Niacinamide for Arthritis (with comments on hyperactivity)
by William Kaufman, M.D., Ph.D.

Joint Dysfunction, Part 1
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CHAPTER I

To read Chapter 2, click this link:  http://www.doctoryourself.com/kaufman7.html

THE COMMON FORM OF JOINT DYSFUNCTION
by William Kaufman, M.D., Ph.D. (1949)
Copyright C 2001 Charlotte Kaufman. Reprinted with permission.
Edited by Andrew W. Saul

(This chapter presents Dr. Kaufman’s protocol for the treatment of arthritis with niacinamide, vitamin B-3.  He also used ascorbic acid (vitamin C), thiamine (B-1), riboflavin (B-2), all in large doses.  His rationale and his measurement methods begin the chapter, but you might wish to scroll down to the section on dosage (“Methods of Treatment”) and read that first.  If you are looking for the doctor's comments relevant to ADHD, scroll to nearly the end of the page and they can be found in boldface type. The chapter closes with case histories and an insightful, practical discussion of patient management.  Graphs and other original illustrations are not provided here, but may be seen in the original text.)

The author’s preface, and all references cited, are posted at http://www.doctoryourself.com/kaufman11.html

INTRODUCTION

The relationship between the continuous administration of adequate amounts of 
niacinamide and improvement in both hypertrophic arthritis and rheumatoid arthritis was 
originally reported in 1943 as part of a clinical study on niacinamide deficiency disease, 
aniacinamidosis, observed in a group of 150 private patients studied during the years 
1941 and 1942 (97). (The term aniacinamidosis was employed by the writer in 1943 to 
define a syndrome which was thought to be the consequence of a niacinamide tissue 
deficiency disease. The term aniacinamidosis would be redefined today (1949) without 
reference to its possible etiology, as the syndrome which is ameliorated or corrected 
when a person ingests certain nontoxic amounts of niacinamide (far in excess of those 
obtainable from his usual diet), and recurs in time when such niacinamide 
supplementation is discontinued.)

The form of aniacinamidosis which was seen by the writer prior to 1943 included, in 
varying degrees of severity, changes in skin texture and pigmentation; subcutaneous 
swellings; tenderness of periosteum, cartilage and voluntary muscle to pressure or 
squeezing; tenderness and enlargement of the liver; gastrointestinal symptoms; 
changes in the morphology of the lingual mucous membrane; and limitation in ranges of 
joint movement. This clinical syndrome of aniacinamidosis was characterized (a) by its 
prompt recession when niacinamide was exhibited orally for a sufficient period of time in 
adequate doses, and (b) by its recurrence, often in the original degree of severity, upon 
premature cessation of therapy with niacinamide. Most persons who were treated 
required maintenance doses of niacinamide continuously to prevent relapse (97).

It was observed in the course of the above study that persons who had clinically both 
aniacinamidosis and obvious arthritis experienced, in response to adequate oral therapy 
with niacinamide over a sufficiently long period of time, clinical improvement in both the 
aniacinamidosis and the arthritis. On the other hand, premature cessation of therapy 
with niacinamide caused a worsening of both the aniacinamidosis and the arthritis. 
Furthermore, when the total dosage of niacinamide per day was reduced from 
apparently adequate to inadequate levels in such persons, there was a more gradual 
recurrence of the severer aspects of aniacinamidosis and a slower worsening of their 
arthritis than occurred with complete cessation of therapy with niacinamide. It was 
noticed that individuals who suffered from both aniacinamidosis and clinically obvious 
arthritis required larger daily doses of niacinamide for recovery from niacinamide tissue 
deficiency disease than those who had no clinically obvious arthritis (97).

With the compulsory enrichment of cereal products in 1943 (25), the niacin content of 
the average American diet was increased from 11 to 17 mg per 2500 calories (30). 
Since 1943, the clinical syndrome of aniacinamidosis as originally described has not 
been seen regularly, but has been supplanted by a syndrome in which most of the 
manifestations of aniacinamidosis as originally described are milder, and many of the 
symptoms and signs of the aniacinamidosis of 1941 and 1942 are absent. However, 
limitation in the ranges of joint movement has continued to be an objective, measurable 
attribute of the metabolic disorder corrected by adequate niacinamide therapy. In 1944, 
in an effort to secure quantitative data concerning the relationship between treatment 
with niacinamide and recovery in arthritic joints, the writer introduced goniometric 
examination of joint ranges of all persons who had at the time of the initial physical 
examination clinically obvious arthritis. In 1945, it was decided to broaden the base of 
this study by routinely measuring the joint ranges of all patients presenting themselves 
for physical examination. For this purpose, there was introduced as part of every 
physical examination an abbreviated goniometric examination of the movement of 20 
joints or joint groups in easily measured, specified ranges. Within five minutes, this 
abbreviated goniometric examination of joint ranges could be performed and recorded 
by the examiner on a special form devised for this purpose. By this method, a suffi-
ciently large number of joints or joint groups were measured in defined ranges to afford 
an adequate and representative sampling of the mobility of the moveable joints of the 
body.

With the introduction of routine measurement of the joint ranges of all new patients who 
presented themselves for examination, it soon became apparent that limitation of joint 
movement in the 20 measured ranges was exceedingly prevalent in many individuals 
without joint complaints or clinically obvious arthritis. Moreover, limitation of joint 
movement in persons without complaints referable to joints was often of the same order 
as that observed in patients (with and without clinically obvious arthritis) who did have 
complaints referable to their joints.

It was decided to simplify the approach to the study of limitation of joint movement by 
combining the numerical values obtained for each of the 20 measurements of joint 
range movement into a single numerical value which was the "weighted" average of all 
these measurements. This "weighted" average was called the JOINT RANGE INDEX. 
As will be shown later, the Joint Range Index is used by the physician in the objective 
appraisal of joint function (joint mobility) in numerical terms, in the clinical classification 
of the various grades of severity of joint dysfunction, in the selection of the initial level of 
niacinamide therapy, in the regulation of subsequent levels of niacinamide therapy, and 
in the observation of the response of joint dysfunction to adequate and inadequate 
niacinamide therapy. In addition, the use of the Joint Range Index enables the patient to 
understand the objective basis for the diagnosis of joint dysfunction in his case, and the 
objective basis for the evaluation of the response of his joint dysfunction to adequate 
and inadequate therapy.

A WORKING HYPOTHESIS:
THE DEGENERATIVE PROCESS AND THE REPARATIVE PROCESS IN JOINTS

Certain inductions have been made from factual data acquired during the clinical study 
of patients with joint dysfunction (with and without clinically obvious arthritis) whose joint 
ranges were measured for the determination of the Joint Range Index at various time 
intervals under various conditions of niacinamide therapy: before niacinamide therapy 
was instituted, during premature cessation of adequate or inadequate niacinamide 
therapy, during the substitution of adequate for inadequate niacinamide therapy, and 
during continuously adequate niacinamide therapy. These inductions have been 
synthesized into a working hypothesis which explains the status of a patient's joints in 
terms of two oppositely directed, coexisting articular processes: the deteriorative 
process, and 'the reparative process.

The deteriorative process consists chiefly of two operational factors tending to cause 
retrograde changes in joint structure and function, (a) "wear and tear in joint structures, 
which results from ordinary or unusual joint uses, and (b) a slowly, moderately or rapidly 
progressive metabolic disorder which is corrected in time by adequate niacinamide 
therapy. This metabolic disorder occurs even in persons subsisting on what is 
considered to be the average "good" or "adequate" diet of today (172) (118) (193).

The reparative process tends to overcome the retrograde articular changes caused by 
the deteriorative process. Even persons subsisting on "good" or "adequate" diets of 
today lack sufficiently potent reparative mechanisms to offset for any prolonged period 
of time the retrograde influences of the deteriorative process in joints. However, with 
supplementation of the average good" or "adequate" diet of today with adequate 
amounts of niacinamide, the articular reparative process becomes sufficiently powerful 
to overcome the retrograde changes in articular tissues produced by the deteriorative 
process, and in time permits improvement in the functional status of joints, as 
objectively demonstrated in the individual patient by serially increasing values of the 
Joint Range Index.

For purposes of this study, it has been postulated (a) that clinically perfect articular 
structures have the fullest ranges of articular movement, (b) that clinically imperfect 
articular structures have less than full ranges of articular movement, and (c) that the 
range of joint movement in moveable joints is a practical measure of the degree of 
clinical perfection of these articular structures. At any given moment, the patient's Joint 
Range Index is an indirect measure of the balance between deteriorative and reparative 
articular processes in the joints whose ranges of movement are determined 
goniometrically.

In an untreated population, the deteriorative process seems to preponderate over the 
reparative process, as is shown by the average tendency of the Joint Range Indices of 
this group to decrease with increasing age (see Graph 1G, page 153).

When the ranges of movement of a given joint are re-measured at any given time 
interval (e.g., one month), there may be no change, an increase, or a decrease in joint 
movement when the second measurement is compared with the first. When there has 
been no change in the range of joint movement, it is postulated that the effects of the 
deteriorative process have been balanced by the effects of the reparative process for 
this time interval, and that no significant change in the functional status of the joint has 
occurred. However, when the range of joint movement has decreased, it is assumed 
that the deteriorative process in articular tissues has been more powerful than the 
reparative process for a sufficient period during this time interval to permit deteriorative 
effects to preponderate over reparative effects, with the result that deterioration has 
occurred in the functional status of the joint. On the other hand, when the range of joint 
movement has increased, it is assumed that the reparative process in articular tissues 
has been more powerful than the deteriorative process for a sufficient period during this 
time interval to permit reparative effects to preponderate over deteriorative effects, with 
the result that there has been improvement in the functional status of the joint.

It may be that some arthritic joints are damaged by a deteriorative process of such 
intensity and duration that joint recovery is not possible, even with prolonged adequate 
niacinamide therapy. Even though initial clinical examination may indicate that eventual 
recovery of these joints is unlikely, only a prolonged trial of adequate niacinamide 
therapy will disclose whether or not such joints actually have been damaged beyond 
repair. It has been observed that deformed arthritic joints which seemed on the initial 
clinical examination to have been irreparably damaged by the deteriorative process 
have shown recovery of the full ranges of joint movement, and a progressive decrease 
in severity of the obvious arthritic deformities with adequate niacinamide therapy over a 
prolonged period of time.

METHOD OF STUDY

The observations recorded in this volume were derived chiefly from the clinical study of 
455 persons of both sexes, ranging in age from 4 to 78 years, who consulted the writer 
from March 1945 to February 1947 in the course of his private practice of internal 
medicine. (In Section IV the frequency distribution by five-year age groups of all patients 
studied is shown in Table 1A; that of all male patients, in Table 1B; that of all female pa-
tients, in Table 1C.) All patients studied were ambulatory. Their occupations were 
varied. Although no attempt has been made to classify the economic status of these 
patients, the majority of these patients would be considered to belong to the moderate 
income groups, and relatively few would be considered to belong to the low income 
groups. They came chiefly from New England. Many had no complaints referable to 
health, but desired a routine physical examination; others had minor or major health 
problems.

For purposes of this study, a detailed enumeration of the incidence of various diseases 
in the population group examined would be of no significance, since it was found that no 
matter what associated diseases the patient had, his joint dysfunction responded in a 
predictable way to adequate therapy with niacinamide, to premature cessation of such 
therapy, or to the substitution of inadequate for adequate therapy. A partial listing of 
various diseases other than joint dysfunction seen in this group of patients may, 
however, be of some interest: gall-bladder disease (with and without stones), chronic 
hypertrophic gastritis, duodenal ulcer, diverticulosis of the colon, cardiospasm, multiple 
intestinal polypi, irritable colon, Paget's disease of bone, post-menopausal osteoporosis, 
multiple sclerosis, syringomyelia, spastic paralysis, chronic and acute anxiety states, 
anginal syndrome, arteriosclerotic heart disease, rheumatic heart disease, anemias, 
myeloge nous leukemias, allergic diseases, fibroid tumors of the uterus, hypothyroidism, 
hyperthyroidism, diabetes, gout and arrested lues (48).

All persons included in this study presented themselves as new private patients. Only in 
this sense was there selection of the population group studied. All patients were 
subjected to an initial examination, which consisted of a detailed history, physical 
examination and certain laboratory studies. These findings were recorded on a special 
form, together with the physician's impressions and therapeutic recommendations. 
Kodachrome transparencies were taken of the tongue, gums and eyes of each patient 
to serve as a point of reference in the objective study of the response of tissues to 
vitamin therapy (105) (106) (107) (37) (39) (183) (191) (114) (35) (174) (8) (109). In 
addition, monochrome photographs were taken of selected patients to document 
clinically obvious arthritic deformities.

During the initial visit, in the course of the general physical examination, certain ranges 
of joint movement were measured in a standard way (149), and the numerical values 
obtained were used in computing the Joint Range Index. The sound-proofed room in 
which the examination was performed was kept at a temperature comfortable for the 
patient, who was completely disrobed save for the covering sheet. Care was taken to 
have the patient adequately draped at all times. The examiner informed the patient 
before each measurement of joint ranges as to what would be done next, indicating that 
maximal joint ranges were to be measured. The ranges of knee and hip movement were 
measured with the patient recumbent. All other joint ranges were measured in the sitting 
position. In addition to measurements of joint ranges, the following data were recorded if 
they were elicited on physical examination of the joints: pain, crepitus (cracking or other 
sound), muscle spasm, redness, unusual warmth, swelling, engorgement or 
accentuation of the periarticular venous pattern, and deformity.

Instruments used in measuring joint ranges were made of metal according to the writer's 
specifications:

A gravity-type goniometer, fashioned after the one described by Cooper (34), was found 
to be a highly versatile instrument (see Figures 1, 2, 3 and 12).

(Figure 1. Illustrates the goniometer, a device for measuring joint movements and 
angles. The calibrations are also shown.)

A graduated collar was devised which permitted the measurement of neck rotation (see 
Figures 4 and 5).

One tool consisted of an angle device with provision for the maintenance of any angle 
by tightening a set screw, and a graduated plate on which the angle device was fitted in 
order to read the angle therefrom (see Figure 7).

A graduated plate was used to measure flexion and extension of the wrist (see Figure 8) 
and, rarely, in markedly deformed hands to measure extension of the 
metacarpophalangeal (knuckle) joints of the fingers (see Figure 11).

A special device was constructed for the measurement of extension of the 
metacarpophalangeal joints of the fingers (see Figures 9 and 10).

MEASUREMENT OF THE RANGES OF JOINT MOVEMENT USED IN COMPUTING 
THE JOINT RANGE

Knees. The patient is adequately draped, lying flat on his back with his body weight 
evenly distributed. He is asked not to contract his lower extremity muscles actively 
during this measurement, since such contraction lessens the range of movement of the 
knee joint. His right thigh is flexed passively by the examiner so that it is at right angles 
to his trunk. The examiner then extends the patient's right leg maximally, taking care not 
to displace the ipsilateral thigh even slightly, and taking care that the patient does not 
flex his contralateral thigh even slightly, as this would cause pelvic tilt. The angle which 
the leg makes with a hypothetical plane passing through the knee joint at right angles to 
the thigh is measured by reading the indicator dial of the gravity-type goniometer, which 
is held with its long axis parallel to the long axis of the right leg. The range of movement 
of the left knee joint is measured in a symmetrical manner (see Figure 2).

(Figure 2. Illustrates the measurement of knee-joint extension, showing a) Knee joint at 
beginning of measurement; b) Knee extended 50%; c) Knee extended 100%.

Hips. The patient is asked not to contract his lower extremity muscles (particularly the 
adductor muscles of his homolateral thigh) since such active muscular contraction 
lessens the range of movement of the hip joint. With the patient lying symmetrically on 
his back, the right thigh is flexed by the examiner so that it remains perpendicular to the 
trunk, care being taken that the right foot is not rotated from a neutral position of rest. 
The right thigh is then abducted maximally by the examiner, care being taken not to 
displace the contralateral buttock from the table. If the contralateral buttock is levered 
off the examining table by the examiner's abduction of the ipsilateral thigh, then 
abduction of the right thigh is maintained, but the patient is permitted to rotate so that 
both buttocks are on the table again and bear weight symmetrically. The gravity-type 
goniometer is then applied so that its long axis parallels the long axis of the right thigh, 
and the appropriate reading of the degree of hip abduction is made and recorded (see 
Figure 3). The range of movement of the left hip joint is measured in a symmetrical 
manner.

Figure 3. Illustrates measurement of hip abduction, showing a) Thigh at beginning of 
measurement; b) Thigh abducted 50%; c) Thigh abducted 100%)

NOTE: For purposes of clarity in illustration, the examiner is pictured as standing be-
hind the thigh that is abducted. In practice, he stands in front of the thigh that is being 
abducted, so that he can easily read without parallax the scale of the gravity-type 
goniometer.

Lateral Rotation of the Neck. The patient is asked to sit symmetrically, and to make 
himself as "tall" as possible. He is asked to hold his neck so that it is neither flexed nor 
extended, nor laterally bent to the right or left. A specially constructed graduated metal 
collar (see Figure 4) is fitted symmetrically at the level of the base of the neck so that 
the 100% graduation always rests on the anteriormost portion of the trapezius ridge, 
and the patient is asked to rotate his head maximally to the right. Since the examiner 
wishes to measure and record maximal values, when the patient reaches his initial 
maximal joint of lateral rotation, he is always urged to do better, to prevent his 
restraining full neck rotation because of subjective discomfort. During measurement of 
lateral neck rotation, the patient is at no time permitted to raise his shoulders, or to flex, 
extend or laterally bend his neck (see Figure 5). When the patient signifies that he has 
achieved maximal rotation of his neck to the right, the measurement of neck rotation is 
made. The range of neck rotation is read directly from the graduations on the neck 
gauge by the examiner, who sights along the plane perpendicular to the center of the 
patient's chin to avoid parallax, ascertaining the graduation on the neck gauge which 
would pass, if extended, through the center of the chin. The measurement of rotation of 
the neck to the left is made in a symmetrical way.

(Figure 4. Illustrates the graduated collar (with degree markings similar to those of a 
protractor) used in the measurement of neck rotation)

(Figure 5. Illustrates the measurement of lateral neck rotation using the graduated 
collar, and shows the position of head at beginning of measurement, the head rotated to 
the right of left 50% and 100%)

Shoulders. The range of circumduction of the shoulder joint is measured by careful 
inspection and estimation rather than by the use of a particular device. In order to be 
certain that maximal ranges are elicited and estimated, the maneuver of circumduction 
of the shoulder is performed several times for each shoulder. The patient is asked not to 
contract his shoulder girdle or upper extremity muscles, since such active muscular 
contraction lessens the range of movement of the shoulder joint. In measuring the range 
of circumduction of the right shoulder, the physician stands to the right of the patient, 
who faces forward, sitting as "tall" as he can, with his shoulders maintained horizontally. 
The physician places his left hand on the patient's right shoulder to prevent its 
displacement from the horizontal position when the patient's right arm is subsequently 
circumducted for measurement. The physician's right hand holds the patient's right 
elbow lightly, slightly flexing the patient's right forearm on the right arm, but not holding 
the right elbow so rigidly as to interfere with subsequent free movement of the shoulder 
joint during circumduction. In this position, the physician circumducts the shoulder joint 
of the right arm in a clockwise direction so that the patient's right elbow describes the 
largest possible "circle" during circumduction (see Figure 6).

(Figure 6 illustrates the method for estimating of the range of shoulder circumduction 
(range of motion in a circling motion). a)  The figure drawn in unbroken lines shows the 
position of the patient, as well as the position of his right upper extremity (marked 0) at 
the beginning and end of the maneuver of shoulder circumduction. The physician's left 
hand maintains the patient's right shoulder horizontally throughout the maneuver of 
shoulder circumduction. The broken lines show three successive positions (50,100,50) 
of the right upper extremity during clockwise circumduction. Estimates of the range of 
shoulder circumduction are made with 0, 50, 100 as positions of reference.

b)  Frontal view of the patient's position and the examiner's hands at the begin-fling and 
end of the maneuver of shoulder circumduction, corresponding to the 0 position in (a).

The movement of shoulder circumduction is graded as 50% when the right arm swept 
upward in maximum circumduction reaches, at the highest point of the arc, the plane 
perpendicular to the sagittal plane of the body at the level of the shoulders. The 
movement of shoulder circumduction is graded as 100% when the arm swept upward in 
maximum circumduction reaches at the highest point of the arc of circumduction the 
plane parallel to the sagittal plane of the body and perpendicular to a horizontal plane 
passing through the level of the shoulders. With some practice, bearing in mind these 
two reference axes, the physician can make estimates of the fractional ranges of 
shoulder circumduction with sufficient accuracy to be included in the computation of the 
Joint Range Index. Circumduction of the left shoulder is measured in a symmetrical 
manner.

(Figure 7 illustrates measurement of the degree of the wrist to bend. Captions follow 
below.)

a) Angle device set at 90 degrees, or 100% of a trigonometric quadrant. Its arms may 
be rotated around its central axis and fixed by a set screw at any desired angle.

b) Measurement of wrist flexion by the angle device. With the wrist held at maximum 
flexion, the arms of this device are brought into apposition with the surface of the 
dorsum of the hand and forearm. The set screw holding the arms of the angle device is 
tightened in this measured position, the angle device is fitted into the graduated plate
(c), and a reading of the angle of flexion is made.

c) Graduated plate with angle device fitted to make reading of the range of wrist flexion 
obtained in (b).

Wrists. The maximum degree of flexion and extension of the wrist is measured either 
with the angle device (Figure 7) or the plate device (Figure 8), using the dorsum of the 
forearm and hand as the surfaces between which all angles are measured.

The plate device is more convenient for this measurement, being used so that the 
central axis of its graduations corresponds to a projection of the center of the right wrist 
joint. The 0 line is held parallel to the long axis of the right forearm, and the 100 line is 
held perpendicular to the projection of the central axis of the right wrist joint. The patient 
is asked not to contract his forearm or hand muscles during this measurement, since 
such active contraction lessens the range of movement of the wrist. Care is taken to 
measure maximal passive flexion and extension, and to sight along the dorsum of the 
hand in such a way that parallax is avoided. The patient is not permitted to flex or 
extend the fingers during the measurement of maximal flexion or maximal extension of 
the wrist. Measurement of flexion and extension of the left wrist is made in a 
symmetrical manner.

(Figure 8 illustrates the measurement of flexion and extension of the wrist with the 
graduated wrist plate, another protractor-like scale to fit the hand. 50% and 100% 
flexing is shown.

For clarity in illustration, (d) and (e) picture the examiner's fingers as exerting pressure 
on the subject's fingertips to induce maximal passive extension. In practice, this 
pressure is exerted on the palm of the hand, just proximal to the metacarpophalangeal 
joints.)

Metacarpophalangeal (Knuckle) Joints. The right hand is inserted into the special device 
(see Figures 9 and 10) with the palm resting on the baseplate. The 100 line of the 
graduated plate is perpendicular to the projection of the central axis of the 
metacarpophalangeal joint to be measured. The patient is asked not to contract his 
forearm or hand muscles during this measurement, since such active muscular 
contraction lessens the range of extension of the metacarpophalangeal joints. Only the 
finger that is being extended by the examiner is permitted to leave the baseplate. The 
index finger is extended maximally by the examiner. This may be done in the face of 
objections from the patient, who may experience pain from this maneuver. The angle of 
extension between the dorsum of the hand and the dorsum of the finger is measured in 
such a way that parallax is avoided. Extension of the second, third, fourth and fifth 
fingers of the right hand is measured successively. The metacarpophalangeal joints of 
the left hand are measured in symmetrical fashion.

(Figure 9.  Illustrates the device for the measurement of extension of the 
metacarpophalangeal (knuckle) joints.  This also resembles a custom-fit protractor, with 
angle measurements in scaled in degrees.)

In some persons, for whom the special device cannot be used because of severe 
deformities of the interphalangeal joints of the hands, the wrist plate with the central cut-
out (see Figure 11) is adapted to the measurement of metacarpophalangeal extension. 
The plate is fitted between the fingers so that the 0 line is perpendicular to the projection 
of the central axis of the metacarpophalangeal joints, with the 100 line parallel to the 
dorsum of the hand and perpendicular to the central axis of the metacarpophalangeal 
joints. In this use of the wrist plate, 100 minus the plate reading measures the 
movement of finger extension at the metacarpophalangeal joints. The patient is asked 
not to contract his forearm or hand muscles during this measurement, since such active 
muscular contraction lessens the range of extension of the metacarpophalangeal joints. 
Extension of the metacarpophalangeal joints is measured, holding the plate as 
described above, for the second, third, fourth and fifth fingers of the right hand. The 
corresponding joints of the left hand are measured in a symmetrical way.

(Figure 10 illustrates the technique for measuring extension of the metacarpophalangeal 
(knuckle) joints. Details shown: Hand in the special device (Fig. 10) at the beginning of 
measurement; (a) lateral view, (d) looking from above downward, (g) frontal view. The 
metacarpophalangeal joint of left forefinger extended 50%: (b) lateral view, (e) looking 
from above downward, (h) frontal view. The metacarpophalangeal joint of left forefinger 
extended 100%: (c) lateral view, (f) looking from above downward, (i) frontal view.

(Figure 11. Illustrates the measurement of extension of metacarpophalangeal joints in 
severely deformed hands, using the wrist plate. Shown: a) Position of hand at beginning 
of measurement. b) Metacarpophalangeal joint of left forefinger extended 50%.
c) Metacarpophalangeal joint of left forefinger extended 100%.

Neck Bending. This measurement is not used in the computation of the Joint Range 
Index, since it has not been made routinely. In some persons, it cannot be measured 
accurately because of their persistent tendency to angulate the shoulders.

The patient sits symmetrically as erectly as he can, with his shoulders held level. His 
neck is neither flexed nor extended, nor rotated to the right or left. The neck is bent 
maximally to the right, and the angle of bending is measured by reading the dial of the 
gravity-type goniometer, applied so that its long axis parallels the long axis of the nose 
(see Figure 12). Left lateral bending of the neck is measured in a symmetrical manner.

(Figure 12 illustrates the measurement of lateral neck bending with the gravity-type 
goniometer. Shown: Position of head at beginning of measurement; Right lateral neck 
bending of 50%; Left lateral neck bending of 50%.)

CERTAIN CONVENTIONS ADOPTED IN MEASURING VARIOUS JOINT RANGES

Save for the range of shoulder joint circumduction, the maximum range of each joint 
movement, when elicited as described previously, approximates one trigonometric 
quadrant of 90 degrees. This is true for (a) extension of the knee joint; (b) abduction of 
the hip joint; (c) right lateral rotation of the neck; (d) left lateral rotation of the neck; (e) 
flexion of the wrist; (f) extension of the wrist; (g) extension of the metacarpophalangeal 
joint. Because the angle of maximal movement of these joint ranges approximates one 
quadrant, it is convenient to measure these ranges in terms of percentages of a 
quadrant rather than in degrees.

This convention was adopted chiefly because patients visualize percentages of a range 
of movement more easily than equivalent measurements expressed in degrees. For all 
measurements except circumduction of the shoulder joint, simple arithmetic 
computation permits, when desired, the conversion from percentages to degrees, since 
10% of a quadrant is equal to 9 degrees.

In a few individuals, the range of maximal wrist flexion is in excess of one quadrant. 
Also, in very few persons, either neck rotation to the right or neck rotation to the left, or 
both, are in excess of one quadrant. In these instances, for purposes of calculating the 
Joint Range Index, movement beyond one quadrant is considered as 100%, or the full 
range.

The conventions used in the measurement of shoulder circumduction have already 
been described (see page 10).

As a convention, the various graduated scales used in the measurement of joint ranges 
were read to the nearest 5% (4.5 degrees). A few readings were made with the angle 
device to 1 % (0.9 degree), but this was found to be an unnecessary refinement for 
purposes of this study.

COMPUTATION OF THE JOINT RANGE INDEX

It will be helpful in understanding the steps used in the computation of the Joint Range 
Index to refer to the form used for recording the measured values of the 20 specified 
joint ranges, and for computing the Joint Range Index (see Figure 13). The numerical 
values obtained upon measurement of the 20 specified joint ranges are entered 
separately into the appropriate space and column of the form at the time of the physical 
examination.

(Figure 13 illustrates the worksheet Dr Kaufman designed and used to record degrees 
of joint dysfunction with his patients.  In addition to angular measurements, he also 
noted clinical data such as intensity of pain, crepitus, muscle spasm, redness, unusual 
warmth, swelling, prominent or engorged venous pattern, deformity, or the presence of 
Heberden’s nodes.)

The Joint Range Index is the arbitrarily weighted mean of the numerical values obtained 
upon the measurement of 20 specified joint ranges. Measurements of the neck, wrists 
and fingers are weighted so that these joints will not unduly affect the numerical value of 
the Joint Range Index, since they show increased ranges of movement more rapidly 
than the larger joints (hips, knees, shoulders) in response to adequate niacinamide 
therapy.

The following steps are employed in computing the Joint Range Index from the 
measurements of 20 specified joint ranges:

The neck rotation index is computed by adding the measured values for the maximal 
ranges of right and left neck rotation and dividing by two. (In computing the various 
indices entering into the final computation of the Joint Range Index, the figures are 
rounded off to the nearest whole number; e.g., 0.5 or over is listed as the next highest 
digit, and less than 0.5 is dropped.)

The resulting quotient is entered into the appropriate space under the heading “Indices.” 
(Neck bending is similarly averaged, although it is not used in calculating the Joint 
Range Index.) Readings for the maximal range of circumduction of the right and left. 
shoulders are entered separately in the proper spaces. Readings for the maximal 
ranges of extension and flexion of the right wrist are added and divided by two, the 
quotient being entered in the appropriate space. A similar computation is made for the 
left wrist, and similarly recorded. Readings for extension of the four 
metacarpophalangeal joints of the right hand are added, divided by four, and the 
quotient entered in the appropriate space. A similar computation is made for extension 
of the four metacarpophalangeal joints of the left hand. Readings obtained for 
measurement of maximal abduction of the right and left hips and for maximal extension 
of the right and left knees are separately recorded in appropriate spaces. The above 11 
values are then added, the sum obtained divided by 11, and the resulting quotient is 
termed the Joint Range Index. This computation is carried to one decimal place. (In 
about 2% of the patients seen from March 1945 to February 1947 the Joint Range Index 
could not be computed because one or more of the component ranges of joint motion 
could not be measured; e.g., in persons who could not flex the thigh to make a right 
angle with the trunk because of severe arthritis of the hip joint, or in persons with one or 
more limbs amputated.)

Thus, the Joint Range Index is precisely defined in terms of the "weighted" average of 
the 20 ranges of joint movement chosen for measurement. A Joint Range Index of less 
than 96.0 is taken to indicate the presence of joint dysfunction.

METHOD OF TREATMENT OF JOINT DYSFUNCTION (This section, consisting of 
pages 20-29, is the heart of Dr Kaufman’s work.)

After completion of his physical examination, the patient was apprised of the normal and 
abnormal findings revealed by the clinical study. Where problems other than joint 
dysfunction existed, these were discussed, and appropriate therapeutic 
recommendations were made. The subject of joint dysfunction was then presented. The 
meaning of the numerical value of the patient's Joint Range Index was explained to him 
in terms of the Clinical Classification of Joint Function (see page 21), and the dynamic 
nature of joint dysfunction was described. The patient was told that joint dysfunction 
was reversible in time when appropriate therapy was taken.

All patients with joint dysfunction who elected to accept treatment were given 
niacinamide in suitable doses, either alone or in combination with other vitamins. 
When indicated the appropriate vitamins were prescribed in addition to 
niacinamide. The water-soluble vitamins used were never prescribed in aqueous 
solution, but as tablets or as dry powders in capsule form. When vitamin A was used, it 
was usually given in conjunction with vitamin D. Vitamin D was always given in 
conjunction with vitamin A; when vitamin D was administered in this study, the daily 
dosage rarely exceeded 6,000 U.S.P.units per 24 hours (14) (10) (38) (56) (59) (95).

Participation in the therapeutic program was entirely voluntary on the part of the patient. 
Some patients at the outset declined to accept treatment for their joint dysfunction. 
When a patient accepted therapy for his joint dysfunction, with each succeeding visit 
after the initial one, improvement or lack of improvement in his joint dysfunction was 
frankly discussed with him. No patient was chided because he was unwilling or unable 
to carry out the program of therapy as it was originally scheduled. Thus, because there 
was no “loss of face," most patients cooperated well and gave an accurate account of 
their deviations, if any, from the suggested therapeutic program. Some patients at the 
end of the first or second month of treatment, or at a later time, felt so much improved 
physically that they discontinued therapy for their joint dysfunction, mistakenly believing, 
in spite of advice to the contrary, that they were "cured," and required no further therapy 
or medical supervision. Some of these persons, who experienced a recurrence of their 
original pattern of symptoms upon premature cessation of therapy, returned 
subsequently for re-evaluation of their therapeutic needs. Other patients, who felt that 
they had not benefited from therapy for their joint dysfunction, did not continue with 
treatment though objectively they responded satisfactorily to adequate therapy, as 
shown by increasing values of the Joint Range Index on serial re-measurements.

Therapy was always individualized. In the therapeutic program introduced for the 
treatment of joint dysfunction, each patient served as his test object in the bio-assay 
of the dosage of niacinamide necessary to reverse his joint dysfunction. Therapy 
with niacinamide (used alone or in combination with other vitamins) was not 
deemed successful unless there continuous, objective improvement, as judged by 
continuously increasing values of the Joint Range Index on consecutive reexaminations. 
(When a patient subsists on a low-protein diet, amounts of niacinamide that would 
ordinarily be adequate for the treatment of his joint dysfunction prove to be inadequate 
for satisfactory improvement. In this case, the dosage of niacinamide is continued at the 
same level, but the protein level of the diet is increased to adequate levels, with 
subsequent satisfactory improvement in the joint dysfunction.) (118) (120) (172).

The clinical classification of joint function in terms of the numerical values of the Joint 
Range Index is listed below:

Clinical Classification of Joint Function
Degree of Joint Dysfunction Joint Range index
No joint dysfunction 96-100
Slight joint dysfunction 86-95
Moderate joint dysfunction  71-85
Severe joint dysfunction 56 -70
Extremely severe dysfunction 55 or less

For each clinical grade of joint dysfunction, the initial dosage schedule of niacinamide 
suggested below effects in time such improvement in joint dysfunction as the writer has 
considered to be clinically satisfactory. (However, since April 1947, it was found that 
dosage schedules 50-100% greater than those recommended below (particularly 
in the moderate, severe and extremely severe grades of joint dysfunction) are 
therapeutically superior, as judged by the patient's clinical response.)

While the initial dosage may be increased as necessary during treatment, it is not 
decreased, even though the Joint Range Index increases in response to adequate 
therapy.

The vitamins were administered orally, usually in equal doses at equal intervals during 
the day, and, in severe and extremely severe joint dysfunction, during the night when 
the patient would spontaneously awaken from sleep. In slight grades of joint 
dysfunction, the daily continuous ingestion of 100 mg of niacinamide after meals 
and at bedtime sufficed for treatment (400 mg/24 hours). Usually adequate in 
moderate joint dysfunction was the continuous ingestion of 150 mg niacinamide 
administered every 3 hours for 6 daily doses (900 mg/24 hours). In extremely 
severe and severe grades of joint dysfunction, 100-150 mg niacinamide were 
prescribed every hour (1500-2250 mg/24 hours), every hour and a half (1110-1650 
mg./24 hours), or every two hours (800-1200 mg/24 hours), depending on the 
severity of the joint dysfunction, the more frequent schedule being used in more 
severe cases (97) (51).

It has been found in the treatment of joint dysfunction that the manner in which 
the daily dosage of niacinamide is divided has an important bearing on the 
therapeutic results achieved; e.g., 300 mg niacinamide given three times daily (900 
mg/24 hours) is inferior in its therapeutic action to 150 mg niacinamide administered 
every 3 hours for 6 daily doses (900 mg/24 hours). Therefore, to define the type of 
therapy used, the writer routinely records the following data: (a) the number of 
milligrams or units administered per dose, and (b) the total number of milligrams or units 
administered per 24 hours.

No untoward effects or clinical signs of toxicity were noted when niacinamide 
(alone or in combination with other vitamins) was administered on the above 
dosage schedules to individuals for short or long periods of observation. Before 
1943, mild hypoglycemia had been noted clinically in a few persons when niacinamide 
exceeded certain dosage levels (97) (135) (51) (62), but this phenomenon has not been 
observed since that time.

"ADEQUATE" AND "OPTIMAL” DOSAGE LEVELS OF NIACINAMIDE IN THE 
TREATMENT OF JOINT DYSFUNCTION

"Adequate" dosage of niacinamide is defined as that clinically safe dosage of 
niacinamide which, when ingested in divided doses throughout the day by a person with 
joint dysfunction whose ordinary diet is not inadequate in protein or calories, and whose 
joints are not subjected to excessive mechanical joint injury, will effect in time what the 
writer has considered to be a satisfactory pattern of increasing values of the Joint 
Range Index. The pattern of recovery from joint dysfunction in response to niacinamide 
therapy, and the numerical limits of increments in the value of the Joint Range Index 
which are considered to be satisfactory for the first month of therapy and for succeeding 
months, are described on page 24.

“Optimal” dosage of niacinamide is defined as that clinically safe dosage niacinamide 
which, when ingested in divided doses during the day by a person with joint dysfunction, 
would permit the most rapid recovery in joint function, as demonstrated by the largest 
possible increments in the values of the Joint Range Index in the shortest possible 
period of time. At present, the optimal dosage of niacinamide for the treatment of joint 
dysfunction has not been determined clinically, although it is hoped to approximate such 
a dosage level eventually. Since adequate dosages of niacinamide have given clinically 
satisfactory results without producing any untoward symptoms or signs of acute or 
chronic toxicity, no attempt has been made in this study to determine the optimal level 
of niacinamide therapy in the treatment of the various clinical grades of joint 
dysfunction.

However, as the higher dosage levels of niacinamide have been cautiously explored in 
the past 22 months, it has been found in severe and extremely severe joint 
dysfunction that divided doses of niacinamide totaling 4 or 5 grams (4,000-5,000 
mg) per 24 hours are therapeutically superior to the lower dosage schedules -
which previously had been considered adequate. Even these higher dosage 
levels of niacinamide may not be optimal for the treatment of joint dysfunction.

The optimal dosage of niacinamide for the treatment of joint dysfunction, as well as the 
limit of human tolerance for niacinamide, can be established only in those medical 
centers equipped to provide careful clinical supervision, and to conduct such chemical, 
metabolic and clinical laboratory studies as would reveal the earliest signs of toxicity, 
should these occur with the administration of progressively higher dosage levels of 
niacinamide.

DESCRIPTION OF JOINT DYSFUNCTION AND ITS TREATMENT FOR THE PATIENT

Since the cooperation of the patient is a prerequisite for the successful therapy of joint 
dysfunction, it was found desirable and necessary before treatment of joint dysfunction 
was instituted to discuss with the patient his various clinical problems (including the 
dynamic nature of joint dysfunction, and its response to niacinamide treatment, and the 
dynamic nature of certain complicating syndromes, and their appropriate treatment), 
and the therapeutic goals. During the course of therapy, it may become necessary to 
review and amplify this discussion for the benefit of the patient as various clinical 
problems arise.

Joint dysfunction is the articular aspect of a generalized, usually slowly 
progressive metabolic disorder which is corrected in time by adequate 
niacinamide therapy. Since the retrograde changes in tissue structure and 
function which characterize this disorder occur insidiously over a period of years, 
many of its symptoms and signs are incorrectly attributed by laymen and 
physicians alike to the so-called "normal" aging process. But these retrograde 
changes in morphology and function of bodily tissues are usually reversible in 
time when adequate levels of niacinamide are supplied continuously to bodily 
tissues. The patient who takes continuously adequate amounts of niacinamide 
experiences, in addition to improvement in joint function, an improvement in his 
general health.

Theoretically, optimal nutrition must be continuously available to bodily tissues to 
ensure the best possible structure and function of tissues (104) (108). While we do not 
know what constitutes optimal nutrition, it has been demonstrated empirically that even 
persons eating a good or excellent diet according to present-day standards 
exhibit measurable impairment in ranges of joint movement which tends to be 
more severe with increasing age (see page 153). It has also been demonstrated that 
when such persons supplement their good or excellent diets with adequate 
amounts of niacinamide, there is, in time, measurable improvement in ranges of 
joint movement, regardless of the patients' ages. In general, the extent of recovery 
from joint dysfunction of any given degree of severity depends largely on the duration of 
adequate niacinamide therapy (see pages 187 and 188).

With the ingestion of adequate amounts of niacinamide continuously for a sufficient 
period of time, a patient whose ordinary diet is not inadequate in protein or calories, 
whose joints are not subjected to excessive mechanical trauma, will recover from joint 
dysfunction at the satisfactory rate of 6.0 to 12.0 Joint Range Index units, or better, in 
the first month of therapy, and 0.5 to 1.0 Joint Range Index unit, or better, for each 
month of therapy thereafter, until a Joint Range Index of 96-100 is reached. (Rarely, 
when a patient has one or more ankylosed joints, he may have no appreciable active or 
passive movement of these ankylosed joints, even after two years of adequate niacin-
amide therapy, although his other joints recover the full ranges of movement in 
response to such therapy. In such cases, the Joint Range Index cannot reach 96-100; 
e.g., when one wrist is ankylosed and has not shown increased movement in response 
to niacinamide therapy, the maximum Joint Range Index attainable is 90.9; and when 
both wrists are ankylosed, the maximal Joint Range Index attainable is 81.8.)

In general, the more severe and more chronic the patient's joint dysfunction, the slower 
is the rate of recovery in response to adequate niacinamide therapy, and the slower his 
subjective appreciation of improvement. The rate of recovery for each patient must be 
established empirically from serial determinations of the Joint Range Index. In order to 
ensure a continuously satisfactory rate of recovery from joint dysfunction, the physician 
must re-examine the patient at intervals during the course of niacinamide therapy. 
Whenever a patient taking the amounts of niacinamide prescribed by the physician, and 
eating a good or excellent diet, fails to make satisfactory improvement in his Joint 
Range Index, in the absence of excessive mechanical joint injury the niacinamide 
schedule must be revised upward to that level which permits satisfactory improvement. 
Failure of the patient to take niacinamide as directed will result in failure to improve at a 
satisfactory rate.

When a patient has joint dysfunction associated with obvious arthritic deformities, he is 
told that the physician cannot predict whether or not in his case articular deformities will 
resolve with adequate niacinamide therapy. However, in response to adequate 
niacinamide therapy for a sufficient period of time, other patients have shown partial or 
complete resolution of their arthritic joint deformities. Some patients with arthritic 
deformities show resolution of some of their joint deformities, but not of others. Only 
careful observation of the patient's deformities on serial re-examinations will indicate 
whether or not his deformities are resolving in response to adequate niacinamide 
therapy. In most instances, the rate of resolution of the deformities will be slow, if it 
occurs at all.

It cannot be predicted whether or not a given joint that appears to be completely 
ankylosed clinically will recover any degree of movement. It has been observed many 
times that joints appearing to be clinically ankylosed prior to therapy tend to have partial 
or complete recovery of movement in response to adequate niacinamide therapy, 
although some ankylosed joints have not shown any degree of movement as a result of 
therapy during an observation period of several years. In response to adequate nia-
cinamide therapy over a sufficient period of time some patients have partial or complete 
recovery of movement in some of their ankylosed joints, but not in others. Only careful 
observation of the ranges of joint movement on serial re-examinations will demonstrate 
whether or not a given ankylosed joint can recover any degree of movement in 
response to adequate niacinamide therapy.

In general, in the absence of complicating factors, the higher the patient's Joint Range 
Index rises in response to adequate niacinamide therapy, the fewer articular symptoms 
he will have; and the better he will feel. However, even though the Joint Range Index 
increases satisfactorily in response to adequate niacinamide therapy, the patient may 
not feel well because of complicating syndromes which are not on the basis of aniacin-
amidosis. Careful clinical study is necessary in order to establish the etiology of 
whatever complicating syndromes may be present and, with appropriate therapy, the 
patient is likely to become free from articular symptoms and to feel well. However, at 
any time symptoms of bodily discomfort may recur which must be studied and given 
appropriate treatment as promptly as possible, if the patient is to feel well again. While 
the patient may obtain temporary relief from articular and other symptoms through the 
use of analgesics, narcotics, sedatives, antihistaminics and local anesthetics, only 
adequate treatment of joint dysfunction and the complicating syndromes is likely to give 
more lasting benefits.

In order to assess the effects of niacinamide therapy on joint dysfunction and on the 
patient's general status, the patient is usually re-studied one month after continuous 
niacinamide therapy has been instituted. If good progress in recovery from joint 
dysfunction is noted at that time, he is reexamined in two months, and thereafter every 
three to six months. For the most part, this schedule of re-examination is found to be 
satisfactory for the supervision of the therapeutic program of patients presenting the 
chronic problems of joint dysfunction, although when the individual's problems are of 
unusual complexity, or when intercurrent problems arise, the time interval between visits 
is shortened.

When a patient with joint dysfunction fails to make the anticipated progress in response 
to niacinamide therapy, he is asked if he has taken the medication as prescribed; if not, 
he is urged to do so. (When a patient has taken multiple vitamin capsules as prescribed 
and has not made satisfactory improvement in his Joint Range Index in response to 
such therapy, the druggist is asked how the vitamin powders were compounded. The 
clinical effectiveness of niacinamide seems to be lessened when niacinamide is mixed 
with ascorbic acid by vigorous trituration, since this favors inter-molecular reactions 
between niacinamide and ascorbic acid in the dry powder state. The occurrence of such 
inter-molecular reactions between niacinamide and ascorbic acid is hindered by the 
preliminary admixture of each dry powder separately with a small amount of calcium 
stearate (0.2%) before the final admixture by sieving.)

It is always emphasized that the patient must take his medication continuously as pre-
scribed until such time as the supervising physician may decide, on the basis of 
objective clinical evidence, that it is necessary to increase the level of niacinamide 
therapy in order to produce continuously satisfactory improvement in the Joint Range 
Index.

However, certain factors other than the ingestion of inadequate amounts of niacinamide 
may tend to depress the Joint Range Index. These include (a) transient or persistent 
mechanical joint injury resulting from unusual or physical exertion (see page 79) or from 
psychogenically sustained hypertonia of somatic muscle (see page 115), (b) rapid and 
excessive gain in weight to obesity levels, (c) excessive ingestion of alcohol, (d) 
inadequate dietary protein. When any of these factors is operative, it is of limited value 
to increase the amounts of niacinamide taken by the patient in an effort to effect 
satisfactory improvement in the Joint Range Index. Instead,  treatment should be 
directed toward lessening the degree of mechanical joint injury, reducing the patient's 
weight to the normal range, interdicting alcohol, and increasing the protein intake to 
adequate levels, respectively.

When indicated, the physician describes for the patient four complicating syndromes
frequently coexisting with joint dysfunction, and their treatment (see page 76). Most of
the articular and non-articular symptoms of a patient with joint dysfunction which are not
corrected by niacininide therapy usually originate as part of these four complicating
syndromes. When the patient understands the etiologic basis of his symptoms, he will
not have anxiety concerning the meaning of symptoms which would otherwise seem
mysterious and alarming. The patient with joint dysfunction who has one or more of
these complicating syndromes is told that he will not feel well unless joint dysfunction
and these coexisting syndromes are correctly identified and successfully treated, and
that in order to accomplish this, his active participation in the clinical investigation and
therapeutic program is required.

TYPICAL IMPROVEMENT IN MOBILITY OF A SINGIE JOINT IN RESPONSE TO 
LEVELS OF NIACINAMIDE THERAPY USED PRIOR TO APRIL 1947

In serial determinations of the mobility of single joints in response to levels of 
niacinamide therapy used prior to April 1947, it was found that niacinamide-induced 
recovery of full joint mobility was an orderly process. (Since April 1947, when higher 
dosage schedules of niacinamide were introduced (see page 21), there has been 
a marked reduction in the incidence of articular pain and discomfort upon 
maximal passive movement of the moveable joints during various stages of 
recovery from joint dysfunction.)

There is described below typical improvement in joint mobility, as illustrated by several 
sequential stages occurring during niacinamide-induced recovery of full mobility of the 
metacarpophalangeal (knuckle) joint.

(Figure 14 is a schematic representation of maximal passive extension of the meta-
carpophalangeal joint at four successive stages (a) (b) (c) (d), during the course of 
niacinamide-induced recovery of full joint mobility. The line touched by the head of the 
arrow in (a) (b) (c) (d) indicates the upper limit of painless extension. The shaded angle 
in (b) and (c) indicates the range of painful passive extension.)

Figure 14(a). On the initial examination before niacinamide therapy was instituted, the 
metacarpophalangeal joint of the forefinger of the right hand could be extended 
passively to 30% of the full range of extension for this joint. No pain or discomfort was 
experienced by the patient during this maneuver. The examiner noted the presence of 
palpatory resistance from the initiation of the movement of passive extension of this 
metacarpophalangeal joint, and this resistance progressively increased as the joint was 
extended from the range of 0% to 30% of the maximal extension; the palpatory 
resistance at the end of the movement was graded as firm. When at the 30% level of 
passive extension a small increase of force in the direction of extension caused no 
further extension of this joint, 30% of the full range of extension was taken as the upper 
limit of maximum passive extension of this metacarpophalangeal joint.

Figure 14 (b). At the end of one month of continuous, adequate niacinamide therapy, 
maximal passive extension of this metacarpophalangeal joint increased to 60% of the 
full range of extension. No pain or discomfort was experienced by the patient when the 
metacarpophalangeal joint was extended from 0% to 40% of the full range of extension. 
The patient experienced localized joint pain, often severe, as the joint was passively 
extended from 40% to 60% of the full range of extension. The examiner's palpatory 
sensation indicated that movement of the joint in passive extension was free from 0% to 
40%, and that there was soft, yielding resistance which progressively increased as the 
finger was extended at the metacarpophalangeal joint from 40% to 60% of the full range 
of movement. When a further small increase of the extending force did not increase the 
degree of extension, 60% of the full range of extension was taken as the upper limit of 
passive extension of this metacarpophalangeal joint. The palpatory resistance at the 
end of the movement of extension was rubbery.

Figure 14 (c).After months of continuous, adequate therapy with niacinamide, maximal 
passive extension of the metacarpophalangeal joint reached 100%; i.e., the full range of 
movement. Passive extension of the metacarpophalangeal joint from 0% to 85% was 
without pain or discomfort; passive extension from 85% to 100% was painful. The 
examiner's palpatory sensation indicated that the movement of this joint was free from 
0% to 85%, and that there was soft resistance, which increased progressively with 
increasing extension of the metacarpophalangeal joint from the level of 85% to 100%. A 
small additional force in the direction of extension when the 100% level was reached did 
not cause further extension of this joint. The palpatory resistance at the end of the full 
range of movement (100%) was rubbery.

Figure 14(d). With a longer period of continuous, adequate niacinamide therapy, it 
was possible to achieve full, free and painless extension of this 
metacarpophalangeal joint to the level of 100%. Slight additional palpatory force in 
the direction of extension with the joint fully extended did not increase the amount of 
movement beyond the full range of extension; i.e., the 100% level. The examiner's 
palpatory sensation indicated that the movement of extension was free from 0% to 
100% of full extension, that the resistance met at the end of this movement was firm, 
and that the patient experienced no pain from this maneuver.

It would appear from clinical observations that, in the absence of joint trauma, there is 
an orderly and sequential pattern of recovery of joint mobility in a patient with joint 
dysfunction in response to continuous, adequate niacinamide therapy provided that the 
patient's diet is not inadequate in protein Or calories. Serial re-examinations of joint 
ranges during the course of continuous, prolonged, adequate niacinamide therapy 
reveal that with the passage of time, there are the following changes:

(a) progressive increases in ranges of joint movement;

(b) progressive shifting of painful zones of joint movement toward the periphery of the 
most recently acquired zones of increased ranges of joint movement, until, ultimately, 
after the fullest range of movement for the joint has been achieved, there is absence of 
pain on the execution of the fullest movement possible for the joint in the specified 
range; and,

(c) progressive shifting of zones of resistance to passive movement toward the 
periphery of the most recently acquired zones of increased ranges of joint movement 
until, ultimately, after the fullest range of movement for the joint has been achieved, 
there is no resistance to passive movement on the execution of the fullest range of 
movement possible for the joint in the specified range of movement.
These dynamic changes in joint mobility occurring during the course of treatment 
suggest that sequential alterations in joint morphology must occur in response to 
continuous, adequate niacinamide therapy to permit the observed changes in joint 
mobility described above.

With cessation of adequate niacinamide therapy, the therapeutically-improved joint 
mobilities cannot be maintained for any prolonged period of time.

SELECTED CASE HISTORIES ILLUSTRATING THE THERAPEUTIC RESPONSE
OF JOINT DYSFUNCTION TO NIACINAMIDE ALONE OR IN COMBINATION WITH 
OTHER VITAMINS

This section presents selected case histories which illustrate and emphasize the 
dynamic nature of joint dysfunction, with and without clinically obvious arthritis, as 
demonstrated by changing values of the Joint Range Index over a period of time in 
response to various levels of niacinamide ingestion. Twenty case histories, abbreviated 
in various degrees, are presented, together with a figure for each case which 
summarizes both the response of the Joint Range Index to the type of vitamin therapy 
employed, and the amounts of the vitamin(s) administered per 24 hours. A few figures 
summarize additionally the changes observed in the Sedimentation Rate during 
therapy.

Cases A through K have been chosen to demonstrate the effect on joint dysfunction of 
(a) adequate therapy with niacinamide, (b) reduction of niacinamide from adequate to 
inadequate levels, and (c) premature discontinuance of niacinamide therapy.
Cases L through T show the effects on joint dysfuntion of adequate and for the 
inadequate therapy with niacinamide administered in combination with of the 
other vitamins. Whenever adequate doses of niacinamide are given in combination with 
other vitamins to persons with joint dysfunction, improvement in joint function, as 
indicated by rising values of the Joint Range Index, is of the same order as would be 
anticipated if niacinamide in the amounts present in the vitamin mixture were the sole 
therapeutic agent. It will be demonstrated by these case histories that joint dysfunction 
(with or without clinically obvious arthritis) is ameliorated in time by adequate therapy 
with niacinamide (alone or in combination with other vitamins). This is true regardless of 
age, sex, occupation, geographic origin, economic level, or associated diseases. 
Whenever adequate therapy with niacinamide is replaced by inadequate therapy or by 
premature cessation of adequate niacinamide therapy, there is a worsening of joint 
function which in time is reflected by decreasing values of the Joint Range Index.

Whenever inadequate therapy with niacinamide is replaced by adequate therapy with 
niacinamide, joint function again improves, as measured by increasing values of the 
Joint Range Index. In general, the expectancy is that, with adequate niacinamide 
therapy for a sufficiently long period of time, the patient's joint function will improve 
continuously so that ultimately the Joint Range Index will measure between 96 and 100 
(no joint dysfunction) and will be maintained at this level for as long as the amount of 
niacinamide ingested by the patient continues to be adequate for his bodily needs. In 
the absence of severe mechanical joint injury, when the diet of the patient is not 
inadequate in protein or calories, two stages are observed in the recovery of joint 
dysfunction in response to adequate niacinamide therapy. First, there is the initial large 
increase in the Joint Range Index of at least 12 units which occurs in a month or less. 
(At the end of one week of continuous adequate therapy with niacinamide alone or in 
combination with other vitamins, those few persons whose Joint Range Indices were 
determined at this interval had an increase in the Joint Range Index which was of the 
same order as that usually observed at the end of one month of therapy.)

This rapid initial improvement in the Joint Range Index is, in all probability, largely the 
result of the resolution of tissue edema in response to adequate niacinamide therapy 
(97) (189). Associated with this rise in the Joint Range Index, the patient often has 
marked subjective improvement in feeling tone. The next stage of recovery from joint 
dysfunction is slow, with a gradual increase in the Joint Range Index of at least 0.5 to 
1.0 unit per month. Recovery from joint dysfunction in response to treatment with 
niacinamide is considered to be clinically satisfactory, and the dosage of niacinamide is 
considered to be adequate, when the Joint Range Index increases at the end of the first 
month and thereafter within the limits of recovery for these time intervals as defined 
above. A lesser rate of recovery in joint dysfunction in response to niacinamide therapy 
is judged to be unsatisfactory, and the niacinamide dosage schedule is then increased 
to a level which will permit recovery from joint dysfunction at a satisfactory rate 
(provided that the patient is not subsisting on a low-protein diet).

Since there are wide individual variations in the need for niacinamide, the physician 
must determine empirically for each patient that level of niacinamide therapy which will 
produce satisfactory improvement in joint dysfunction. On the whole, the suggested 
dosage schedules (see page 22) will cause satisfactory improvement in joint 
dysfunction. However, on any of these dosage schedules, at any time there may be 
stabilization of the Joint Range Index until the dosage level of niacinamide is suitably in-
creased, whereupon the Joint Range Index will rise again in a satisfactory manner. In 
order for the patient to make the best possible progress in recovery from joint 
dysfunction, periodic re-examinations must be performed by the physician so that the 
niacinamide dosage schedule may be adjusted as necessary to ensure serially rising 
values of the Joint Range Index until the level of 96-100 (no joint dysfunction) is 
reached, and subsequently, to maintain the patient at this level.

In recovering from joint dysfunction, especially of a severe grade, a patient is likely to be 
less impressed by the physician's Opinion that satisfactory improvement has been 
made in response to adequate niacinamide therapy, than by his own sudden realization 
that he is again able to use his body in ways that were impossible for a long time before 
the institution of niacinamide therapy; e.g., he is able to turn his head enough to enable 
him to park his car without difficulty; he can go up and down stairs with ease; after 
sitting in a movie theatre for hours, he does not experience prolonged stiffness and 
discomfort upon arising from his seat; he can trim his toenails without difficulty.

The selected case histories presented below demonstrate the usefulness of the routine 
determination of the Joint Range Index in evaluating the severity of the patient's joint 
dysfunction, in following his response to niacinamide therapy, and in regulating dosage 
levels of niacinamide during the course of treatment. However, in most instances, if the 
patient who is recovering from joint dysfunction is to feel well, it is also necessary to 
evaluate whatever additional coexisting clinical problems he may have, and to institute 
whatever therapeutic measures may be indicated. In subsequent sections, certain 
complicating syndromes will be described, which may cause arthralgia as well as other 
articular and non-articular symptoms, often complicating the treatment of joint 
dysfunction.

CASE A. No.309, female, age 26, housewife, married.

This case history illustrates, in a woman with clinically obvious rheumatoid arthritis, (a) 
improvement in joint function as measured by increasing values of the Joint Range 
Index in response to adequate niacinamide therapy, (b) impairment in joint function as 
measured by a lowered Joint Range Index as a result of substitution of inadequate for 
adequate therapy, and brief cessation of therapy, and (c) subsequent improvement in 
joint function as measured by an increased Joint Range Index in response to the re-
introduction of more adequate niacinamide therapy. (These results are summarized in 
Figure 15.)

When she was 16 years old, she was hospitalized for special study of her joint disorder, 
and was informed upon completion of this clinical investigation that she had arthritis. 
Her bone and joint symptoms were not ameliorated by the therapeutic program which 
was then recommended, and, indeed, became progressively worse, especially since her 
marriage at the age of 20, when she first started to do housework. The amount of her 
housework was considerably increased in volume after her two children were born.

Her presenting complaints include marked limitation of motion and pain (both at rest and 
on the initiation of joint movement) in the hip joints, knees, low back, neck, and fingers. 
She states that these joint symptoms are becoming progressively more severe, and are 
worsened by changes in weather and by any form of physical activity, including her 
housework. Although she has worn many different types of shoes, her feet have never 
been comfortable. She is irritable and tired, and frequently awakens during the night 
because of joint discomfort and muscular aching. Often she awakens in the morning 
feeling more tired than she did when she went to bed the night before.

Physical Examination: B.P. 130/80. P. 84. R. 18. T. 99.4 degrees. Wt. 135 lbs. Ht. 65 ½ 
inches. She seems tired, and looks older than her stated age. She moves slowly, as if 
guarding against rapid movements of her joints which might give her increased pain. 
Her posture is poor. Slight dorsal kyphosis and slight pelvic tilt are evident upon 
inspection. Her proximal interphalangeal joints of the fingers of both hands are 
thickened and swollen. Her skin is yellow, dry, slightly inelastic, and has a prominent 
reticular pattern. She has severe tenderness on moderate digital pressure over the 
maxillary and frontal sinuses, over the chondral ribs, the lower third of the sternum and 
chondrosternal junctions, the right trochanter, the lowermost third of the tibias bilaterally, 
the third, fourth and fifth cervical vertebrae and the lumbar vertebrae.

The liver edge is at the level of the costal margin in the right mid-clavicular line at the 
end of deep inspiration, and is tender to palpation. Her tongue shows hyperemia of the 
anterior third and atrophy of papillae. Her teeth are in good repair, although the gums 
are slightly retracted, infiltrated and swollen. Her conjunctivae are slightly thickened, 
and show some increased vascularity. Tickle sense is absent everywhere. She has 
hypopallesthesia. Her initial Joint Range Index (65.6) indicates severe joint dysfunction.

She was given 100 mg of niacinamide to take every 3 hours for 6 daily doses (600 
mg/24 hours) and in one month there was improvement in her Joint Range Index and in 
her general health. She appeared less tired. She stated that she had experienced less 
pain, stiffness and limitation of movement since treatment with niacinamide had been 
instituted. Her color had improved, and her skin appeared less yellow. Her liver was not 
tender to palpation. The tenderness on digital pressure over the bony prominences, 
which was so marked on the previous examination, had practically disappeared. Tickle 
sense was present. She had recovered normal vibratory sensation. However, since the 
rate of recovery of her lingual mucous membrane in response to therapy with 
niacinamide was considered to be somewhat slow, the dosage of niacinamide was 
increased to 100 mg. every 1 ½ hours for 9 daily doses (900 mg/24 hours). She took 
this amount of niacinamide daily for about 300 days, and showed subjectively and ob-
jectively continuous and progressive improvement. The numerical value of her Joint 
Range Index rose from 65.6 to 90.2 in 300 days. Thus, according to the Clinical 
Classification of Joint Function, she had progressed from severe joint dysfunction to 
slight joint dysfunction.

Since she had shown an excellent response to therapy, she was asked to return for her 
next re-examination in six months, at which time her Joint Range Index had fallen to 
78.2, with a concomitant return of many of her presenting symptoms. Upon inquiry, the 
following facts were elicited:

Shortly after her last visit, she knew that she was feeling better than she had ever felt in 
her life and thought, therefore, that she was "cured." She gradually decreased her 
niacinamide intake, and finally, for three weeks before her examination, took none.

As a result of her self-prescribed change in the therapeutic program, she had regressed 
clinically in all respects. Clinically, her joint dysfunction regressed from slight (90.2) to 
moderate (78.2). A new dosage schedule of niacinamide was prescribed (150 mg every 
3 hours for 6 daily doses, or 900 mg/24 hours), which she took faithfully.

When therapy with niacinamide was thus re-introduced, her Joint Range Index was 
78.2. In 84 days it rose to 86.4, and in 184 days to 91.2. Thus, she had again 
progressed from moderate to slight joint dysfunction. Her symptoms referable to bones 
and joints disappeared, and there has been progressive resolution of her abnormal 
physical signs.

Since she has gained some insight into the dynamic nature of her joint dysfunction, it 
appears likely that this patient will continue with her therapy as directed. It is anticipated 
that with continuously adequate niacinamide therapy she will in time achieve a Joint 
Range Index of 96-100 (no joint dysfunction).

CASE B. No.147, female, age 61, housewife, married.
This case history illustrates, in a woman with severe hypertrophic arthritis, (a) 
improvement in joint function, as measured by an increased Joint Range Index in 
response to a given dosage of niacinamide, (b) slight impairment in joint function as 
measured by a lowered Joint Range Index resulting from a small decrease in the 
niacinamide dosage from the previous level, and (c) an accelerated improvement in the 
Joint Range Index as a result of two successive increases in the niacinamide level (see 
Figure 16).

She has had joint discomfort for many years, and moderate deformities of the fingers for 
at least 10 years. Six to seven years ago she first noticed severe pain in her hip joints. 
Her knees are very stiff. All her life she has had curvature of the spine, and has had a 
good deal of pain in the back. Recently she has had increased fatigability and insomnia.

Physical Examination: She looks older than her stated age. B.P. 140/80. Wt. 159 ½ lbs. 
Ht. 65 inches. She has tenderness on digital pressure over the sternum, medial 
epicondyles, iliac crest, trochanter, styloid process of the radius, sacroiliac joints. 
Marked kyphoscoliosis is noted. Her tongue shows evidences of infiltration and atrophy 
of papillae. The edge of the liver, which is one finger's breadth below the rib margin in 
the right mid-clavicular line on deep inspiration, is tender to palpation. Bony 
prominences of the lower extremities are hyperpallesthetic to the tuning fork. Tickle 
sense is absent. Plantar dysesthesia is present.

This patient had severe joint dysfunction, as measured by her Joint Range Index of 
68.2. She was asked to take 100 mg. of niacinamide every 1½ hours. In a month, she 
had experienced marked improvement in her Joint Range Index, and considerable 
subjective relief from joint discomfort. The plantar dysesthesia was no longer present. 
Liver enlargement had diminished markedly (liver tenderness and enlargement 
disappeared after a longer period of therapy). Hyperpallesthesia of the lower extremities 
was replaced by a normal vibratory sensation. Tongue showed the improvement 
expected with one month of niacinamide therapy. She looked younger than on her initial 
visit. She had no further difficulty with fatigability or insomnia.

She continued to make good progress clinically for over 300 days, when she reduced 
her niacinamide intake from 1200 mg/24 hours as originally prescribed, to 1000 mg./24 
hours in divided doses of 100 mg. per dose. With this self-administered reduction in 
niacinamide dosage, her Joint Range Index decreased from 85.5 to 84.9.

The level of niacinamide was increased to 150 mg. every 1 ½  hours (1500 mg/24 
hours) with an increase in her Joint Range Index from 84.9 to 90.1 in 267 days. The 
niacinamide dosage was then increased to 200 mg. every 1½ hours (2000 mg./24 
hours) with an increase in the Joint Range Index from 90.1 to 92.8 in 58 days.

Thus, in a period of almost two years, this patient's Joint Range Index rose from 68.2 
(severe joint dysfunction) to 92.8 (slight joint dysfunction). It is anticipated that with 
continuously adequate niacinamide therapy, she will in time achieve a Joint Range 
Index of 96-100 (no joint dysfunction).

CASE C. No.325, female, age 63, housewife, married.

This case history illustrates, in a woman with moderate hypertrophic arthritis, continuous 
improvement in joint function, as measured by increasing values of the Joint Range 
Index in response to adequate niacinamide therapy (Figure 17 summarizes this case).

For more than 10 years, she has had "chronic rheumatism," as well as many episodes 
of "acute rheumatism" characterized by painful transient swellings of her hands, wrists, 
knees and ankles. Her present complaints include generalized stiffness of joints (severe 
for an hour after she awakens in the morning) and accentuation of muscular, periosteal 
and articular discomfort with weather changes. While her wrists, shoulders and fingers 
have been painful and swollen "off and on," her knees have given her the greatest, most 
persistent discomfort. In the past year her knees have become so painful that she has 
had many sleepless nights.

Physical Examination: B.P. 170/80. Wt. 180 lbs. Ht. 61 ¾ inches. She is moderately 
obese, tired-looking, hyperkinetic. Her skin is relatively inelastic, has increased 
brownish pigmentation, and the normal reticular pattern is accentuated. The 
conjunctivae show thickening and increased vascularity. She has some circumcorneal 
injection. Her teeth are in good repair. The gingival membrane is thickened and 
retracted, but there is no evidence of gingival infection. Her tongue shows marked 
atrophy and infiltration of lingual papillae. Her Joint Range Index of 65.8 indicates 
severe joint dysfunction. She has a moderate upper dorsal kyphosis. Her wrists, fingers 
and knees are swollen. No objective signs of impaired nerve function are elicited. Her 
Sedimentation Rate Index is 0.4 mm/min. (Wintrobe-normal range 0.1 - 0.3 mm/min.). 
Hemoglobin 11.8 g./100 cc. (acid hematin photo-electric colorimeter). An x-ray of her 
knees taken immediately before therapy was instituted showed evidence of a 
hypertrophic type of osteoarthritis.

Niacinamide (150 mg every 3 hours for 6 daily doses, which is 900 mg/24 hours) was 
prescribed. After one month of therapy, she reported subjective improvement in her 
general feeling tone. Objectively her skin and tongue showed improvement. The 
prominent swellings had disappeared from the sites enumerated above. Her kyphosis 
seemed less prominent. She appeared younger and more vigorous than when first 
seen.

She stated on her fourth visit that she felt almost entirely free from all joint discomfort at 
the end of about 100 days of continuous therapy with niacinamide. She was particularly 
pleased that she was no longer awakened at night by knee pain. Objectively, her tongue 
and skin continued to show resolution of the abnormalities noted at the initial 
examination.

During five months of treatment, she has made objective improvement in joint function, 
as indicated by an increase in the Joint Range Index from 65.8 (severe joint
dysfunction) to 83.2 (moderate joint dysfunction).

CASE D. No.461, female, age 68, widow, invalid.
This case history illustrates, in a woman with severe chronic rheumatoid arthritis, 
improved joint function as measured by increasing values of the Joint Range Index and 
by decreasing values of the Sedimentation Rate Index in response to therapy with 
niacinamide in the early months of such therapy (see Figure 18).

Much of the initial history had to be elicited with the patient reclining on a couch 
because she was too tired to sit up. She states that she had her first attack of "acute 
rheumatism" more than 40 years ago. These attacks of "rheumatism" recurred 
irregularly at frequent intervals until 2 years ago, when they apparently ceased. They 
were characterized by abruptly increased swelling, stiffness, pain and limitation in the 
range of joint movement. The joints were hot to the touch, but not red. In the course of 
these various attacks, not a single joint or joint group the body was "missed." However, 
not all of the joints were involved at any one time. The acute episodes usually lasted 2 
or 3 days and were followed by her ordinary chronic joint discomfort, which was 
somewhat more endurable than the severe exacerbations of her difficulty. However, in 
the past 5 years, her chronic discomfort and disability have increased so much that she 
doesn't think "it's worth going on living this way.

For more than 25 years, she has had severe deformities which have become 
progressively worse, so that now her hands are of little use to her. In addition, her 
wrists, elbows, shoulders, knees, ankles, feet (including the toes) are deformed, swollen 
and painful. For many years she has not been able to move her right wrist actively or 
passively, presumably because of complete ankylosis of the wrist joint; the range of 
movement of the left wrist is negligible. The ulnar deviation of her fingers prevents her 
from doing very much with her hands. She cannot raise her arms in abduction high 
enough to comb her hair nor can she fully extend her elbow joints. She is unable to flex 
or extend her ankles appreciably. Her toes are fixed in abnormal positions by joint 
deformities. Her knees, the most painful joints in her body, are hot and swollen. She 
thinks her knees have become markedly worse in the past year. Even with assistance 
she can scarcely get out of a chair because the pain in her knees is so severe that she 
thinks her legs might suddenly “let go." She is unable to walk upstairs and for years has 
lived on the first floor of her house. For more than 5 years, she has been unable to turn 
her head. If she wants to see someone behind her or to the side, she has to turn her 
whole body. For the past 5 years when she wakes at night and wants to turn her head, 
she has to turn her whole body in bed since her neck won't turn. Since her knee 
deformities do not permit full extension of these joints, when she is recumbent in bed 
she has to have two large pillows under her knees to support them in the least un-
comfortable position. When she arises in the morning she is "terribly stiff" for about an 
hour. This severe stiffness recurs late in the afternoon.

During the past 5 years, she has had severe wasting of the muscles everywhere, but 
most markedly in her forearms and hands. She has suffered for the past 10 years from 
paresthesias of certain fingers of her hands.

She has an allergic colitis which is subject to exacerbations when she eats certain 
offending foods, such as milk, onions and chocolate. In the past 5 years, she has slowly 
and progressively lost more than 40 pounds in weight. She is so tired that for the past 5 
years she has been unable to be up for longer than half an hour at a time.

Her arthritis had not been helped by any form of treatment which she had received to 
date.

Physical Examination: She is an extremely tired, crippled, chronically ill woman who is 
emaciated and has practically no subcutaneous fat. Extreme wasting of somatic 
musculature is noted. Wt. 90 ¾ lbs. Ht. 67 ¾ inches. B.P. 124/82. P.80. R. 18. Grips: R. 
24, L. 20 (normal range for women 60-80). The skin is inelastic and thickened 
everywhere. There is a pervading color of light brown that is not sunburn. The reticular 
pattern of the skin is moderately accentuated. Severe callusing of the feet is noted. 
There is marked swelling noticeable in her face, around her elbows, wrists, fingers, 
knees, ankles, feet. Digital pressure over the bony eminences causes no pain, although 
severe pain can be elicited from every moveable joint upon maximal passive or active 
movement. Examination of the eyes reveals circumeorneal injection and conjunctival 
thickening. The optic disc out-lines are not distinct. Arteries are slightly tortuous, being 
narrowed from 0 to 2-plus; the veins and arteries are 2-plus infiltrated. No nicking or en-
gorgement is seen. The vermilion borders of the lips are thickened and magenta-
colored. No cheilosis is noted. The gums show slight pitting and moderate infiltration 
and retraction. The tongue is magenta-colored, and its substance is swollen. The lateral 
lingual margins show complete atrophy of all papillae. Elsewhere, fungiform papillae are 
extinguished and filiform papillae are atrophic. There are many transverse fissures in 
the lingual mucous membrane. Her thyroid gland is 1-plus enlarged in the isthmus, but 
the lobes are not enlarged. Trachea in the midline. Chest is negative to auscultation and 
percussion excepting for emphysema. Heart is enlarged by percussion, the point of 
maximal impulse being 8 ½ cms in the 6th intercostal space. She has a soft, 1-plus non-
transmitted mitral systolic murmur. Apical sounds are distant and of fair quality. No liver 
tenderness. No organs or masses are felt in the abdomen. Her temporal, branchial and 
radial arteries are slightly thickened. Her abdominal arteries, aorta, right and left internal 
iliac vessels are thickened and tender. Right and left posterior tibials pulsate 3-plus and 
are firm. The dorsalis pedis arteries are not palpable. She has moderately severe dorsal 
kyphosis and swollen ankles, knees, wrists and fingers. The fingers, held in marked 
ulnar deviation, are markedly deformed, as are her toes. The wrists are apparently 
ankylosed. Crepitus is elicited from the neck joints and from all moveable extremity 
joints. Vibratory sensation in the right lower extremity (toes, malleolus and tibia) is more 
marked than in the left. Vibratory sensation in the upper extremities within normal limits. 
No plantar dysesthesia. Tickle sense 2-plus on forehead, absent elsewhere. Sense of 
light touch and sense of motion and position are intact.

Urinalysis negative. Hemoglobin 9.0 g/100 cc (acid hematin photoelectric colorimeter). 
Sedimentation Rate Index 1.65 mm/min. (Wintrobe-normal 0.1-0.3 mm/min.).

Her Joint Range Index was 45.0, indicating extremely severe joint dysfunction. (In order 
to obtain an initial value for her Joint Range Index, measurement of hip and knee 
ranges used in computing the Joint Range Index was made in the usual way, save for 
the fact that the marked flexion deformities of the knees caused some pelvic tilt with the 
patient recumbent. However, on the 139th day, the flexion deformity of the knees could 
no longer be demonstrated. Also, since the fixation of the fingers of the deformed hands 
did not permit extension of all of her fingers to the zero, or neutral level - i.e., the level 
where the finger would be neither flexed nor extended - a new convention was 
introduced in this instance. When the fingers on maximal extension did not reach the 
zero line, the percentage of the quadrant between the dorsura of the finger being 
measured and the zero line was noted with a minus sign, and tile finger index was 
derived in the usual way, adding algebraically the various measured values obtained for 
each hand.)

She was asked to take 150 mg of niacinamide hourly during the day (2400 mg/24 
hours). After 34 days of such therapy, she stated that she had been feeling stronger, 
and that she tired somewhat less readily than formerly. She stated emphatically that her 
shoulders were almost entirely comfortable, and moved much more freely. She could 
comb her hair for the first time in 5 years. Her knees were still painful, and she was not 
as "spry getting out of a chair" as she would like to be, but she was able to get out of a 
chair without assistance. Her color, she thought, had improved.

When she walked, she held herself more erectly and moved with better balance than 
she had when first seen. She seemed mentally alert and responsive. She was able to 
get up from her chair without assistance, although she had some difficulty in doing so, 
and some pain in her knees. Her skin had become a little more elastic and was lighter in 
color. The reticular pattern of the skin was less prominent. Her lingual mucous 
membrane showed some signs of improvement. The tissue swellings previously noted 
had almost disappeared. She had gained 1 ¼ lbs in weight. Her Joint Range Index had 
increased from 45.0 to 58.5. The venous pattern around the knee joints was much less 
prominent than it had been when she was first seen. She could extend her knees 
almost completely, and was able to lie flat on the examining table without a pillow under 
her head, and required only a small pillow under her knees for comfort. The ulnar 
deviation of the fingers was less marked than when she was first seen. The 
Sedimentation Rate Index had improved slightly, having declined from 1.65 to 1.50 
mm/min. In 76 days of treatment with niacinamide, her Joint Range Index had stabilized 
at 58.2. There was no discernible tissue edema. She had had further improvement in 
her feeling tone. She was very much more comfortable physically, and was troubled 
hardly at all by pain and discomfort in her joints. Her stiffness was markedly decreased. 
Since her Joint Range Index had apparently stabilized, the dosage of niacinamide was 
increased so that she took on alternate hours 150 mg and 200 mg of niacinamide (2800 
mg/24 hours).

In 139 days she had a Joint Range Index of 61.5. She thought that her was improved 
considerably. She weighed 5 lbs. more than when first seen. She was generally more 
cheerful and seemed to be more youth-in appearance and behavior. She could now be 
up for several hours at a time without requiring a nap. She was able for the first time in 
many years to go upstairs without assistance, although she still had moderate pain in 
her knee joints on doing so. She could get out of a chair easily without assistance and 
with very little discomfort. She was able to lie flat on the examining table without pillows 
under her head or knees, and without pain or subjective discomfort. Her Sedimentation 
Rate Index had decreased from 1.50 mm/min. (34th day) to 0.44 mm/min. (139th day). 
Her niacinamide schedule was increased from the previous level to 250 mg per hour 
(4000 mg/24 hours), since it was felt at this time that the severity of her joint dysfunction 
warranted such a therapeutic trial at that time.

About 3 weeks before her next scheduled visit, she was feeling so well that she took 
liberties with her diet, eating foods (milk, onions, chocolate) to which she knew she was 
extremely allergic. The ingestion of these offending foods activated her allergic colitis, 
as a result of which she lost 4 lbs. in 10 days. She had resumed her usual diet (avoiding 
milk, onions and chocolate) about 10 days before her visit, and was again feeling better, 
although her colon was still somewhat irritable and hyperactive. Save for this interlude 
of allergic colitis, which she considered to be an unimportant incident, she felt very well 
physically.

In 202 days of niacinamide therapy, she was almost completely free from joint 
symptoms, including pain. Her Joint Range Index had risen from 61.5 (139th day) to 
62.9 (202th day). Her elbows, which could not be fully extended initially, were now 
easily extended. Her right wrist, which had been clinically completely ankylosed, now 
moved 10% in extension and 0% in flexion. The left wrist, which on the initial 
examination had moved 0% in extension and 10% in flexion, now moved 15% and 50%, 
respectively. She was able to lie on the examining table without any pillows under her 
head or knees. She was able to get out of a chair as any normal person would. Her 
knees, which had been originally markedly swollen, were markedly decreased in size. 
Since the initial visit, there had been a decrease in the transverse diameter of the knees 
of 0.44 inch across the right knee and 1.38 inches across the left knee (measured 
across the broadest part of the knees).

Summary: This case history illustrates the effects of niacinamide therapy in the early 
months of such therapy in a person with extremely severe joint dysfunction (severe 
chronic rheumatoid arthritis of long duration). A summary of certain clinical and 
laboratory data obtained during the various office visits is listed in Table 0A.

Subjectively, as a result of treatment with niacinamide, in the early months of therapy 
this patient experienced a sense of well-being, including greater strength, less 
fatigability and freedom from joint pain and stiffness. She had less limitation in the 
ranges of joint motion. She had an increased appetite and enjoyment of food. She had a 
new zest for living.

Her weight loss between the 139th day and 202nd day was attributed to her allergic 
colitis, which she induced by eating foods to which she knew was hypersensitive.

Her severe hand deformities showed some signs of resolution, so that the fingers which 
were formerly fixed in ulnar deviation could now be passively brought into the normal 
position without pain. The wrist joints which were clinically ankylosed showed some 
tendency toward renewed movement, although objectively the right wrist was not 
considered to have shown significant improvement thus far. The left wrist showed 
marked improvement, and it is anticipated that in time, with continuously adequate 
niacinamide therapy, there will be further movement of this joint both in flexion and 
extension.

During the above period of clinical observation the increased Joint Range Index, 
decreased Sedimentation Rate Index, increased weight, decrease in joint swelling and 
in generalized tissue edema, increased hemoglobin, red blood count and hematocrit, all 
indicate the arrest and partial reversal of her severe chronic rheumatoid arthritis, as a 
direct result of therapy with niacinamide as the sole therapeutic agent. Further observa-
tion of this patient is necessary in order to determine the maximal degree of clinical 
recovery possible for her in response to continuously adequate niacinamide therapy 
over a much longer period of time.

CASE E. No.339, female, age 78, spinster.
This case history illustrates, in an elderly woman with severe acute rheumatoid arthritis 
(probably superimposed on mild chronic hypertrophic arthritis), improvement in joint 
function as evidenced by rising values of the Joint Range Index in response to adequate 
therapy with niacinamide (see Figure 19).

This woman considered that for her age she had enjoyed excellent health until 6 months 
ago, when her younger sister, aged 75, had a stroke. Before her sister's illness, the 
patient had never done much physical work. However, since the sister did not wish to 
be hospitalized, or to be taken care of by strangers, the patient undertook to give 
nursing care to her sister at their home. The bedrooms were on the second floor, and 
the patient made many extra trips up and down the rather steep flight of stairs, usually 
carrying her sister's meals to her. She was so busy with her sister's care that she 
neglected to eat her usual abundant diet, substituting starchy foods for high-protein 
foods.

After a month of such increased physical activity and change in her dietary habits, she 
was aware of pain, stiffness and swelling of her joints. She took 8-10 aspirin tablets (0.3 
g) a day with only slightly increased comfort. Although prior to her sister's illness she 
had been able to go up and down stairs without difficulty, now she could not climb the 
stairs without gripping the banister with her left hand and pulling herself upward step by 
step in this way.

Her sister improved gradually over a period of several months, so that at the time of her 
initial visit she had much less to do physically, although she continued to have a high-
carbohydrate diet. Her joints continued to give her trouble, so that she had constantly 
severe pain in the neck, severe low back pain, and painful swelling of the knees, ankles, 
wrists, hands, elbows and shoulder joints. She had persistent numbness and tingling of 
her hands, which were so swollen that she could not "make a fist." She noticed that 
many of her joints were extremely hot to the touch, and that she had considerable 
crepitus in most of her joints. Every morning for several hours she felt stiff, until the 
aspirin "took hold." Her stiffness recurred toward evening, when it was not relieved by 
aspirin. With changes in weather, she had increased joint discomfort. Her sleep was 
disturbed and restless because of her joint discomfort. She had lost 16 lbs. in the past 3 
months. She felt that she was becoming progressively weaker, and felt exhausted most 
of the time.

Physical Examination: T. 99.2 degrees. P.74. R. 18. B.P. 150/90. Wt. 156 lbs. Ht. 62 ¼ 
inches. Grips: R. 20, L. 12 (normal range for women 60-80). She is a sick old lady who 
is apparently in great pain during the interview and physical examination. She seems 
dulled mentally. Her voice is quavery and quernious. She walks with extreme slowness 
and some dysequilibrium.

Her Joint Range Index is 62.9, indicating severe joint dysfunction. The joints of the left 
side of her body are somewhat more involved by the arthritic process than those of the 
right. She has marked dorsal kyphosis. Her knees, ankles, wrists, hands, elbows and 
shoulder joints show the marked swelling seen in classic rheumatoid arthritis. Prominent 
venous engorgement around the knees is noted. Her extremity joints are hot to the 
touch. A few subcutaneous periosteal nodules are felt on the ulna and tibia.

Her skin is yellow-brown and somewhat atrophic. The reticular pattern of the skin is 
accentuated. She has a few ecchymoses. Many hyperkeratotic hair follicles are 
observed on the extensor surfaces of her extremities. She has Bit6t spots. Her 
edentulous gums are swollen and reddened. Her tongue shows hyperemia of the tip 
and lateral margins, and marked atrophy of papillae. Her heart is enlarged by 
percussion, the point of maximal impulse being felt 10 cm. to the left of the mid-sternal 
line in the 5th intercostal space. Throughout systole there is heard a 8-plus, moderately 
high-pitched, rough, non-transmitted aortic systolic murmur. The lungs are 
emphysematous but otherwise negative to physical examination. The liver margin is felt 
3 fingers' breadth below the costal margin in the right midclavicular line at the end of 
deep inspiration, and is 8-plus tender. No other organs or masses are felt. Reflexes are 
within the range of normal. Her dorsalis pedis arteries are firm, pulsate 8-plus and are 
equal; her posterior tibial arteries are firm, pulsate 1-plus and are equal. Tickle sense is 
absent, but vibratory sense, sense of light touch and sense of motion and position are 
intact. Her Sedimentation Rate Index is extremely elevated, being 1.80 mm/min 
(Wintrobe-normal 0.14).3 mm./min.). Hemoglobin 11.4 /100 cc (acid hematin 
photoelectric colorimeter).

Niacinamide was prescribed, to be taken 150 mg. every 3 hours for 6 doses daily (900 
mg/24 hours). After 22 days of this therapy, much of her joint swelling had resolved, 
although she still complained of pain and stiffness. She walked and sat more erectly 
than on her first visit. She walked with better balance, and more rapidly than she had 
originally. Her liver margin was palpated 2 fingers' breadth below the right costal margin 
in the right mid-clavicular line on deep inspiration, and was 2-plus tender. Her Joint 
Range Index had risen from 62.9 (severe joint dysfunction) to 73.2 (moderate joint 
dysfunction).

In 84 days of therapy, her Joint Range Index had apparently stabilized at 72.8. Although 
slight ankle edema still persisted, edema around other joints was no longer evident. Her 
Sedimentation Rate Index had decreased from 1.80 mm/min to 1.00 mm/min. In order 
to be completely free from bone and joint symptoms she required only one aspirin tablet 
a day. Her voice had lost its quaver. She seemed to be more alert mentally and more 
vigorous physically. There had been considerable improvement in her lingual mucous 
membrane.

In 172 days of treatment, her Sedimentation Rate Index had improved further, so that it 
was 0.85 mm/min and her Joint Range Index had risen to 76.2. She stated emphatically 
that she felt better than she had in many years, and was almost entirely free from joint 
discomfort and pain. She was delighted to report that she no longer required the help of 
aspirin to be comfortable. Her liver was no longer enlarged or tender to palpation. Wt. 
158 lbs.

At the end of 280 days of treatment, her Sedimentation Rate Index had fallen to 0.65 
mm/min and her Joint Range Index had risen to 80.7. She was able for the first time in 
almost a year to go upstairs without either pulling herself up by the banister or climbing 
up the steps hand over hand, foot over foot, as an animal would. Her skin had become 
more elastic and less atrophic. Her color was improved, and the yellow-brown color had 
been disappearing. No evidences of joint swelling could be made out. The ulnar and 
tibial subcutaneous nodules originally present could no longer be identified. She had no 
evidence of liver enlargement or swelling of the liver on palpation.

However, since the rate of recovery of her lingual mucous membrane in response to 
therapy with niacinamide was considered to be somewhat slow, it was decided to 
increase her dosage schedule from 150 to 180 mg. of niacinamide per capsule, to be 
taken one every 3 hours for 6 daily doses (an increase from 900 to 1080 mg. of 
niacinamide per 24 hours).

For one month she adhered faithfully to the revised program of therapy, and felt in such 
excellent health and spirits that she became careless, reducing her niacinamide intake 
to approximately one capsule every 3 1/2 hours for 5 daily doses (900 mg niacinamide 
per 24 hours).

When she was next seen on the 355th day of niacinamide treatment, her Joint Range 
Index had risen from 80.7 to 84.1, although the Sedimentation Rate Index had risen 
slightly from 0.65 to 0.75 mm./min. When she was informed that the Sedimentation Rate 
Index was less good than previously, she agreed to take her medication faithfully.

On the 417th day, her Joint Range Index had risen from 84.1 to 86.0, and her 
Sedimentation Rate Index had fallen from 0.75 to 0.56 mm/min. At this time she was 
euphoric, and did not remember when she had felt so well. She was physically and 
mentally vigorous. Her voice was clear, resonant and decisive. With considerable 
satisfaction, she reported a renewed interest in being with people, and in entertaining 
guests. She looked younger than when first seen, appearing to be closer to 60 than 80 
years of age. She had been entirely free from bone and joint symptoms, and had not 
taken any aspirin for about 8 months. She could walk up and down stairs without 
difficulty and without any sense of physical impairment or exhaustion.

Her carriage was erect, although she still had a dorsal kyphosis which would be graded 
as moderate. Her skin was smoother, softer, less atrophic and more elastic than it was 
on her first examination; the reticular pattern was less marked than it had been, but still 
accentuated. She had no discernible joint swellings or deformities. There was no 
hepatic tenderness or enlargement. The lingual mucous membrane showed a more 
satisfactory rate of recovery than it had to date in response to niacinamide therapy. Her 
muscular strength as measured by the dynamometer had improved (Grips: R. 50, L. 
46). Hemoglobin 12.0 g/100 cc (acid hematin photoelectric colorimeter).

Summary: This elderly lady with severe joint dysfunction (acute severe rheumatoid 
arthritis probably superimposed on a mild chronic hypertrophic arthritis) showed in 417 
days in response to treatment with niacinamide as the sole therapeutic agent, an 
improvement in the Joint Range Index from 62.9 (severe joint dysfunction) to 86.0 
(slight joint dysfunction). Her Sedimentation Rate Index improved from the exceedingly 
high rate of 1.80 mm/min to 0.56 mm/min. (Wintrobe-normal 0.1 - 0.3 mm/min). Her 
muscular strength (grips) as measured with a dynamometer in pounds per square inch 
rose from the initial measurement of R. 20, L. 12 to R. 50, L. 46 (normal range for 
women 60-80). In addition to the objective improvement in all of her joints and in her 
general health, there was a striking decrease in her apparent age. It is anticipated that 
with continuously adequate niacinamide therapy she will in time achieve a Joint Range 
Index of 96-100 (no joint dysfunction).

CASE F. No.85, female, age 69, housewife, married.

This case history illustrates, in a woman with severe joint dysfunction and severe, 
chronic hypertrophic arthritis, (a) improved joint function, as measured by an increased 
Joint Range Index in response to adequate therapy with niacinamide for one month, (b) 
impaired joint function, as measured by a lowered Joint Range Index, as a result of 
substitution of inadequate for adequate niacinamide therapy, and (c) improved joint 
function, as measured by subsequent increases in the Joint Range Index in response to 
the re-introduction of more adequate therapy with niacinamide (see Figure20).

She has had arthritis for a long time. For at least 10 years, she has had marked 
deformities of the hands. Her arthritic symptoms have become more severe in the past 
6 months, during which time she has been increasingly tired, more forgetful and more 
irritable.

Physical Examination: B.P. 168/78. Wt. 118 lbs. Ht. 62 ½ inches. Her skin has a 
yellowish cast and is inelastic, with a markedly accentuated reticular pattern. She has 
no periosteal tenderness on digital pressure, and no liver tenderness or enlargement. 
The lingual papillae are atrophic. Sedimentation Rate Index 0.75 mm/min. (Wintrobe-
normal 0.1-0.3 mm/min). Hemoglobin 9.9g/100 cc (acid hematin photoelectric 
colorimeter). White blood count 8,000. Her Joint Range Index was 59.6, indicating that 
her joint dysfunction fell within the lower range of the severe grade of joint dysfunction. 
Hypertrophic deformities of the joints of the fingers were noted.

She had severe joint dysfunction (severe hypertrophic arthritis). She was given 
niacinamide, 150 mg every 3 hours for 6 doses daily (900 mg/24 hours). For one month 
she took the medication as prescribed, making the expected improvement in her Joint 
Range Index, which rose to 78.3. During the next two months she gradually reduced her 
dosage of niacinamide, with a concomitant fall in the Joint Range Index. She then 
resumed taking the niacinamide as originally directed, with subsequent improvement in 
the Joint Range Index.

Since her Joint Range Index appeared to have stabilized (80.2 and 80.7), her 
niacinamide intake was increased to 250 mg every 3 hours for 6 doses daily, with a 
resultant improvement in the Joint Range Index. In 349 days her Sedimentation Rate 
Index decreased from 0.75 to 0.35 mm/min (Wintrobe-normal 0.1-0.3 mm/min). In 735 
days her Joint Range Index had risen from 59.6 to 88.7, a shift from the lower range of 
severe joint dysfunction to slight joint dysfunction. This patient subsequently discon-
tinued treatment because she mistakenly thought she was cured, since she felt so well.

CASE C. No.336, female, age 29, private secretary, single.

This case history illustrates, in a woman with moderate joint dysfunction, without 
clinically obvious arthritis, (a) improvement in joint function as measured by increasing 
values of the Joint Range Index in response to adequate niacinamide therapy, (b) 
impairment in joint function as measured by a lowered Joint Range Index in response to 
premature cessation of niacinamide therapy, and (c) subsequent improvement in joint 
function as measured by an increased Joint Range Index in response to the re-
introduction of adequate niacinamide therapy (see Figure 21).

Her presenting symptoms are increasing fatigue and irritability. She has no symptoms 
referable to bones and joints.

Physical Examination: She looks and acts tired. Her skin has a yellowish cast, and is 
generally coarse. She has marked atrophy and infiltration of the lingual papillae. Her 
liver on deep inspiration is felt at the costal margin in the right mid clavicular line and is 
1-plus tender. She shows no clinical evidence of arthritis, although her Joint Range 
Index of 73.7 indicates moderate joint dysfunction.

In response to 150 mg of niacinamide every 3 hours for 6 daily doses (900 mg/24 
hours) she displayed progressive improvement in her joint dysfunction, as shown by 
increasing values of the Joint Range Index (a value of 90.4 was 6btained after 207 days 
of continuous niacinamide therapy). This patient experienced also improvement in her 
general health, with complete resolution of excessive fatigue and irritability, and con-
comitant improvement in the lingual mucous membrane.

She lost interest in continuing with therapy, and for four months took no medication. 
There was a gradual recurrence of her presenting symptoms, and she returned for 
study and treatment. Her Joint Range Index had dropped from 90.4 on the 207th day to 
79.5 on the 442nd day. With resumption of therapy, her Joint Range Index rose from 
79.5 on the 442nd day to 92.7 on the 470th day, and to 96.5 on the 725th day.

CASE H. No.208, male, age 10, schoolboy.
This case history illustrates, in a boy with moderate joint dysfunction, without clinically 
obvious arthritis, improvement in joint function as measured by an increasing Joint 
Range Index in response to adequate therapy with niacinamide (see Figure 22).

He has experienced ill-health, including many severe infections. He is jittery, nervous 
and apparently unable to fix his attention on anything for even short periods of time. He 
has paresthesias in the legs if he sits for more than half an hour. He is irritable and 
easily tired.

Physical Examination: B.P. 110/70. Wt. 67 lbs. Ht. 55 ¼ inches. His skin is yellow-brown 
everywhere, and roughened and discolored, particularly over the knees, ankles, elbows 
and hands. The reticular pattern is slight. He has many ecchymoses, particularly on the 
right leg. There is tenderness on pressure over the sternum, sternoclavicular junction 
and chondrosternal junction. He has mild atrophic changes in the lingual papillae. The 
conjunctivae lack lustre, but are not otherwise abnormal. Teeth are in good repair. 
Gums are swollen, slightly hyperemic, slightly retracted. No infection of the gums was 
noted. The liver edge is 2-plus tender and 2 fingers' breadth below the costal margin in 
the right middavicular line. He has plantar dysesthesia lasting 35 seconds. He has 
hyperpallesthesia in the lower extremities. Tickle sense is absent on the legs, but 
present elsewhere. Standing, he is unable to touch his fingers to the floor with knees 
unbent, the distance from fingers to floor with maximal bending being well over 12 
inches. The Joint Range Index of 78.0 indicated moderate joint dysfunction.

After one month of treatment with niacinamide (100 mg three times a day after meals 
and at bedtime; 400 mg/24 hours), his Joint Range Index showed improvement. 
Tenderness and enlargement of the liver had disappeared, as had his abnormal 
neurologic signs. There was a marked improvement in his personality.

In 1,003 days of continuous niacinamide therapy, this boy's Joint Range Index has 
improved from 78.0 (moderate joint dysfunction) to 98.2 (no joint dysfunction). He is 
now able to bend over as described above and touch the floor with his fingers. His color 
is no longer yellow. He is cheerful, cooperative and alert, and has stopped being a 
"problem child." He does not suffer from irritability or excessive fatigability

CASE I. No.431, female, age 87, interior decorator, divorced.

Figure 23 illustrates, in a woman with moderate joint dysfunction and moderate 
hypertrophic arthritis, improvement in joint dysfunction, as measured by a continuously 
rising Joint Range Index.

CASE J. No.808, female, age 39, commercial artist, widow.

This case history illustrates, in a woman with moderate joint dysfunction (mild, clinically 
obvious hypertrophic arthritis), (a) improved joint function, as measured by an increased 
Joint Range Index in response to adequate therapy with niacinamide for one month, (b) 
impaired joint function as measured by a lowered Joint Range Index, as a result of 
substitution of inadequate for adequate niacinamide therapy, and (c) improved joint 
function as measured by subsequent increase in the Joint Range Index in response to 
the re-introduction of more adequate therapy with niacinamide
Figure 24).

She had a "nervous breakdown" 3 ½ years ago when her husband died, was followed 
by typical menopausal symptoms. She has had transient low back pain and right 
shoulder discomfort after a day's work at the drawing board. She has had for the past 3 
years persistent stiffness of joints.

Physical Examination: B.P. 130/90. Wt. 153 lbs. Ht. 66 inches. Hemoglobin 11.8g/100 
cc (acid hematin photoelectric colorimeter). She has generalized pallor, and moderate 
accentuation of the reticular pattern of skin. Her Joint Range Index of 79.4 indicated 
moderate joint dysfunction

For the control of her menopausal symptoms she was given 50 micrograms of ethinyl 
estradiol once daily for a week, and thereafter every other day. In addition, she was 
given 150 mg of niacinamide every 3 hours for 6 daily doses (900 mg/24 hours), which 
she took for one month with the expected improvement in her Joint Range Index to 
86.6.

However, the next month, though she continued the ethinyl estradiol at the prescribed 
level, upon the advice of a "friendly druggist" she dropped the amount of niacinamide 
ingested to 600 mg/24 hours, taking 100 mg instead of 150 mg every 3 hours for 6 daily 
doses, with a resultant fall in her Joint Range Index to 81.4. Subsequently, she resumed 
taking niacinamide at the level originally recommended, and her Joint Range Index rose 
from 81.4 to 87.3.

Thus, in four months her Joint Range Index shifted from 79.4 (moderate joint 
dysfunction) to 87.3 (slight joint dysfunction), even though for one month the patient had 
reduced her niacinamide from adequate to inadequate levels.

CASE K. No.416, male, age 60, accountant, married.

This case history illustrates, in a male with severe joint dysfunction (mild but clinically 
obvious hypertrophic arthritis); improvement in joint function as measured by increasing 
values of the Joint Range Index in response to adequate niacinamide therapy (see 
Figure 25).

He was given 160 mg of niacinamide every 2 hours for 8 doses daily (1200 mg/24 
hours) and in 315 days of such therapy his Joint Range Index rose from 65.5 to 91.8, a 
shift from severe to slight joint dysfunction. With this therapy, he experienced a feeling 
of physical well-being and vigor such as he had not had for many years.

CASE L. No.413, male, age 61, mechanical engineer, widower.

This case history illustrates, in a man with severe joint dysfunction (clinically obvious 
hypertrophic arthritis), improvement in joint function as measured by increasing values 
of the Joint Range Index in response to therapy with niacinamide in combination with 
other vitamins (see Figure 26).

This man suffered for more than 6 years from severe, persistent headaches (occipital 
and cervical pain) which varied in intensity from day to day, but from which he had no 
relief, in spite of a regular, liberal intake of aspirin. In the past 2 years his headaches 
had become increasingly more severe. He has noticed crepitus in many of his joints, 
especially in the neck. He is stiff in the morning when he first awakens, and when the 
weather changes. His shoulders have been painful. At times he has noticed marked 
stiffness and pain in his finger joints.

Physical Examination: He is a tired, listless adult male who looks older than his stated 
age. B.P. 120/80. P. 70. R. 18. T. 97.2 degrees. Wt. 143 ½ lbs. Ht. 67 ¼ inches. His 
pigmentation is yellowish-brown. The skin of his neck and face has a sharkskin-like 
appearance, and the reticular pattern is markedly accentuated on his body. His 
fingernails are thickened. Callusing at pressure points is very noticeable. He has many 
hyperkeratotic hair follicles on the extensor surfaces of his arms and thighs, and on his 
abdomen and buttocks. He has marked tenderness on digital pressure over the 
ensiform process and the maxillary sinuses. His occipital bone is tender to digital 
pressure. His eyes show marked circumeorneal injection and photophobia. There is 
some thickening and increased vascularity of the conjunctivae. He is edentulous; the 
gums have a purplish, swollen appearance. His tongue is magenta-colored and showed 
marked atrophy and hypertrophy of papillae. He has cheilosis, perhaps partly the result 
of ill-fitting dentures. His liver margin is felt 3 fingers' breadth below the right costal 
margin in the right mid-clavicular line on deep inspiration. His posterior tibial and 
dorsalis pedis arteries pulsate 2-plus. He has marked plantar dysesthesia. Tickle sense 
is absent, although his sense of light touch, sense of motion and position and vibratory 
sense are intact. He has moderate dorsal kyphosis and moderate deformities of the 
fingers. His Joint Range Index was 67.5.

He was given a vitamin dosage schedule as follows:

Per Dose   Per 24 Hours
Niacinamide 162.5 mg   975 mg
Riboflavin                                  7 mg                              42 mg
Thiamine HCl                            3 mg                              18 mg
Ascorbic Acid                         225 mg                          1350 mg

At the end of one month of the above therapy, there was a marked change in his 
appearance. He seemed less listless and lethargic. He looked younger in appearance. 
His color was less brown. There was increased range of movement in his neck, and he 
had much less spasm of the neck muscles. He stated that his headaches were much 
less severe than formerly, that his spirits were much improved, and that he was less 
tired generally. However, his tongue, gums and eyes showed little resolution of their 
severe deficiency signs at this time. His Joint Range Index had risen to 77.8. He had no 
evidence of liver enlargement or tenderness.

With the passage of time and the continuance of therapy at the prescribed level, there 
has been progressive improvement in his tissues and m his Joint Range Index. His 
dorsal kyphosis is now less apparent. He now has headaches at rare intervals, which 
tend to be mild and occur only when he has held his head in an awkward position for a
considerable period of time; e.g., when he studies blueprints. With each successive 
visit, he has appeared to be a younger, more vigorous man.

With continuous therapy with niacinamide in combination with other his Joint Range 
Index rose in 190 days from 67.5 (severe joint dysfunction) to 87.1 (slight joint 
dysfunction).

CASE  No. 427, male, age 45, attorney, married.

This chart illustrates, in a man with severe joint dysfunction (without arthritis), 
improvement in joint function, as judged by increasing of the Joint Range Index in 
response to therapy with niacinamide in combination with other vitamins (see Figure 
27).

This patient's Joint Range Index rose from 67.7 (severe joint dysfunction) to 86.0 (slight 
joint dysfunction) in 178 days of therapy.

CASE N. No. 337, female, age 36, business woman, single.

This chart demonstrates, in a woman with moderate joint dysfunction (without clinically 
obvious arthritis), continuous improvement in joint function, as demonstrated by 
increasing values of the Joint Range Index in response to therapy with niacinamide in 
combination with other vitamins (see Figure 28).

This patient had hypothyroidism which was controlled with 90 mg of thyroid (U.S.P.) 
daily. A 3-week lapse in the ingestion of thyroid caused a recurrence of her hypothyroid 
symptoms, and the resumption of thyroid caused these symptoms to disappear. This 
lapse in thyroid therapy did not influence the pattern of recovery of her joint dysfunction. 
Her Joint Range Index rose from the initial value of 75.8 (moderate joint dysfunction) to
92.5.(slight joint dysfunction) in 385 days of continuous vitamin therapy.

Case 0. No.194, female, age 52, business woman, married.

This case history illustrates, in a woman with moderate joint dysfunction (without 
clinically obvious arthritis), (a) improvement in joint function in response to a given level 
of vitamin therapy which proved to be inadequate, as demonstrated by stabilization over 
a period of time the Joint Range Index below the 96-100 level, and (b) subsequent 
improvement in joint function, as indicated by rising values of the Joint range Index in 
response to a small increase in the level of vitamin therapy

For 511 days this patient was given the following vitamins:

Per Dose Per 24 Hours
Niacinamide 100 mg          400 mg
Ascorbic Acid            100 mg          400 mg

With the above level of treatment, her Joint Range Index rose from 79.0 to 83.0 in 70 
days. In 295, 391 and 511 days the Joint Range Index measured 89.2, 89.8 and 89.2, 
respectively.

Her dosage schedule was changed to:

Per Dose   Per 24 Hours
Niacinamide  100 mg   600 mg
Ascorbic Acid  100 mg   600 mg
 
 
 
 

Subsequently, her Joint Range Index rose, so that on the 632nd day after the initial visit, 
it was 91.7, and in 748 days it was 93.4, indicating a shift from moderate to slight joint 
dysfunction. In 910 days of therapy her Joint Range Index rose to 96.9 (no joint 
dysfunction).

CASE P. No.362, male, age 28, attorney, single

This chart illustrates that a man with moderate joint dysfunction (without obvious 
arthritis) and mild untreated hypothyroidism (basal metabolic rate -18%) had no change 
in his Joint Range Index as a result of the daily ingestion of 60 mg of thyroid substance 
(U.S.P.) for 30 days. However, when he received in addition to his thyroid medication an 
adequate dosage of niacinamide in combination with certain other vitamins, there was 
improvement in his Joint Range Index (see Figure 30).

CASE Q. No.278, female, age 47, housewife, married.

This case history illustrates, in a woman with severe joint dysfunction (with clinically 
obvious hypertrophic arthritis), cyclically, (a) improved joint function as shown by an 
increased Joint Range Index in response to adequate therapy with niacinamide in 
combination with other vitamins, (b) impaired joint function as shown by a lowered Joint 
Range Index as a result of substitution of inadequate for adequate therapy, and (c) 
improved joint function as shown by increased Joint Range Index in response to re-
introduction of more adequate therapy (see Figure 31).

She has been aware of soreness in her joints, stiffness and limitation of movement for 
more than 10 years. She has had soreness of the tongue off and on for many years.

Physical Examination: She is a tired woman who looks older than her stated age. B.P. 
110/70. Wt. 114 lbs. Ht. 63 inches. Hgb. 10.5 g/100 cc. (acid hematin photoelectric 
colorimeter). Her skin is wrinkled, dry, yellow-brown. There is accentuation of the 
reticular pattern, increased callusing and a marked tendency to freckling. Her eyes 
show conjunctival thickening and injection. She is partially edentulous. The gums are 
pitted, infiltrated, swollen and retracted. Tongue shows moderate atrophy of papillae, 
with considerable redness of the tip and lateral margins. The margin of the liver is 
tender and just palpable at the costal margin. She has hyperpallesthesia in the bony 
eminences of the lower extremities. Plantar dysesthesia is in excess of 20 seconds. 
Tickle sense is present on the forehead, but not elsewhere. She has a low Joint Range 
Index of 67.9, indicative of severe joint dysfunction.

The following vitamins were prescribed in the manner indicated:
Per Dose          Per 24 Hours
Niacinamide 150 mg    900 mg
Riboflavin   4mg 24 mg
Thiamine HC1   2mg 12 mg
Ascorbic Acid  175 mg 1,050 mg
Vitamin A 5,000 units 15,000 units
Vitamin D 1,000 units 3,000 units

At the end of one month, her Joint Range Index showed the expected increase in 
response to therapy. Her color was less yellow-brown than originally. Her liver was no 
longer palpable or tender. The intensity of her neuropsychiatric symptoms had 
lessened. She was less tired, less irritable, and had marked lessening in her subjective 
sensations referable to joints. Her hyperpallesthesia was replaced by normal vibratory 
sensation. Plantar dysesthesia had disappeared. Slight tickle sense was present 
everywhere.

This patient had considerable difficulty in maintaining the therapeutic program as 
originally prescribed for her because at various times during treatment she suffered 
from anxiety states, fearing that she was pregnant. During these periods of anxiety, she 
invariably reduced her vitamin intake. Her vitamin intake as she reported it is shown in 
Figure 29, together with corresponding fluctuations in the Joint Range Index.

In spite of her difficulties in taking the medications as prescribed, she managed to take 
sufficient amounts over a period of time so that eventually her joint dysfunction 
improved from severe (Joint Range Index 67.9) to slight (Joint Range Index 92.3) in 682 
days.

CASE R. No.77, female, age 57, nurse, unmarried.

This case history illustrates, in a woman with severe joint dysfunction (clinically obvious 
hypertrophic arthritis), (a) initial improvement in joint function, as shown by an increased 
Joint Range Index in response to adequate therapy with niacinamide in combination 
with other vitamins, and (b) gradual decline of the Joint Range Index as a result of 
progressively greater departure from adequate therapy (see Figure 32).

She has not worked for 5 years because she has suffered from gastrointestinal 
symptoms consisting mainly of heartburn and indigestion occur-ring about an hour after
meals, relieved by bicarbonate of soda. Repeated x-ray studies have revealed no 
abnormalities of the gastro-intestinal tract. She has mild menopausal symptoms.

During the 5 years that she has been unemployed, she has lived without cost to herself 
with her sister and brother-in-law. Her poor health was used by her as an excuse for not 
doing even minimal housework.

Physical Examination: She is tense, tired and impatient. Wt. 150 lbs. Ht. 63 inches. B.P. 
130/84. Skin is yellow, with the reticular pattern moderately accentuated, as is callusing. 
She has moderate, early Bitot spots. Her receded gums are hyperemic, and slightly 
edematous. The anterior third of the tongue is reddened, and there is moderate atrophy 
of papillae. She has liver tenderness graded as 2-plus, with the liver edge at the level of 
the costal margin. Her Joint Range Index showed severe joint dysfunction (61.6).

She was given a regimen of therapy, including a bland diet, anti-spasmodic and 
vitamins prescribed in the manner indicated below:
Per Dose   Per 24 Hours
Niacinamide 175 mg 1,050 mg
Riboflavin 4.5 mg 27 mg
Thiamine HC1 3.5 mg 21 mg
Ascorbic Acid 175 mg 1,050 mg

In one month she had made the expected progress, as indicated by improvement in her 
physical condition and in the Joint Range Index of 76.1. When she realized that she was 
improving physically, she became panicky and developed many new psychosomatic 
symptoms, including severe headaches with a bizarre pattern and syncopal spells. The 
psychiatrist who studied her elicited the information that she hated to work, and when 
her brother-in-law found that she was feeling better, he would probably insist that she 
work as a nurse and contribute to her own support. As a result of the family situation, 
she gradually decreased the amount of vitamins taken so that ultimately she was taking 
about one-third the amount which had been prescribed. The approximate pattern of 
reduction in dosage as she described it is shown in Figure 32. At no time did she have 
insight into her basic emotional problems.

CASE S. No.201, male, age 52, manufacturer, unmarried.
This case history illustrates the effect on the Joint Range Index of varying levels of 
vitamin intake over a relatively long period of time (see Figure 33).

This man did not get along well with one of his business partners. The periods when he 
was under the greatest emotional strain at work corresponded exactly with the periods 
when he failed to take his vitamin therapy as prescribed. Conversely, when there was 
greater harmony at work, he had no difficulty in adhering strictly to the prescribed 
program.

While intellectually he appreciated the above relationship, when he was emotionally 
disturbed he was unable to keep his vitamin therapy at the recommended levels. 
However, at each interview he reported the approximate amounts of the medications 
that he had been able to take for each time interval between examinations. His initial 
Joint Range Index was 72.6 (moderate joint dysfunction), and in 509 days his Joint 
Range Index was 89.0 (slight joint dysfunction). The Joint Range Indices reflected 
alterations in the level of his vitamin ingestion.

CASE T. No. 345, female, age 41, housewife, married.
I
This case history illustrates, in a woman with moderate joint dysfunction (without 
clinically obvious arthritis), (a) improved joint function in response to one month of 
therapy with niacinamide in combination with other vitamins, (b) impaired joint function 
as measured by a lowered Joint Range Index as a result of premature cessation of 
vitamin therapy, and (c) improved joint function as measured by subsequent increase in 
the Joint Range Index in response to re-introduction of vitamin therapy at a higher level 
than originally (see Figure 34).

Her Joint Range Index was 80.7 at the time of the initial visit. For one month she took 
the following vitamins:

Per Dose   Per 24 Hours
Niacinamide 150 mg 600 mg
Riboflavin 5 mg 20 mg
Thiamine HCl 2.5 mg 10 mg
Pyridoxine HCl  5 mg. 20 mg
Ascorbic Acid 200 mg. 800 mg

At the end of one month of such therapy her Joint Range Index had risen to 84.9. For 6 
months she took no further therapy, and when she returned at the end of this time for 
examination, her Joint Range Index had fallen to 79.7. Vitamins were prescribed for her 
as follows:

Per Dose  Per 24 Hours
Niacinamide 190 mg 1,140 mg
Riboflavin 7 mg 42 mg
Thiamine HCl 4 mg 24mg
Pyridoxine HCl 6 mg 36 mg
Ascorbic Acid 250 mg 1,500 mg

At the end of one month of the above therapy, her Joint Range Index had risen to 92.6. 
Although not indicated in Figure 34, in 693 days this patient had a Joint Range Index of 
96.4 (no joint dysfunction).

SOME REASONS WHY CERTAIN PATIENTS WITH JOINT DYSFUNCTION 
FAILTOTAKE NIACINAMIDE THERAPY AS DIRECTED

As will be seen subsequently, not all of the 455 patients who were studied clinically 
accepted niacinamide therapy for joint dysfunction and returned for the necessary re-
examinations. Analysis of the data in Section IV indicates that 80.7% of the total 
population studied (78.5% of all males and 82.1% of all females) accepted niacinamide 
therapy for some period of time. It has been learned directly or indirectly that certain 
patients continued with niacinamide therapy without returning for necessary medical 
supervision; the exact number of such patients is not known. Therefore, less than 20% 
of the patients with joint dysfunction who were studied clinically did not accept 
niacinamide therapy. While it is not always possible to ascertain the reasons why a 
patient fails to take niacinamide therapy as prescribed, some of the apparent reasons 
are presented below.

The patient is unwilling to accept a method of medical treatment that is unfamiliar 
to him. Sometimes, a patient may believe that diet alone should be adequate to 
supply all his nutritional needs, and thinks that he can "get along" as his 
ancestors did, without vitamin therapy. Some patients desire only a thorough 
physical examination and an evaluation of their health status, and are uninterested in 
any form of therapy. Sometimes, a patient feels that it is a sign of weakness to take 
medications unless he is acutely ill, and will submit to treatment only for the duration of 
any medical or surgical emergency that may arise. Some patients want magical cures, 
and do not wish to undertake any treatment that requires sustained, active patient-
physician cooperation; they feel that the treatment demands too much of them, 
especially the taking of medications at stated intervals, and the necessity for re-
examinations. Certain patients are very impatient, and want treatment that will give 
"immediate results." They may request that instead of the niacinamide treatment they 
be given injections (gold, sulfur, liver, bacterial vaccine, vitamin "shots"). Some patients 
who present themselves for clinical study want only to be reassured that they are in 
perfect health, even though they may have major medical or surgical problems, and 
want to be told that any imperfections they may have are of no significance. Other 
patients want only to be told that they are ill, and should "take it easy," or take a long 
vacation, or be relieved of responsibilities and duties. Some patients are "shopping" for 
an operation. Other patients want only to have prolonged and expensive hospitalization, 
with special studies and treatment. Some patients who consult the physician unwillingly, 
at the insistence of a friend or relative, have no intention of following any medical 
advice. Some patients present themselves for study only to satisfy their curiosity about 
the physician and his methods.

Sometimes, a patient may be discouraged from taking niacinamide therapy for 
joint dysfunction by a "friendly" and crusading nurse, druggist, or physician, who 
insists that the niacinamide therapy of joint dysfunction is unnecessary or 
useless, and tells the patient that he needs no such treatment, or that he should 
try some other type of therapy which is in more general use.

A patient usually does not continue with niacinamide therapy of joint dysfunction when, 
on the first day of therapy, he takes niacin-containing medications dispensed mistakenly 
by the druggist instead of niacinamide, and experiences, unexpectedly, severe flushing 
and other unpleasant symptoms characteristic of niacin reactions (113). (No flushing or 
other untoward reactions have been observed in properly selected patients with joint 
dysfunction who have taken as much as four grams of niacinamide daily for a year or 
more.)

A few patients have initial difficulties in forming regular habits of taking medication 
during the first months of treatment of joint dysfunction. Unless certain patients are seen 
at relatively frequent intervals, they lose interest in continuing with niacinamide therapy. 
Some patients do not take medications as prescribed as a device for gaining the 
attention of family and physician.

Sometimes a patient will not take niacinamide therapy for joint dysfunction because he 
develops a strong negative transference reaction to the physician. Occasionally, such 
reactions may appear as masked negative transference reactions, when at the initial 
visit the patient seems excessively cordial, agreeing with everything the physician says, 
speaking confidently of how well he expects to feel in the future under the physician's 
care. Such a patient may never return for re-examination. If he does return, he never 
takes niacinamide therapy as prescribed, stating he is "too busy to take the medicine," 
that he has "too many pills to take," that he "forgets" to have his prescription refilled. He 
then states with apparent pleasure that he doesn't "feel better in any way," or that the 
treatment hasn't helped at all," even though he may continue to return for serial re-
examinations.

Some patients who have joint dysfunction and one or more of the four complicating
syndromes are impatient and unwilling to cooperate in the clinical investigation of their 
complicating syndromes, and they soon drop therapy.

A patient who does not have articular symptoms or arthritic deformities often sees no 
reason why he should take any medical therapy, even though his joint dysfunction may 
be severe. A patient who has articular symptoms and arthritic deformities may believe 
that his symptoms and deformities are not sufficiently troublesome to him to warrant the 
nuisance and expense of treatment.

Some patients with recurrent or continuous articular symptoms (with or without clinically 
obvious arthritis) are often unable to accept the fact that their joint dysfunction can be 
reversed in time, and if they begin niacinamide therapy, it is with the greatest 
skepticism. These patients, previously studied by many physicians over a period of 
years, had been advised repeatedly that there was no effective therapy for their articular 
illness. Thus, unless they feel subjectively improved within a few weeks of beginning 
treatment, they usually drop therapy.

Certain patients who enjoy secondary gains from their articular illness may not begin 
niacinamide therapy for fear that they may be "cured"; if they do accept therapy, they 
always take less than the prescribed amount of niacinamide.

In some instances of severe or extremely severe joint dysfunction with clinically obvious 
arthritis, but not in all instances, there may be a relatively long latent period between 
objective improvement in the Joint Range Index and subjective awareness of improved 
health as a result of therapy. Some persons who do not feel better subjectively during 
this period, fail to continue with therapy, in spite of objective evidence for clinical im-
provement. Such persons often drop therapy prematurely.

Whenever certain patients are exposed to an anxiety-producing situation, they reduce 
their vitamin intake to inadequate levels, and when the tensional situation has passed, 
they resume vitamin treatment as directed.

Some patients are afraid of "powerful" medicines, and when they have made good 
improvement in response to niacinamide therapy, they reduce their niacinamide intake 
for fear that the medicine is "too strong."

Certain suspicious patients reduce the niacinamide level below the recommended 
dosages, or stop niacinamide therapy prematurely without informing the physician of 
this. If such a patient's Joint Range Index has been maintained at a high level in 
response to a sufficient period of adequate niacinamide therapy, there may be some lag 
between the reduction in niacinamide intake and the decrease in his Joint Range Index. 
Such patients use this as proof that the physician is wrong about joint dysfunction and 
its proper treatment. Some of these patients who return for study after having 
discontinued niacinamide therapy for a year or more, show demonstrable regression of 
the Joint Range Index.

A patient with joint dysfunction who has mental symptoms which are extinguished by 
adequate niacinamide therapy may experience such marked improvement in his feeling 
tone during the first month of adequate niacinamide therapy that he may mistakenly 
believe he is "cured," even though he has made only the expected improvement in his 
joint dysfunction. He is likely to drop niacinamide therapy prematurely, and usually 
experiences a slow or rapid recurrence of his mental symptoms.

Some patients have a response to niacinamide therapy which seems to be the clinical
equivalent of "decreased running" observed in experimental animals (226). When these
animals are deprived experimentally of certain essential nutriments, they display
"excessive running," or hyperkinesis. When these deficient animals receive the
essential nutriments in sufficient amounts for a sufficient period of time, there is
exhibited a marked "decrease in running," or hypokinesis. Thus, certain patients may
discontinue therapy because they believe they feel less well as a result of niacinamide.
They may have the impression that vitamin therapy is depriving them of their usual abundant
energy, and may state that they are being "de-pepped" by the treatment.

A patient in this group may wonder whether or not his vitamin medications 
contain a sedative. He recalls that before vitamin therapy was instituted, he had a great 
deal of energy and "drive,” and considered himself to be a "very dynamic person." 
Analysis of his history indicates that prior to niacinamide therapy, even though he often 
felt tired, he did not need to rest or relax during the day, since he found it easier td 
“keep on going” than to stop and rest, and that he suffered from a type of compulsive 
impatience, starting many projects which he left unfinished as a new interest distracted 
him, returning perhaps after a lapse of time to complete the original project. Without 
realizing it, he was often careless and inefficient in his work, but was "busy all the time." 
With vitamin therapy, such a patient becomes unaccustomedly calm, working more 
efficiently, finishing what he starts, and he loses the feeling that he is constantly driving 
himself. He has leisure time that he does not know how to use. When he feels tired, he 
is able to rest, and does not feel impelled to carry on in spite of fatigue. All these 
changes he interprets to mean that vitamin therapy has robbed him of his vitality. If such 
a patient can be persuaded to continue with niacinamide therapy, in time he comes to 
enjoy a sense of well-being, realizing in retrospect that what he thought in the past was 
a super-abundance of energy and vitality was in reality an abnormal "wound-up" feeling, 
which was an expression of aniacinamidosis.

Some patients become tired of taking medications for prolonged periods of time, and 
stop niacinamide therapy for joint dysfunction.

Rarely, patients are unable to continue with niacinamide therapy for economic reasons.

LIMITATIONS OF THIS STUDY
Certain limitations were imposed on this study by the nature of the writer's private 
practice:

1. No repeated determinations of the Joint Range Index could be performed on a large 
sampling of the untreated population over a prolonged period of time.

2. No control series could be studied which had been treated with placebos, single 
vitamins other than niacinamide, or multiple vitamin mixtures not containing 
niacinamide.

3. No large series of determinations of the Joint Range Index could be made from two 
separate sets of measurements made in the same individual on the same day. 
(However, it was found in a trial with a small series of subjects that two Joint Range 
Indices determined from two separate sets of joint range measurements made on the 
same day in the same individual agreed within plus or minus 0.3.)

4. No routine x-ray studies of the joints whose ranges were measured for inclusion in 
the Joint Range Index could be obtained. However, a sufficient sampling of x-rays of 
measured joints was obtained in the course of this study to indicate that it would be of 
value to have such x-ray documentation, routinely performed before treatment was 
instituted, and at intervals during the course of treatment.

5. No standard photographic method was available for taking serial photographs which 
could be used in making accurate, detailed comparisons of gross joint morphology 
before therapy and at various intervals during the course of prolonged, adequate 
niacinamide therapy. In documenting the gross morphology of joint deformities, certain 
variables must be controlled rigidly if serial photographs are to be strictly comparable; 
e.g., positioning of the deformed joints, lighting, lens aperture, film exposure, size of film 
image, film development, type of printing paper, exposure of printing paper, size of print 
image, and print development.

6. No attempt was made clinically to find the highest dosage level of niacinamide which 
could be tolerated safely by patients with joint dysfunction, or to explore the effects of 
such doses on the rate of recovery in joint dysfunction. Only those dosages of 
niacinamide which seemed to be clinically safe and therapeutically effective were 
employed in the treatment of joint dysfunction.

7. No gross or histopathologic studies could be performed on the joint structures of 
patients with joint dysfunction in the course of this study.

8. No highly specialized chemical or metabolic studies could be performed prior to 
treatment with niacinamide, or subsequently, to follow in a patient with joint dysfunction, 
(a) the fate of the ingested niacinamide and the concomitant metabolic changes in body 
chemistry and metabolism during the course of adequate treatment of joint dysfunction; 
(b) changes in body chemistry and metabolism induced by the substitution of inade-
quate for previously adequate niacinamide therapy; (c) changes in body chemistry and 
metabolism induced by the premature cessation of adequate niacinamide therapy.

(End of Chapter 1, which consists of pages 1-75. The author’s preface, and all references cited, are posted at http://www.doctoryourself.com/kaufman11.html )

To read Chapter 2, click this link: http://www.doctoryourself.com/kaufman7.html

Andrew W. Saul

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