Vitamin D deficiency leads to cancer

Vitamin D3 protects against cancer

background

Epidemiological data, as well as study data, suggest that vitamin D supplementation can reduce the incidence of metastatic cancer and reduce cancer mortality. Laboratory studies and tests on animal models show that vitamin D can inhibit carcinogenesis and slow the progression of a tumor.

It was observed that vitamin D promotes cell differentiation, inhibits the proliferation of cancer cells and has anti-inflammatory, immunomodulatory, proapoptotic and antiangiogenic effects. Vitamin D has also been shown to reduce tumor invasiveness and the tendency to metastasize, leading to decreased cancer mortality. Higher serum 25-hydroxyvitamin D levels in cancer patients at diagnosis have been associated with longer survival.

In the vitamin D and omega-3 study (VITAL), vitamin D did not reduce the incidence of primary cancer or cardiovascular endpoints. However, vitamin D supplementation reduced overall cancer mortality compared to placebo (hazard ratio [HR] 0.83 [95% confidence interval [CI] 0.67-1.02]). Meta-analyzes of studies also showed a reduction in cancer mortality, but not in incidence.

Interestingly, in the exploratory subgroup analyzes of the VITAL study, new cases of cancer were slightly reduced in patients with a normal body mass index (BMI), but not in overweight or obese patients. This suggests that obesity-related factors can weaken the effects of vitamin D supplementation [1, 2].

Goal setting

A research group led by Dr. Paulette Chandler from the Brigham and Women's Hospital at Harvard Medical School in Boston, USA, main author of the current publication [3], investigated the question of whether there is vitamin D in adults without a cancer diagnosis3-Supplementation may reduce the risk of developing advanced cancer (metastatic or fatal) and whether BMI may modify the effect.

methodology

VITAL is a randomized, double-blind, placebo-controlled, 2 × 2 factorial clinical study with vitamin D.3 and marine omega-3 fatty acids for the primary prevention of cancer and cardiovascular diseases. This multicenter clinical study was carried out in the USA. Men aged 50 and over and women aged 55 and over who had no cancer or cardiovascular disease at the start of the study could take part.

The study participants received vitamin D as a dietary supplement3 (Colecalciferol, 2000 IU / day) or marine omega-3 fatty acids (1 g / day) or both active supplements or placebo.
For the present secondary analysis, the primary outcome parameter was a composite incidence of metastatic and fatal invasive cancer. Further analyzes included the investigation of the BMI (<25, 25 to <30 and ≥30) as an effect modifier of the associations observed.

Results

In 1,617 of 25,871 randomized VITAL participants (51% female; mean [SD] age: 67.1 [7.1] years) within a mean intervention period of 5.3 years (range 3.8-6.1 years) diagnosed with invasive cancer. As reported in previous publications [1, 2], no significant differences between the treatment arms were found for cancer incidences.

However, advanced cancer stages (metastatic or fatal) were found in significantly fewer patients in the vitamin D group (226 of 12,927 patients [1.7%]) than in the placebo group 274 of 12,944 patients [2.1%]) ( HR 0.83 [95% CI 0.69-0.99]; P = 0.04).

Stratification according to BMI revealed metastatic or fatal cancer in the vitamin D arm in significantly fewer people with a normal BMI (BMI <25: HR 0.62 [95% CI 0.45-0.86]) than in People who are overweight or obese (BMI 25 to <30: HR 0.89 [95% CI 0.68-1.17]; BMI ≥30: HR 1.05 [95% CI 0.74-1.49 ]) (P = 0.03 for the interaction of the BMI).

Conclusion

In this randomized clinical trial, supplementation with high-dose vitamin D was reduced3 over five years, the incidence of advanced (metastatic or fatal) cancer in the total cohort of adult subjects without cancer at baseline. The greatest risk reduction was observed in subjects of normal weight.
The study is registered on ClinicalTrials.gov under number NCT01169259. The study was supported by various national health institutes. The investigational drugs were provided free of charge by Pharmavite LLC, Pronova BioPharma and BASF. Quest Diagnostics analyzed serum 25-hydroxyvitamin D for free.

  1. Manson et al. (2019) Vitamin D supplements and prevention of cancer and cardiovascular disease. New England Journal of Medicine, DOI: 10.1056 / NEJMoa1809944
  2. Manson et al. (2020) Principal results of the VITamin D and OmegA-3 TriaL (VITAL) and updated meta-analyzes of relevant vitamin D trials. Journal of Steroid Biochemistry and Molecular Biology, DOI: 10.1016 / j.jsbmb.2019.105522
  3. Chandler et al. (2020): Effect of vitamin D3 supplements on development of advanced cancer - a secondary analysis of the VITAL randomized clinical trial. JAMA Network Open, DOI: 10.1001 / jamanetworkopen.2020.25850