Vitamin D and Health

Cancers
6.201 Ecological studies have reported an increase in risk of several cancers with increasing latitude
(WHO/IARC, 2008) 64 . Since the intensity of sun exposure decreases with increasing latitude, and on
the basis that sun exposure is a proxy for vitamin D status, it has been suggested that vitamin D
protects against cancer. This is supported by some cell culture studies (Cross et al., 1991; Halline et
al., 1994) which found that 1,25(OH) 2 D inhibited growth of malignant cell culture lines and reduced
tumour development and growth in animal studies (Mokady et al., 2000; Tangpricha et al., 2005).
6.202 IOM Report: The IOM reviewed the evidence on vitamin D and risk of all cancers, breast cancer,
colorectal cancer and prostate cancer.
6.203 For all cancers, the IOM concluded that interpretation of the evidence was limited by the small
number of studies, inconsistent associations and absence of large-scale RCTs. For colorectal cancer, it
was noted that epidemiological studies, overall, reported an inverse association with serum 25(OH)D
concentration but that there was a paucity of randomised intervention studies and those that were
available had not shown a significant benefit. For breast and prostate cancers, the IOM concluded
that prospective studies showed inconsistent associations but RCTs were sparse. It concluded that the
evidence on cancer was considered insufficient to support development of DRIs.
Evidence considered since IOM report (Tables 37-39, Annex 2)
RCTs
6.204 Four RCTs have examined cancer risk in relation to supplemental vitamin D (Trivedi et al., 2003;
Wactawski-Wende et al., 2006; Lappe et al., 2007; Avenell et al., 2012). A meta-analysis (Keum &
Giovannucci, 2014) of these 4 trials (n=45,151; 4333 cases) reported that vitamin D supplementation
(10-27.5 µg/400-1100 IU per day) over 2-7 years had no effect on cancer risk (RR=1.00; 95% CI, 0.94-
1.06; p=0.998) with no evidence of heterogeneity (I 2 =0%).
6.205 A meta-analysis (Sperati et al., 2013) of two of these RCTs (Lappe et al., 2007; Avenell et al., 2012)
reported no effect of vitamin D supplementation (20-27.5 µg/800-1100 IU daily) on risk of breast
cancer (n=5372; RR=1.11; 95% CI, 0.74-1.68).
6.206 The AHRQ update (Newberry et al., 2014) did not identify any new RCTs on the effect of vitamin D
supplementation on risk for total cancer.
Cohort studies
6.207 Numerous prospective cohort studies have considered the relationship between serum 25(OH)D
concentration and cancer risk. Most information is available for colorectal, breast and prostate
cancers. These studies are, however, subject to confounding by behavioural and lifestyle factors that
influence serum 25(OH)D concentrations. McCullough et al. (2010) measured correlates of serum
25(OH)D concentration in a large control population of the ‘Cohort consortium vitamin D pooling
project of rarer cancers’ covering a worldwide geographical area, including men and women from US,
Chinese and Finnish cohorts. Statistically significant positive correlates of serum 25(OH)D
concentration included male sex, vigorous physical activity and alcohol intake. Significant inverse
correlates were BMI, diabetes, sedentary behaviour and smoking.
6.208 The AHRQ update (Newberry et al., 2014) identified 2 cohort studies of the association between
serum 25(OH)D concentration and all-cause cancer. One of these (de Boer et al., 2012) followed white
64 The International Agency for Research on Cancer is the specialised cancer agency of the World Health Organization.
74