Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Clinical Research

Vitamin D deficiency: a potential risk factor for cancer in obesity?

International Journal of Obesity volume 46, pages 707–717 (2022)Cite this article

Subjects

Abstract

Obesity is considered an abnormal or excessive accumulation of adipose tissue, due to a prolonged positive energy balance that arises when energy intake is greater than energy expenditure, leading to an increased risk for the individual health and for the development of metabolic chronic diseases including several different types of cancer. Vitamin D deficiency is a metabolic alteration, which is often associated with the obesity condition. Vitamin D is a liposoluble vitamin, which plays a pivotal role in calcium-phosphate metabolism but extraskeletal effects have also been described. Among these, it plays an important role also in adipocyte physiology and glucose metabolism, typically dysregulated in subjects affected by obesity. Moreover, it is now recognized that Vitamin D also influences the processes of cell proliferation, differentiation, adhesion potentially leading to carcinogenesis. Indeed, data indicate a potential link between vitamin D levels and cancer, and higher vitamin D concentrations have been associated with a lower risk of developing different kinds of tumors, including breast, colon, lymphoma, lung, and prostate cancers. Thus, this review will revise the literature regarding this issue investigating and highlighting the potential mechanism of action, which might lead to new therapeutical options.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Vitamin D deficiency and correlation with different type of cancers.

Similar content being viewed by others

References

  1. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser. 2000;894:1–253.

    Google Scholar 

  2. Wang YC, McPherson K, Marsh T, Gortmaker SL, Brown M. Health and economic burden of the projected obesity trends in the USA and the UK. Lancet. 9793;378:815–25.

    Article  Google Scholar 

  3. Risk NCD. Factor collaboration. Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants. Lancet. 2016;387:1377–96.

    Article  Google Scholar 

  4. Keaver L, Webber L, Dee A, Shiely F, Marsh T, Balanda K, et al. Application of the UK foresight obesity model in Ireland: The health and economic consequences of projected obesity trends in Ireland. PLoS ONE. 2013;8(Nov):e79827.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Ashwell MLM, Richardson J, Rickayzen B. Waist-to-height ratio is more predictive of years of life lost than body mass index. PLoS ONE. 2014;9:e103483.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Fitch A, Fox C, Bauerly K, Gross A, Heim C, Judge-Dietz J, et al. Prevention and management of obesity for children and adolescents. Bloomington (MN): Institute for Clinical Systems Improvement (ICSI); 2013.

  7. Aung K, Lorenzo C, Hinojosa MA, Haffner SM. Risk of developing diabetes and cardiovascular disease in metabolically unhealthy normal-weight and metabolically healthy obese individuals. J Clin Endocrinol Metab. 2014;99(2):462–8.

    Article  CAS  PubMed  Google Scholar 

  8. Heymsfield SB, Scherzer R, Pietrobelli A, Lewis CE, Grunfeld C. Body mass index as a phenotypic expression of adiposity: quantitative contribution of muscularity in a population-based sample. Int J Obes. 2009;33:1363–73.

    Article  CAS  Google Scholar 

  9. Okorodudu DO, Jumean MF, Montori VM, Romero-Corral A, Somers VK, Erwin PJ, et al. Diagnostic performance of body mass index to identify obesity as defined by body adiposity: a systematic review and meta-analysis. Int J Obes . 2010;34:791–9.

    Article  CAS  Google Scholar 

  10. Galic S, Oakhill JS, Steinberg GR. Adipose tissue as an endocrine organ. Mol Cell Endocrinol. 2010;316:129–39.

    Article  CAS  PubMed  Google Scholar 

  11. The Third Expert Report, DIet, nutrition, physical activity and cancer: a global perspective. Continuous Update Project Expert Report. https://www.wcrf.org/dietandcancer.

  12. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U. S. adults. N Engl J Med. 2003;348:1625–38.

    Article  PubMed  Google Scholar 

  13. Vecchié A, Dallegri F, Carbone F, Bonaventura A, Liberale L, Portincasa P, et al. Obesity phenotypes and their paradoxical association with cardiovascular diseases. Eur J Intern Med. 2018;48(Feb):6–17.

    Article  PubMed  Google Scholar 

  14. Liberale L, Bonaventura A, Vecchie A, Matteo C, Dallegri F, Montecucco F, et al. The role of adipocytokines in coronary atherosclerosis. Curr Atheroscler Rep. 2017;19:10.

    Article  PubMed  Google Scholar 

  15. de Koning L, Merchant AT, Pogue J, Anand SS. Waist circumference and waist-to-hip ratio as predictors of cardiovascular events: meta-regression analysis of prospective studies. European Heart J. 2007;28:850–6.

    Article  Google Scholar 

  16. Freisling H, Arnold M, Soerjomataram I, O’Doherty MG, Ordonez-Mena JM, Bamia C, et al. Comparison of general obesity and measures of body fat distribution in older adults in relation to cancer risk: meta-analysis of individual participant data of seven prospective cohorts in Europe. Br J Cancer. 2017;116:1486–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Pischon T, Lahmann PH, Boeing H, Friedenreich C, Norat T, Tjonneland A, et al. Body size and risk of colon and rectal cancer in the European Prospective Investigation Into Cancer and Nutrition (EPIC). J Natl Cancer Inst. 2006;98:920–31.

    Article  PubMed  Google Scholar 

  18. Ryan AM, Duong M, Healy L, Ryan SA, Parekh N, Reynolds JV. et al. Obesity, metabolic syndrome and esophageal adenocarcinoma: epidemiology, etiology and new targets. Cancer Epidemiol. 2011;3:309–19.

    Article  Google Scholar 

  19. Bikle DD. Extraskeletal actions of vitamin D. Ann N Y Acad Sci. 2016;1376:29–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Bikle DD. Extra renal synthesis of 1,25 dihydroxyvitamin D and its Health Implications. Clin Rev Bone Min Metab. 2009;7:114–25.

    Article  CAS  Google Scholar 

  21. Holick MF. Cancer, sunlight and vitamin D. J Clin Transl Endocrinol. 2014;1:179–86.

    PubMed  PubMed Central  Google Scholar 

  22. Holick MF. Vitamin D and sunlight: strategies for cancer prevention and other health benefits. Clin J Am Soc Nephrol. 2008;3:1548e54.

    Article  Google Scholar 

  23. Freedman DM, Looker AC, Abnet CC, Linet MS, Graubard BI. Serum 25-hydroxyvitamin D and cancer mortality in the NHANES III study (1988-2006). Cancer Res. 2010;70:8587e97.

    Article  Google Scholar 

  24. Garland CF, Gorham ED, Mohr SB, Grant WB, Giovannucci EL, Lipkin M, et al. Vitamin D and prevention of breast cancer: pooled analysis. J Steroid Biochem Mol Biol. 2007;103:708e11.

    Article  Google Scholar 

  25. Nair R, Maseeh A. Vitamin D: the “sunshine” vitamin. J Pharmacol Pharmacother. 2012;3(Apr):118–26.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Pereira-Santos M, Costa PR, Assis AM, Santos CA, Santos DB. Obesity and vitamin D deficiency: a systematic review and meta-analysis. Obes Rev. 2015;16:341–9.

    Article  CAS  PubMed  Google Scholar 

  27. Greco EA, Lenzi A, Migliaccio S. Role of hypovitaminosis D in the pathogenesis of obesity-induced insulin resistance. Nutrients. 2019;11:pii: E1506.

    Article  Google Scholar 

  28. Di Nisio A, De Toni L, Sabovic I, Rocca MS, De Filippis V, Opocher G, et al. Impaired release of vitamin D in dysfunctional adipose tissue: new cues on vitamin D supplementation in obesity. J Clin Endocrinol Metab. 2017;102:2564–74.

    Article  PubMed  Google Scholar 

  29. Migliaccio S, Di Nisio A, Mele C, Scappaticcio L, Savastano S, Colao A. Obesity programs of nutrition, education, research and assessment (OPERA) group. Obesity and hypovitaminosis D: causality or casualty? Int J Obes Suppl. 2019;9:20–31.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Jones G, Strugnell SA, DeLuca HF. Current understanding of the molecular actions of vitamin D. Physiol. Rev. 1998;78:1193–231.

    Article  CAS  PubMed  Google Scholar 

  31. Battault S, Whiting SJ, Peltier SL, Sadrin S, Gerber G, Maixent JM. Vitamin D metabolism, functions and needs: fromscience to health claims. Eur J Nutr. 2013;52:429–41.

    Article  CAS  PubMed  Google Scholar 

  32. Bouillon R, Marcocci C, Carmeliet G, Bikle D, White JH, Dawson-Hughes B, et al. Skeletal and extraskeletal actions of vitamin D: current evidence and outstanding questions. Endocr Rev. 2019;40(Aug):1109–51.

    Article  PubMed  Google Scholar 

  33. Hyppönen E, Power C. Hypovitaminosis D in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors. Am J Clin Nutr. 2007;85:860–8.

    Article  PubMed  Google Scholar 

  34. Compston JE, Vedi S, Ledger JE, Webb A, Gazet JC, Pilkington TR. Vitamin D status and bone histomorphometry in gross obesity. Am J Clin Nutr. 1981;34:2359–63.

    Article  CAS  PubMed  Google Scholar 

  35. Vanlint S. Vitamin D and obesity. Nutrients. 2013;5:949–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Ruiz-Ojeda FJ, Anguita-Ruiz A, Leis R, Aguilera CM. Genetic factors and molecular mechanisms of vitamin D and obesity relationship. Ann Nutr Metab. 2018;73:89–99.

    Article  CAS  PubMed  Google Scholar 

  37. Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr. 2000;72:690–3.

    Article  CAS  PubMed  Google Scholar 

  38. Drincic AT, Armas LA, Van Diest EE, Heaney RP. Volumetric dilution, rather than sequestration best explains the low vitamin D status of obesity. Obesity (Silver Spring). 2012;20:1444–8.

    Article  CAS  Google Scholar 

  39. Carrelli A, Bucovsky M, Horst R, Cremers S, Zhang C, Bessler M, et al. Vitamin D storage in adipose tissue of obese and normal weight women. J Bone Miner Res. 2016;32:237–42.

    Article  PubMed  Google Scholar 

  40. Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K. International agency for research on cancer handbook working group. Body fatness and cancer-viewpoint of the IARC working group. N Engl J Med. 2016;375:794–8.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Czech MP. Insulin action and resistance in obesity and type 2 diabetes. Nat Med. 2017;23(Jul):804–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Frystyk J, Vestbo E, Skjaerbaek C, Mogensen CE, Orskov H. Free insulin-like growth factors in human obesity. Metabolism. 1995;44:37–44.

    Article  CAS  PubMed  Google Scholar 

  43. De Pergola G, Silvestris F. Obesity as a major risk factor for cancer. J Obes. 2013;2013:291546.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Pollak M. The insulin and insulin-like growth factor receptor family in neoplasia: an update. Nat Rev Cancer. 2012;12(Feb):159–69.

    Article  CAS  PubMed  Google Scholar 

  45. Gérard C, Brown KA. Obesity and breast cancer - Role of estrogens and the molecular underpinnings of aromatase regulation in breast adipose tissue. Mol Cell Endocrinol. 2018;466(May):15–30.

    Article  PubMed  Google Scholar 

  46. Allott EH, Masko EM, Freedland SJ. Obesity and prostate cancer: weighing the evidence. Eur Urol. 2013;63:800–9.

    Article  CAS  PubMed  Google Scholar 

  47. Vigneri PG, Tirrò E, Pennisi MS, Massimino M, Stella S, Romano C, et al. The insulin/IGF system in colorectal cancer development and resistance to therapy. Front Oncol. 2015;5:230.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Bulun SE, Chen D, Moy I, Brooks DC, Zhao H. Aromatase, breast cancer and obesity: a complex interaction. Trends Endocrinol Metab. 2012;23(Feb):83–9.

    Article  CAS  PubMed  Google Scholar 

  49. Chu R, van Hasselt A, Vlantis AC, Ng EK, Liu SY, Fan MD, et al. The cross-talk between estrogen receptor and peroxisome proliferator-activated receptor gamma in thyroid cancer. Cancer. 2014;120:142–53.

    Article  CAS  PubMed  Google Scholar 

  50. Renehan AG, Roberts DL, Dive C. Obesity and cancer: pathophysiological and biological mechanisms. Arch Physiol Biochem. 2008;114:71–83.

    Article  CAS  PubMed  Google Scholar 

  51. Sun X, Casbas-Hernandez P, Bigelow C, Makowski L, Jerry DJ, Schneider SS, et al. Normal breast tissue of obese women is enriched for macrophage markers and macrophage-associated gene expression. Breast Cancer Res Treat. 2012;131:1003–12.

    Article  CAS  PubMed  Google Scholar 

  52. Lane BR, Stephenson AJ, Magi-Galluzzi C, Lakin MM, Klein EA. Low testosterone and risk of biochemical recurrence and poorly differentiated prostate cancer at radical prostatectomy. Urology. 2008;72:1240–5.

    Article  PubMed  Google Scholar 

  53. Park J, Morley TS, Kim M, Clegg DJ, Scherer PE. Obesity and cancer–mechanisms underlying tumour progression and recurrence. Nat Rev Endocrinol. 2014;10:455–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Catalano S, Marsico S, Giordano C, Mauro L, Rizza P, Panno ML, et al. Leptin enhances, via AP-1, expression of aromatase in the CF-7 cell line*. J Biol Chem. 2003;278:28668–76.

    Article  CAS  PubMed  Google Scholar 

  55. Fusco R, Galgani M, Procaccini C, Franco R, Pirozzi G, Fucci L, et al. Cellular and molecular crosstalk between leptin receptor and estrogen receptor-{alpha} in breast cancer: molecular basis for a novel therapeutic setting. Endocr Relat Cancer. 2010;17:373–82.

    Article  CAS  PubMed  Google Scholar 

  56. Tarasiuk A, Mosińska P, Fichna J. The mechanisms linking obesity to colon cancer: An overview. Obes Res Clin Pract. 2018;12:251–9.

    Article  PubMed  Google Scholar 

  57. Stattin P, Lukanova A, Biessy C, Söderberg S, Palmqvist R, Kaaks R, et al. Obesity and colon cancer: does leptin provide a link? Int J Cancer. 2004;109:149–52.

    Article  CAS  PubMed  Google Scholar 

  58. Barb D, Williams CJ, Neuwirth AK, Mantzoros CS. Adiponectin in relation to malignancies: a review of existing basic research and clinical evidence. Am J Clin Nutr. 2007;86:s858–66.

    Article  PubMed  Google Scholar 

  59. Grossmann ME, Nkhata KJ, Mizuno NK, Ray A, Cleary MP. Effects of adiponectin on breast cancer cell growth and signaling. Br J Cancer. 2008;98:370–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Yoneda K, Tomimoto A, Endo H, Iida H, Sugiyama M, Takahashi H, et al. Expression of adiponectin receptors, AdipoR1 and AdipoR2, in normal colon epithelium and colon cancer tissue. Oncol Rep. 2008;20:479–83.

    CAS  PubMed  Google Scholar 

  61. Morris PG, Hudis CA, Giri D, Morrow M, Falcone DJ, Zhou XK, et al. Inflammation and increased aromatase expression occur in the breast tissue of obese women with breast cancer. Cancer Prev Res. 2011;4:1021–9.

    Article  CAS  Google Scholar 

  62. van Kruijsdijk RCM, van der Wall E, Visseren FLJ. Obesity and cancer: the role of dysfunctional adipose tissue. Cancer Epidemiol Biomarkers Prev. 2009;18:2569–78.

    Article  PubMed  Google Scholar 

  63. Harvey AE, Lashinger LM, Hursting SD. The growing challenge of obesity and cancer: an inflammatory issue. Ann N Y Acad Sci. 2011;1229:45–52.

    Article  CAS  PubMed  Google Scholar 

  64. Balaban S, Lee LS, Schreuder M, Hoy AJ. Obesity and cancer progression: is there a role of fatty acid metabolism? Biomed Res Int. 2015;2015:274585.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Argolo DF, Hudis CA, Iyengar NM. The impact of obesity on breast cancer. Curr Oncol Rep. 2018;20:47.

    Article  PubMed  Google Scholar 

  66. Shah MS, Fogelman DR, Raghav KP, Heymach JV, Tran HT, Jiang ZQ, et al. Joint prognostic effect of obesity and chronic systemic inflammation in patients with metastatic colorectal cancer. Cancer. 2015;121:2968–75.

    Article  CAS  PubMed  Google Scholar 

  67. Crujeiras AB, Díaz-Lagares A, Carreira MC, Amil M, Casanueva FF. Oxidative stress associated to dysfunctional adipose tissue: a potential link between obesity, type 2 diabetes mellitus and breast cancer. Free Radic Res. 2013;47:243–56.

    Article  CAS  PubMed  Google Scholar 

  68. Mahalingaiah PK, Ponnusamy L, Singh KP. Chronic oxidative stress causes estrogen-independent aggressive phenotype, and epigenetic inactivation of estrogen receptor alpha in MCF-7 breast cancer cells. Breast Cancer Res Treat. 2015;153:41–56.

    Article  CAS  PubMed  Google Scholar 

  69. Udensi UK, Tchounwou PB. Oxidative stress in prostate hyperplasia and carcinogenesis. J Exp Clin Cancer Res. 2016;35:139.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Carini F, Mazzola M, Rappa F, Jurjus A, Geagea AG, Al Kattar S, et al. Colorectal carcinogenesis: role of oxidative stress and antioxidants. Anticancer Res. 2017;37:4759–66.

    CAS  PubMed  Google Scholar 

  71. Rogers CJ, Prabhu KS, Vijay-Kumar M. The microbiome and obesity-an established risk for certain types of cancer. Cancer J. 2014;20:176–80.

    Article  CAS  PubMed  Google Scholar 

  72. Cani PD, Jordan BF. Gut microbiota-mediated inflammation in obesity: a link with gastrointestinal cancer. Nat Rev Gastroenterol Hepatol. 2018;15:671–82.

    Article  CAS  PubMed  Google Scholar 

  73. Goedert JJ, Jones G, Hua X, Xu X, Yu G, Flores R, et al. Investigation of the association between the fecal microbiota and breast cancer in postmenopausal women: a population-based case-control pilot study. J Natl Cancer Inst. 2015;107:djv147.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Golombos DM, Ayangbesan A, O’Malley P, Lewicki P, Barlow L, Barbieri CE, et al. The role of gut microbiome in the pathogenesis of prostate cancer: a prospective, pilot study. Urology. 2018;111:122–8.

    Article  PubMed  Google Scholar 

  75. Bähr I, Jahn J, Zipprich A, Pahlow I, Spielmann J, Kielstein H. Impaired natural killer cell subset phenotypes in human obesity. Immunol Res. 2018;66:234–44.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Mondul AM, Weinstein SJ, Layne TM, Albanes D. Vitamin D and cancer risk and mortality: state of the science, gaps, and challenges. Epidemiol Rev. 2017;39:28–48.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Ma Y, Zhang P, Wang F, Yang J, Liu Z, Qin H. Association between vitamin D and risk of colorectal cancer: a systematic review of prospective studies. J Clin Oncol. 2011;29:3775–82.

    Article  CAS  PubMed  Google Scholar 

  78. Touvier M, Chan DS, Lau R, Aune D, Vieira R, Greenwood DC, et al. Meta-analyses of vitamin D intake, 25-hydroxyvitamin D status, vitamin D receptor polymorphisms, and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev. 2011;20:1003–16.

    Article  CAS  PubMed  Google Scholar 

  79. Negri M, Gentile A, de Angelis C, Montò T, Patalano R, Colao A, et al. Vitamin D-induced molecular mechanisms to potentiate cancer therapy and to reverse drug-resistance in cancer cells. Nutrients. 2020;12:1798.

    Article  CAS  PubMed Central  Google Scholar 

  80. Xu Y, Shao X, Yao Y, Xu L, Chang L, Jiang Z, et al. Positive association between circulating 25-hydroxyvitamin D levels and prostate cancer risk: new findings from an updated meta-analysis. J Cancer Res Clin Oncol. 2014;140:1465–77.

    Article  CAS  PubMed  Google Scholar 

  81. Kristal AR, Till C, Song X, Tangen CM, Goodman PJ, Neuhauser ML, et al. Plasma vitamin D and prostate cancer risk: results from the selenium and vitamin E cancer prevention trial. Cancer Epidemiol Biomarkers Prev. 2014;23:1494–504.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Schenk JM, Till CA, Tangen CM, Goodman PJ, Song X, Torkko KC, et al. Serum 25- hydroxyvitamin D concentrations and risk of prostate cancer: results from the prostate cancer prevention trial. Cancer Epidemiol Biomarkers Prev. 2014;23:1484–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Miles FL, Goodman PJ, Tangen C, Torkko KC, Schenk JM, Song X, et al. Interactions of the insulin-like growth factor axis and vitamin D in prostate cancer risk in the prostate cancer prevention trial. Nutrients. 2017;9:378.

    Article  PubMed Central  Google Scholar 

  84. Nair-Shalliker V, Bang A, Egger S, Clements M, Gardiner RA, Kricker A, et al. Post-treatment levels of plasma 25- and 1,25-dihydroxy vitamin D and mortality in men with aggressive prostate cancer. Sci Rep. 2020;10:7736.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Chen GC, Zhang ZL, Wan Z, Wang L, Weber P, Eggersdorfer M, et al. Circulating 25-hydroxyvitamin D and risk of lung cancer: a dose-response meta-analysis. Cancer Causes Control. 2015;26:1719–28.27.

    Article  CAS  PubMed  Google Scholar 

  86. Zhang L, Wang S, Che X, Li X. Vitamin D and lung cancer risk: a comprehensive review and meta-analysis. Cell Physiol Biochem. 2015;36:299–305.

    Article  PubMed  Google Scholar 

  87. Harvie M, Hooper L, Howell AH. Central obesity and breast cancer risk: a systematic review. Obes Rev. 2003;4:157–73.

    Article  CAS  PubMed  Google Scholar 

  88. Amir E, Cecchini RS, Ganz PA. et al. 25-Hydroxy vitamin-D, obesity, and associated variables as predictors of breast cancer risk and tamoxifen benefit in NSABP-P1. Breast Cancer Res Treat. 2012;133:1077–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Murphy N, Knuppel A, Papadimitriou N, Martin RM, Tsilidis KK, Smith-Byrne K. et al. Insulin-like growth factor-1, insulin-like growth factor-binding protein-3, and breast cancer risk: observational and Mendelian randomization analyses with ~430 000 women. Ann Oncol. 2020;31:641–9.

    Article  CAS  PubMed  Google Scholar 

  90. Housa D, Housova J, Vernerova Z, Haluzik M. Adipocytokines and cancer. Physiol Res. 2006;55:233–44.

    Article  CAS  PubMed  Google Scholar 

  91. Cui Y, Rohan TE. Vitamin D, calcium, and breast cancer risk: a review. Cancer Epidemiol Biomark Prev. 2006;15:1427–37.

    Article  CAS  Google Scholar 

  92. Feldman D, Krishnan AV, Swami S, Giovannucci E, Feldman BJ. The role of vitamin D in reducing cancer risk and progression. Nat Rev Cancer. 2014;14:342–57.

    Article  CAS  PubMed  Google Scholar 

  93. Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S, et al. Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med. 2019;380:33–44.

    Article  CAS  PubMed  Google Scholar 

  94. Krishnan AV, Feldman D. Mechanisms of the anti-cancer and anti-inflammatory actions of vitamin D. Annu Rev Pharmacol Toxicol. 2011;51:311–36.

    Article  CAS  PubMed  Google Scholar 

  95. Giammanco M, Di Majo D, La Guardia M, Aiello S, Crescimannno M, Flandina C, et al. Vitamin D in cancer chemoprevention. Pharm. Biol. 2015;53:1399–434.

    Article  CAS  PubMed  Google Scholar 

  96. Fleet JC, DeSmet M, Johnson R, Li Y. Vitamin D and cancer: a review of molecular mechanisms. Biochem J. 2012;441:61–76.

    Article  CAS  PubMed  Google Scholar 

  97. Keum N, Giovannucci E. Vitamin D supplements and cancer incidence and mortality: a meta-analysis. Br J Cancer. 2014;111:976–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Chung M, Lee J, Terasawa T, Lau J, Trikalinos TA. Vitamin D with or without calcium supplementation for prevention of cancer and fractures: an updated meta-analysis for the U.S. Preventive Services Task Force. Ann Intern Med. 2011;155:827–38.

    Article  PubMed  Google Scholar 

  99. Wactawski-Wende J, Kotchen JM, Anderson GL, Assaf AR, Brunner RL, O’Sullivan MJ, et al. Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med. 2006;354:684–96.

    Article  CAS  PubMed  Google Scholar 

  100. Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007;85:1586–91.

    Article  CAS  PubMed  Google Scholar 

  101. Trivedi DP, Doll R, Khaw K-T. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomized double blind controlled trial. BMJ. 2003;326:469.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch. Intern. Med. 2007;167:1730–7.

    Article  CAS  PubMed  Google Scholar 

  103. Keum N, Lee DH, Greenwood DC, Manson JE, Giovannucci E. Vitamin D supplementation and total cancer incidence and mortality: a meta-analysis of randomized controlled trials. Ann. Oncol. 2019;30:733–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Manson J. Vitamin D and omega-3 supplements for preventing cancer and other chronic diseases. Oncology . 2019;33:36–8.

    PubMed  Google Scholar 

  105. Lappe J, Watson P, Travers-Gustafson D, Recker R, Garland C, Gorham E, et al. Effect of vitamin D and calcium supplementation on cancer incidence in older women: a randomized clinical trial. JAMA. 2017;317:1234–43.

    Article  CAS  PubMed  Google Scholar 

  106. Shapses SA, Lee EJ, Sukumar D, Durazo-Arvizu R, Schneider SH. The effect of obesity on the relationship between serum parathyroid hormone and 25-hydroxyvitamin D in women. J Clin Endocrinol Metab. 2013;98:E886–90.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Saarnio E, Pekkinen M, Itkonen ST, Kemi V, Karp H, Ivaska KK, et al. Low free 25-hydroxyvitamin D and high vitamin D binding protein and parathyroid hormone in obese Caucasians. A complex association with bone? PLoS ONE. 2018;13:e0192596.

    Article  PubMed  PubMed Central  Google Scholar 

  108. Renehan AG, Zwahlen M, Egger M. Adiposity and cancer risk: new mechanistic insights from epidemiology. Nat Rev Cancer. 2015;15:484–98.

    Article  CAS  PubMed  Google Scholar 

  109. Autier P, Mullie P, Macacu A, Dragomir M, Boniol M, Coppens K, et al. Effect of vitamin D supplementation on non-skeletal disorders: a systematic review of meta-analyses and randomised trials. Lancet Diabetes Endocrinol. 2017;5:986–1004.

    Article  CAS  PubMed  Google Scholar 

  110. Rejnmark L, Bislev LS, Cashman KD, Eiríksdottir G, Gaksch M, Grübler M, et al. Non-skeletal health effects of vitamin D supplementation: a systematic review on findings from meta-analyses summarizing trial data. PLoS ONE. 2017;12:e0180512.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Manousaki D, Richards JB. Low vitamin D levels as a risk factor for cancer. BMJ. 2017;359:j4952.

Download references

Author information

Author notes

  1. These authors contributed equally: Silvia Migliaccio, Andrea Di Nisio.

Authors and Affiliations

  1. Department of Movement, Human and Health Sciences, University Foro Italico, Roma, Italy

    Silvia Migliaccio

  2. Department of Medicine, Operative Unit of Andrology and Medicine of Human Reproduction, University of Padova, Padova, Italy

    Andrea Di Nisio

  3. Obesity and Lipodystrophy Centre at the Endocrinology Unit, University Hospital of Pisa, Pisa, Italy

    Silvia Magno

  4. Department of Clinical Medicine and Surgery, Endocrinology Unit, University Federico II, Napoli, Italy

    Fiammetta Romano

  5. Cattedra Unesco “Educazione alla salute e allo sviluppo sostenibile”, University “Federico II”, Napoli, Italy

    Luigi Barrea, Anna Maria Colao, Giovanna Muscogiuri & Silvia Savastano

Authors
  1. Silvia Migliaccio
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andrea Di Nisio
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Silvia Magno
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fiammetta Romano
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Luigi Barrea
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anna Maria Colao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Giovanna Muscogiuri
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Silvia Savastano
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors were involved in the design of this study and made substantial contributions to this paper. S.M., A.D.N., S.M., F.R., and L.B. conducted paper selection and analysis. All authors critically revised and approved the final version of the paper.

Corresponding author

Correspondence to Silvia Migliaccio.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Migliaccio, S., Di Nisio, A., Magno, S. et al. Vitamin D deficiency: a potential risk factor for cancer in obesity?. Int J Obes 46, 707–717 (2022). https://doi.org/10.1038/s41366-021-01045-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41366-021-01045-4

Search

Advanced search

Quick links