The experimental and theoretical data on the actions and
uses of Vitamin E. is so conflicting, and in many cases so indefinite, that little more can be done than to point
out what has been the most valuable of the experimental work and what are the most likely of the theories brought forward to explain the possible effect of its lack.
Points that have already been discussed will only be
referred to pi/in this section with An indication as
to where this has been done.
A short history of the vitamin is given to start
with. Then the chemical isolation of the vitamin is
traced from when a _n. a -'known factor influencing normal
reproduction was first thought to be present in
wheat germ oil till the vitamin was synthesised. Details of the chemical tests are given and it is
noted that Emmerie and Engel's method is the best.
The test may be applied to estimations of the
Vitamin E. content of the blood serum. Methods of
biological assay of the vitamin are discussed and
the difficulties in performing this are noted.
There does not seem to be a very close agreement
between the two methods for estimating quantities
of Vitamin E, but if it was proved both by chemical
tests and biological assay that synthetic
tocooherol and natural Vitamin E had similar
effects on experimental animals, it would be
possible to dispense with the latter test and
use only the former. Little information on the
action of Vitamin E is derived from the chemical
studies except that it is unlikely to play a part in the oxidation -reduction processes of the
cell, as when tocopherol is oxidised it gives rise
to physiolosically inert substances.
The next section deals with certain physiological
problems. It is noted that defects,in absorption in
individual animals and human beings may explain why
conditions stated to be due to deficiency of the
Vitamin may arise only in certain cases while others
remain normal on the same diet. These individual
variations may also apply to the utilisation of the
vitamin. Examples of diets used to produce Vitamin
E. deficiency in experimental animals are given and
the evidence for the occurrence of a natural
deficiency of Vitamin E. in animal and human diets
is reviewed. The occurrence of the vitamin in
nature is so widespread that this seems unlikely
although the question cannot be settled till the
absolute quantity of the vitamin in various diets
is estimated and till it is known what are the
minimal requirements for the vitamin, if any, needed
by various animals and by man.
as these requirements are not known the dose of
the vitamin needed to cure pathological st,etes due to
deficiency of the vitamin can only be estimated by
the effect that various doses have in curing these
conditions. There is no doubt that lack of the vitamin
caused disturbances of the reproductive and nervous
systems of rats, but it is not so certain that similar
conditions in human beings ere also caused by this
deficiency. So in the present state of our knowledge
the only way to estimate the curative dose in man, is
to find the amount of the vitamin which cures a similar
condition in the rat, and calculate it by means of
relativ: wei hts. This is obviously unsatisfactory
but till it is known whether the vitamin is needed
by man at all, it would be better to have a standard
scale of dosage so that the work of various
investigators could be more easily compared. A list
of the proprietary preparations used in clinical
medicine is given and in most cages the amount of
tocopherol that these contain is stated.
The fact that little storage of the vitamin
occurs in the body is noted. The storage that does
occur1takes place mainly in the subcutaneous and
intraperitoneal fat. The means of supply of the
vitamin from the mother to the young in experimental
animals is described. It takes place almost
entirely through the mammary gland and very little
through the placenta. That the supply is small
in amount is proved by the fact that it is insufficient
in females to prevent resorption in the first
gestation or to protect males from testicular damage
for more than seventy to eighty days.
Excess of the vitamin apparently produces no
harmful effects but certain ceses of hypersensitivity
to the vitamin are quoted. It is not quite certain
if these were really due to the vitamin itself or to
other impurities in the preparations used.
Finally it is noted that excretion of the vitamin
only occurs when the intake is high and that excretion
in the faeces occurs at a lower intake than excretion
in the urine.
After these introductory sections a study is made
of the results of a deficiency of the vitamin on the
various systems of man and of animals. First the
effect of. Vitamin E deficiency on cell metabolism is
considered. It is thought that the vitamin may be
needed for the normal function of the cell nucleus
and that lack of it may result in an interference
with cell division. It may act as a morphological
hormone necessary for synthesis of the nuclear
chromatin or for its physio- chemical structure.
Certainly if this was so it would offer a common
etiological cause for all the effects of Vitamin E
deficiency, the occurrence of lesions in certain
situations such as the nervous system, the developing
embryo and the germinal layers of the testis, being
an acute manifestation of the deficiency in cells
which are rapidly dividing or have been previously
damaged by some other noxious agent. Changes in the
cytoplasm of these cells are almost certainly
secondary to nuclear changes. Against this theory of
restricted cell division is the occurrence of signs of
uncontrolled cell proliferation which has been found
to occur in developing chicks deprived of Vitamin E.
It is also suggested that Vitamin E plays a part
in the oxidation -reduction processes of the cells,
especially in those of the fats. There is little
evidence for this as the oxidation processes and
general metabolism of Vitamin E deficient animals
d. e not lowered. It is possible that the Vitamin has
an anti-oxigenic action, protecting the cells against
harmful antoxidising fatty acids, although this is
improbable also has its protecting power does not
correspond to its Vitamin E activity in the various
types of tocopherol.
The next section deals with the pathological
conditions of cells deprived of Vitamin E. In chick
embryos it is found that lack of Vitamin E results
in some of the cells proliferating in an uncontrolled
fashion. Actual lymphosareoma and reticular cell
sarcoma were noted in some of the animals although it
is doubtful if these were primarily clue to Vitamin E
deficiency. The occurrence of fibroma of the uterus
is apparently more frequent in Vitamin E. deficient
rats and some Authors have found that Vitamin E. raised
the threshold of resistance to the production of
experimental tumours in these animals. Many other
Authors have failed to confirm this latter finding.
Other Experimenters produced tumours by administration
of wheat germ oil, but this was almost certainly due
to carcinogenic substances in the oil and not to
Vitamin E. However the fact that Vitamin E. is
supposed to stimulate the growth of cells and its
deficiency to prevent cellular division, and that it
is chemically related to human carcinogenic agents
makes it more lusty that excess of the vitamin and not
a lack should result in malignant changes. This
question cannot be cleared up till further experiments
are carried out and till it is known if Vitamin E has
similar functions in different species of animals.
It was thought that lack of the vitamin might
effect the haematological organs. A leukaemic litre
condition and a haemolytic anaemia have been noted in
chicks deprived of Vitamin E. but it has not been
proved if this was the real cause of these conditions.
The bulk of experimental evidence indicates that
Vitamin E excess or deficiency has no effect on the
blood picture or on iron metabolism. Vitamin E has
no place in the therapy of blood diseases in clinical
medicine. It has been tried in wounds and such
conditions where cellular proliferation is taking
place, but, although there have been some reports
of its value in these conditions, they have been
insufficient for any conclusions to be drawn from
them.
Then the effect of Vitamin E. defeciency on the female reproductive system Is
no doubt that the vitamin is necessary for the normal completion of pregnancy in rats. If it is deficient
the embryo dies and is absorbed. The pathological
changes occurring in the embryo prior to and after
death are described in detail. It is noted that the
foetal placenta is primarily affected, showing such
changes as atrophic allontoic projections, but the
maternal placenta is apparently only involved
secondarily to the foetal changes. Lesions in the
embryos of Vitamin E. deficient chicks are also
described as they differ from those described in
the case of the rat.
