Medical Oncology

, 36:69 | Cite as

Vitamin D supplementation and colorectal cancer prognosis

  • Yuanliang Yan
  • Zhicheng Gong
  • Zhijie XuEmail author
Letter to the Editor

The study by Ng et al. [1] addresses an issue of major current interest that confirmed a relationship between high-dose vitamin D3 added to standard chemotherapy and increased progression-free survival (PFS) in patients with advanced or metastatic colorectal cancer (CRC). We all agree that such meaningful findings could generally affect the clinical practice in CRC management.

However, several confounding factors in their study should be taken into account discreetly and roundly. (1) The 36-month follow-up might be insufficient. After 7.3 years of median follow-up, Fuchs et al. [2] concluded that higher post-operative serum 25-hydroxyvitamin D concentrations were associated with better survival outcome in CRC patients. (2) The Kaplan–Meier curves had a p value of 0.07, and thus showed no statistical significance of PFS between the different doses of vitamin D3 groups. However, p value very close to the threshold of 0.05 has been identified to be always misunderstood in clinical importance and should be carefully viewed in this trial. (3) The authors found that tumor objective response rate in patients receiving high-dose vitamin D3 (95% CI 45–70%) was a little lower than that among patients receiving standard-dose vitamin D3 (95% CI 50–75%). These unsatisfactory findings might be due to the limited sample size and biased demographics, especially the races. The participants were mainly enrolled from the white Americans (75% and 79% in the two groups, respectively). If the study was performed on the population from different national races, there might have been a greater chance to achieve more significant beneficial outcome. (4) The risk of serious side effects was not fully disclosed upon use of large vitamin D3 supplementation. In fact, the posttreatment withdrawal in high-dose vitamin D3 group (n = 8) was apparently higher than that in standard-dose group (n = 0). (5) Differences in expression of vitamin D receptors or vitamin D-related genetic variation could contribute to the increased risk and poor prognosis of CRC [3]. The variation tendencies of vitamin D-associated biomarkers were not evaluated within these study participants.



This work is supported by National Natural Science Foundation of China (81803035, 81703036, and 81572946).

Compliance with ethical standards

Conflicts of interest

All authors declare no competing interests.


  1. 1.
    Ng K, Nimeiri HS, McCleary NJ, Abrams TA, Yurgelun MB, Cleary JM, et al. Effect of high-dose vs standard-dose vitamin D3 supplementation on progression-free survival among patients with advanced or metastatic colorectal cancer: the SUNSHINE Randomized Clinical Trial. JAMA. 2019;321(14):1370–9. Scholar
  2. 2.
    Fuchs MA, Yuan C, Sato K, Niedzwiecki D, Ye X, Saltz LB, et al. Predicted vitamin D status and colon cancer recurrence and mortality in CALGB 89803 (Alliance). Ann Oncol Off J Eur Soc Med Oncol. 2017;28(6):1359–67. Scholar
  3. 3.
    Bhasin N, Alleyne D, Gray OA, Kupfer SS. Vitamin D regulation of the uridine phosphorylase 1 gene and uridine-induced DNA damage in colon in African Americans and European Americans. Gastroenterology. 2018;155(4):1192–1204.e9. Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pharmacy, National Clinical Research Center for Geriatric Disorders, Xiangya HospitalCentral South UniversityChangshaChina
  2. 2.Department of PathologyXiangya Hospital, Central South UniversityChangshaChina

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