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Association between serum 25-hydroxyvitamin D concentration and the risk of colorectal cancer: A cross-sectional study

Published on Friday, 27 June 2025

Abstract

Background: The role of vitamin D in the prevention of colorectal cancer (CRC) has been the focus of research, but the results of relevant studies are not entirely consistent. While most studies indicate that vitamin D has a protective effect against CRC, there are also research reports stating that at high serum levels, there is no significant association between vitamin D and CRC, or even an increased risk. Additionally, there are still differences in the recommended serum 25-hydroxyvitamin D [25(OH)D] concentrations among various guidelines or committees. This study examined the association between serum 25-hydroxyvitamin D concentrations and the risk of CRC in US adults.

Methods: This study included 43,678 adult participants from the National Health and Nutrition Examination Survey (NHANES) 2001-2018, and logistic regression modelling was used to examine the association between serum 25(OH)D concentrations and the risk of CRC. We grouped participants according to the classification criteria of the various guidelines available for vitamin D, and controlled for confounding using a multi-model strategy, adjusting for key covariates such as gender, age, race, education level, marital status, family income to poverty ratio (PIR), body mass index (BMI), smoking habits, drinking habits, diabetes, hypertension, dyslipidemia, calcium intake, and total folate intake. We also performed trend tests to evaluate the linear relationship between serum 25(OH)D concentrations and CRC risk, used restricted cubic spline (RCS) plots to assess the dose-response relationship, and conducted further subgroup analyses with interaction tests to examine potential variations in the association across different population groups. We focused on the association between serum 25(OH)D concentration ≤ 75 nmol/L and CRC, again using multivariable logistic regression with a multi-model strategy and RCS plots.

Results: A total of 43,382 participants without CRC and 296 participants with CRC were included in this study. In the fully adjusted model, participants with serum 25(OH)D < 50 nmol/L had more than twice the risk of developing CRC compared to those with levels of 50- < 75 nmol/L ( <30 nmol/L: Odds Ratio [OR] = 2.038, 95% Confidence Interval [CI]: 1.011-4.109; 30- < 50 nmol/L: OR = 2.090, 95% CI: 1.361-3.211). The negative correlation between serum 25(OH)D concentration and the risk of CRC was significant when serum 25(OH)D concentration was ≤ 75 nmol/L (P < 0.001). Each 1 nmol/L increase in serum 25(OH)D concentration was associated with an approximately 2.3% reduction in the risk of CRC (95% CI: 0.964-0.990).

Conclusions: Our findings indicate a strong inverse association between serum 25(OH)D concentrations and the risk of CRC, particularly when levels are ≤75 nmol/L. Maintaining serum 25(OH)D above 75 nmol/L is associated with a lower CRC risk and may serve as a cost-effective preventive strategy. Public health measures, including routine vitamin D screening in high-risk populations and targeted supplementation, could further support CRC prevention efforts.

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About this publication.

- The Di Bella Method (A Fixed Part - Dihydrotachysterol, Alfacalcidol, synthetic Vitamin D3);

- Vitamin D (analogues and/or derivatives) and cancer - In vitro, review and in vivo publications;

- The Di Bella Method (A Fixed Part - Calcium, 2 grams per day, orally);

- The Di Bella Method (A Variable Part - Omega 3 Essential/Unsaturated Fatty Acids. From 1.5 grams up to 3.0 grams per day orally);

The Di Bella's Method: Use of Vitamin D analogues and/or derivatives - together with others chemical compounds - in several Oncological Pathologies:

- A retrospective observational clinical study of triple negative breast cancer cases treated with Di Bella Method: A preliminary data;

- The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma;

- A retrospective observational study on cases of anaplastic brain tumors treated with the Di Bella Method: A rationale and effectiveness;

- Recurrent Glioblastoma Multiforme (grade IV – WHO 2007): a case of complete objective response achieved by means of the concomitant administration of Somatostatin and Octreotide – Retinoids – Vitamin E – Vitamin D3 – Vitamin C – Melatonin – D2 R agonists (Di Bella Method – DBM) associated with Temozolomide;

- The Di Bella Method DBM improved survival objective response and performance status in a retrospective observational clinical study on 23 tumours of the head and neck;

- Chronic Lymphocytic Leukemia: Long-Lasting Remission with Combination of Cyclophosphamide, Somatostatin, Bromocriptine, Retinoids, Melatonin, and ACTH;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in advanced non-small-cell lung cancer patients with low performance status;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in chemotherapy-pretreated patients with advanced lung adenocarcinoma and low performance status;