Can Sunlight Brighten the Future of Cancer Prevention?

Shoshanna Robinson, Mercer University College of Pharmacy

Vitamin D has been stated to protect against cancer and has been studied accordingly in cancer mortality. This breakthrough came after colon cancer mortality rates were observed to decrease with vitamin D. [1] An inverse relationship may in fact exist between the risk of cancer and increased vitamin D from sunlight exposure. [2] Cell culture and in vivo animal studies have shown this association of vitamin D preventing cancer while human trials have been awaiting. [3]

Effect of Vitamin D and Calcium Supplementation on Cancer Incidence in Older Women A Randomized Clinical Trial [4]
Design Double-blind, placebo-controlled, population-based randomized clinical; N= 2,303
Objective To determine if dietary supplementation with vitamin D3 and calcium reduces the risk of cancer among older women
Study Groups Placebo (n= 1,147); vitamin D3 + calcium treatment (n= 1,156)
Methods The treatment group received cholecalciferol (2000-IU capsule) once daily and calcium carbonate (500-mg tablet) three times daily while placebo group received an identical number of daily doses.  A total of 17 study follow-up visits occurred at a rate of every 6 months. Participants were asked to limit vitamin D supplementation, outside of the intervention, to 800 IU per day. Participants also were asked to limit additional calcium to 1500 mg per day as directed to be consistent with a previous study.
Duration 4 years
Primary Outcome Measure First diagnosis of any type of cancer (excluding nonmelanoma skin cancers) and change in vitamin D levels over time
Baseline Characteristics
Vitamin D3 + Calcium Placebo
Mean age, years 65.2 65.2
Mean height, cm 162.1 162.0
Mean weight, kg 78.5 79.3
Mean body mass index, kg/m^2 29.9 30.2
Mean serum 25-hydroxyvitamin D, ng/mL 32.8 32.8

Median Supplementation (IQR)

Calcium supplements, mg/d 600 (5-1050) 600 (0-1000)
Vitamin D supplements, IU/d 734 (100-1200) 700 (0-1000)
Dietary calcium, mg/d 641 (460-893) 641 (454-892)
Dietary vitamin D, IU/d 103 (60-176) 107 (60-173)

Race/ethnicity, n (%)

White 1149 (99.4) 1142 (99.6)
American Indian or Alaska

Native

4 (0.4) 4 (0.3)
Asian, black, unknown 3 (0.3) 1 (0.1)
Hispanic 9 (0.8) 2 (0.2)

Other characteristics, n (%)

Surgical menopause 423 (36.6) 389 (33.9)
Bilateral oophorectomy 315 (27.3) 280 (24.4)
Current smoker 75 (6.5) 66 (5.7)
Never smoker 768 (66.4) 773 (67.4)
Estrogen therapy 186 (16.1) 168 (14.7)
Estrogen agonist or

antagonist therapy

19 (1.64) 38 (3.3)
Results
Participants With First Diagnosis of Cancer Vitamin D3 + Calcium Placebo Total

Cancer Site Year 1, n

Breast 4 5 9
Breast in situ 1 0 1
Colon or rectum 0 0 0
Colon or rectum in situ 0 0 0
Endometrium 0 1 1
Lung 1 0 1
Melanoma 0 1 1
Melanoma in situ 0 0 0
Neuroendocrine 1 0 1
Ovary 0 0 0
Other 4 5 9
Other in situ 0 0 0
Total 11 12 23

Cancer Site Years 1-4, n

Breast 16 23 39
Breast in situ 3 1 4
Colon or rectum 4 4 8
Colon or rectum in situ 0 2 2
Endometrium 2 3 5
Lung 5 2 7
Melanoma 1 2 3
Melanoma in situ 1 2 3
Neuroendocrine 2 4 6
Ovary 0 5 5
Other 11 15 26
Other in situ 0 1 1
Serum 25-Hydroxyvitamin D Level Vitamin D3 + Calcium, n Vitamin D3 + Calcium, n

Mean (95% CI), ng/mL

Placebo Group, n Placebo Group, n

Mean (95% CI), ng/mL

p value
Visit 1 (baseline) 1,156 33.0 (32.3 to 33.6) 1146 32.7 (32.1 to 33.3) < 0.001
Visit 3 (12 mo) 989 43.9 (43.2 to 44.7) 1002 31.6 (30.9 to 32.3) < 0.001
Visit 5 (24 mo) 966 44.3 (43.6 to 45.0) 966 31.7 (31.0 to 32.4) < 0.001
Visit 7 (36 mo) 938 45.1 (44.3 to 45.9) 925 32.4 (31.7 to 33.1) < 0.001
Visit 9 (48 mo) 980 42.5 (41.7 to 43.3) 992 30.9 (30.2 to 31.6) < 0.001
Mean (visit 2 [6 mo] to visit 9) 1,047 43.6 (42.9 to 44.3) 1,056 31.6 (31.0 to 32.2) 12.0 < 0.001
Adverse Events Common Adverse Events (vitamin D3 + calcium vs placebo): renal calculi (n= 16 vs. 10); one elevated serum calcium value (n= 6 vs 2)
Serious Adverse Events: N/A
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions Supplementation with vitamin D3 and calcium compared with placebo did not result in a lower risk of all-type cancer at 4 years.

With the population including a majority of non-hispanic, white females, the generalizability of these results across different demographics is limited.  As the placebo group could have supplemented their own vitamin D and calcium to a lesser degree than the intervention group, considering its validated appropriateness for women of this age range, this may have introduced bias to the results. It may be difficult to ever determine causative effects of vitamin D on cancer due to the role that family history, lifestyle factors, and genetics all play.

 

References

[1] Garland CF, Garland FC. Do sunlight and vitamin D reduce the likelihood of colon cancer? Int J Epidemiol. 1980;9(3):227-231.

[2] Bauer S, Hankinson S, Bertone-Johnson E, Ding E. Plasma vitamin D levels, menopause, and risk of breast cancer: dose-response meta-analysis of prospective studies.

[3] Welsh J. Cellular and molecular effects of vitamin D on carcinogenesis. Arch Biochem  Biophys. 2012;523(1):107-114.

[4] 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. 2017;317(12):1234-1243.

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