Study: Vitamin D Crucial for Colorectal Cancer Prevention and Treatment

Vitamin D in its role in supporting the immune system has been discussed in recent decades. Perhaps it has been more openly discussed in the past few years due to the plandemic.

A Hungarian study by M. Feketeet al titled “Vitamin D and Colorectal Cancer Prevention: Immunological Mechanisms, Inflammatory Pathways, and Nutritional Implications” published on 15 April 2025 is a review study at 31 pages with the main text at 20 pages. The remaining pages are references.

The study reviewed “a total of 50 clinically relevant cohort studies … comprising 1,305,997 participants”. Obviously, studies such as clinical guidelines, opinion pieces and review articles were excluded.

Although it is focused on colorectal cancer (CRC), it does discuss in general terms the biological effects of Vitamin D, the immunological mechanisms and responses. In this sense, it is a little more informative than some papers.

It is impossible to summarize the paper, one might as well read it, but merely a few points are reproduced below. The writers at Opinyuns are not offering medical advice. We are simply reporting in a limited manner on the published material.

The active form of vitamin D, calcitriol, binds to the VDR, a steroid hormone receptor that regulates gene expression. While the VDR is most abundant in the intestines, it plays a regulatory role in various organ systems. Calcitriol exerts a range of biological effects, influencing crucial physiological processes. It regulates calcium and phosphorus metabolism by controlling the intestinal absorption of these minerals, mobilizing calcium from bones, and facilitating renal reabsorption. These actions help maintain proper serum and extracellular calcium and phosphorus concentrations, essential for bone metabolism and other metabolic functions.

Vitamin D also plays an essential role in other areas: it supports communication between nerve cells, regulates blood pressure, improves cholesterol levels in blood, “enhances immune responses and improving the protection of respiratory epithelial cells” and has anti-aging effects.

Key anti-tumor mechanisms of vitamin D in CRC are as follows: ● Inhibition of cancer cell growth: calcitriol induces G1 cell cycle arrest, reducing CRC cell proliferation, and restoring sensitivity to tumor suppressors like TGF-β. ● Regulation of the Wnt/β-Catenin pathway: the Wnt/β-catenin pathway is frequently hyperactivated in CRC. Calcitriol reduces β-catenin activity and increases E-cadherin expression, stabilizing cell–cell adhesion and reducing tumor invasiveness. ● Antiangiogenesis: calcitriol inhibits angiogenesis by downregulating VEGF and NF-κB signaling, limiting the tumor’s blood supply. ● Induction of apoptosis: calcitriol promotes pro-apoptotic proteins (BAX, BAK) while inhibiting anti-apoptotic proteins (BCL-2), driving CRC cell death. ● Anti-inflammatory effects: calcitriol reduces CRC-associated inflammation by inhibiting prostaglandin synthesis, stress-activated kinases, and pro-inflammatory cytokines.

There are multiple ways vitamin D can reduce the risk of CRC.

One of the primary ways vitamin D influences CRC development is by reducing colonic inflammation. The activation of the CYP27B1 enzyme catalyzes the conversion of vitamin D to its active form, which then triggers various anti-inflammatory pathways. These pathways mitigate the inflammatory microenvironment that accelerates CRC progression.

Vitamin D influences the sirtuin family

…particularly Sirtuin 1 (SIRT1), which plays a crucial role in deoxyribonucleic acid (DNA) repair and aging processes. A decrease in SIRT1 activity can inhibit cancer cell proliferation, while the active metabolite of vitamin D, 1,25(OH)2D3, activates SIRT1 and exerts an antiproliferative effect on colorectal cancer cells.

It also impacts gut microbiome

…contributing to intestinal barrier integrity, stem cell regulation, and the control of inflammatory processes. Animal studies suggest that vitamin D deficiency increases CRC risk, while human research indicates that vitamin D supplementation reduces intestinal inflammation and promotes the enrichment of beneficial gut bacteria.

The vitamin D levels vary in each study but higher levels are associated with better outcomes. The below is a ballpark figure.

An Australian cohort study found that lower 25(OH)D levels (<50 nmol/L) were associated with a higher risk of colon and rectal cancer, while higher 25(OH)D levels (≥75 nmol/L) were linked to a lower risk of cardiovascular diseases and certain cancer-related mortalities.

The authors recommend a diet with natural vitamin D such as “such as fatty fish (salmon, mackerel, tuna), egg yolks, and vitamin D-fortified dairy products”. The levels investigated were different in each study and the appropriate intake level depends on the condition of the subject.

Vitamin D supplementation is the most effective method for increasing 25(OH)D concentrations, as it can be carried out year-round and under controlled conditions. Research indicates that a daily dose of 2000 IU (50 μg) is the optimal minimum dose for adults of normal weight, allowing them to reach a 30–40 ng/mL level with minimal safety concerns. This dose can be taken daily, weekly (15,000 IU), or monthly (60,000 IU), with compliance typically being better with weekly or monthly dosing. Low-dose supplementation is also recommended for individuals seeking to reach the optimal level over a longer period, though it may take several months to achieve a steady-state concentration. For this reason, it is recommended to take larger “bolus” doses during the first one to two weeks to reach the optimal vitamin D level more quickly.

In short, vitamin D “plays a crucial role in both CRC prevention and treatment” as it “influences cancer cell proliferation, inflammation, cell death mechanisms, and the activity of the Sirtuin protein family”.

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