Vitamin D supplementation and digestive tract cancers

Vitamin D supplementation and cancer

• in the Vitamin D and Omega-3 Trial (VITAL) study, 2000 IU of vitamin D3 administered daily
  • study authors concluded:
    • daily high dose vitamin D supplementation for 5 years among initially healthy adults did not reduce incidence of cancer or major cardiovascular events
      
      
• a meta-analysis (2) of randomized clinical trials (RCTs) investigated vitamin D3 supplementation in the general population
  • study authors concluded that:
    • vitamin D3 did not reduce cancer mortality in the main meta-analysis of all RCTs because the observed risk reduction by 6% was not statistically significant
    • however, a subgroup analysis revealed that vitamin D3 administered daily, in contrast to bolus supplementation, reduced cancer mortality by 12%
      
      
• vitamin D supplementation and digestive tract cancers
  • in a post hoc analysis of a randomized clinical trial including 392 patients with digestive tract cancer, 5-year relapse-free survival was significantly higher in the vitamin D group (80.9%) than the placebo group (30.6%) among patients in the p53-immunoreactive subgroup but not in the non-p53-immunoreactive subgroup (3)
    • TP53 gene produces the protein p53 - suppresses cancer by controlling cell division, DNA repair, and apoptosis, and has been called “the guardian of the genome" (4)
    • vitamin D3, through its active form, 1,25-dihydroxyvitamin D3, or 1,25(OH)2D3, binds the VDR (vitamin D receptor) to regulate cellular proliferation, differentiation, apoptosis, and angiogenesis, all related to its potential anticancer activities
      • p53 mutations result in overproduction of mutant p53 (mutp53)
        • mutp53 binds to the promoter region of the VDR responsive elements
          • interaction is thought to elicit an antiapoptotic state and reduce the 1,25(OH)2D3-VDR’s ability to upregulate expression of proapoptotic genes
  • study authors state that findings suggest that vitamin D supplementation may reduce the risk of relapse or death in this subgroup of patient
  • a review notes (4):
    • patients who had detectable serum anti-p53 antibody and received 2000 IU daily had a significant, more than 2.5-fold improvement in relapse or death compared with the placebo group that had detectable p53 immunoreactivity
    • observed 27% absolute risk reduction translates to a number needed to treat of 4
    • in those patients who had no p53 immunoreactivity, 2000 IU of vitamin D3 daily provided insignificant benefit for 5-year relapse-free survival.

Notes:

• beneficial effects of vitamin D have been reported for cancers at various sites, and p53 oncosuppressor is the most frequently mutated gene in approximately half of cancers and relatively common across cancers at all primary sites (3)
  • findings suggest that p53 and its related molecules may be plausible targets of vitamin D's anticancer effect

Reference:

• Manson JE et al. VITAL Research Group.Vitamin D supplements and prevention of cancer and cardiovascular disease. NJEM 2019;380(1):33-44
• Kuznia et al.Efficacy of vitamin D3 supplementation on cancer mortality: systematic review and individual patient data meta-analysis of randomised controlled trials. Ageing Res Rev.2023;87:101923
• Kanno K, Akutsu T, Ohdaira H, Suzuki Y, Urashima M. Effect of Vitamin D Supplements on Relapse or Death in a p53-Immunoreactive Subgroup With Digestive Tract Cancer: Post Hoc Analysis of the AMATERASU Randomized Clinical Trial. JAMA Netw Open. 2023;6(8):e2328886. doi:10.1001/jamanetworkopen.2023.28886
• Holick MF. The Death D-Fying Vitamin D3 for Digestive Tract Cancers—The p53 Antibody Connection. JAMA Netw Open. 2023;6(8):e2328883. doi:10.1001/jamanetworkopen.2023.28883