A STUDY OF THE EFFECTS OF THIAMINE
ON CHILDREN WITH SPEECH NON-FLUENCY
EDWARD M. PENSION
A rlSSERTATION PRI'SENTED TO THE GRADUATEE COUNCIL OF
THF UNIVERSITY OF FLORIDA
IN PARTL.L FULFILMENT OF THE F.EQUIREMENTs FOR THE
DEGREE OF DOCTOR OF PHILOSOPHY
UNIVERSITY OF FLORIDA
UNIVERSITY OF FLORIDA
3 1262 08552 3560
4"ii..; - i.
The conduction of this investigation and the completion of this
dissertation have necessitated considerable cooperation on the part of
over one thousand specific professional and lay individuals. Elements
of time and space do not permit adequate recognition of mary people who
aided this investigation and abetted the report of its results. There
are several individuals, however, to whom the author is compelled to
extend heartfelt acknowledgment. Foremost among these is D. Lester L.
Hale, Professor of Spe, who served as laj advisor and chairman of
the graduate committee for the writer. Without Dr. Hale's great crea-
tive imagination, his insight into the specific research problem in-
volved and his advice and guidance in the writing of this dissertation,
this project could not have bee undertaken. The writer is especially
grateful to Dr. Hale for his practice of allowing freedom of thought,
encouraging independence of action and stimulating the desire to do
more. Special recognition is taken of the wise counsel and friendly
guidance which the writer received from Professor H. P. Constant, Chair-
man of the Department of Speech.
The writer is also indebted to Dr. George K. Davis, Professor of
Animal Nutrition and Head of the Animal Nutrition Laboratory, who, as a
member of the writer's Graduate Committee, rendered helpful direction in
the nutritional and bio-chemical aspects of the study. The fact that
the laboratory analyses which were vital to this research were conducted
at the Animal Nutrition Laboratory is due largely to the cooperative
invitation of Dr. Davis.
Further thanks are given to Dr. Roy E. Tew, Assistant Professor
of Speech, Dr. James C. Dixon, Associate Professor of Psychology, and
Dr. Henry Wuaderlich, Associate Professor of Psychology, who offered
val-able advice eoneerning experimental design and who helped to cof
prise an instructive and inspiring graduate committee.
The investigation required considerable cooperation from the
ainmeeville comumity. Dr. RayBond Camp, Gainesville pediatrician, con-
tributed to the research design and his willingness to recommend prospec-
tie subjects, together with his professional and intellectual curiosity,
plped a large part in the progress of the experiment. Marvin Kokomoor,
M. D., and F. wmory Bell, M. D., also referred potential subjects to the
investigator and attested to their satisfactory medical status.
It se the writer's good fortune to have had an industrious and
insightful panel of judges comprised of Mr. Thomas B. Abbott, Miss Flora
Armbruster, Mr. Robert Arthur, Dr. McKenzie U. Buck, Miss Jean Daley,
Mr. William P. Dorn, Dr. Letter L. Hale, Mr. Earl Howell, Miss Marie T.
Mulkern and Dr. Roy E. Twn.
The witer is indebted to Lederle Laboratories Division of the
Ameries m gaMmid CGemay of New York for their generous contributions
of M1klmine and placebo tablets.
Particular ackuoledgment is given to all of the children oho
served ea lrally as subjects, and to their parents who suffered
multiple ineenemiseeeu in their desire to help this research.
Let it be eleerly stated that this project would never have
bem s eemeeived, condaeted or ooneluied without the aetive support of
the writer's fadly. To his father, Michael Penon, goes the writer's
warm gratitude and proud affection, for his continued interest in things
academic. His philosophies have inspired; his advice has calmed; and
his lov has enriched. To his wife, AnnaBelle Wad Pemson, the writer
attributes a major portion of the success of this undertaking. She
worked tirelessly throughout on such exotic tasks as sterilizing
urine-eample jars, and counting vitamin and placebo tablets and first
draft typing. The extent of her effort is only exceeded by her loyalty,
patience, and lovability.
TABE (F COMMENTS
AO EDG RS . .. . ......... . ..... .
I. IMERGDUCTIO .. . . . . . . . 1
Statement of Purpose . . . . . . . 1
Review of Stuttering Theories and Research . 1
Thiaaine and serve In rity ........ . 21
II. DESCRIPTION OF PROQEDIRE . . . . . ... .
The Subjects .. . ........... 52
Dosege and Medioal Approval and Preecription . 55
Ixperimental Design . . . . . . . 57
Methods Used in Analying the Reaults . . . 64
III. PRESERTATIOI AND EVALUATION OF THE DATA . . . . 66
Difficulties Encoutered ... ....... 66
Fidi . . . . . . . . . . 69
IV. SIuWAs AND CONCLUSIONS . . . . . . . . 79
luios . .. . . . . . . . 79
Reeesmsation ...... . .... 80
ARMI . ... ...... ...... ....... 81
BIBLIORAMf .......... ........ ...... 103
BIOGRAPHIML MNE . . . . . . . . . . . .
OCA PME I
The objective of this chapter is to describe the background of
research, reporting, and reasoning by authors of relevant literature
which points to the rationale of the present study a makes clear its
Statement of Purpose
It is the pupose of the present work to study the effects of
thiamine (vitamin BI) upon children whose speech has been rated by
trained judges as "non-fluent."
Review of Stuttering Theories and Research
For over two thousand years the problem of stuttering has been
a subject of study, theorization, and treatment.1 During this time,
people who have stuttered have been exposed to varying kinds and de-
grees of superstition and quackery, scientific research, and rational
treatment. Even so, the origin of stuttering remains, to a large ex-
tent, unknown. This does not appear to be due to a lack of effort
expended or time consumed on the subject. There have been many varied
1G M. Klingbell, "The Historical Background of the Modern
Speech Clinic," The Journal of Speech and Hearing Disorders, IV, Part
I (June, 1939), 115.
descriptions of symptoms, theories of oausation, and attempts at treat-
ment. The following historical background on the subject of stuttering
is not meant to be all-inclusive, but it should serve to illustrate the
long and varied history of stuttering as a problem for study.
In its early history, according to Bryngelson, stuttering rns
thought to be ewueed by gods and devils and therefore related to the
soul of man.
Klingbell recorded that Herodotus, the Greek historian, (c 48L
- Uk4 B.C.), reported the treatment of Battos, son of Polyanestos, by
a Pythian priestess. She recommended emigration south to Libya so that
he might escape the evil god causing his affliction.3
Later, the tongue became the enter of attention as is sug-
gested by the many theories meeribed to it and the many treatments
prescribed for it. According to Klingbell's historical account,
Aristotle (c 384 322 B.C.) was among the first to describe the cause
of stuttering as being centered in the tongue. Aurelius Celsue (e 42
B.C. 37 A.D.), an early medical encyclopedist, agreed with Aristotle
and suggested a treatment regimen which included massaging the tongue
and throat, eating pungent substances, and performing physical and
respiratory exercises. Glen, (c 131 201 A.D.) recommended cauteri-
sation of the tongue. In the sixth century Petius believed a cure for
Bryag Bryanglsen, "Investigations in the Etiology and Nature
of Dysphe~ta and its 9Fptem, Stuttering," The Journal of Speech Dis-
orders, TII (Saroh, 19ht), 15.
3Klingbell, "The Historical Background of the Modern Speech
Clinie," up. cit., 115.
stuttering could best be accomplished by a division of the frenum. An
Arabian king's court philosopher and physician, Abu Ali Al Husain
Avicenna, (980 1037) blamed stuttering on the tongue, lesions of the
brain and nerves, accompanied by spasms of the.epiglottis. Frances
SBacon appears to have been of the opinion that stuttering and
other speech defects are caused by the coldness and dampness of the
tongue, or on occasion by its dryness. If the tongue were hot
and dry, he suggested ice or cooled lotions be applied. If the tongue
were too cold or damp, he prescribed internal applications of wine.
Klingbell pointed out that some of the early alleged authorities traced
th of stuttering from the t ong to other structures. For ex-
ample, Johann Gottfried von Hahn, court physician to King Frederick,
blamed all speech defects on the hyoid bone.
In his discussion of stuttering etiology, Bryngelson indicated
that Galen and Petius were among several of the early experts who
attempted surgery on the tongue in an effort to cure stuttering.4 By
and large, this surgery apparently had as its objective the elevation
of the tongue. Some surgeons cut a transverse wedge into the tongue
and sewed the edges of the gap together. Bryngelson reported that
stuttering symptoms frequently disappeared following surgery because
loss of blood, surgical shock, or infection had caused the patient's
death. Other attempts at a surgical cure for stuttering consisted of
the removal of the tonsils and uvula. Certz employed peppermint oil
4Bryngelson, "Investigations in the Etiology and Nature of
Dysphemia and Its Symptom, Stuttering," op. cit., 16.
and chloroform in an effort to allay the spasms of the stutterer's dia-
The emergenee of physiologic theories ms advanced by the
belief that stuttering represented an synergy a malfunctioning of
the musculature involved in speaking. The therapy consisted of phonetic
drills to induce better coordination. Darwin appeared to be the founder
of this school of thought, and among its other exponents Bryngelson
listed Carpenter, Hunt, Kussmal, Gutman, Tyllie and Bell.
kk-uen, Kenyon, rqle and Martin represented a point of view
which eonfidered stuttering to be a physical habit due to a disoriented
peyehe.5 The treatment suggested in this instance was still largely
physical, but the transition to a theory expounding psychological treat-
mnt, as vell as eausation, was rapidly forthcoming. Bryngelson made
careful note of this change:
Now stuttering as interpreted as being the result of a
basic emotional instability a 'complex,' social morbidity,
or hyperactivity of the affective life of the stutterer.
3vwn modern medical books mentioning stuttering, describe it
in this fashion. Although the queetionaire method as uied
at first, better results were proclaimed when the doctor and
patient eould work clinically in conference. Mental hygiene
and peyheotherapy were the vogue in treatment. Fletcher and
Blumel are the two meet outstanding exponents of this
school. In erept the ideas of Blanton and Swift. The former
thought that stuttering was due to transient auditory amnesia;
the latter visual central astenia. Images by these men
were treated like specific organ had been treated at an
As psysheonalysis began to have its influence in the field of
mental health, its effects were als felt in the field of speech therapy.
Appelt, Rosenbach, Dubois, Coriat, Steckel, Netskatschen, and Hudson
advocated psychoanalytic treatment for the "speech neuroses."
n and Travis in the 1920's, introduced a modern scientific
approach to the study of this seemingly mysterious phenomenon stut-
tering. This.approach included laboratory and clinical research which
attempted to discover differences, physiological and/or psychological,
between stutterers amd non-stutterers. It would seem that if such
differences could be found, they might provide important clues as to
the nature of the eause or causes of stuttering.
Robert West summarized the observable differences between
stutterers and non-stutterers as follows:
There are certain demonstrable differences between the
stutterer and the non-stutterer, aside from the spams that
occur during speech. The chief of thee are (1) the slow-
ness of diadochocinesis of the stutterer's articulatory
muscles and (2) his lack of vocal inflection.9
West went on to suggest that these two differences may be re-
lated; the lack of inflection being a manifestation of a spasticity of
musculature, which also causes sluggish articulatory movements.
Emil Froesehels indicated that "Stuttering is a nervousness,
7Klingbell, "The Historical Background of the Modern Speech
Clinic," op. cit., 121.
8ryngelson, "Investigations in the Etiology and Nature of
Dysphemia and Its Sympton, Stuttering," op. cit., 16-17.
9Robert West, Lou Kennedy, and Anna Carr, The Rehabilitation of
Speech (New Ycrk: Harper & Bros., 1947), 87.
kwieh as a rule rise in early childhood."10 James S. Greene, when
deeeribing the underlying characteristics of stuttering wrote, "Stut-
tering is a nervowu affleetion."1 He further suggested that some
children have an inherited nervous constitution predisposing them to
stutter. He explained that they may go along without any difficulty
unless a trameu or accident occurs to precipitate the disorder. He
deeeribed the oneet of stuttering in this way:
Stuttering isn't simply a bed habit that time will cure
it is a nervous disorder. It is a signal that the child
is meeting some situation, or is wnder soae strain with
which his nervous system cannot adequately cope.12
Lee Bdnvrd Travis seems to have had this point of view in mind
when he wrote:
The stutterer, as do meot other types of speech defec-
tivei, represents a certain lack of maturation of the central
nervous system which results either in malignation of the
highest neurophysiologieal levels involved in speech or the
predisposition of these levels to disintegration when ex-
poeed to necieeptive stimuli.13
According to Engene F. Hahn's summarisation, E. J. Boone, a
British authority, appeared to eoneur with Travis. Boone considered
the easee of stuttering to be two:
The enmdogeon er constitutional, by whieh the child
lamil Fresehels, "Differences in the Symptomology of Stutter-
ing in the U. S. and in Europe," The Journal of Speech Disorders, VI
(-rah, 1941), k4.
Jame S. Grsene, "Hope for the Stutterer," Hygeia, XXIV
(February, 1966), 120.
1Le Edward Trwris, Speosh Patholog (New York: D. Appleton
& eO., 1931), 25k.
inherits neuropathic tendencies, which predispose him to
stammer; the exogenous or environmental factors, among which
are included shock, fright, illnesses, and strain. The in-
stability of the nervous system is the primary cause of
stamering, while the environmental factors, by weakening
the individual's physical and psychical resistance, serve to
reveal the latent tendency. The actual stammer is not in-
herited, but the child may inherit the nervous instability
of the parents. The secondary factors will then contribute
to the general instability of the nervous system.l1
A psychosomatic theory of stuttering has been presented by I. W.
Karlin. He related the development of myelinization to the onset of
stuttering. He believed that the slower the development of myeliniza-
tion, the greater the chance for stuttering. The stuttering is then
enhanced by environmental pressures. He stated:
If stuttering continues, emotional factors and habit
formation begin to play a greater role in perpetuating this
disorder. In the older child and in the adult the emotional
factors and established neuromuscular habits become the pre-
dominant causative agents of stuttering.15
West, then, would seem to have found some justification for the
many theories which suggest a relationship between stuttering and the
nervous system. Using a neurological test for stutterers, he found that
in sloess of diadochocinesis, stutterers resemble spastics. The
stutterer's lack of vocal energy, according to West, suggests "a lack
of muscular energy an asthenia an inability to produce inflections
because inflections require muscle contractions and the energy is not
Eugene F. Hahn, Stuttering: Significant Theories and There-
pies (Stanford University Press, Stanford University, 1943), 122.
15. W. Karlin, "A Psychosomatic Theory of Stuttering," The
Journal of Speech Disorders, XII (September, 1947), 322.
1West, The Rehabilitation of Speech, op. cit., 87.
With West's findings in mind, it seems relevant to take note of
am experiment which tested the effect of preetigmin on ten chronic
stutterers. Proetigmin, a tension-reducing drug which acts to depress
the muscle tome, wa administered to stutterers from fourteen to forty
years of age for fourteen months. The dosege wa four 15 ag. tablets
a day. For the duration of the experiment, speech training was inten-
tionally avoided. The authors concluded:
There seemed to be good reason to believe that prostignin
did have seo effect en the severity of the spasm during
the early weeks of its use and possibly later, making it
easier for patiente to manage the stutter . the tension
erected by the severe space, was reduced. . To all out-
ard appearances the stutter is a muscle spasm.17
Although there seems to be some agreement as to the importance
of the normusrmeular differences between the stutterer and the non-
esutterer, the unanimity is neither complete nor enduring. This seems
to be the point of departure at whiok place researchers embark in many
different experimental direetien. It would seem wise to consider, at
this point, them, the possible underlying or leos observable differ-
eoee@ between the stutterer and the non-etutterer which might hav
eamwtiv or effective relation to the already mentioned obeervable
difference of hypertonisity.
There have been numerous metabolic and bioehemieal studies made
aling this line, and an account of some of these studies should help
lead the my toward seeing the justification of the present reeearoh
1Howard J. Sehaitel and Roy F. Street, "Prostignin and the
nCrowie S atterer," The Journal of Speeeh and Nearing Disorders, XIV
(Juae, 199), 1)3.
in a clear light.
In 19, H. E. Starr gave the following reasons for selecting
the saliva as a means of investigating the relationship metabolism
might have with stuttering:
This fluid is constantly being secreted, swallowed, and
passed through the physiological cycle. It may be readily
collected for examination at all times and places. It may be
regarded practically as transformed protoplasm of the secret-
ing cell, with admixture of salts and other substances vir-
tually dialysed from the blood, and affected to a greater or
lesser degree by the conditions obtaining in the oral cavity
and by the constituents of the alveolar air. The glands of
secretion have abundant neural connections with both the
cranial and sympathetic nervous systems. Thus of the three
principal sets of ealivary glands sublingual, submauxl-
lary, and parotid each one is innervated by both cranial
arnd sympathetic nerves.18
The results of Starr's research showed that 73.7 per cent of the
stammerers examined in his survey of the University of Pennsylvania
Speech Clinic were sub-breathers, and had their systems overloaded with
In'another study in 1929, Starr found that stutterers have
characteristic high alveolar carbon dioxide as opposed to non-stutterers.
It is quite evident that the sub-breathing stammerer is
overloaded with carbon dioxide. Not overloaded beyond phys-
iological limits to sueh an extent to be classified as patho-
logical, he is overloaded beyond the limits of the
psychologically normal. As he improves under treatment,
H. E. Starr, "The Hydrogen Ion Concentration of the Mixed
Saliva Considered as an Index of Fatigue and of Emotional Excitation,
and Applied to a Study of the Metabolic Etiology of Stammering," The
American Journal of Psychology, XXXIII (1922), 39%.
largely by meins of intensive breathing exercises, his alveolar
EO2 dimir.ihes and with it, of course, the partial pressure of
the carbon dioxide in the blood.20
On the basis of his studies, Starr emphasized the relationship
between payehological and physiological processes:
We need simply to recognize the fact that the physiolog-
ieal parallels the psychological and is indicated by the
ehemistry of the individual . even motivation, that most
psychical of psychological processes, is correlated with or
parallels metabolism. Z
E. B. Twitwer reported a study made by M. Trmper which found
a correlation between the types of breathing and the red cell aount and
hemoglobin content. This research included 101 subjects who showed
symptoms of stuttering. Tramper concluded that shallow breathers have
a heato-respiratory compensation, which means that an increase in the
red eell volue and hemoglobin content of the blood compensates par-
tially for the inadequate respiratory reactions. He proposed that the
earsity of voemn staeorers is due, in part, to the lower viscosity of
their blood, thieh in turn, is due to a lower red oell volme.22
James F. Bender omented upon the above findings of Trusper as
His finding of a high erythrocyte count in the stutterer's
blood is especially important in the light of W. B. Cannon's
researehee that erythrecytes are increased during emotional
ehamnes and that the increase is due to a sympathetic
i. E. Starr, "Psychologisal Coneoeitants of High Alveolar
Carbon Dioxide," The Psychological Clinic, XVII (March, 1928), 12.
22B. B. Twibtsy, "Stamering in Relation to Hemo-Respiratory
Faetors," The Quarterly Journal of Speech, XVI (June, 1930), 278-83.
stimulation of the spleen. Thus, the high blood sugar content
is believed to be indicative of the emotionality of the stut-
Wendell Johnson, Genevieve Stearns, and Edn Warweg conducted a
study in 1933 which had as its purpose the detection of any alterations
in the chemical composition of the blood In stutterers which might show
a relationship to the muscular spasms and increased musle tonus in
stuttering. They suariied the results of their research in this
1. The sera calcian values of fifteen stutterers were
found to be wholly normal, tending toward the upper limits
of the normal range. These findings were interpreted as
evidence that the increased muscle tonus and muscular spasms
observed in stuttering are not associated with low calcium
tetany in these cases.
2. No alteration in the normal relationships between
serum calcium and serum potassium or inorganic phosphorus
3. The fasting blood sugar level of fifteen stutterers
was not altered from the normal. Severe stuttering of one
half hour's duration was insufficient to alter the level of
blood sugar of one subject. It would appear, from these re-
sults, that the emotional reactions associated with stutter-
ing in these cases are not associated with any disturbance
of carbohydrate metabolism.24
George Kopp conducted metabolic studies of stutterers when he
was at the University of Wisconsin. This research represented an
effort to determine how the metabolism of the stutterer differed from
that of the non-stutterer as evidenced by blood serum calcium,
23James F. Bender, The Personality Structure of Stuttering
(New York: Pitman, 1939), 33.
24eadell Johnson, et. al., "Chemical Factors and the Stutter-
ing Spasm," The Quarterly Journal of Speech, XIX (June, 1933), 413-lI.
inerganie phosphate, potassium, chloride, cholesterol, non-protein
nitrogen, albumin, total protein, globulin, and glucose. The reasons
why Kopp hose the blood as the basis for his study would seem to lend
further relevanoe to the present study.
The blood is the medium in which all metabolic exchanges
are made and is therefore the eovirowment in which muscle and
merve tissue live and function. Since normal life and func-
tion are depeoient upon a definite equilibrium of the blood
contents, the coinerse holds that abnormal function may be
due to a disturbed equilibrium of the blood contents as re-
flected in the metabolism and composition of the nerve and
mucle. The composition of the nerve and muesle determines
whether the reception of and reaction to stimuli of all kinds
can be elaesified as normal. The nerve impulse is not an
entity within itself. The clonie and tonic myospeems of the
stutterer are faetamL evidence of abnormal function. It is
evident that if the afferent, assoeiational, or efferent
nerve impulse of the stutterer differ, then somewhere along
the nerve fiber, its eell or ganglion, will be found the change
in composition that must predispose the change in the charac-
ter of the impulse. Likewise if the musculature of the stut-
terr is different from that of the non-stutterer, the
difference mut be one of composition.2
The differences between the blood of the stutterers and the non-
atutterere ere meetly within the normal range. Kopp listed his
fidings as fellowE:
Stutterers have a higher total serum ealcium than non-
The inorganic phosphate is higher in stutterers than in
The poteesium is loeer in stutterers than in normal.
The total protein, albumin, and globulin are lower in
stutterr than in non-e-utterers.
There is no great difference in non-protein nitrogen
B-erge Keop, "natabelic Studies of Stutterers," Speeh Mono-
,MEkh!, I (September, 193k), 123-2k.
between the two groups.
There is no appreciable difference in diffusible calcium,
cholesterol, and chloride for the two groups.
The stutterers have a high blood sugar as compared with
The blood pattern of the stutterer, as shown by the corre-
lations of total serum calcium, potassium, inorganic phosphate,
total protein, and non-protein nitrogen, is practically the
reverse of the pattern of the non-stutterer.26
These findings led Kopp to conclude that, "Stuttering is a mani-
festation of a disturbed metabolism." Kopp believes that someday stut-
tering might be controlled by dietary means which would regulate the
metabolism of the child. He added, "The metabolic changes which take
place in producing and maintaining stuttering must first be estab-
In a study which compared the blood distribution among fifty
stutterers and thirty-eight thousand people who had previously been
typed in investigations carried on in the United States, Jeanette
Anderson and Mary L. Whealdon found no significant differences in the
blood distribution of stutterers and normals.2
I. T. Karlin and A. E. Sobel made a study of the chemical com-
position of the blood of twelve stutterers and twelve children with more
normal speech. Each stutterer was matched with a non-stutterer of the
28Jeanette Anderson and Mary L. Whealdon, "A Study of Blood
Distribution Among Stutterers," The Journal of Speeh Disorders, VI
(March, 191), 23.
aMe age, sex, height and weight. The authors found no statistically
significant differences between the two groups.29
Because of his belief in the justification of nutritional
studies of stutterers, Robert E. Card conducted research on the rela-
tionship of allergy to stuttering. He studied case histories of 104
stutterers and their families. He eoneluded that:
Similarities between the factors of stuttering and asth-
mtic relations; the positive histories of allergy in the
stutterer's families; the fact that every stutterer tested
showed a marked degree of sensitivity; and the degree of
stuttering seemed to be in direct proportion to the severity
of reaction to the intradermal tests -- all of which indi-
eates the likelihood of stuttering being in such cases a
manifeeuation of allergic reaction.30"
In 1938, A. M. Kennedy and D. A. Williams also found a rela-
tionship between stuttering and histories of allergy. In a study of
one hundred stutterers, they found fifty-two stutterers had personal
histories of allergy and, of the rest, all but one had family histories
of allergy. They compared these one hundred stutterers with a group of
one thoueesd non-stutterers of whom only 37 per cent had personal and/
or family historiee of allergy. On this basis, they concluded that
some individuals have a predisposition to both stuttering and allergy.31
I.. Karlin and A. K. Sobel, "A Comparative Study of the
Blood Chemistry of Stutterers and Non-Stutterers," Speech Monographs,
VII (1940), 82.
30obert 1. Gard, "A Study of Allergy in Relation to Stutter-
ing," The Journal of Speeh Disorders, IV (September, 1939), 229.
31A. M. Kennedy and D. A. Williams, "Association of Stammering
and Allergic Diatheis," British tedieal Journal (December 24, 1938),
E. M. Glaser, in 1936, conducted a survey of the possible rela-
tionship between stuttering and endocrine malfunctioning. The survey
consisted of consulting twenty-nine endocrinologists concerning their
experience with patients who stuttered. Among Glaser's findings is
this report of Dr. Murray B. Gordon of the Long Island College of Medi-
I reported five cases of childhood myxedema and
hypothyroidism in children in which stammering occurred dur-
ing the course of thyroid treatment. I considered it as a
manifestation of a general nervous excitation following dis-
turbance of the central nervous rsstem. The stammering
disappeared on discontinuing the thyroid extract and re-
appeared on its resumiption.32
Dr. Harry A. Solomon, of Bellevue Hospital, wrote Glaser as
Two cases of stuttering occurred in a group of congenital
thyroid insufficiency (cretin) cases. In no other form of
endocrine dycrasia have I ever noted this defect. In adult
hypothyroidism (iyxedema), primary or secondary slowness of
speech, jumbling and difficulty in pronouncing words is a
constant feature. This is due to the disturbed function of
the nervous system when deprived of the stimulating influence
of a specific hormone, thyrox.Ln.33
A more recent study concerning the relationship between endo-
crine malfunctioning and stuttering was reported by Marion Kramer in
1947. In an unpublished thesis, Kramer reported an experiment con-
ducted at Stanford University Medical School in which it was found that
epinephrine injections into women nhose ovaries had been removed,
32E.. Glaser, "Possible Relationship Between Stuttering and
Endocrine Malfunctioning," The Journal of Speech Disorders, I (Septam-
ber, 1936), 84.
seemed difficulty in fluency resulting in temporary stuttering.34
Martin F. Palmer and Anna Mae Gillett conducted a study of
tmenty-one stutterers and tiwnty-four normal speakers. The study com-
pared the heart rhythm of the two groups. The authors surmised that
"Stuttering is the result of a sex-linked, neuro-physiologico-netabolic
It become evident, in light of these related studies, that in-
vestigatione eoneerning the possible neuro-physiologieo-metabolic
etiology of stuttering appear not only varied in their points of attack,
but seem controversial in their conclusions as well. Cognizance must be
taken of the frequency of inference and the temptation to theerize
present in many studies of this nature. Harris 1Hill, in 1941, evaluated
eritisally the bioohemioal investigations conducted up until that time:
In all instanees where differences between stutterers and
normal speakers wre purportedly obtained, the differences
wre esapared with and shown to approximate closely, changes
in so-called normal persons during muscular activity and effee-
tie behavior. . In case of biochemical differences, no
findings warrant any assumption of special metabolic or chemi-
el agents which are oaueal. The phenomes of stuttering oan
rll be explained if principles of normal behavior are adhered
te without attempting to eke the stutterer a unique animal in
frion romer, "A Critical Examination of Studies on Physio-
logieal Aspeete of Stuttering," (Unpublished M. A. thesis, Stanford
Martin F. Palmer and Anna Me* Gillett, "Respiratory Cardiac
ArrIythmia in Stuttering," The Journal of Speeeh Disorders, IV (June,
3Harris Hill, "Stuttering; I. A Critical Review and Evaluation
of Biehemieal Investigatione," The Journal of Speech Disorders, IX
Granted, then, that there has been no conclusive evidence ad-
vanced which establishes physical, metabolic, or neurological differ-
ences between the stutterer and the non-stutterer which can be considered
causal. However, it appears permissable, if not mandatory, that further
staxty be undertaken in these areas. It should be clear that if evidence
of such differences were to be uncovered, it would still be impossible
to discount th, research results which have accrued from developmental
or environmental theories of stuttering causation. A brief review of
the evidence supporting the environmentalist's point of view seem
especially cogent here, because it will tend to demonstrate that the
present study is not designed to refute this evidence, but rather the
rationale of the current investigation is wholly consistent with and
partly dependent upon the evidence already established by developmental
or environmental research.
According to Wendell Johnson's diagnosogenic theory of stutter-
ing causation, most children go through a period during which hesitations,
repetitions and prolongations non-fluency, per se, are normal con-
comitants of speech utterance.37 Johnson stated:
These repetitions and hesitations are not accompanied by
any apparent tension or anxiety on the part of the child.
They seem to occur somewhat more frequently when the child is
*talking over his head,* when he lacks sufficient knowledge
of what he is talking about, when the listener does not re-
spond readily to Ihat the child says, or his vocabulary does
not contain the seemingly necessary words. Such conditions
appear to occur often in the speaking experience of very
37Wendell Johnson, Peple in Quandaries (New York: Harper &
Bros., 196), 445.
Johnson further describes this non-flueney as occurring more frequently
when the child is talking in the face of competiblen. Mor non-fluency
seems to occur twen the ehild as feelings of shame or guilt brought on
by parental scolding or rejection. This is especially true when the
seolding or rejection have reference to his right or ability to speak.
There is also indication that non-fluency increases during "language
spurts," such as during the transition from the use of single words to
the speaking of short sentences, or from the utterance of simple sen-
tenees, or when the child begins to use the pronoun I in place of me.
It is interesting to note that Johnson first became interested
in studying the effect of labeling or diagnosing these non-fluent
pattern as "stuttering," when he was made aware of the fact that among
the Bannock and Shoshone Indians there are no stutterers. Upon in-
vestigation it was learned that these tribes had no word for "stutter-
ing" in their language. They had a relatively permissive attitude
teowrd speech and speech development, and, in fact, had no label to use,
no nmm to oall, and no differences to point-up regarding non-fluent
speech.4 It is.this very aet of labeling an otherwise hormal pattern
of speech that Johnson believes brings on the feelings of anxiety, ten-
sion, and fear of speaking situations so evident in the older stutterer.
The fear leads to avoidance attempts, and these attempts, in turn,
result in hypertense, reinforced stuttering. It was Johnsons promise,
then, that when a child is made to feel that his speech is thought of
as different, wrong, abnormal, bad or stuttering, he will come to
anticipate, apprehend. attempt to avoid the stuttering, and finally he
will stutter with excessive tension.
Subsequent investigations by Johnson, those mentioned below,
and others, have tended to support the cogency of Johnson's theory.41
Some of the recent studies, for example, have established the vital in-
fluence of parents and their reaction to non-fluency.
Oliver Bloodstein investigated the possibility that parents of
stutterers make diagnoses of stuttering more frequently than parents of
non-stutterers. He found that parents of stutterers do diagnose stutter-
ing more readily as "stuttering," and they also diagnose non-stuttering
more quickly as stuttering.
Using various scales of parental domination as tests for parents
of stutterers and non-stutterers, John P. Moncur reported "Parental
domination ws indicated by the responses of more mothers of stutterers
than by those of the others of the non-stutterers on all phases of the
h~lendell Johnson, et. al., "A Study of the Onset and Develop-
ment of Stuttering," The Journal of Speech Disorders, VII (September,
4Oliver Bloodstein, William Jaeger, and Jack Tureen, "A Study
of the Diagnosis of Stuttering by Parents of Stutterers and Non-
Stutterers," The Journal of Speech and Hearing Disorders, XVII (Septem-
ber, 1952), 308-O9.
3John F. Moncur, "Parental Domination in Stuttering," The
Journal of Speech and Hearing Disorders, VII (June, 1952), 155.
Although P. J. Glasner conducted a study which demonstrated that
"No specific emotional or environmental factor produces stuttering with
asy significant regularity," he did find that enviroTmental pressures,
especially speech pressures, were foreground in the stuttering
Granting, then, that there does appear to be a vital relation-
ship between environment and the ontogenesis of stuttering, we still
cannot exclude from the realm of possibility that non-environmental
differences do exist between individuals who are relatively susceptible
to environmental pressures and those who are relatively unsusceptible.
The search for neuro-physieal or metabolie differences between adults
has revealed nothing of significance. However, the extreme paucity of
stuttering research dealing with children has left many investigative
stones unturned. Charles Van Riper concurred with this belief when he
stated, "Much of the mystery of stuttering is due to the tendency of
investigators to confine their observation to the adult case, with
little regard for the development of the disorder. The research on
children has been merger. ..4
It has been previously stated that it was the purpose of the
present work to study the effects of thiamine (vitamin B1) upon children
whse speech hea been rated by trained judges as "non-fluent." Sueh a
4P. J. Glasmer, "Personality Characteristies and Emotional
Problems in Sttteerers UWder the Age of Five," The Journal of Speech
and Hearing Disorders, XIV (June, 1949), 138.
4Gh rlee Van Riper, S Correction Principles and Methods,
3rd. ed. (Nw Tork: Prentie-Rall, Ine., 195), 343.
study might or might not uncover physical differences between fluent and
non-flient children. The factor of differences was not the primary con-
cern. The principle interest of such an investigation has been
described by Elizabeth R. Alexander, who did the exploratory forerunner
of the current project. She stated:
It has been ared that hesitant speech among children
learning to talk is not only common, but quite normal and
that pathological stuttering is instilled only when these
tendencies become complicated by personality conflict. Emo-
tional reactions on the part of the child to his non-fluency
in turn may accelerate the development of his stuttering.
Hypertensions, fatigue, restlessness, and general nervous
irritability whichappear so consistently among children who
see to have a predisposition to stutter, suggest that treat-
ment to reduce those factors might have a secondary effect
of reducing the tensions of fhe faltering speech.46
Having completed a review of stuttering theories and research,
and having stated the purpose of the present work, it becomes necessary
to explain the possible relationship of thiamine to speech, and specif-
ically, to non-flnt speech. That which follows will include a
description of thiamine, its biological function and therapeutic usee,
its history and nutritional sources, its role in carbohydrate metabo-
lism, and its relationship to the central nervous system.
Thiamine and Nerve Integrity
Several elementary, but necessary, definitions will aid in the
exposition of thiaaine and its relationship to the present study.
4Elizabeth R. Alexander, "An Experimental Study of the Effec-
tiveness of the Administraticn of Thiamine Hydrochloride in Preventing
Siutterirg Among Pre-School Children," (Unpublished M. A. thesis, Uni-
versity of Florida, 1950), vi.
1. Vitamin: According to Walter Eddy, a vitain is a chemical
eompouiid thoe preaenoe in the diet is essential to the Bmintenance of
growth and health, and hose absence from the diet or inadequate supply
results in specific manifeetations of ill health or pathology.
2. Thiamine: The word "thiamine" will be the preferred symbol
for that vitamin of the B-eomplex group occasionally called thiamine
hydrochloride, vitamin B1, or aneurine.
3. Coearboxylase: Cocarboxylase is the active form of thiamine
in tissue oxidation. It is the thiamine pyrophosphate (pyro an acid
forced from another acid by action of heat, and pyrophosphata a salt
of pyrophoric acid).
Eddy's brief historical account of thiacine, indicates that it
wa first isolated, in 1925, by Janeew and Donath. Later, WilliPms
improved their yield and established the chemical nature of this
vit n. 48
lddy explains that "study of biological oxidation has shown
that mry of the vitamins are actively concerned in oxidation reactions.
They form important action or 'prosthetic' groups in the enzymes arnd
seema~yr that the body use for transport of hydrogen, or activation
of oxygen in the oxidation by which food energy is made available.
Sinee the principal fuel food is sugar, whn sugar is oxidized in
47w;, r H. Eddy, That Are the Vitamins? (New York: Beinhold
Publishing Corp., 19 1).
tissue cells, it is converted into water and carbon dioxide, and energy
is liberated in the process.
Man's need for thiamine bears a direct relation to his calorie
intake and to his ingestion of carbohydrate calories in particular. The
phosphorylated thiamine, or oearba~ ylase, is apparently as effective as
the thiamne chloride. Eddy related that when brain tissue of thiamine
deficient pigeons was subjected to the breakdown of glucose to lactic
acid, it was noted that there as an abnormal increase in lactic acid.
It was fur noted t the addition of thiamine restored tissue
respiration in the presence of lactic acid, but produced no increase in
the absence of the lactate. This led to a search for another inter-
mediate pyruvic acid. Eddy provided a brief but lucid explanation
of this aspect of thiamine metabolism:
In the conversion of glucose to carbon dioxide and water
in tissue cells, one of the final steps in the process is the
formation of pyruric acid and its conversion to carbon diox-
ide and water by oxidation and decarboxylation. The increase
in pyruvic acid in the blood of thiamine deficient individ-
uals and its prevention by thianine dosage suggested that Bl
fitted into the steps of glucose metabolism at the pyruvic
acid stage. Beriberi oases show an increase of pyruvic acid
in the circulating blood; increased blood pyruvate is today
used as a diagnostic sign of thiamine deficiency.
A forward step in the explanation of how B1 might act was
provided by the isolation from yeast of a coenzyme by Lohman
and Schuster in 1937. This'coenzyme turned out to be a co-
carboxylase, in other words, the coenzyme operating with the
carboylase enayme in splitting carbon dioxide from an
organic acid such as pyruvie. Chemical analysis of this co-
carboxylase proved it to be the pyrophosphate ester of B1 or
S. Ochoa and R. A. Peters reported that there is a greater
amount of cocarbozylase than thiamine in animal tissue. They further
stated that eoearboxylase can be synthesized from the vitamin by the
liver, but rot by the intestinal mucoa.51
B. C. P. Jansen pointed out that the discovery of coearboxylase
in yeast, and its ability to change pyruvic acid to acetaldehyde,
clearly demonstrated that thiamine in the phosphorylated form played a
part in yeast breakdown of sugar. Whatever the by-products between
pyrruie acid and the ultimate carbon dioKide and water, thiamine pyro-
pphepbate is an essential feetor in the transformation. Inadequate
supply of thiamine results in failure to eliminate pyruvic acid and
failure to eemplete the final steps of glucose coiwersion into energy.52
This failure, of the metabolic of a fuel in a tissue, accord-
ing to Eddy, "is bond of itself to cripple the full efficiency of that
tiseus. Secondarily, regions innervated by nerves so affected will
niesesarily fail to get meoal control, producing results which vary
with the tissm or organs so affected."5
The information offered above form the basis of the thiamine
rationale important to the present study. A review of the experimental
use of thiamine will reveal further possible relationship between it and
te neurology of speech.
A study by W. M. Gorier, tich considered the rationale of
51S. D0hea and R. A. Peters, "Sygntesis of Cocarboxylase,"
Iture, Ai2 (1938), 358.
5B. C. P. Jbnmei, "The Physiology of ThiamiNe," Vitamin and
NMemmes, VII (1909), 83.
J531d, What Are the Vitamis?, op. cit.
vitamin therapy with cases of shock and anoxia, would seem to contribute
relevant data and information basic to the comprehension of thiamine
rationale.4 Shock was induced in a number of dogs by fractional bleed-
ing and thiamine administered to half of them with an apparently bene-
ficial result. "T thiamine treated dogs lived longer than did the
controls."'5 This result led the author to consider whether the
thiamine was acting in its normal manner as a coenayme in tissue metab-
olism be e an nil in shock wus in some way thiamine deficient, or
whether the thiamine was acting in som other manner. According to
Govier, "A diagnostic test well known to clinicians is the estimation
of the Irle of pyruic acid in the blood . since breakdown of
pyruie acid requires phosphoylated thiamine or cocarboxylase as a co-
enzyme, a deficiency of thiamine will cause pyruvate to pile p in the
circulating blood." Blood pyruvate determinations were done on a
number of animals in shock, d the pyruvate level of te circulating
blood was seen to rise from a normal amount of 1.0 to 2.0 ag. per
hundred cubic centimeters to or 5.0 ag. per hundred cubic centi-
meters of blood. lee is actually t seen in most cases of
beriberi. The author concluded "t either these animals became thia-
mine deficient as ohock was induced, or that their thiamine became
54. X. Govier, "Rationale for Use of Vitamins in the Therapy
of Shock and Anoxia," J. Am. Med. Assoc., 126 (1944), 749-50.
incapable of functioning in a normal manner" For an insight into
ame of the mechanisms involved, further direct reference would seem
It was mentioned before that the inbermediate group of
dogs, having normal plasma thiamine levels, were benefited
by thiamine therapy. One explanation of this fact would be
that the animals' ewn tissue thiamine bear-e ineffective.
I have also mentioned that the thiamine must be phosphorylated
to diphospho-thiamine or cocarboxylase in order to be effec-
tive as a coeasyme in pyrurate metabolism. In the tissues
there is probably an equilibrium between thiamine (and/or its
monopherphate) and cocarbozylaee as lsorwn in this reaction:
Thiamine + Phosphate Cocarboxylase
Under normal conditions most of the thiamine is in the
pkosphorylated form, but it seemed possible that under ab-
normal conditions, sueh as in shook, the earcoboxylase might
become dephoepherylated, thus shifting the equilibrium to
the left and soneomitantly reducing the amount of metabol-
ieally "active" thiamine. Ochem has shown in vitro that
under anaerobic conditions such breakdown of coearboxylase
does occur, probably by means of a phoephatase. We have con-
fired his results. Both eoearboxylase and total thiamine
were determined in the skeletal muscle, liver and duodenum
of dogs before and after shock, and after thiamine therapy.
Dephoephorylation of eooarboxylase occurred in 92 per cent of
the seeoe in the mueele, in 69 per cent of the oasese th
duodeum and in 46 per cent of the liver samples. The magni-
tuie of the elphoepkerylation was variable, there being some
tendency for more dephosphcylation to occur in dogs which
Wed into sheek with relatively small amounts of bleeding.
Ttht results have been confirmed by Alexander.
Thus these animals, although well supplied with thiamine,
amre in a sense vitamin B1 deficient, sinee their thiamine
was in a form whiek was ueless in tissue metabolism. Admin-
istratien of more thiamine in large does to thee dogs as
treatment resulted in resyi heis of eoearbexylaee. Large
doees af thiamine are probably required in order to raise the
intracellular concentration of thiamine so that resynthesis
mw occur, even when oxidative promeses supplyig energy for
phkosporylation of thiamine are greatly reduced.
DeCaro and co-workers examined the content of lactic and
pyruvic acids in blood and tissues of normal and thiamine deficient
rats after injections of pyruvate and lactate. Intrapcitoneal injec-
tion of 0.5 to 1.0 mg. of sodii lactate per g. bodyweight caused an
increase in the lactic acid content of the blood and muscles of normal
rats and of rats deprived of vitamin Bl, and a slight increase in
pyruvic acid content in the muscle and brain of normal rats. Similar
injections of sodium pyruvate were followed by an increase in the
lactic acid content of noral musle and of blood, muscle and brain of
deprived rats, and an increase in the pyruvic acid content of the
muscle and brain of normal rats, and of the blood, muscle and brain of
The disease complex that includes magaesophagus (cardiospam)
megacolon, and mega-ureter is considered by E. Etzel to be due to a
chronic vitamin B1 deficiency. The deficiency causes a degeneration
of the cells of Auerbach's plexus with a resulting achalasis of the
sphincters concerned. A further study of 170 cases with sixteen
autopsies confirmed this conclusion. A statistical review of 621
cases observed in the last eighteen years, showed -iat the disease
occurred at all ages, but that the majority of persons affected were
young farm laborers between the ages of fifteen niid twenty-five years
from the poor, central and northeastern part of the State. The diet
L. DeCaro, et. al., "The Content of Lactic and IPyruvic Acids
in Blood and Tissues of normall and Vitamin B1 Defieient Rats After In-
gestions of Pyruvate and Lactate," Boll. Soc. Ital. Biol. Sper., XT
wa m inly of beea, polished rior, maioc flour and crue eame sugar,
with eoasioilly supplaents of dried meat, eggs, potatoes, vegetables
and milk. Smh a diet s deficient in vitamin 1, and this fact,
togaMar with the marked suseepti~ility to the disease of young males,
with their high oalerie requireants al, therefore, high vitamin B,
requirements, is oemidered as further evidence of the importanee of
viteaLn B in thlSieleoa of this disau eeplx.60
In metabolism experiments with zats, Henmnn found that during
deprivtion of thiamine the exygen eomu ption fell mokedly, declining
SMt rapidly in the terminal stages of defiiiensy with the onset of
A study by 1. L. Hardt and I. V. Still of the thiamine content
at swat rwvaled considerable loss of thinine in swat which might
hnn serious physiological eoneoquenoes for workers and athletes with
am inedequa intake of the vitein..
I. Saty reported that in pigeons deprived of vitamin B1 there
me an imerse in the isrenmlin eenrtet of the aremals in the early
stag of defieieey, but a great derease a symptoms of beriberi
began to appear. TIM adrelin content of the blood of deprived
pipes was lower then normal in the first te weeks on the deficient
K. Eteel, 'y the Diseas OCselex that Ineludes Megmspha-
gur (eeaiemrpam), Mrgeelean and Maga Ureter Caueed by Chronic
Titemin l DefieiasyT", Amer. J. M6d. Sti., CCIII (19k), 87-100.
61. Hemresn, "Vitamin B Deieieney and OCp en Oa i uptiom in
te," eiPe. ler's IteIhr., C~II (11i), 23.
L. L. Hardt and Z. T. Still, "Thiamine in Sweat," Pree. See.
gmp. iBel. d., xmImIIII (191l), Td7-.4.
diet and later mh above normal. Similar changes were observed in the
adrenalin content of rats deprived of vitamin B1. When pigeons were
given 1 ag. of vitamin B1 daily, there was a decrease in the adrenalin
content of the adrenals and an increase in blood adrenaline up to te
days of the over-dosing, but if the large doses were continued, the
adrenalin content of the adrenals rose to normal ad the blood adrenalin
fell, thoug not to normal.6
An experiment by S. Ochoa was concerned with further determining
enymic synthesis of cocarboxylase in animal tissues. A anary of his
findings is presented below:
1. Liver slices, lirei or dispersionss" from avitaminous
pigeons convert added vitamin B1 into eocarboylase to an ex-
tent hich does greatly surpass the normal cocrboxylase
content of the tisue. Optimmlly, with small amounts of'
vitamin, 30 pe cent of this may be converted ino cocar-
boxylase in 30-60 minutes at 380.
2. Brain and muscle preparations are much less active;
preparations from duodenal msmos (pig) shoLwd no activity
under various experimental conditions.
3. With liver, synthesis is dependent on an active respira-
tion and is highest at alkaline reactions (optimm about pH8.5).
The synthesis is inhibited by iodoacetic acid but not wash
affected by NaF.
4. An essential part of the enayme catalysing the synthesis
5. Soluble enzymes which, when no respiration is possible,
destroy cocarboxylase, are present in liver, kidaey, muscle and
brain; their activity is highest in those tissues (liver and
Kidney) which also show the highest synthetic capecity.64
63. Sarfy, "The Effect of Vitamin B1 on the Adrenaline Content
of the Adretal Glands and Blood," Hoppe-Seyler's Ztsehr., CQLXII (1939),
64S. Oshe, "Esymic Synthesis of Ceesrbeaylase in Animal
Tissues," Biochem. J., XXXIII (1939), 1262-70.
Ime" Helt, Jr. determined the thiamine requirements of normal
intfant by ue of a urinary eeretion procedure which involved finding
the intake that would maintain urinary exertion at the apper limit of
the ame of minimum elxretion. The requirement varied between 0.14 ag.
ant .fl9 mg. per day in the seven subjects stdied.65 The thiamine re-
quirwmuto of pve-sehool ohildrm were considered by H. Oldhan to be
0.59 ag. per 1,00l ealries.6 William and co-workers dsesribed the
lowest mniva thiimine requirement of an as being 0.46 ag. per 1,000
amlerie.67 Te sensept of minim food requirement as defined by
HElt as "tiat intake whieh will just protest against definite clinical
ymptee."68 N poriwed a owneis insight into the limitations of
asseeming rltaonn requirements:
The problem of amss ing vitamin requiremnts has bee
seepli ated by the discovery of a number of variable factors
*iek may influence thom. Viteain requirements are conditioned
by pathelegiael preossesm wieh affect absorption or utilisa-
ties or increase the need for particular factors. But eves
in thein riml subject there ae wide fluctuations in require-
mets eased by the matue of the food, its effect on the
beeearial syntasmis of vitamin in the intestine, ad its eon-
tset of antri-itamins. Alteotiam in the diet or beeterio-
static drugs are knera to afftet the synthesis of vitamins in
the intestine. Vitamins present in the diet may be destroyed
imame Kelt, Jr., at. al., "Te Thiamine Requiremnt of the
Mwrl lWaa," J. latritiorn--XII (194l9), 53-66.
"K. OldMm, et. al., "A Study of the Ribeflavin and Thiamine
kALr winar of Ghilhd- of Preshool Age," J. Nutrition, XXVII (19i ),
67R. Willian at. al., "cObeeratioen on Indued Thiamine
kBfleinMe in Min," Aroh. mTn.th ., LxTI (19b0), 7850-.
66%at, 'The Thiamie RequLrement of the Mermal Infant," 2E.
before ingestion by exposure, processing or king, and in the
intestine they my be rendered unavailable by agents which com-
pete with, combine with, absorb or destroy them.69
Holt also described his preference for methods of determining
Thiamine deficiency has been measured by assays of thia-
mine in biopsied tissues, by determination of thiamine in
serum, by the cocarboxylase level of the blood cells, by the
pyruvate levels or the rpyruate ; lactat ratio of th blood
serum, and by various excretion procedures for measuring
urinary thiamine. The biopsy technique, aside from obvious
objections, is undesirable because of its inaccuracy and the
paucity of "normal" standards. Pyruvate levels and Pyruvate:
lactate ratios are influenced by non-specific factors (exer-
cise, excitement) which ar difficult to control in infants
and were therefore to be avoided. The analytical methods for
blood thiamine and cocarboxylase measurement at the time our
study was begun were not considered sufficiently reliable and
accurate, and some urinary excretion procedure therefore
seemed the best method for estimating the degree of di-
IW. Wainlo reported that thiamine requirement appeared to be
lower with a diet containing muoh protein.71
R, C. Wright and E. M. Scott supported the view that, with a
.high-fat diet, lack of thiamine is less serious because the normal oxida-
tion of fat, unlike that of carbohydrate, by-passes the oxidation of
71W. W. Wainio, "The Thiamine Requirement of the Albino Rat as
Influenced by the Substitution of Protein for Carbohydrate in the Diet,"
J. Nutrition, XXIV (1942), 317-29.
C. C. Wright and E. M. Scott, "i-yruvate and Aketoglutarate
Metabolism in Thiamine Deficiency," J. Biol. Chea., CCFI (195~), 725-33.
Rxperiments with rate weighing from 55 g., deprived and not de-
prived of thiamne9, and with some of these subjected to paired feeding,
showed that only deprivation of vitamin B1 had aiy affect in causing a
rise in bleed pyric acid.73
Although there appear to be several questions concerning the
effect of thiamine on the nervowa system which are still unanwered,
my recent studies have sentributed both accumlative data and interest-
ing theories. According to A. TOR huralt, sewral hypotheses have been
p"- forward regarding the participation of specific chemical substances
in the action potential. He eltaued to have brought together at least
three sush "action substtnees," acetylcholine, thiamine, and potassium.
A wry aall quantity of aeetyleholine appears to be liberated in nerrve
during tke passage of the impulse. About ten times as much thiamine
(located in the sheath) is also formed. It is believed by Yon Muralt
that "aestyleholine formation is essential for the excitation or re-
erewy proesee and that anearin (thiawine) is a reservoir substance
eleoSey oeeneted with the fomation and disappeerance of aestyl-
ebeline."7 F. yse claimed that like aeerleholine, thimine is
supposed to exist in two fome, bound and free. He considered it to be
of gaeml agreement that thiamine is oe~eered in the formation of
aseate from pyruate.75 Ton Muralt found that OR mild oxidation of
7G. Fetwri, "Behavior of Blood Pyrwate in URlernutrition,"
Boll. Sae. Ital. 3bel. Ser., XXIX (1953), 290-92.
%. Tern Mult, "CheMieal Intermediate in Nerve Action,"
nature, OU.T (194k), 767.
75i. Wyms, "The Two Forms of Aeetylcholine and Thiaine," ely.
Rsiol. Aeta., II (194), 121.
nerve with ferricyanide in an alkaline medium, thiamine is changed to
thiochrome and longitudinal or cross sections of nerve show an intense
violet fluorescence of the yelin sheaths. In degenerating nerves of
guinea pigs a decrease in thiamine content ean be detected by this
methd within twenty-fo hours after section.76
In a later article, von Muralt stated, ". . thiamine is
essential for the maintenance of the internal chemical equilibrium of
the neurons (nerve cell and peripheral nerve). The store of thiamine
in the cell is continuously used up in maintaining this equilibrium, and,
as the cell is not able to synthesize is vitamin, a constant require-
mnt from other sources is the result."77 In consideration of that is
the role of thiamine in the chemical equilibrium of the neurone, why is
thiamine permanently used mp in maintaining this equilibrium, and what
is the requirement of a neurone at rest and during activity, n Nuralt
admitted that these questions seemed so simple and yet were so diffi-
cult to answer with even a first approximation of the problem.
The extracts of fifty frozen nerves (fifty excited and fifty
unexcited) were fed to various groups of rats in a state of avitaminosis.
The average increase of pulse rate after extract feeding revealed that
the extracts from stimulated nerves contain a measurable amount of thia-
mine, whereas the extracts of unstimulated nerves contain only a
76 on Muralt, "hemieal Intermediate in Nerve Action," op. eit.,
7A. von Muralt, "Thiamine and Peripheral Neuro-physiolog,"
Vitamins and Hormones, V (197), 114-15.
esthreehold amomt of thiamine, if awy, according to von Muralt.8
Thimnme is liberated in tea to tweety time greater amounts than
aeetylekoline and especially is this true during excitation. The pre-
aeding statements were repeatedly stressed in ron Huralt's report. It
ws observed by Wyss and Wyss that after poisoning a nerve with
memoideesetie amid, more thiamine is obtained in the extract of resting
rrnee than in the extract of emaited nerres. In the poisoned nerve
thiamine is liberated in the rating metabolism and "fixed" in the
process of excitation (wuder condition in which the sequence of chemi-
eal relations has been altered by the poisoning, the poisoned nerve
wsa a behavior opposite to that of the normal nerve).79
D. shmrnasehn and H. B. Steinbeh studied the axene of the
squid and found that oeearbemylaee is enmeentrated on the surface of
tke axome. If the serves are in electrotonem at the moment of fixa-
tion, an aees nation of thiamine is observed at the site of the anode,
whieh is an in~ieation that thimine is liberated in relation to
anbelie, rather than to eatabolie, proeesee. These findings would
eem to support ven Muralt in his view that thiaine plays an important
rele in mrve metabolism and that "during the state of liberation, or
hertly afterward, a certain liberation of thiamine takes plaee whioh
A. von a ualt, "Stimulated and Umetimulated Nerve Content of
Thiaine," Arch gee. PIysiol., CGXVII (19a3).
7A. Wyss and F. Wyes, "Coparimsn of Extractions of Thiamine
free Peisoned and Iited Nerves," Experoenia, I (194), 160.
D. ~h ma-mWh and H. B. Steinbek, "Thimnine Concentration
in qitd Ase,"* J. MeWureal siol., V (1942), 109.
disappears almost as quickly as.it is produced."81 It ma emphasized
that the experimental findings wre fragmentary and their evaluation
might be influenced by further experimental work.
P. Kaiser mentioned that thiamine inhibits the action of
acetylcholine on the heart: "Awt ing that normally this action
counterbalances the action of acetylcholine (which is liberated as a
result of the natural action of the vagus), then a state of aritaminosis
should produce bradyoardia."82 Williams and colleagues observed this in
man at the first stages of avitaminosis.83
The content of thiamine was studied by von Muralt and J. Zemp
in the frog sciatic nerve. Stimulation significantly increases the
value of thiamine.
C. Casella and L. G. DeCaro pointed out that even when grave
neurological signs of thiamine deficiency are present, the rate of
conduction and action potential are normal in the sciatic nerve.8
Another recent investigation in this area was reported by W. A.
Mannell and R. J. Roesiter. They reported:
81A. von Muralt, "Chemical Intermdiate in Nerve Action," op.
82P. Kaiser, "Thiamine and Acetylcholine in Bradycardia," Arch.
ges. Physiol., CCXXII (19al), d50.
8R. D. Williams, et. al., "Induced Thiamine Deficiency and the
Thiamine Requirement of Man" Arch. Internal Ned., IXIX (192), 725.
A. von Muralt and J. Zemp, "Thiamine Content in Frog Sciatic
Nerve," Arch. gee. Physiol., CCXXXXVI (1943), 746.
85C. Caella and L. G. DeGaro, "Cnduction and Aetion Potential
of Nerve of Rats Deprived of Vitamin BI," Arch. Sei. Biol., XXXII
Rats received for W4 days an adequate bseal diet or one
deficient in vitamin BI. In same rats the aciatic nerve was
out and, after eight day, the concentration of nucleic acid
and phospholipin in intent and degenerating nerve was eeti-
mated. The ales were spared with thee for animals of the
sam age receiving adequate vitamin B1, called age controls,
for younger animals receiving adequate diet but killed hen
the bodyweight was the sa as in deprived rats, called weight
controls, and for animals of the sam age receiving adequate
diet restricted in amount, called wight and age controls.
In the age controls eoneestrations of nusleic acid and
phospholipin in nerve tissue decreased with increasing age
and bodyweight, and the previous observation was confirmed
that, in the intact sciatic nerve of the rat, the concentra-
tion of n mleic aeid was oharacteristie of age but not of
bodyweight, and the coneentration of phospholipin was char-
acteristie of body$ight but not of age. In rats deprived of
vitamin 1B, the sonsentration of nucleic acid as less than
in the wight controls, but did not differ from that in the
weight eaotrols but were greater than in the age controls.
After section of the seiatic nerve, increase in the eon-
ewration of nucleiei i ads occurred more slowly in rats de-
priwd of vitamin B1 than in the wight controls, which were
yeoger animals, but at the same rate as in the other two
mets of rontrols. The decrease in concentration of
leeosolipin in nerves from .deprived animals took place acre
slowly them in nerves freo aqy control. The result distin-
uitshsd the effects of vitamin BI deficiency from those of
laek of protein or of total calories.
There s no evidence that during degneration of the
sciatic mnrve proliferating Sehwam eells provided esymeu
hish destroyed the wrelin sheath, since there was no destrue-
tion of melin or lees of eplin lipids.8
Vitamin and aeetyleheline formation in isolated brain matter
s examined by P. J. Mann and J. H. Quaetel. Their findings are
eu rised below.
Is appreciable differcenee were found in the capacity of
intact bwain slices, from oral and polyneritic piLeegn,
to syte~isse aebyleholine ader suitable aerobic conditions
in a biarbomate Leeke pyrvate medium. If, however, a
S. . Lnmell and J. Rossiter, effectt of Thiamine De-
fiiemey en the COnmentration of Nueleic Aeid and Phospholipid in In-
tet and seetone werve," Brit. J. INtrities, VIII (1954), 56-64.
Imdium containing a relatively high concentration, 0.03 M, of
potassium ions was used, the polyneuritic pigeon brain syn-
thesised acetylcholine at a rate less than the normal, but
this was increased to normal by addition of vitamin B1. No
such increase occurred when the vitamin was added in similar
circumstances to slices of normal pigeon brain. The presence
of vitamin BI affected the synthesis of acetylcholine by
polyeuritic brain only in the presence of pyruvate.87
Thiamino was ascertained in the cerebrospinal fluid by G. Saker
by means of the PyVcomyces test. The amount of vita-in B1 present vw
very variable and bore no relation to the amount present in the blood
or to the clinical condition of the patient. Intravenous injection of
vitamin BI was followed by an increase in the amount found in the
cerebrospinal fluid; vitamin B1 rapidly passed into the blood when in-
M. Prados and R. L. Swank reported an investigation of vascular
and interstitial cell changes in vitamin deficient animals. In pigeons
and kittens made chronically or acutely deficient in thiamine, a study
was made of the vascular lesions in the brain. Yasodilation, probably
caused by increased permeability of te vessels due to accumulation of
metabolites from disturbed carbohydrate metabolism and consequent
collection of fluid and red oells in the perivascular spaces, was the
first sign of damage, and infiltration of the surrounding tissue
followed. The distribution of the vascular lesions corresponded with
that of degenerating neurones. Neuronal lesions were always found
8p. J. Mann and J. H. Quastel, "Yitamin BE and Acetylcholine
Formation in Isolated Brain," Nature, GXXXXV (190), 856-57.
G. Saker, "Aaeurin in the Osrebrospinal Fluid," Klin.
Woehensehr., XIX (190), 99-102.
surrounding hemorrhages. Selling of the oligodendrocytes and
elaseate&eiroeeis of astroeytes were observed in the brains of kittens
with acute deficiency symptoms, but in kittens with chronic deficiency,
the oligodendroeytes were almost unchanged and the astrocytes beae
hyperplastie and hypertephied. Theee changes were considered to be
Don-specific and related to the glioeis which occurs when neurons die.
It is not thought that vitamin BI has specific anti-degenerative prop-
erties for nervens tissues.
Unlike other tissues studied by J. Selcedo and co-workers, the
brains of rate maintained their thiamine concentrations in the face of
a deficit of thiamine for a considerable period, after *aich there
enear an abrupt fall in thiamine content. The critical point at which
the brain begins to lose its thiamine correeponds to the attainant of
the minimum level of uriary thiamine excretion. This finding would
sem to support the view that the point of urinary excretion is of
physiological significance. The authors suggested tiat the point of
iniima excretion in the urine is a highly useful criterion for measur-
ing thimine requirments umder various condition.
Functional studies of the nervous system in experimental
beriberi eonBdeted by C. F. G urch appear to furnish directly related
material. A sumary of his work is presented belew.
0MR.Prwad an R. L, Sank "Taceular and Interstitial Cell
Ghagee in Thiamine-Deficient Animala," Aeh. Nearol. Pgsyhiat., XXXXII
"J. Seloedo, Jr., et. al., "The Relation Between Urinary Ex-
eretion and Tiase Coementratioms of Thiamine in Rate," J. Nutrition,
XXXVI (1948), 307-13.
1. e characteristic neurologic symptoms of beriberi re-
sulting from lack of vitamin B (B1) in the at are 1, changes
in auscular tonus; 2, ataxia; 3, disturbances of equilibrium;
and 4, hyper-excitability. Muscular tremors and weakness some-
tims occur but true convulsions an paralysis ar n pa of
the beriberi syndro.
2. The labyrinths righting reflex is lost in beriberi at
the onet of disturbances of equilibrium, but the ne~k and
body righting reflexes are preserved. A pathologic tail re-
flex exhibited by beriberi rate gives evidence of the spread-
ing of the refllc arc in the spinal cord.
3. Evidence is presented of the functional integrity of
the peripheral nerves and proprioceptive nerve endings in
beriberi in the rat by the method of recording nerve action
U. Vestibular function is significantly altered in beri-
beri. The duration of nystagmus following a standardized
rotational stimulus increases progressively following with-
drawal of vitamin B (Bi) from the diet, preceding the appear-
ance of other neurologic symptoms.
5. This prolongation of vestibular response is character-
istic of vitamin B (Bl) deficiency. Inanition, otitis, and
deficiency of vitamin D do not appreciably affect the mean
result of the vestibular test, thile deficiency in vitamin A
diminishes the result. In vitamin G (B2), a small terminal
increase was noted.
6. The vestibular function test is sensitive to the rela-
tive insufficiency of vitamin B (BI) resulting from depriving
the animal of fat (with its "sparing action" upon vitamin B.)
7. The chief neurologic manifestation of beriberi in the
rat can be accounted for on the basis of leeions in the
vestibular nuclei. The finding of perivascular hemorrhage.
in this region is confirmed but thee lesios are regarded as
secondary to insidious tissue changes resulting from specific
lack of vitamin B (8i).91
Injection of 0.1 to 0.2 ml. of a 0.2 per cent solution of lactic
or pyruvic acid into the brains of pigeons produced convulsions similar
C. F. Church, "Functional Studies of the Mervou. System in
Experimental Beriberi," Am. J. Physiol., Ill (1935), 660.
to thee. observed in birds deprived of vitamin Bl. The effect mas
appearetly specific for lactic and pyruric acid as the injection of
similar amounts of physiological salt solution or of larger aaomts of
sedia acetate produced no convulsions. These obeerratione by I. I.
Witaeaen and C. Angeloseu, are take as further evidence of the effect
of acomulation of pyrurie and lactic acids in the brain in easing
autbe yWptem of vitamin B1 defieiene.92
R. R. Sank aad H. H. Jasper obserred that when pigeon were
dpriTed of thiamine, there was a progressive increase in the amplitude
of the potentials reeerded by the enoephalogram up to about three times
the meowl value. In the final stages of deficiency, there was marked
slei ng down and depression of brain potentials. If vitamin BI was
administered, the brain potentials returned to normal within a few
hok s. It ea suggested that the changes in brain potentials indicate
mrked feeilitatior of sortieal discharge during the initial phases of
vitsan 11 defieimey before depreeion occurs.9
Rietopathologieal sttiies were reported by Smak upon pigeons
subjeeted to total or partial thiamine deprivation, to starvation alone,
r te steamtion and deprivation ef thiamine. The state of aente de-
fieiear mwe amifeeted by epistheteecs. Pow or no merphologioal
II. I. Niteame and C. Angeleewm, "Itheds for Galiing Conyvl-
aioes Siilar to Thee Seen in Polyneiritis by Intraserebral Injeetion
at Lacse er Pyrwie Acid," Zteasr. Vitamin foreeh., ILL (1942), 82-85.
3R. R. Simik and H. H. Jasper, 'leetroemeephalograms of
Thimie-Deficient Pignes," Arah. Nemrol. Psyehiat., IIXTII (1942),
changes w-re detected in aute cases, but in chronic cases, a degenera-
tion of both peripheral and spinal neurons was demonstrated. The ex-
tent of degeneration of sciatic nerve fibers corresponded closely with
the degree of paralysis observed. Further studies of thiamine defi-
ciency in pigeons were mde with diets described above giving acute and
chronic symptoms. Histological examination s ma of the brains of
seventy deprived pigeons and of normal birds, by various methods of
fixing and staining designed to demonstrate Dth neurofibrillar struc-
ture of the neuron. The first visible change in the neuron was a
degeneration of the distal part of the axon, moving towards the center
and accompanied by slight shrinkage of thr cells. Large nerve fibres
degenerated first, medium sized ones, later, while the sw fibres
usually remained intact even in severe deficiency. Birds with marked
opisthotonos sometimes showed no neurological lesions. Study of
opisthotonos in acutely deficient birds indicated that th movement
was probably du to selective release of vestibular centers from
labyrinthine control. In chronic vitamin B1 deficiency, pigeons without
opisthotonos showed moderate degeneration of all central and peripheral
terminations of vestibular nerves. In both acute and chronic states of
deficiency there was no consistent degeneration in the optic lobes, the
nucleus rotunda of the thalam~u, the reticular formation or the
secondary vestibulo-cochlear centers.
From curative studies it appeared that neurons showing early
9R. L. Swank, "Avian Thimine Deficiency," J. Exp. oed., LXXI
digunration ohange could be retored to normal by administration of
vitain B1, but that aewvely affueted ems continued to deenerate.
bmain hemorrhages observed in some birds wre apparently secondary to
chaaes in axvns and sell bodies, and had no relation to the clinical
sewdition aoesrding to work by SRnk and Prado.9
J. I. Oseoperan's study on the Tifluease of thiamine on the
sm.eeptibility of chieks to avian enoephale7elitis is ummarised below.
QW-4sy old leghorn hicks, divided into three groups,
reeeiving law, staeptiw, ad se~i im level of thiamine wre
inmelated with a virus suspension of avian oeephaloryelitis.
The shieks receiving the highet level of thiaine wre pro-
teated be the greatest degree.
Ina another rie of oon-day old lhite leghorn chisks
ere gile an optiim level of tiMine in the ration for two
Wasks, then divided into three groups receiving lewls of
tRiamin aa indicted in the previous experimnnt for two weeks,
at Ate end of ksieh time they wre inoculated. In this ease
all the chicks receiving the lowest level of thiamine were
prothted to the greatest degree.
It is evident that the protection afforded against this
virms depended upon a nraer of factors, tich included the
age of the ehiek, the preioes state of nutrition and the
state of nutritiea- at the tim of ineeulation.96
S. Steme sttuied he effsetiMver of thiamine therapy in
seral dgemnrative and infectiois disorders of the nervous system,
smk as tabes dem slis, rlro yphilis, and poliomylitis. Intraspinal
pyridelcm awi thkamieo therapy,. (in combination ith artificial fever
in ahebu half ie ease.), resulted in an improved feeling of
95. L. SwB k and I. Pradoe, "Avin ThiamiLne Deicieney 2,"
Arle. OI el. Payesiat., XXXXVII (19W!), 97-131.
i. f seqrman, et. al., "The Influnce of Thiamine on the
aseepbiility of Qieks te Atil Bmneephalewelitis," J. Bet., LII
(1W ), 467.
well-being, increase in performance ability, and greater range of move-
aeit in the affected extremities. Treatment was more effective in
patients with weakness on effort and muscle cramps but showing little
muscle atrophy, and also in patients with so residual muscle power.
On the other hand, chronic case of poliomyelitis ith no muscle power,
or only a little, exhibited no significant change in strength of de-
liz .nfluenee of exe on the growing rat in the presence
and absence of vitamin B1 was investigated by N. B. Guerrant and RI A.
Dutcher. Forced exercise in rats deprived of vitamin Bl reduced the
feed intake nd g rate, ad accelerated th onet of paralytic
symptoms. In rats receiving vitamin B1, fore exercise reduced th
growth rate and increased the r of fiscal pellets excreted. The
animals that were confined without exercise showed slightly greater
food consumption and excreted greater quantities of beces than exercised
rats. The et of paralysis was slower in confined rats deprived of
vitamin E1 than in exercised animals. These findings did net resemble
those with animals deprived of vitamin A, but the differenmee might be
explained by the differences in the physiological functions of the two
The work output of frog muscles was increased by additions of
7S. Stone, "Pyridoxine and Thiamine Therapy in Disorders of
the Nervous System," Nutrition Reviews, II (MIy, 1951), 131.
9N. B. Guerrant and R. A. Dutcher, "The Influence of Exercise
on the Growing Rat in the Presenoe and Abeen~s of Vitamin BI," J-
Nutrition, XX (1940), 589-98.
thiamine hydroehlorid or additions of thiamine pgrophosphate, in a
btudy by N. W. Shok and W. H. Sebrll.99
Perfomanee in wduranee testa of holding the arm horizontal or
heading the breath for prolonged periods did not appear to be affected
r administration of vitamin Bl. Psyrhologieal fators were shown to
inflwmnee the teste hich war, therefore, not considered to give re-
liable inmlweaon of seula r control, ameording to the investigators
P. T. Karperish awd I. Millman.
W. Crsee reported the effect of administering vitamin B1 and
gliesee in meOte experimental exhastion in different humn subjects on
ke bisyele arge~ster. A erbination of vitamin B, and gleose was
hiley effeetive. In vitamin B1 deficiency, administration of glucose
alm had no effect, but benefit acrued as eon as vitamin B1 also mu
atdListwred. This ras suggested as a method of deonstrating vitamin
i defeis my. An iereeed requirement for vitamin B during work at
kigh tempratues ma also demonstrated, defending possibly on in-
rensued emeretion of vitamin 1 or eoearboxylase in the aet.101 I
amsther wrtIelU Breese stated that, maximaa work which amn be produced
by homa objects is imereaed by tie addition of thiamine. MItabolic
"I. W. Sock and W. N. Sabrell, wRelation Betmeen Thiamine
and Go-earbeylaee Com~entoiten and Work Out-put of Perfaed Freg
Mmlee," Freeo. See. epti. Biol. ed., LII (19i5), 21-17.
loop. W rviwh and N. R1UU1 "Titn n B1 and Enduraee,"
Ntw o 1. J. M, ., OKXOI (19*2), S81-82.
14v. Brse, *The Wffeet of Titamia BI and Gloees on Acute
kpWer i ntal, Iaustion," Arbeit.. Pr iol., XI (190), 117-38.
rate and efficiency are not influenced."1
1. WI. Tuttle reported that the reaction time of hypo-vitaminotic
men was longer than those with adequate thiamine consumption.03
It was reported by R. F. Harrell that thiamine increased or in-
px-ved acuity of vision, skill at games, reaction time, reading,
arithetical process, nmorising, and intelligence. Her procedure
involved the administration of 2 ag. per day of thiamine to thirty-
seven children and a placebo to thirty-five carefully matched con-
Harrell's findings would seem to be at least partly contradicted
by this summary of a study by O'Shea ard colleagues:
From observation on four adult subjects and four controls
we may conclude:
1. Foresight and judgment, as measured by performance on
mme tests, are impaired when the subjects are deficient in
the B vitamins and are improved after therapy with thiamine
or with the B complex.
2. General intelligence, reasoning, ability (reading),
and speed of hand mus le coordination (tapping) *how no meas-
urable deterioration then the subjects are deficient in the B
vitamins and noe provement after therapy with thiamine or with
the B eomplcu.105
10W. Droese, "The Effect of a Mixture of Vitamin B and GlI-
cese on Physioal Efficiemey," Muneh. Med. Woehemhr., XXXIII (19k1),
103. W. Tuttle, et. al., "The Effeet of Low Thiamine Intake e
the Reaetion Tim of Won," ederation Proe., VII (1948), 126.
1S. F. Harrell, "Mital Response to Added Thiamim," J. Nutri-
tion, XXI (1946), 283-98.
10SH. 1. O'Shae, et. al., "Mental Changes in Experimental
Deficiency," An. J. Med. Si., CCIII (1942), 396.
1. C. Robertson conducted a carefully controlled investigation
patterned after the study of Harrell. Robertson used identical twins
s subjects and controls, and found no significant changes that could
be attribaedt to thimine supplemnt.106
In view of the purpose of the present investigation, and the
studies mntioaed above relating nutrition to behavior, it sems
interesting to take notices of a proeamemnt by the Nutrition Foumda-
tion, Ins., wih appeared in the August, 1954 issue of Nutrition Re-
The complex interrelationships vbeween nutrition and
behavior represent an interesting but underdeveloped sector
of the siense of human nutrition . ..
The effects of nutrition represent phenomna challenging
modern social sciemee by the need for combining the approaches
ef anthropology, aeciology, and psychology. The problem of
atrition and paehe ean and must be approached from the
meatepsyehologie point of view (offeet of nutrition on behav-
ier), as -ell as by considering the emotional significance of
foods ad sting to the individual and to the group.107
It seems advisble at this point to consider further the thso-
retisal rationale upe tkiceh the me of thiamin for stuttering or non-
flamsy is based. Lecstr Hale ummarised:
The obrtl nerMus system depeAs upon earbohydrate as
a sweeps of emwF y and thiatn is needed in carbohydrate
mesfablia. 1oA tIhee is a re6ustion in normal thiamin in-
tshe, the nsar l n erous system is likely to suffer. Gen-
varely, if added stain is placed upon the nervous system,
1e6. C. Rebertkw, "The Effset of Added Thiamine on Growth,
Visire and Learning, Using Identical Twins," J. Nutrition, XXXIT
WTle t]trition Feerdation, Inc., "Nutrition and Behavior,"
IhRttioa Serie ., XII (August, 1954), 237-40.
or there is a greatly augmented metabolism, there is increased
thiamin requirement. If normal thiamin intake is not suffi-
cient to meet these conditions or thiamin is being inadequately
assimilated, neurological imbalance may result.108
Louis Goodman and A. Gilman point out that symptoms of mild
thiamine deficiency are not as characteristic as severe deficiency and
may escape diagnosis.09 Hale emphasized that thiamine deficiencies
ay exist without outward manifestations until circumstances of addi-
tional stress are placed on the system. He postulated that "A residual
diathesis may exist in the thiamin level, and this accounts in part for
the narrow margin of safety in some individuals who seem predisposed to
Hale's coamnts on the effect of "stress" upon the individual
appear to be particularly relevant to a recent discussion of this topic
by Benjamin Ershoff:
Any factor that interferes with the digestion, absorption,
or utilization of nutrients, or increases their destruction or
excretion may result in malnutrition despite the apparent ade-
quacy of the diet fed. Body requirements for eeential
nutrients may furthermore be significantly increased for pur-
poses of detoxification or by factors such as physical exer-
tion, fever, drugs, toxins, burns, fractures, and other trauma,
major surgical procedures, abnormal environmental conditions
and others. The net result of such factors is an increased
body requirement beyond the usual or average range and the pre-
cipitation of nutritional deficiencies on diets that would
otherwise be adequate.
Lester L. Hale, "A Consideration of Thiamin Supplement in
Prevention of Stuttering in Preschool Children," JSHD, XVI (DeeWmber,
109Louis Goodman and A. Gilmam, The Pharmacological Basis of
Therapeutics (New York: Mec~illan, 1941).
lHsale, "A Consideration of Thiamin Supplement in Prevention of
Stuttering in Preschool Children," op. cit., 330.
It is erroneous to state that "stress" per s
increase nutritionl requirement, for stores. is net a
specific mwarying and distinct entity. "Stress" is a sbate
of the organism, a resultant of those prooeee an organism
employs in attempting to maintain hemostasis under nMfavor-
able alterations in the environment (including the internal
milieu). Furthermore, since life itself is a preeoc in
whioh the organic attempts to maintain itself in a changing
eairoment, "MtrL1ee im inherent in life itself. The in-
oereed nutritional requirementi following exposure to stress
r agents reealt ot as a coeequenoe of "stress" per se, but
rather from the increased requirement for specific nutrients
due to the physiologic effects of the particular stress or
It is moa elear by Hale that the ontegeoaeis of speech can be
both a souree of A specific stress to the individual, and it can be
affected by internal s well as external untoward conditions. He
The ese and fluency of the conditioned reflex.e of speech
are erot easily upset T~en the symergie mrements are being
first acquired as syieols of thought and feeling during the
prmeehool ago. If thiaain can be of any assistance in con-
trolling stuttering, it is felt that it would be of most pre-
ventive value in tie yog eild.112
Elisabeth R. Alemanter esoducted an eapleratory inrestif nation of
thiamine as a stuttering preventive among pre-sehool children.1 In
this eixparimest, teo ag. of thiamine were adnistered three times daily
to a selected grap of ten pre-b eel children twho showed beginning
sympjtes of stu8tering. Another group of children with non-fluent
iBen3amn H. Breahff, *Nutrition and Strees," Nutrition Re-
vim, XIII (Febr ary, 195), 3-4.
%llale, "A Consideration of Thiamin Supplemat in Prevention of
Stuttering in Preachool Children," op. cit., 339.
EliaZ bth R. Alexander, "An EJperimStal Stady of the Effee-
tibuuees of the Admilstratien of Thiamin Hydreekleride in Preventing
Stuttering Aeng Pre-Scheol Children," op it., vi.
speech, from the sane environment, were given a placebo during te same
period of time. At the end of one month, the groups were reversed and
observations of both groups continued for another month. Neither the
parents nor the investigator knew which dose the child was receiving,
and improvement was judged on the basis of these individuals evalua-
Alexander smmaried her findings as follows:
1. Unquestionable speech improvement in 55 per cent of
all the eases.
2. There may have been an improvement in an additional
20 per cent of the cases.
3. No ipt can be claid in 20 per cent of the
4. Of the two and three year olds in the experiment, 80
per cent were unquestionably improved.
-. Only 50 per cent of the four year ol wr definitely
6. It is doubtful that either of the two five year olds
made m improvement.
7. There was negative evidence of the effect of thiamin
on the speech pattern of the seven and eight year olds.
8. In four cases where there was regression of speech
fluency occurring following the cessation of thiamin therapy,
there was improvement noted again after thiamin was resumed.
9. One of the cases which was reported as unimproved dur-
ing thiamin therapy, showed an increase of tensions, heita-
tions, and other stuttering symptoms after the thiamin had
10. With only one exception, cases that showed marked re-
duction of stuttering symptoms made the improvement within the
first two weeks of treatment.11
Alexander concluded, "aneugh evidence of improvTen nt in suffi-
cient ambers of canee indicates that the administration of thiamin
hydrochloride may be effective in preventing stuttering in pre-eehool
Several recomeadations for further study wre made by Alexander,
and they would appear to be of extreme relevance to the current study.
She suggested tat future research in this area should include objective
determinations of the thiamine statiu of the subject before and during
tHe test deee. A further reome nation was made to the effect that
mtheods of determining impraoemnnt be subjected to more controlled
Although it is principally Alexaner's study upon thich the
premmt research is baed, it may be relevant to report E. M. Penson's
study of the effect of thimine on twenty adults who stutter. Using a
seuterbalansed thiamine-and-plasebe design similar to Alexander's,
1. No positive evidee was fowud that would justify a
definite satetmMt that thia a erves as a factor facili-
toting speech tuning.
2. On the theer hand, no evide*e was fold that would
jwtify a definite statemt that thimin does not serve as
a father facilitating speech training.
3. The results indieate some poseiility that thiamin
my have contributed to speeek irwvement.
4. In spite of the indefiiteneec of the results, there
seM to be meugh indiesMaen of see possible eentribution
of thiamin to speech improvement to warrant further investi-
This chapter has presented a brief historical background to the
subject of stuttering and non-fluency. Reference has been made to
studies related to the efficacy of thiramine Investigations directly
relevant to this research have beeo reviewed.
The purpose of the present study is to investigate the effect
of thiamine on children with speech non-fluency, using the recommended
additional controls of determining thiamine status through assay and
dietary history, and determining speech improvement by relatively
Chapter II describes the procedure followed during the course
of the study, and the methods used to determine and evaluate results.
Edward M. Penson, "An Exploratory Study of the Effect of
Thiamin Hydroehloride on Adults Who Stutter," (Unpublished M. A. thesis,
Ohio University, 1951), 95.
DESCRIPTION GF PROZDURE
The age of the children need as subjects ranged from 3.0 years
to 7.1 years. The mean age was 5.015 years. The median age was 5
years, as was the mode. Dorothy Davis Tuthill, in her study of non-
flueae in the speech of young children, designated two to seven years
of age as the range mest likely to include normally non-fluent utter-
ares1 Weadell Joheon conurred with this age range. The present
*auty did not include children wider three years of age, because them
ehildre wre net amenable to sueoessful urie sampling nor were they
adaptable to the speech rating situations which required comected,
peptaaeeus dieouras in the absenee of a parent.
There wre twenty-two male experimental subjects and ten female
eperimetal subjects in the stwdy. Although we are dealing with non-
fluant speech behavior, it my be significant that, in the present study,
the sma distribution of the subjects compared favorably with national
inedenee estimates of stuttering in the ale and female as cited in
3oretby Davis, "The Relation of Repetitions in the Speeeh of
Twa' Gihildreo to Oertain Mesures of Language Maturity and Situational
FPatere: Part I," The Jeurnal of SpeeWh Disorders, IT (Deeember, 1939),
Aimmem, Peasle in Qandries., op. cit., 45.
the report of the White House Conference on Special Education.
There were several sources from lwich the thirty-two non-fluent
experimental subjects and twenty-two fluent control subjects wre
1. Subjects were referred by three pediatricians of the commu-
nity for screening by a panel of at least seven trained judges who
rated degrees of fluency-non-fluency on a five point scale. The panel
of judges and the construction of the rating scale are described in
more detail below.
2. Subjects were obtained through a "pre-screening" survey,
conducted by the investigator and a co-worker, of seven private nursery
schools. If a child responded appropriately during the survey, his
parents were invited to have the child seen later by the fluency rating
panel. A child's responses ware thought to be "appropriate" for panel
screening if his speech appeared to the investigator and co-worker to
be either sufficiently fluent to warrant considering him as a potential
fluent control subject, or sufficiently non-fluent to warrant considera-
tion as a potential non-fluent experimental subject.
3. Subjects were obtained through a survey conducted by the
investigator and co-worker of the kindergarten and first grade of four
public schools. If a child responded appropriately during the survey,
he wms seen later by the panel.
4. Subjects were obtained through invitations extended to the
3White House Conference on Child Health and Protection, Special
Education, Chapter on "The Child Defective in Speech" (New York: D.
parents by the investigator, who obtained the parents' names and
addresses frem pre-sehool registration lists. If the parents accepted
the invitation, the children were given appointments to be seen by the
panel for fluency rating.
5. Subjects were obtained through the process of parents re-
ferring other parents to the investigator for possible inclusion in the
study. The children referred in this mimer were seen by the panel if
they responded appropriately during the pre-sereening survey conducted
by the investigator and co-worker.
In this maner a total of 1,352 children are pre-ecreened. Of
this msber, fifty-sewvn were considered by the investigator and co-
werar to be non-fluent. Forty-four of these children with non-fluent
wspoh wee seen by the panel, and in forty-one eases, the panel also
eoeaidered them to be non-fluent. Me experimental subjects dropped out
f the study onee they had started. One control subject discontinued
her participation after the first week, because of her inability to
digest the adinistered tablet.
It seei releswMt to note that Davis' study found that "the
awm ag e hild repeated fourteen words in eery thousand words he
spoke .. There as individual variation on this measure with a
auber of children tending to repeat words more than the average. . ."
It my appear that the present sudy aeovered a lew incidenee of
mijs, "The Relation of Repetitioe in the Speech of Young
thildres to Certain Meaures of Language Matrity and Situational
Fatees: Peat I," op. sit., 311.
non-fluency, in view of Davis' belief that non-fluent speech is part
of the speech pattern of all children at some time from their second to
their seventh year However, this was not the case if one considers
that airy of the younger children observed may not yet have entered a
relatively non-fluent period, while a large number of the older children
may have already completed this non-fluent stage.
It should be clearly established that at no time during the ex-
periment were the parents or children informed of the particular aspect
of speech being studied. Only three of the parents were aware of the
non-fluecy aspect of the study prior to its outset, arnd in these in-
stances the fathers were members of the rating panel. All other parents
were informed that the study was concerned with investigating the rela-
tionship between nutrition and general speech development. Individual
reports dealing with the child's general speech picture tere sent to the
parents. After the study as completed, the parents were informed of
the specific factors studied and the results were made known to them.
Dosage and Medical Approval and Prescription
In the previous study of non-fluency involving the effect of
thiamine on children of this age, 10 ag. of thiamine were administered
three times each day.7 In the present investigation, it ws decided
7Elisabetk R. Alexander, "An ExperiemBtal Study of the Effee-
tiveess of the Administration of Thiamin Hydrochloride in Preventing
Stuttering Among Pre-School Children," op. cit., vi.
that a substantial increase in dosage might aid in obtaining more lucid
results. It should be pointed out that orally ingested thiamine is non-
texic, even in deses which are several times larger than the usual daily
ibNate.8 This aeurance from H. R. Rosewberg was substantiated by L.
eeodMan and A. Gilman:
Toxic does of thiamine are may thousand times greater
than the therapeutic, and thus the vitamin has a very high
therapeutic index. There is no reason to expect untoward re-
atione frm enn the most vigorous therapeutic regimen with
The doe used in this project was 25 mg., adinistered in tablet
fem., three times daily.
After a shild was designated, by virtue of the panel's ratings,
as being a potential subject, and the parents indicated their wLlling-
Mne to participate, the child's pbyiian or pediatrician as contacted
by the investigator. The medial doctor made one of three promounoe-
meate: (1) the ehild is physically fit and ean be included in the
stuly; (2) the child has not been examined recently enough, and if the
parents will permit the child to be examined, (and the findings are
negative), the shild oen be included in the study; (3) the child's
phlyiel satus does not warrant his inclusion in the study.
In addition to tkis precaution, a letter, containing a preserip-
tive and expositiomal statement was presewted to the parents.10 The
%. R. seeber, Chemisty ad Psiolegy of the Vitamins (New
Terkt Interssieme r Pllecis, 19$2), 169.
tSwBeuma and 6ilsa, The Pharsecologieal Basis of Theapeutics,
e* eds., M12i6.
letter as signed by Raymond S. Camp, M. D., a pediatrician of the eity
in vich the sty was conducted.
By and large, the experimental design consisted of two groups
of non-fluent, experimental subjects which were counterbalanced, and a
third group consisting of fluent, control subjects.
Group I, consisting of sixteen non-fluent subjects, received 25
mg. of thiamine three time daily for a period of five or four weeks.
Thi was followed by the administration of a placebo for an equal
Group II, consisting of sixteen non-fluent subjects, who were
matched with subjects in Group I as rigidly as possible in regard to
age, sex, socio-economic status, and degree of non-fluency, received the
placebo during the first experimental period. During the next period,
the subjects in this group received 25 mg. of thiamine three times
Group III, consisting of twenty-two fluent control subjects,
were matched with a non-fluent subject in the manner already mentioned.
The thiamine and placebo tablets were indistinguishable from
each other in aspects of size, shape, color, texture and type of eon-
tainer. Because thiamine has a rather characteristic odor, several
drops of flavoring such as spirit of peppermint, were applied to each
bottle of thiamine and placebo.
Changes in speech symptom or degrees of nee-flueney, were
determined by a panel consisting of as aIy as eleven, and a minimum of
sem n judges. Thee juigee were: (1) Speeh Pathologists with the
Ph.D. in Speech; or (2) Graduate students working toward an advanced
degree with a major in Speeh Pathology, who had clinical experience
with stuttering and non-fluency.
At the outeet of the judges training period, a seven point
male was wed.
1. Flueney relatively free frame observable non-fluency.
2. "Normaly neo-fluent uader exciting condition only.
3. Oeeasional or mild non-flumey without mueeular tension.
k. Moderately severe non-flueney, acompanied oceasionally by
5. Severe, or frequent, or consistent non-flueny, accompanied
jy moderately severe muscular tension.
6. Severe, or frequent, or consistent non-fluaecy accompanied
by severe, or frequent, or consistent muscular tension.
7. Secondary of full fledged stuttering, including starter,
areidamee, and hypertension.
Although agreement ameng the judges appeared to be high, the
investigate and the judges agreed that the validity of the seale was
in .dout. The high apgr ent had eenaisted, for the most part, of
ratings of "point new" on the seale. After several diaesusions, it
beeene elear that the phrase, "uader eseiting senditions only," cem-
tadmed in point Itw, served to prevent the judges from committing thea-
naklee regarding abeervable and cenaistent non-flueney. Furthermore,
the father of "muesular tension" contained in points three, four, five,
and six tended to ake the scale a deuble or "two-qmlitied" ee. Moet
of the judges concurred with the writer to the effect that while non-
fluency is an obe le behavior, muscular tension must, in part, be
assumed as well as observed.
For the above mentioned reasons, then, the rating seals described
below was adopted and used.
2. Mild non-fluency
3. Moderately severe non-fluency
4. S re non-fluency (primary stuttering)
5. Stuttering (with secondary characteristics)
P. M. Symonds indicated that seven is the optiaal number of
steps in a rating scale. He said, "nmre than seven yields an increase
in reliability tat is hardly worth the trouble."1 E. S. Conklin,
however, concluded on the basis of an analysis of 23,000 judgments,
that the maximum number of steps in a scale designed to rate a behav-
ioral quality is five.12 J. P. Guilford suggested that the number of
points on a given rating scale should depend on the motivation and
abilities of te observers, and these qualities should be screened
before the actual judgments begin.1 Joseph WepmaR used a seven point
scale in judging esophageal speech and believes it was too definitive
11P. M. Symords, "On the Loss of Reliability in Ratings Due to
Coarsenees of the Seale," J. Exper. Psyehol., VII (1924), 460.
E. S. Conklin, "The Scale of Values Method for Studies in
Genetic Psychology," Univ. Ore. Pub., II (1923), 2.
13J. P. Guilfort, Psychometric Methods (NIw York: MeGrew-Hill
Book Co., Inc., 1936), 263-79.
ara dBeanding for his purpose. George Shames used a five point scale
in his investigation of prognostic evaluations in speech therapy, and
foad that this asie seale mws atisfactory.1
Before the members of the panel began rating the fluency of
actual subjects, they had reached a coefficient of correlation during
training seesione of .94.
The panel of judges observed the subjects an average of one
tim every alternate week of the experimental periods. On the weeks
that the subjects wre not observed by the panel, two judges (the in-
votigator and on judge) observed the subjects in the children's home
envirommet. It wa felt that the reliability of the panel as suffi-
cient to permit the tw judges to become a reaseoble extension of the
penel. The panel was muinformed regarding the dosage being .administered
te a given subject; nor were they told which subjects were experimental
and wIich were control.
During the regular panel sessions the following procedure as
1. The judge wre seated in two rows on the observer's side
ef a oonemay vision glass. They were requested to rate the five minute
speek ample of emeo shild saeoring to the five point seale, and
reee their ratings on a form provided. The panel members were also
kb-pfh M. f"lpm, "The Objective aswrew ent of Progressive
Bsephagel Spesh Development," The Jeural of Speee& and Hearing Dis-
wrfl,* XVIII (September, 1953), W-.
eorge Shomes, "An Investigation of Pregeois and Evaluation
in Spei Therlfy," J. S. H. D., XVII (Deoember, 192), 387.
16 ix C
requested to count the number of hesitations, repetitions, or prolonga-
tions they heard and to record this number on their rating fori. These
non-fluency counts w~ not sed for determining change of speech flu-
ency. The counting was requested because the process of counting non-
fluencies seemed to help the judges achieve a more objective rating of
each subject's speech.
2. The investigator brought a subject into a room on the re-
flection side of the one-way vision glass. They were seated with the
child facing the front of the mirror, and the investigator diagonally
across a table from him with his profile to the mirror. The child was
told, "I will show you a picture, a you make up a story about it. Tell
me a story about this picture." The subject was then shown a picture
from the Chilra's Apperception Test.17 Thee pictures were presented
in the following order:
first No. 1
second No. 10
third No. 7
fourth No. 8
fifth No. 2
sixth No. 3
seventh -- No.
eighth Ho. $
ninth No. 6
Leopold Bellak and Semya Bellak, CQildren's Apperception
Test (New York: C. P. S. Ce., 1952).
tenth No. 9
This methed seemed to obtain a relatively spontaneous sample of connected
dissouse without the handieop of the adaptation effect. The investiga-
ter, in general, made two types of verbal response to the subjects'
statements. He ade cements which wre essentially neutral, suoh as,
O h," "Is that so?", "I suppose,""I ee," etc. bWh a five minute
ample of speech had not been obtained, another picture ms presented
and th performance repeated. If a five minute speech sample still had
not been obtained, the investigator asked the subject direct questions
sues ms, "If you could play any game you wanted to, what would you
play?', "How do you play that?", "What do you want to be when you get
big?", "What does a do that you'd like to do?" Following a
fie minute sample of speech the subject was given a toy balloon and a
lollipop and was returmd to his parent.
In order to aseertain a possible relationship betaen changes
in speoeh fluency and changes of thiamine status, three twenty-four hour
urine aplae wre obtained for the purpose of thiamine asay. These
realts were then aompard to the amount of eah subject's thiamine in-
take which wM determined by means of a dietary history.18 The follor-
ing Wedule was maintaiaed:
1. For one week the mother of each subject completed a dietary
history. No tablets were administered during this week.
2. At the end of this first week, a twenty-four hour urine
sample wa obtained and refrigerated after a preservative, Toluene, wm
3. The dietary survey was continued throughout the experimental
period. After the first week, the subject received either 25 rg. of
thiamine or a placebo, three times daiy, for a period of ~t more than
five at nt lss tan weeks.
h. At the end of this first experimental period, another twenty-
four hour rin sample was obtained.
5. The subjects who had been receiving thiamine were then ad-
ministered placebo and vie versa. The dietary history as maintained
during this second experimental period.
6. At the termination of the second experimental period, a
third tiwnty-four hr urine sample was obtained.
Prior to the onset of tnh investigation, a brief pilot s
was conducted in an effort to tt the efficacy of the method used to
determine i level. Twenty adults, n who stutter, and ten who
purportedly do not stutter, were included in the pilot study. Each
subject maintained a dietary history for three weeks and ingested 22.4
mg. of thiamine three tine daily during the second and third week.
Two twenty-four hour urine samples were obtained, one at the end of the
first week, and one at the end of the third wek.
A modification of the thiochrome method of thiamine assay was
used in both the pilot study and the actual investigation.1 The modi-
fication is described by 0. Mickelsen as follows:
19The Association of Vitamin Cbemists, Ine., Methods of Vitamin
Assay (few York: Interseience Pub., Inc., 1947).
In work with urine it has been shown, that maeh if not all
of the substances interfering with true blank readings oen be
eliaimated by adding 0.50 to 0.55 ml. of a mixture of equal
parts of conaentrated HC1. ad 85 per cent of Ii3k to the re-
aetieo veesls containing the aeay solution ad te blank
eolutimo before shaking with iobutyrl alcohol. This brings
the pH within the ran e of 8 to 9.5 tare a white precipitate
appears. Under these conditions, this thiochrome ay be oom-
plebely extracted from aque solution with isobutyl alcohol,
but mn thiamine flareseent subetanees are largely eliminated.
Etiaods Used in AnalyAing the Results
In as much as the purpose of this research as to study the
effects of thiaine on children with speseh non-fluency, several com-
pwisem. were me betmman the non-fluent ecperimental and the fluent
ea.trol groups, a. several relationships between thiamine status and
spea flaMney steatu wer tested. The following point were analyzed
in eder to establish resulted:
1. The subjects' fluency, as rated by the panel of judges, wes
studied prior to the administration of thiamine or plaeebo, during both
the thuidne aad piaee~ e dese, and them the three ratings were eon-
C. T levels of tiiamdne in the urine of experimental subjects
wre eaq red with tie thamine levels of control subjects before the
atnij rwrltten of either dee.
3. The thiminle lame of experimatal subjects ware compared
Mith theme of the eotatol subjects after the adminitratien of thiamine.
k. Tets were eA of the possible relationship between thia-
mime le0el of the urine ad speech fluency.
5. A stauy ws made of the peeeible relationship betwem the
sayMe in thiaine levels (from the pre-dea to the thiamine dees
samples) and fluency ratings.
6. A comparison was made of the experimental group and the
control group's intake of thiamine (as determined by the dietary record
'report) before either dose was administered.
7. In view of the usually inverse relationship between thia-
mine and carbohydrate mentioned in the first chapter, a comparison was
umde of the experimental group's ingestion of carbohydrate and the con-
trol group's ingestion of carbohydrate.
8. The relationship between thiamine intk and carbohydrate
intake was determined.
9. The fact that the admirsntration of the doses was reversed,
mar.e it advisable to compare the level of thiamine in the urine of
those subjects taking thiamine first with those taking it as their
10. The intake of thiamine through the usual daily diet wr
compared in subjects tho received the thiamine first and thoee who re-
ceived the placebo first.
PRESITATION AND ETALVTION OF THE DATA
The results of the stay are reported in light of the data
obtained through the rating panel's jtudgmets, laboratory determina-
tions of urine thiamine levels, and dietary reports of thiamine and
earbeydrate intake. The findings presented here wmre dram from the
myriad of raw data obtained throughout the course of the study. This
raw data is available to the reader in the form of a eoaposite of re-
Before indicating the findings of this investigation, it would
see wise to diseuet briefly some of the difficulties enoountered dur-
ing the ecurse of the study. The evaluation of the data must be
qualified on the basis of several uneontrollable variables.
1. The problem of obaining subjects ras emphatically ant
eamrintly premntt throughout the study. This as not surprising in
view of the insewveniees required of the subjects and parents ia-
velved. At any rate, in an effort to obtain isffiieent numbers of
*sebjets, the iwestigater was formed to decrease the number of visits
seek subject me to the speech rating panel. Further, the gradual
increase in the number of subjects as the study progressed caused
subject to begin their participation at different timn.. As a conse-
quence, subjects who began the experiment in January my have been
compared with subjects who begah in March. The reasonable hesitation
on te part of some parents to have their children participate also
caused the experimental period to be held to a minimum This may not
have hindered the laboratory aspect of the sty, but it probably pre-
vented the speech rating panel from obtaining a sufficient number of
ss h samples during the thiamine and placebo doses.
2. It mas impossible to control several factors involved in
the study. The investigator is left to assume that each subject in-
gested three tablets per day as directed. It ut also be assumed
that the parents involved reported the dietary intake accurately, and
equally important, did not increase the child's food intake, quantita-
tively or qualititatively, o they began participating. The further
assumption must be made that each urine sample collected was a con-
tinuous, twenty-four hour sample. It is difficult to estimate the
accuracy of such assumptions.
3. At the outset of the study it was anticipated that a con-
sistent panel of trained judges would rate each subject during each of
the subject's consecutive visits. Although the cooperation of the
panel was maximum, it ams nevertheless humanly impossible for several
of the panel members to be present during every rating session. There-
fore, the panel's judgments were not amenable to such reflective
measures as correlations of coefficients or analysis of variance. It
was for this reason that the mean ratings of the panel for each subject,
on each occasion was used as an indication of agreement. This would
em to be justified because in this ore the man is not distorted by
the extreme of the judgments. NEentially, the mean rating represents
the pael's rating for a given session.
I. It me hoped that a clear reflection of thr. thiamine status
of subject would be derived from eoaputing the percentage of thiamine
exeretion (which in turn is a reflection of the amount ingested and
tie rvlme of thiamine in the urine per day). However, the percentage
figure did not illustrate increase in thiamine concentration in the
wine. The amber of mierogran of thiaine per al. as revealed to
be five to nine time as great after the thiamine dose, but the dose
aM meentially serenty-five times as great as the usual thiamine in-
taie. This tremdoes increase was not revealed by studying the
volme of urine and the per cent of thiamine within that volume. P.
C. Leoag had similar findings in experiments with rate and concluded
that insuffiient urinary excretion of the saturated thiamine dose
was a sed by the fact that the body fluids were not sufficient to
penit urimary eneretion of the massive doee. A considerable mount
of sisk a eee my have been eliminated through feees and perspira-
teo.n In vies of this difficulty, it wa decided that a consideration
of the oeeeeMtration of thiamine per ml. of urine would more adequately
reflect thLamine status than the volu of urine and its quantity of
9P. C. Leemg, "Vitamin B in the Animal Organim: A Quantita-
tie S3tUy of the Metabolism of Ii in Rate," Bieeam. J., XXXI (1937),
microgram per ml.
1. According to the rating panel's judgments, there was not a
significant difference in thefluency of subjects who were administered
thiamine and those wo were given placebo.
A comparison of speech ratings during the pre-dose speech
screening, the thiamine does, and the placebo doses can be seen in
Table I, on the next page. A slight, gradual improvement in fluency
was made during the progress of the investigation, but this may be a
reflection of the fact that only subjects who were judged as 2.00 or
higher on the scale during the pre-dose screening wer designated as
experimental subjects. As the study continued, som judgments of lees
than 2.00 were likely to accrue. Regardless of this tendency of the
subjects to show slight improvement throughout the course of the study,
it is clear that as mueh increase in fluency occurred during the
placebo dose as occurred during the thiamine doee.
2. There was not a significant difference in the concentration
of thiamine in the urine samples of the experimental subjects and the
urine samples of control subjects before the administration of thiamine.
Experimental Subjects: N = .1i2 Tper ml. SD .20
Control Subjects: M = .100 rper al. SD w .14
It was clearly indicated by the presence of thiamine in the
urine that neither group was thinaine deficient to begin with. Appar-
ently the subjects of both groups did not suffer from any metabolic
"lesions" which might have prevented their thiamine intake from being
i-f r 0 00 Q-l0 a0 0_*0 0 0 Q mA r00
aeO Ca COC 00o- 00 0-I Ago00
0-0 Selo< 0 0 Sa 0 0S
lrow,% 0"Or- rO -A
-S %0 S em NO *do so
nc~W~ w # .-Noa Id -4 C HH
%e^nggosoo sm iao
~~7 3 a=rW %C '-\otn-tn mn HlO
properly assimilated and utilized.
3. The relationship of the urine thiamine level and speech
ratings (before the administration of thiamine), was not significant as
revealed by means of the Pearson product-moment coefficient of correla-
r = + 0.3 Not significant At the % level of confidence.
This appears to indicate a slight tendency, probably within the
realm of chance, that the greater the concentration of thiamine in the
urine, the greater the non-fluency. If thiamine were to have been con-
sidered as having a direct and beneficial effect upon non-fluency, it
would have been reasonable to assume that vhen the non-fluency had been
judged as relatively severe, there would have been an accompanying
condition of relatively low thiamine level. According to the findings
of this investigation, there was no relationship between low thiamine
levels and high degree of non-fluency. The circumstance of higher
thiamine levels accompanying more severe non-fluency did not occur
consistently enough to be considered significant, and may, in part, be
explained by the fact that the non-fluent group was larger and there-
fore had greater variations in thiamine levels than did the fluent
4. The relationship of the urine thiamine level and speech
ratings after the administration of thiamine was revealed as not being
r + 0.032
This finding would seem to indicate that saturated does of
thiamine did not serve to change the non-fluency pattern in either
direetioa. Inrease in thiamine lvel did not maifest itself in subse-
quwnt and consistent decrease in non-fluency.
5. The relationship of the change in thiamine levels (after the
administration of thiamine) and fluency ratings did not appear to be
r + O.Sk5
This consideratio of the amount of change in the concentration
of thiamine -kich ocerrm d after the increased doege, indicated that
the subjects in whom this change was greatest had no aecoepanying
ehag.e in nos-fluency. For that matter, those subjects who revealed
little ehenge in thiamine levels after the thiaine doe showed no
significant che"e in men-fluency.
6. A comparison of the pre-ose intake of thiamine in the eo-
perimeetal group and.the control group revealed that the experimental
*tjects had a significantly higher intake of thiaiLne.
cxperimntal Subjeet.: N = t.1A mg.
Control Subjetec: = 0.984 mg.
This finding was, in part, refle ted in finding number 2, in
that the experimental group's greater tkiamine intake would seem to
neewant for the greater eeneeatratie of thiamine in the urine. The
fact that the non-fluet greup consieA more thiamine in their diets
Mtan the flent group, (despite the fact tet neither group wes thia-
mim deficient), my be explaind in view of the greater variations
seenrring within the non-fluent group. It is reasumable to aseme
that the lrer the group, the greater will be the variation aong the
ubje o within that group. Then too, dietary tkiamine intake is a
difficult factor to evaluate properly because mall and temporary diet-
ary changes from day to day and from meal to meal may be revealed
clearly in the average daily thiamine intake and consequently are
weighted heavily in comparisons of the average of B1 intake of the two
7. A comparison of the experimental and control groups' intake
of dietary thiamine during the thiamine dosage, revealed that the ex-
periental group tended to have a higher intake of thiamine.
Experimental Subjects: I w 76.333
Control Subjects: x i 75.966
This appeared to be a significant difference at the one per nt level
of confidence. The greater uber of subjects in the experimental
group permitted a larger variability between subjects and this may, in
part, account for the difference between the two groups.
8. The subjects mho were given thiamine as the first dose as
compared w th subjects who received thiamine as the second doee were
not significantly different in the quantity of microgram per al. of
urine they excreted.
Thiamine First: M w 0.378 microgree per al.
Thiamine Second: IN 0.412 micrograms per al.
If the subjects who received thiaine as their first does had
shown improvement and then continued this improvement during the placebo
period, it might have been assumed that the beneficial effect of thia-
mine vas being carried over into the placebo period. However, the fact
that those subjects who received placebo first showed as much improve-
ment as those who received placebo after taking thiamine, would teed to
negate arw assumption that thiamine had a beneficial effect that was
eoetiamed after the oeseation of the vitamin doee.
9. A comparison of the micrograms per al. or urine of the ex-
perimental and control groups, following the administration of thiamine,
revealed no signifieent difference between the two groups.
xperJaental Subjects: KM .392 microgram per al.
Control Subjects: M = .347 microgram per al.
This finding is net surprising in view of finding amber 2,
hiekh indicated there w.re no difference between the two groups in
thiadne eeneetration before the thiamine does Taken together, the
two finding rather definitely preelude any differeueee between the two
grepe in regard t the need for, or use of thiamine.
10. The subjects administered thiamine as the first dose, as
eeopred with thee who were given thiamine as the second dose, were not
signifieeatly different in their intake of thiaine through their regu-
Thiamie First: x = 76.S9 mg.
Thiadar Seeed: I = 76.59 mg.
It ws apparent that Hie administration of eeeentrated doses
of thiamine did not esue the subjeete to ineresee their ingestion of
feeds thiek eotained thimime.
11. A emparisen of the pre-dose urine .mple and the plaeebo
does wine imple, revealed no significant differences in the volume of
taM das per al. of rime.
P dee re: M = .1t mieroGrame per al.
Flsmbe does: I w .191 mieregram. per al.
It was clear tah an increased thimiMe eemeentration in the
rine m w not ma tadmied for ai eppreeiable legth of time. This
appears to agree with previous studies of thiamine-urine levels before
and after thiamine intake.
12. The relationship of the intake of thianine through inges-
tion of food and the speech ratings (before the administration of
thiamine) ws not significant.
r a + 0.07
This ws reflected in finding n-ber 3, and both findings
teded to exclude the existence of a relationship, inverse or direct,
between thiamine ingestion and judgments of speech fluency.
13. Ter appeared to be some indication that the administra-
tion of thiamine is related to an increase in carbohydrate intake, but
this indication did not seae to be statistically convincing in view of
the small number of subjects involved.
Carbohydrate during Pre-dose Dietary Survey: M = 158.25 g
Carbohydrate during Thiamine Administration: N 170.14 g
Carbohydrate during Placebo Administration: N = 159.36 g
For the subjects studied there is a probability of eighty-five chances
out of one hundred that thiamine caused an increase in carbohydrate in-
Although finding number 10 revealed that thiamine doeage did net
cause subsequent increase in dietary thiamine intake, finding number 13
seemed to indicate that if thiamine caused an increase in appetite, it
was reflected in greater ingestion of carbohydrate as might be expected
from previous studies of the effect of thiamine on the appetite and
subsequent increase in various nutrients.
14. There seemed to be a negative correlation between earbo-
hydrate intake before the doe- and the degree of non-flmsmy.
r -0.509 Significant at the 1% level of eonfidenee.
In general, then, there is an indication that the higher the intake of
arbehydrate on the pre-dose dietary survey, the greater the fluency.
This relationship might have been consistent enough to be con-
sidered ea l; however, the following seven findings served to negate
the signifiea!ne of this relationship between high oarbehydrate intake
and the severii~ of nen-flueney. The fast that such a definite rela-
tionehip was revealed in the first place may be attributed to the diffi-
ealty involved in quantitative consideration of carbohydrate intake. As
stated earlier, carbohydrate intake varies greatly from day to day and
mal to meal, (not only for a given group, but individually as well).
CoLperisome of earbahydrate daily averages frequently reflect temporary
estremes of either high or low carbohydrate ingestion. In view of this
fast, together with a consideration of the seven findings which follow,
it ms believed that a predictable relationship between high arbo-
hydrate intake did not euist.
1.. The relationship of earbehydrate intake and fluency during
the administration of thiamine, nm not significant.
16. Iken the erbehydrate intake of subjects who were adminis-
tern thiamine for the first dose were compared with the earbotydrate
irnfta of subjects who ere given thiamine for the esond doee, no
simgfieant difference w discovered.
Oarbehdrate Intake, thiamine dose first: I 16 l6.4 g.
urbehdrate Intake, thiamine does second: N = 163.42 g.
17. The correlation between carbohydrate intake and judged
degree of neo-fluency during the placebo dose was not significant.
r = + 0.176
18. A comparison of the carbohydrate intake of the experimental
and control groups before the administration of either dose revealed a
difference hich was barely significant.
Experimental Subjects: M = 158.25 g SD = 23.03
ntrol Subjects: = I0.17 g SDB 36.07
This finding provided significant evidenee wich pointed to the
inconsistency of finding umber 14. If greater carbohydrate intake were
related to greater fluency, it wourl be logical to assume that the
fluent control subjects would hae. had higher carbohydrate intakes
than the non-fluent experimental groups. Finding number 18 revealed
the inaccuracy of such an assumption.
19. A comparison of the carbohydrate intake of the experimental
and control groups during the thiamine dose revealed no significant
difference between the two groups.
t = 1.69
20. The negative correlation between the carbohydrate intake
(before the administration of either doee) and the quantity of thiamine
per al. of urine (before either dose) did not appear to be significant.
r = -.136
21. The negative correlation between carbohydrate intake ed
the quantity of thiamine per al. of urine (during the administration of
thiamine) was apparently not signifiont.
r = -.14.
22. A comparison of ten adult sale stutterers with ten adult
mer uaitterer, revealed esaentially no differeees between the iwo
groups in regard to total urine excretion, tiamine levels before the
dam amd thiamine leels after the does. There wre virtually no
differe es between the two groups as far as dietary intake is oocerned.
These appeared to be a greater range of variability among-the stuttering
grsap, bat this probably is explained by the fact that the stuttering
rowp was largely comprised of stulents at the bUiveraity of Florida
and their iagetion of both liuids and solids proved to be irregular
S1MA AlN CONCLUSIONS
Assuming that the panel's rating of speech on a five point scale
provided an accurate measure of non-fluency, and assuming that labora-
tory analyses and dietary histories provided reliable pictures of
nutritional status, several conclusions were reached.
1. There appeared to be no consistent, significant differences
betmwen those subjects judged as non-fluent and those judged as fluent.
2. In general, there appeared to be no justification for stat-
ing that thiamine had an observably favorable effect upon speech non-
fluency of the subjects involved.
3. There appeared to be no justification for stating that
thiamine had an obeervably unfavorable effect upon the speech non-
fluency of the subjects involved.
4. The results of this investigation would seem to indicate
that there was some additional support for the previous studies which
have found no physical differences between those individuals who stutter
or are non-fluent and those who arereelatively fluent.
In view of such factors as the small number of non-fluent
children uncovered during the study, the many divergent viewpoint
raelrdig the natum of nmo-flusny hkich were mnif- td within the
rating panel whIn it first assembled, and the existence of apparently
diff~rnt types of noa-tnumr, the following recoxmadations for
separate or conjoint rviearel were mde.
1. A sta of the i mdimme of non-flnuey should be conducted,
at should easier factoe swsh as the soele-esoMwie level of parents
eltd e mad ealt erl helarateritien of the faiLy, mhw Jr of siblings,
md eriemmem permiasivT essl regarding speek.
2. An investigation of ti validity and reliabilityrC judgment
ef mam-flw y should be mai, and ought to include rating bz trained
and mtraimed judges.
3. A stuA of the nature of non-flueacy should be conJeted,
ad ghouLd include consideration of different typos of non-fluency,
eeqpriia m of bgees of nmular tetnae during non-flunt utterance
md a momes for a possible traditional stage between n-nfiu enBy which
is neIIr ad that whish should be regarded as pathologeal (msecndm
SPEEGI S IE AND RELATED RESEARCH
DARSt OF SPEECH
SPEG AND HEARING CLINIC
UNIVERSITY OF FILRIDA
I would like to take this opportunity to thank you for your
participation in our research project. The cooperation we have received
has been very encouraging, and we certainly appreciate the important
help you have given us. In may instances we have not sent out thee
reports as promptly as we would have liked, but we hope you will uder-
stand the may problems thich arise when dealing with large naibers of
individuals in a limited period of time and with moderate resource.
That which follow is a brief report on the aspect of our stu
in which your child participated. It consists of a description of how
your child appeared to perform according to the Juadgment of our seve
qualified panel members.
Geeeral S Surrey__
OIher fa better
Thank you ag tu for yew kindrau and seoopation. We will be
gled to try to aw r &an question you miigt have eonerning this
tvuy, mad if we eau erve you in a~y amy pleau let us know.
Sin ere] yours,
EdRard M. PMson
March 3, 1955
Mr. Edwrd N. Penson is doing some research for his doctor's
degree at the University of Florida which requires the administration
of certain tablets to the children who are being used as subjects for
his controlled study. Theee tablets have been made up and given to
this research project by a pharmaceutical firm and are entirely nutri-
tional in nature and could not, under ay circumstances, be considered
harmful. I have bee in elo s contact with Mr. Peneon in the develop-
ment and conduct of this stuzy and am thoroughly aware of the contents
of these tablets and the instructions for their use. While it would
not be necessary to obtain medical prescription in order to purchase
similar tablets from a drug store, in order to give medical approval of
this procedure you may regard this letter as y prescription for their
use in connection with Mr. Penson's research.
Raymond S. Camp, M.D.
Ju6lgo kw ar -mwber
FPl*n circle a point o Rthe sele aesording to your Judgmnt of the
degr of mea-f1mey for this individual.
EMIAXPAST SIRG LUXIC Smr C SUPPER Wk C
COMPOSITE OF DATA
Vol .of arbo-
Urine/ B ~B Inta hydrate Mean % B1 Ex-
Subject Dose ml. -ml. ?ay ag. Intake g. Fluency created
* = A = Control subject (fluent)
/ pre Before either dose
x Placebo dose
Tol.t 1 Carbo-
nIm A/ BA nltaIke hIdrate ioan % 31 Ex-
Sabject Dom m1. ?/ml. m /64 ue. Iatake g. Fluenyg created
-A I Oatrol subjest (fluent)
pr Defore r eit dews
x Plasebe des*
Vol.of Bi Carbo-
Urine/ B B Ia drate Mean % B1 l -
Subject Dose al. r/l. ra g. Intake g. Fluency created
= A = Control subject (flimut)
pre = Before either dose
x w Plaoebo dose
Urine/ B D Intake hydrate Mean % B1 E-
Silbjat Done a l. ?1. 7/gr mgg. Intake g. Fluency created
* A a Osbrol subject (flumt)
/ pre Before either dee
x lamebe ien,
APP DIX F
INUTSTIGAT(O S SUBJECTIVE DESCRIPTION
OF SUBJECTS' NOI-FLUETCY
Subject: 21, Age: 5, Sox: Male
This subjects' non-fluency seemed to be characterized by both
repetition of syllables and prolongation of souds in the initial posi-
tion. The frequency and severity of the non-flue~y did not appear to
vary significantly from the first observation to the last. The quantiyg
of the speech sample obtained during observation sessions was adequate
throughout the dy. Toward the end of the investigation, the subject
seemed to become familiar with the speech sampling procedure and dis-
course tended to be more freely elicited.
Subject: 22, Age: 4i. Sex: Male
This child's pattern of non-fluemy appeared to consist of
frequent pauses between phrases and between words within a phrase.
There seemed to be some decrease in non-fluency during the final stages
of the investigation (during the administration of the placebo dose).
This subject appeared to be eKtremely shy and speech responses were
elicited with difficulty. Repeated exposure to the observation see-
sions did met see to effect the subject's twendney to be reticent.
Subject: 23, Age: 4I, SeK: Female
Analysis of this individual's non-fluuey revealed repetition
of syllablee and words. Mild and ineonwistnt i mnt pro ent seemed to
oewr during the lat stage of the investigation (during the thiwJ
dose). Te child apparently had little or no hesitsamy in regard to
expressing herself throgheut oeh operation Ession. On several
oeseaioa she related that she wanted to "talk about those pictures "
and daring *eh interview, her discourse was accompanied by consider-
able facial and veeal animeion.
Sjlnets 24, Age: Selx Male
r and large, this ambjeot' non-fluency wa esharaeterised by
shirt, per-teme, but infrequnt blocks which aeurred at the begin-
ang of som weord. Tbher did nat appear to be ag eemnistent improve-
mam in flueay during lb e eose of the study. The child vrbelized
ith eemprabive ease, but rarely followed a given line of thought for
a Iy legt of time. He appeared to be rather excitable and gae the
impreseim of being easily distracted.
Sbjeet: 25, Afsl j* Saes Hale
This subject's am-flmy consisted of repetition s of phrase,
wirds, and syllabes. Proleigations or blacks wee essentially non-
smistent. The sbjet was rated by the panel as being ore nmo-fluent
Iring the plebe sa ritta n eeo than at the time of his pre-dose
smneraig. His an-fluen appeared to baeem more hyperteme a the
atred pegremed. There seemed to be no tmiLdmy on the part of the
Ahlb to d.hdr fram the interview situation. He cooperated on all
seasrion ad em'presie his enjoymat aftar Seehk s ion.
Subject: 26, Age: 3, Sex: Male
Analysis of this child's non-fluency revealed a pattern ~omist-
ing of frequent repetitions of words and occasional blacks on sounds in
the initial position. Third pattern was siMilar to the stutterin
pattern of the boy' s father, who considers himself a "controlled stut-
trer." There iwas n marked abatement of the r-fluey during either
dose. The smbje5t seemed willing enough to enter the interview session,
and considering the age of the child, verbal output was at least ade-
Subject: 27, Age: 3, Sx: Male
This subject's non-fluency wa characterized "' frequent rope-
titione of syllables, words, and phrases. Cocasionally the pattern
include a relatively hyprtemee block on sounds in the initial posi-
tion. There semed to be a mild decrease in the quantity and seerirl
of the non-flueney as Lthe study continued. This yawngster verbalised
quite freely, ad the interview smsaton revealed his apparent pro-
pe~nity for story-teling, teasing, and argument.
Subject: 28, Age: 6, Sex: Male
The non-fluency demonstrated by this child eonsist3d or repeti-
tios of sounds, ayllables, and less frequently, words. Other non-
fluent patterns were virtually absent. There appeared to be slight
improvement during the laet weeks of the thiamine dose. This subject
beg u each interview session with a protest against his participation
in the study. owevcr, his conversation during, th- sessions was beth
voluminous and continuous.
S3mbs.t. 29, Age 4is Sex: Male
Coasideraton of this subject's non-flueney suggested a pattern
of sound proleogations and oasseonal blocks on saoada in the initial
poaiton. During my given oomesation there wee eonsidwaable varia
eL in the frqueaey and nserit of the non-fluemy. There seemed to
be som increase in non-fluesy toward the ad of the thiaine dose and
the begiming of the placebo don. This subject appeared to be rather
sky tirougoot the eeurse of the satw, but after the initial interview,
speck was elicited with eoparative ease.
subject: 30, Age:s ip, SM: Male
Proleagatioa, hasitatiens, and repetition were all part of
this sbjeet' e pattern of men-flueney. Most of these non-flnncies
seemed to be atterd without apparent tension and their freqawmcy varied
frer ea mamat to the anxt. The non-luent symptoms did not em to
chage in on direction or the other from the first interview to the
last. The child usually attempted to withdraw from the interview situa-
tiem, and uttreane we quatitatively all throughout the stucy.
SJb.t.et 31, Ages 5, Scs hamle
This mIbjeet' s nn-fluney consisted primarily of blocks and
prolematios f souds in the initial position. On oeession, thee
ma- 4luiuae were meea ied tl varying degrees of observable nmeular
taesion. Thee did wt aperw to be wa significant or eeoaistae
camgas in the syt~ptem from the outset of the inresttigation unti its
enslaiten. Tie ehild did mnt give th interviewer the iprasion of
btl. amept~oally tqa, and veral output was adequate during eash