By Mercy Kagoda, MD, MPH

Private Practitioner, Pasadena, CA

Dr. Kagoda reports no financial relationships relevant to this field of study.

SYNOPSIS: A self-report of any vitamin D supplementation is associated with a decrease in colorectal polyps; adjusted odds ratio (aOR) 0.57 (95% confidence interval [CI], 0.33-0.96) in high-latitude conditions. A self report of meeting 600 IU of vitamin D, the recommended daily intake for that region, is associated with a decrease in high-risk adenomatous polyps, with an aOR of 0.78 (95% CI, 0.62-0.99) in high-latitude conditions.

SOURCE: Sutherland RL, Ormsbee J, Pader J, et al. Vitamin D supplementation reduces the occurrence of colorectal polyps in high-latitude locations. Preventive Medicine 2020;135:106072.

We obtain vitamin D from our diet, or our skins make it when exposed to ultraviolet B radiation. Vitamin D3 is metabolized in the skin from 7-dehydrocholesterol. The liver metabolizes vitamin D to 25OHD, which is then metabolized to 1,25(OH)2D in the kidneys. The function of vitamin D in bone health and immune system functioning is accepted and widely studied, and more recently, vitamin D supplementation has been investigated for its role in preventing colon cancer. This study helps provide further information on the role of vitamin D supplementation and the presence of colorectal polyps in populations living in high-latitude locations.

This cross-sectional study uses data collected from the largest publicly funded center for early detection and screening of colon cancer in Canada: Forzani & MacPhail Colon Cancer Screening Center (CCSC). Data collection included a colonoscopy report with a histological type of any identified polyps and questionnaires completed prior to the colonoscopy.

Three questionnaires were used: a Canadian Diet History Questionnaire (I or II, depending on when the intake was completed), a Health and Lifestyle Questionnaire, and an International Physical Activity Questionnaire. The Canadian Diet History Questionnaire (DHQ) was used to determine fiber intake, vitamin D dietary intake, and supplement use. The DHQ was developed by the National Cancer Institute Risk Factor Assessment branch and also is used in the United States; the Canadian version includes foods that are specific to Canada.¹

The primary outcomes of this study included vitamin D supplementation, total vitamin D intake, and their association with any type of colorectal polyps. Participants were recruited from the CCSC. Table 1 shows the study’s inclusion and exclusion criteria. Characteristics of the populations sampled included age, sex, ethnicity, education, marital status, alcohol use, smoking status, physical activity, family history of cancer, nonsteroidal anti-inflammatory drug use, vitamin D supplementation, and fiber intake. Table 2 shows a breakdown of population characteristics for the study.

The data analysis used logistic regression models. Crude and adjusted odds ratios were used to evaluate the association between vitamin D supplementation and high-risk adenomatous polyps. Likelihood ratio tests were used to evaluate effect modifiers, and chi-square tests were used to evaluate whether the characteristics were associated with vitamin D use. Results showed that, for those who reported taking any vitamin D supplementation, the risk for polyps was lower than that of those who reported not taking any vitamin D supplement; ORcrude = 0.59 (0.46-0.76). The risk for polyps dropped further for those who reported taking at least the recommended daily intake (RDI) of vitamin D; ORcrude = 0.75 (0.65-0.87). These results were adjusted for age, sex, body mass index, smoking status, alcohol use and fiber intake, as these variables were identified as confounders. Interestingly, there was no significance for meeting vitamin D RDI and high-risk adenomatous polyp (HRAP) detection; ORcrude = 0.8 (0.5-1.2).

Commentary

This study showed that self-reported vitamin D supplementation was associated with a decrease in the occurrence of any colorectal polyps and, specifically, HRAPs. The main strength of this study was that it avoided outcome bias, since the questionnaire was completed prior to the colonoscopy and the colonoscopy results.

Another advantage of this study is that it used HRAPs as a primary outcome. HRAPs are considered to be more informative for determining risk for colorectal cancer during screening. Unfortunately, the study was too underpowered to pick up significance for risk reduction regarding vitamin D for HRAPs. This study did not show a significance for meeting vitamin D RDI and HRAPs; ORcrude = 0.8 (0.5-1.2).

Serum vitamin D concentration would have clarified the association between serum vitamin D level and HRAPs. Per email communication with the lead author, at the time, they were not collecting blood samples for any biorepository participants and were unable to measure serum vitamin D levels. They have since begun collecting various biological samples. This also was not a racially diverse study.

Prior studies suggest a different mechanism and role for vitamin D in prevention of an initial polyp vs. prevention of recurrent polyps. A study by Crockett et al on vitamin D supplementation and recurrent polyps found no effect of either calcium or vitamin D on polyps (sessile serrated adenomas polyps in particular) during the treatment phase, when participants were receiving 1,200 mg/day of calcium and 1,000 IU/day of vitamin D2. However, six to 10 years after supplementation with calcium and vitamin D, there was an increased risk of sessile serrated adenomas polyps; relative risk 3.82 (1.26-11.57).²

Crockett et al also discuss findings from a chemoprevention trial, which found that “smokers were at higher risk of recurrent conventional adenomas when given a combination of aspirin, calcium and calcitriol. These results suggest that smokers may be particularly sensitive to calcium mediated effects that promote colorectal neoplasia.”

Further studies are needed to understand the effect of vitamin D supplementation for prevention of a primary polyp vs. recurrent polyps. This may bring to mind the epidemiological studies concerning beta carotene supplementation effects and tobacco smoke in lung cancer — the alpha-Tocopherol Beta Carotene Cancer Prevention Study and the Carotene and Retinol Efficacy Trial.^3,4 Vitamin supplementation may not always have the desired effect.

Another interesting consideration the authors discussed is that the effect of vitamin D supplementation may be influenced by the vitamin D receptor genotype. The authors cite a study by Barry et al that suggests the effect of vitamin D3 supplementation on advanced colorectal cancer risk may be the result of differences in the vitamin D receptor gene.⁵ Since genotype frequencies vary by race, the effect of vitamin D supplementation also may vary in different populations.

In summary, this study suggests that vitamin D supplementation may be beneficial in primary prevention of any colorectal polyps in the population described. However, given that prior studies examining secondary prevention of colorectal polyps have contradictory results, further studies, specifically those that include measurement of serum vitamin D levels, need to be done prior to recommending vitamin D as a means of primary prevention of colorectal polyps.

REFERENCES

1. National Cancer Institute. Differences between DHQ II and the Canadian DHQ II (C-DHQ II). National Institutes of Health. Updated July 24, 2020. https://epi.grants.cancer.gov/dhq2/about/summary.html
2. Crockett SD, Barry EL, Mott LA, et al. Calcium and vitamin D supplementation and increased risk of serrated polyps: Results from a randomised clinical trial. Gut 2019;68:475-486.
3. Alpha-Tocopherol Beta Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 1994;330:1029-1035.
4. Goodman GE, Omenn GS, Thornquist MD, et al. The Carotene and Retinol Efficacy Trial (CARET) to prevent lung cancer in high-risk populations: Pilot study with cigarette smokers. Cancer Epidemiol Biomarkers Prev 1993;2:389-396.
5. Barry EL, Peacock JL, Rees JR, et al. Vitamin D receptor genotype, vitamin D3 supplementation, and risk of colorectal adenomas: A randomized clinical trial. JAMA Oncology 2017;3:628-635.