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Vitamin D

Vitamin D

Common Names

  • Vitamin D
  • Sunshine vitamin

For Patients & Caregivers

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Adequate vitamin D intake is needed for bone health and other important biologic functions. There are links between increased vitamin D intake and reduced risk of breast and colorectal cancers, but protection against other cancers remains unclear.

Vitamin D is an essential vitamin that is found in certain foods such as fortified milk and cereals, egg yolks, and fish. It is also produced in skin that is exposed to sunlight. Its primary function is to maintain adequate blood calcium and phosphorus levels by increasing absorption of these minerals from the diet through the small intestine. When dietary calcium intake is too low, vitamin D helps move calcium stores from the bones into the blood.

Vitamin D is also involved in many other biologic functions such as immune and hormone regulation, and has anti-cancer properties. Intake of vitamin D through diet may protect against breast or colorectal cancers or improve markers of prostate cancer. However, effects against other cancers remain unclear.

The Institute of Medicine recommends a higher Dietary Allowance of vitamin D at 600 IU/day with the Upper level Intake at 4,000 IU/day for bone health. Scientists know that it is helpful to take vitamin D supplements when patients are deficient in this vitamin, and certain populations including cancer patients can be especially prone to this deficiency. However, there is some debate about what level of supplementation is appropriate. Patients should consult with their physicians if more vitamin D is needed for health maintenance or to treat deficiency.

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  • To prevent or treat cancer
    Intake of vitamin D through diet may protect against breast or colorectal cancers or affect markers for prostate cancer. However, vitamin D by itself does not prevent or treat cancer. Other large studies show that high vitamin D levels do not reduce the risk of many other cancers, and may increase risk for pancreatic or aggressive prostate cancer. More studies are needed to evaluate vitamin D in different populations.
  • For immune regulation
    Vitamin D contributes to hormone regulation and other processes involving immune function. In addition, a deficiency in this vitamin can be prevalent in certain populations, including those with cancer or autoimmune disorders. However, studies on effects of vitamin D supplementation on immune regulation are lacking.
  • To prevent osteoporosis
    Several clinical trials and population studies show that adequate levels of vitamin D intake are needed to prevent osteoporosis and bone fractures. In postmenopausal women and elderly populations, vitamin D supplementation may improve bone mineral density and help to prevent fractures.
  • To prevent multiple sclerosis (MS)
    A recent study involving a large number of women suggests that correcting vitamin D deficiency may reduce future risk of MS.
  • To treat seasonal affective disorder (SAD)
    Vitamin D supplementation does not appear to improve SAD.
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  • You take aluminum hydroxide: Vitamin D supplementation may increase the absorption and blood level of aluminum.
  • You take atorvastatin: Vitamin D reduces blood levels of atorvastatin, but it also helps to lower cholesterol concentrations.
  • You take thiazide diuretics: Vitamin D supplementation may increase serum calcium levels.
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Rare: Gastrointestinal symptoms, kidney disease, kidney stones, excess calcium in blood or urine

Case reports of high blood calcium levels and kidney disease from ingesting high levels of vitamin D have occurred.

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  • Although rare, too much vitamin D can cause abnormally high levels of calcium in the blood or urine, or kidney stones.
  • Patients with kidney stones, kidney disease, high blood calcium levels, gastrointestinal disease, heart disease, liver disease or other diseases associated with disorders of calcium metabolism should seek medical advice before taking supplemental vitamin D.
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For Healthcare Professionals

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Calciferol, ergocalciferol (D2), calcitriol, cholecalciferol (D3)
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Vitamin D refers to several forms of fat-soluble vitamins found in fortified milk and cereals, egg yolks, and fish. The two forms utilized in humans are ergocalciferol (D2) and cholecalciferol (D3). Sunlight can promote the synthesis of D3 in the skin. Vitamin D maintains serum calcium and phosphorus levels by regulating their absorption and excretion, and is important for bone formation. Other biologic functions include its role as an antiproliferative agent (1), and as a pro-differentiation hormone (2) with anti-inflammatory and immunoregulatory properties (3). Low levels of vitamin D are associated with a greater risk of mortality (13), may affect cardiovascular health (14), and increase the risk for development of multiple sclerosis in women (74), but a large study found no association between lower levels and cognitive function (15). However, deficiency during pregnancy may affect the neuro-cognitive development of newborns (75). Deficiency can also cause rickets or other bone disorders, and may be a risk factor for extra-skeletal diseases (45). Furthermore, deficiencies can be particularly prevalent with certain demographics including time of the year or living in northern climates (9); in non-Caucasian race (46) or obese individuals (47); with chronic use of steroids or anticonvulsants; or with diseases such as autoimmune disorders (3), cystic fibrosis (48), kidney disease, and cancer (46) (48) (49).

Clinical data show that vitamin D improves bone mineral density and fracture prevention in the elderly (4) (5) and in postmenopausal women (6). But data are conflicting for primary fracture prevention in men or women following vitamin D and calcium supplementation (7) (8) (9). In another study, high-dose vitamin D had no benefit on lower extremity function, and was associated with increased risk of falls (64).

Findings from studies evaluating its effect on cardiovascular (CV) risk factors have varied across populations and regimens: In a Women’s Health Initiative sub-study, calcium+vitamin D and hormone therapy had a greater effect than either intervention alone or placebo (67); but daily vitamin D did not appear to improve CV risk factors or physical function in a large long-term trial of older adults (68). Yet in another placebo-controlled trial, vitamin D supplementation benefited diabetic patients with coronary artery disease who were vitamin D-deficient (69). In addition, a single large dose of vitamin D2 improved endothelial function in type-2 diabetic patients (11). In non-dialysis patients with chronic kidney disease, D3 was more effective than D2 in raising serum D levels (70). Dietary vitamin D intake was also shown to be inversely associated with mortality from stroke (76).

In other trials, supplementation was found ineffective in reducing the incidence or severity of upper respiratory tract infections (URTIs) in healthy adults (16) or in preventing viral upper respiratory tract infections in children (71). It also did not reduce infections or antibiotic use in an elderly population (17), or improve seasonal affective disorder (SAD) (18) (19). But supplementation may reduce relapse risk in patients with Crohn’s disease (12), and D3+calcium can help prevent weight gain in postmenopausal women (10). In addition, a single oral high-dose of D3 significantly improved fatigue in healthy persons who were vitamin D-deficient (72).

Vitamin D has also been examined for its benefits as a preventive agent and as a treatment for many types of cancer. In animal models, dietary vitamin D3 demonstrated chemopreventive effects against breast cancer equivalent to those elicited by calcitriol without causing hypercalcemia (20). In humans, vitamin D from sunlight exposure and dietary intake may have protective effects against breast cancer (21) (22), and correlates with observations in many breast cancer survivors who were vitamin D-deficient (23). In postmenopausal women who do not use estrogen therapy, vitamin D and calcium supplementation may reduce the incidence of colorectal cancer (24) (25); and in women with grade 1 cervical intraepithelial neoplasia, long-term supplementation resulted in regression and in improved metabolic status (66). However, in a large trial of healthy postmenopausal women with mean vitamin D levels above those of the US population, taking vitamin D3+calcium did not lower cancer risk after 4 years of supplementation (73). In patients with advanced hormone-refractory prostate cancer, vitamin D improved pain and muscle strength (26), and slowed the rate of rise of prostate specific antigen (13). In older patients with diffuse large B-cell lymphoma, supplementation normalized vitamin D levels and enhanced efficacy of rituximab (27). Active vitamin D compounds may also decrease the incidence of post-transplant malignancy among kidney transplant recipients (28).

Other data reveal that vitamin D deficiency was highly prevalent in advanced pancreatic cancer (42) and colorectal cancer patients (43). And increased vitamin D intake reduced the risk of colorectal cancer (29) (30) (31) (32) (33), but had no effect on colorectal adenomas (65). High circulating vitamin D levels may also not reduce the risk of non-Hodgkin lymphoma (34), ovarian (35), kidney (36), endometrial (37), skin (38), or esophageal and gastric (39) cancers, and may significantly increase risk of pancreatic (40) or aggressive prostate cancer (41).  Meta-analyses evaluating vitamin D supplementation for cancer prevention in adults indicate that although it decreases cancer mortality and all-cause mortality, the findings are at risk of error due to the small numbers of participants across studies and attrition bias (44). Contradictory conclusions of a recent meta analysis which included long-term follow up data suggest that vitamin D supplementation does not reduce the incidence of cancer or cancer mortality (77).

Vitamin D may also have a protective effect against influenza in infants (78). The Institute of Medicine recommends a Daily Dietary Allowance of vitamin D at 600 IU/day with the Upper Level Intake at 4,000 IU/day for bone health (50). Oral supplementation has been shown to be the safest way to increase vitamin D levels (51), although considerable debate continues on how this may translate to optimizing vitamin D status (45). Therefore, patients should consult with their physicians if a deficiency is suspected to assess the amount of vitamin D needed for health maintenance and to avoid side effects such as kidney stones or high levels of calcium in blood or urine.

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Fatty fish, fish liver oils, egg yolks, fortified milk and cereals (5)

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  • Cancer prevention
  • Immune regulation
  • Osteoporosis
  • Multiple sclerosis
  • Seasonal affective disorder (SAD)
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The most biologically active metabolite of vitamin D is calcitriol, which regulates calcium and phosphate homeostasis (52). In humans, the primary function of vitamin D is to maintain normal levels of serum calcium and phosphorus concentrations by enhancing small intestine dietary absorption efficiency of these minerals. 25-hydroxyvitamin D [25(OH)D] enhances the efficiency of calcium and phosphorus absorption along the entire small intestine, but primarily in the duodenum and jejunum (5). When dietary calcium intake is insufficient, 25(OH)D and parathyroid hormone (PTH) mobilize monocytic stem cells in the bone marrow to become mature osteoclasts. These osteoclasts mobilize calcium from the bones, thereby maintaining blood calcium levels (50). Vitamin D is thought to have physiological effects in other parts of the body as well because vitamin D receptors (VDRs) are found in the cells of other organs that include intestines, kidney, stomach, brain, prostate, breast, and white blood cells (2) (53).

The anticancer effect of vitamin D is thought to be due to induction of cell differentiation (1) (54) and antiproliferation (55). In lymphoma cells, interventional 25(OH)D3 to normalize levels (>30 ng/mL) resulted in significantly stronger antibody-dependent cell-mediated cytotoxicity, suggesting benefit in D-deficient individuals receiving rituximab (27). In xenograft models of breast cancer, dietary D3 elevated circulating D levels and increased CYP27B1 expression in both tumor and intestines, suggesting it stimulates local calcitriol synthesis in the tumor microenvironment and promotes the ensuing paracrine/autocrine actions that contribute to its anticancer activity (20). The upregulation of CYP27B1 expression by tumors was unique to D3 versus calcitriol in the same tissue (20). In other animal models, a positive feedback signaling loop between the serine-protein kinase ATM (ataxia telangiectasia mutated) and the VDR was identified as critical for cancer chemoprevention by vitamin D (56).

Calcitriol, the hormonally active form of vitamin D3, targets the vitamin D degrading enzyme CYP24A1, which is most abundant in the kidney, but also expressed in several other tissues (57). CYP24A1 overexpression in colon, ovary, breast, lung, and esophageal malignancies, likely leads to degradation of the locally available D3, impairing its antitumorigenic action in the tumor tissue (57).

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Individuals with kidney stones, kidney disease, high blood calcium levels, gastrointestinal disease, heart disease, liver disease or other diseases associated with disorders of calcium metabolism should seek medical advice before taking supplemental vitamin D (9).

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Rare: Gastrointestinal symptoms, renal disease, nephrolithiasis, hypercalcemia, hypercalciuria (9) (44).

Case Reports
Life-threatening hypercalcemia: In two women resulting from intake of over-the-counter vitamin-D concentrated supplements that were 100 — 1,000 times higher than stated on the label (58). Hypercalcemic crisis: In a 30-year-old woman after taking large quantities of vitamin D for an unknown period of time (59).
Acute renal failure and hypervitaminosis A: In a 51-year old woman after consuming an over-the-counter vitamin D supplement, which also caused vitamin A toxicity possibly due to renal failure related to the hypercalcemia induced by vitamin D toxicity (60).

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  • Aluminum hydroxide: May increase the absorption and blood level of aluminum (61).
  • Atorvastatin: Vitamin D reduces blood levels of atorvastatin but it also helps lower cholesterol concentrations (62) .
  • Thiazide diuretics: May increase serum calcium level (63).
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  1. Tanaka H, Abe E, Miyaura C, et al. 1 alpha,25-Dihydroxycholecalciferol and a human myeloid leukaemia cell line (HL-60). Biochem J. Jun 15 1982;204(3):713-719.

  2. Antico A, Tampoia M, Tozzoli R, et al. Can supplementation with vitamin D reduce the risk or modify the course of autoimmune diseases? A systematic review of the literature. Autoimmun Rev. Dec 2012;12(2):127-136. doi: 10.1016/j.autrev.2012.07.007

  3. Feskanich D, Willett WC, Colditz GA. Calcium, vitamin D, milk consumption, and hip fractures: a prospective study among postmenopausal women. Am J Clin Nutr. Feb 2003;77(2):504-511.

  4. Rodriguez-Martinez MA, Garcia-Cohen EC. Role of Ca(2+) and vitamin D in the prevention and treatment of osteoporosis. Pharmacol Ther. Jan 2002;93(1):37-49.

  5. Jackson RD, LaCroix AZ, Gass M, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med. Feb 16 2006;354(7):669-683. doi: 10.1056/NEJMoa055218

  6. Moyer VA, Force* USPST. Vitamin D and calcium supplementation to prevent fractures in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. May 7 2013;158(9):691-696. doi: 10.7326/0003-4819-158-9-201305070-00603

  7. Avenell A, Mak JC, O’Connell D. Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men. Cochrane Database Syst Rev. 2014;4:CD000227. doi: 10.1002/14651858.CD000227.pub4

  8. Caan B, Neuhouser M, Aragaki A, et al. Calcium plus vitamin D supplementation and the risk of postmenopausal weight gain. Arch Intern Med. May 14 2007;167(9):893-902. doi: 10.1001/archinte.167.9.893

  9. Sugden JA, Davies JI, Witham MD, et al. Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low vitamin D levels. Diabet Med. Mar 2008;25(3):320-325. doi: 10.1111/j.1464-5491.2007.02360.x

  10. Jorgensen SP, Agnholt J, Glerup H, et al. Clinical trial: vitamin D3 treatment in Crohn’s disease - a randomized double-blind placebo-controlled study. Aliment Pharmacol Ther. Aug 2010;32(3):377-383. doi: 10.1111/j.1365-2036.2010.04355.x

  11. Gross C, Stamey T, Hancock S, et al. Treatment of early recurrent prostate cancer with 1,25-dihydroxyvitamin D3 (calcitriol). J Urol. Jun 1998;159(6):2035-2039; discussion 2039-2040.

  12. Tomaschitz A, Pilz S, Ritz E, et al. Independent association between 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D and the renin-angiotensin system: The Ludwigshafen Risk and Cardiovascular Health (LURIC) study. Clin Chim Acta. Sep 6 2010;411(17-18):1354-1360. doi: 10.1016/j.cca.2010.05.037

  13. Slinin Y, Paudel ML, Taylor BC, et al. 25-Hydroxyvitamin D levels and cognitive performance and decline in elderly men. Neurology. Jan 5 2010;74(1):33-41. doi: 10.1212/WNL.0b013e3181c7197b

  14. Murdoch DR, Slow S, Chambers ST, et al. Effect of vitamin D3 supplementation on upper respiratory tract infections in healthy adults: the VIDARIS randomized controlled trial. JAMA. Oct 3 2012;308(13):1333-1339. doi: 10.1001/jama.2012.12505

  15. Avenell A, Cook JA, Maclennan GS, et al. Vitamin D supplementation to prevent infections: a sub-study of a randomised placebo-controlled trial in older people (RECORD trial, ISRCTN 51647438). Age Ageing. Sep 2007;36(5):574-577. doi: 10.1093/ageing/afm091

  16. Dumville JC, Miles JN, Porthouse J, et al. Can vitamin D supplementation prevent winter-time blues? A randomised trial among older women. J Nutr Health Aging. Mar-Apr 2006;10(2):151-153.

  17. Krishnan AV, Swami S, Feldman D. Equivalent anticancer activities of dietary vitamin D and calcitriol in an animal model of breast cancer: importance of mammary CYP27B1 for treatment and prevention. J Steroid Biochem Mol Biol. Jul 2013;136:289-295. doi: 10.1016/j.jsbmb.2012.08.005

  18. Blackmore KM, Lesosky M, Barnett H, et al. Vitamin D from dietary intake and sunlight exposure and the risk of hormone-receptor-defined breast cancer. Am J Epidemiol. Oct 15 2008;168(8):915-924. doi: 10.1093/aje/kwn198

  19. Robien K, Cutler GJ, Lazovich D. Vitamin D intake and breast cancer risk in postmenopausal women: the Iowa Women’s Health Study. Cancer Causes Control. Sep 2007;18(7):775-782. doi: 10.1007/s10552-007-9020-x

  20. Neuhouser ML, Sorensen B, Hollis BW, et al. Vitamin D insufficiency in a multiethnic cohort of breast cancer survivors. Am J Clin Nutr. Jul 2008;88(1):133-139.

  21. Wactawski-Wende J, Kotchen JM, Anderson GL, et al. Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med. Feb 16 2006;354(7):684-696. doi: 10.1056/NEJMoa055222

  22. Van Veldhuizen PJ, Taylor SA, Williamson S, et al. Treatment of vitamin D deficiency in patients with metastatic prostate cancer may improve bone pain and muscle strength. J Urol. Jan 2000;163(1):187-190.

  23. Obi Y, Ichimaru N, Hamano T, et al. Orally active vitamin d for potential chemoprevention of posttransplant malignancy. Cancer Prev Res (Phila). Oct 2012;5(10):1229-1235. doi: 10.1158/1940-6207.capr-12-0218

  24. Garland C, Shekelle RB, Barrett-Connor E, et al. Dietary vitamin D and calcium and risk of colorectal cancer: a 19-year prospective study in men. Lancet. Feb 9 1985;1(8424):307-309.

  25. Garland CF, Garland FC, Gorham ED, et al. The role of vitamin D in cancer prevention. Am J Public Health. Feb 2006;96(2):252-261. doi: 10.2105/AJPH.2004.045260

  26. Lappe JM, Travers-Gustafson D, Davies KM, et al. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. Jun 2007;85(6):1586-1591.

  27. Ma Y, Zhang P, Wang F, et al. Association between vitamin D and risk of colorectal cancer: a systematic review of prospective studies. J Clin Oncol. Oct 1 2011;29(28):3775-3782. doi: 10.1200/JCO.2011.35.7566

  28. Weinstein SJ, Purdue MP, Smith-Warner SA, et al. Serum 25-hydroxyvitamin D, vitamin D binding protein and risk of colorectal cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Int J Cancer. Mar 15 2015;136(6):E654-664. doi: 10.1002/ijc.29157

  29. Purdue MP, Freedman DM, Gapstur SM, et al. Circulating 25-hydroxyvitamin D and risk of non-hodgkin lymphoma: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Am J Epidemiol. Jul 1 2010;172(1):58-69. doi: 10.1093/aje/kwq117

  30. Zheng W, Danforth KN, Tworoger SS, et al. Circulating 25-hydroxyvitamin D and risk of epithelial ovarian cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Am J Epidemiol. Jul 1 2010;172(1):70-80. doi: 10.1093/aje/kwq118

  31. Gallicchio L, Moore LE, Stevens VL, et al. Circulating 25-hydroxyvitamin D and risk of kidney cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Am J Epidemiol. Jul 1 2010;172(1):47-57. doi: 10.1093/aje/kwq115

  32. Zeleniuch-Jacquotte A, Gallicchio L, Hartmuller V, et al. Circulating 25-hydroxyvitamin D and risk of endometrial cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Am J Epidemiol. Jul 1 2010;172(1):36-46. doi: 10.1093/aje/kwq114

  33. Caini S, Boniol M, Tosti G, et al. Vitamin D and melanoma and non-melanoma skin cancer risk and prognosis: A comprehensive review and meta-analysis. Eur J Cancer. Jul 30 2014. doi: 10.1016/j.ejca.2014.06.024

  34. Abnet CC, Chen Y, Chow WH, et al. Circulating 25-hydroxyvitamin D and risk of esophageal and gastric cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Am J Epidemiol. Jul 1 2010;172(1):94-106. doi: 10.1093/aje/kwq121

  35. Stolzenberg-Solomon RZ, Jacobs EJ, Arslan AA, et al. Circulating 25-hydroxyvitamin D and risk of pancreatic cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Am J Epidemiol. Jul 1 2010;172(1):81-93. doi: 10.1093/aje/kwq120

  36. Ahn J, Peters U, Albanes D, et al. Serum vitamin D concentration and prostate cancer risk: a nested case-control study. J Natl Cancer Inst. Jun 4 2008;100(11):796-804. doi: 10.1093/jnci/djn152

  37. Van Loon K, Owzar K, Jiang C, et al. 25-Hydroxyvitamin D Levels and Survival in Advanced Pancreatic Cancer: Findings From CALGB 80303 (Alliance). J Natl Cancer Inst. Aug 2014;106(8). doi: 10.1093/jnci/dju185

  38. Wesa KM, Segal NH, Cronin AM, et al. Serum 25-Hydroxy Vitamin D and Survival in Advanced Colorectal Cancer: A Retrospective Analysis. Nutr Cancer. Feb 3 2015:1-7. doi: 10.1080/01635581.2015.998838

  39. Bjelakovic G, Gluud LL, Nikolova D, et al. Vitamin D supplementation for prevention of cancer in adults. Cochrane Database Syst Rev. 2014;6:CD007469. doi: 10.1002/14651858.CD007469.pub2

  40. Aspray TJ, Bowring C, Fraser W, et al. National Osteoporosis Society Vitamin D Guideline Summary. Age Ageing. Jul 28 2014. doi: 10.1093/ageing/afu093

  41. Hauser K, Walsh D, Shrotriya S, et al. Low 25-hydroxyvitamin D levels in people with a solid tumor cancer diagnosis: the tip of the iceberg? Support Care Cancer. Jul 2014;22(7):1931-1939. doi: 10.1007/s00520-014-2154-y

  42. Duerbeck NB, Dowling DD, Duerbeck JM. Vitamin d: hero or hype. Obstet Gynecol Surv. Dec 2013;68(12):799-810. doi: 10.1097/ogx.0000000000000003

  43. Siwamogsatham O, Alvarez JA, Tangpricha V. Diagnosis and treatment of endocrine comorbidities in patients with cystic fibrosis. Curr Opin Endocrinol Diabetes Obes. Aug 7 2014. doi: 10.1097/MED.0000000000000096

  44. Skversky AL, Kumar J, Abramowitz MK, et al. Association of glucocorticoid use and low 25-hydroxyvitamin D levels: results from the National Health and Nutrition Examination Survey (NHANES): 2001-2006. J Clin Endocrinol Metab. Dec 2011;96(12):3838-3845. doi: 10.1210/jc.2011-1600

  45. Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. Available at: http://www.ncbi.nlm.nih.gov/books/NBK56070/. 2011 Accessed August 11, 2014.

  46. Terushkin V, Bender A, Psaty EL, et al. Estimated equivalency of vitamin D production from natural sun exposure versus oral vitamin D supplementation across seasons at two US latitudes. J Am Acad Dermatol. Jun 2010;62(6):929 e921-929. doi: 10.1016/j.jaad.2009.07.028

  47. Beer TM. ASCENT: the androgen-independent prostate cancer study of calcitriol enhancing taxotere. BJU Int. Sep 2005;96(4):508-513. doi: 10.1111/j.1464-410X.2005.05675.x

  48. Stumpf WE, Sar M, Reid FA, et al. Target cells for 1,25-dihydroxyvitamin D3 in intestinal tract, stomach, kidney, skin, pituitary, and parathyroid. Science. Dec 7 1979;206(4423):1188-1190.

  49. Popadic S, Ramic Z, Medenica L, et al. Antiproliferative effect of vitamin A and D analogues on adult human keratinocytes in vitro. Skin Pharmacol Physiol. 2008;21(4):227-234. doi: 10.1159/000135639

  50. Ting HJ, Yasmin-Karim S, Yan SJ, et al. A positive feedback signaling loop between ATM and the vitamin D receptor is critical for cancer chemoprevention by vitamin D. Cancer Res. Feb 15 2012;72(4):958-968. doi: 10.1158/0008-5472.can-11-0042

  51. Hummel D, Aggarwal A, Borka K, et al. The vitamin D system is deregulated in pancreatic diseases. J Steroid Biochem Mol Biol. Jul 29 2014. doi: 10.1016/j.jsbmb.2014.07.011

  52. Kaptein S, Risselada AJ, Boerma EC, et al. Life-threatening complications of vitamin D intoxication due to over-the-counter supplements. Clin Toxicol (Phila). Jun 2010;48(5):460-462. doi: 10.3109/15563650.2010.486382

  53. Genzen JR. Hypercalcemic crisis due to vitamin D toxicity. Lab Med. Spring 2014;45(2):147-150.

  54. Granado-Lorencio F, Rubio E, Blanco-Navarro I, et al. Hypercalcemia, hypervitaminosis A and 3-epi-25-OH-D3 levels after consumption of an “over the counter” vitamin D remedy. a case report. Food Chem Toxicol. Jun 2012;50(6):2106-2108. doi: 10.1016/j.fct.2012.03.001

  55. Demontis R, Leflon A, Fournier A, et al. 1 alpha(OH) vitamin D3 increases plasma aluminum in hemodialized patients taking AI(OH)3. Clin Nephrol. Sep 1986;26(3):146-149.

  56. Schwartz JB. Effects of vitamin D supplementation in atorvastatin-treated patients: a new drug interaction with an unexpected consequence. Clin Pharmacol Ther. Feb 2009;85(2):198-203. doi: 10.1038/clpt.2008.165

  57. Chandler PD, Scott JB, Drake BF, et al. Risk of hypercalcemia in blacks taking hydrochlorothiazide and vitamin D. Am J Med. Aug 2014;127(8):772-778. doi: 10.1016/j.amjmed.2014.02.044

  58. Bischoff-Ferrari HA, Dawson-Hughes B, Orav EJ, et al. Monthly High-Dose Vitamin D Treatment for the Prevention of Functional Decline: A Randomized Clinical Trial. JAMA Intern Med. 2016 Jan 4:1-10.

  59. Baron JA, Barry EL, Mott LA, et al. A Trial of Calcium and Vitamin D for the Prevention of Colorectal Adenomas. N Engl J Med. 2015 Oct 15;373(16):1519-30.

  60. Hin H, Tomson J, Newman C, et al. Optimum dose of vitamin D for disease prevention in older people: BEST-D trial of vitamin D in primary care. Osteoporos Int. Mar 2017;28(3):841-851.

  61. Nowak A, Boesch L, Andres E, et al. Effect of vitamin D3 on self-perceived fatigue: A double-blind randomized placebo-controlled trial. Medicine (Baltimore). Dec 2016;95(52):e5353.

  62. Lappe J, Watson P, Travers-Gustafson D, et al. Effect of Vitamin D and Calcium Supplementation on Cancer Incidence in Older Women: A Randomized Clinical Trial. JAMA. Mar 28 2017;317(12):1234-1243.

  63. Munger KL, Hongell K, Aivo J, et al. 25-Hydroxyvitamin D deficiency and risk of MS among women in the Finnish Maternity Cohort. Neurology. 2017;Epub before print.

  64. Sheerah HA, Eshak ES, Cui R, Imano H, Iso H, Tamakoshi A; Japan Collaborative Cohort Study Group. Relationship Between Dietary Vitamin D and Deaths From Stroke and Coronary Heart Disease: The Japan Collaborative Cohort Study. Stroke. 2018 Feb;49(2):454-457.

  65. Goulão B, Stewart F, Ford JA, MacLennan G, Avenell A. Cancer and vitamin D supplementation: a systematic review and meta-analysis. Am J Clin Nutr. 2018 Apr 1;107(4):652-663.

  66. Zhou J, Du J, Huang L, Wang Y, Shi Y, Lin H. Preventive Effects of Vitamin D on Seasonal Influenza A in Infants: A Multicenter, Randomized, Open, Controlled Clinical Trial. Pediatr Infect Dis J. 2018 Jan 8. [Epub ahead of print]

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