%0 Generic
%A Gwenzi, Tafirenyika
%C Heidelberg
%D 2025
%F heidok:36945
%R 10.11588/heidok.00036945
%T The Potential of Vitamin D Supplementation to Enhance Prognosis of Colorectal Cancer Patients: Role of Vitamin D on Inflammatory Modulation
%U https://archiv.ub.uni-heidelberg.de/volltextserver/36945/
%X Low vitamin D status, measured by serum 25-hydroxyvitamin D [25(OH)D], is common in the post-operative period among CRC patients and is associated with poor long-term prognosis. Moreover, elevated post-operative systemic inflammation is strongly linked to long term adverse outcomes in CRC patients. Pre-clinical and to some extent clinical evidence suggest that calcitriol, the most active form of vitamin D, can modulate immune-inflammatory response. I explored the potential role of vitamin D supplementation (VIDS) in modulating inflammatory response towards improving the prognosis of CRC patients undergoing surgery.  I assessed the prognostic value of post-operative vitamin D status on long-term CRC survival outcomes and examined the role of the vitamin D receptor Cdx2 genotype in a cohort of 2819 CRC patients. Patients with deficient vitamin D status [25(OH)D < 30nmol/L] had significantly shorter survival than those with insufficient or sufficient status [25(OH)D ≥ 30nmol/L]. These associations were particularly evident in patients with the GG genotype of Cdx2, but not in those with the AA/AG genotype. These results suggest that post-operative vitamin D status is a potentially modifiable prognostic factor among CRC patients, especially for carriers of the GG Cdx2 genotype. Future randomized clinical trials (RCTs) should assess the efficacy of tailored VIDS to improve vitamin D status as well as clinical outcomes among CRC patients with low 25(OH)D. Such interventions should also evaluate the efficacy of VIDS among patient subgroups by vitamin D Cdx2 genotype.  In a follow-up project, I conducted a meta-analysis of RCTs involving 592 patients with cancer or precancerous lesions to evaluate the effects of VIDS on systemic inflammatory biomarkers. The results showed a significant reduction in serum tumor necrosis factor-alpha levels. VIDS also showed potentially large effects on reducing serum interleukin-6 (IL-6) and small effects on reducing C-reactive protein levels, although these were not statistically significant. Despite the limited number of small and variable-quality studies, the results support the hypothesis that VIDS may provide anti-inflammatory benefits to patients with cancer or precancerous lesions. Further high-quality RCTs are needed, with larger patient numbers and tailored VIDS dosage regimens over extended intervention periods. The design of such future studies should also take into account factors that determine VIDS efficacy, such as baseline vitamin D status and potential interactions with genetic and clinical factors.  Finally, I assessed the effects of personalized VIDS on post-operative systemic inflammatory biomarkers in CRC patients with low vitamin D status in a RCT. In 126 CRC patients with serum 25(OH)D levels <60 nmol/L, an initial personalized loading dose, followed by 2000 IU of VIDS daily for 12 weeks showed significant increases in serum 25(OH)D and substantial decreases in serum IL-6 levels compared to the placebo group. Although reductions in interferon-gamma and matrix metalloproteinase-1 were observed, they were not statistically significant. Additional exploratory analyses suggested that VIDS might lower serum levels of pro-inflammatory biomarkers CUB domain-containing protein 1, C-X-C motif chemokine 11, and C-X-C motif chemokine 6, warranting further investigation.  Overall, personalized VIDS can correct vitamin D deficiency and attenuate pro-inflammatory responses in CRC patients with low serum 25(OH)D levels. Given the high prevalence of vitamin D inadequacy among operable CRC patients and its association with poor clinical outcomes, routine clinical screening for vitamin D inadequacy and personalized VIDS may be a promising approach to improve patient outcomes. Besides bone and muscle health, VIDS can provide additional benefits as a supportive anti-inflammatory therapy for CRC patients undergoing surgery. Ultimately, personalized VIDS could enhance long-term prognosis and quality of life, offering a cost-effective, safe, and widely available option. In addition, this dissertation highlights the connection between vitamin D, systemic inflammation, and CRC prognosis, paving the way for possible new therapeutic and preventive strategies to improve patient prognosis.