Vitamins and herbal preparations, particularly those sold in
health food stores, are considered by many to be innocuous, but
several have potential as toxins when taken in excessive amounts
over a period of time. Also, herbal preparations may contain toxic
contaminants that can cause acute poisoning. This chapter covers
the available vitamins and selected herbals; agents compounded with
vitamins, such as iron, are covered in other chapters.
Hypervitaminosis from the fat-soluble vitamins A, D, and E can
produce chronic toxicity (after weeks to months of excessive ingestion)
or subacute toxicity (after days to a few weeks). Of the water-soluble
vitamins, niacin, pyridoxine, and ascorbate are associated with
toxicity (Table 199-1).
Table 199-1 Symptoms
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Table 199-1 Symptoms
|Vitamin A||Chronic toxicity: blurred vision, appetite loss, abnormal
skin pigmentation, hair loss, dry skin, pruritus, long-bone pain,
bone fractures, rare cases of pseudotumor cerebri, and hepatic failure.|
Vitamin D||Subacute toxicity: hypercalcemia, anorexia, nausea, abdominal
pain, lethargy, weight loss, polyuria, constipation, confusion,
|Vitamin E||Chronic toxicity: nausea, fatigue, headache, weakness, and
(thiamine)||No toxicity observed, even with ingestion of large doses
over prolonged periods|
(riboflavin)||No toxicity observed, regardless of amount ingested|
Vitamin B3 (niacin)||Acute toxicity: niacin flush, dose >100 milligrams, redness,
burning, and itching of the face, neck, and chest, rarely hypotension|
|Chronic toxicity: doses >2000 milligrams/d, abnormalities
of liver function, impaired glucose tolerance, hyperuricemia, skin
dryness, and discoloration|
(pyridoxine)||Subacute and chronic toxicity: doses >5 grams/d
or more over several weeks, peripheral neuropathy with unstable
gait, numbness of the feet, similar symptoms in the hands and arms, marked
loss of position and vibration senses|
|Vitamin B12||No toxicity observed, even with ingestion of large doses|
|Folate||No toxicity observed, even with ingestion of large doses|
|Vitamin C (ascorbate)||Chronic toxicity: attacks of gout, nephrolithiasis, intrarenal
deposition of oxalate crystals with renal failure, large doses can
produce diarrhea and abdominal cramps|
Dietary vitamin A from animal sources is primarily in the form
of an ester, retinyl palmitate. After ingestion, the ester form
is hydrolyzed in the GI tract to retinol (vitamin A1 alcohol).
Retinol is then absorbed into intestinal mucosal cells where it
combines with a fatty acid to again become a retinyl ester. The
retinyl ester then travels through the lymphatic system and blood
stream to storage sites in the liver. Carotenoids are dark colored
compounds found in plants, about 10% of which, principally β-carotene,
the human body can metabolize into retinol. The liver contains approximately
95% of the vitamin A stores of the entire body.
Vitamin A forms part of the visual pigments of the retina (rhodopsin
and iodopsin), is important for the formation of mucus-secreting
cells of the columnar epithelium, maintains bone growth, and maintains
cellular membrane stability. The daily adult recommended doses range
from 4000 international units (IU) for women to 5000 IU for men.
Hypervitaminosis A generally occurs when children are given excessive amounts
of a high-potency supplement.1 Retinol is bound
to a liver protein (retinol-binding protein) and is stored in this
bound form. As the liver binding and storing capacities are exceeded,
blood levels of retinyl ester loosely bound to low-density lipoproteins increase. This loosely bound vitamin
is believed to be toxic to cell membranes. Members of Mawson’s
Antarctic expedition (1911–1913) are said to have died
from hypervitaminosis A after eating the livers of their dogs to
try to avoid starvation.
When the total dosage is similar, water-miscible preparations
are more toxic than oily preparations because of better absorption.
High doses of vitamin A must be ingested for long periods before
signs and symptoms of hypervitaminosis A develop.2 There
is a high degree of variability among patients in the amounts necessary
to develop hypervitaminosis. Dialysis patients can be at risk of
developing a type of vitamin A toxicity in which resorption of bone
Symptoms of hypervitaminosis A include blurred vision,
appetite loss, abnormal skin pigmentation, loss of hair, dry skin,
pruritus, long-bone pain, and an increased incidence of bone fractures.
Massive doses can additionally cause pseudotumor cerebri and hepatic
The treatment of hypervitaminosis A depends on the condition
of the patient. Generally, when vitamin A is discontinued, the symptoms
resolve over a period of time and no additional treatment is needed.
β-Carotene, a precursor of vitamin A, may be
rarely associated with toxicity but does not generally cause hypervitaminosis
A. In diabetics and patients with hypothyroidism, however, large
doses of β-carotene can cause a yellowish discoloration
of the skin, which fades once β-carotene is stopped.
This phenomenon is not uncommon in infants and toddlers who consume
large amounts of carrots and other pigmented vegetables.
Vitamin D activity comes from two major compounds: calciferol (vitamin
) and ergocalciferol (vitamin D2
). The naturally
occurring provitamin forms of each of these two compounds (7-dehydrocholesterol
for D3 and ergosterol for D2) convert to the active
forms following irradiation by ultraviolet light. Most studies in
humans have been performed using vitamin D3 (cholecalciferol),
which is converted in the body to 1,25-dihydroxycholecalciferol,
the physiologically active form of vitamin D.
Absorption of vitamin D is aided by bile and takes place in the
jejunum. From there, it is transported via lymph chylomicrons to
the portal circulation. When it reaches the liver, it is hydroxylated
to 25-hydroxycholecalciferol. From the liver, it travels to the
kidney, where it is hydroxylated a second time to 1,25-dihydroxycholecalciferol.
The major function of 1,25-dihydroxyhydrocalciferol is to elevate
the plasma calcium and phosphorus levels to enable ...