Vit D3 and Colorectal Cancer

Dr. Weeks’ Comment: Inexcusably, when patients are referred or self-refer to me from nationally renown cancer  cancer centers like Mass General, Johns Hopkins, MD Anderson etc  over the past 20 years,  the oncologists there NEVER did a 25-OH D3 test.  How many peer-reviewed scientific articles at PubMed teach about the causal relationship between low vitamin D3 and Cancer?  Only  10,369!


Vitamin D Deficiency Elevates Colorectal Cancer Risk

David A. Johnson, MD

November 15, 2018

Hello. I’m Dr David Johnson, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia. Welcome back to another GI Common Concerns.

How many of you talk to your patients about vitamin D as a supplement? My message for you today is that I think we should. I certainly have changed my practice to reflect that.

We traditionally recognize vitamin D as the key vitamin for regulation of bone metabolism and homeostasis, but I want you to think out of the box here. This is incredibly important because vitamin D has a profound effect on the immune system and the intestinal barrier function. We know that vitamin D receptors regulate an active metabolite of vitamin D highly expressed in both the small and large bowel. It’s critical to regulatory actions in the gut, as it relates to proliferation and differentiation, intestinal barrier function, innate immunity, and host response. We know that vitamin D expression declines in particular as it relates to late-stage colon cancer, and it’s absent in colorectal cancer metastasis.[1,2]

Vitamin D affects the microbiome. There’s a mechanistic role in T-cell trafficking and a significant effect as it relates to the immune function. Regarding the potential for promotion of synthesis and the bad things that upregulate cancers and inflammation, we know that vitamin D actually inhibits the response of tumor necrosis factor-alpha. There’s an anti-inflammatory response with cytokine interleukin-10.[1,2]

In mouse models with vitamin D receptor overexpression, you actually can reduce the animal-related colitis.[3] If you knock out that receptor, they get spontaneous enterocolitis. If you see this knockout in humans, they really don’t respond well to any therapy other than stem cell transplant.

Vitamin D Levels and Colorectal Cancer

I wanted to share with you an article[4] that is going to be published in the Journal of National Cancer Institute in 2019, but I think it’s ready for primetime and needs to be understood now. It relates to the risk reduction for vitamin D and potential for vitamin D replacement.

This new study supports the idea that vitamin D deficiency makes a difference. Researchers pooled data from 17 study cohorts (5706 colorectal cancer patients and 7107 controls) to determine colorectal cancer risk at various ranges of vitamin D. They used the traditional measure for vitamin D deficiency of < 30 nmol/L. The threshold for sufficient bone health is around 50 to < 62.5 nmol/L. Vitamin D levels in this range were associated with a risk reduction for colorectal cancer of 19%, while those in the range of 87.5 to < 100 nmol/L were associated with a 27% risk reduction.

The results essentially show that the more vitamin D you get, the better. However, there seemed to be a plateau effect at 100 nmol/L. It didn’t mean that more was better forever; there wasn’t a linear relationship. Nonetheless, it raises the bar for vitamin D supplementation in our patients.

Putting It Into Practice

I’ve also used supplementation in patients with diverticulitis, which we know to occur more frequently in patients with lower vitamin D. When you get into some of the anti-inflammatory effects of vitamin D on proliferation, differentiation, barrier function, and immune response, it makes sense to start looking at this in inflammatory/infectious disease as well.

In summary, vitamin D is really essential in homeostasis and signaling. It affects the microbiome and has a direct effect on host intestinal inflammation. We do know that this certainly plays out in inflammatory bowel disease.[5]

It remains to be determined whether supplementation makes a big difference as far as clinical outcomes. However, to me, there’s clear evidence that it modulates inflammation, maintains epithelial integrity, and reduces intestinal proliferation. In my practice, it’s ready for primetime. I think it should be in yours as well.

Start to look at supplementation; perhaps measure the patient’s vitamin D levels, and monitor and target it in patients—particularly those at risk. I do think this represents translational, bench-to-bedside research that is ready for primetime now.

I hope this leads you in the next discussion with your patients about ways to use vitamin D beyond bone homeostasis.


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