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vitamin D - Coggle Diagram

- - - - vitamin D slowed the growth of colorectal cancer in patients with started chemotherapy. [23]
      - vitamin D improves treatment of many types of cancer, by potentiating the anti-tumoral activity of chemotherapeutic agents and enhancing the cytotoxic effect of ionizing irradiation [22]
- - - - higher vitamin D levels are associated with lower risk of incident CRC as well as improved survival in patients with established CRC.
        
        One of the largest observational nested case-control study (520000 participants) concluded that there is a strong inverse association between 25(OH)D concentration and CRC[118]
    - - observational studies have shown low Vitamin D levels being associated with poor outcomes such as low over-all survival [53,62,63], confounding factors such as performance status of the patient were not taken into account (patients with advanced disease, with poor performance status living indoor, leading to low Vitamin D levels).
    - - The predominant evidence from these studies supports an inverse association of vitamin D with adenoma incidence104, CRC incidence, and mortality105, 106. Based on a systematic review, one study suggested that the benefits associated with serum 25(OH)D may require at least 75 nmol/L (30 ng/mL), with optimal levels between 90-100 nmol/L (36–40 ng/mL) for multiple health outcomes including CRC107. Because this level of sufficiency cannot typically be achieved with currently recommended vitamin D intake of 600 and 800 IU/d for younger and older adults108, respectively, some authorities have called for an increase in recommended vitamin D intake to ≥1000 IU/d109, 110.
      - 25575572 IF 22
  - - - Patients were randomized to receive oral supplemental capsules of vitamin D (2000 IU/d; n = 251) or placebo (n = 166) from the first postoperative outpatient visit to until the end of the trial
        
        did not result in significant improvement in relapse-free survival at 5 years
      - conflicting results
        
        one concluded that supplementation with calcium and vitaminD (400IU/d) for 7 years had no effect on the incidence of colorectal cancer in post menopausal women,8
        
        another demonstrated that cancer incidence was lower in postmenopausal women taking calcium plus vitaminD (1100 IU/d) than in those taking placebo.9
        
        no RCT of secondary prevention for relapse or death has been conducted
    - - The Legacy Health system produced by Dr Eric Anderson is being used as a pilot study to test whether there is an association between baseline vitamin D levels, vitamin D supplementation, and survival in patients with stage III colon and stage II/III rectal cancer receiving chemotherapy (NCT02603757). A randomized, multicenter, doubleblinded phase III study (NCT03389659), exploring the effect of vitamin D3 in combination with XELOX/mFOLFOX or XELOX/mFOLFOX as first-line chemotherapy in previously untreated advanced or metastatic CRC (mCRC), is currently in progress.
    - - In contrast with adenoma recurrence RCTs, the Women's Health Initiative (WHI), the largest RCT with CRC incidence as a secondary outcome, did not find any reduction in CRC after a mean of 7 years of supplementation with calcium and vitamin D65
        
        However, several limitations may have contributed to the null findings, including: high calcium intake at baseline, poor compliance, complex factorial design, and insufficient duration of treatment and/or follow-up66-68. In a reanalysis, a 17% reduction of CRC incidence with calcium supplementation was observed among WHI participants not already taking calcium or vitamin D at randomization69. Findings from other smaller trials have been similarly inconclusive70, 71. Furthermore, contrary to prior adenoma RCTs, the initial results of another RCT of calcium and vitamin D supplementation failed to detect a reduction in risk of recurrent adenoma among 2,259 individuals, adding complexity to the calcium-CRC relationship72.
      - compelling data from epidemiologic and experimental studies support the potential chemopreventive effects of vitamin D against CRC development, although the evidence from RCTs is inconclusive. A large ongoing RCT of vitamin D supplementation that includes cancer as a primary outcome, the VITamin D and OmegA-3 TriaL125, will hopefully provide more direct data on this topic. Until then, it would be reasonable to ensure that patients obtain a sufficient level of vitamin D to maintain a plasma level of 25 (OH)D greater than at least 36 ng/mL.
  - - - 26260259 IF 3.8
        
        The SRb assay results indicate that the LoVo cell line is the most sensitive to the vitamin D analogues examined (lowest IC50 values)
        
        moderately differentiated cells (LoVo and HT29 cell lines) are more sensitive to vitamin D analogs compared with poorly differentiated HCT116 cells.
        
        this correlation does not hold for the MTT assay results
        
        the HTC116 cell line was the most resistant.
      - 2557557 IF 22
        
        In mice with colitis, a CRC risk factor, consumption of a high vitamin D diet attenuated inflammation, indicating that vitamin D may have an important role in inflammation-associated carcinogenesis115
    - - 25954093 IF 5.742
        
        Vitamin D has the ability to inhibit cell proliferation and increase apoptosis in vitro.
  - - - Many prospective cohort studies have reported a non–statistically significant lower risk of colorectal cancer with higher prediagnostic concentrations of 25-hydroxyvitamin D (25(OH)D), the accepted measure of vitamin D status (2)
      - individual studies have used different assays and laboratories, and vitamin D concentrations differ noticeably across assay methods
        
        these studies, and the meta analyses that combine them, are unable to explore the vitamin D–colorectal cancer relationship on the same absolute scale
      - individual studies have had limited power to examine associations by sex and other population characteristics
      - The relatively few randomized clinical trials (RCTs) of vitamin D supplementation and colorectal cancer or adenoma have not demonstrated statistically significant effects (5,6)
        
        study size, duration and timing of supplementation, and compliance may have contributed to the null findings (5,7).
        
        the RCTs could not evaluate a wide range of vitamin D exposures.
    - - Despite this compelling epidemiologic evidence and biologic plausibility, the results of vitamin D supplementation have been disappointing in all 65, 71, 122 but one70 RCT that assessed cancer incidence as a secondary outcome. However, similar to calcium RCTs, limitations in study design still leave open the possibility that vitamin D may indeed have a chemopreventive role. A recent systematic review hypothesized that confounding by inflammatory processes involved in both CRC development and 25(OH)D deficiency might account for the inverse association between vitamin D and CRC in observational studies123.
      - However, we recently found that rigorous adjustment for inflammatory markers had little effect on the robust inverse association observed between 25(OH)D and CRC risk, indicating that confounding by inflammation was not a sufficient explanation124.
- - - - They reported an inverse association between geographical latitude (solar radiation), vitamin D status and CRC incidence and mortality in United States[116].
  - - - the risk of colon cancer was estimated to be 70% lower in people with serum 25(OH)D levels of 20ng/mL or more compared with those with levels less than 20ng/mL.3
- - - - exerts its effects through interaction with its cognate intracellular nuclear receptor, the vitamin D receptor (VDR),
- - - - some specific haplotypes are associated with CRC
        
        BsmI (intron 8), poly(A) long (18-22 repeats), and FokI (exon 2), and reported an association of the bLF and BLF haplotypes with the risk of colon cancer
    - - Vitamin D functions by binding to and activating the nuclear VDR. A polymorphism in VDR, BsmI, has been consistently associated with CRC113.
  - - - vitamin D also antagonizes Wnt signaling in colon cancers cells
    - - bet catentin
        
        The active form of vitamin D, 1,25(OH)2D3, promotes binding of β- catenin to the vitamin D receptor and increases expression of E-cadherin, thus decreasing the available β-catenin molecules that can bind to TCF/LEF transcription factors [85].
    - - Vitamin D exerts anti-inflammatory effects through bile acid catabolism, suppression of NFκB and COX2 signaling, and enhanced production of interleukin-10 (IL10).
  - - - vitamin D is able to alter DNA methylation
        
        not yet clear [19]
        
        increase
        
        positively associated with methylation of genomic long interspersed nuclear element-1 (LINE1) in human rectal mucosa [20]
        
        decrease
        
        circulating 25-OH vitamin D was negatively associated with adenomatous polyposis coli (APC) promoter methylation [20]
        
        vitamin D intake was correlated with decreased promoter methylation of dickkopf1 (DKK1) and Wnt5A (both considered Wnt antagonists) in CRC tumors [21]
    - - may influence the expression of crucial genes which encode proteins involved in the metabolism of vitamin D, such as CYp24A1