Vitamin D and Health

serum 25(OH)D concentration increased. However, 3 of the studies (Visser et al., 2006; Jia et al.,
2007; Melamed et al., 2008) suggested a U-shaped dose-response relationship, with a slight increase
in all-cause mortality at the highest serum 25(OH)D concentrations. Sambrook et al. (2004, 2006)
found no relationship between serum 25(OH)D concentration and mortality risk. Semba et al. (2009)
did not observe a U-shaped relationship but median serum 25(OH)D concentration in the highest
exposure category was 64 nmol/L.
7.27 A meta-analysis of 14 prospective cohort studies (Zittermann et al., 2012) 77 reported a summary RR
for mortality of 0.71 (95% CI, 0.50-0.91) for serum 25(OH)D concentration ≥ 75 vs < 50 nmol/L. In the
parametric model, the estimated summary RRs (95% CI) for mortality were 0.86 (0.82-0.91), 0.77
(0.70-0.84), and 0.69 (0.60-0.78) for individuals with an increase in serum 25(OH)D concentration of
12.5, 25 and 50 nmol/L respectively, from a median reference category of 27.5 nmol/L. There was no
significant decrease in mortality risk when serum 25(OH)D concentrations were 87.5 nmol/L above the
reference category.
Pregnancy and lactation
7.28 Data on adverse effects of vitamin D intakes during pregnancy or lactation are lacking. No adverse
effects were observed in 2 studies (Wagner et al., 2006; Hollis et al., 2011) which supplemented
pregnant women with vitamin D doses ≥ 100 μg/d (4000 IU).
Infants and children
7.29 A disorder termed idiopathic infantile hypercalcaemia (IIH) was first recognised in the 1950s when a
small number of infants presented with failure to thrive, vomiting, dehydration, fever and
nephrocalcinosis (Schlingmann et al., 2011). The outbreak was attributed to increased doses of
vitamin D (up to 100 μg/4000 IU per day) from infant formula and fortified milk. Fortification levels of
vitamin D in cod liver oil concentrate, dried milk powder, infant cereals and evaporated milk products
was subsequently reduced. Vitamin D intakes of infants in the 1960s (6.25-30 μg/250-1200 IU per
day) was found to be substantially lower than in the 1950s (100 μg/4000 IU per day) and incidence of
hypercalcaemia in infants had almost halved (Bransby et al., 1964). Occasional case reports of
infantile hypercalcaemia have been published since, but these have related to specific genetic
polymorphisms (see full COT statement).
7.30 Early studies (Jeans & Stearns, 1938) showed that excess vitamin D could reduce linear growth in
infants but this was not observed at doses up to 54 μg/d (2160 IU/d) (Fomon et al., 1966). The
absence of effect was supported by a large prospective study of Finnish children (n=10,060)
supplemented with 50 μg/d (2000 IU/d) of vitamin D (Hypponen et al., 2011). Growth was also not
affected in breast-fed children whose mothers were given 25 or 50 μg/d (1000 or 2000 IU/d) of
vitamin D from birth (Ala-Houhala et al., 1986). Calcium concentration, in studies where it was
measured, was unaffected by vitamin D supplementation.
7.31 A number of studies in babies and infants have explored the effect of vitamin D supplementation on
serum 25(OH)D concentration (Ala-Houhala et al., 1986; Vervel et al., 1997; Zeghoud et al., 1997;
Gordon et al., 2008). Various regimens of vitamin D supplementation were administered (highest
dose was 1250 μg (50,000 IU)/twice weekly for 6 weeks) but hypercalcaemia was not observed.
7.32 Fewer data are available for older children but hypercalcaemia was not observed in children (n=8; age,
10-17y) receiving 350 μg (14,000 IU) per week of vitamin D 3 for 8 weeks (Maalouf et al., 2008). Similar
findings were reported in another study by the same group (El-Hajj Fuleihan et al., 2006) in which
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