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CLINICAL SCIENCES

Case Study

Effects of resistance exercise and creatine


supplementation on myasthenia gravis: a
case study
JEFFREY R. STOUT, JOAN M. ECKERSON, ERIC MAY, CYNTHIA COULTER, and
GREG E. BRADLEY-POPOVICH
Exercise Science Department, Department of Neurology, and Department of Physical Therapy, Creighton University,
Omaha, NE 68178

ABSTRACT
STOUT, J. R., J. M. ECKERSON, E. MAY, C. COULTER, and G. E. BRADLEY-POPOVICH. Effects of resistance exercise
and creatine supplementation on myasthenia gravis: a case study. Med. Sci. Sports Exerc., Vol. 33, No. 6, 2001, pp. 869 872.
Purpose: The purpose of this case study was to determine the effects of 15 wk of resistance exercise and creatine (Cr)
supplementation on body composition, training volume, peak strength, and complete blood chemistry in a patient with myasthenia
gravis (MG). Methods: The patient was a 26-yr-old man who was taking prednisone and azathioprine for his condition. The
patient self-administered 5 g of Cr per day in addition to resistance exercise 3 times per week. Fasting blood samples were
obtained and body weight (BW) and fat free mass (FFM; via hydrostatic weighing) were measured before and after training and
Cr supplementation. In addition, isokinetic (Cybex II) peak strength for leg extension (LE), leg flexion (LF), and volume load
(repetition mass lifted) for the first and last resistance training session were determined. Results: After Cr supplementation
and training, the results demonstrated increases in BW (6.8%), FFM (4.3%), upper body volume load (37.0%), lower body volume
load (15.0%), and peak strength for LE (37.0%) and LF (12.5%). Moreover, blood chemistry values remained within normal limits
for the duration of the 15-wk study. Conclusion: These data suggest that resistance exercise plus Cr supplementation may
promote gains in strength and FFM in patients with MG. Key Words: NEUROMUSCULAR DISEASE, WEIGHT-TRAINING,
ERGOGENIC AID

tent, improved energy shuttling, and/or enhanced skeletal


muscle protein synthesis (3,13,27).
Within the last several years, Cr supplementation has
been explored as a therapeutic intervention for various neuromuscular and neurodegenerative disorders (24 27), since
skeletal muscle PC concentrations have been shown to be
low in many of these conditions (16,26). Recently, Tarnopolsky and Martin (24) demonstrated that acute (10 d) Cr
supplementation significantly increased strength and total
body mass in patients with a variety of neuromuscular
diseases, including mitochondrial cytopathies, dystrophies/
congenital myopathies, and polymyositis.
Patients with myasthenia gravis (MG) typically exhibit
skeletal muscle wasting, neuromuscular fatigue, and weakness (9). These symptoms are believed to be caused by a
functional blocking or loss of postsynaptic acetylcholine
receptors at the neuromuscular junction (7), as well as a
decreased PC content in skeletal muscle (16). To date, no
research has investigated the effects of resistance exercise
with Cr supplementation in patients with MG. Therefore,
the purpose of this case study was to determine the effects
of 15 wk of resistance exercise and Cr supplementation on

n skeletal muscle, creatine (Cr) is primarily stored as


free Cr and phosphocreatine (PC) and is found naturally
in foods such as meat. Phosphocreatine is the primary
fuel reserve for the resynthesis of adenosine triphosphate
during anaerobic exercise (18). Therefore, rapid depletion of
muscle PC is believed to be a limiting factor when performing maximal anaerobic work (12,14). In healthy subjects,
several studies have demonstrated ergogenic benefits from
acute Cr supplementation on strength, running, cycling, and
jumping (1,4,21,22,27). Furthermore, recent studies have
also demonstrated that Cr supplementation during resistance
training resulted in greater increases in fat-free mass (FFM),
muscular-strength, and training volume load when compared with resistance training alone (2,15,23). Possible
mechanisms responsible for the ergogenic effects of Cr
supplementation include increased skeletal muscle PC con-

0195-9131/01/3306-0869/$3.00/0
MEDICINE & SCIENCE IN SPORTS & EXERCISE
Copyright 2001 by the American College of Sports Medicine
Received for publication May 2000.
Accepted for publication September 2000.

869

body composition, strength, and blood chemistry profile in


a patient with MG.
CASE HISTORY
E.M. is a 26-yr-old medical student who was diagnosed
with MG in May 1995. Before the onset of the disease, he
was a full-time college student, played college baseball, and
was an avid weightlifter and runner. For 3 months before
diagnosis, he noticed that he was becoming gradually
weaker during weight training and experienced a slight loss
in body weight. One month before diagnosis, his maximum
bench press strength was 136 kg. However, at diagnosis, he
was unable to perform one push-up. He presented with
symptoms of unilateral ptosis progressing to both eyes,
diplopia, and muscle atrophy. At the time of diagnosis, he
weighed approximately 85 kg and had 5 6% body fat (via
skin-fold).
He began a regimen of Mestinon (60 mgd-1), Imuran
(azathioprine; 150 mgd-1), and prednisone (60 mgd-1).
After approximately 6 wk of medical treatment, his ocular
symptoms were controlled. However, the extreme weakness
and muscle atrophy persisted. He began to exercise again at
low levels, which prevented further weakness; however, he
was unable to regain his lost strength and muscle mass. He
continued to train at very minimal levels until undergoing a
thymectomy performed via sternotomy in September 1995.
At 3 months postsurgery, he independently began lifting
weights and exercising aerobically. Despite dedicated training, he was unable to improve his strength and muscle mass
above his postdiagnosis baseline. Pressing exercises involving the chest and triceps appeared to be most affected, and
these muscle groups showed the most evidence of atrophy
(left right).
Over the next 18 months, E.M. was stable and began
tapering off medications. During this time, he continued to
train regularly without gains in strength or mass. He had
completely discontinued medication by the end of the summer in 1997. That fall, after the beginning of medical
school, he began experiencing visual symptoms of ptosis
and diplopia and was placed on a reduced pharmacotherapeutic regimen of prednisone (40 mgd-1) and Imuran (150
mgd-1). The symptoms were controlled after approximately
4 wk of medication, and his condition remained stable
through the summer of 1998. During this time, he continued
to train with only minor gains in strength and mass.
Beginning in the fall of 1998, E.M. began to notice a
decrease in his strength and a gradual reduction in his body
weight (BW), despite making no changes in his exercise
regimen or diet. From September to December, he lost
approximately 4.5 kg of FFM, which was most noticeable in
his shoulders, chest, and neck. In late November 1998, he
again experienced frequent diplopia. After consulting his
neurologist in January 1999, computerized tomography,
magnetic resonance imaging, and thallium imaging studies
were ordered to investigate the etiology of the symptoms. A
mass of tissue, believed to be thymic remnants, was noted in
the mediastinum. Because evidence exists showing that the
870

Official Journal of the American College of Sports Medicine

presence of residual thymic tissue could cause a recurrence


or exacerbation of MG, the tissue was considered as a
possible source of symptoms. As a result of these findings,
E.M. elected to have a repeat sternotomy in April 1999. At
the time of surgery, his BW had decreased from his usual
83.0 kg to 74.8 kg, with a noticeable loss of muscle mass
and strength.
After surgery, E.M. was restricted from lifting weights for
3 months and continued his medication (prednisone 40
mgd-1, Imuran 150 mgd-1) regimen. During this time, he
gradually continued to increase his aerobic activity level and
was able to maintain his BW between 74.8 and 77.1 kg. In
July 1999, E.M. resumed his resistance training program
(one exercise per each major muscle group for 3 4 sets, 3
times per week) and began to self-administer 5 g of Cr (FSI
Nutrition, Omaha NE; U.S. Patent No. 5,925,378) per day
for 15 wk.

METHODS
Before any measurements, E.M. and his physician signed
an informed consent to participate in this case study. Body
composition was assessed before and after Cr supplementation and training via underwater weighing (UWW) with
correction for residual volume (RV) by using the oxygen
dilution method of Wilmore (28). Residual volume was
determined on land with the subject seated as in UWW. The
average of similar scores (within 0.1 L) from two to three
trials was used as the representative RV.
Underwater weight was measured in a submersion tank in
which a seat was suspended from a Chatillon 9-kg scale.
The average of the two to three highest weighings from 6 to
10 trials was used as the representative underwater weight.
Percent body fat was calculated from body density (Db) by
using the revised formula of Brozek et al. (5), and fat free
mass (FFM) was derived mathematically. In addition, a
complete blood chemistry panel (Table 1) was obtained at
weeks 0, 6, and 15.
Training volume (repetitions mass lifted) for upper
body (dumbbell bench press, machine lat pulldown, dumbbell shoulder press) and lower body (leg extensions and leg
curls) was monitored throughout the resistance-training program. In addition, maximal isokinetic leg flexion (LF) and
leg extension (LE) strength of the dominant leg (based on
kicking preference) was measured using a calibrated Cybex
II dynamometer at 60s-1 at baseline and postsupplementation (15 wk).

DISCUSSION
Recent investigations (10,11) using male subjects (age
range 19 60 yr) have shown that Cr loading (20 gd-1) for
5 d, or 3 gd-1 for 30 d, elevated whole-muscle Cr stores by
an average of 20%, with as much as 20% stored in the form
of PC. The male patient in this study was within the age
range of those used in previous investigations and selfadministered 5 gd-1 of Cr for 15 wk. Therefore, although
muscle PC levels were not directly measured in the present
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TABLE 1. Blood chemistry values.

Blood cell count


WBC (103 L)
RBC (106 L)
Hemoglobin (gdL1)
Hematocrit (%)
MCV (m3)
MCH (PG)
MCHC (G/DL)
RDW (%)
Platelet (103)
Differential
Neutrophils, absolute (103)
Absolute lymph (103)
Monocytes, absolute (103)
Eosinophils, absolute (103)
Neutrophils (%)
Lymph (%)
Monocytes (%)
Eosinophils (%)
Basophils (%)
RBC size
RBC color
RBC shape
General chemistry
ALP (IUL1)
AST (IUL1)
ALT (IUL1)
Bilirubin total (mgdL1)
Bilirubin direct (mgdL1)
Albumin (gdL1)

Week
0

Week
6

Week
15

8.8
4.46
13.8
40.5
90.7
31.0
34.1
14.1
205

5.1
4.53
13.8
40.1
88.3
30.3
34.3
13.8
208

4.6
4.54
13.9
41.2
90.6
30.7
33.9
13.0
198

5.0
3.2
0.5
0.0
57
36
7
0
0
Normal
Normal
Normal

2.6
2.1
0.3
0.0
51
42
7
1
0
Normal
Normal
Normal

2.8
1.5
0.3
0.0
59
33
6
1
1
Normal
Normal
Normal

41
20
21
0.9
0.2
4.5

51
31
21
0.6
0.1
4.6

52
39
23
0.9
0.1
4.8

White blood cell (WBC); red blood cell (RBC); mean corpuscular volume (MCV); mean
corpuscular hemoglobin (MCH); mean corpuscular hemoglobin concentration (MCHC);
red cell distribution width (RDW); alkaline phosphatase (ALP); aspartate aminotransferase (AST); alanine aminotransferase (ALT).

study, the results of previous investigations (10,11) suggest


that Cr supplementation likely resulted in an increase in
muscle PC concentration.
Tarnopolsky and Martin (24) have previously demonstrated that acute (10-d) Cr supplementation significantly
increased strength and total mass in patients with various
neuromuscular diseases. The results of this case study indicated that 15 wk of Cr supplementation and resistance
training increased BW (6.8%), FFM (4.3%), upper body
volume load (37.0%), lower body volume load (15.0%), and
peak strength for LE (37.0%) and LF (12.4%) (Table 2).
These results are similar to previous studies using healthy
male subjects, which reported increases in FFM ranging
from 3.9% to 4.6%, as well as significant increases in upper
and lower body strength after 4 8 wk of resistance training
and Cr supplementation (8,15,23). As indicated in the case
history, while in remission, E.M. was unable to make significant gains in strength or FFM as a result of his resistance
exercise program, which may have been a consequence of
his medication. Miller et al. (19) have demonstrated that MG
patients orally receiving 40 mgd-1 to 100 mgd-1 of prednisone experienced a decrease in maximal voluntary
strength. Although we cannot determine to what extent each
intervention (creatine and exercise) contributed to changes
in strength and body composition, it should be noted that
during the entire 15 wk, E.M. was receiving 60 mgd-1 of
prednisone. Although it could be speculated that creatine
may attenuate the decline in neuromuscular function in MG
CREATINE SUPPLEMENTATION FOR MYASTHENIA GRAVIS

patients receiving corticosteroids, future studies are warranted to validate this theory.
The possible mechanisms responsible for the effects of Cr
supplementation on body composition and strength include:
1) a significant increase in PC content, which would allow
for a greater total training volume (8,27) and, consequently,
a greater training stimulus; and/or 2) a Cr-driven increase in
protein synthesis (3,13), possibly through enhanced satellite
cell mitotic activity (6). The results of this case study support the hypotheses of Earnest et al. (8) and Volek et al. (27),
who suggested that increasing PC stores in skeletal muscle
though Cr supplementation during a resistance-training program may promote greater physiological adaptation over
time when compared with training alone.
Recently, Kreider et al. (15) monitored the effects of Cr
supplementation and resistance exercise for 28 d on complete blood chemistry responses (cell blood counts with
percent differentials) in healthy male athletes. No adverse
effects were reported and the hematological parameters remained within normal clinical limits (15). In the present
study, we also monitored complete blood chemistry values
for adverse reactions and possible exacerbation of reported
side effects (hepatotoxicity, bone marrow depression and
nausea) from E.M.s medications (prednisone and azathioprine; Table 1). The blood chemistry values remained within
normal limits throughout the 15 wk of supplementation and
training, which is in agreement with the findings of Kreider
et al. (15). Further, E.M. reported no gastrointestinal distress
and/or any other medical problems. In addition, there was no
report of skeletal muscle cramping during resistance training sessions. It has been suggested that Cr supplementation
may adversely affect kidney function; therefore, future studies should also measure serum creatinine levels and glomular filtration rate.
Future double-blind research should be conducted to
validate the effects of Cr supplementation and resistance
training on a larger sample of patients with MG. Certainly, the use of a single subject was a limitation of this
study. However, from a clinical viewpoint, healthcare
practitioners must be cognizant that many patients selfadminister physical activity and an array of over-thecounter supplements without knowledge of their side
effects. Notably, the aggressive resistance exercise program implemented by this patient is in contrast to the
TABLE 2. Body composition, peak strength, and training volume values.
Week 0
Body composition
BW (kg)
FFW (kg)
Peak strength
Leg extension (Nm)
Leg flexion (Nm)
Training volume (reps mass lifted)
Dumbell bench press (kg)
Lat pulls (kg)
Shoulder press (kg)
Leg extension (kg)
Leg curls (kg)

Week 15

%
Change

77.7
69.0

83.4
72.1

6.8
4.3

146.5
114.0

231.9
130.2

37.0
12.4

1225
1819
1071
1315
2672

2064
2858
1615
1687
2908

40.7
36.4
33.7
22.1
7.9

Body weight (BW); fat free weight (FFW).

Medicine & Science in Sports & Exercise

871

relatively conservative activity typically recommended


for patients with MG (20). Furthermore, it is important
that clinicians who treat or counsel these individuals
become educated about the potential benefits (or detriments) of such substances and exercise programs. This
expanded knowledge base may also better prepare clinicians to develop collaborative relationships with their
patients, whereby patients can play an active role in
devising their own treatment strategies under medical
supervision, the advantages of which are substantial for
adherence and outcomes (17).
In conclusion, the results of this study may lend support to previous investigations (15, 24 26) regarding the

safety and the potential value of combining resistance


exercise and Cr supplementation on strength and body
composition in patients with various neuromuscular disorders, including MG. However, it should be noted that
the increase in strength and FFM observed in this study
may have been due to the strength training per se and the
contribution from creatine is not measurable.
We would like to thank FSI Nutrition (Omaha, NE) for supplying
the creatine for this study.
Address for correspondence: Jeffrey R. Stout, FACSM, Nutricia,
Scientific Affairs Dept., 6111 Broken Sound Parkway NW, Boca
Raton, FL 33487; E-mail: jstout@nutriciausa.com.

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