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Active Vitamin D level should not be used for Prospective Studies of Cancer – Aug 2018

Serum 1,25-Dihydroxy vitamin D Level Is Inappropriate for Use in Prospective Studies of Cancer Incidence

Circulation Journal Vol.82, August 2018
William B. Grant, PhD, Sunlight, Nutrition, and Health Research Center, P.O. Box 641603 San Francisco, CA 94164-1603, USA. wbgrant at infionline.net; www.sunarc.org,

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To the Editor:
In a recent paper, Umehara and colleagues reported that baseline serum 1,25-dihydroxyvitamin D [1,25(OH)2D] levels in a 10-year follow-up study in Japan were significantly inversely correlated with all-cause, cardiovascular, and respiratory infection mortality rates but not significantly correlated with the all-cancer mortality rate.1 However, it has been found from ecological studies that cancer mortality rates are inversely correlated with solar UVB doses in Japan2 and other mid-latitude countries.3 Solar UVB exposure is the most important source of vitamin D for most people. In addition, serum 25-hydroxytamin D [25(OH)D] levels are inversely correlated with cancer incidence, especially for short follow-up times,4 and with survival after cancer diagnosis.5 The preponderance the evidence supports the UVB-vitamin D-cancer hypothesis.6

Most observational studies do not investigate the relationship between serum 1,25(OH)2D levels and cancer risk. There are at least a couple of reasons for not doing so.

  • One reason is that serum 25(OH)D levels are considered the most important index of vitamin D status, so are routinely measured.
  • The second reason, important for cancer, is that most organs can readily convert serum 25(OH)D to 1,25(OH)2D as needed via 1-a hydroxylase.7

A search of pubmed.gov found 1 paper that investigated mortality rates with respect to both serum 25(OH)D and 1,25(OH)2D levels. Although it found significantly increased risk of all-cancer mortality rates for 25(OH)D level <20 ng/mL, it found limited significant correlations with 1,25(OH)2D level after adjustment for various cancer risk-modifying factors.8

Disclosure: I receive funding from Bio-Tech Pharmacal, Inc. (Fayetteville, AR) and have received funding from the Vitamin D Society (Woodstock, ON, Canada) and the Vitamin D Council (San Luis Obispo, CA).


  1. Umehara K, Mukai N, Hata J, Hirakawa Y, Ohara T, Yoshida D, et al. Association between serum vitamin D and all-cause and cause-specific death in a general Japanese population: The Hisayama Study. Circ J 2017; 81: 1315 -1321.
  2. Mizoue T. Ecological study of solar radiation and cancer mortality in Japan. Health Phys 2004; 87: 532 - 538.
  3. Moukayed M, Grant WB. Molecular link between vitamin D and cancer prevention. Nutrients 2013; 5: 3993 - 4023.
  4. Grant WB. 25-Hydroxyvitamin D and breast cancer, colorectal cancer, and colorectal adenomas: Case-control versus nested case-control studies. Anticancer Res 2015; 35: 1153 -1160.
  5. Li M, Chen P, Li J, Chu R, Xie D, Wang H. Review: The impacts of circulating 25-hydroxyvitamin D levels on cancer patient outcomes: A systematic review and meta-analysis. J Clin Endocrinol Metab 2014; 99: 2327 -2336.
  6. Grant WB. Roles of solar UVB and vitamin D in reducing cancer risk and increasing survival. Anticancer Res 2016; 36: 1357 -1370.
  7. Garland CF, Gorham ED, Mohr SB, Garland FC. Vitamin D for cancer prevention: Global perspective. Ann Epidemiol 2009; 19: 468 - 483.
  8. Lee DM, Vanderschueren D, Boonen S, O’Neill TW, Pendleton N, Pye SR, et al. Association of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone with mortality among middle-aged and older European men. Age Ageing2014; 43: 528 - 535.
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