The Vitamine Manual by Walter H. Eddy
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11 Produced by Juliet Sutherland, Richard Prairie, Charles Franks
and the Online Distributed Proofreading Team.
THE VITAMINE MANUAL
A Presentation of Essential Data
About the
New Food Factors
BY
WALTER H. EDDY
ASSOCIATE PROFESSOR PHYSIOLOGICAL CHEMISTRY
_Teachers College, Columbia University_
CONTENTS
CHAPTER I
HOW VITAMINES WERE DISCOVERED
CHAPTER II
THE ATTEMPTS TO DETERMINE THE CHEMICAL NATURE OF A VITAMINE
CHAPTER III
THE METHODS USED IN TESTING FOR VITAMINES
CHAPTER IV
THE YEAST TEST FOR VITAMINE B
CHAPTER V
THE SOURCES OF THE VITAMINES
CHAPTER VI
THE CHEMICAL AND PHYSIOLOGICAL PROPERTIES OF THE VITAMINES
CHAPTER VII
HOW TO UTILIZE THE VITAMINES IN DIETS
CHAPTER VIII
AVITAMINOSES OR THE DISEASES THAT RESULT FROM VITAMINE DEFICIENCIES
CHAPTER IX
BIBLIOGRAPHY
PREFACE
The presentation of essential data concerning vitamines to succeeding
groups of students has become increasingly difficult with the development
of research in this field. The literature itself has assumed a bulk that
precludes sending the student to original sources except in those
instances when they are themselves to become investigators. The demand on
the part of the layman for concise information about the new food factors
is increasing and worthy of attention. For all of these reasons it has
seemed worth while to collate the existing data and put it in a form which
would be available for both student and layman. Such is the purpose of
this little book.
It has been called a manual since the arrangement aims to provide the
student with working material and suggestions for investigation as well as
information. The bibliography, the data in the chapter on vitamine
testing, the tables and the subdivision of subject matter have all been
arranged to aid the laboratory workers and it is the hope that this plan
may make the manual of especial value to the student investigator. The
management also separates the details necessary to laboratory
investigation from the more purely historical aspects of the subject which
we believe will be appreciated by the lay reader as well as the student.
No apologies are made for data which on publication shall be found
obsolete. The whole subject is in too active a state of investigation to
permit of more than a record of events and their apparent bearing.
Whenever there is controversy the aim has been to cite opposing views and
indicate their apparent value but with full realization that this value
may be profoundly altered by new data.
Since the type of the present manual was set, Drummond of England has
suggested that we drop the terminal "e" in Vitamine, since the ending
"ine" has a chemical significance which is to date not justified as a
termination for the name of the unidentified dietary factors. This
suggestion has been generally adopted by research workers and the spelling
now in use is _Vitamin_ A, B, or C. It has hardly seemed worth while
to derange the entire set up of the present text to make this correction
and we have retained the form in use at the time the manuscript was first
set up. The suggestion of Drummond, however, is sound and will undoubtedly
be generally adopted by the research workers in the subject.
Attempt has been made to cover all the important contributions up to
April, 1921. Opportunity has permitted the inclusion of certain data of
still later date and undoubtedly other important papers of earlier date
will have been overlooked.
It is a pleasure to acknowledge the assistance received in the preparation
of the manuscript from Dr. H. C. Sherman, Dr. Mary S. Rose and Dr. Victor
La Mer. Their suggestions have been most valuable and greatly appreciated.
WALTER H. EDDY.
_Department of Physiological Chemistry, Teachers College, Columbia
University, New York City, April, 1921_
CHAPTER I
HOW VITAMINES WERE DISCOVERED
In 1911 Casimir Funk coined the name Vitamine to describe the substance
which he believed curative of an oriental disease known as beri-beri. This
disease is common in Japan, the Philippines and other lands where the diet
consists mainly of rice, and while the disease itself was well known its
cause and cure had baffled the medical men for many years. Today in
magazines, newspapers and street car advertisements people are urged to
use this or that food or medicament on the plea of its vitamine content.
In less than ten years the study of vitamines has increased to such an
extent that it is difficult to find a chemical journal of any month of
issue that does not contain one or more articles bearing on the subject.
Such a rapid rise to public notice suggests an importance that justifies
investigation by the laity as well as the chemist and in the pages that
follow has been outlined in simple language the biography of this newest
and lustiest of the chemist's children.
Dr. Funk christened one individual but the family has grown since 1911 to
three members which for lack of better names are now called vitamines "A,"
"B," and "C." There are now rumors of another arrival and none dare
predict the limits of the family. Had these new substances been limited to
their relation to an obscure oriental disease they would have of course
commanded the medical attention but it is doubtful whether the general
public would have found it worth while to concern themselves. It is
because on better acquaintance they have compelled us to reform our ideas
on nutrition of both adults and babies and pick out our foods from a new
angle, that we accord them the attention they demand and deserve. Granting
then, their claim upon our attention, let us review our present knowledge
and try to see with just what we are dealing. This will be more easily
accomplished if we consider the vitamines first from the historical side
and reserve our attention to details of behavior until later.
A limited diet of polished rice and fish is a staple among the peoples of
the Orient. When the United States Government took over the Philippine
Islands in 1898 it sent there a small group of scientists to establish
laboratories and become acquainted with the peculiarities of the people
and their troubles. One of the first matters that engaged their attention
was the condition of the prisons which were most unsanitary and whose
inhabitants were poorly fed and treated. Reforms were put into operation
at once and the sanitary measures soon changed these prisons to places not
quite so abhorrent to the eye. In trying to improve the diets of the
prisoners little change was made in their composition because of the
native habits but the reformers saw to it that the rice fed should be
clean and white. In spite of these measures the first year saw a
remarkable increase in the disease of beri-beri, and the little group of
laboratory scientists had at once before them the problem of checking a
development that bid fair to become an epidemic. In fact, the logical
discoverers of what we now know as the antineuritic vitamine or vitamine
"B" should have been this same group of laboratory workers for it was
largely due to their work between the years 1900 and 1911 that the ground
was prepared for Funk's harvest.
The relation of rice to this disease was more than a suspicion even in
1898. In 1897 a Dutch chemist, Eijkman, had succeeded in producing in
fowls a similar set of symptoms by feeding them with polished rice alone.
This set of symptoms he called polyneuritis and this term is now commonly
used to signify a beri-beri in experimental animals. Eijkman found that
two or three weeks feeding sufficed to produce these symptoms and it was
he who first showed that the addition of the rice polishings to the diet
was sufficient to relieve the symptoms. Eijkman first thought that the
cortical material contained something necessary to neutralize the effects
of a diet rich in starch. Later however, he changed his view and in 1906
his position was practically the view of today. In that same year (1906)
F. Gowland Hopkins in England had come to the conclusion that the growth
of laboratory animals demanded something in foods that could not be
accounted for among the ordinary nutrients. He gave to these hypothetical
substances the name "accessory food factors." To Hopkins and to Eijkman
may therefore be justly attributed the credit of calling the world's
attention to the unknown substances which Funk was to christen a little
later with the name vitamines. Other workers, of course, knew of these
experiments of Eijkman and Hopkins and in 1907 two of them, Fraser and
Stanton, reported that by extracting rice polishings with alcohol they had
secured a product which if added to the diet of a sufferer from beri-beri
seemed to produce curative effects. It is obvious that logic would have
decreed that some of these workers should be the ones to identify and name
the curative material. But history is not bound by the rules of logic and
it was so in this case. Another student had been attracted to the problem
and was working at the time in Germany where he also became acquainted
with Eijkman's results and began the investigation of rice polishings on
experimental lines. This student was Casimir Funk and a little later he
carried his studies to England where he developed the results that made
him the first to announce the discovery of the unknown factor which he
christened vitamine. Funk's studies combined a careful chemical
fractioning of the extracts of rice polishings with tests for their
antineuritic power upon polyneuritic birds, after the manner taught by
Eijkman. By carrying out this fractioning and testing he obtained from a
large volume of rice polishings a very small amount of a crystalline
substance which proved to be curative to a high degree. A little later he
demonstrated that this same substance was particularly abundant in
brewers' yeast. From these two sources he obtained new extracts and
carefully repeated his analytical fractionings. The result was the
demonstration that they contained a substance which could be reduced to
crystalline form and was therefore worthy of being considered a chemical
substance. In 1911, before Fraser and Stanton or any other workers had
been able to show to what their curative extracts were due, Funk produced
his product, demonstrated its properties and claimed his right to naming
the same. At that he barely escaped priority from still another source.
The chemists in Japan were naturally interested in this problem and
possessed an able worker by the name of Suzuki. Suzuki and his co-workers
Odake and Shimamura were engaged in the same fractioning processes with
polishings and entirely independently of Funk or other workers they too
succeeded in isolating a curative substance and published their discovery
the same year as Funk, 1911. Their methods were later shown to be
identical up to a certain point. Suzuki called his product "Oryzanin."
Funk's elementary analyses had shown the presence of nitrogen in this
product and his method of extraction indicated that this nitrogen was
present in basic form. For that reason he suggested that his product
belonged to a class of substances which chemists call "amines." Since its
absence meant death and its presence life what more natural than to call
it the Life-amine or Vita-amine. This is the origin of Funk's
nomenclature.
Both Funk's original crystals and Suzuki's oryzanin were later shown to be
complexes of the curative substances combined with adulterants and we do
not yet know just what a vitamine is or whether it is an amine at all but
no one since 1911 has been able to get any nearer to the identification
than Funk and while he has added much data to his earlier studies he has
himself not yet given us the pure vitamine. For that reason it has been
suggested by various people that the name vitamine should not be used
since it has no sufficient evidence to support it. Hopkins of England had
suggested the name "accessory food factors." E. V. McCollum holds that we
should call them the "unidentified dietary factors" and added later to
this phrase, the terms water-soluble "B" and fat-soluble "A" after the fat
soluble form was discovered. Most chemists feel, however, that the purpose
of nomenclature is brevity combined with ready recognition of what you are
discussing and that it is unnecessary to change the name vitamine until we
know exactly what the substances are. The result is that while still a
mystery chemically they remain under the name of vitamine and the kinds
are distinguished by the McCollum terms "fat-soluble" A, "water-soluble"
B, and "C."
We see that beri-beri then was responsible for Funk's adding to our
chemical entities a new member but it does not yet appear why this entity
concerns our normal nutrition. To get this relation we must turn for a
moment to the state of knowledge in 1911 in regard to foods and their
evaluation and what was going on in this field of study at the time.
A great advance in measuring food value was the discovery of the
isodynamic law. Translated into ordinary language this law states that
when a person eats a given amount of a given kind of food, that food may
liberate in the body practically the same amount of energy that it would
produce if it were burned in oxygen outside of the body. The confirmation
of this law permitted us to apply to the measurement of food the same
method we had already learned to use in measuring coal. For convenience
the physicists devised a heat measure unit for this purpose and naturally
called it by a word that means heat, namely, "calorie." Using this unit
and applying the isodynamic law it was merely necessary to determine two
things; first, how many calories a man produces in any given kind of work,
second how many calories a given weight of each kind of food will yield,
and then give the man as many calories of food as he needs to meet his
requirements when engaged in a given kind of labor. The measurement and
tabulation of food values in terms of calories and the investigation of
the calorie needs of men and women in various occupations has been one of
the great contributions of the past twenty years of nutritional study and
to the progress made we owe our power to produce proper rations for every
type of worker. Army rations for example are built up of foods that will
yield enough calories to supply the needs of a soldier and during the
recent war extended studies conducted in training camps all over the
United States have shown that when the soldier eats all he wants he will
consume on the average about 3600 calories per day. In France the American
soldier's ration was big enough to yield him 4200 calories per day if he
ate his entire daily allowance.
But calories are not the only necessities. A pound of pure fat will yield
all the calories a soldier needs in a day but his language and morals
wouldn't stand the strain of such a diet. Neither would his health, for
not only does his body demand fuel but also that it be of a special kind.
While there are many kinds of foodstuffs, chemical analysis shows that
they are mainly combinations of pure compounds of relatively few
varieties. The chemists call these proteins, fats, carbohydrates, and
salts. Meats, eggs, the curd of milk, etc., are the principal sources of
protein. Sugars and starches are grouped together under the name of
carbohydrate. By salts is meant mineral matters such as common salt, iron
and phosphorus compounds, etc. In selecting foods it was found that the
body required that the proportions of these four substances be kept within
definite limits or there was trouble. We know now that a man can get along
nicely if he eats 50 grams of protein per day and makes up the rest of his
calories in carbohydrates and fats, provided that to this is added certain
requirements in salts and water.
It is also obvious that the foods given must be digestible and palatable.
We had reached this status some time before 1911. But, a short time before
this, there had arisen a controversy as to the relative value of different
types of proteins. The animal- vs. vegetable-protein controversy was one
of the side shows of this affair. This controversy had led to a careful
study of the different kinds of proteins that are found in foodstuffs.
Through a brilliant series of chemical investigations for whose
description we haven't time or space here, chemists had shown that every
protein was built up of a collection of acids which were different in
structure and properties, that there were some seventeen of these in all
and that any given protein might have present all seventeen or be lacking
in one or more and that the proportions present varied for every type of
protein. It was then obvious that proteins could not be considered as
identities. More than that, it was the necessary task of the food expert
to separate all proteins into their acids or building stones and not only
show what was present and how much but determine the role each played in
the body. To this task many set their faces and hands.
From the results there has accrued much progress in the evaluation of
proteins but an unexpected development was the part played by these
investigations in the story of the vitamines.
About 1909-1910 Professors Osborne and Mendel under a grant from the
Carnegie Institution began a detailed investigation into the value of
purified proteins from various sources. In their experiments they used the
white rat as the experimental animal and proceeded to feed these animals a
mixture consisting of a single purified protein supplemented with the
proper proportions of fat carbohydrate, and mineral salts. Since the food
furnished was composed of pure nutrients and always in excess of the
appetite of the rat the necessary number of calories was also present.
These researches were published as a bulletin (No. 156) by the Carnegie
Institution in 1911, the same year that Funk announced his Vitamine
discoveries. It was timely in this respect for one of Osborne and Mendel's
discoveries was that no matter how efficient the mixture in all the
requirements then known to the nutrition expert, the rats failed to grow
unless there was added to the diet a factor which they found in milk. In
searching for this factor they made a still further discovery for on
fractioning the milk they soon learned that the unknown factor was
distributed in two different parts of the milk, namely in the butter fat
and in the protein free and fat-free whey. The absence of either milk
fraction was sufficient to prevent growth. The 1911 publication merely
described these results without attempting to explain the nature of the
growth producing factors but the vitamine hypothesis of Funk naturally
suggested to these authors that their two unknown factors might be similar
in nature to his beri-beri curative factor and their announcement may be
justly considered a point of junction of nutrition theories with the
vitamine hypothesis.
The peculiarity of butter fat as a growth stimulus had been considered
from another angle by a German worker, Stepp. In 1909 this student of
nutrition had tried to estimate the importance of various types of fats in
the same way that was later done with proteins, to determine whether, like
proteins, the quality of the fats varied in nutritive efficiency. His
experiments were also conducted with white rats and the main outlines of
his methods and observations were as follows: Rats fed on a bread and milk
diet grew normally. If now the bread and milk mixture was extracted with
alcohol-ether the residue was found to be inadequate for growth or
maintenance. Stepp assumed that this failure could naturally be ascribed
to the removal of the fat by the alcohol-ether mixture. To determine the
efficiency of different kinds of fats he then proceeded to substitute in
combination with the alcohol-ether extracted diet amounts of purified fats
corresponding to what was removed by the alcohol-ether. The results were
totally unexpected for _none_ of the purified fats substituted were
adequate to secure growth! When, however, he evaporated off his alcohol-
ether from the extract of the bread and milk and returned that residue to
the diet, growth was resumed as before. The conclusion was obvious, viz.,
that alcohol-ether takes out of a mixture of bread and milk some factor
that is necessary to growth and that factor is not fat but something
removed by the extraction with the fat. These results led Stepp to suspect
the existence of an unidentified factor but he was unable to identify it
as a lipoid. He makes the following statement which is now significant:
"It is not impossible that the unknown substance indispensable to life
goes into solution in the fats and that the latter thereby become what may
be termed carriers for these substances." These studies were published
between the years 1909 and 1912 and were therefore concurrent with those
of Funk and Osborne and Mendel.
But there was still another set of studies that led up to this vitamine
work. In 1907 E. V. McCollum began the study of nutrition problems at the
Wisconsin Experiment Station. At the time he was especially interested in
two papers that had been published just previous to his entrance into the
problem. One of these papers by Henriques and Hansen told how the authors
had attempted to nourish animals whose growth was already complete on a
mixture consisting of purified gliadin (the principal protein from the
quantity viewpoint in wheat), carbohydrates, fats, and mineral salts. In
spite of the fact that the nitrogen of this mixture was sufficient to
supply the body needs, as proved by analysis of the excreta, the animals
steadily declined in weight from the time they were confined to this diet.
The authors had assumed that the gliadin was deficient in a substance
necessary to growth (lysine) but since their studies were begun only after
the animals had reached maximum growth they expected that the growth
factor would not be necessary. Why had their animals declined in weight?
The second paper that interested McCollum was by Wilcock and Hopkins.
These authors carried out experiments similar to those of the paper just
cited but using corn protein (zein) in place of gliadin. This protein had
already been shown to be deficient in a chemical constituent known as
tryptophan. Animals fed on the zein mixture died in a few days but the
inexplicable thing was that when the missing tryptophan was added to the
diet the animals lived a little longer but finally declined and died. Why?
McCollum wished to answer this "Why?" These experimenters had complied
with every known law of nutrition and yet their mixtures failed to nourish
the animals. What was lacking? Earlier work at the Station by Professor
Babcock suggested an interesting line of attack and in collaboration with
Professors Hart and Humphries, McCollum began a series of studies that
have become classic contributions to the vitamine hypothesis and brought
this worker into the field as one of the most important contributors to
the subject. His initial experiments may be briefly summarized as follows:
Young heifer calves weighing 350 pounds at the start and as nearly alike
in size and vigor as could be obtained were selected as experimental
animals. These were divided into groups and fed with rations so made up as
to be alike in so far as chemical analysis could determine, but differing
in that the sources of the ration were divided between three plants. One
group was supplied with a ration obtained entirely from the wheat plant. A
second group derived their ration solely from the corn plant. A third from
the oat plant and a fourth or control group from a mixture of oat, wheat
and corn. By chemical analysis each group received enough of its
particular plant to produce exactly the same amount of protein, fat and
carbohydrate and all were allowed to eat freely of salt. All groups ate
practically the same amount of feed, and digestion tests showed that there
was no difference in the digestibility of the different rations. Exercise
was provided by allowing them the run of a yard free of all vegetation. It
was a year or more before any distinct change appeared in the different
groups. At that time the cornfed animals were in fine condition. On the
contrary, the wheat-fed group were rough coated, gaunt in appearance and
small of girth. The oat-fed group were better off than the wheat-fed but
not in so good shape as the corn-fed. In reproduction the corn-fed animals
carried their young well. They were carried for the full term and the
young after birth were well formed and vigorous. The wheat-fed mothers
gave birth to young from three to five weeks before the end of the normal
term. The young were either born dead or died within a few hours after
birth. All were much under weight. The oat-fed mothers produced their
young about two weeks before the normal period. Of four young, so born,
one was born dead, two so weak that they died within a day or two and the
fourth was only saved by special measures. The young of the oat-fed
mothers were of nearly the same size, however, as those of the corn-fed
mothers. After the first reproduction period, the mothers were kept on
this diet another year and the following year repeated the same process
with identical results. During the first milk-producing period the average
production per day was 24.03 pounds per day for the corn-fed, 19.38 pounds
for the oat-fed, and 8.04 pounds for the wheat-fed. During the second
period it was 28.0, 30.1, and 16.1 pounds per day respectively during the
first thirty days.
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