904
chapter 38
Vitamin Metabolism
of the USA. RDA values have been established for
mineral elements, energy, protein, electrolytes, and
water. Those for the vitamins are given in
Appendix IV.
Overdosage of vitamins A and D produces
hypervita-
minosis.
In recognition of this, the FDA has ruled that
vitamin A in doses greater than 10,000 IU and vitamin D
in doses greater than 400 IU should be available on a
prescription-only basis and that all products containing
quantities of a vitamin in excess of 150% of its RDA be
classified as a drug. Hypervitaminosis D was discussed in
Chapter 37; vitamin A toxicosis is discussed below. The
toxicity of high doses of vitamin B
6
is also covered later
in the chapter.
Certain vitamins can be synthesized by humans in lim-
ited quantities. Niacin can be formed from tryptophan
(Chapter 17). This pathway is not active enough to sat-
isfy all the body’s needs; however, in calculating the RDA
for niacin, 60 mg of dietary tryptophan is considered equi-
valent to 1 mg of dietary niacin. In Hartnup’s disease (see
Table 38-1 and Chapter 17), a rare hereditary disorder in
the transport of monoaminomonocarboxylic acids (e.g.,
tryptophan), a pellagra-like rash may appear, suggesting
that over a long period of time dietary intake of niacin
is insufficient for metabolic needs. This pattern also oc-
curs in carcinoid syndrome in which much tryptophan is
shunted into the synthesis of 5-hydroxytryptamine.
Vitamin D is synthesized in the skin, provided radiant
energy is available for the conversion (Chapter 37):
photons
7-Dehydrocholesterol -----
>
cholecalciferol (vitamin D3)
(38.1)
This pathway is adequate to supply the body’s need for
vitamin D, provided exposure to sunlight is adequate. Vita-
min D becomes a vitamin when environmental conditions
prevent synthesis of an adequate supply by the skin.
Physiological age-related changes in the elderly can
affect the nutritional status. Decreased active intestinal
transport and atrophic gastritis impair the absorption of
vitamins and other nutrients. Reduced exposure to sun-
light can lead to decreased vitamin D synthesis. Many
drugs may impair both appetite and absorption of nutri-
ents. Some examples of unfavorable drug-nutrient interac-
tions are drugs that inhibit stomach acid production (e.g.,
omeprazole); drugs that reduce vitamin Bi
2
absorption;
anticonvulsant drugs (e.g., barbiturates, phenytoin, prim-
idone) that act by inducing hepatic microsomal enzymes
which accelerate inactivation of vitamin D metabolites and
aggravate osteoporosis(Chapter 37); interference with fo-
late metabolism by antifolate drugs (methotrexate) used
in the treatment of some neoplastic diseases; and vita-
min Bg metabolism affected by isoniazid, hydralazine, and
D-penicillamine.
Examples
of
negative
impacts
of
vitamins
on
drug
action
are
vitamin
B6-dependent
action of peripheral conversion of L-3,4-dihydroxypheny-
lalanine (L-dopa) to L-dopamine that is mediated by aro-
matic L-amino acid decarboxylase and prevents L-dopa’s
transport across the blood-brain barrier; also ingestion of
large amounts of vitamin K-rich foods or supplements,
and action of warfarin on anticoagulation (Chapter 36).
L-Dopa is the metabolic precursor of L-dopamine and is
used in the treatment of Parkinson’s disease (Chapter 32).
Thus, L-dopa is administered along with a peripherally act-
ing inhibitor of aromatic L-amino acid decarboxylase (e.g.,
carbidopa). Vitamins A (and retinoids), C, and E are an-
tioxidants. Randomized trials of dietary supplementation
of antioxidant vitamins to determine their favorable and/or
unfavorable physiological effects on cardiovascular dis-
eases, cancer, and other chronic diseases are in progress.
38.1
Fat-Soluble Vitamins
The fat-soluble vitamins share many properties despite
their limited chemical similarity. They are absorbed into
the intestinal lymphatics, along with other dietary lipids,
after emulsification by bile salts. Lipid malabsorption ac-
companied by steatorrhea usually results in poor uptake
of all the fat-soluble vitamins. Deficiency disease (except
in the case of vitamin K) is difficult to produce in adults
because large amounts of most fat-soluble vitamins are
stored in the liver and in adipose tissue. The fat-soluble
vitamins are assembled from isoprenoid units; this fact is
apparent from examination of the structures of vitamins A,
E, and K; cholesterol, the precursor of vitamin D, is derived
from six isoprenoid units (Chapter 18). Specific biochem-
ical functions for vitamins A, D, and K are known, but a
role for vitamin E, other than as a relatively nonspecific
antioxidant, remains elusive.
Vitamin A
Nutrition and Chemistry
The role of vitamin A in vision is fairly well understood,
but the other functions of vitamin A are only beginning
to be elucidated (e.g., mucus secretion, maintenance of
the integrity of differentiated epithelia and of the immune
system, growth, and reproduction). Loss of night vision
(nyctalopia) is an early sign of vitamin A deficiency, and
clinical features of well-developed deficiency include epi-
dermal lesions, ocular changes, growth retardation, glan-
dular degeneration, increased susceptibility to infection,
and sterility.
Natural and synthetic compounds with vitamin A activ-
ity and inactive synthetic analogues of vitamin A are col-
lectively termed
retinoids.
The most biologically active,
