THE ANTISCORBUTIC VITAMINE[22]
[22] Vitamine is used throughout this monograph as synonymous with
"accessory food factor" or "food hormone" as a convenient descriptive
term, without any intention of connoting a definite chemical substance.
We shall not discuss the subject of vitamines in general, but confine
ourselves to the more limited field of the antiscorbutic vitamine. The
recognition of the "accessory" dietary factors is of such recent date,
however, that it will be well to consider briefly how attention came to
be directed to them and how their existence was ascertained. As in the
case of so many scientific discoveries, it is difficult to point to the
exact time when the advance was made. On looking back we find that
Lunin, in 1881, noting that mice were unable to live on a diet
consisting of protein, fats, carbohydrates, salts and water, came to the
conclusion "that other substances indispensable to nutrition must be
present in milk besides caseinogen, fat, lactose and salts." This work
did not stimulate similar investigations, nor did Lunin, as might have
been expected, allude to scurvy. The work which focussed attention on
this novel aspect of dietetics was the report of Eijkman, in 1897, to
the effect that when fowl are fed decorticated rice, they develop a
disease resembling beriberi, and that the paralytic symptoms disappear
on feeding them rice polishings or its alcoholic extract. Here, for the
first time, was a positive rather than a negative experiment, and one
capable of simple verification. The subject was placed on a scientific
basis by the classic investigation of Hopkins, who experimented with
purified food substances, and demonstrated how diets which were
deficient could be rendered adequate. As early as 1906 he wrote "the
animal body is adjusted to live either upon plant tissues or other
animals, and these contain countless substances other than the proteins,
carbohydrates and fats." "In diseases such as rickets, and particularly
in scurvy, we have had for long years knowledge of a dietetic factor,
but though we know how to benefit these conditions empirically, the
real errors in the diet are to this day quite obscure." The work of
Osborne and Mendel, and McCollum and Davis in this country, of
Schaumann, Funk, Stepp and others, all led to the conclusion that
purified diets are unable to satisfy the nutritive requirements of rats
or mice, and that extracts of the natural foods suffice to render the
diet adequate.
The same rule holds for man, who, when deprived of these vitamines,
develops the so-called deficiency diseases--typically modern disorders.
Regarded as a group, they are a consequence of our altered mode of life
and peculiar civilization. They follow naturally upon the development of
immense cities housing millions of people, who necessarily must receive
perishable foodstuffs produced at a great distance. To even a greater
extent they are the product of countless ingenious methods devised
mainly to render foods stable--drying, heating, the addition of
preservatives--most of which accomplish their object, but incidentally
rob the food of its essential vitamine.
None of the vitamines has been isolated in a pure state. The nearest
approach to this desired end has been the work of Funk, who obtained the
water-soluble vitamine in a state of such concentration that about 3 mg.
sufficed to cure a pigeon of polyneuritis. In considering the attributes
of the antiscorbutic vitamine, it must be borne in mind that this factor
is referred to as it exists in various foods; for example, in orange
juice or in cabbage, and furthermore, that the method of ascertaining
its presence or concentration is limited to the crude biological test of
animal feeding.
The antiscorbutic factor is distinguished by being the most sensitive of
the three vitamines, the most unstable, the least resistant to physical
or chemical processes. It may be regarded as one of the most delicate
indicators of the biological integrity of foodstuffs; however, as Falk
and his co-workers have shown, the enzyme property of living matter is
still more readily destroyed. The antiscorbutic vitamine is soluble in
water, and therefore is termed by some the "water-soluble C" factor. It
is also soluble in alcohol, as shown by the experiments of Hess and
Unger and of Harden and Zilva, and the therapeutic tests on infants of
Freise and of Freudenberg.[23] It possesses, therefore, the solubility
of the water-soluble vitamine. Some have suggested that it may be
derived from this vitamine, others that instead of one there may be a
series of antiscorbutic factors--suggestions based on pure hypothesis.
Holst and Froelich showed that this vitamine passes, without appreciable
loss, through dialyzing parchment, and Harden and Zilva (2) that it can
pass through a porcelain filter. The latter, using the method of
Seidell, demonstrated that this vitamine is not adsorbed by fine
precipitates such as fuller's earth, differing in this respect from the
water-soluble vitamine; and that in a mixture of equal volumes of
autolyzed yeast and orange juice, the antiscorbutic vitamine remained
unaffected, whereas the water-soluble A was entirely removed.
[23] Freise cured a case of infantile scurvy by giving about 2 c.c. of
an extract obtained from turnips by means of absolute alcohol. Seven
weeks were necessary to cause a disappearance of symptoms. Freudenberg
employed an extract of carrots, prepared with 96 per cent. alcohol, and
effected a quicker cure.
One of the most distinctive characteristics of the antiscorbutic factor
is its _sensitiveness to even moderately high degrees of heat_. In this
respect it differs markedly from the water-soluble or so-called
"antineuritic vitamine" which withstands exposure to high temperature.
The reaction of the antiscorbutic vitamine in this regard is not a
simple one, and cannot be expressed by a mere statement of the degree of
heat and the length of exposure. Numerous other factors, especially the
reaction of the medium, but also the physical environment, must be taken
into consideration--for example, cabbage is more resistant to the action
of heat than its juice. An understanding of the relation of
antiscorbutics to heat may perhaps best be obtained by considering the
subject in connection with some definite foodstuffs. The most exhaustive
study from a quantitative standpoint is that of Delf. She showed that
when cabbage is subjected for an hour to a temperature of 80° to 100°
C., 90 per cent. of its antiscorbutic vitamine is lost, and that 80 per
cent. is lost when a temperature of 90° to 100° is maintained for twenty
minutes, or a temperature of 60° for a period of sixty minutes. This
experiment shows that the destructive influence of heat is enhanced to a
comparatively slight degree by a rise of temperature, only about
threefold when it is raised from 60° C. to the boiling point. This
result points to a temperature coefficient of about 1.5 to 10° C. of
temperature. It is suggested by Delf that this low coefficient of
destruction is opposed to the enzyme or protein-like theory of the
nature of the vitamine, and suggests a simpler constitution. On the
other hand, we must bear in mind that the proteins which have been used
in experiments and found to possess a high coefficient of heat, have
been tested in the pure state, whereas the vitamine of the cabbage is
bound up in the cell.
Experiments with this vitamine as found in milk accord with the above
investigation, demonstrating that intensity of heat is not as
destructive as prolonged heating. This agrees with the clinical
experience that milk which has been boiled for a few minutes does not
induce scurvy as readily as pasteurized milk which has been heated for
45 minutes to 140° or 165° F. (Hess and Fish).
As demonstrated by tests with orange and with lemon juice, the
antiscorbutic vitamine is greatly protected from the destructive effect
of heat when it is associated with an acid. This was shown first by
Holst and Froelich and has been confirmed by numerous observers. An
excellent example of marked thermostability conferred on a food by its
acid reaction is furnished by the tomato, which is strongly
antiscorbutic even after it has been subjected to the canning process.
Conversely, Harden and Zilva have shown that the vitamine is destroyed
by alkali even when dilute (one-fiftieth normal sodium hydrate) and kept
in contact at room temperature; this alteration does not take place at
once, but in the course of several hours.
It is true that the antiscorbutic factor is peculiarly sensitive to
_drying_, but there are exceptions to this rule, so that it is incorrect
to state, as does the British Report of the Medical Research Committee,
that "it may be regarded as an axiom that dry or dried foodstuffs will
not prevent scurvy." We have shown that fresh milk dried by the
Just-Hatmaker process may retain by far the greater moiety of its
virtue. In this regard rapidity of desiccation and subsequent protection
from oxidative processes are important factors. The general rule holds
true, however, that this vitamine, in contradistinction to the
"water-soluble" vitamine, is readily damaged and destroyed by drying.
This vitamine is peculiarly sensitive to _aging_, especially when it is
present in an alkaline or neutral medium; but even in an acid medium its
potency soon diminishes. Harden and Zilva found this to be the case with
lemon juice stored for a fortnight in the cold room, and our experience
has been similar in regard to orange juice kept in the refrigerator
under a layer of liquid petrolatum. In milk the antiscorbutic factor
diminishes with age, especially following pasteurization, in the course
of which most of the acid-forming bacteria have been destroyed. Aging
has the least effect when the food with which the vitamine is associated
has been dried. This is true not only of lemon and of orange juice as
demonstrated experimentally and clinically, but even of milk, which even
after it has been dried and stored for months, may still possess marked
curative value.[24]
[24] Reference is made to a milk dried by the Just-Hatmaker process,
containing about 3 per cent. of moisture. The clinical data on which
this conclusion is based are given in the previous chapter.
Experiments by Harden and Zilva showed that exposure of lemon juice to
_ultra-violet rays_ for eight hours does not influence its antiscorbutic
activity, that exposure of autolyzed yeast for the same length of time
likewise does not impair its "antineuritic" potency, but that under
identical conditions the fat-soluble factor in butter becomes
inactivated. Similar tests carried out by the author with orange juice
led to the same result. It thus appears that one of the vitamines--not
the most unstable--manifests a peculiar sensitiveness to a certain form
of physical or chemical action.
In view of the fact that _shaking_ partly destroys pepsin and rennin, as
shown by Shaklee and Meltzer, it would be of interest to ascertain
whether this process brings about any impairment of the antiscorbutic
vitamine. Particular interest is attached to this question because it is
generally recognized that milk loses some of its potency in the course
of handling--whatever may be comprised by this term. In experiments on
the fat-soluble vitamine Steenbock and his co-workers found that
"somewhere in the course of the manipulation to which the butter fat had
been subjected, factors had been introduced which were responsible for a
vitamine destruction."
Before discussing the question of the manner in which the antiscorbutic
vitamine functionates, it may be well to state briefly the type of the
disturbance which its deficiency occasions. The chief manifestation is
damage to the integrity of the endothelium of the vessels, resulting in
hemorrhage--whether from diapedesis or from rhexis or both of these
conditions, the microscope does not inform us. Nor can it be stated
positively that the endothelium has not been injured by a secondary
toxic or bacterial factor. However this may be, the end result of the
deficiency is endothelial damage, a pathologic condition which may be
demonstrated clinically in scurvy by the "capillary resistance test"
(chapter VII). The other marked functional alteration in scurvy is
increased susceptibility to infection; but how a vitamine deficiency
induces this vulnerability cannot be explained. Clinical tests show that
the blood contains sufficient antitoxin (diphtheria) to afford
protection. Harden and Zilva found that "guinea-pigs fed on an
unrestricted mixed diet, on a quantitatively restricted mixed diet, and
a scorbutic diet showed no differentiation in amboceptor and agglutinin
titres, and in the complement activity of the blood." If this is to be
interpreted as indicating that the protective substances of the body
undergo but little alteration, we must consider whether susceptibility
to infection, as well as tendency to hemorrhage, is not due largely to
alteration in the cement substance of the endothelial and epithelial
membranes.
=The Mode of Action of the Vitamine.=--One of the most interesting as
well as puzzling questions in regard to the antiscorbutic vitamine
concerns the manner in which it prevents or cures scurvy. It is a
subject which at present is in a state of flux, hardly having emerged
from the realm of hypothesis, so that detailed consideration will profit
little. At first the _modus operandi_ was explained and accepted as
enzyme action, but it was soon evident, in view of the thermostability
of the vitamine, that it could not be classed as a ferment or enzyme in
the generally-accepted sense of this term. In general, it may be stated
that there are two main views: one that the vitamine acts directly, and
the other that it acts indirectly through the function of the endocrine
glands. _Direct action_, furthermore, may be accomplished in at least
one of three ways. The vitamine may (1) serve as a source of nutriment
for the tissues, (2) exert an antitoxic effect on toxic products, or (3)
function as a catalyzer. The first interpretation is evidently the
simplest and conforms to the long-established knowledge of caloric food
factors. That such small amounts as 2 c.c. of orange juice daily should
suffice to protect an animal from nutritional disaster runs counter,
however, to former conceptions of food nutrition. Further than this
there is little against this viewpoint. In its favor is the fact that,
up to a certain point, antiscorbutics act in direct ratio to the amount
given; for example, 2 c.c. of canned tomato juice is insufficient to
prevent scurvy in guinea-pigs, 3 c.c. will protect some but not all of
a series, whereas when the amount is increased to 4 c.c. daily all
animals will be saved. As we are considering new food factors it is
manifestly unwise to judge them by old standards, and to decide offhand
that they cannot possess such a high degree of nutritive power. This
question must be regarded as still open.
The antitoxic theory suffers from the fact that the toxic origin of
scurvy cannot be established. Before this is possible, it is clear that
it will be difficult to bring forward convincing evidence of a
neutralizing substance. Against this theory is the fact that elimination
therapy is of no avail in the treatment of infantile scurvy. Hess and
Unger (1919) failed to alleviate the symptoms by means of catharsis,
diuresis, sweating and repeated intravenous injections of normal salt
solution. In its favor it may be advanced, in a general way, that the
vitamine, in many characteristics, resembles an antitoxin--in its
extreme lability, its destruction by heat, aging and alkalies. On the
other hand, antitoxins also are readily destroyed by acid which, as has
been shown, exerts a protective influence on the antiscorbutic factor.
The rapidity of action of the vitamines, one of the most impressive
phenomena, calls to mind the neutralizing action of an antitoxin, and
probably has given rise to the analogy. Williams suggests that the
vitamines have "a general, non-specific, antitoxic or eliminative
action" on toxic substances resulting from the metabolic decomposition
of food.
The theory has been advanced that the action of the vitamines is
catalytic. Although this viewpoint has been taken regarding the
water-soluble rather than the antiscorbutic vitamine, it will be well to
review briefly the work on which it is based. Among the first to suggest
this hypothesis were Vedder and Clark, who noted a relationship between
the amount of vitamine required by fowls and their carbohydrate intake.
Funk in 1913 made a similar observation in regard to beriberi, and in
the following year, with von Schoenborn, showed that a vitamine-free
diet led to hyperglycæmia, with diminished amount of hepatic glycogen,
and that the addition of water-soluble vitamine diminished the
hyperglycæmia and increased the liver glycogen. The work of Burge and
his co-workers on the catalase content of tissue led to a similar
conclusion. Their results may be summarized by the statement that the
oxidative processes are hampered and fail to balance the autolytic
changes, and, furthermore, that a relationship exists between the
catalase activity, acidosis and normal oxidative processes. This theory
would presuppose that scurvy is due to the formation of toxins which are
normally in process of continual destruction in the body. According to
some, these catalyzed toxic substances are metabolic in character,
originating from incompletely oxidized food; according to another
interpretation, they are the product of autolyzed tissue cells (tissue
toxins). The difficulty with this explanation is that scurvy cannot be
prevented or cured by a diet containing food of high catalytic power.
For example, wheat embryos which, according to recent investigations of
Crocker and Harrington, have a high catalytic activity, were found of no
therapeutic value in relation to infantile scurvy (Hess, 3).
This problem has been approached from quite a different angle. As is
well known, certain bacteria require serum, blood, milk, etc., in order
to grow satisfactorily on artificial culture media. It has been
established recently, primarily by the work of Lloyd, that this
peculiarity in the cultivation of microörganisms is due largely to
their requirement of vitamine. She found a relationship of the inverse
order between the amount of amino acid present in the culture medium and
the amount of vitamine required to stimulate the growth of strains of
meningococcus. Reasoning from this experience, she suggests that the
action of the accessory growth factors is to increase the reaction
velocity of the proteolytic metabolism. Here we find the vitamines once
more regarded as catalyzers. This author, however, associates their
activity with proteolytic rather than with carbohydrate metabolism.
Interesting and suggestive work of similar nature has been carried out
in relation to the growth of protozoa and of yeasts (Eddy).
Investigations of this kind, dealing with unicellular organisms
propagated on a simple food, have the advantage of greatly simplifying
the problem.
The recent work of Dutcher falls under this caption, differing merely in
the fact that he attributes to the vitamines an _indirect action_. He
has demonstrated that the tissues of polyneuritic birds show a decrease
in catalase activity to a point 56 per cent. below normal, and that this
activity is largely restored when the birds are cured with vitamine.
According to this writer the vitamine functions as a metabolic
stimulant, and its lack results in a depression of the body oxidations
with an accompanying formation of toxic metabolic products, injurious to
the nervous system. The action is regarded as coming about in an
indirect manner, being accomplished through the hormone action of the
vitamines on one or more glands of internal secretion.
The _endocrine hypothesis_, suggested by Funk in his monograph, is not
without some corroborative evidence. In testing the pharmacologic action
of the water-soluble vitamine, Uhlmann found that it stimulated the
various glands of the digestive tract, in this respect acting like
pilocarpine. Some years ago Albert expressed the opinion that the action
of this vitamine was "vagotropic" like atropine, and recently Dutcher
has reported definite relief and cessation of polyneuritic symptoms by
means of pilocarpine (0.5 mg. subcutaneously). He claims equally good
results from thyroxin, the hormone of the thyroid gland, from desiccated
thyroid and from tethelin (pituitary). Voegtlin and Myers conclude, as
the result of experiments with brewers' yeast, that the chemical and
physical properties of secretin and vitamine are identical.
The early work of Funk and Douglas, which showed that various _glands of
internal secretion_ diminish in size and undergo degenerative changes
when the diet is vitamine-free, the newer work of McCarrison and of
Dutcher to the same effect, clearly point to an intimate relationship
between some of the endocrine glands and the vitamines. As regards
scurvy, the only work is that of Rondoni, McCarrison and of LaMer and
Campbell on the adrenal glands, which were found by all to be enlarged
in guinea-pigs suffering from this disorder. These investigations must
be regarded as tentative rather than conclusive until confirmed by
similar necropsy reports in man. In this connection it should be noted
that thyroid, parathyroid or suprarenal extract is of no avail in the
treatment of scurvy. This failure may, however, be explained by the fact
that the normal balance of glandular activity was not established. We
must bear in mind, however, that although the vitamines may influence
the secretion of the glands of internal secretion, this explanation does
not satisfactorily account for the symptoms of the "deficiency
diseases." These disorders do not in the slightest respect resemble the
clinical pictures which we are accustomed to associate with a lack of
activity of the glands of internal secretion. If the polyneuritis of
beriberi and the hemorrhages of scurvy are attributable to a diminished
secretion of the endocrine glands, then it will be necessary to revise
present conceptions of their physiologic functions.
=The Fate of the Vitamine in the Body.=--One of the most important
questions in relation to the antiscorbutic vitamine, quite apart from
its chemical nature, physiologic function, and its source, is its fate
in the human body after it has reached the alimentary canal or been
carried to the tissues. It can be readily appreciated that our knowledge
of this aspect is very meagre. We shall endeavor, however, to detail
what little is known of this subject, conscious of the fact that
investigations of the next few years may contradict our present
viewpoints.
Most of the constituents necessary for the construction of tissue or for
carrying on its functions can be synthesized by the animal body from the
basal foodstuffs. It has been ascertained within the past decade that
certain constituents--for example, some amino-acids of the protein
molecule--are building-stones which cannot be primarily elaborated by
the cells, but must be supplied by the food. At present the
vitamines--including the antiscorbutic vitamine--are included in this
new and essential group of substances which the human organism cannot
manufacture. Animal experiments seem to bear out this conception of the
vitamine whether we regard them as dynamic or as indispensable tissue
elements in the structural sense.
A closely-related but less fundamental question is that of _the ability
of man to store vitamines_--whether the tissues can hoard an excess of
these factors, or whether, in this respect, we are carrying on a
precarious hand-to-mouth existence in regard to cellular nutrition. It
is of course clear that at all times the various organs and tissues must
contain a certain amount of the vitamines. This has been shown for the
water-soluble or "antineuritic vitamine" by the fact that even the
organs of birds which have died of polyneuritis contain an appreciable
quantity of the specific vitamine, although an insufficiency of this
very factor has led to their death. That such is the case is
demonstrated for the antiscorbutic vitamine by the fact that muscle
tissue contains sufficient antiscorbutic to protect individuals
subsisting largely on a diet of which raw meat constitutes the sole
antiscorbutic agent (Stefánsson). It is very probable that some organs
contain more of the vitamines than others; this has been proved for the
"antineuritic" factor, and seems to hold good for the antiscorbutic--the
liver being particularly rich. No quantitative study has been carried
out from this point of view regarding the antiscorbutic vitamine, and it
would be well worth our while to ascertain the relative antiscorbutic
potency of the various organs of the body. Some time ago we undertook
experiments to determine whether the guinea-pig is capable of storing
this vitamine. One series of guinea-pigs was fed daily 6 c.c. of orange
juice for a period of two weeks, whereas another series, of about the
same weight, was given, in addition to the basal ration, only 3 c.c.
per capita (the minimal protective dose). After this preliminary period
both series were placed on a diet containing practically no
antiscorbutic. Both groups came down with scurvy after about the same
interval, leading to the conclusion that there could have been little if
any storing of the excess vitamine by those which received twice the
"minimal protective dose." The experiments of Harden and Zilva, who fed
a concentrated lemon juice, showed that this potent agent also was
unable to provide against a subsequent period of antiscorbutic
deficiency. It should be realized that the results of these tests on
guinea-pigs cannot be applied to man without tests on other species.
It might be thought that _the blood_--the purveyor of the vitamines to
the tissues--would be particularly rich in these essential factors.
Such, however, was not our experience in respect to the antiscorbutic
vitamine. The blood possibly varies greatly in this respect according to
the diet of the individual, or even according to the interval elapsing
after the ingestion of antiscorbutic food. Our opinion is based on the
surprisingly poor therapeutic effect of blood transfusion in the
treatment of scurvy. To illustrate: An infant weighing about fifteen
pounds received six intravenous injections of citrated blood--one of 200
c.c., given by the direct method, and a month later five smaller
transfusions with citrated blood, which aggregated 205 c.c.[25] In spite
of this addition of blood, the hemorrhage and congestion of the gums did
not disappear, nor the general condition improve, as would have happened
had 50 or 75 c.c. of orange juice been given by mouth. It seems probable
that small quantities of vitamine are being transmitted at all times by
the blood and supplied to the cells, but that its normal content of this
factor is not great. The antiscorbutic potency of blood may perhaps be
compared to that of milk. Animal investigation may show that various
vessels--for example, those supplying or draining certain glandular
organs--differ in the antiscorbutic quality of the blood which they
carry. It is evident, therefore, that many transitory factors may
influence the vitamine content of the blood, and that--as in the case of
milk and fruits and vegetables--we are not dealing with a constant and
unvarying agent.
[25] The dates and quantities of the transfusions were as follows: March
26th, 200 c.c.; April 27th, 30 c.c.; April 28th, 35 c.c.; April 29th, 30
c.c.; May 2nd, 75 c.c.; May 3rd, 35 c.c.
Nothing whatsoever is known concerning the _excretion_ of the
antiscorbutic vitamine. No attempts have been made to recover it from
the urine, or to ascertain if, when large amounts are ingested, the
excess is thrown off by the body. This suggests the question--a
corollary of that raised in connection with the vitamine content of the
blood--whether it is immaterial if the vitamine is taken frequently in
small amounts, or is provided only occasionally and at longer intervals
in larger amounts. Is it of no moment whether the infant receive its
quota of antiscorbutic every few hours through the medium of the breast
milk, or only once a day in the form of orange juice or tomato? If we
turn to studies on the other vitamines for enlightenment as to the
possibility of excretion, we find that Muckenfuss recovered the
water-soluble factor from ox bile and from human urine.[26] In this
article he proposes the interesting question of a possible variation in
the vitamine output under pathological conditions, which may be
responsible for the development of functional disturbances in children.
[26] This investigation was carried out by means of activating fuller's
earth with these fluids. This method is inapplicable to the
antiscorbutic vitamine, which is not adsorbed by this material. An
attempt to feed concentrated human urine to guinea-pigs resulted in
their death.
It would be of interest to know the _fate of the antiscorbutic vitamine
in the gastro-intestinal tract_. How is it affected by a lack of the
acid gastric juice, or by the alkaline intestinal secretions, or by the
bacteria in the lumen of the gut? From which part of the intestine is it
largely absorbed? May an appreciable amount undergo destruction before
this is accomplished? None of these questions can be answered
satisfactorily in the present state of our knowledge, but they suggest
that the mere fact that an adequate quota of antiscorbutic vitamine is
provided in the food does not necessarily insure an adequate supply for
the tissues. If in addition to the question of intake we must take into
account that the vitamines may suffer various vicissitudes, it may come
to pass that pathological conditions at times destroy or render them
partially inactive. In this way we may account for irregularities in the
clinical course of disorders associated with vitamine deficiency.
Of prime importance, however, is the effect of the vitamines _on the
glands of the alimentary tract and on the digestive processes_. A
diminution of gastric juice, or in some instances a total absence, has
been observed in adult scurvy, and noted by us in two cases of infantile
scurvy. As mentioned elsewhere, some consider the function of the
water-soluble vitamine analogous to that of secretin. In applying this
hypothesis to scurvy it must be borne in mind that the sequence may be
reversed, that the lack of vitamine may not lead to the gastric achylia,
but that the achylia may come about secondarily as the result of the
malnutrition.
We have referred to _"irregularities" in the course of the "deficiency
diseases."_ A careful perusal of the literature leaves one with the
impression that the most experienced observers are not entirely
satisfied with the exclusively etiologic relationship of the vitamine to
its respective nutritional disorder. In regard to scurvy, more
particularly, there are numerous scattered reports where the disorder
did not yield to antiscorbutic foods as might have been expected, or
where, on the other hand, it suddenly and inexplicably retrogressed,
although there had been no alteration in the dietary.[27] These
instances are not common, but they occur from time to time, and their
occurrence must be accounted for. In relation to beriberi and avian
polyneuritis improvement of this kind has frequently been explained on
the theory of a sudden mobilization of vitamines from the tissues. There
is, however, no data on which to base such explanations, and it may be
that a lack of parallelism between vitamine intake and the clinical
course may be due at times to processes taking place in the alimentary
tract.
[27] Neumann, for example, writes that he has seen at least four
children whose condition was not improved, although in addition to the
milk, they took asparagus, spinach, and other vegetables or apple sauce.
Some years ago we had a similar experience. It has likewise happened
that infantile scurvy did not recur, although the diet was the same as
that which originally led to the disorder.
The fat-soluble vitamine has been termed by some the growth vitamine.
All the vitamines, however, are closely associated with the function of
growth, which their deficiency tends to inhibit. In the chapter on
symptomatology, it will be pointed out that infants suffering from
scurvy fail to grow normally both in length and in weight. To a certain
extent this may be due to a loss of appetite, which is one of the
characteristic phenomena accompanying the scorbutic condition. On the
other hand, this anorexia may be secondary and not primary to the
impairment of the growth impulse, which may lead to a dysfunction of
various body processes.
It is of little value to look ahead and try to foresee what the next
decade will bring forth in regard to the nature of the vitamines.
Investigation has broadened remarkably during the past few years and now
embraces the chemical field--chemical and adsorption methods, the large
realm of biology, including studies in physiology and pharmacology; and
recently pathology has once more been called upon to aid in the solution
of the problem. Probably additional vitamines will be discovered. From
time to time it has been suggested that a specific growth vitamine
exists quite distinct from the three which are recognized, and recently
Mellanby has suggested still another food factor--a specific "rachitic
vitamine." When we reflect that the characteristic functions of the
various organs--the kidneys, liver, etc.--must depend on essential
differences in chemical structure, the complexity of the entire problem
of unidentified factors becomes evident.[28]
[28] For recent and comprehensive reviews of the vitamines the reader is
referred to papers by A. B. Macallum (Trans. Royal Canadian Institute,
Toronto, 1919) and by W. H. Eddy (Abstracts of Bacteriol. 1919, Vol.
iii, 313.)