https://doi.org/10.37275/bsm.v6i2.447 FREE PDF

Cancer Metabolism might be fought by many things – such as vitamin D – Oct 2023        
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