Increased Vitamin D Intake Associated With Lower Risk of Early-Onset CRC

Increased intake of vitamin D was associated with a decreased risk of early-onset colorectal cancer (CRC) and precursors in younger women between the ages of 25 years and 42 years, according to data from a prospective cohort study published in Gastroenterology.¹

Results showed that compared with women who consumed less than 300 IU of vitamin D daily, the HR was 0.51 (95% CI, 0.30-0.86) for those who consumed 300 IU to 450 IU daily, and 0.49 (95% CI, 0.26-0.93) for those who consumed 450 IU or more per day (P for trend = .01). No evidence of a nonlinear association was reported (P for nonlinearity = .50). Moreover, the HR per 400 IU/day increase was 0.46 (95% CI, 0.26-0.83).

“Vitamin D has known activity against CRC in laboratory studies. Because vitamin D deficiency has been steadily increasing over the past few years, we wondered whether this could be contributing to the rising rates of CRC in young individuals,” Kimmie Ng, MD, MPH, study author and director of the Young-Onset Colorectal Cancer Center at Dana-Farber Cancer Institute, stated in a press release.² “We found that total vitamin D intake of 300 IU per day or more — roughly equivalent to three 8-oz. glasses of milk — was associated with an approximately 50% lower risk of developing young-onset CRC.”

Although the incidence of CRC has decreased in the United States and many other countries, the rate of adults younger than 50 years of age developing CRC has been on the rise. Due to delays in screening and other clinicopathologic features, cases of early-onset CRC tend to be is usually diagnosed at a more advanced stage. Moreover, although a large portion of early-onset cases do not have a family history of CRC, other known risk factors like obesity have been found to increase the risk of early-onset CRC.

Findings from previous studies have suggested that vitamin D intake may be a protective factor against CRC. However, it remains unknown whether vitamin D intake is linked with risk of early-onset CRC. With consumption of vitamin D–rich food, such as milk, fish, and eggs declining, investigators sought to examine whether vitamin D intake correlated with the risk of early-onset CRC.

To conduct this research, investigators analyzed data from the Nurses’ Health Study (NHS) II, a prospective cohort study of 116,429 female nurses between the ages of 25 years and 42 years. The trial began in 1989 and those enrolled on the NHS II study completed self-administered questionnaires every 2 years on demographics, lifestyle factors, and health-related information. These questionnaires were complemented by assessment of dietary intake through the use of food frequency questionnaires done every 4 years.

Those with inflammatory bowel disease, a previous diagnosis of CRC, implausible data for baseline energy intake or missing data for baseline vitamin D intake were not included in the analysis. Total vitamin D intake was calculated by adding dietary vitamin D intake and supplemental vitamin D intake from supplements or multivitamins.

Body mass index was calculated based on reported height and weight, with weight updated every 2 years. Investigators examined total energy, red meat, processed meat, fiber, calcium, folate, and alcohol. Smoking status was updated biennially for calculation of pack-years smoked. Physical activity was self-reported with questionnaires done every 2 to 4 years. Television viewing time was also used as a measure for sedentary behavior.

The primary end point for the study was the incidence of early-onset CRC, defined as CRC diagnosed before the age of 50 years.

“We also identified unreported lethal CRC cases through family members, the postal system, and the National Death Index. For all deaths due to CRC, we requested consent from the next of kin for acquisition of medical records,” the study authors wrote. “Physicians who were blinded to exposure status reviewed medical records to verify CRC diagnosis and recorded histopathologic findings and anatomic location.”

Of the 94,205 women studied, 111 cases of early-onset CRC during 1,250,560 person-years of follow-up were identified from 1991 to 2015, and the median vitamin D intake among them was 372 IU/day. Moreover, participants under the age of 50 years were less likely to have a high BMI, smoke cigarettes, consume alcohol, spend significant amounts of time watching television, or consume red meat. Additionally, these participants were more likely to consume more dietary fiber, folate, and calcium; use more aspirin and multivitamins; and be physically active and have healthy dietary habits.

Additional data showed that sources of vitamin D intake were inversely associated with reduced risk of early-onset CRC. A stronger association was observed for dietary vitamin D (HR per 400 IU/day increase, 0.34; 95% CI, 0.15-0.79) than supplemental vitamin D (HR per 400 IU/day increase, 0.77; 95% CI, 0.37-1.62). Moreover, vitamin D from dairy products was a significant contributor for this association (HR per 400 IU/day increase, 0.32; 95% CI, 0.12-0.84).

Investigators documented a total of 1,439 newly diagnosed conventional adenomas and 1,878 serrated polyps among participants younger than 50 years of age who had undergone a lower endoscopy from 1991 to 2011. Higher vitamin D intake was also associated with lower risk in this population. Compared with those who consumed less than 300 IU/day, the HR of any conventional adenoma was 0.71 (95% CI, 0.56-0.89) for those who consumed 600 IU/day or less, and the HR for any serrated polyp was 0.85 (95% CI, 0.70-1.03).

“Our results further support that avoiding low vitamin D status is important in younger adults for health and possibly CRC prevention,” study authors wrote. “If confirmed, our findings could potentially lead to recommendations for higher vitamin D intake as an inexpensive low-risk complement to CRC screening as CRC prevention strategy for adults younger than age 50.”

References

1. Kim H, Lipsyc-Sharf M, Zong X, et al. Total vitamin D intake and risks of early-onset colorectal cancer and precursors. Gastroenterology. Published online July 7, 2021. doi:10.1053/j.gastro.2021.07.002
2. Shining new light on vitamin D and cancer. News release. Harvard University. August 17, 2021. Accessed August 20, 2021. https://bit.ly/3sDBg3s