The effect of vitamin D supplementation on survival in patients with colorectal cancer: systematic review and meta-analysis of randomised controlled trials

Vaughan-Shaw, Peter G; Buijs, Louis F.; Blackmur, James P.; Τheodoratou, Evropi; Zgaga, Lina; Din, Farhat V N; Farrington, Susan M.; Dunlop, Malcolm

doi:10.1038/s41416-020-01060-8

Cited by 78 publications

(53 citation statements)

References 49 publications

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“…In the general population of Denmark (latitude 55–57°N) in 2012–2014, women had higher circulating 25(OH) D than men and were supplement users to a greater extent [ 24 ]. Observational studies and meta-analyses on populations from the wider European territories and in North America, Japan, and Australia have shown that high vitamin D level may lower CRC risk [ 1 , 2 , 25 , 26 ] and improve prognosis [ 3 , 4 , 27 – 30 ]. A prospective study in the United States in patients with metastatic CRC on first-line systemic therapy revealed that those randomized to high-dose vitamin D supplementation had better outcome than the control patient group given a standard vitamin D dose [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

“…Evidence over the past decades supports that vitamin D has a beneficial effect on colorectal cancer (CRC) development and outcome [ 1 – 4 ]. The primary circulating form of vitamin D, 25-hydroxyvitamin D [25(OH) D], is mainly dependent on the exposure to ultraviolet B solar radiation, and levels are therefore depleted during the winter season at high latitudes unless the dietary supplementation is adequate [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

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Sex disparities in vitamin D status and the impact on systemic inflammation and survival in rectal cancer

et al. 2021

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Background We reported previously that rectal cancer patients given curative-intent chemotherapy, radiation, and surgery for non-metastatic disease had enhanced risk of metastatic progression and death if circulating levels of 25-hydroxyvitamin D [25(OH) D] were low. Here we investigated whether the association between the vitamin D status and prognosis pertains to the general, unselected population of rectal cancer patients. Methods Serum 25(OH) D at the time of diagnosis was assessed in 129 patients, enrolled 2013–2017 and representing the entire range of rectal cancer stages, and analyzed with respect to season, sex, systemic inflammation, and survival. Results In the population-based cohort residing at latitude 60°N, 25(OH) D varied according to season in men only, who were overrepresented among the vitamin D-deficient (< 50 nmol/L) patients. Consistent with our previous findings, the individuals presenting with T4 disease had significantly reduced 25(OH) D levels. Low vitamin D was associated with systemic inflammation, albeit with distinct modes of presentation. While men with low vitamin D showed circulating markers typical for the systemic inflammatory response (e.g., elevated erythrocyte sedimentation rate), the corresponding female patients had elevated serum levels of interleukin-6 and the chemokine (C-X-C motif) ligand 7. Despite disparities in vitamin D status and the potential effects on disease attributes, significantly shortened cancer-specific survival was observed in vitamin D-deficient patients irrespective of sex. Conclusion This unselected rectal cancer cohort confirmed the interconnection of low vitamin D, more advanced disease presentation, and poor survival, and further suggested it may be conditional on disparate modes of adverse systemic inflammation in men and women. Trial registration ClinicalTrials.govNCT01816607; registration date: 22 March 2013.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sex disparities in vitamin D status and the impact on systemic inflammation and survival in rectal cancer

et al. 2021

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“…Thus, even more pronounced preventive effects of vitamin D 3 supplementation on cancer progression than reported by the VITAL study might be expected in studies focusing on cancer patients with 25(OH)D levels <20 ng/mL. Vitamin D insufficiency and deficiency are common among cancer patients [ 21 ], and preliminary results of randomized trials of vitamin D 3 supplementation for cancer patients showed encouraging results, although they were mostly underpowered [ 25 , 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

Prevention of Advanced Cancer by Vitamin D3 Supplementation: Interaction by Body Mass Index Revisited

et al. 2021

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Meta-analyses of randomized controlled trials (RCTs) have demonstrated a protective effect of vitamin D3 (cholecalciferol) supplementation against cancer mortality. In the VITAL study, a RCT including 25,871 men ≥ 50 years and women ≥ 55 years, protective effects of vitamin D3 supplementation (2000 IU/day over a median of 5.3 years) with respect to incidence of any cancer and of advanced cancer (metastatic cancer or cancer death) were seen for normal-weight participants but not for overweight or obese participants. We aimed to explore potential reasons for this apparent variation of vitamin D effects by body mass index. We conducted complementary analyses of published data from the VITAL study on the association of body weight with cancer outcomes, stratified by vitamin D3 supplementation. Significantly increased risks of any cancer and of advanced cancer were seen among normal-weight participants compared to obese participants in the control group (relative risk (RR), 1.27; 95% confidence interval (CI), 1.07–1.52, and RR, 1.44; 95% CI, 1.04–1.97, respectively). No such patterns were seen in the intervention group. Among those with incident cancer, vitamin D3 supplementation was associated with a significantly reduced risk of advanced cancer (RR, 0.86; 95% CI, 0.74–0.99). The observed patterns point to pre-diagnostic weight loss of cancer patients and preventive effects of vitamin D3 supplementation from cancer progression as plausible explanations for the body mass index (BMI)—intervention interactions. Further research, including RCTs more comprehensively exploring the potential of adjuvant vitamin D therapy for cancer patients, should be pursued with priority.

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“…Starting from these premises, other studies focused on the potential usefulness of vitamin D supplementation to improve CRC patient management. A systematic review with a meta-analysis of randomized controlled trials by Vaughan-Shaw et al examined the effect of vitamin D supplementation on survival outcomes in patients with CRC, concluding that supplementation imparts a 30% reduction in adverse survival outcomes overall, with a 24% reduction in CRC-specific death and a 33% reduction in disease progression or death [ 164 ]. Overall, vitamin D seems to have a promising role as a prognostic factor for CRC patients’ outcome and an easy element to improve in case of deficiency, being widely available and cheap to apply in large populations at all ages.…”

Section: Micronutrients and Molecular Tuning Of Colorectal Carcinogenesismentioning

confidence: 99%

Heterogeneity of Colorectal Cancer Progression: Molecular Gas and Brakes

Gaiani

Marchesi

Negri

et al. 2021

IJMS

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The review begins with molecular genetics, which hit the field unveiling the involvement of oncogenes and tumor suppressor genes in the pathogenesis of colorectal cancer (CRC) and uncovering genetic predispositions. Then the notion of molecular phenotypes with different clinical behaviors was introduced and translated in the clinical arena, paving the way to next-generation sequencing that captured previously unrecognized heterogeneity. Among other molecular regulators of CRC progression, the extent of host immune response within the tumor micro-environment has a critical position. Translational sciences deeply investigated the field, accelerating the pace toward clinical transition, due to its strong association with outcomes. While the perturbation of gut homeostasis occurring in inflammatory bowel diseases can fuel carcinogenesis, micronutrients like vitamin D and calcium can act as brakes, and we discuss underlying molecular mechanisms. Among the components of gut microbiota, Fusobacterium nucleatum is over-represented in CRC, and may worsen patient outcome. However, any translational knowledge tracing the multifaceted evolution of CRC should be interpreted according to the prognostic and predictive frame of the TNM-staging system in a perspective of clinical actionability. Eventually, we examine challenges and promises of pharmacological interventions aimed to restrain disease progression at different disease stages.

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The effect of vitamin D supplementation on survival in patients with colorectal cancer: systematic review and meta-analysis of randomised controlled trials

Cited by 78 publications

References 49 publications

Sex disparities in vitamin D status and the impact on systemic inflammation and survival in rectal cancer

Sex disparities in vitamin D status and the impact on systemic inflammation and survival in rectal cancer

Prevention of Advanced Cancer by Vitamin D3 Supplementation: Interaction by Body Mass Index Revisited

Heterogeneity of Colorectal Cancer Progression: Molecular Gas and Brakes

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