The Vitamins 183becomes rarefi ed, so that the bones fracture with
minimal trauma.
The name scurvy is derived from the Italian scor-
butico, meaning an irritable, neurotic, discontented,
whining, and cranky person. The disease is associated
with listlessness and general malaise, and sometimes
changes in personality and psychomotor performance
and a lowering of the general level of arousal. These
behavioral effects can be attributed to impaired syn-
thesis of catecholamine neurotransmitters, as a result
of low activity of dopamine β-hydroxylase.
Most of the other clinical signs of scurvy can be
accounted for by the effects of ascorbate defi ciency on
collagen synthesis, as a result of impaired proline and
lysine hydroxylase activity. Depletion of muscle car-
nitine, due to impaired activity of trimethyllysine and
γ-butyrobetaine hydroxylases, may account for the
lassitude and fatigue that precede clinical signs of
scurvy.
Anemia in scurvy
Anemia is frequently associated with scurvy, and may
be either macrocytic, indicative of folate defi ciency, or
hypochromic, indicative of iron defi ciency.
Folate defi ciency may be epiphenomenal, since the
major dietary sources of folate are the same as those
of ascorbate. However, some patients with clear meg-
aloblastic anemia respond to the administration of
vitamin C alone, suggesting that there may be a role
of ascorbate in the maintenance of normal pools of
reduced folates, although there is no evidence that any
of the reactions of folate is ascorbate dependent.
Iron defi ciency in scurvy may well be secondary to
reduced absorption of inorganic iron and impaired
mobilization of tissue iron reserves (see below). At the
same time, the hemorrhages of advanced scurvy will
cause a signifi cant loss of blood.
There is also evidence that erythrocytes have a
shorter half-life than normal in scurvy, possibly as a
result of peroxidative damage to membrane lipids
owing to impairment of the reduction of tocopher-
oxyl radical by ascorbate.
Vitamin C requirements
Vitamin C illustrates extremely well how different
criteria of adequacy, and different interpretations of
experimental data, can lead to different estimates
of requirements, and to reference intakes ranging
between 30 and 90 mg/day for adults.
The requirement for vitamin C to prevent clinical
scurvy is less than 10 mg/day. However, at this level
of intake wounds do not heal properly because of the
requirement for vitamin C for the synthesis of colla-
gen in connective tissue. An intake of 20 mg/day is
required for optimum wound healing. Allowing for
individual variation in requirements, this gives a ref-
erence intake for adults of 30 mg/day, which was the
British recommended daily allowance (RDA) until
1991.
The 1991 British reference nutrient intake (RNI)
for vitamin C is based on the level of intake at which
the plasma concentration rises sharply, showing that
requirements have now been met, tissues are satu-
rated and there is spare vitamin C being transported
between tissues, available for excretion. This criterion
of adequacy gives an RNI of 40 mg/day for adults.
The alternative approach to determining require-
ments is to estimate the total body content of vitamin
C, then measure the rate at which it is metabolized,
by giving a test dose of radioactive vitamin. This is
the basis of both the former US RDA of 60 mg/day
for adults and the Netherlands RDA of 80 mg/day.
Indeed, it also provides an alternative basis for the
RNI of 40 mg/day.
The problem lies in deciding what is an appropriate
body content of vitamin C. The studies were per-
formed on subjects whose total body vitamin C was
estimated to be 1500 mg at the beginning of a deple-
tion study. However, there is no evidence that this is
a necessary, or even a desirable, body content of the
vitamin. It is simply the body content of the vitamin
of a small group of people eating a self-selected diet
rich in fruit. There is good evidence that a total body
content of 900 mg is more than adequate. It is three
times larger than the body content at which the fi rst
signs of defi ciency are observed, and will protect
against the development of any signs of defi ciency for
several months on a completely vitamin C-free diet.
There is a further problem in interpreting the results.
The rate at which vitamin C is metabolized varies with
the amount consumed. This means that as the experi-
mental subjects become depleted, so the rate at which
they metabolize the vitamin decreases. Thus, calcula-
tion of the amount that is required to maintain the
body content depends on both the way in which the
results obtained during depletion studies are extrapo-
lated to the rate in subjects consuming a normal diet
and the amount of vitamin C in that diet.