An Evidence-Based Review of the Pathophysiology, Treatment, and Prevention of Exercise-Associated Muscle Cramps

We performed a computerized search of published articles written in English from 1900 to 2020 pertaining to the pathophysiology, treatment, and prevention of EAMCs. We searched the PubMed, Cochrane, CINAHL, SPORTDiscus, and PEDRo databases using Boolean operators combined with the following search terms: exercise associated muscle cramp, cramping, exercise, dehydration, electrolytes, fatigue, rehydration, treatment, and prevention. We also reviewed reference lists for further information on the topic. From this review, we developed 16 recommendations for treating and preventing EAMCs and graded each recommendation using the Strength of Recommendation Taxonomy (SORT) grading scale (Table 2).¹⁰ 

The dehydration and electrolyte imbalance theory is the oldest theory and is primarily based on clinical observations. It proposes that EAMCs occur when sweating causes a contracture of the interstitial fluid space, increasing excitatory neurochemicals and mechanical pressure on motor-nerve terminals.⁸ 

Many observations over the last 100 years seemingly supported the dehydration and electrolyte imbalance theory. First, early researchers¹¹  speculated that EAMCs were due to 3 factors: sweat-induced fluid and electrolyte (primarily chloride) losses, hard work by people unacclimated to the heat, and exposure to high temperatures. However, fluid and electrolyte balance measures were often unreported, and many patients were experiencing an acute gastrointestinal illness (eg, vomiting or diarrhea). Regardless, EAMCs were linked to work-induced fluid losses. Second, EAMCs diminished with saline administration in a small case series.¹¹  Third, tennis players (n = 17)¹²  and American football players with a cramp history (n = 5)¹³  tended to have higher sweat rates (∼2.5 L/h) and sodium losses (up to 2.7 g/h) than noncrampers. Similarly, American football players with sweat sodium losses >1.18 g or sweat chloride losses >2.3 g during a workout were approximately 9 times more likely to be EAMC prone.¹⁴  Finally, Ohno et al¹⁵  counted the number of volitionally induced hamstrings cramps after 9 men lost 0.5% (control group), 1%, 2%, or 3% of their body mass passively in a sauna. They observed no cramps with 0.5% or 1% body mass reductions. When dehydrated to −2% or −3% of body mass, 3 participants cramped in each condition.

Conversely, expert opinion^4,6,9  and other evidence from experimental^16,17  and observational studies^1,3,18–21  did not support the dehydration and electrolyte imbalance theory. First, the theory proposes a conflicting physiological argument.⁹  Athletes with EAMCs lose large volumes of sweat, which would result in significant losses of plasma volume and lead to increased plasma osmolality. Consequently, fluid should leave the interstitial fluid space and enter the vasculature. However, crampers also purportedly lose significant amounts of sodium as “salty sweaters.”⁸  The electrolyte loss would decrease plasma osmolality, resulting in little or no fluid moving out of the interstitial space.⁹  Second, plasma characteristics in athletes with and those without EAMCs were often within normal limits and comparable after exercise.^1,20  Several authors^1,20,22  demonstrated no differences in plasma volume, red cell volume, body mass lost, or plasma electrolyte concentrations during competition between athletes with and those without EAMCs. The comparable blood characteristics between groups would suggest similar osmotic pressures systemically, though some researchers⁸  argued that blood samples did not reflect conditions near the cramping muscles. Yet when participants were dehydrated to −6% of their body mass, no changes in muscle resting membrane potential occurred.²³  Third, even though sodium and chloride losses and the sweat rate predicted EAMC-prone athletes in American football, this relationship was not clinically meaningful in 10 other sports.¹⁴  Moreover, when diet, hydration status, environmental conditions, and exercise intensity and duration were controlled, no differences in sweat characteristics were identified among athletes with various EAMC susceptibilities.¹⁶  Fourth, because dehydration and electrolyte losses are systemic, if the dehydration and electrolyte imbalance theory was true, then EAMCs should occur in any muscle, not only the working muscles. Fifth, athletes prone to EAMCs consumed similar volumes of fluid during exercise as noncrampers.¹³  Sixth, stretching relieved cramping but did not alter fluid or electrolyte levels.⁵  Finally, electrically induced cramp susceptibility was unchanged when participants lost 3% to 5% of their body mass and approximately 4 g of sodium and when fatigue was minimized,¹⁷  suggesting that dehydration and electrolyte losses had minimal effects on cramp susceptibility.

The altered neuromuscular control theory was proposed in 1997 and updated in 2009 as a new explanation for EAMCs.⁹  This theory suggests that EAMCs occur when fatigue and other risk factors contribute to a final common pathophysiological pathway to produce an imbalance between excitatory and inhibitory stimuli at the α motor nerve. The theory arose out of observations that fatigue altered muscle spindle and Golgi tendon organ firing rates in an animal model.^24,25  These afferent activity changes could lead to overexcitation of the motor nerves. Authors^1,9  of prospective cohort studies of athletes with EAMCs have subsequently identified risk factors more consistent with fatigue-induced alterations in nervous system excitability (eg, poor conditioning, higher exercise intensities) than dehydration or electrolyte losses. Most EAMCs occur in exercising or actively contracting muscles⁵  that cross multiple joints (eg, gastrocnemius, hamstrings).¹  Muscles that cross multiple joints often contract in already shortened positions; thus, the amount of muscle inhibition coming from Golgi tendon organs is reduced.²⁶  Exercise-associated muscle cramps also typically occur near the end of competitions, when fatigue is likely greatest.^1,20  In laboratory studies, investigators confirmed the importance of muscle afferents²⁷  and spinal pathways in cramp development,²⁸  and noncrampers produced greater amounts of inhibition than crampers.²⁷  Moreover, cramps could be induced volitionally in the absence of dehydration or electrolyte losses.²⁹  Collectively, these findings indicated that nervous system alterations were needed for EAMCs to occur and that the final common pathway to EAMCs was altered in neuromuscular control.

This theory better explains clinical and laboratory observations of cramping but is not without limitations and questions. When first proposed, the theory emphasized the importance of fatigue-induced alterations in afferent activity, resulting in overexcitation at the α motor neuron. However, it is unclear how fatigue alters this signaling: if a fatigue threshold must be reached before patients experience EAMCs, or whether fatigue-induced changes in excitability can be modulated by other factors. What is known is that well-trained and conditioned athletes still develop EAMCs. Also, training history does not always predict EAMC occurrence.^30,31  Thus, fatigue cannot be the sole generator of EAMCs, and other factors can alter neuromuscular control. Contrary to the theory, in 1 laboratory study, researchers³²  noted that localized, fatiguing contractions decreased electrically induced cramp susceptibility. Lastly, authors of many of the laboratory studies^17,24–27  that supported this theory used low-frequency electrical stimulation to induce cramps. This technique allows cramp susceptibility in different muscles³³  to be examined and can discriminate between crampers and noncrampers.³⁴  However, the muscles studied are often small (eg, flexor hallucis brevis) and different than the muscles that usually develop EAMCs during exercise. Thus, questions exist about the applicability of the findings to EAMCs.

Building on the Schwellnus theory,⁹  Miller⁴  recently proposed an EAMC pathophysiology model focused on how multiple risk factors interact to elicit a chain reaction that alters neuromuscular control and induces EAMCs (Figure 1). In this model,⁴  he theorized that numerous unique intrinsic and extrinsic factors coalesce through different pathways and elicit EAMCs. For example, consider an athlete who sustains a muscle injury. This injury may cause deconditioning, pain, and an inability to tolerate the same exercise intensities and durations as before the injury. Consequently, these risk factors coalesce, alter neuromuscular control, and elicit EAMCs.

This model also proposes that a factor threshold must be reached before EAMCs occur and that this threshold may be positively or negatively mitigated by other risk factors. Therefore, when predisposed individuals with intrinsic risk factors are exposed to extrinsic factors and exceed their factor threshold, EAMCs occur. This multifactorial theory and factor threshold may explain why EAMCs occur in some individuals and some situations but not others. Further examination is needed to clarify which factors contribute to EAMCs, how these factors coalesce, and whether some factors are more or less important to EAMC development.

Exercise-associated muscle cramps normally occur acutely during or after exercise. The diagnosis of EAMCs is based on a thorough clinical examination and history.³⁵  Acutely, patients present in noticeable pain, often resulting in slowing or ceasing activity altogether.^1,3  Patients often report subtle muscle twitching before the EAMCs began (cramp-prone state). Cramping muscles appear rigid, with the joint often locked in its end range of motion. Clinicians observe visible and palpable knotting or tautness, a key sign differentiating EAMCs from exertional sickling cramps. Fasciculations that wander over the muscle are also possible.³⁵  Athletes with more serious EAMCs that occur concomitantly with other serious medical conditions (eg, hyponatremia) warrant additional evaluation and diagnosis and should be immediately referred for further medical care (Table 1).^2,35 

Clinicians should develop treatment protocols for acute EAMCs. Ideally, the treatment approach is individualized (Figure 2 and Table 3) and EAMC treatments are continued for up to 1 hour because susceptibility to EAMCs remains high even after cessation.²⁹ 

Although most patients can finish exercising after mild EAMCs, some athletes cannot complete their competitions because of EAMCs.^3,36  In these cases, rest helps to normalize neuromuscular activity and allows treatments to address the underlying risk factors that contributed to EAMC development (eg, depleted muscle energy).²⁹  The patient should be placed in a position of comfort. Similarly, pain-relieving agents (eg, cryotherapy, massage, electrical stimulation) may provide relief from the EAMCs by interrupting the pain-spasm-pain cycle.⁴  As the athlete rests, clinicians should identify and address the factors that may have precipitated EAMC development.

The fastest, safest, and most effective treatment for an active EAMC is self-administered or clinician-administered gentle stretching.^5,22,35  No researchers have examined which type of stretching most effectively relieves active EAMCs, but static stretching increases tendon tension, and elongated muscles produce the greatest Golgi tendon organ inhibition.²⁶  This may help restore the balance between excitatory and inhibitory signaling and explain the reduction in muscle activity observed when cramping muscles are stretched.⁹  Stretching also physically separates the contractile proteins, which is beneficial as muscle shortening is required for cramping.⁵  If stretching fails to relieve EAMCs, clinicians should seek advanced medical care.

Athletes can drink water or carbohydrate-electrolyte beverages ad libitum during EAMC treatment if tolerated because these liquids both restore plasma volume and osmolality over time and rehydrate effectively.^37,38  However, stretching will alleviate EAMCs more quickly than rehydration. Oral fluids require ≥13 minutes to be absorbed into the bloodstream though this timing can be prolonged depending on the beverage's contents (eg, acidity, electrolyte, and carbohydrate content).³⁸  Also, these drinks are hypotonic compared with plasma, so it can be dangerous to try and fully replace the electrolytes lost during exercise by consuming only sport drinks (Table 4). Ingesting such large volumes of hypotonic fluids will dilute the blood and could result in life-threatening hyponatremia.

In most situations, rehydration should be oral due to its simplicity, accessibility, and myriad of delivery options (eg, cup, water bottle, prepacked container). Intravenous (IV) fluids are popular among professional athletes, yet they must be administered by a trained person and pose certain risks (eg, infection, air embolism, arterial puncture).³⁹  Authors of numerous studies^38,39  have examined oral versus IV fluid administration on hydration status and noted comparable restoration of plasma osmolality, plasma volume, skin blood flow, stroke volume, cardiac output, heart rate, skin temperature, rectal temperature, performance, and fluid regulatory hormone responses. Interestingly, perceptual measures (eg, thirst, thermal sensation, and rating of perceived exertion) are often lower with oral rehydration because IV fluid delivery bypasses fluid volume receptors in the mouth (ie, baroreceptors).⁴⁰  Although either fluid delivery method can be used to treat EAMCs, IV fluid administration should be saved for time-sensitive situations (ie, <15 minutes) or when patients cannot consume fluids orally (eg, too much pain, repeated vomiting).

Transient receptor potential (TRP) receptors detect temperature and sensations in the mouth, oropharynx, esophagus, and stomach. Ingredients such as vinegar, cinnamon, capsaicin, and ginger activate these receptors and, in theory, may affect neural function if potent enough.^41,42  Two of the more popular TRP agonists are pickle juice and mustard due to their high concentrations of vinegar, salt, or both.⁴³  In 1 single-blinded study,⁴⁴  ingesting small volumes (<100 mL) of pickle juice relieved cramps 45% faster (68.6 seconds) than no fluids and 37% faster (49.1 seconds) than water. This effect was neither immediate (∼90 seconds) nor the result of electrolytes consumed as the small volumes of pickle juice did not affect plasma volume, plasma electrolyte concentrations, or plasma osmolality.^44,45  Instead, the investigators⁴⁴  hypothesized that vinegar triggered an oropharyngeal reflex that inhibited cramping. Conversely, only anecdotal evidence exists regarding mustard's efficacy in relieving acute EAMCs. However, the efficacy of mustard is not likely due to electrolyte replacement because ingesting large volumes (∼135 g) had no effect on plasma electrolyte concentrations, plasma osmolality, or plasma volume up to 60 minutes postingestion.⁴⁵ 

Authors of other studies assessed the effect of spicy, capsaicin-based TRP agonists on cramp susceptibility. While the researchers in 1 study⁴²  reported longer times before cramping, higher contraction forces necessary to induce cramping, and lower muscle activity during cramping, all participants still cramped after ingesting the TRP-agonist drink. Conversely, Behringer et al⁴¹  noted insignificant changes in cramp susceptibility, perceived muscle pain, cramp intensity, and maximal isometric force from 15 minutes to 24 hours postingestion of a TRP agonist. Further work is needed on TRP agonists and EAMCs.

The ingestion of TRP agonists is usually benign, even though gastrointestinal tolerance varies considerably. If used, clinicians should provide them in small volumes (<100 mL) and only when oral solutions are tolerated and no food allergies are present. If symptoms are not relieved relatively quickly (<2 minutes), other treatments should be used.

Potassium is generally not considered an electrolyte of interest in EAMCs, yet bananas are sometimes used during treatment due to their high potassium and glucose content. However, no evidence exists on their efficacy. Some data suggested they are unlikely to help by increasing blood potassium; dehydrated participants who ingested 1 or 2 servings of bananas postexercise did not experience increases in plasma potassium concentrations or plasma volume until 60 minutes after consumption.⁴⁶  Interestingly, plasma glucose increased significantly in the 2-servings trial, but this effect occurred 15 minutes postingestion. If poor nutrition is suspected as a risk factor for an athlete's EAMCs, we advise clinicians to advocate for a well-rounded pre-exercise nutrition plan and consult with a registered dietitian before implementing dietary interventions.

Quinine and quinine products (eg, tonic water) were once a popular treatment for cramping.⁴⁷  These have fallen out of favor because they require a prescription, and the United States Food and Drug Administration banned all over-the-counter quinine products for cramping in the mid-1990s. A Cochrane review⁴⁷  of 23 trials showed that quinine reduced the number and intensity of cramps, though the extent of this reduction was clinically unimpressive, with a mean reduction of less than 2 cramps over a 2-week period (95% CI = −2.2, −1.42). Interestingly, cramp duration, which is the variable of interest in the acute treatment of EAMCs, was not reduced. Importantly, minor and major adverse events were reported in many of the trials (eg, gastrointestinal distress, thrombocytopenia).⁴⁷  Consequently, we do not recommend using quinine for EAMCs.

The first step in the diagnosis and treatment of a patient presenting with recurrent EAMCs is a thorough medical evaluation to rule out any intrinsic risk factors, including a history of injury, past EAMC history, chronic medical conditions, medication use, or allergies (Figure 2 and Table 3).³⁵  If an underlying condition is identified, that condition should be treated before implementing EAMC prevention strategies.

After ruling out underlying conditions, the clinician should thoroughly question the patient to determine if pertinent extrinsic or intrinsic risk factors exist. Risk factors consistently associated with EAMCs include pain,²¹  a history or previous occurrence of EAMCs,^21,22,48  muscle damage or injury,^18,21,31,48  prolonged exercise durations,^1,20,30,48  and faster finishing times than anticipated.^2,22  Consequently, setting realistic goals, obtaining regular and sufficient sleep,⁴⁹  incorporating rest and recovery sessions in training schedules, and training at similar intensities and in similar environments to competition may help stave off many risk factors known to contribute to EAMCs.

The strongest and most recent evidence^4,9  suggested that EAMCs are due to changes in the neuromuscular system, yet most diagnostic questions revolve around factors that affect nervous system excitability (Table 3). These questions can be asked before and after each EAMC to help clinicians identify consistent risk factors. Targeted prevention strategies for those risk factors can then be attempted.

Many EAMC prevention recommendations have been advocated, but unfortunately, most either lack support from strong patient-oriented studies or are based on anecdotes (Table 2). Indeed, much of the published EAMC prevention advice is derived from studies of electrically induced cramps rather than EAMCs, is anecdotal, is often too generic (eg, consume more salt), or fails to account for the complexity of EAMC pathogenesis. Moreover, many patients and clinicians lack an understanding of the possible causes and risk factors for EAMCs and are overly confident about the contributions of hydration and electrolytes to EAMCs.⁵⁰  Sadly, an overemphasis on hydration and electrolyte consumption to prevent EAMCs contributed to the deaths of 2 high school athletes from hyponatremia in 2014.⁴  Therefore, we advocate for clinicians to educate athletes about EAMC causes and safe hydration practices before implementing prevention strategies,³⁸  take a multifactorial approach to EAMC prevention, implement EAMC prevention strategies cautiously and with thorough documentation, and at a minimum, perform a thorough medical examination before implementing any of the following strategies.

Sport drink consumption and electrolyte supplementation are frequently touted as effective for preventing EAMCs, though the content of sports drinks and electrolyte supplementation products varies greatly (Table 4).⁵¹  Despite the fact that electrolyte tablets and magnesium supplementation are frequently promoted to prevent cramping, the authors⁵²  of a Cochrane review reported that magnesium supplementation offered no clinically meaningful benefits in terms of cramp frequency, intensity, or duration compared with placebo. However, in the 1920s, investigators¹¹  observed that workers prevented EAMCs by consuming saline or adding salt to their beverages. Bergeron⁵¹  described a tennis player who prevented EAMCs by increasing dietary salt intake by 6000 to 8000 mg/day, increasing caloric intake by 5000 to 6000 kcal/day, improving pre-event hydration status, and adding salt to sports drinks when the athlete felt EAMCs were imminent. When participants ingested a 6% carbohydrate-electrolyte beverage with added salt during a calf-fatiguing protocol, EAMCs occurred after 36.8 ± 17.3 minutes, compared with 14.5 ± 5.0 minutes when nothing was consumed.⁵³  More recently, researchers⁵⁴  noted that a 2% carbohydrate-electrolyte beverage decreased electrically induced muscle cramp susceptibility. However, in both studies,^53,54  the athletes still experienced cramping, and the experimental designs prohibited identification of the ingredient responsible for this effect because the drink contained multiple ingredients (eg, electrolytes and carbohydrates). Still, the large carbohydrate load (18.3 to 57 g/L) may have been responsible as plasma electrolyte values decreased postingestion.⁵⁴  In theory, carbohydrate-electrolyte drinks could help prevent EAMCs by increasing muscle glycogen and delaying fatigue,³⁸  but more well-designed studies are needed to identify the active ingredients and minimal and optimal dosages for effectiveness. Clinicians should be wary of sport drinks that contain stimulants (eg, caffeine), which may cause an increase in nervous system excitability and, theoretically, predispose patients to EAMCs.⁵⁵ 

Conversely, the authors^1,18,20,22  of several studies failed to show differences in plasma electrolyte concentrations in athletes with and those without EAMCs. Sodium supplementation did not differ between ultramarathoners with and those without EAMCs.^19,48  Further examination of electrolyte supplementation and EAMCs is needed.

If clinicians suspect hydration is a risk factor for recurrent EAMCs, we recommend sweat testing. Determining the sweat rate is relatively simple and only requires body weight to be measured before and after exercise. Clinicians must also know the duration of exercise and the volume or weight of any fluids ingested or lost (ie, urination).³⁸  Determining the sweat electrolytes lost is more complicated and requires expensive equipment. Nonetheless, sweat electrolyte estimates are available for many sports.¹⁴  Ideally, sweat tests would be performed under similar environmental, equipment, and exercise conditions as during competition for accuracy. Combining sweat test results with a well-balanced, nutritious diet that considers the athlete's unique carbohydrate, fluid, and electrolyte needs will better ensure that he or she is prepared for exercise and minimize the risk of hyponatremia.³⁸ 

Some clinicians use IV fluids to prevent EAMCs and believe they are effective.³⁹  Unfortunately, no large-scale clinical trials have demonstrated that IV fluid administration reduces the occurrence of EAMCs or is more effective than oral fluid administration.³⁹  Because EAMCs are not life threatening and oral rehydration can safely restore fluid and electrolyte deficits,³⁸  we recommend clinicians avoid using IV fluids prophylactically.

Although static stretching effectively treats EAMCs,^5,22,35  it appears to be ineffective as a prophylactic strategy. In a laboratory study,⁵⁶  three 1-minute bouts of static or proprioceptive neuromuscular facilitation (hold-relax with agonist contraction) stretching did not lower cramp susceptibility. In observational studies of athletes, investigators^21,22,30  also consistently failed to demonstrate relationships among flexibility, range of motion, and stretching frequency, duration, or timing and EAMC occurrence. Moreover, Golgi tendon organ inhibition was unaffected by a single bout of clinician-applied static stretching to the triceps surae both immediately and up to 30 minutes poststretching.⁵⁷  Thus, pre-event stretching is unlikely to produce the long-lasting inhibition from Golgi tendon organs that would help prevent the overexcitation of the α motor-neuron pool thought to contribute to EAMC development.

Neuromuscular retraining with exercise shows promise for EAMC prevention. Wagner et al³  found that a triathlete's hamstrings EAMCs were eliminated by lowering hamstrings activity during running and improving gluteal strength and endurance. To achieve this outcome, the patient required few professional visits (once a month for 8 months) and just a short (20-minute) daily at-home protocol.³  More recently, marathoners who experienced EAMCs were less likely to perform once-per-week lower extremity strength training in the 3 months leading up to a race than their noncramping counterparts (25% versus 48%, respectively),¹⁸  suggesting that strength training may be helpful in preventing EAMCs. Fatigue is hypothesized to be a main factor in EAMC development and overexertion is often tied to EAMCs,⁹  so it is vital to ensure that athletes exercise with appropriate work-to-rest ratios.^2,31  Future researchers should explore if and how sport-specific exercise or endurance activities may prevent EAMCs.

Advances in our understanding of EAMC pathogenesis have emerged in the last 100 years and suggested that alterations in neuromuscular excitability and, to a much lesser extent, dehydration and electrolyte losses are the predominant factors in their pathogenesis. Strong evidence supports EAMC treatments that include exercise cessation (rest) and gentle stretching until abatement, followed by techniques to address the underlying precipitating factors. However, little patient-oriented evidence exists regarding the best methods for EAMC prevention. Therefore, rather than providing generalized advice, we recommend clinicians take a multifaceted and targeted approach that incorporates an individual's unique EAMC risk factors when trying to prevent EAMCs.