Content uploaded by Nicole Lois Nelson
Author content
All content in this area was uploaded by Nicole Lois Nelson on Jul 11, 2016
Content may be subject to copyright.
INVITED REVIEW
A NARRATIVE REVIEW OF EXERCISE-ASSOCIATED MUSCLE CRAMPS:
FACTORS THAT CONTRIBUTE TO NEUROMUSCULAR FATIGUE AND
MANAGEMENT IMPLICATIONS
NICOLE L. NELSON, MSH, LMT, and JAMES R. CHURILLA, PhD, MPH
Clinical and Applied Movement Sciences, Brooks College of Health, University of North Florida, 1 UNF Drive, Jacksonville,
Florida 32224-2673, USA
Accepted 3 May 2016
ABSTRACT: Although exercise-associated muscle cramps
(EAMC) are highly prevalent among athletic populations, the eti-
ology and most effective management strategies are still unclear.
The aims of this narrative review are 3-fold: (1) briefly summarize
the evidence regarding EAMC etiology; (2) describe the risk fac-
tors and possible physiological mechanisms associated with neu-
romuscular fatigue and EAMC; and (3) report the current
evidence regarding prevention of, and treatment for, EAMC.
Based on the findings of several large prospective and experi-
mental investigations, the available evidence indicates that
EAMC is multifactorial in nature and stems from an imbalance
between excitatory drive from muscle spindles and inhibitory
drive from Golgi tendon organs to the alpha motor neurons
rather than dehydration or electrolyte deficits. This imbalance is
believed to stem from neuromuscular overload and fatigue. In
concert with these findings, the most successful treatment for an
acute bout of EAMC is stretching, whereas auspicious methods
of prevention include efforts that delay exercise-induced fatigue.
Muscle Nerve 000:000–000, 2016
In this review we focus on exercise-associated mus-
cle cramps (EAMC), which have been defined as
painful, spasmodic, and involuntary contractions of
skeletal muscle that occur during or immediately
after exercise and have no underlying metabolic,
neurological, or endocrine pathology.
1
Nocturnal
cramps or cramps associated with metabolic abnor-
malities are not considered EAMC and are beyond
the scope of this review. Exercise-associated muscle
cramps have also been called heat cramps; however,
this term has lost favor, as cramping has been docu-
mented during exercise in cooler conditions.
2,3
The clinical presentation of EAMC includes
acute pain, stiffness, and bulging or knotting of the
muscle. Exercise-associated muscle cramps often last
from 1 to 3 minutes and generally occur in multi-
joint muscle groups when contracting in a short-
ened position (e.g., quadriceps, hamstrings, triceps
surae).
4–6
The severity of EAMC can range from
mild discomfort, with limited effects on physical
performance, to extreme pain and debilitation.
7
EAMC are among the most common conditions
that require medical intervention, either during or
immediately upon completion of athletic events,
representing up to two-thirds of complaints
reported during endurance-related competitions.
5,8
In a 12-year summary report of marathon medical
issues, cramping accounted for 6.1% of medical
encounters, with 1.2 cases of EAMC per 1,000 par-
ticipants.
9
Most recently, a prospective study of
26,354 ultramarathon runners revealed that 1 in
every 526 race starters developed EAMC.
1
The 2 main theories behind EAMC, the dehy-
dration and electrolyte imbalance theory and the
altered neuromuscular control theory, have been
reviewed elsewhere, and the strongest evidence
supports a neuromuscular etiology.
7,10,11
Briefly,
the serum electrolyte and dehydration theory pos-
tulates that the extracellular fluid compartment
becomes increasingly contracted due to sweating,
leading to a loss of interstitial volume. In addition,
excessive sweating can lead to concomitant
sodium, calcium, magnesium, chloride, and potas-
sium deficits.
12–14
It follows that a mechanical
deformation of nerve endings and an increase in
the surrounding ionic and neurotransmitter con-
centrations leads to hyperexcitable motor nerve
terminals and spontaneous discharge.
15
Although some researchers have reported an
association between EAMC and electrolyte defi-
cits,
16–19
those investigations have some methodo-
logical limitations. First, the studies were all
observational, where causation may not be inferred
due to potential confounding factors. Second, dur-
ing the days of testing, no study participants had
EAMC, despite having either serum or sweat elec-
trolyte losses.
16–19
Third, sample sizes were small in
each of those investigations, limiting power and
external validity. Finally, adjustments were not
made for known EAMC correlates, such as partici-
pant fitness level, exercise intensity, fatigue, previ-
ous injury, and acclimatization, in many of those
studies. In addition, several prospective cohort
studies and case–control studies reported no
Abbreviations: ACSM, American College of Sports Medicine; BMI, body
mass index; CTF, cramp threshold frequency; EAMC, exercise-associated
muscle cramps; EIMC, electrically induced muscle cramps; GTO, Golgi
tendon organ; KT, kinesio taping
Key words: dehydration; electrolyte deficit; muscle fatigue; muscular
cramps; neuromuscular control
Correspondence to:N.L. Nelson; e-mail: nicole.nelson@unf.edu
V
C2016 Wiley Periodicals, Inc.
Published online 00 Month 2016 in Wiley Online Library (wileyonlinelibrary.
com). DOI 10.1002/mus.25176
Exercise-Associated Muscle Cramps MUSCLE & NERVE Month 2016 1
differences in hydration status or plasma concen-
trations of electrolytes between cramp-prone and
non–cramp-prone participants.
1,3,8,20–25
The plausibility of hydration status and electro-
lyte concentrations causing EAMC also seems ques-
tionable, as it is often relieved by stretching of the
affected muscles,
20,26
or by activation of the Golgi
tendon organs (GTOs).
27
These treatments would
certainly be incongruous for a condition mediated
by electrolyte deficit and dehydration. Likewise, the
systemic nature of electrolyte deficits and dehydra-
tion does not explain the fairly consistent presenta-
tion of cramping only within working muscles.
The “altered neuromuscular control theory,”
popularized by Schwellnus, posits that EAMC result
from altered reflex control mechanisms in
response to neuromuscular fatigue.
10
Specifically,
muscle overload and fatigue engender an imbal-
ance of the excitatory drive from muscle spindles
and the inhibitory drive from GTOs. The result is
an increase in excitatory drive to the alpha motor
neuron, which ultimately produces a localized
cramp. It has been observed that runners who
develop EAMC almost exclusively report a subjec-
tive feeling of muscle fatigue before onset of
EAMC.
28
In addition, EAMC has been shown to
occur in athletes toward the end of games or
races.
3,25,28
The theory also explains the increased
baseline electromyographic (EMG) activity
recorded between bouts of cramping in athletes
who are experiencing fatiguing exercise.
24
This
hypothesis has experimental support, as skeletal
muscle fatigue has been shown to reduce inhibi-
tory input to alpha motor neurons from the GTOs
and to increase excitatory input from the muscle
spindles in animal models.
27,29,30
It has also been
shown that, when skeletal muscle contracts in a
shortened position, there is depressed signaling
from the GTOs, which explains why stretching is
the best-known and most effective treatment for
acute EAMC.
7,27,31
Along these same lines, electri-
cal stimulation of tendon afferents has been shown
to successfully relieve muscle cramping.
27
Specifi-
cally, Khan and Burne
27
induced cramps in the
gastrocnemius of subjects using maximum volun-
tary contraction while the muscle was in a short-
ened position. In all cramping subjects, reflex
inhibition was observed after Achilles tendon elec-
trical stimulation, with all subjects reporting relief
of the cramp. This finding lends further support
to the theory that abnormal spinal reflex activity is
associated with muscle cramping.
In summary, support for the dehydration and
electrolyte theory is based on low-level evidence in
the form of case series, case–control data, and
anecdotal observations. These observations have
not been supported in recent prospective cohort
investigations, where athletes have experienced
EAMC when fully hydrated and sufficiently supple-
mented with electrolytes. In addition, evidence
from human and animal models has demonstrated
that altered spinal reflex activity during fatigue is
associated with skeletal muscle cramping. Finally,
stretching has been shown to restore the balance
between excitatory and inhibitory impulses to the
alpha motor neuron and is the most effective rem-
edy for acute EAMC, offering further support to
the altered neuromuscular control theory.
To date, the phenomenon of neuromuscular
fatigue is poorly understood. By summarizing
recent EAMC investigations that explored possible
risk factors and management strategies, it is our
hope to further elucidate the mechanisms behind
neuromuscular fatigue and the imbalance of inhib-
itory and excitatory drives that elicits EAMC.
Accordingly, in this review we report the current
evidence regarding neuromuscular fatigue risk fac-
tors and prevention and treatment methods.
ALTERED NEUROMUSCULAR CONTROL RISK
FACTORS
History of EAMC. EAMC susceptibility varies widely
among individuals; some routinely develop EAMC
and others, despite being similarly matched for
conditioning duration and intensity, demonstrate
cramp resistance (Fig. 1).
8,23
Along these lines,
Miller et al.
32
reported that cramp susceptibility is
correlated with an individual cramp threshold fre-
quency (CTF), defined as the minimum electrical
stimulation required to evoke a muscle cramp.
32
They reported significantly (P<0.001) lower CTF
in participants with a positive cramp history than
in those with no history of cramping.
Several recent observational investigations have
reported that athletes with a history of EAMC were
more likely to cramp during or shortly after exer-
cise than those who had no history of EAMC.
8,20,25
Schwellnus et al.
8
reported that triathletes who
experienced EAMC while participating in an Iron-
man event, or in the 6 hours after the race, had a
significantly higher reported history of EAMC com-
pared with the triathletes who did not cramp (P<
0.001). More specifically, a history of cramping in
the previous 10 events, was strongly associated with
EAMC. A prospective, longitudinal investigation of
103 male rugby players described significant differ-
ences in the history of cramps among players who
experienced EAMC throughout the season com-
pared with those who did not (P50.004).
25
Family History and Genetics. The findings regard-
ing family history of cramping and EAMC are
somewhat equivocal. A recent, prospective study
and a case–control study reported that a positive
family history of EAMC was not associated with the
2Exercise-Associated Muscle Cramps MUSCLE & NERVE Month 2016
risk of developing EAMC during endurance
events.
8,20
Conversely, a cross-sectional study of
1,300 marathoners reported an association
between family history of EAMC and a history of
EAMC.
28
This study was subsequently supported in
a case–control investigation in which cramp-prone
triathletes were shown to be significantly more
likely to have a family history of EAMC when com-
pared with non–cramp-prone triathletes (P<
0.001).
23
Interestingly, those researchers also
reported that there was a significant family history
of EAMC on the male side of the family, suggest-
ing a possible genetic component of EAMC.
Despite equivocal findings regarding an associa-
tion between family history and EAMC, a recent
case–control investigation reported that a struc-
tural component of the extracellular matrix of soft
tissue is associated with EAMC.
33
Specifically, the
researchers discovered that the COL5A1 rs12722
CC genotype, a polymorphism associated with
structural and mechanical properties of collagen
fibrils and musculoskeletal soft tissue injury, was
significantly associated with a history of EAMC (P
50.034). Thus, the extracellular matrix of muscle
tissue, which has also been implicated in delayed-
onset muscle soreness, may play a role in facilitat-
ing EAMC.
Gender. Gender-related differences have been
shown to be associated with EAMC.
1,23
The SAFER
II study, an investigation of medical injuries over
the course of an ultramarathon race, reported that
male runners had a higher incidence of EAMC
than female runners (P50.0482).
1
Shang et al.
23
discovered that there were significantly more men
(P50.011) than women among triathletes who
were grouped based a self-reported history of
EAMC. A plausible explanation for this finding is
that women have been found to be less fatigable
than men when exercising at similar relative inten-
sities.
34
Although gender-related mechanisms of
fatigue are not fully understood, it has been pro-
posed that the skeletal muscles of men possess a
greater proportional area of fast-twitch (type II)
FIGURE 1. Factors associated with exercise-associated muscle cramps.
Exercise-Associated Muscle Cramps MUSCLE & NERVE Month 2016 3
fibers in muscles of locomotion than women.
35,36
As type II fibers are known to be more fatigable
compared with type I fibers due to lower capillary
and mitochondrial densities, this may explain the
relationship between gender and EAMC incidence.
In addition, during moderate- to high-intensity
endurance exercise, women have been shown to
oxidize more fat and less carbohydrate than men
at the same relative activity intensity.
36,37
The
capacity to utilize lipid for fuel during endurance
events may also explain the gender differences in
fatigability and, ultimately, EAMC in the late stages
of endurance events.
Age. There is limited evidence to indicate a rela-
tionship between older age and EAMC in endur-
ance and team sport competitions.
1,25
The SAFER
II investigation showed that runners >50 years of
age also had a greater incidence of EAMC than
those in the 41–50-year category (P50.0007).
1
A
prospective study of rugby players showed that ath-
letes in the senior division of competition (n559,
mean age 21.1 64.1 years) had a significantly
greater risk of EAMC (P<0.001) than those in
the younger division (n544, 15.8 60.9 years).
Conversely, several large, prospective and case–con-
trol investigations have reported no association
between EAMC and age.
8,20,23,24
Body Size. Several studies have investigated
increased body mass index (BMI) and body weight
as independent risk factors for EAMC. A recent
prospective cohort investigation of triathletes
showed no significant differences in BMI or body
weight between athletes who cramped during an
event or up to 6 hours after the event and those
who did not.
8
In support of these findings, a
cohort study of ultradistance runners showed no
significant between-group differences in body
weight between runners who cramped and those
who did not.
20
In a case–control study involving
Ironman triathletes with a history of cramps (n5
216) and triathletes with no history of cramps (n
5217), no significant between-group differences
were found for BMI (P50.493).
23
Although ele-
vated body mass and BMI are known to have per-
formance implications in endurance events,
38
based on current evidence, they do not appear to
be associated with EAMC.
The evidence regarding any association
between height and EAMC is limited and equivo-
cal. Schwellnus et al.
8
found no significant differen-
ces in height between triathletes who cramped
during an Ironman event and those who did not
(P50.882). In contrast, Shang et al.
23
reported
that triathletes with a self-reported history of
EAMC were taller when compared with those hav-
ing no EAMC history (P50.003). Interestingly, in
that case–control study, the difference in height
remained significant, even after adjustment for
gender (P50.007). The authors speculated that
the differences in the biomechanics of the lower
leg in taller athletes may alter running economy
and, ultimately, contribute to premature fatigue
and EAMC.
Exercise Intensity and Duration. Exercise intensity
and duration have been the most extensively inves-
tigated risk factors related to fatigue and EAMC.
There has been a consistent association between
EAMC and prolonged activity performed at vigor-
ous intensities.
3,8,23,25,28
Schwabe et al.
1
discovered
that those in the sub–6-min/km category had a
higher incidence of EAMC when compared with
those in the 6–7-min/km category (P50.0066),
but no difference in EAMC incidence when com-
pared with runners in the >7-min/km category (P
50.0921).
1
Shang et al.
23
found that triathletes
categorized as cramp-prone had faster overall fin-
ishing times (P<0.043) compared with those cate-
gorized as non-crampers. It should be noted that
the 2 groups were similarly matched for previous
performance, training duration, intensity, and fre-
quency before the event. Those findings echo
results from a recent prospective study of 210 tri-
athletes.
8
Athletes were grouped as crampers or
non-crampers, based on the incidence of EAMC
during the event. Although the triathletes were
matched for pre-event training times and training
volume, it was found that faster overall finishing
time was a significant independent risk factor for
EAMC (P50.01).
Playing in an advanced-level rugby league has
also been shown to be a predictor of EAMC.
25
This
finding may be attributed to the fact that the
length of games in the advanced league are longer
than in lower competition levels and that EAMC
almost exclusively developed in the final 10
minutes of the games. Moreover, the season length
in the junior competition spans 9 weeks, whereas
the season length for senior players spans 26
weeks. The study reported that, as the number of
games increased, there was a slightly higher (P5
0.051) EAMC incidence, suggesting there may be a
positive relationship between EAMC and the num-
ber of games played during a season.
Previous or Current Injury. Shang et al.
23
found
that cramp-prone athletes were more likely to have
a history of tendon and/or ligament injury (P<
0.022) when compared with non-cramping ath-
letes. They speculated that soft tissue injury could
trigger an increase in reflex alpha motor activity,
resulting in EAMC. Another plausible explanation
is that previously injured areas may be vulnerable
4Exercise-Associated Muscle Cramps MUSCLE & NERVE Month 2016
to development of premature fatigue due to weak-
ness of the localized muscles.
A recent prospective investigation showed an
association between lower back pain, which was
severe enough to miss playing time, and EAMC in
the calf muscles of rugby players.
25
This was the
first study to reveal such a relationship; however,
the researchers reasoned that low back pain results
in altered neural transmission in the nerves supply-
ing the lower limb, resulting in calf cramps.
Although several biopsychosocial factors are known
to cause back pain,
39,40
and this study did not
identify the source of the low back pain, further
investigation is warranted to reveal the exact
nature of the relationship between low back pain
and EAMC.
In summary, several observational studies have
addressed potential risk factors for EAMC. The
strongest evidence indicates that a previous history
of EAMC, male gender, and prolonged and rela-
tively vigorous exercise are the best predictors of
EAMC in endurance and team sport events. These
results, however, should be interpreted with cau-
tion, as they are based on observational studies
where causation cannot be inferred. In addition,
although neuromuscular fatigue may be central to
the etiology of EAMC, it is important to note that
muscle fatigue is a vague and poorly understood
condition. Moreover, it is still unclear why certain
athletes are more susceptible to fatigue and
EAMC. Toward this end, well-designed experimen-
tal studies are needed to elucidate the precise
mechanisms that may trigger fatigue and subse-
quently lead to decreases in GTO activity and
increases in muscle spindle activity.
Notwithstanding this lack of detailed study, the
findings of this exploratory review of EAMC corre-
lates should provide practitioners and researchers
with some preliminary data for which to screen
athletes and guide further EAMC research.
TREATMENT AND PREVENTION
In practice, management strategies for EAMC
are diverse, likely owing to the uncertainty of
EAMC etiology. In this section we summarize the
investigations that have reported on the efficacy of
treatment and prevention strategies for EAMC.
Electrical Cramp Induction. Over a 6-week time
frame, Behringer et al.
41
applied electrical muscle
stimulation twice weekly to both calf muscles of
intervention participants (n510). The stimulation
was applied to 1 calf in a shortened position,
which elicited cramping, while the contralateral
calf was stimulated with the ankle in a neutral posi-
tion, which hindered muscle cramping. The
researchers measured CTF for both legs of the
intervention participants, as well as non-treated
control participants (n55) at 3 and 6 weeks. The
CTF of the calf muscles receiving stimulation in a
shortened position was increased significantly at 3
(P<0.001) and 6 (P<0.001) weeks, whereas no
significant changes were noted at either assessment
point in the contralateral legs of the intervention
participants or in the calf muscles of participants
in the control group. In a follow-up study, Beh-
ringer et al.
42
found that 2 bouts of electrically
induced muscle cramps (EIMC), induced 1-week
apart in the gastrocnemius of an intervention
group (n58), raised the CTF significantly for 24
hours in each of the 2 bouts (P<0.05). The CTF
remained elevated for 1 week in the EIMC partici-
pants, although this finding was not considered
statistically significant after 24 hours. Control
group participants (n55) received no EIMC and
experienced no change in their CTF at any assess-
ment point. The authors of these studies proposed
that application of EIMC may rebalance the excita-
tory and inhibitory inputs to the alpha motor neu-
rons by eliciting adaptations in the central nervous
system. Although inducing painful skeletal muscle
cramps may not seem like an acceptable preventive
measure for the majority of individuals, athletes
who routinely experience EAMC during vigorous
training and competition may view electrical induc-
tion as a worthwhile performance-enhancing solu-
tion to EAMC.
Kinesio Taping and Compression Garments. The use
of lower leg compression stockings and kinesio tap-
ing (KT) have increased in popularity in recent
years. Although little empirical evidence supports
the use of these training aids for prevention of
EAMC, compression and KT are thought to attenu-
ate soft-tissue vibrations upon ground impact,
thereby improving muscle activation, which may
offset fatigue-induced changes in running mechan-
ics.
43,44
A small, prospective cohort study explored
the effects of KT on calf pain and incidence of
EAMC.
45
The researchers applied the KT to the tri-
ceps surae muscles of 6 triathletes before racing.
Athletes were asked after the event about EAMC
incidence, and none of them had cramping in the
triceps surae group. Interestingly, 2 athletes had
quadriceps EAMC during the events. The research-
ers proposed that application of tape creates con-
volutions in the skin of the athlete, which
engenders an increase in local blood flow and
reduces pressure on mechanoreceptors, ultimately
decreasing the incidence of EAMC.
Massage Therapy. It has been proposed that the
mechanical pressure during massage alters neural
excitability, and these neural changes may reduce
the potential for cramping.
46,47
Sefton et al.
48
dis-
covered a reduction in the Hoffman (H)-reflex,
Exercise-Associated Muscle Cramps MUSCLE & NERVE Month 2016 5
which was used to measure the excitability of the
motor neuron pool in study participants who
received a 1-hour full-body massage. Behm et al.
46
found that massage decreased spinal reflex excit-
ability, with significant reductions in subjects who
received 30 seconds of tapotement (a percussive
massage stroke). Despite these neural changes
induced by massage, experimental evidence is still
needed to determine whether it actually facilitates
a balance between excitatory impulses from muscle
spindles and inhibitory impulses from GTOs. From
a performance perspective, given the potential to
reduce spinal level reflex excitability, it is unclear
whether massage performed immediately before
an event would result in performance decrements.
As such, further investigation is warranted to deter-
mine whether treatment variables, such as the rela-
tive timing of massage, depths of pressure, speed
of stroke, and type of massage stroke, influence
EAMC without negatively impacting performance.
Electrolyte Supplementation and Hydration. Despite
the lack of empirical evidence in support of the
dehydration–electrolyte theory, salt tablets and
magnesium supplementation are commonly used
among athletes as a means to treat and prevent
EAMC.
49
Given the lack of substantive data linking
electrolyte deficits and dehydration with EAMC, it
is unlikely that salt tablets or magnesium supple-
mentation would be effective. It is, however, sensi-
ble for practitioners to encourage athletes and
exercise participants to follow hydration and elec-
trolyte supplementation guidelines to prevent heat-
related illness. Accordingly, health professionals
should recommend fluid replacement during and
after physical activity for athletes and exercise par-
ticipants. The American College of Sports Medi-
cine (ACSM) position on fluid replacement is that
athletes consume a volume of fluid that prevents
more than a 2% body weight loss from perspira-
tion.
50
The ACSM also acknowledges the interper-
sonal variability in sweating rates and sweat
electrolyte concentrations, so that fluid replace-
ment may best be determined by measuring body
weight before and after exercise.
Corrective Exercise. To date, the performance of
corrective exercises engineered to improve biome-
chanics, muscular imbalances, and postural issues
has very little scientific basis in treatment and pre-
vention of EAMC. There is some evidence showing
that EAMC is correlated with tendon injuries.
23
If
this is the case, incorporation of eccentric exercise,
a treatment used for tendinopathies,
51,52
may be a
feasible remedial choice for cramp-prone athletes.
In a similar fashion, plyometric activity may have a
place in prevention of EAMC. This training
method is characterized by a rapid eccentric mus-
cle action immediately followed by a rapid shorten-
ing of the same muscle, and may improve
neuromuscular function. Accordingly, future study
within the context of EAMC is needed to deter-
mine the optimal frequency, intensity, and dura-
tion of these training practices. Although
neuromuscular re-education and attempts to nor-
malize muscular imbalances would seem to be rea-
sonable approaches to preventing cramps, there is
a paucity of data to support these methods. There
is very limited evidence in this area, although 1
case study investigated the effects of strengthening
and neuromuscular re-education of the gluteus
maximus muscle in a triathlete prone to EAMC of
the hamstrings.
53
Given the agonistic relationship
of the hamstrings and the gluteus maximus
muscles, the researchers reasoned that weakness of
the gluteus maximus could increase the relative
contribution of the hamstring muscles during run-
ning and lead to overuse, premature fatigue, and
ultimately EAMC. After several weeks of progressive
gluteus maximus strengthening and neuromuscu-
lar training, the subject completed 3 triathlons
without hamstring cramping.
Stretching. Although Schwellnus et al.
8
found no
association between history of stretching and devel-
opment of EAMC (P50.43), it appears that
stretching is the most effective treatment in reliev-
ing acute fatigue-induced muscular cramping.
6,20,26
The literature has consistently shown that short-
ened muscles that span 2 joints are more prone to
cramping.
4–6
In view of this, stretching seems to be
a plausible treatment. Although the precise mecha-
nism is unclear, it has been suggested that passive
stretching may increase tension in the GTO, result-
ing in increased afferent reflex inhibition to the
alpha motor neuron.
27,30,54
Quinine. The use of 200–300 mg/day of quinine
has been shown to reduce the incidence of noctur-
nal and idiopathic muscular cramps.
55,56
Quinine
has been associated with thrombocytopenia
57
; con-
sequently, quinine supplementation for muscle
cramping is no longer allowed in the United
States. Furthermore, there are no published data
to suggest that quinine is useful for EAMC.
Pickle Juice. Consumption of small amounts of
pickle juice is another common treatment for
EAMC.
49,58
Pickle juice contains high concentra-
tions of salt along with acetic acid, which is
thought to trigger a reflex that increases inhibitory
neurotransmitter activity in cramping muscles.
58,59
One case report indicated that drinking 30–60 ml
of pickle juice relieved EAMC within 30–35 sec-
onds after consumption by restoring electrolyte
balance.
58
Miller et al.
59
compared the effects of
6Exercise-Associated Muscle Cramps MUSCLE & NERVE Month 2016
consumption of 1 ml/kg of body weight of pickle
juice to a similar volume of de-ionized water imme-
diately after cramp induction in the flexor hallucis
brevis muscles of 12 hypohydrated (3%) men. The
researchers reported that cramp duration was 49.1
614.6 seconds shorter after pickle juice ingestion
compared with the water condition (P<0.05). In
addition, when comparing the 2 conditions, no sig-
nificant differences in plasma composition were
found for up to 5 minutes after consumption. The
authors reported the amount of ingested pickle
juice had a negligible effect on extracellular fluid
electrolyte concentrations and hypothesized that
the decrease in cramp duration was attributed to
an inhibition of the orophyaryngeal reflex, which
reduces alpha motor neuron activity of cramping
muscles throughout the body. In support of these
data, Miller et al.
60
found no significant changes in
plasma electrolyte concentrations within 1 minute
of consumption of 1 ml/kg body mass of pickle
juice among 9 euhydrated men. No changes in
plasma sodium, magnesium, calcium concentra-
tions, plasma osmolality, or plasma volume 60
minutes after consumption were reported (P
0.05). The authors ultimately concluded that, if
EAMC are triggered by electrolyte deficits due to
sweating, small volumes of pickle juice are unlikely
to restore any deficit induced by exercise.
Hyperventilation Strategies. A recent case series
consisting of 3 participants assessed hyperventila-
tion as a treatment for EAMC.
61
The researchers
hypothesized that hypoventilation with resulting
respiratory acidosis may be a contributing factor to
muscular cramping. One participant was instructed
to hyperventilate (20–30 deep breaths/min) while
experiencing a cramp. The investigators reported
complete resolution of cramps within 1 minute of
the breathing technique on 5 separate occasions.
Another participant in the series performed the
hyperventilation technique after developing EAMC
two-thirds of the way through a 100-mile mountain
bike ride. The subject reported complete resolu-
tion of symptoms without recurrence.
In summary, we found several promising
strategies for EAMC management, including neu-
romuscular re-education of weak muscles, hyper-
ventilation, and KT for management of EAMC. It
is worth noting that the studies describing these
approaches were all observational studies. Well-
controlled, high-quality trials are needed to fully
determine treatment efficacy. Although massage
therapy is certainly a plausible EAMC management
strategy, no conclusive evidence exists to support
its effectiveness for EAMC. In well-controlled labo-
ratory studies, consumption of small amounts of
pickle juice has been shown to reduce the dura-
tion of EAMC. Electrical cramp induction has
been shown to increase CTF in 2 laboratory-based
studies. Although this strategy may prove to be a
viable treatment option for athletes who experi-
ence repeated EAMC during competition, it would
likely be viewed as impractical for the large major-
ity of those with EAMC. Finally, stretching appears
to be the most effective method for alleviating
acute bouts of EAMC.
LIMITATIONS AND FUTURE DIRECTIONS
There are some limitations to our review. First,
the review may be subject to selection bias, as no
systematic method was used to select relevant
articles. Second, it is limited by the information
provided in the included primary studies. With
respect to treatment and prevention, many studies
had small sample sizes or were of a case study or
case series design, and were not powered for multi-
ple statistical tests, thus limiting the ability to
detect clinically meaningful improvements. In
addition, among studies that investigated treat-
ment or prevention methods, few used multiple
measurement points to evaluate the success of
these methods. For the effects of treatments to be
fully explored, regular assessment across a range of
times and among varying EAMC populations is
needed.
With regard to the mechanisms behind EAMC,
many studies relied on self-report questionnaires
to determine EAMC status, meaning that recall
bias is an inherent limitation. The available evi-
dence supports the altered neuromuscular control
theory, in which fatigue is a central component.
However, it is important to recognize that fatigue
is a multidimensional construct that remains rela-
tively understudied in EAMC research. In addition,
there is a lack of understanding of the origins of
fatigue in different physical tasks of differing dura-
tions and intensities. Although current EAMC stud-
ies have shed some light on the physical
components of fatigue, such as relative exercise
intensity and duration and gender-based differen-
ces in fatigability, it is unknown how other inde-
pendent contributors of fatigue, such as sleep
quality and anxiety, are involved in the genesis of
EAMC. As such, there is a need for more high-
quality trials investigating skeletal muscle fatigabil-
ity and the mechanisms that may promote effective
approaches to delay the onset of muscle fatigue.
Interestingly, the use of various periodization mod-
els has gone unexplored relative to preventing
EAMC. Periodization is a concept that involves sys-
tematic variation in program design, largely to pro-
mote long-term training and performance
improvements, and to prevent overtraining. As
fatigue appears to be the most salient factor of
Exercise-Associated Muscle Cramps MUSCLE & NERVE Month 2016 7
EAMC, it is not unreasonable to assume that peri-
odically varying exercise volume and training
intensity may offset EAMC. Along these same lines,
it would be worthwhile to investigate whether any
correlation exists between overtraining syndrome
and the incidence of EAMC.
Despite strong support for the altered neuro-
muscular control theory, the available evidence
does not exclude the possibility that electrolyte dis-
turbances and dehydration play a role in the etiol-
ogy of EAMC among certain individuals. It may be
the case that certain people are more sensitive to
hydration and electrolyte disturbances. Further
investigation is warranted to determine the rele-
vance of these interpersonal differences.
CONCLUSIONS
The development of EAMC is more common in
the later stages of athletic events and is more prev-
alent among athletes who exercise at relatively vig-
orous intensities. In addition, several large
prospective cohort investigations have shown no
association between hydration status, electrolyte
concentrations, and EAMC. Based on these consid-
erations, the altered neuromuscular control theory
is the most cogent descriptive model that explains
the origins of EAMC. Although the available evi-
dence supports a neuromuscular foundation that
stems from fatigue, further research is needed to
elucidate the specific risk factors that contribute to
neuromuscular fatigue and underlie EAMC. Owing
to the limited understanding of fatigability and the
involved mechanisms, the most effective preven-
tion methods are unknown. Strong evidence indi-
cates that stretching is the most effective method
for treating acute muscle cramps.
REFERENCES
1. Schwabe K, Schwellung MP, Derman W, Swanevelder S, Jordaan E.
Less experience and running pace are potential risk factors for medi-
cal complications during a 56 km road running race: a prospective
study in 26 354 race starters—SAFER study II. Br J Sports Med 2014;
48:905–911.
2. Jones B, Rock P, Smith L, Matthew WT. Medical complaints after a
marathon run in cool weather. Phys Sportsmed 1985;13:103–110.
3. Maughan R. Exercise induced muscle cramp: a prospective biochemi-
cal study in marathon runners. J Sports Sci 1986;4:31–34.
4. Dickhuth H, R€
ocker K, Niess A, Horstmann T, Mayer F, Striegel H.
Exercise-induced, persistent and generalized muscle cramps: a case
report. J Sports Med Phys Fitness 2002;42:92–94.
5. Kantorowski PG, Hiller WD, Garrett WE, Douglas PS, Smith R,
O’Toole M. Cramping studies in 2600 endurance athletes. Med Sci
Sports Exerc 1990;22(suppl):S104.
6. Schwellnus MP, Derman EW, Noakes TD. Aetiology of skeletal mus-
cle ‘cramps’ during exercise: a novel hypothesis. J Sports Sci 1997;15:
277–285.
7. Miller KC, Stone MS, Huxel KC, Edwards JE. Exercise-associated mus-
cle cramps: causes, treatment, and prevention. Sports Health 2010;2:
279–283.
8. Schwellnus MP, Drew N, Collins M. Increased running speed and
previous cramps rather than dehydration or serum sodium changes
predict exercise-associated muscle cramping: a prospective cohort
study in 210 Ironman triathletes. Br J Sports Med 2011;45:650–656.
9. Roberts WO. A 12-yr profile of medical injury and illness for the
Twin Cities Marathon. Med Sci Sports Exerc 2000;32:1549–1555.
10. Schwellnus MP. Cause of exercise associated muscle cramps
(EAMC)—altered neuromuscular control, dehydration or electrolyte
depletion? Br J Sports Med 2009;43:401–408.
11. Edouard P. Exercise associated muscle cramps: discussion on causes,
prevention and treatment. Sci Sports 2014;29:299–305.
12. Liu L, Borowski G, Rose L. Hypomagnesemia in a tennis player. Phys
Sportsmed 1983;11:79–80.
13. Levin S. Investigating the cause of muscle cramps. Phys Sportsmed
1993;21:111–113.
14. O’Toole ML, Douglas PS, Laird RH, Hiller DB. Fluid and electrolyte
status in athletes receiving medical care at an ultradistance triathlon.
Clin J Sport Med 1995;5:116–122.
15. Layzer RB. The origin of muscle fasciculations and cramps. Muscle
Nerve 1994;17:1243–1249.
16. Bergeron M. Heat cramps during tennis: a case report. Int J Sport
Nutr 1996;6:62–68.
17. Bergeron MF. Heat cramps: fluid and electrolyte challenges during
tennis in the heat. J Sci Med Sport 2003;6:19–27.
18. Horswill CA, Stofan JR, Lacambra M, Toriscelli TA, Eichner ER,
Murray R. Sodium balance during U.S. football training in the heat:
cramp-prone vs. reference players. Int J Sports Med 2009;30:789–794.
19. Stofan JR, Zachwieja JJ, Horswill CA, Murray R, Anderson SA,
Eichner ER. Sweat and sodium losses in NCAA football players: a pre-
cursor to heat cramps? Int J Sport Nutr Exerc Metab 2005;15:641–
652.
20. Schwellnus MP, Nicol J, Laubscher R, Noakes T. Serum electrolyte
concentrations and hydration status are not associated with exercise
associated muscle cramping (EAMC) in distance runners. Br J Sports
Med 2004;38:488–492.
21. Braulick KW, Miller KC, Albrecht JM, Tucker JM, Deal JE. Significant
and serious dehydration does not affect skeletal muscle cramp
threshold frequency. Br J Sports Med 2013;47:710–714.
22. Jung AP. Functional rehabilitation. Exercise-associated muscle cramps
and functional return to sport. Athl Ther Today 2006;11:48–68.
23. Shang G, Collins M, Schwellnus MP. Factors associated with a self-
reported history of exercise-associated muscle cramps in Ironman tri-
athletes: a case-control study. Clin J Sport Med 2011;21:204–210.
24. Sulzer NU, Schwellnus MP, Noakes TD. Serum electrolytes in iron-
man triathletes with exercise-associated muscle cramping. Med Sci
Sports Exerc 2005;37:1081–1085.
25. Summers KM, Snodgrass SJ, Callister R. Predictors of calf cramping
in rugby league. J Strength Cond Res 2014;28:774–783.
26. Maquirriain J, Merrello M. The athlete with muscular cramps: clinical
approach. J Am Acad Orthop Surg 2007;15:425–431.
27. Khan S, Burne J. Reflex inhibition of normal cramp following electri-
cal stimulation of the muscle tendon. J Neurophysiol 2007;98:1102–
1107.
28. Manjra S, Schwellnus M, Noakes T. Risk factors for exercise associ-
ated muscle cramping (EAMC) in marathon runners. Med Sci Sports
Exerc 1996;28(suppl):S167.
29. Hutton RS, Nelson DL. Stretch sensitivity of Golgi tendon organs in
fatigued gastrocnemius muscle. Med Sci Sports Exerc 1986;18:69–74.
30. Nelson DL, Hutton RS. Dynamic and static stretch responses in mus-
cle spindle receptors in fatigued muscle. Med Sci Sports Exerc 1985;
17:445–450.
31. Bertolasi L, De Grandis D, Bongiovanni LG, Zanette GP, Gasperini
M. The influence of muscular lengthening on cramps. Ann Neurol
1993;33:176–180.
32. Miller KC, Knight KL. Electrical stimulation cramp threshold fre-
quency correlates well with the occurrence of skeletal muscle cramps.
Muscle Nerve 2009;39:364–368.
33. O’Connell K, Posthumus M, Schwellnus MP, Collins M. Collagen
genes and exercise-associated muscle cramping. Clin J Sport Med
2013;23:64–69.
34. Hunter SK. Sex differences in human fatigability: mechanisms and
insight to physiological responses. Acta Physiol 2014;210:768–789.
35. Porter MM, Stuart S, Boij M, Lexell J. Capillary supply of the tibialis
anterior muscle in young, healthy, and moderately active men and
women. J Appl Physiol 2002;92:1451–1457.
36. Roepstorff C, Thiele M, Hillig T, Pilegaard H, Richter EA,
Wojtaszewski JFP, et al. Higher skeletal muscle alpha2AMPK activa-
tion and lower energy charge and fat oxidation in men than in
women during submaximal exercise. J Physiol 2006;574:125–138.
37. Mittendorfer B, Horowitz JF, Klein S. Effect of gender on lipid
kinetics during endurance exercise of moderate intensity in
untrained subjects. Am J Physiol Endocrinol Metab 2002;46:E58.
38. Knechtle B. Relationship of anthropometric and training characteris-
tics with race performance in endurance and ultra-endurance ath-
letes. Asian J Sports Med 2015;6:73–90.
39. Kamper SJ. Multidisciplinary biopsychosocial rehabilitation for
chronic low back pain: Cochrane systematic review and meta-analysis.
BMJ 2015;350:h444.
40. Nordin M, Vischer TL, Waddell G. Common low back pain: preven-
tion of chronicity biopsychosocial analysis of low back pain. Baillieres
Clin Rheumatol 1992;6:523–557.
8Exercise-Associated Muscle Cramps MUSCLE & NERVE Month 2016
41. Behringer M, Moser M, McCourt M, Montag J, Mester J. A promising
approach to effectively reduce cramp susceptibility in human muscles:
a randomized, controlled clinical trial. PLoS One 2014;9:1–7.
42. Behringer M, Link TW, Montag JCK, McCourt ML, Mester J. Are
electrically induced muscle cramps able to increase the cramp
threshold frequency, when induced once a week? Orthop Rev 2015;
7:55–59.
43. Wakeling JM, Nigg BM. Modification of soft tissue vibrations in the
leg by muscular activity. J Appl Physiol 2001;90:412–420.
44. Kase K, Wallis J, Kase T. Clinical therapuetic applications of the kine-
sio taping method. Ken Ikai: Tokyo; 2002.
45. Marban RM, Rodriguez EF, Navarrete PI, Vega DM. The effect of
Kinesio taping on calf’s injuries prevention in triathletes during com-
petition. Pilot experience. J Hum Sport Exerc 2011;6:305–308.
46. Behm DG, Peach A, Maddigan M, Aboodarda SJ, DiSanto MC,
Button DC, et al. Massage and stretching reduce spinal reflex excit-
ability without affecting twitch contractile properties. J Electromyogr
Kinesiol 2013;23:1215–1221.
47. Lee H, Wu S, You J. Quantitative application of transverse friction
massage and its neurological effects on flexor carpi radialis. Man
Ther 2009;14:501–507.
48. Sefton JM, Yarar C, Berry JW. Massage therapy produce short-term
improvement in balance, neurological, and cardiovascular measures in
older persons. Int J Ther Massage Bodywork Res Educ Pract 2012;5:16–27.
49. Stone MB, Edwards JE, Stemmans CL, Ingersoll CD, Palmieri RM,
Krause BA. Certified athletic trainers’ perceptions of exercise-
associated muscle cramps. J Sport Rehabil 2003;12:333–342.
50. Sawka MN, Burke L, Eichner E, Maughan R, Montain S, Stachenfeld
N. ACSM position stand: exercise and fluid replacement. Med Sci
Sports Exerc 2007;39:377–390.
51. Mafi N, Lorentzon R, Alfredson H. Superior short-term results with
eccentric calf muscle training compared to concentric training in a
randomized prospective multicenter study on patients with
chronic Achilles tendinosis. Knee Surg Sports Traumatol Arthrosc
2001;9:42–47.
52. Masood T, Kalliokoski K, Magnusson SP, Bojsen-Møller J, Finni T.
Effects of 12-wk eccentric calf muscle training on muscle-tendon glu-
cose uptake and SEMG in patients with chronic Achilles tendon
pain. J Appl Physiol 2014;117:105.
53. Wagner T, Behnia N, Ancheta WL, Shen R, Farrokhi S, Powers CM.
Strengthening and neuromuscular reeducation of the gluteus maxi-
mus in a triathlete with exercise-associated cramping of the ham-
strings. J Orthop Sports Phys Ther 2010;40:112–119.
54. Miller KC, Burne JA. Golgi tendon organ reflex inhibition following
manually applied acute static stretching. J Sports Sci 2014;32:1491–
1497.
55. Diener H, Dethlefsen U, Dethlefsen-Gruber S, Verbeek P. Effective-
ness of quinine in treating muscle cramps: a double-blind, placebo-
controlled parallel-group, multicenter trial. Int J Clin Pract 2002;56:
243–246.
56. El-Tawil S. Quinine for muscle cramps. Cochrane Database of Syst
Rev 2015;4:CD005044.
57. Quinine and profound thrombocytopenia. Aust Adverse Drug React
Bull 2002;21:10.
58. Williams RB, Conway DP. Treatment of acute muscle cramps with
vinegar: a case report. J Athl Train 2001;36(suppl):S106.
59. Miller KC, Mack GW, Knight KL, Hopkins TY, Draper DO, Fields PJ,
et al. Reflex inhibition of electrically induced muscle cramps in hypo-
hydrated humans. Med Sci Sports Exerc 2010;42:953–961.
60. Miller KC, Mack G, Knight KL. Electrolyte and plasma changes after
ingestion of pickle juice, water, and a common carbohydrate-
electrolyte solution. J Athl Train 2009;44:454–461.
61. Murphy PM, Murphy CA. Hyperventilation as a simple cure for severe
exercise-associated muscle cramping. Pain Med 2011;12:987–987.
Exercise-Associated Muscle Cramps MUSCLE & NERVE Month 2016 9
