The Vitamins 145Osteomalacia also occurs in the older people. Here
again the problem may be inadequate exposure to
sunlight, but there is also evidence that the capacity
to form 7-dehydrocholesterol in the skin decreases
with advancing age, so that older people are more
reliant on the few dietary sources of vitamin D.
Although vitamin D is essential for prevention and
treatment of osteomalacia in older people, there is less
evidence that it is benefi cial in treating the other
common degenerative bone disease of advancing age,
osteoporosis, which is due to a loss of bone matrix,
rather than enhanced release of calcium from bone
with no effect on the organic matrix, as is seen in
osteomalacia. The result is negative calcium balance
and loss of bone mineral, but secondary to the loss of
organic matrix, owing to progressive loss of estrogens
and androgens, rather than failure of the vitamin D
system.
Vitamin D requirements and
reference intakes
It is diffi cult to determine requirements for dietary
vitamin D, since the major source is synthesis in the
skin. Before the development of methods for mea-
surement of calcidiol the diagnosis of subclinical
rickets was by detection of elevated alkaline phospha-
tase in plasma; nowadays, the main criterion of ade-
quacy is the plasma concentration of calcidiol.
In older people with little sunlight exposure, a
dietary intake of 10 μg of vitamin D/day results in a
plasma calcidiol concentration of 20 nmol/l, the lower
end of the reference range for younger adults at the
end of winter. Therefore, the reference intake for older
people is 10 μg/day, whereas average intakes of vitamin
D from unfortifi ed foods are less than 4 μg/day.
There is little evidence to establish what are appro-
priate plasma concentrations of calcidiol; certainly
the lower end of the reference range for young adults
at the end of winter in a temperate climate is a mini-
malist goal, and is not much higher than the level at
which biochemical signs of defi ciency occur. However,
unfortifi ed foods will not meet even this goal.
There is increasing evidence that high vitamin D
status is associated with a lower incidence of various
cancers, diabetes, and the metabolic syndrome, sug-
gesting that desirable intakes are higher than current
reference intakes. Widespread fortifi cation of foods
would improve vitamin D status, but might also put
a signifi cant proportion of the population at risk of
hypervitaminosis and hypercalcemia. Increased sun-
light exposure will improve vitamin D status without
the risks of toxicity, but excessive sunlight exposure is
a cause of skin cancer. The main problem in trying to
balance improved vitamin D status through increased
sunlight exposure, and increased risk of skin cancer,
is that there is very little information on the amount
of sunlight exposure required for the synthesis of a
given amount of vitamin D.Vitamin D toxicity
During the 1950s, rickets was more or less totally
eradicated in Britain and other temperate countries.
This was due to enrichment of a large number of
infant foods with vitamin D. However, a small number
of infants suffered from vitamin D poisoning, the
most serious effect of which is an elevated plasma
concentration of calcium. This can lead to contrac-
tion of blood vessels, and hence dangerously high
blood pressure, and calcinosis, that is the calcifi cation
of soft tissues, including the kidney, heart, lungs, and
blood vessel walls.
Some infants are sensitive to intakes of vitamin D
as low as 50 μg/day. To avoid the serious problem of
vitamin D poisoning in these susceptible infants, the
extent to which infant foods are fortifi ed with vitamin
D has been reduced considerably. Unfortunately, this
means that a small proportion, who have relatively
high requirements, are now at risk of developing
rickets. The problem is to identify those who have
higher requirements and provide them with
supplements.
The toxic threshold in adults is not known, but
those patients suffering from vitamin D intoxication
who have been investigated were taking supplements
providing more than 250 μg/day.
Although excess dietary vitamin D is toxic, exces-
sive exposure to sunlight does not lead to vitamin D
poisoning. There is a limited capacity to form the
precursor, 7-dehydrocholesterol, in the skin, and
a limited capacity to take up cholecalciferol from
the skin. Furthermore, prolonged exposure of previ-
tamin D to UV light results in further reactions to
yield lumisterol and other biologically inactive
compounds.Interactions with drugs and other nutrients
As discussed above, vitamin D receptors form het-
erodimers with RXR, so that vitamin D-dependent