162 Introduction to Human Nutrition
Although the nutritional etiology of pellagra is well
established, and tryptophan or niacin will prevent or
cure the disease, additional factors, including defi -
ciency of ribofl avin or vitamin B 6 , both of which are
required for synthesis of NAD from tryptophan, may
be important when intakes of tryptophan and niacin
are only marginally adequate.
During the fi rst half of the twentieth century, of the
87 000 people who died from pellagra in the USA
there were twice as many women as men. Reports of
individual outbreaks of pellagra, both in the USA and
more recently elsewhere, show a similar gender ratio.
This may well be the result of inhibition of trypto-
phan metabolism by estrogen metabolites, and hence
reduced synthesis of NAD from tryptophan.
Several bacterial, fungal and environmental toxins
activate ADP-ribosyltransferase or poly(ADP-ribose)
polymerase, and it is possible that chronic exposure
to such toxins will deplete tissue NAD(P) and hence
be a contributory factor in the development of pella-
gra when intakes of tryptophan and niacin are
marginal.
Niacin requirements
On the basis of depletion/repletion studies in which
the urinary excretion of niacin metabolites was mea-
sured after feeding tryptophan or preformed niacin,
the average requirement for niacin is 1.3 mg of niacin
equivalents/MJ energy expenditure, and reference
intakes are based on 1.6 mg/MJ.
Average intakes of tryptophan in Western diets will
more than meet requirements without the need for a
dietary source of preformed niacin.
Assessment of niacin status
Although the nicotinamide nucleotide coenzymes
function in a large number of oxidation and reduc-
tion reactions, this cannot be exploited as a means of
assessing the state of the body’s niacin reserves,
because the coenzymes are not fi rmly attached to
their apoenzymes, as are thiamin pyrophosphate,
ribofl avin, and pyridoxal phosphate, but act as cosub-
strates of the reactions, binding to and leaving the
enzyme as the reaction proceeds. No specifi c meta-
bolic lesions associated with NAD(P) depletion have
been identifi ed.
The two methods of assessing niacin nutritional
status are measurement of the ratio of NAD/
NADP in red blood cells and the urinary excretion of
niacin metabolites, neither of which is wholly
satisfactory.Niacin toxicity
Nicotinic acid has been used to lower blood triacyl-
glycerol and cholesterol in patients with hyperlipid-
emia. However, relatively large amounts are required
(of the order of 1–6 g/day, compared with reference
intakes of 18–20 mg/day). At this level of intake,
nicotinic acid causes dilatation of blood vessels and
fl ushing, with skin irritation, itching, and a burning
sensation. This effect wears off after a few days.
High intakes of both nicotinic acid and nicotin-
amide, in excess of 500 mg/day, also cause liver
damage, and prolonged use can result in liver failure.
This is especially a problem with sustained-release
preparations of niacin, which permit a high blood
level to be maintained for a relatively long time.8.9 Vitamin B 6
Apart from a single outbreak in the 1950s, due to
overheated infant milk formula, vitamin B 6 defi ciency
is unknown except under experimental conditions.
Nevertheless, there is a considerable body of evidence
that marginal status and biochemical defi ciency may
be relatively widespread in developed countries.
Vitamin B 6 is widely distributed in a variety of
foods. However, a considerable proportion of the
vitamin in plant foods may be present as glucosides,
which are probably not biologically available, although
a proportion may be hydrolyzed by intestinal
bacteria.
When foods are heated, pyridoxal and pyridoxal
phosphate can react with the ε-amino groups of lysine
to form a Schiff base (aldimine). This renders both
the vitamin B 6 and the lysine biologically unavailable;
more importantly, the pyridoxyl-lysine released
during digestion is absorbed and has antivitamin B 6
antimetabolic activity. Overall, it is estimated that
some 70–80% of dietary vitamin B 6 is available.Vitamers
The generic descriptor vitamin B 6 includes six vita-
mers: the alcohol pyridoxine, the aldehyde pyridoxal,
the amine pyridoxamine, and their 5′-phosphates.
There is some confusion in the older literature,
because at one time “pyridoxine,” which is now used
specifi cally for the alcohol, was used as a generic