Contents - IARC

Vitamin D and Cancer
4.3. Exogenous sources of vitamin D
4.3.1 Dietary sources of vitamin D
There is good evidence from randomised trials that a dietary intake of vitamin D increases serum
levels of 25-hydroxyvitamin D (Cranney et al.,2007). However, a few foods naturally contain
appreciable amounts of vitamin D3 to have an impact on dietary intake: fish liver, fish liver oils, fatty fish
and egg yolks. It has been verified that oily fish such as salmon, mackerel and bluefish are excellent
sources of vitamin D3. Interestingly, novel investigations have shown that farmed salmon, the most
widely consumed fish in the US, contained about one quarter of the vitamin D3 found in wild Alaskan
salmon (Lu et al.,2007; Chen et al.,2007b).
Some countries practice fortification of certain foods with vitamin D, most often milk, cereals,
margarine and/or butter and infant formula with up to 25 µg vitamin D3 per litre. In other countries
pregnant women or newborn children are prescribed between 10 and 25 µg vitamin D daily. The
mean intake of vitamin D in different studies varies by age group, food and supplementation habits
and gender. Recent publications from various parts of Europe have shown that a substantial part of
the population including pre-school children has a vitamin D intake below the recommended daily
doses.
4.3.2 Vitamin D2 and vitamin D3
Exogenous vitamin D comprises of two closely related substances of nutritional importance:
vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol). Vitamin D3 is formed from its precursor 7-
DHC which is amply found in human and animal skin. Vitamin D2 is formed by UV radiation from its
precursor ergosterol and occurs in plants, especially yeasts and fungi. However, plants are a poor
source of vitamin D2. Synthetic vitamin D2 is produced by UV irradiation of ergosterol to be added to
food or given as supplements. The two vitamins only differ by the side chain to the sterol skeleton. The
World Health Organization (WHO) has recommended as early as 1950 that 1 IU vitamin D be
equivalent to 25 ng crystalline vitamin D3, and no distinction was made between vitamin D3 and
vitamin D2 (WHO, 1950). Both forms of vitamin D are biologically inactive and require further
enzymatic activation in the organism.
The biological equivalence of the two vitamin D isoforms is at the centre of a controversy. A
double-blind randomised trial showed that orally administered vitamin D3 increases the serum vitamin
D status (25-hydroxyvitamin D3 plus 25-hydroxyvitamin D2) more efficiently (factor = 1.7) than vitamin
D2 when given in equimolar amounts over 14 days to healthy volunteers (Trang et al.,1998). The
assumption that vitamins D2 and D3 have equal nutritional value is probably wrong and should be
reconsidered (Trang et al.,1998; Houghton and Vieth, 2006). Also, some studies suggest that vitamin
D2 supplementation can suppress endogenously formed 25-hydroxyvitamin D3 and also 1α,25dihydroxyvitamin
D3 (Tjellesen et al.,1986; Hartwell et al.,1989; Harris et al.,1999), but a study by
Matsuoka et al.,(1992) showed no interference of intakes of 1,250 µg per day of vitamin D2 and
vitamin D3 release from the skin after UVB exposure.
A recent randomised, placebo-controlled, double-blinded study of healthy adults aged 18-84
years demonstrated that a daily 25 µg dose of vitamin D2 was as effective as 25 µg vitamin D3 in
maintaining serum 25-hydroxyvitamin D levels (Holick et al.,2008). Vitamin D2 did not negatively
influence serum 25-hydroxyvitamin D3 levels.
Considered altogether, these data suggest that vitamin D2 seems to be equally as effective as
vitamin D3 in maintaining 25-hydroxyvitamin D status.
4.3.3 Limiting rate for exogenous vitamin D pathway
Byrne et al.,(1995) meta-analysed dose-responses to vitamin D supplementation within
recommended dose ranges and found an average increase of 0.88 ng/mL in 25-hydroxyvitamin D
levels per µg per day of vitamin D (Byrne et al.,1995). Other studies found that the incremental
consumption of 1 µg per day of vitamin D3 by healthy young adults raises serum 25-hydroxyvitamin D
by 0.4 ng/mL (Vieth, 2006; Lappe et al.,2007). A large meta-analysis of 17 randomised trials (mainly
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