Pancreatic Cancer survival 2.3 X more likely if good level of Vitamin D – meta-analysis Sept 2023

There are 2 meta-analyses on this page

25-hydroxyvitamin D concentration is positively associated with overall survival in advanced pancreatic cancer: A systematic review and meta-analysis - 2023

Nutrition Research Vol 117, Sept 2023, Pages 73-82 https://doi.org/10.1016/j.nutres.2023.07.001 PDF is behind a paywall
Jing Li a #, Haiyan Zhang a #, Hongda Zhu b, Zhu Dai a

Studies have shown that 25-hydroxyvitamin D (25(OH)D) is predictive of survival following a diagnosis of cancer. However, evidence of the relationship between 25(OH)D and the survival of patients with pancreatic cancer has been inconsistent. We hypothesized that circulating 25(OH)D concentrations may be positively correlated with better prognosis in advanced pancreatic cancer. PubMed, EMBASE, Cochrane Library, and Web of Science database entries through April 2023, along with the reference lists of related studies, were searched. Additionally, we extracted observational studies reporting the association between 25(OH)D concentrations and the outcome of interest (overall survival [OS]) in advanced pancreatic cancer patients aged 18 years or older. Ultimately, 7 articles involving 2369 patients were included in this systematic review and meta-analysis. The results indicated that 25(OH)D concentrations were positively correlated with OS (hazard ratio = 2.37; 95% confidence interval, 2.22–2.54; P < .001). No association was found between 25(OH)D and progression-free survival. There was significant heterogeneity between studies in terms of OS (I2 = 85.5%, P < .001). Our subgroup analysis revealed that this high heterogeneity may be attributed to the studies’ different regions, designs, sample sources, and detection methods of 25(OH)D. Additionally, Begg's and Egger's tests indicated the presence of publication bias. To our knowledge, this is the first meta-analysis to evaluate the association between 25(OH)D concentrations and OS among patients with pancreatic cancer. Our results suggested that circulating 25(OH)D concentrations were positively correlated with OS, indicating that 25(OH)D may be a potential prognostic marker in advanced pancreatic cancer.

Graphical abstract
This systematic review and meta-analysis was performed to evaluate the association between circulating 25-hydroxyvitamin D (25(OH)D) concentration and survival outcomes among patients with advanced pancreatic cancer. The results showed that 25(OH)D concentrations were positively correlated with overall survival among patients with pancreatic cancer, indicating that 25(OH)D concentration may be a potential prognostic marker in advanced pancreatic cancer.

Introduction
Pancreatic cancer is considered a fatal disease and is 1 of the most aggressive and deadly types of malignant tumors [1]. It has been reported that the 5-year survival rate of patients with pancreatic cancer varies in different regions and countries in the world; however, these rates have consistently remained below 10% [2]. This is partly because pancreatic cancer tends to metastasize to lymph nodes or distant sites at an early stage because of its high capacity for invasion and migration [3]. To date, except for the onset stage, there are few known patient characteristics or circulating markers that can predict the survival time of patients with pancreatic cancer.

The classical role of vitamin D (VD) is to maintain calcium homeostasis and help regulate bone metabolism [4]. Initially, it was considered to have autocrine and paracrine effects until the discovery that multiple cells throughout the body can express both vitamin D receptors (VDRs) and the hydroxylase necessary to produce calcitriol [5]. VD is predominantly synthesized from 7-dehydrocholesterol in the skin on exposure to sunlight, whereas the remaining VD is obtained from dietary sources. VD itself has low activity at physiological concentrations and requires 2 successive hydroxylation reactions. It is first metabolized by 25-hydroxylase (CYP2R1 and CYP27A1) to 25-hydroxyvitamin D (25(OH)D) in the liver. Notably, 25(OH)D is the primary circulating form of VD and a clinical marker. Subsequently, 25(OH)D is further metabolized by 1α-hydroxylase, mainly in the proximal tubule of the kidney, to 1α,25-dihydroxyvitamin D [6], the most biologically active form of VD. It can bind to VDRs that influence target genes involved in intracellular signaling pathways, including cell growth, differentiation, adhesion, and apoptosis [7]. This altered cellular mechanism plays a key role in cancer development and suggests a potential relationship between VD and cancer.

Multiple experimental studies have indicated that VD participates in pancreatic carcinogenesis and demonstrated the therapeutic potential of VD analogs via the engagement of VDRs in tumor and supportive cells within the tumor stroma [8,9]. Notably, an inverse association between serum 25(OH)D concentration and risk for cancer has been commonly reported in epidemiological studies [10]. Additionally, there is widespread interest in evaluating the association between circulating 25(OH)D and patient prognosis. Some clinical studies have revealed longer overall survival (OS) in patients with pancreatic cancer and sufficient 25(OH)D concentrations [11]. However, the results of this type of study were inconsistent with those of other studies, showing no significant relationship between circulating 25(OH)D concentrations and survival outcomes [12].

Therefore, to assess the effect of 25(OH)D on survival outcomes in advanced pancreatic cancer patients, we performed a systematic review and meta-analysis to evaluate the association between circulating 25(OH)D concentrations and OS. We hypothesized that 25(OH)D concentrations may be positively correlated with OS in advanced pancreatic cancer.

Section snippets

Literature search
We searched PubMed, EMBASE, Web of Science, and Cochrane library databases (on April 2023) for cohort studies assessing the association between circulating 25(OH)D concentrations and OS in patients with advanced pancreatic cancers. Medical Subject Headings including “Pancreatic Neoplasms” and “Vitamin D” were used to choose qualified studies, and these were further combined with keyword searches in titles and abstracts. Additionally, the references cited in all selected studies and published…

Study selection
A flowchart of the study retrieval process is shown in Fig. 1. A total of 2166 potential studies were identified from the initial search of the previously mentioned databases, of which 538 were duplicates. After removing duplicate records and screening the titles and abstracts, 846 records remained. The full-text documents of these records were assessed, resulting in the exclusion of 839 records. The exclusion criteria were as follows: (1) review articles (n = 445); (2) animal experiments (n…

Discussion
This meta-analysis is the first to evaluate the association between 25(OH)D concentrations and OS among patients with pancreatic cancer and to assess the potential prognostic value of 25(OH)D. Our results supported the notion that a positive correlation existed between 25(OH)D and OS in patients with pancreatic cancer, which was consistent with our hypothesis.

Pancreatic cancer is a prevalent disease characterized by a low survival rate, primarily because it is often detected at advanced stages, …

Conclusion
In conclusion, our study indicated that 25(OH)D concentrations were positively correlated with OS, which may provide useful prognostic information for advanced pancreatic cancer patients. However, more studies are needed to validate this finding, and the mechanism behind the observation should be evaluated in further studies…

Some titles of references

• Vitamin D and pancreatic cancer
• Vitamins in pancreatic cancer: a review of underlying mechanisms and future applications
• Vitamin D for cancer prevention: global perspective
• Vitamin D receptor is expressed in pancreatic cancer cells and a vitamin D3 analogue decreases cell number
• The vitamin D system is deregulated in pancreatic diseases
• Vitamin D and melanoma and non-melanoma skin cancer risk and prognosis: a comprehensive review and meta-analysis
• Relationships among body mass index, longitudinal body composition alterations, and survival in patients with locally advanced pancreatic cancer receiving chemoradiation: a pilot study
• The vitamin D dose response in obesity
• High prevalence of vitamin D deficiency in urban health checkup population
• Vitamin D, parathyroid hormone, and cardiovascular events among older adults
• Sex steroids induced up-regulation of 1,25-(OH)2 vitamin D3 receptors in t 47d breast cancer cells
• Evidence of sexual dimorphism in placental vitamin D metabolism: testosterone inhibits calcitriol-dependent cathelicidin expression
• Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease
• Current epidemiology of pancreatic cancer: challenges and opportunities
• Pancreatic cancer: a review of epidemiology, trend, and risk factors
• Pancreatic cancer: a review of current treatment and novel therapies
• Vitamin D binding protein and bone health
• Sex differences in vitamin D metabolism, serum levels and action
• Calcipotriol targets lrp6 to inhibit wnt signaling in pancreatic cancer
• Activation of vitamin D receptor signaling downregulates the expression of nuclear foxm1 protein and suppresses pancreatic cancer cell stemness
• Vitamin D for the prevention and treatment of pancreatic cancer
• Prediagnostic plasma 25-hydroxyvitamin D and pancreatic cancer survival

40% less likely to die of Pancreatic Cancer if high vitamin D - meta-analyis Jan 2024

The association between circulating 25-hydroxyvitamin D and pancreatic cancer: a systematic review and meta-analysis of observational studies
Eur J Nutr. 2024 Jan 3. doi: 10.1007/s00394-023-03302-w PDF behind paywall
Yajing Shen 1 2, Junfen Xia 3, Chuncheng Yi 1 2, Tiandong Li 1 2, Peng Wang 1 2, Liping Dai 2 4, Jianxiang Shi 2 4, Keyan Wang 2 4, Changqing Sun 1 5, Hua Ye 6 7

Purpose: The relationship between circulating 25-hydroxyvitamin D 25(OH)D and pancreatic cancer has been well studied but remains unclear. The purpose of this study was to elucidate the association between circulating 25(OH)D and pancreatic cancer by using a meta-analytic approach.

Methods: PubMed, Embase, and Wed of Science databases were searched through October 15, 2022. A random or fixed-effects model was used to estimate the pooled odds ratio (OR), risk ratio (RR), hazard ratio (HR) and their 95% confidence intervals (CIs).

Results: A total of 16 studies including 529,917 participants met the inclusion criteria, of which 10 reported incidence and 6 reported mortality. For the highest versus lowest categories of circulating 25(OH)D, the pooled OR of pancreatic cancer incidence in case-control studies was 0.98 (95% CI 0.69-1.27), and the pooled HRs of pancreatic cancer mortality in cohort and case-control studies were 0.64 (95% CI 0.45-0.82) and 0.78 (95% CI 0.62-0.95), respectively. The leave-one-out sensitivity analyses found no outliers and Galbraith plots indicated no substantial heterogeneity.

Conclusion: Evidence from this meta-analysis suggested that high circulating 25(OH)D levels may be associated with decreased mortality but not incidence of pancreatic cancer. Our findings may provide some clues for the treatment of pancreatic cancer and remind us to be cautious about widespread vitamin D supplementation for the prevention of pancreatic cancer.

95 References

1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 Countries. CA Cancer J Clin 71:209–249. https://doi.org/10.3322/caac.21660 - DOI - PubMed
2. Siegel RL, Miller KD, Wagle NS, Jemal A (2023) Cancer statistics, 2023. CA Cancer J Clin 73:17–48. https://doi.org/10.3322/caac.21763 - DOI - PubMed
3. You L, Lv Z, Li C, Ye W, Zhou Y, Jin J, Han Q (2021) Worldwide cancer statistics of adolescents and young adults in 2019: a systematic analysis of the Global Burden of Disease Study 2019. ESMO Open 6:100255. https://doi.org/10.1016/j.esmoop.2021.100255 - DOI - PubMed - PMC
4. Gillen S, Schuster T, Meyer Zum Büschenfelde C, Friess H, Kleeff J (2010) Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med 7:e1000267. https://doi.org/10.1371/journal.pmed.1000267 - DOI - PubMed - PMC
5. Ferlay J, Colombet M, Soerjomataram I, Dyba T, Randi G, Bettio M, Gavin A et al (2018) Cancer incidence and mortality patterns in Europe: estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer 103:356–387. https://doi.org/10.1016/j.ejca.2018.07.005 - DOI - PubMed
6. Tempero MA (2019) NCCN guidelines updates: pancreatic cancer. J Natl Compr Canc Netw 17:603–605. https://doi.org/10.6004/jnccn.2019.5007 - DOI - PubMed
7. Clinton SK, Giovannucci EL, Hursting SD (2020) The World Cancer Research Fund/American Institute for cancer research third expert report on diet, nutrition, physical activity, and cancer: impact and future directions. J Nutr 150:663–671. https://doi.org/10.1093/jn/nxz268 - DOI - PubMed
8. Qin X, Chen J, Jia G, Yang Z (2023) Dietary factors and pancreatic cancer risk: an umbrella review of meta-analyses of prospective observational studies. Adv Nutr 14:451–464. https://doi.org/10.1016/j.advnut.2023.02.004 - DOI - PubMed - PMC
9. Zheng W, McLaughlin JK, Gridley G, Bjelke E, Schuman LM, Silverman DT, Wacholder S et al (1993) A cohort study of smoking, alcohol consumption, and dietary factors for pancreatic cancer (United States). Cancer Causes Control 4:477–482. https://doi.org/10.1007/bf00050867 - DOI - PubMed
10. Peila R, Coday M, Crane TE, Saquib N, Shadyab AH, Tabung FK, Zhang X et al (2022) Healthy lifestyle index and risk of pancreatic cancer in the women’s health initiative. Cancer Causes Control 33:737–747. https://doi.org/10.1007/s10552-022-01558-x - DOI - PubMed - PMC
11. Michaud DS, Giovannucci E, Willett WC, Colditz GA, Fuchs CS (2003) Dietary meat, dairy products, fat, and cholesterol and pancreatic cancer risk in a prospective study. Am J Epidemiol 157:1115–1125. https://doi.org/10.1093/aje/kwg098 - DOI - PubMed
12. Chatterjee R, Fuss P, Vickery EM, LeBlanc ES, Sheehan PR, Lewis MR, Dolor RJ et al (2021) vitamin D supplementation for prevention of cancer: the D2d cancer outcomes (D2dCA) ancillary study. J Clin Endocrinol Metab 106:2767–2778. https://doi.org/10.1210/clinem/dgab153 - DOI - PubMed - PMC
13. Haykal T, Samji V, Zayed Y, Gakhal I, Dhillon H, Kheiri B, Kerbage J et al (2019) The role of vitamin D supplementation for primary prevention of cancer: meta-analysis of randomized controlled trials. J Community Hosp Internal Med Persp 9:480–488. https://doi.org/10.1080/20009666.2019.1701839 - DOI
14. Reid IR, Bolland MJ, Grey A (2014) Effects of vitamin D supplements on bone mineral density: a systematic review and meta-analysis. Lancet 383:146–155. https://doi.org/10.1016/s0140-6736(13)61647-5 - DOI - PubMed
15. Vanhevel J, Verlinden L, Doms S, Wildiers H, Verstuyf A (2022) The role of vitamin D in breast cancer risk and progression. Endocr Relat Cancer 29:R33-r55. https://doi.org/10.1530/erc-21-0182 - DOI - PubMed
16. Kim H, Lipsyc-Sharf M, Zong X, Wang X, Hur J, Song M, Wang M et al (2021) Total vitamin D intake and risks of early-onset colorectal cancer and precursors. Gastroenterology 161:1208-1217.e9. https://doi.org/10.1053/j.gastro.2021.07.002 - DOI - PubMed
17. Kanaan Y, Copeland RL (2022) The link between vitamin D and prostate cancer. Nat Rev Cancer 22:435. https://doi.org/10.1038/s41568-022-00493-y - DOI - PubMed
18. Jones G (2013) Extrarenal vitamin D activation and interactions between vitamin D2, vitamin D3, and vitamin D analogs. Annu Rev Nutr 33:23–44. https://doi.org/10.1146/annurev-nutr-071812-161203 - DOI - PubMed
19. Wilson LR, Tripkovic L, Hart KH, Lanham-New SA (2017) vitamin D deficiency as a public health issue: using vitamin D2 or vitamin D3 in future fortification strategies. Proc Nutr Soc 76:392–399. https://doi.org/10.1017/s0029665117000349 - DOI - PubMed
20. Holick MF (2004) vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr 79:362–371. https://doi.org/10.1093/ajcn/79.3.362 - DOI - PubMed
21. Green J (1951) Studies on the analysis of vitamins D. 4. Studies on the irradiation of ergosterol and 7-dehydrocholesterol and the analysis of the products for calciferol, vitamin D3, and component sterols. Biochem J 49:232–243. https://doi.org/10.1042/bj0490232 - DOI - PubMed - PMC
22. Bikle DD (2014) vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol 21:319–329. https://doi.org/10.1016/j.chembiol.2013.12.016 - DOI - PubMed - PMC
23. Afzal S, Brøndum-Jacobsen P, Bojesen SE, Nordestgaard BG (2014) vitamin D concentration, obesity, and risk of diabetes: a mendelian randomisation study. Lancet Diabetes Endocrinol 2:298–306. https://doi.org/10.1016/s2213-8587(13)70200-6 - DOI - PubMed
24. Vimaleswaran KS, Berry DJ, Lu C, Tikkanen E, Pilz S, Hiraki LT, Cooper JD et al (2013) Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts. PLoS Med 10:e1001383. https://doi.org/10.1371/journal.pmed.1001383 - DOI - PubMed - PMC
25. Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF (2000) Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 72:690–693. https://doi.org/10.1093/ajcn/72.3.690 - DOI - PubMed
26. Savastano S, Barrea L, Savanelli MC, Nappi F, Di Somma C, Orio F, Colao A (2017) Low vitamin D status and obesity: role of nutritionist. Rev Endocr Metab Disord 18:215–225. https://doi.org/10.1007/s11154-017-9410-7 - DOI - PubMed
27. Fernandes MR, Barreto WDRJ (2017) Association between physical activity and vitamin D: a narrative literature review. Rev Assoc Med Bras (1993) 63:550–556. https://doi.org/10.1590/1806-9282.63.06.550 - DOI
28. Bicakli DH, Uslu R, Güney SC, Coker A (2020) The relationship between nutritional status, performance status, and survival among pancreatic cancer patients. Nutr Cancer 72:202–208. https://doi.org/10.1080/01635581.2019.1634217 - DOI - PubMed
29. Kubiak J, Kamycheva E, Jorde R (2021) Tracking of serum 25-hydroxyvitamin D during 21 years. Eur J Clin Nutr 75:1069–1076. https://doi.org/10.1038/s41430-020-00814-0 - DOI - PubMed
30. Borel P, Caillaud D, Cano NJ (2015) vitamin D bioavailability: state of the art. Crit Rev Food Sci Nutr 55:1193–1205. https://doi.org/10.1080/10408398.2012.688897 - DOI - PubMed
31. Stolzenberg-Solomon RZ (2009) vitamin D and pancreatic cancer. Ann Epidemiol 19:89–95. https://doi.org/10.1016/j.annepidem.2008.03.010 - DOI - PubMed
32. Sanchez GV, Weinstein SJ, Stolzenberg-Solomon RZ (2012) Is dietary fat, vitamin D, or folate associated with pancreatic cancer? Mol Carcinog 51:119–127. https://doi.org/10.1002/mc.20833 - DOI - PubMed - PMC
33. Mohr SB, Garland CF, Gorham ED, Grant WB, Garland FC (2010) Ultraviolet B irradiance and vitamin D status are inversely associated with incidence rates of pancreatic cancer worldwide. Pancreas 39:669–674. https://doi.org/10.1097/MPA.0b013e3181ce654d - DOI - PubMed
34. Bao Y, Ng K, Wolpin BM, Michaud DS, Giovannucci E, Fuchs CS (2010) Predicted vitamin D status and pancreatic cancer risk in two prospective cohort studies. Br J Cancer 102:1422–1427. https://doi.org/10.1038/sj.bjc.6605658 - DOI - PubMed - PMC
35. Giovannucci E, Liu Y, Rimm EB, Hollis BW, Fuchs CS, Stampfer MJ, Willett WC (2006) Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J Natl Cancer Inst 98:451–459. https://doi.org/10.1093/jnci/djj101 - DOI - PubMed
36. Yuan C, Qian ZR, Babic A, Morales-Oyarvide V, Rubinson DA, Kraft P, Ng K et al (2016) Prediagnostic plasma 25-hydroxyvitamin D and pancreatic cancer survival. J Clin Oncol 34:2899–2905. https://doi.org/10.1200/jco.2015.66.3005 - DOI - PubMed - PMC
37. Schwartz GG, Eads D, Rao A, Cramer SD, Willingham MC, Chen TC, Jamieson DP et al (2004) pancreatic cancer cells express 25-hydroxyvitamin D-1 alpha-hydroxylase and their proliferation is inhibited by the prohormone 25-hydroxyvitamin D3. Carcinogenesis 25:1015–1026. https://doi.org/10.1093/carcin/bgh086 - DOI - PubMed
38. Pettersson F, Colston KW, Dalgleish AG (2000) Differential and antagonistic effects of 9-cis-retinoic acid and vitamin D analogues on pancreatic cancer cells in vitro. Br J Cancer 83:239–245. https://doi.org/10.1054/bjoc.2000.1281 - DOI - PubMed - PMC
39. Kawa S, Yoshizawa K, Tokoo M, Imai H, Oguchi H, Kiyosawa K, Homma T et al (1996) Inhibitory effect of 220-oxa-1,25-dihydroxyvitamin D3 on the proliferation of pancreatic cancer cell lines. Gastroenterology 110:1605–1613. https://doi.org/10.1053/gast.1996.v110.pm8613068 - DOI - PubMed
40. Colston KW, James SY, Ofori-Kuragu EA, Binderup L, Grant AG (1997) vitamin D receptors and anti-proliferative effects of vitamin D derivatives in human pancreatic carcinoma cells in vivo and in vitro. Br J Cancer 76:1017–1020. https://doi.org/10.1038/bjc.1997.501 - DOI - PubMed - PMC
41. van Duijnhoven FJB, Jenab M, Hveem K, Siersema PD, Fedirko V, Duell EJ, Kampman E et al (2018) Circulating concentrations of vitamin D in relation to pancreatic cancer risk in European populations. Int J Cancer 142:1189–1201. https://doi.org/10.1002/ijc.31146 - DOI - PubMed
42. Stolzenberg-Solomon RZ, Jacobs EJ, Arslan AA, Qi D, Patel AV, Helzlsouer KJ, Weinstein SJ et al (2010) Circulating 25-hydroxyvitamin D and risk of pancreatic cancer: cohort consortium vitamin D pooling project of rarer cancers. Am J Epidemiol 172:81–93. https://doi.org/10.1093/aje/kwq120 - DOI - PubMed - PMC
43. Weinstein SJ, Stolzenberg-Solomon RZ, Kopp W, Rager H, Virtamo J, Albanes D (2012) Impact of circulating vitamin D binding protein levels on the association between 25-hydroxyvitamin D and pancreatic cancer risk: a nested case-control study. Cancer Res 72:1190–1198. https://doi.org/10.1158/0008-5472.Can-11-2950 - DOI - PubMed - PMC
44. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D et al (2000) Meta-analysis of observational studies in epidemiology—ā proposal for reporting. Jama-J Am Med Assoc 283:2008–2012. https://doi.org/10.1001/jama.283.15.2008 - DOI
45. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L et al (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372:n71. https://doi.org/10.1136/bmj.n71 - DOI - PubMed - PMC
46. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP (2007) Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. BMJ 335:806–808. https://doi.org/10.1136/bmj.39335.541782.AD - DOI
47. Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25:603–605. https://doi.org/10.1007/s10654-010-9491-z - DOI - PubMed
48. Institute of Medicine Committee to Review Dietary Reference Intakes for vitamin D, Calcium (2011) The National Academies Collection: Reports funded by National Institutes of Health. National Academies Press (US) Copyright © 2011, National Academy of Sciences., Washington (DC)
49. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH et al (2011) Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96:1911–1930. https://doi.org/10.1210/jc.2011-0385 - DOI - PubMed
50. Chevalley T, Brandi ML, Cashman KD, Cavalier E, Harvey NC, Maggi S, Cooper C et al (2022) Role of vitamin D supplementation in the management of musculoskeletal diseases: update from an European Society of Clinical and Economical Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) working group. Aging Clin Exp Res 34:2603–2623. https://doi.org/10.1007/s40520-022-02279-6 - DOI - PubMed - PMC
51. Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B (2006) Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr 84:18–28. https://doi.org/10.1093/ajcn/84.1.18 - DOI - PubMed
52. DerSimonian R, Laird N (2015) Meta-analysis in clinical trials revisited. Contemp Clin Trials 45:139–145. https://doi.org/10.1016/j.cct.2015.09.002 - DOI - PubMed - PMC
53. DerSimonian R (1996) Meta-analysis in the design and monitoring of clinical trials. Stat Med 15:1237–48. https://doi.org/10.1002/(SICI)1097-0258(19960630)15:12<1237::AID-SIM301>3.0.CO;2-N - DOI - PubMed
54. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188. https://doi.org/10.1016/0197-2456(86)90046-2 - DOI - PubMed
55. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560. https://doi.org/10.1136/bmj.327.7414.557 - DOI - PubMed - PMC
56. Jeon SM, Shin EA (2018) Exploring vitamin D metabolism and function in cancer. Exp Mol Med 50:1–14. https://doi.org/10.1038/s12276-018-0038-9 - DOI - PubMed
57. Marigoudar JB, Sarkar D, Yuguda YM, Abutayeh RF, Kaur A, Pati A, Mitra D et al (2022) Role of vitamin D in targeting cancer and cancer stem cell populations and its therapeutic implications. Med Oncol 40:2. https://doi.org/10.1007/s12032-022-01855-0 - DOI - PubMed
58. Chiang KC, Chen TC (2009) vitamin D for the prevention and treatment of pancreatic cancer. World J Gastroenterol 15:3349–3354. https://doi.org/10.3748/wjg.15.3349 - DOI - PubMed - PMC
59. Mondul AM, Weinstein SJ, Layne TM, Albanes D (2017) vitamin D and cancer risk and mortality: state of the science, gaps, and challenges. Epidemiol Rev 39:28–48. https://doi.org/10.1093/epirev/mxx005 - DOI - PubMed - PMC
60. Wolpin BM, Bao Y, Qian ZR, Wu C, Kraft P, Ogino S, Stampfer MJ et al (2013) Hyperglycemia, insulin resistance, impaired pancreatic β-cell function, and risk of pancreatic cancer. J Natl Cancer Inst 105:1027–1035. https://doi.org/10.1093/jnci/djt123 - DOI - PubMed - PMC
61. Muscogiuri G, Sorice GP, Prioletta A, Policola C, Della Casa S, Pontecorvi A, Giaccari A (2010) 25-Hydroxyvitamin D concentration correlates with insulin-sensitivity and BMI in obesity. Obesity (Silver Spring) 18:1906–1910. https://doi.org/10.1038/oby.2010.11 - DOI - PubMed
62. Vaidya A, Williams JS, Forman JP (2012) The independent association between 25-hydroxyvitamin D and adiponectin and its relation with BMI in two large cohorts: the NHS and the HPFS. Obesity (Silver Spring) 20:186–191. https://doi.org/10.1038/oby.2011.210 - DOI - PubMed
63. Earthman CP, Beckman LM, Masodkar K, Sibley SD (2012) The link between obesity and low circulating 25-hydroxyvitamin D concentrations: considerations and implications. Int J Obes (Lond) 36:387–396. https://doi.org/10.1038/ijo.2011.119 - DOI - PubMed
64. McPhail S, Johnson S, Greenberg D, Peake M, Rous B (2015) Stage at diagnosis and early mortality from cancer in England. Br J Cancer 112(Suppl 1):S108–S115. https://doi.org/10.1038/bjc.2015.49 - DOI - PubMed - PMC
65. Zwaigenbaum L, Stone W (2008) Early detection. Autism 12:427–432. https://doi.org/10.1177/1362361308097836 - DOI - PubMed
66. Fernández-Lázaro D, Seco-Calvo J (2023) Nutrition, nutritional status and functionality. Nutrients. https://doi.org/10.3390/nu15081944 - DOI - PubMed - PMC
67. Zhang X, Chen Y, Jin S, Bi X, Chen D, Zhang D, Liu L et al (2020) Association of serum 25-Hydroxyvitamin D with vitamin D intervention and outdoor activity among children in North China: an observational study. BMC Pediatr 20:542. https://doi.org/10.1186/s12887-020-02435-9 - DOI - PubMed - PMC
68. Holick MF (2017) The vitamin D deficiency pandemic: approaches for diagnosis, treatment and prevention. Rev Endocr Metab Disord 18:153–165. https://doi.org/10.1007/s11154-017-9424-1 - DOI - PubMed
69. Weinstein SJ, Mondul AM, Yu K, Layne TM, Abnet CC, Freedman ND, Stolzenberg-Solomon RZ et al (2018) Circulating 25-hydroxyvitamin D up to 3 decades prior to diagnosis in relation to overall and organ-specific cancer survival. Eur J Epidemiol 33:1087–1099. https://doi.org/10.1007/s10654-018-0428-2 - DOI - PubMed - PMC
70. Rasmussen LS, Yilmaz MK, Falkmer UG, Poulsen L, Bøgsted M, Christensen HS, Bojesen SE et al (2021) Pre-treatment serum vitamin D deficiency is associated with increased inflammatory biomarkers and short overall survival in patients with pancreatic cancer. Eur J Cancer 144:72–80. https://doi.org/10.1016/j.ejca.2020.10.038 - DOI - PubMed
71. Haas M, Kern C, Kruger S, Michl M, Modest DP, Giessen C, Schulz C et al (2015) Assessing novel prognostic serum biomarkers in advanced pancreatic cancer: the role of CYFRA 21–1, serum amyloid A, haptoglobin, and 25-OH vitamin D3. Tumour Biol 36:2631–2640. https://doi.org/10.1007/s13277-014-2885-x - DOI - PubMed
72. McGovern EM, Lewis ME, Niesley ML, Huynh N, Hoag JB (2016) Retrospective analysis of the influence of 25-hydroxyvitamin D on disease progression and survival in pancreatic cancer. Nutr J 15:17. https://doi.org/10.1186/s12937-016-0135-3 - DOI - PubMed - PMC
73. LeFevre ML (2015) Screening for vitamin D deficiency in adults: U.S. preventive services task force recommendation statement. Ann Intern Med 162:133–140. https://doi.org/10.7326/m14-2450 - DOI - PubMed
74. Kantor ED, Rehm CD, Du M, White E, Giovannucci EL (2016) Trends in dietary supplement use among US adults from 1999–2012. JAMA 316:1464–1474. https://doi.org/10.1001/jama.2016.14403 - DOI - PubMed - PMC
75. Adams JS, Hewison M (2012) Extrarenal expression of the 25-hydroxyvitamin D-1-hydroxylase. Arch Biochem Biophys 523:95–102. https://doi.org/10.1016/j.abb.2012.02.016 - DOI - PubMed - PMC
76. Zugmaier G, Jager R, Grage B, Gottardis MM, Havemann K, Knabbe C (1996) Growth-inhibitory effects of vitamin D analogues and retinoids on human pancreatic cancer cells. Br J Cancer 73:1341–1346. https://doi.org/10.1038/bjc.1996.256 - DOI - PubMed - PMC
77. Schwartz GG, Eads D, Naczki C, Northrup S, Chen T, Koumenis C (2008) 19-nor-1 alpha,25-dihydroxyvitamin D2 (paricalcitol) inhibits the proliferation of human pancreatic cancer cells in vitro and in vivo. Cancer Biol Ther 7:430–436. https://doi.org/10.4161/cbt.7.3.5418 - DOI - PubMed
78. Albrechtsson E, Jonsson T, Möller S, Höglund M, Ohlsson B, Axelson J (2003) vitamin D receptor is expressed in pancreatic cancer cells and a vitamin D3 analogue decreases cell number. Pancreatology 3:41–46. https://doi.org/10.1159/000069149 - DOI - PubMed
79. Armas LA, Hollis BW, Heaney RP (2004) vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab 89:5387–5391. https://doi.org/10.1210/jc.2004-0360 - DOI - PubMed
80. Skinner HG (2008) vitamin D for the treatment and prevention of pancreatic cancer. Cancer Biol Ther 7:437–439. https://doi.org/10.4161/cbt.7.3.5585 - DOI - PubMed
81. Sherman MH, Yu RT, Engle DD, Ding N, Atkins AR, Tiriac H, Collisson EA et al (2014) vitamin D receptor-mediated stromal reprogramming suppresses pancreatitis and enhances pancreatic cancer therapy. Cell 159:80–93. https://doi.org/10.1016/j.cell.2014.08.007 - DOI - PubMed - PMC
82. Hennig R, Ding XZ, Adrian TE (2004) On the role of the islets of Langerhans in pancreatic cancer. Histol Histopathol 19:999–1011. https://doi.org/10.14670/hh-19.999
83. Bear AS, Vonderheide RH, O’Hara MH (2020) Challenges and opportunities for pancreatic cancer immunotherapy. Cancer Cell 38:788–802. https://doi.org/10.1016/j.ccell.2020.08.004 - DOI - PubMed - PMC
84. Maestro B, Molero S, Bajo S, Dávila N, Calle C (2002) Transcriptional activation of the human insulin receptor gene by 1,25-dihydroxyvitamin D(3). Cell Biochem Funct 20:227–232. https://doi.org/10.1002/cbf.951 - DOI - PubMed
85. Provvedini DM, Tsoukas CD, Deftos LJ, Manolagas SC (1983) 1,25-dihydroxyvitamin D3 receptors in human leukocytes. Science 221:1181–1183. https://doi.org/10.1126/science.6310748 - DOI - PubMed
86. Lemire JM, Adams JS, Sakai R, Jordan SC (1984) 1 alpha,25-dihydroxyvitamin D3 suppresses proliferation and immunoglobulin production by normal human peripheral blood mononuclear cells. J Clin Invest 74:657–661. https://doi.org/10.1172/jci111465 - DOI - PubMed - PMC
87. Chen S, Sims GP, Chen XX, Gu YY, Chen S, Lipsky PE (2007) Modulatory effects of 1,25-dihydroxyvitamin D3 on human B cell differentiation. J Immunol 179:1634–1647. https://doi.org/10.4049/jimmunol.179.3.1634 - DOI - PubMed
88. Mahon BD, Wittke A, Weaver V, Cantorna MT (2003) The targets of vitamin D depend on the differentiation and activation status of CD4 positive T cells. J Cell Biochem 89:922–932. https://doi.org/10.1002/jcb.10580 - DOI - PubMed
89. Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C (2010) vitamin D: modulator of the immune system. Curr Opin Pharmacol 10:482–496. https://doi.org/10.1016/j.coph.2010.04.001 - DOI - PubMed
90. Mora JR, Iwata M, von Andrian UH (2008) vitamin effects on the immune system: vitamins A and D take centre stage. Nat Rev Immunol 8:685–698. https://doi.org/10.1038/nri2378 - DOI - PubMed - PMC
91. Lemire JM, Adams JS, Kermani-Arab V, Bakke AC, Sakai R, Jordan SC (1985) 1,25-Dihydroxyvitamin D3 suppresses human T helper/inducer lymphocyte activity in vitro. J Immunol 134:3032–3035 - DOI - PubMed
92. Schlingmann KP (2021) vitamin D-dependent Hypercalcemia. Endocrinol Metab Clin North Am 50:729–742. https://doi.org/10.1016/j.ecl.2021.08.005 - DOI - PubMed
93. Tebben PJ, Singh RJ, Kumar R (2016) vitamin D-mediated hypercalcemia: mechanisms, diagnosis, and treatment. Endocr Rev 37:521–547. https://doi.org/10.1210/er.2016-1070 - DOI - PubMed - PMC
94. Ureña P, Jacobson SH, Zitt E, Vervloet M, Malberti F, Ashman N, Leavey S et al (2009) Cinacalcet and achievement of the NKF/K-DOQI recommended target values for bone and mineral metabolism in real-world clinical practice–the ECHO observational study. Nephrol Dial Transpl 24:2852–2859. https://doi.org/10.1093/ndt/gfp144 - DOI
95. Melamed ML, Eustace JA, Plantinga L, Jaar BG, Fink NE, Coresh J, Klag MJ et al (2006) Changes in serum calcium, phosphate, and PTH and the risk of death in incident dialysis patients: a longitudinal study. Kidney Int 70:351–357. https://doi.org/10.1038/sj.ki.5001542 - DOI - PubMed

Vitamin D Life – Cancer - Pancreatic category contains

Risk of Pancreatic Cancer significantly reduced by each of:
Vitamin D, Vitamin K, Magnesium, Vitamin D Receptor Activators, and Omega-3
Perhaps the combination would reduce PC risk by >90%
   if taken for at least 2, and perhaps 5 years

• Pancreatic cancer 55 percent less likely if optimal vitamin D (vs low) – Nov 2017
• Pancreatic Cancer survival 2.3 X more likely if good level of Vitamin D – meta-analysis Sept 2023
• Pancreatic Cancer is increasing – Vitamin D and Omega-3 should reduce the risk
• Pancreatic Cancer – live a year longer if have high vitamin D and good Vitamin D Receptor – Aug 2018
• People consuming more Vitamin K1 were 40 percent less likely to get Pancreatic Cancer – Oct 2021
• Pancreatic Cancer risk increased 24 percent for every 100 mg less of Magnesium intake – Dec 2015

81+ Vitamin D Life Cancer meta-analyses

This list is automatically updated