III. Vitamin E toxicity
A) How toxic is vitamin E?
Toxicity of vitamins is divided into two categories based on RDA recommendations.
(1) Vitamins that are safe enough for administration at 50-100 times the RDA
recommended value.
(2)
Vitamins that have to be monitored by health care professionals due to
adverse effects at doses 10 times the RDA value. 4
Vitamin E falls under category (1) and has been show to be safe at doses well
exceeding 100 times the RDA value. 4
How is vitamin E’s safety understood?
1) The number of doses given each day
- All vitamins have no toxic effect with one dose even if given in
a large amount.
2) The method of administration of the vitamin
-
Injections avoid first pass metabolism that could cause the
introduction of toxic components that would normally be
metabolized before entering the circulatory system.
3) The health status of the patient
-
This is usually evaluated by age or if the person is with child.
4) Drug interactions
-
Most interactions result in decreased toxicity but it still must be
considered with high doses of certain vitamins. 4
Safety in adults
Vitamin E supplementation is considered safe. It is even recommended in certain
instances because of potential and known benefits as already discussed under “use of
vitamin E with concomitant disease states.” Other health related conditions in adults
that have demonstrated beneficial effects are people who have genetic anemias,
intermident claudation, premenstrual syndrome, tardive dyskinesia, and patients
undergoing hemodialysis. 4
There does exit a population of patients who should avoid supplementation of vitamin
E. Patients who are on warfarin therapy can be at risk of bleeding complications
especially if they are vitamin K deficient. Vitamin E at high doses has been shown to
block the absorption of other fat-soluble vitamins. In this case, vitamin K would not
be absorbed resulting in a deficiency of this vitamin used in the clotting cascade. 4
Safety in infants
Vitamin E has been used in premature infants to prevent defiance related effects.
Unfortunately, its use in this infant population has proven to be fatal and should be
avoided regardless of its method of administration. According to the Committee on
Fetus and Newborn (CFN), elevated doses of vitamin E cannot be administered to
infants who weigh less than 1.5 kilograms. 4
In summation, vitamin E supplementation posses no problem to adults. Animal and
human studies have demonstrated it to be noncarcinogenic and it has no reproductive
side effects. However, it should be avoided in children because of its known lethal
effects in premature infants.
B) Side effects of megadosing
Adults
Several reports have demonstrated that doses greater than 1000 IU of vitamin E can
cause headache, fatigue, nausea, double vision, muscular weakness, mild creatinuria,
and gastrointestinal distress. 1
Infants
From past medical treatment of vitamin E to premature infants, several fatal
conditions developed. One of these was “E-feroly” syndrome. “E-feroly” was a
commercially available intermuscular suspension of vitamin E. Its use was intended
as a preventative measure against retrolental fibroplasin, bronchopulmonary
dysplasia, and intraventricular hemorrhage in low birth weight children. Due to its
hazardous side effects it was banned from the market. The symptoms of “E-ferol”
syndrome include pulmonary deterioration, hepatomegaly, cholestatic jaundice,
ascites, splenomegaly, azotemia, thrombocytopenia, and death, which occurred in 40,
reported cases. 4
Another fatal phenomenon associated with megadoses of vitamin E in premature
infants is called necrotizing enterocolitis. The development of this condition along
with sepsis has been attributed to several causes related to vitamin E treatment. One
is the direct action of the vitamin itself, another is vitamin E in the RRR
conformation, and the last may be due to the presence of excipients in the dosage
formulation. 4