Vitamin D as an Anti Colorectal Cancer Agent in 2024 – a Review of the Evidence

Vitamin D has a protective effect against colorectal cancer, but it is patient and population dependent.

According to the WHO, colorectal cancer (CRC) is the second biggest cause of cancer-related deaths worldwide.¹ In 2020, there were 1.9 million new cases, and experts predict that this number will grow significantly in the coming years. Alongside this, vitamin D deficiency is also a global issue, affecting roughly a billion people.^2,3 Vitamin D is an essential nutrient made by our bodies when sunlight touches our skin. We can also get it from food, including milk, fish, egg yolks, and beef.⁴ Vitamin D supplements can be helpful, but because it’s fat soluble, your body will find it easier to absorb from food.

Colorectal cancer has risk factors that are both controllable and uncontrollable. Some of the controllable risk factors are related to the lifestyle of an individual, such as dietary intake, smoking, and drinking alcohol.¹ So where does vitamin D fit into this? Scientists speculate that higher incidence rates of colorectal cancer in areas with low sunlight exposure might be attributable to lower levels of vitamin D. 

On the journey to understanding cancer, experts noticed a curious trend: certain regions of the world basking in less sunlight reported more cases of colorectal cancer. Could a lack of sunshine, and thus a deficiency in vitamin D, be fueling higher cancer rates? This question fired up experts, and they dove deeper into the potential link between vitamin D and colorectal cancer.

What evidence do we have?

In the quest to unravel the mysteries of colorectal cancer, scientists have published many studies exploring the role of vitamin D, and the results are thought-provoking.

A 2011 study by Dr. Kimmie Ng and others of the Dana-Farber institute, looked at 515 people with stage 4 colorectal cancer and found that a staggering 82% had low levels of circulating Vitamin D.⁵  

Another big study, led by Dr. Marjorie McCullough from the American Cancer Society in 2018, pooled data from different international populations and looked at 5,706 people with colorectal cancer and 7,107 without it.⁶ They established that people with low levels of vitamin D had a 31% higher risk of getting colorectal cancer. Having higher vitamin D levels in the body was related to substantially lowered colorectal cancer risk, particularly in women. 

This study uncovered another important point in parallel: could dosage be important? The researchers suggest the vitamin’s cancer-fighting powers against colorectal cancer might depend on how much you take. It turns out having  higher levels of vitamin D in your blood (75-100 nmol/L) might be the best way to reduce your risk of colorectal cancer. This recommended level is higher than what’s currently suggested for just keeping bones healthy.

In 2019, a noteworthy study by Dr. Chen Yuan of the Dana-Farber Cancer Institute and Harvard Medical School, involving 1,041 individuals battling advanced colorectal cancer, added another striking detail: nearly two-thirds of the patients were lacking in vitamin D.⁷ By collecting blood samples they identified that 63% of patients were vitamin D deficient and 31% were vitamin D insufficient (towards the lower range of acceptable vitamin levels). This could be due to the burden cancer presents on the body, inadequate nutrition, or limited physical activity from illness. Intriguingly, this research also highlighted that higher vitamin D levels related to longer survival times among the patients, suggesting a potential ally in the fight against this formidable cancer.

In an interesting twist, the VITAL study, a large and on-going investigation in the USA, found that taking vitamin D supplements did not affect the chances of getting colorectal cancer, among others, for the population as a whole, but it hinted at a positive effect on survival rates.⁸ This study tracked 25,871 people, without cancer at the start, over five years, splitting them into groups where 12,927 took vitamin D and 12,944 took a placebo. While they didn’t see a significant difference in colorectal, prostate, or breast cancer rates between the two groups, a closer look revealed a 17% decrease in overall cancer mortality and a 25% reduction in all-cancer risk for African American populations.

Where does the answer lie?

A second, deeper analysis of the VITAL study, showed that vitamin D supplements did affect certain people.⁹ Of those taking vitamin D, there were 17% fewer cases of people with advanced metastatic cancers, than those taking the placebo. The effect was strongest (38% reduction in cancer risk) in leaner individuals with a body mass index under 25. This could be because conditions such as obesity present health issues that affect how well vitamin D works. This adds to the idea that the vitamin has an impact, but it might not be a one-size-fits-all solution.

Scientists have since started digging deeper into whether genetics has any relationship to vitamin D and colorectal cancer.

Dr. Linda M. Dong, from the Fred Hutchinson Cancer Research Center, and others investigated whether certain genes in the vitamin D pathway, like those that activate (CYP27B1) and deactivate (CYP24A1) vitamin D, have any connection to colon cancer risk.¹⁰ They collected blood samples and in-depth interviews (about diet and lifestyle) from people in the Kaiser Permanente Medical Care Program of Northern California, an eight-county area in Utah, and the metropolitan Twin Cities area of Minnesota. They selected 1,600 people diagnosed with colorectal cancer and 1,949 without. By looking at differences in vitamin D-related genes between people, they found that those with a rare version of CYP27B1 (IVS4-66T>G) had a 17% less risk of developing colon cancer. 

By further studying genetic differences, along with other aspects of vitamin D’s complex relationship with cancer, researchers hope to unlock why some benefit more from vitamin D and develop personalized treatments in fighting off colorectal cancer. 

References

1. Colorectal cancer (no date) World Health Organization. Available at: https://www.who.int/news-room/fact-sheets/detail/colorectal-cancer#:~:text=Colon%20cancer%20is%20the%20second,estimated%20to%20have%20occurred%20worldwide. (Accessed: 26 April 2024). 
2. Cui, A. et al. (2023) ‘Global and regional prevalence of vitamin D deficiency in population-based studies from 2000 to 2022: A pooled analysis of 7.9 million participants’, Frontiers in Nutrition, 10. doi:10.3389/fnut.2023.1070808. 
3. Siddiqee, M.H. et al. (2021) ‘High prevalence of vitamin D deficiency among the South Asian adults: A systematic review and meta-analysis’, BMC Public Health [Preprint]. doi:10.21203/rs.3.rs-328883/v1. 
4. Vitamin D (no date) NIH Office of Dietary Supplements. Available at: https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/ (Accessed: 26 April 2024). 
5. Ng, K. et al. (2011) ‘Vitamin D status in patients with stage IV colorectal cancer: Findings from intergroup trial N9741’, Journal of Clinical Oncology, 29(12), pp. 1599–1606. doi:10.1200/jco.2010.31.7255. 
6. McCullough, M.L. et al. (2018) ‘Circulating vitamin D and colorectal cancer risk: An international pooling project of 17 cohorts’, JNCI: Journal of the National Cancer Institute, 111(2), pp. 158–169. doi:10.1093/jnci/djy087. 
7. Yuan, C. et al. (2019) ‘Plasma 25-hydroxyvitamin D levels and survival in patients with advanced or metastatic colorectal cancer: Findings from CALGB/SWOG 80405 (alliance)’, Clinical Cancer Research, 25(24), pp. 7497–7505. doi:10.1158/1078-0432.ccr-19-0877. 
8. VITAL the vitamin D AND omega-3 trial (VITAL) (no date) Findings about the vital study. Available at: https://www.vitalstudy.org/findings.html (Accessed: 26 April 2024). 
9. Chandler, P.D. et al. (2020) ‘Effect of Vitamin D3 Supplements on Development of Advanced Cancer’, JAMA Network Open, 3(11). doi:10.1001/jamanetworkopen.2020.25850. 
10. Dong, L.M. et al. (2009) ‘Vitamin D Related Genes, CYP24A and CYP27b1, and Colon Cancer Risk’, Cancer Epidemiology, Biomarkers & Prevention, 18(9), pp. 2540–2548. doi:10.1158/1055-9965.epi-09-0228.