Vitamin D Status May Play a Pivotal Role in Colon Cancer Prevention

Nancy A. Melville and Amy Reyes

October 28, 2021

In ongoing efforts to investigate a link between vitamin D and colorectal cancer, new research shows that women who consume higher levels of vitamin D – particularly from dietary sources – have a reduced risk of developing early-onset colorectal cancer, compared with those who have lower levels.

This is according to an observational study published in the journal Gastroenterology. The study included 94,205 women (aged 25-42 years) who were followed between 1991 and 2015 during which 111 incident cases of early-onset colorectal cancer were diagnosed. Among 29,186 women who had at least one lower endoscopy from 1991 to 2011, 1,439 newly diagnosed conventional adenomas and 1,878 serrated polyps were found.

Women who consumed the highest average levels of total vitamin D of 450 IU per day, compared with those consuming less than 300 IU per day, showed a significantly reduced risk of early-onset colorectal cancer. Consuming 400 IU each day was associated with a 54% reduced risk of early-onset colorectal cancer.

"If confirmed, our findings could potentially lead to recommendations for higher vitamin D intake as an inexpensive low-risk complement to colorectal cancer screening as a prevention strategy for adults younger than age 50," wrote the study authors, led by Edward L. Giovannucci, MD, ScD, of the Harvard School of Public Health, Boston.

Associations between vitamin D levels and colorectal cancer have been documented in review articles over the years. The link is the subject of 10 recently completed or ongoing clinical trials. Few studies have focused on early colorectal cancer and vitamin D intake. Unlike advanced colorectal cancer, the early-onset form of the disease is not as strongly associated with the traditional risk factors of a family history of colorectal cancer and it is therefore believed to be more strongly linked to other factors, such as lifestyle and diet – including vitamin D supplementation.

The Evidence Is In, but It's Incomplete

In addition to the new study in Gastroenterology, other observational studies, as well as laboratory and animal studies, suggest that vitamin D plays a role in inhibiting carcinogenesis. Vitamin D, researchers theorize, contains anti-inflammatory, immunomodulatory, and tumor angiogenesis properties that can slow the growth of tumors, but the evidence is mixed.

A meta-analysis of 137,567 patients published in 2013 in Preventive Medicine found an inverse association between 25-hydroxyvitamin D (25[OH]D) and total cancer mortality in women, but not among men. Three meta-analyses published in 2014 and 2019 found that vitamin D supplementation does not affect cancer incidence but does significantly reduce total cancer mortality rates by 12%-13%.

In 2019, researchers led by Marjorie McCullough, ScD, RD, senior scientific director of epidemiology research for the American Cancer Society, described a causal relationship between circulating vitamin D and colorectal cancer risk among 17 cohorts from a pooled analysis. "Our study suggests that optimal circulating 25(OH)D concentrations for colorectal cancer risk reduction are 75-100 nmol/L, [which is] higher than current Institute of Medicine recommendations for bone health," she and colleagues wrote. Their findings were published in the Journal of the National Cancer Institute.

The Vitamin D and Omega-3 Trial (VITAL) published in 2019 in the New England Journal of Medicine, showed no significant effect of vitamin D3 supplementation of 2,000 IU/day in lowering the risk of invasive cancer or cardiovascular events.

Despite the mixed results, studies offer valuable insights into cancer risks, said Scott Kopetz, MD, PhD, codirector of the colorectal cancer moon shot research program at the University of Texas MD Anderson Cancer Center, Houston.

The Gastroenterology study is noteworthy because it focuses on early-onset colorectal cancer, he said.

"[The authors] demonstrate for the first time that there is an association of vitamin D intake with early-onset colorectal incidence, especially in the left side of the colon and rectum where the increase in early onset colorectal cancer manifests," Kopetz said. "The analysis suggests that it may require long-term vitamin D intake to derive the benefit, which may explain why some shorter-term randomized studies failed to demonstrate."

In animal models, vitamin D3 is "estimated to lower the incidence of colorectal cancer by 50%," according to Lidija Klampfer, PhD, formerly a molecular biologist and senior research scientist with the Southern Research Institute, Birmingham, Ala.

Klampfer, a founding partner of ProteXase Therapeutics, is the author of an article on vitamin D and colon cancer published in 2014 in the World Journal of Gastrointestinal Oncology.

"The levels of vitamin D3 appear to be an essential determinant for the development and progression of colon cancer and supplementation with vitamin D3 is effective in suppressing intestinal tumorigenesis in animal models," she wrote. "Studies have shown that 1,25 dihydroxyvitamin D3 can inhibit tumor-promoting inflammation leading to the development and progression of colon cancer."

The Hazards of a Vitamin D Deficiency

A severe vitamin D deficiency is associated with compromised bone and muscle health, calcium absorption, immunity, heart function and it can affect mood. Other studies have linked vitamin D deficiency to colorectal cancer, blood cancers, and bowel cancer.

Serum 25(OH)D is the primary circulating form of vitamin D and is considered the best marker for assessing vitamin D status, says Karin Amrein, MD, MSc, an endocrinologist with the Medical University of Graz (Austria). She was the lead author of a review on vitamin D deficiency published in January 2020 in the European Journal of Clinical Nutrition.

The Global Consensus Recommendations define vitamin D insufficiency as 12-20 ng/mL (30-50 nmol/L) and a deficiency as a serum 25OHD concentration less than 12 ng/mL (30 nmol/L). A deficiency in adults is usually treated with 50,000 IU of vitamin D2 or D3 once weekly for 8 weeks followed by maintenance dosages of cholecalciferol (vitamin D3) at 800-1,000 IU daily from dietary and supplemental sources.

Screening is recommended for individuals who exhibit symptoms and conditions associated with a vitamin D deficiency, but there is little agreement on recommended serum levels because every individual is different, according to the U.S. Preventive Services Task Force which updated its vitamin D recommendations in April for the first time in 7 years.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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