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Archived Comments for: The effect of pre-diagnostic vitamin D supplementation on cancer survival in women: a cohort study within the UK Clinical Practice Research Datalink

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  1. Pre-diagnostic prescription vitamin D supplementation is not a good indicator of the effect of vitamin D on cancer survival.

    William B. Grant, Sunlight, Nutrition, and Health Research Center

    30 October 2015

    The paper by Jeffreys and colleagues reports that pre-diagnostic prescription vitamin D supplementation is not related to cancer survival among UK women [1].  They furthermore state "Previous observational findings of beneficial effects of vitamin D supplementation on cancer survival my be confounded."

    Unfortunately, this is a flawed study, and the review of the related peer-reviewed journal literature is incomplete.

    The major flaw number two was assuming that those supplemented with vitamin D would have higher 25-hydroxyvitamin D [25(OH)D] concentrations at the time of cancer diagnosis.  No information was provided on why those supplemented were supplemented or what their 25(OH)D concentration was at any time.  Most likely they were diagnosed with some vitamin D deficiency disease such as osteoporosis, so had low 25(OH)D concentrations at the time of the prescriptions.  The residence time of 25(OH)D is a few weeks, so 25(OH)D concentrations were not necessarily high at the time of cancer diagnosis.

    A minor flaw is that what type and how much vitamin D was prescribed was not discussed.  Vitamin D2 is much less effective than vitamin D3.  As shown in Figure 6 in a paper by Chowdhury et al. [2], the relative risk for all-cause mortality rate for trials using vitamin D3 was 0.89 (95% confidence interval, 0.80-0.99) while that for vitamin D2 was 1.04 (0.97-1.11).

    Regarding the journal literature, a number of relevant papers were overlooked.  For example, a nine-year follow-up study in Norway found "Higher circulating serum levels of 25-OHD were positively associated with the survival for cancers of the breast, colon, lung and lymphoma."  [3].  A review of cancer survival disparities between black and white Americans found that the disparities were consistent with the fact that blacks have mean 25(OH)D concentrations about 40% lower that white Americans [4].

    The mechanisms whereby vitamin D reduces risk of cancer are well known [5].  The 25(OH)D concentration-cancer incidence relation appears to be robust for breast cancer based on 11 case-control studies from seven countries [6].  As noted in a letter to the editor in BMJ, the effect of vitamin D on cancer survival appears to be stronger than its effect on cancer incidence [7].

    Thus, the conclusions of Ref. 1 should be viewed skeptically.  

    In addition, the results of a related paper by the same authors should also be questioned.  They reported "We found little evidence that vitamin D (largely with calcium) supplementation is associated with decreased breast, lung, ovarian, and uterine cancer risk." [8].  The abstract does not provide any information on 25(OH)D concentration or the amount of vitamin D supplementation.  Their results contrast with a more careful analysis of the Women's Health Initiative (WHI) in the U.S.:  "In the WHI CaD [400 IU/d vitamin D3 +1500 mg/c calcium], interactions between the use of either personal calcium or vitamin D supplements and CaD were found for total, breast and colorectal cancers but not for fracture or mortality.  In 15,646 women (43%) who were not taking personal calcium or vitamin D supplements at randomization, CaD significantly decreased the risk of total, breast, and invasive breast cancers by 14-20% and nonsignificantly reduced the risk of colorectal cancer by 17.  In women taking personal calcium or vitamin D supplements, CaD did not alter cancer risk (HR: 1.06-1.26)." [9]


    1. Jeffreys M, Redaniel MT, Martin RM.  The effect of pre-diagnostic vitamin D supplementation on cancer survival in women: A cohort study with the UK Clinical Practice Research Datalink.  BMC Cancer.  2015;15(1):670.
    2. Chowdhury R, Kunutsor S, Vitezova A, Oliver-Williams C, Chowdhury S, Kiefte-de-Jong JC, et al.  Vitamin D and risk of cause specific death: Systematic review and meta-analysis of observational cohort and randomised intervention studies.  BMJ. 2014;348:g1903.
    3. Tretli S, Schwartz GG, Torjesen PA, Robsahm TE.  Serum levels of 25-hydroxyvitamin D and survival in Norwegian patients with cancer of breast, colon, lung, and lymphoma: A population-based study.  Cancer Causes Control.  2012;23(2):363-70.
    4. Grant WB, Peiris AN.  Differences in vitamin D status may account for unexplained disparities in cancer survival rates between African and White Americans.  Dermatoendocrinol. 2012;4(2):85-94.
    5. Moukayed M, Grant WB.  Molecular link between vitamin D and cancer prevention.  Nutrients.  2013;5(10):3993-4023.
    6. Grant WB. 25-Hydroxyvitamin D and breast cancer, colorectal cancer, and colorectal adenomas: case-control versus nested case-control studies, Anticnacer Res. 2015;35(2):1153-60.
    7. Grant WB, Garland CF.  Vitamin D has a greater impact on cancer mortality rates than cancer incidence rates.  BMJ 2014;348:g2862.
    8. Redaniel MT, Gardner MP, Martin RM, Jeffreys M.  The association of vitamin D supplementation with the risk of cancer in postmenopausal women.  Cancer Causes Control. 2014;25(2):267-71.
    9. Bolland MJ, Grey A, Gamble GD, Reid IR.  Calcium and vitamin D supplements and health outcomes: A reanalysis of the Women's Health Initiative (WHI) limited-access data set.  Am J Clin Nutr. 2011;94(4):1144-9


    Competing interests

    I receive funding from Bio-Tech Pharmacal, Inc. (Fayetteville, AR) and the Vitamin D Society (Woodstock, ON, Canada) and have received funding from the Vitamin D Council (San Luis Obispo, CA).