Abstract
Background
Lower limb muscle cramps are common and painful. They can limit exercise participation, and reduce quality of sleep, and quality of life. Many interventions are available for lower limb cramps; some are controversial or could cause harm, and often, people experience no benefit from the interventions used. This is an update of a Cochrane Review first published in 2012. We updated the review to incorporate new evidence.
Objectives
To assess the effects of non‐drug, non‐invasive therapies for lower limb muscle cramps.
Search methods
In August 2018 and May 2020, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, the World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, and reference lists of included studies. We imposed no restrictions by language or publication date.
Selection criteria
We included all randomised controlled trials (RCTs) of non‐drug, non‐invasive interventions tested over at least four weeks, for lower limb muscle cramps in any group of people, except pregnant women. The primary outcome was cramp frequency. Secondary outcomes were cramp pain severity, cramp duration, health‐related quality of life, quality of sleep, participation in activities of daily living, proportion of participants reporting lower limb muscle cramps, and adverse events.
Data collection and analysis
Two review authors independently selected trials, assessed risk of bias, and cross‐checked data extraction and analyses according to standard Cochrane procedures.
Main results
We included three trials, with 201 participants, all 50 years of age and older; none had neurological disease. All trials evaluated a form of stretching for lower limb muscle cramps.
A combination of daily calf and hamstring stretching for six weeks may reduce the severity of night‐time lower limb muscle cramps (measured on a 10 cm visual analogue scale (VAS) where 0 = no pain and 10 cm = worst pain imaginable) in people aged 55 years and older, compared to no intervention (mean difference (MD) ‐1.30, 95% confidence interval (CI) ‐1.74 to ‐0.86; 1 RCT, 80 participants; low‐certainty evidence). The certainty of evidence was very low for cramp frequency (change in number of cramps per night from week zero to week six) comparing the stretching group and the no intervention group (MD −1.2, 95% CI −1.8 to −0.6; 80 participants; very low‐certainty evidence).
Calf stretching alone for 12 weeks may make little to no difference to the frequency of night‐time lower limb muscle cramps in people aged 60 years and older (stretching group median number of cramps in the last four weeks (Md) 4, interquartile range (IQR) 8; N = 48; sham stretching group Md 3, IQR 7.63; N = 46) (U = 973.5, z = ‐0.995, P = 0.32, r = 0.10; 1 RCT, 94 participants; low‐certainty evidence). This trial did not report cramp severity.
The evidence is very uncertain about the effects of a combination of daily calf, quadriceps, and hamstring stretching on the frequency and severity of leg cramps in 50‐ to 60‐year‐old women with metabolic syndrome (N = 24). It was not possible to fully analyse the frequency data and the scale used to measure cramp severity is not validated.
No study reported health‐related quality of life, quality of sleep, or participation in activities of daily living. No participant in these three studies reported adverse events. The evidence for adverse events was of moderate certainty as the studies were too small to detect uncommon events.
In two of the three studies, outcomes were at risk of recall bias, and tools used to measure outcomes were not validated. Due to limitations in study designs that led to risks of bias, and imprecise findings with wide CIs, we cannot be certain that findings of future studies will be similar to those presented in this review.
Authors' conclusions
A combination of daily calf and hamstring stretching for six weeks may reduce the severity of night‐time lower limb muscle cramps in people aged 55 years and older, but the effect on cramp frequency is uncertain. Calf stretching alone compared to sham stretching for 12 weeks may make little or no difference to the frequency of night‐time lower limb muscle cramps in people aged 60 years and older. The evidence is very uncertain about the effects of a combination of daily calf, quadriceps, and hamstring stretching on the frequency and severity of leg cramps in 50‐ to 60‐year‐old women with metabolic syndrome. Overall, use of unvalidated outcome measures and inconsistent diagnostic criteria make it difficult to compare the studies and apply findings to clinical practice.
Given the prevalence and impact of lower limb muscle cramps, there is a pressing need to carefully evaluate many of the commonly recommended and emerging non‐drug therapies in well‐designed RCTs across all types of lower limb muscle cramps. A specific cramp outcome tool should be developed and validated for use in future research.
Plain language summary
Non‐drug treatments for leg and foot cramps
What is the aim of this review?
People commonly have muscle cramps at night while trying to sleep, during exercise, during pregnancy, and during haemodialysis (filtering of blood for people with severe kidney problems). Cramps can also occur at other times, and can be especially frequent and severe in children and adults with nerve diseases (for example, Charcot‐Marie‐Tooth disease).
There are many treatments available for leg and foot cramps. Most have not been tested in well designed clinical trials. Using untested interventions is not ideal, as people may be wasting their time or money, and may be exposing themselves to risk of harm. In this Cochrane Review, we collected and analysed all relevant studies to find out if any non‐drug interventions were helpful for cramps in the legs and feet.
Key messages
There is very little evidence from randomised trials to help people make decisions about non‐drug treatments for leg or foot cramps. We cannot be certain if any non‐drug therapy is particularly helpful, because there are not enough studies on which to base decisions, and cramps have generally not been well measured. No study tested non‐drug therapies in people under age 50 years, or with neurological disease. The current evidence provides some support that combining daily calf and hamstring stretching may reduce the severity of night‐time lower limb muscle cramps in people 55 years of age and older, but the effect on the frequency of cramps is not clear; the certainty of the evidence is very low.
What was studied in this review?
We were interested in studies that compared stretching, exercise, massage, relaxation, fatigue avoidance, night‐time temperature control, changes in sleeping and sitting positions, and splints worn while sleeping to each other, to no treatment, or to placebo or sham (pretend) treatment. We excluded studies that examined cramps in pregnancy (as they are covered in another Cochrane Review), or invasive treatments (such as surgery or acupuncture).
We wondered if therapies could reduce how often cramps occurred, how painful they were, how long each cramp lasted, how many people experienced cramps, how well people could sleep, or join in daily activities, and if there were any harmful effects.
What are the main results of the review?
Three studies (201 participants) provided low‐ or very low‐certainty evidence on the effectiveness of stretching to reduce lower leg cramps in people aged 50 years and older. One study received government funding; the other two did not report a funding source.
A combination of daily calf and hamstring stretching (compared to no intervention) may reduce the severity of night‐time lower limb muscle cramps in people over 55 years old (1 RCT, 80 people).
Calf stretching alone (compared to sham stretching) may lead to little or no difference in how often people, aged 60 years and older, have night‐time cramps in any lower limb muscle, although limitations in the study's design make it difficult to see how the results relate to clinical practice (1 RCT, 97 people).
The evidence is uncertain whether a combination of daily calf, quadriceps, and hamstring stretching (compared to no intervention) reduces the frequency and severity of leg cramps in 50‐ to 60‐year‐old women with metabolic syndrome (a group of health conditions leading to increased risk of heart diseases and related problems), as serious imitations in the study's design limited our confidence in the results (1 RCT, 24 women).
None of the people in the trials reported any side effects with treatment but we can only be moderately confident in this finding as the trials were small.
No study reported the effects of treatment on quality of sleep, quality of life, or participation in activities of daily living. No study tested non‐drug treatment in people with neurological disease, during exercise, or night‐time cramps in younger adults.
How up to date is this review?
We searched for studies published up to May 2020.
Summary of findings
Summary of findings 1. Calf and hamstring stretching compared to no intervention for lower limb muscle cramps in older adults.
| Calf and hamstring stretching compared to no intervention for lower limb muscle cramps in older adults | ||||||
| Patient or population: older adults with lower limb muscle cramps Setting: physical therapy clinic in Groningen, The Netherlands Intervention: calf and hamstring stretching Comparison: no intervention | ||||||
| Outcomes | Anticipated absolute effects | Relative effect (95% CI) | Number of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Risk with no intervention | Risk with calf and hamstring stretching | |||||
|
Change in cramp frequency (cramps per night) (after 6 weeks) |
The median number of cramps per night was 2 | The median number of cramps per night was 1 (Mann‐Whitney U test versus no intervention P = 0.002)* |
80 (1 RCT) | ⊕⊝⊝⊝ Very lowa | The effect of calf and hamstring stretching on the frequency of cramps at 6 weeks is very uncertain | |
| Adverse events | Neither group reported any adverse events. | 80 (1 RCT) |
⊕⊕⊕⊝ Moderateb | There are probably no adverse events with calf and hamstring stretching | ||
|
Change in cramp severity (0 to 10 VAS; higher = worse pain) (after 6 weeks) |
The mean change in cramp severity was 0 points | Cramp severity improved on average 1.3 points more (1.74 points more to 0.86 points more) in the stretching group than in the non‐stretching group | ‐ | 80 (1 RCT) | ⊕⊕⊝⊝ Lowc | Calf and hamstring stretching may reduce the severity of cramps at 6 weeks |
| Proportion of participants experiencing cramps | not reported | |||||
| Health‐related quality of life | not reported | |||||
| Quality of sleep | not reported | |||||
| Activities of daily living | not reported | |||||
| *A Mann Whitney U test was conducted due to the skewness of data. **The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence High certainty. We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty. We are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty. Our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect Very low certainty. We have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect | ||||||
| RCT: randomised controlled trial; CI: confidence interval | ||||||
aDowngraded three times, for imprecision and study limitations: the CI spans results that would lead to different clinical decisions, it is unclear if all outcomes were reported, and participants were not blinded. bDowngraded once for imprecision: although similar stretching interventions also report no adverse effects, the study may be too small to detect uncommon, yet important adverse effects. cDowngraded twice for study limitations: participants were not blinded, and it is unclear if all outcomes were reported.
Summary of findings 2. Calf stretching compared to placebo stretching for lower limb muscle cramps in older adults.
| Calf stretching compared to placebo stretching for lower limb muscle cramps in older adults | ||||||
| Patient or population: older adults with lower limb muscle cramps Setting: 28 general practices in southern England Intervention: calf stretching Comparison: placebo stretching | ||||||
| Outcomes | Anticipated absolute effects | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Risk with sham stretching | Risk with calf stretching | |||||
|
Cramp frequency (number of cramps in the last four weeks) (after 12 weeks) |
The median cramp frequency was 3 cramps | The median cramp frequency was 4 cramps (Mann‐Whitney U test versus sham stretching P = 0.32)* |
‐ | 94 (1 RCT) | ⊕⊕⊝⊝ Lowa | Calf stretching may have little or no effect on the frequency of cramps at 12 weeks. |
| Adverse events | There were no significant adverse effects reported; publication of trial provided no definition for significant adverse effects. | ‐ | 94 (1 RCT) |
⊕⊝⊝⊝ Very lowb | There may be no adverse events with calf stretching, but the evidence is very uncertain. | |
| Cramp severity | not reported | |||||
| Proportion of participants experiencing cramps | not reported | |||||
| Health‐related quality of life | not reported | |||||
| Quality of sleep | not reported | |||||
| Activities of daily living | not reported | |||||
| *A Mann Whitney U test was conducted due to the skewness of data. | ||||||
| GRADE Working Group grades of evidence High certainty. We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty. We are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty. Our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect Very low certainty. We have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect | ||||||
| RCT: randomised controlled trial; CI: confidence interval | ||||||
a Downgraded twice for study limitations: not all outcomes were reported, it is unclear if there was risk of attrition bias, and the outcome measure is at risk of recall bias. Duration of leg cramps and subsequent general practitioner attendance were planned in the study protocol but not reported. bDowngraded three times: once for imprecision – although other studies of similar stretching interventions also report no adverse effects, the study may be too small to detect uncommon, yet important adverse effects; once for indirectness – the published trial report provided no definition of "significant adverse effects"; and once for study limitations – it is unclear if there was risk of attrition bias.
Summary of findings 3. Calf, quadriceps, and hamstring stretching compared to no stretching for leg cramps in 50‐ to 60‐year‐old women with metabolic syndrome.
| Calf, quadriceps, and hamstring stretching compared to no stretching for leg cramps in 50‐ to 60‐year‐old women with metabolic syndrome | ||||||
|
Patient or population: 50‐ to 60‐year‐old women with metabolic syndrome Settings: GP clinics, Fuman, Gilan Province, Iran Intervention: calf, quadriceps, and hamstring stretching Comparison: no stretching | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect (95% CI) | No of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Assumed risk | Corresponding risk | |||||
| No stretching | Calf, quadriceps, and hamstring stretching | |||||
|
Cramp frequency (number of cramps in preceding week) (after 6 weeks) |
The mean frequency of cramps with no stretching was 2.58 cramps per week. | The mean frequency of cramps after stretching was 0.75 cramps fewer per week (1.40 fewer to 0.10 fewer) than in the no stretching group | ‐ | 24 (1 RCT) |
⊕⊝⊝⊝ Very lowa,b | The effect of calf, quadriceps, and hamstring stretching on the frequency of cramps after 6 weeks is very uncertain. |
| Adverse events | No adverse events were reported in either group. | ‐ | 24 (1 RCT) |
⊕⊕⊕⊝ Moderatec | There may be no adverse events with calf, quadriceps, and hamstring stretching | |
|
Cramp severity (0 to 10 VAS; higher = more pain) (after 6 weeks) |
The mean severity of cramps with no stretching was 6.50 points. | The mean severity of cramps after stretching was 3.42 points lower (4.33 lower to 2.51 lower). | ‐ | 24 (1 RCT) |
⊕⊝⊝⊝ Very lowa,d | Calf, quadriceps, and hamstring stretching may reduce the severity of cramps after 6 weeks, but the evidence is very uncertain |
| Proportion of participants experiencing cramps | Not reported | |||||
| Health‐related quality of life | Not reported | |||||
| Quality of sleep | Not reported | |||||
| Activities of daily living | Not reported | |||||
| *The basis for the assumed risk is the mean control group risk. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence High certainty. We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty. We are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty. Our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect Very low certainty. We have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect | ||||||
| RCT: randomised controlled trial; CI: confidence interval | ||||||
aDowngraded twice for study limitations: the outcome is subject to recall bias, participants (who assessed outcomes) were not blinded, and it is unclear if all outcomes were reported. bDowngraded once for imprecision: the study is small with wide CI. cDowngraded once for imprecision: although similar stretching interventions also report no adverse effects, the study may be too small to detect uncommon, yet important adverse effects. dDowngraded once for indirectness: the outcome measure is not validated.
Background
Description of the condition
Muscle cramps are highly prevalent, especially in older adults and people with neurological disease, and have a substantial impact on physical and psychological health (distress, less sleep). Muscle cramps are sudden, involuntary, painful contractions of skeletal muscle (Norris 1957; Jansen 1991a; El‐Tawil 2015), which are characterised electrically by repetitive firing of motor unit action potentials at high rates up to 150 per second (Miller 2005). Cramps can be excruciatingly painful (Kanaan 2001; Jansen 2002), and can cause pain immediately following the cramp and for days afterwards (Leung 1999; Jansen 2002). Recent research has demonstrated that night‐time calf cramps are associated with poorer quality of sleep, and that night‐time calf cramps, cramps in people with cirrhosis, and cramps in adults and children with Charcot‐Marie‐Tooth disease (CMT) are associated with lower quality of life (Redmond 2008; Burns 2010; Chatrath 2012; Hawke 2013b; Katzberg 2019). In a cross‐sectional study of 70 Australian children, aged 5 to 16 years, with CMT, leg cramps were identified as the strongest independent correlate of reduced quality of life (Burns 2010). In people undergoing haemodialysis, muscle cramps can prevent them from being on dialysis for a full cycle, and can lead to chronic under‐dialysis (Canzanello 1992).
Muscle cramps can occur at any time throughout the day or night (Abdulla 1999). They can affect people of any age (Jansen 1991; Miller 2005), although they are uncommon in children younger than eight years of age (Leung 1999). Cramps usually affect muscles of the legs (Naylor 1994; Hirai 2000), particularly the calf muscles (Jansen 1991; Manjra 1996; Abdulla 1999; Leung 1999). Most cramps resolve spontaneously, within 10 minutes (Naylor 1994; Abdulla 1999), but some have been reported to last up to one hour (Abdulla 1999). In most cases, cramps occur irregularly, often appearing and disappearing spontaneously for long periods, irrespective of treatment (Jansen 1999; Blyton 2012).
No large, randomly sampled population studies have been conducted to determine the prevalence of lower limb muscle cramps. In a nationwide randomised study of general muscle cramps in nearly 2000 Dutch adults, approximately one in every three people reported at least one muscle cramp during the prior year (Jansen 1991a). Similarly, of over 1000 people surveyed in southern Germany, approximately one in every three people reported a history of nocturnal calf cramps, and one in every four had experienced cramps within the four weeks prior to completing the questionnaire (Gulich 1998). In a separate study of 365 people aged 65 years and over, one in two people reported leg cramps at rest (for example while sleeping; (Abdulla 1999)).
Compared to the general population, leg cramps are more prevalent in pregnant women (Jansen 1991; Jansen 1991a); people over 60 years of age (Naylor 1994; Gulich 1998; Hirai 2000); people undergoing haemodialysis (Canzanello 1992; Kobrin 2007); and people with cirrhosis (Angeli 1996; Chatrath 2012), fibromyalgia (Yunus 1996), arthritis (Yunus 1996; Abdulla 1999), motor neuron disease (for example amyotrophic lateral sclerosis; (Forshew 2003)), lumbar spinal canal stenosis (Matsumoto 2009), peripheral neurological deficit (Haskell 1997), paraesthesia (Yunus 1996); varicose veins (Gulich 1998; Hirai 2000); and CMT (Burns 2009; Redmond 2009). The underlying cause of lower limb muscle cramps is not well understood. Two enduring hypotheses suggest the involvement of abnormal excitability of motor nerve terminals and instability of groups of anterior horn cells due to spinal disinhibition (Roeleveld 2000). Recently, calf muscle cramps in children with CMT and adults without neurological disease have both been independently associated with other clinical features of neurological dysfunction, including tremor, fasciculation (muscle twitching), lower limb tingling, and muscle weakness (Blyton 2011; Hawke 2013).
Description of the intervention
Many interventions have been tried in the management of lower limb muscle cramps. The most common interventions can be broadly categorised as drug or non‐drug interventions. Common drug interventions include quinine sulphate (El‐Tawil 2015), gabapentin (Miller 2005), magnesium (Frusso 1999; Roffe 2002; Sohrabvand 2006), vitamin E (Connolly 1992; Burnakis 2000), calcium channel blockers (Baltodano 1988), naftidrofuryl oxalate (Young 1993), and calcium (Sohrabvand 2006). Non‐drug interventions reported in the literature include: muscle stretching (Daniell 1979; Jones 1983; Simchak 1991; Leclerc 1996; Leung 1999; Kanaan 2001; Miller 2005; Matsumoto 2009); massage (Jones 1983; Kanaan 2001; Matsumoto 2009); relaxation (Joekes 1982); sensory nerve stimulation (Bentley 1996); footwear changes (Roberts 1965); weight loss (Roberts 1965); physical exercise (Miller 2005); avoidance of physical fatigue (Roberts 1965); heat therapy (Jones 1983); compression garments (Young 2009); night ankle dorsiflexion splints (Miller 2005); salt baths (Blyton 2012); placebo (Miller 2005); reassurance (Butler 2002); changes to sleeping position (Gootnick 1943; Moss 1948; Cutler 1984; Warburton 1987; Abdulla 1999; Leung 1999; Kanaan 2001); and changes to sitting position (Roberts 1965). More controversial historical interventions include sleeping with a horseshoe (Simchak 1991), a magnet (Fowler 1973), camphor (Blyton 2012), corks (Warburton 1987), or potatoes beneath the mattress (Warburton 1987).
Why it is important to do this review
Management of leg cramps can be frustrating and difficult for physicians and people with cramps alike (Riley 1995; Butler 2002). Many people experience little or no benefit from the interventions prescribed (Sontag 1988; Abdulla 1999; Miller 2005; Blyton 2012), and many more receive no intervention at all (Naylor 1994; Gulich 1998; Abdulla 1999). Four Cochrane Reviews have focused on interventions for muscle cramps. These reviews assessed: treatment of muscle cramps in pregnancy (Zhou 2015); treatment of cramps in amyotrophic lateral sclerosis/motor neuron disease (Baldinger 2012); quinine for muscle cramps (El‐Tawil 2015); and magnesium for skeletal muscle cramps (Garrison 2020). Garrison 2020 found no clinically meaningful effect of magnesium supplementation for older adults, and inconsistent results that require further research for pregnant women. El‐Tawil 2015 concluded that there was low‐quality evidence that quinine (200 mg to 500 mg daily) reduced the number of cramps, and the number of days during which cramps were experienced; due to reliable reports that an overdose of quinine can cause serious harm including death, more research is needed to clarify the best dose and duration of treatment, as well as alternatives to quinine for cramps.
A systematic review of non‐drug interventions for lower limb muscle cramps serves two purposes. First, it enables healthcare providers, users, and policy decision makers to make better informed decisions about the treatment of lower limb muscle cramps; and second, it serves to identify interventions that require further evaluation in clinical trials.
This is an update of a review first published in 2012, undertaken to incorporate new evidence (Hawke 2012).
Objectives
To assess the effects of non‐drug, non‐invasive therapies for lower limb muscle cramps.
Methods
Criteria for considering studies for this review
Types of studies
We considered all randomised controlled trials (RCTs) and quasi‐RCTs of non‐drug interventions for the prevention of lower limb muscle cramps for inclusion. Quasi‐RCTs are trials that allocate participants using methods such as alternation, case record number, or date. We included quasi‐RCTs as evidence from RCTs is lacking.
Studies were only eligible for inclusion if all participants reported lower limb muscle cramps at baseline, or if randomisation was stratified for the presence of lower limb muscle cramps. We excluded trials of acute treatment of muscle cramps, that is, a treatment to alleviate the cramp, which is only used when a muscle is cramping.
We accepted any diagnosis of a muscle cramp, unless there was a clear contradiction with the broad definition used in this review (cramp as a sudden, involuntary, painful contraction of skeletal muscle). Where possible, we differentiated muscle cramp from other conditions of the lower limbs, including intermittent claudication, ischaemic rest pain, restless leg syndrome, muscle strain, chronic compartment syndrome, and hypnagogic jerks. We planned to report definitions of 'cramp' used in included studies in the 'Characteristics of included studies' table.
We included cross‐over trials and multi‐arm trials that included eligible comparisons.
There were no restrictions on the basis of language or publication status.
Types of participants
We included all people (men, women, and children) who experienced lower limb muscle cramps. We included people with cramps during any activity or condition, including (but not limited to) cramps associated with exercise, haemodialysis, sleep, and neurological conditions. We excluded women with cramps during pregnancy, as this is covered by another Cochrane Review (Zhou 2015).
Types of interventions
We included all non‐drug and non‐invasive interventions used for at least four weeks. These may have included, but were not limited to, muscle stretching, splints, massage, warmth, change in sleeping position, placebo, relaxation, footwear, weight loss, compression garments, neuromuscular electrostimulation, muscle strengthening, regular exercise, and changes to physical activity.
We excluded drug interventions and invasive interventions (including surgery and acupuncture or dry needling). For this review, drug interventions included any intervention taken orally (such as tablets, capsules, tonics), by injection, by rectal or vaginal suppository, or by inhalation. We also excluded topically applied medicines (for example glyceryl trinitrate patches); however, topically applied preparations that are not thought to alter body function directly and independently (such as oils used in massage) were eligible for inclusion. We included multi‐arm trials if they included eligible comparisons, and studies in which all participants received the same drug therapy as 'background therapy'.
We also excluded reflexology, as reflexology was excluded from the original review. We plan to include reflexology, acupuncture, and dry needling in future review updates.
Types of outcome measures
Primary outcomes
Cramp frequency, measured as number of cramps per week
When analysing cramp frequency, we planned to use change from baseline frequency where possible. As frequency data are likely to be skewed, we requested raw data from trial authors to look for zero counts, and to test for normality. Data were analysed as described under Measures of treatment effect.
Secondary outcomes
Adverse events
Cramp pain severity
Cramp duration
Proportion of participants reporting lower limb muscle cramps
Health‐related quality of life
Quality of sleep
Participation in activities of daily living, including physical activity
If we included data from only one study in an analysis, we measured the outcome at the time point used in the original study. If we included data from more than one trial in an analysis, we planned to group the outcomes by the time points 'four weeks to three months', and 'more than three months'. In this instance, we planned the time point 'more than three months' to be the preferred time point reporting primary and secondary outcomes. We planned to standardise all outcome data combined in meta‐analysis to an appropriate follow‐up period, for example, cramps per week after four months, combined with cramps per week after six months.
Search methods for identification of studies
Electronic searches
We searched the following databases on 14 August 2018 and as noted:
the Cochrane Neuromuscular Specialised Register via the Cochrane Register of Studies (CRS‐Web; searched 17 May 2020; Appendix 1);
the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies (CRS‐Web; searched 17 May 2020; Appendix 2);
MEDLINE (1946 to 15 May 2020; Appendix 3);
Embase (1974 to 2020 Week 20; Appendix 4);
the World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch/; Appendix 5; searched 14 August 2018; inaccessible 17 May 2020);
www.clinicaltrials.gov; (17 May 2020; Appendix 6).
We did not search AMED, LILACS, CINAHL or SPORTDiscus.
Searching other resources
We checked the references of included studies for other suitable trials.
Data collection and analysis
Selection of studies
Two authors (FH and HK or SS) independently assessed the titles and abstracts of all trials identified by the search. The same two review authors then independently assessed full‐text copies of potentially relevant studies for inclusion. We did not mask for authorship and results. We resolved disagreements by discussion between FH and HK or SS, and did not require arbitration by a third review author. We sought and followed guidance from Cochrane Neuromuscular regarding the eligibility of six trials for inclusion (Coppin 2005; Aguilar‐Ferrándiz 2013; Aguilar‐Ferrándiz 2014; Holmes 2014; Simó 2015; Atik 2016). We included a PRISMA flow chart to illustrate the study selection process (Moher 2009).
Data extraction and management
Two review authors (FH and SS) independently extracted outcome data. One review author (FH) extracted other data from the published report using a standardised, pilot‐tested form, and a second review author (SS) cross‐checked the data. One author (FH) entered statistical data into Review Manager 5 (RevMan 5; Review Manager 2020), and a second author (VC) checked the data. We contacted the study authors, as necessary, to request missing information or clarifications. Gholizadeh 2017 was published in Farsi; an author (FP) translated it for the review, and extracted the data onto our data extraction form. We were unable to check numerical data against the trial report, as data were not reported as roman numerals.
Assessment of risk of bias in included studies
Two review authors (FH and SS) independently rated risk of bias of the included trials using the following criteria, as described in the Cochrane Handbook of Systematic Reviews of Interventions (Higgins 2011):
sequence generation;
concealment of allocation;
blinding of participants;
blinding of personnel who administered the intervention;
blinding of outcome assessors;
incomplete data;
selective outcome reporting;
other sources of bias, such as ambiguous outcome categories in outcomes measures.
We assigned each 'Risk of bias' criterion a judgement of 'high risk', 'low risk' or 'unclear risk'. ‘Unclear risk’ indicated an unclear or unknown risk of bias; or that an entry was not relevant to the study at hand. We presented results in the 'Risk of bias' table. We generated a ‘Risk of bias' summary figure, using RevMan 5, to present all of the judgements in a cross‐tabulation of study by entry (Review Manager 2020).
Had we had to contact study authors for missing information regarding risk of bias, we planned to ask open‐ended questions to reduce the risk of leading; for example we would have asked the open‐ended question ‘How did you decide which treatment the next participant should receive?’ in preference to ‘Did you conceal the allocation sequence?’. This was not required.
Measures of treatment effect
Where possible, we analysed continuous data using mean differences (MD) and 95% confidence intervals (CI). To pool data derived from different scales measuring the same variable, we planned to calculate standardised mean difference (SMD). This was not required. We analysed count data (for example number of muscle cramps) as continuous data (mean number of cramps per person per week), and considered the likelihood of data being highly skewed because of those reporting no cramps and those reporting many cramps.
Cramp frequency (number of cramps in a given time period) is a form of count data, so were to be analysed as continuous data only if they were normally disturbed. When cramp frequency data were skewed, and there were no zero counts, we would have considered log transformation of the data. Where there were zero counts, the data were not suitable for transformation and subsequent re‐analysis in RevMan 5. In these cases, we reported the results of the analyses as reported in the original publications, and contacted the study author for raw data, so we could use the Mann‐Whitney U test for a sensitivity analysis in SPSS (IBM Corp 2013; Pallant 2007). In future updates of this review, we will analyse cramp frequency using a responder analysis.
Unit of analysis issues
We planned to include cross‐over trials; however, we would have only considered data from the first intervention phase, as clinical trials of interventions for muscle cramps have detected significant carryover effects (particularly for quinine), and the effectiveness of washout periods for interventions for muscle cramps is unknown (Dunn 1993; Jansen 1997; Coppin 2005). Due to the substantial and variable carryover effect of quinine, we excluded studies that discontinued quinine less than three months prior to the study intervention.
We planned to analyse relevant data from multi‐arm studies in a way that avoided 'double‐counting' of participants in shared intervention groups, e.g. by combining groups to create a single pair‐wise comparison, or splitting the ‘shared’ group, as appropriate.
Dealing with missing data
Where available, we planned to extract data from intention‐to‐treat (ITT) analyses. If the original researchers did not conduct ITT analyses and sufficient raw data were available, we planned to complete ITT analyses before entering data into RevMan 5, to limit attrition bias (Review Manager 2020).
Assessment of heterogeneity
We assessed clinical heterogeneity across trials, and if trials were sufficiently clinically homogenous in terms of participants, interventions, and outcomes, we would have included them in meta‐analyses.
If conducting a meta‐analysis, we planned to quantify inter‐trial statistical inconsistency using I² (Higgins 2021). The I² value was to be calculated by: I² = 100%[(Q‐df)/Q] where Q is Cochran's heterogeneity, Chi² statistic and df is the degrees of freedom. The Cochran's Q is determined by summing the squared deviations (SDs) of each trial's estimate from the overall meta‐analytic estimate, and a P value obtained by comparing the statistic with a x² distribution with k ‐ 1 degrees of freedom (where k is the number of trials). We planned to use the following guide to interpret the I² values:
0 to 40% might not be important;
30 to 60% may represent moderate heterogeneity;
50 to 90% may represent substantial heterogeneity;
75 to 100% considerable heterogeneity.
We would have avoided the use of absolute cut‐off values, but would have interpreted I² in relation to the size and direction of effects and strength of evidence for heterogeneity (e.g. P value from the Chi‐squared test, or CI for I²) (Higgins 2021).
Assessment of reporting biases
If we had been able to pool more than 10 trials, we would have created and examined a funnel plot to explore publication bias. We searched clinical trials registries to identify trial protocols, clinical trial registrations, or abstracts indicating the existence of unpublished studies.
Data synthesis
We used RevMan 5 for statistical analyses. We analysed different interventions for lower limb muscle cramps separately. As we did not expect trials to be very similar, we planned to use random‐effects model to incorporate heterogeneous trials in meta‐analysis.
Subgroup analysis and investigation of heterogeneity
Providing sufficient data were available, we planned to conduct subgroup analyses according to cramp type and aetiology, for example, night cramps versus exercise‐associated cramps versus haemodialysis cramps versus cramps in people with neuromuscular disease.
We would have followed the same methodological principles for meta‐analyses of subgroups, as we did for the primary analyses. If meta‐analyses were conducted within multiple subgroups, we planned to compare the magnitude of effect estimates for subgroups informally between groups.
We did not plan to compare the statistical significance of the pooled effect estimates for individual subgroups, as the likely unequal information loading of subgroups would have affected the power to detect effects (Higgins 2021).
Sensitivity analysis
We planned to conduct sensitivity analyses by excluding trials that did not conceal allocation and blind the participants.
If we found that one or more outliers contributed to heterogeneity, and a reason for the outlying result was apparent, we planned to conduct analyses both with and without outlying trials as a component of sensitivity analysis (Higgins 2021).
Where skewed data precluded the analysis of cramp frequency data in RevMan 5, we presented the results from the analysis published in the original study publication, and performed an additional sensitivity analysis using the Mann‐Whitney U test.
Summary of findings and assessment of the certainty of the evidence
We prepared 'Summary of findings' tables for all comparisons for the outcomes cramp frequency, cramp severity, health‐related quality of life, quality of sleep, participation in activities of daily living, proportion of participants experiencing cramp, and adverse events outcomes, using GRADEpro GDT software (GRADEpro GDT).
We used the GRADE approach to grade the certainty of the evidence (Higgins 2021). One review author (FH) used the five GRADE considerations (study limitations, consistency of effect, imprecision, indirectness, and publication bias) to assess the quality of a body of evidence (studies that contributed data for the prespecified outcomes). We used methods and recommendations described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2021). We considered RCTs to provide high certainty evidence if the five factors above were not present to any serious degree, but downgraded the certainty to moderate, low, or very low with the presence of one or more of the factors. We downgraded once if a GRADE consideration was serious, and twice if very serious. We justified all decisions to downgrade the quality of studies in the footnotes, and made comments to aid readers' understanding of the review where necessary.
We documented any changes from the published protocol in the Differences between protocol and review section of the review (Hawke 2010).
Results
Description of studies
Results of the search
The electronic search updates in May 2020 retrieved a total of 1040 new citations (39 from the Cochrane Neuromuscular Specialized Register; 313 from CENTRAL; 220 from MEDLINE; 444 from Embase; and 24 from ClinicalTrials.gov). Of these, we identified 30 as being potentially relevant. We contacted authors of Macias‐Rodriguez 2014 to seek further information about whether participants reported cramps at baseline, in a study published as a conference abstract, but did not receive a reply. We contacted authors of ISRCTN10576209 to ask if all participants reported cramps at baseline, or if randomisation was stratified for cramps, and NCT03864770 to determine if the study was ongoing or if data were available for publication. Responses were received from authors of both registrations. Searching of reference lists of the included trials and online registries did not retrieve any additional potentially relevant trials. The study flow diagram is presented in Figure 1.
1.
Study flow diagram.
Included studies
We included two new trials to this update (Hallegraeff 2012; Gholizadeh 2017). One trial was included in the original review (Coppin 2005). We identified both new trials by electronic searching. Details of all trials are presented in the Characteristics of included studies tables. Gholizadeh 2017 was published in Farsi and translated by FP.
The included studies evaluated interventions for night‐time lower limb cramps in older people (Coppin 2005; Hallegraeff 2012), and for leg cramps in 50 to 60 year‐old women with metabolic syndrome (Gholizadeh 2017). One trial reported receiving external (National Health Service) funding to support the research (Coppin 2005); the other two studies did not report a funding source. One trial was conducted as a component of a Masters degree (Gholizadeh 2017).
Hallegraeff 2012 included 80 people over 55 years of age who had experienced nocturnal leg cramps at least once per week. Coppin 2005 included 94 people 60 years of age or over who in the preceding three months had received a repeat prescription from their general practitioner of quinine for night‐time cramps. Gholizadeh 2017 included 24 women age 50 to 60 years with metabolic syndrome. Hallegraeff 2012 and Coppin 2005 were conducted in the Netherlands and the UK, respectively. Gholizadeh 2017 took place in Iran.
Hallegraeff 2012 compared hamstring and calf stretching with no intervention. Each stretch was held for 10 seconds and repeated three times with 10 seconds of relaxation between each stretch. It is not clear if this set of stretching was conducted more than once per day. In Coppin 2005, each participant was allocated to either a calf stretching or sham stretching group. Calf stretches were completed by leaning into a wall for 10 seconds, repeated once after a five second break, three times per day. After six weeks, participants were told that they could continue the stretching exercises if they wished and also themselves decide whether or not to continue taking quinine sulphate tablets. Participants in the sham stretching group were also given an instruction sheet describing the stretching exercise program. Participants were allocated to one of four groups: (1) advised to discontinue taking quinine sulphate and begin a calf stretching program; (2) advised to discontinue taking quinine sulphate and begin a sham stretching program; (3) advised to continue taking quinine sulphate and begin a calf stretching program; or (4) advised to continue taking quinine sulphate and begin a sham stretching program. No washout period was provided for participants advised to discontinue taking quinine sulphate, which excluded two groups from this review. Published results in Coppin 2005 were only for 1‐, 2‐, and 12‐week follow‐up and there was no separation within the stretching and sham stretching groups of those participants who continued quinine sulphate versus those who discontinued quinine sulphate. This review included only the 97 participants who were advised to continue taking quinine sulphate (those in groups 3 and 4). Of these, 49 were allocated to the stretching group and 48 were allocated to the sham stretching group. No participant was lost to follow‐up, yet, owing to incomplete data, we included only 48 participants from the stretching group and 46 participants from the sham stretching group in the analysis. In an attempt to avoid the confounding effects of changing interventions and to exclude participants who were advised to discontinue taking quinine sulphate, we contacted trial authors to provide six‐week follow‐up data for the participants who were advised to continue taking quinine sulphate in the stretching and sham stretching groups in Coppin 2005. They provided only 12 weeks' follow‐up data for the primary outcome 'number of cramps in the last four weeks'. As cramp frequency data were not normally distributed and log transformation was not appropriate due to the zero counts, we conducted a Mann‐Whitney U test to measure the difference between groups. Gholizadeh 2017 compared calf, hamstring and quadriceps stretching with no intervention. Each stretch was held for 10 to 15 seconds and repeated three to six times, 3 times per day for 6 weeks.
In Hallegraeff 2012, the primary outcome was change in the average number of nocturnal leg cramps per day over a one‐week period after six weeks of intervention. This was assessed in the week prior to starting the six‐week stretching program and again in the final week of the stretching program. As cramp frequency data were not normally distributed and log transformation was not appropriate due to the zero counts, we reported results as in the original study publication and conducted an additional sensitivity analysis using a Mann‐Whitney U test. At baseline, the mean cramp frequency for all participants was 3.3 cramps per day. This is far more than the number of cramps reported at baseline in trials of quinine and magnesium for cramps, in which participants reported about four cramps per week at baseline. We contacted Dr Hallegraeff to check if the outcome was cramps per week rather than cramps per day. Dr Hallegraeff confirmed the outcome was cramps per day and suggested the cramp high frequency rate may be due to a selection bias resulting from the use of an advertising appeal to recruit community members to participate, through which people with more frequent cramps may have been more likely to respond to their advertisement. Some uncertainty remains over the number of cramps reported by participants in the study. This is particularly troublesome as cramps were not defined in the published report.
The secondary outcome was the severity of nocturnal leg cramps, measured using a 10 cm visual analogue scale (VAS) with 0 cm representing no pain and 10 cm representing the worst pain the participant could imagine. Recordings were again made in the daily diary over the same one‐week periods.
Outcomes in Gholizadeh 2017 eligible for inclusion in this systematic review were frequency and severity of muscle cramps. Outcomes were assessed in the week prior to starting the six‐week stretching program and again after the final week of the stretching program. Cramp frequency was recorded as participant self‐reported number of cramps in the past week. As cramp frequency data are count data, and are likely to not be normally distributed, we contacted the authors requesting raw data to perform a Mann‐Whitney U test as per protocol but did not receive a response from the authors. Cramp severity was also by retrospective self‐report, using a 0‐10 VAS to indicate the average pain of their cramps in the last week (0 = no pain, 10 = worst cramp). As the standard scale upper anchor was changed from 'worst pain imaginable' to 'worst cramp', this is not a validated tool.
No study reported health‐related quality of life, quality of sleep, or participation in activities of daily living outcomes. All three studies stated whether participants reported adverse events.
Detailed information about participant eligibility criteria and interventions for all studies are in the table Characteristics of included studies.
Excluded studies
We excluded 28 of the potentially relevant trials after reading the full‐text reports. Reasons for exclusion were:
not all participants reported cramps at baseline, and randomisation was not stratified for cramps (Aguilar‐Ferrándiz 2013; Aguilar‐Ferrándiz 2014; Holmes 2014; Simó 2015; Atik 2016; ISRCTN10576209);
presence of lower limb cramps was not measured at baseline (Dodd 2011; Abdel‐Aziem 2010; Kudo 2013; Leung 2014; Maas 2014; Backus 2016; Sung 2016);
intervention duration was less than four weeks (Mastnardo 2016);
intervention was drug therapy (Hidaka 2012; Sebo 2014; Supakatisant 2015; Mansouri 2017; Maor 2017);
intervention was reflexology (Ozdemir 2013);
trials were not randomised or controlled clinical trials (as defined by Higgins 2011; (Nishant 2014; Atik 2016B));
cramps were in pregnant women (Beyaz 2011; Fard 2016); or
the trial was a laboratory study of cramp susceptibility (Jung 2005; Behringer 2015).
For one study, we received no response from study authors for clarification as to whether lower limb cramp was an outcome, so we excluded the study (Macias‐Rodriguez 2014). Details of individual excluded trials are presented in the table Characteristics of excluded studies.
Risk of bias in included studies
Assessment of risk of bias for all included studies is described in the 'Characteristics of included studies' table and is summarised in Figure 2.
2.
Risk of bias summary: review authors' judgements about each 'Risk of bias' item for each included study
Allocation
Coppin 2005 and Hallegraeff 2012 adequately reported generation of a randomisation sequence and allocation concealment. In Gholizadeh 2017, randomisation was accomplished by taking participant names out of a box; the first 12 names were placed in the control group. This is a predictable rather than a random sequence, so we deemed the risk of bias as unclear. As trialists had access to the names as they were drawn from the box, and allocation was not therefore secure, we deemed the risk of bias from the method of allocation concealment as high.
Blinding
In all studies, personnel who administered the interventions were aware of group assignment. This was due to the physical nature of the interventions, and placed all studies at high risk of performance bias.
In Coppin 2005, participants were blinded to their group assignment by comparing the stretching intervention to sham stretching. In Gholizadeh 2017 and Hallegraeff 2012, the experimental stretching was compared to no intervention.
As participants self‐assessed the presence and severity of cramps, only Coppin 2005, which blinded participants, was able to blind outcome assessors for cramp outcomes, and therefore, we determined it was at low risk of detection bias.
Incomplete outcome data
We judged risk of attrition bias as unclear for one study (Coppin 2005). In the 12‐week data provided by the trial authors, data were missing for one participant from the intervention group and two participants from the control group, with no reasons provided for missing data; therefore, we judged the risk of attrition bias as unclear.
For the other two studies, all participants completed the study.
Selective reporting
Gholizadeh 2017 and Hallegraeff 2012 do not refer to a published study protocol, so we judged the risk of reporting bias as unclear. We judged Coppin 2005 at high risk of reporting bias, as the trial registration stated that outcomes would include duration of leg cramps and subsequent general practitioner attendance, but the published paper did not provide data for these outcomes.
Other potential sources of bias
We identified high risk of recall bias in two studies (Coppin 2005; Gholizadeh 2017). In Coppin 2005, participants were asked, after 12 weeks, to recall how many night cramps they had experienced in the preceding four weeks. In Gholizadeh 2017, participants were asked to recall the frequency of cramps in the preceding week, and to state the average pain severity of these cramps. These outcomes have a high risk of recall bias. This source of bias was avoided in Hallegraeff 2012, through the use of a daily diary.
Effects of interventions
See: Table 1; Table 2; Table 3
We did not conduct a meta‐analysis because of differences in interventions and outcomes between studies.
Hamstring and calf stretching versus sham stretching
One study (N = 80) Investigated hamstring and calf stretching in older adults (Hallegraeff 2012).
Primary outcome
Cramp frequency
Hallegraeff 2012 compared the mean number of cramps per night in 40 older adults advised to perform hamstring and calf stretching daily and 40 older adults who received no intervention. In the study publication, cramp frequency was analysed parametrically, as the change in number of cramps per night from week zero to week six within each group. The certainty of evidence was very low for the comparison of cramp frequency in the stretching group (mean −2.0, standard deviation (SD) 1.3) and the no intervention group (mean −0.8, SD 1.3); the between group mean difference (MD) was −1.2, 95% CI −1.8 to −0.6; 80 participants; very low‐certainty evidence). The mean (SD) frequency of night‐time leg cramps in the stretching group at the end of the study was 1.4 (1.4) cramps per night.
Individual participant data were available as an eAddendum through the Journal of Physiotherapy. These data were analysed non‐parametrically for sensitivity analysis in this review. The Mann‐Whitney U test found participants in the stretching group (Md 1, IQR 1.75; 40 participants) had fewer cramps per night than those in the control group (Md 2, IQR 3; 40 participants) (U = 489; z = ‐3.089; P = 0.002; r = 0.35). A statistical report of this analysis is available on request to Fiona Hawke.
We judged the certainty of the evidence to be very low, as the confidence interval (CI) from the original publication spanned results that would lead to differing clinical decisions, participants were not blinded, and it was unclear if all outcomes were reported. See Table 1.
Secondary outcomes
Adverse events
No participant reported adverse events (80 participants; moderate‐certainty evidence). We judged the certainty of the evidence to be moderate, as other included studies of similar stretching interventions also reported no adverse effects, yet the study may be too small to detect uncommon, yet important, adverse effects. See Table 1
Cramp pain severity
Hallegraeff 2012 measured cramp pain severity on a 10 cm VAS (0 cm = no pain; 10 cm = worst pain imaginable) in 50 older adults advised to complete hamstring and calf stretching daily, and 50 older adults who received no intervention. After six weeks, the results indicated that there may be a greater reduction in cramp pain severity in the stretching group (mean −1.3, SD 1.1) than in the no intervention group (mean 0.0, SD 0.9) (mean difference (MD) −1.30, 95% CI −1.74 to −0.86; 80 participants; low‐certainty evidence; Analysis 1.1). We judged the certainty of the evidence to be low, as participants were not blinded, and it was unclear if all outcomes were reported. See Table 1.
1.1. Analysis.
Comparison 1: Calf and hamstring stretching versus no intervention for lower limb muscle cramps, Outcome 1: Change in cramp severity after 6 weeks (0 to 10; higher = worse pain)
Cramp duration
Not measured
Proportion of participants reporting lower limb muscle cramps
Not measured
Health‐related quality of life
Not measured
Quality of sleep
Not measured
Participation in activities of daily living, including physical activity
Not measured
Calf stretching versus sham stretching
One study Investigated calf stretching in older adults with night‐time cramps (Coppin 2005),
Primary outcome
Cramp frequency
Coppin 2005 compared the recalled number of cramps in the final four weeks of the 12‐week intervention period between 48 adults advised to complete daily calf stretching, and 46 participants advised to complete daily sham stretching. Sham stretches are described in the 'Characteristics of included studies' table. We think it is unlikely that the sham stretches would have affected cramp frequency or severity. Authors of Coppin 2005 provided individual participant data for analyses. As this review includes only selected participants from Coppin 2005, and no analysis reported in the original publication is suitable for reproducing here, we reported the Mann‐Whitney U test as the primary analysis, which we had intended to conduct as a sensitivity analysis. A Mann‐Whitney U test indicated that stretching may make little to no difference to the median number of cramps in the last four weeks (stretching group median (Md) 4, interquartile range (IQR) 8, 48 participants; sham stretching group Md 3, IQR 7.63, 46 participants) (U = 973.5; z = −0.995; P = 0.32; r = 0.10). We judged the certainty of the evidence to be low, as not all outcomes were reported, it is unclear if there was risk of attrition bias, and the outcome measure was at risk of recall bias. See Table 2.
Secondary outcomes
Adverse events
There were no 'significant' adverse effects reported (94 participants; very low‐certainty evidence). The trial authors did not provide a definition of 'significant' adverse effects. We judged the certainty of the evidence to be very low, as other included studies of similar stretching interventions also reported no adverse effects, the definition of significant adverse effects was unclear, it was unclear if there was attrition bias, and the study may be too small to detect uncommon, yet important adverse effects. See Table 2.
Cramp pain severity
Not measured
Cramp duration
Duration of leg cramps, although a planned outcome in the study protocol, was not reported.
Proportion of participants reporting lower limb muscle cramps
Not measured
Health‐related quality of life
Not measured
Quality of sleep
Not measured
Participation in activities of daily living, including physical activity
Not measured
Hamstring, quadriceps, and calf stretching versus no intervention
One study investigated the effects of stretching on cramps in 50 to 60 year‐old women with metabolic syndrome (Gholizadeh 2017).
Primary outcome
Cramp frequency
Gholizadeh 2017 compared the mean (SD) number of cramps per week between 12 women advised to complete hamstring, quadriceps, and calf stretching daily, and 12 women who received no intervention. Due to the small number of participants, and because frequency data are often not parametric due to zero counts, our preference was to analyse frequency data non‐parametrically for this review. This was not possible using data reported in the published paper, and the trial authors did not respond to our request for data. The evidence for cramp frequency was very uncertain. In the published report, the mean (SD) number of cramps per week after six weeks of intervention was 1.83 (0.83) in the stretching group and 2.58 (0.79) in the no intervention group. We analysed the results as continuous data in RevMan 5 comparing reported cramps among women in the stretching group and those in the no intervention group (MD −0.75, 95% CI −1.40 to −0.10; 24 participants; very low‐certainty evidence; Analysis 2.1). We judged the certainty of the evidence to be very low as, although data were non‐parametric, we analysed them parametrically, the outcome measure was not validated and was subject to recall bias, the size of the study was small, participants were not blinded, and it was unclear if all outcomes were reported. See Table 3.
2.1. Analysis.
Comparison 2: Calf, quadriceps, and hamstring stretching versus no intervention for leg cramps, Outcome 1: Cramp frequency after 6 weeks
Secondary outcomes
Adverse events
Study authors reported that none of the women reported adverse events (24 participants, moderate‐certainty evidence). We judged the certainty of the evidence to be moderate, as other included studies of similar stretching interventions also reported no adverse effects, yet the study may be too small to detect uncommon, yet important, adverse effects. See Table 3.
Cramp pain severity
Gholizadeh 2017 measured cramp pain severity on a 0 to 10 VAS (0 = no pain, 10 = worst cramp) in 12 women advised to complete hamstring, quadriceps, and calf stretching daily, and 12 women who received no intervention. The evidence on cramp severity after six weeks for women in the stretching group compared to women who received no intervention was very uncertain (MD −3.42, 95% CI −4.33 to −2.51; 24 participants; very low‐certainty evidence; Analysis 2.2). We judged the certainty of the evidence to be very low, as the outcome measure is not validated and is subject to recall bias, the participants were not blinded, the study size is small and it is unclear if all outcomes were reported. See Table 3.
2.2. Analysis.
Comparison 2: Calf, quadriceps, and hamstring stretching versus no intervention for leg cramps, Outcome 2: Cramp severity after 6 weeks
Cramp duration
Not measured
Proportion of participants reporting lower limb muscle cramps
Not measured
Health‐related quality of life
Not measured
Quality of sleep
Not measured
Participation in activities of daily living, including physical activity
Not measured
Discussion
Summary of main results
This review update includes three studies (201 participants). These studies evaluated interventions for night‐time lower limb muscle cramps in older people and leg cramps in women age 50 to 60 years with metabolic syndrome. Cramps were the primary outcome in both studies that recruited older adults (Coppin 2005; Hallegraeff 2012), but not in the study involving women with metabolic syndrome (Gholizadeh 2017).
Results indicated that a combination of calf and hamstring stretching may reduce the severity of night‐time cramps over 6 weeks in people 55 years of age and over, when compared to no intervention (Table 1). At the end of the study, participants in the stretching group reported a mean 1.4 (SD 1.4) cramps per night, which leaves room for improvement. The certainty of evidence for cramp frequency was very low.
A study comparing lean‐to‐wall calf stretching to sham (fake) stretching in people over 60 years of age who have also been taking quinine sulphate for their muscle cramps did not measure cramp severity. Lean‐to‐wall calf muscle stretching held for 10 seconds three times per day may not reduce frequency of night‐time cramps (of unspecified muscles) after 12 weeks (Table 2).
The evidence is very uncertain about the effects of a combination of daily calf, quadriceps, and hamstring stretching on the frequency and severity of leg cramps in 50‐ to 60‐year‐old women with metabolic syndrome. At the end of the study, participants in the stretching group reported a mean 1.83 (SD 0.83) cramps per week (Table 3).
Studies did not measure health‐related quality of life, quality of sleep, or participation in activities of daily living.
No participant in these three studies reported adverse events. The adverse event evidence was of moderate certainty as the studies were too small to detect uncommon events.
Overall completeness and applicability of evidence
When this review was first published in 2012, it included only one paper (Coppin 2005). We added two more papers in this update (Gholizadeh 2017; Hallegraeff 2012). Some types of lower limb muscle cramps, and many commonly used interventions have yet to be evaluated in randomised trials.
Randomised trials have yet to evaluate the effects of non‐drug, non‐invasive interventions for lower limb muscle cramps associated with exercise or neurological disease. No study has included anyone less than 50 years of age. As lower limb muscle cramps can have a profound impact on people with neurological disease, including children, this should be a priority for future research (Burns 2010; Blyton 2011).
Non‐drug therapies yet to be evaluated include neuromuscular electrostimulation, muscle strengthening, massage, avoiding physical fatigue and indolence, maintaining warm lower limb temperature throughout the night, night ankle dorsiflexion splints, footwear changes (for example, high heel avoidance), and changes to sleeping and sitting positions.
No study measured the impact of non‐drug therapy for lower limb muscle cramps on health‐related quality of life, quality of sleep, or participation in activities of daily living. No study reported the particular lower limb muscles that cramped. This limits the completeness of the evidence, as cramps in some muscles may respond to particular interventions more than cramps in other muscles.
The applicability of some of the evidence that is available is severely limited by deficiencies in study design.
Certainty of the evidence
See Table 1, Table 2, and Table 3.
Certainty of evidence presented in this review ranges from very low (cramp frequency and severity) to moderate (adverse effects). For all comparisons, only a single study contributes evidence. Due to limitations in study design that create risks of bias, and due to some broad CIs which make findings imprecise, we cannot be certain that findings of future studies will be similar to those presented in this review. We also note that the intervention ‘dosage’ may not have been optimal, although not to the extent that we downgraded the evidence for indirectness. We downgraded evidence from a study in women with metabolic syndrome for indirectness due to use of a non‐validated scale. We found no clear evidence of unpublished, completed studies of non‐drug treatments for cramps.
Coppin 2005 estimated a minimum sample size of 128 participants with complete outcomes to detect a reduction of three to four cramps in 4 weeks. As this review excludes those participants who were advised to stop taking quinine at the start of the trial, the analysis in this review of data from the remaining 94 participants with complete outcomes in Coppin 2005 may be underpowered to detect a clinically important effect. Based on the results of Coppin 2005, however, Hallegraeff 2012 estimated a minimum sample size of 32 participants per group, which Hallegraeff 2012 achieved. However, for frequency of night‐time cramps the confidence interval (CI) spanned results that would lead to differing clinical decisions (Hallegraeff 2012).
Gholizadeh 2017 did not report a power calculation. Considering the power calculations performed by Coppin 2005 and Hallegraeff 2012, we are confident that the 12 participants per group in Gholizadeh 2017 would not be sufficient to detect a clinically important effect.
In Hallegraeff 2012, which compared calf and hamstring stretching with no intervention, participants were not blinded, and it is unclear if all outcomes were reported (Table 1). Of the included studies, this study was at lowest risk of recall bias. This was achieved by using a daily diary, in which participants recorded the number of cramps per day and cramp severity on a 10 cm visual analogue scale (VAS). However, as participants were not blinded to their group allocation, some of the benefit detected might be due to placebo effect.
Lean‐to‐wall calf muscle stretching was compared with sham stretching for night‐time cramps over 12 weeks in people aged 60 years and over in Coppin 2005. Certainty of evidence is low as not all outcomes were reported, it is unclear if there is risk of attrition bias, and the outcome measure is at risk of recall bias (Table 2). After six weeks, participants in both the stretching and sham stretching groups were allowed to swap or discontinue stretching treatments and to decide for themselves whether or not to continue taking quinine sulphate. As we included only those participants who were advised at baseline to continue taking quinine sulphate, no published data were suitable for use in analysis and trial authors provided only 12‐week follow‐up data when contacted. It is not known how many participants in the stretching and sham stretching groups included in this review swapped or discontinued stretching exercises, or discontinued taking quinine sulphate after six weeks. This study design does not reflect clinical practice and seriously limits interpretation as it is impossible to isolate the effect of the intervention assigned at baseline.
The inclusion criteria in Coppin 2005 did not address if the participants experienced cramps at baseline or addressed the location of the night‐time cramps. While night‐time cramps often affect the calf muscle, other muscles of the lower limb and upper limb muscles can be affected. The location of cramp is important in this study, as the intervention was a stretching program targeting calf muscles only. At the 12‐week follow‐up, participants were asked in a postal survey how many cramps they had experienced in the last four weeks. This outcome is subject to recall bias. The outcome also does not focus on the number of calf muscle cramps experienced. As the stretching interventions targeted only the calf muscles, the effect of calf muscle stretching on calf muscle cramps is an important, yet unaddressed, component of the outcome measure. There are no data available on the severity of cramps experienced. This is an important outcome in trials of interventions for muscle cramps, as it is possible that the severity of cramps may reduce without a notable reduction in cramp frequency.
For the comparison of calf, quadriceps and hamstring stretching compared with no intervention for leg cramps in women age 50 to 60 years with metabolic syndrome, the outcomes are subject to recall bias, participants (who assessed outcomes) were not blinded, and it is unclear if all outcomes were reported. In addition, frequency data may be non‐parametric yet have been analysed parametrically (Gholizadeh 2017).
Duration of individual stretches recommended in the three studies ranged from 10 to 15 seconds. This may be shorter than what is routinely recommended in clinical practice by many health professionals. In a study to determine optimum stretch duration in people over 65 years of age, Feland and colleagues demonstrated that the longest hamstring stretch hold time (60 seconds, compared to 30 seconds, 15 seconds and no stretching) resulted in a greatest gains in range of motion and the most sustained increase in range of motion (Feland 2001).
The stretches prescribed in Coppin 2005 may also be less intense than those routinely recommended in clinical practice, as stretches were performed for both legs at the same time. As discussed above, calf muscle stretching was advised for participants regardless of the location of their night‐time muscle cramp. This may not reflect standard clinical practice, where stretching therapies may target the affected muscles, or indeed the implicated neural pathway.
Potential biases in the review process
We searched without language restriction, for published and unpublished studies. One included paper was published in Farsi and translated for this review. Only one review author extracted data from this study, which poses a risk of bias. We identified one ongoing study that will be eligible for inclusion once completed (NCT03864770). Authors of that study responded to our correspondence, but were not in a position to provide data at that time. Authors of one other study, which investigated use of a physical exercise program in people with cirrhosis of the liver, published only as a conference abstract, did not respond to emails asking if muscle cramps were an outcome, so we excluded the study (Macias‐Rodriguez 2014). No unpublished study is included in this review, yet there is no clear evidence of a publication bias.
Agreements and disagreements with other studies or reviews
The Cochrane Review 'Interventions for leg cramps in pregnancy' assesses the effectiveness and safety of different interventions for treating leg cramps in pregnancy (Zhou 2015). To prevent overlap, and because the mechanism is potentially distinct, all trials evaluating interventions for leg cramps in pregnancy were excluded from the current review. The authors of Zhou 2015 found no trials that evaluated non‐drug therapies for lower limb muscle cramp. As in the current review, Zhou 2015 was unable to conduct a meta‐analysis due to inconsistencies in outcome measurement and reporting, noted limitations in study design and size; they called for standardised measures to assess the frequency, intensity, and duration of leg cramps, and for more trials of non‐drug therapies.
All other Cochrane Reviews of interventions for muscle cramps focused on drug therapies (magnesium in Garrison 2020; quinine in El‐Tawil 2015; all drug therapies for cramps in amyotrophic lateral sclerosis and motor neuron disease in Baldinger 2012).
To our knowledge, no other systematic reviews of non‐drug therapies for lower limb muscle cramps have been conducted.
Authors' conclusions
Implications for practice.
A combination of daily calf and hamstring stretching may reduce the severity of night‐time lower limb muscle cramps in people aged 55 years and older, but the effect on cramp frequency is uncertain, as the quality of the evidence is very low. Calf stretching alone may not be effective for reducing the frequency of night‐time lower limb muscle cramps in people aged 60 years and older, although limitations in the study's design impede interpretation of the results and clinical applicability. It is also uncertain whether a combination of daily calf, quadriceps, and hamstring stretching reduces the frequency and severity of leg cramps in 50‐ to 60‐year‐old women with metabolic syndrome, as the quality of the evidence is very low, with serious imitations in the study's design that erode our confidence in the results. Overall, the lack of uniform diagnostic criteria and outcome measures make it difficult to compare the studies.
Implications for research.
This review highlighted the need for rigorously designed randomised trials to evaluate the effectiveness of non‐drug therapies for lower limb muscle cramps. Future research should explore the effectiveness of the wide range of the available and emerging non‐drug therapies for cramps associated with exercise, haemodialysis, sleep, and neurological conditions. Researchers should consider comparing stretches to sham stretches in future studies. Published reports of future trials should include high quality descriptions of all aspects of methodology (including cramp definition) to enable appraisal and comparison to similar studies.
Researchers should develop and validate an outcome measure (including clinically important effects) for lower limb muscle cramps, and consider including measures of health‐related quality of life and quality of sleep in future clinical trials. Outcomes should at least include cramp location, severity, and frequency; measures of frequency should not rely on participants' retrospectively recalling the number of cramps experienced over a period of time. More research is required to determine clinically important differences for people who experience night‐time muscle cramps, to improve power calculations in future research.
In particular, hamstring, quadriceps, and calf stretching should be evaluated in people with neurological disease (including Charcot‐Marie‐Tooth disease) and for exercise‐associated lower limb cramps. Longer duration of stretching, and the addition of other therapies may further reduce cramp frequency and severity.
What's new
| Date | Event | Description |
|---|---|---|
| 22 June 2020 | New citation required but conclusions have not changed | Methods amended to:
We changed the title from Non‐drug therapies for lower limb muscle cramps to Non‐drug therapies for the secondary prevention of lower limb muscle cramps, to make it clear that the review does not include treatment of acute cramps. Sadler SG, Katzberg HD, and Pourkazemi F replaced Kate Walker as authors for this update. |
| 17 May 2020 | New search has been performed | Literature search updated; two new studies included (Gholizadeh 2017; Hallegraeff 2012) |
History
Protocol first published: Issue 4, 2010 Review first published: Issue 1, 2012
Acknowledgements
We thank Dr Richard Coppin and Professor Paul Little for providing raw data for use in this review, and Francoise Schyns, Professor Deirdre Walsh, Dr Ralf Wojke, and Professor Michel Vayssairat for responding to requests for additional information about their research to determine eligibility for inclusion.
We thank the editorial team of Cochrane Neuromuscular, particularly Ruth Brassington for her kind assistance, and Angela Gunn and Farhad Shokraneh for running database searches.
Peer reviewers of this update were: Magdalena Maria Dudziec, Kingston University, UK; Scott Garrison, University of Alberta, Canada; Joannes Hallegraeff, SOMT University of Physiotherapy, Amersfoort, Netherlands; Sarah Nevitt (Cochrane Neuromuscular Statistical Editor), University of Liverpool, UK; and Janet Wale, Australia.
This project was supported by the National Institute for Health Research via Cochrane Infrastructure funding to Cochrane Neuromuscular. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS or the Department of Health. Cochrane Neuromuscular is also supported by the MRC Centre for Neuromuscular Disease and the Motor Neuron Disease Association.
We thank Mrs Kate Walter for her work on earlier versions of the review.
Appendices
Appendix 1. Cochrane Neuromuscular Specialised Register CRS‐Web search strategy
#1 cramp* or spasm* or contracture or eamc AND INREGISTER 220
#2 "charley horse*" or "charlie horse*" AND INREGISTER 0
#3 #1 OR #2 AND INREGISTER 220
#4 leg OR legs or calf or foot or feet or thigh or thighs or hamstring* or gastrocnemius or quadricep* AND INREGISTER 855
#5 "lower limb*" or "lower extremit*" AND INREGISTER 254
#6 #4 or #5 AND INREGISTER 981
#7 #3 and #6 AND INREGISTER 75
#8 #3 and #6 AND NOTINCENTRAL 3
Appendix 2. CENTRAL CRS‐Web search strategy
#1 cramp* or spasm* or contracture or eamc AND CENTRAL:TARGET 8006
#2 "charley horse*" or "charlie horse*" AND CENTRAL:TARGET 0
#3 #1 OR #2 8006
#4 leg OR legs or calf or foot or feet or thigh or thighs or hamstring* or gastrocnemius or quadricep* AND CENTRAL:TARGET 44211
#5 "lower limb*" or "lower extremit*" AND CENTRAL:TARGET 14493
#6 #4 or #5 52207
#7 #3 and #6 880
#8 2018* OR 2019 OR 202* AND CENTRAL:TARGET 256014
#9 #7 AND #8 144
Appendix 3. MEDLINE Ovid search strategy
Database: Ovid MEDLINE(R) ALL <1946 to May 15, 2020>
Search Strategy:
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
1 randomized controlled trial.pt. (505645)
2 controlled clinical trial.pt. (93673)
3 randomized.ab. (479316)
4 placebo.ab. (207697)
5 randomly.ab. (333026)
6 trial.ab. (505098)
7 groups.ab. (2044798)
8 or/1‐7 (2948834)
9 exp animals/ not humans.sh. (4698942)
10 8 not 9 (2508573)
11 (cramp$3 or spasm$ or contracture or eamc).mp. (65994)
12 (charley horse$ or charlie horse$).mp. (9)
13 11 or 12 (65998)
14 (leg$1 or calf or foot or feet or thigh$ or hamstring$ or gastrocnemius or quadricep$).mp. (395584)
15 (lower limb$ or lower extremit$).mp. (106038)
16 14 or 15 (458424)
17 10 and 13 and 16 (609)
18 remove duplicates from 17 (603)
19 (201808* or 201809* or 201810* or 201811* or 201812* or 2019* or 202*).dc,dp,dt,ed,ep,ez,yr. (3157638)
20 18 and 19 (80)
Appendix 4. Embase Ovid search strategy
Database: Embase <1974 to 2020 Week 20>
Search Strategy:
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
1 crossover‐procedure.sh. (63087)
2 double‐blind procedure.sh. (172275)
3 single‐blind procedure.sh. (38871)
4 randomized controlled trial.sh. (602804)
5 (random$ or crossover$ or cross over$ or placebo$ or (doubl$ adj blind$) or allocat$).tw,ot. (1773798)
6 trial.ti. (298627)
7 or/1‐6 (1958207)
8 (animal/ or nonhuman/ or animal experiment/) and human/ (1966497)
9 animal/ or nonanimal/ or animal experiment/ (3965224)
10 9 not 8 (3292044)
11 7 not 10 (1796203)
12 (article in press or conference abstract or embase or inprocess).st. (25609027)
13 11 and 12 (1499439)
14 (cramp$3 or spasm or spasms or contracture or eamc or charley horse$ or charlie horse$).mp. (103767)
15 (leg$1 or calf or foot or feet or thigh$ or hamstring$ or gastrocnemius or quadricep$).mp. (547315)
16 (lower limb$ or lower extremit$).mp. (145173)
17 15 or 16 (610605)
18 13 and 14 and 17 (1205)
19 remove duplicates from 18 (1197)
20 (201808* or 201809* or 201810* or 201811* or 201812* or 2019* or 202*).ce,cs,dc,dd. or (Aug 2018 or Sep 2018 or Oct 2018 or Nov 2018 or Dec 2018 or 2018* or Jan 2019 or Feb 2019 or Mar 2019 or Apr 2019 or May 2019 or Jun 2019 or Jul 2019 or Aug 2019 or Sep 2019 or Oct 2019 or Nov 2019 or Dec 2019 or 2019* or Jan 202* or Feb 202* or Mar 202* or Apr 202* or May 202* or 202*).dp. (3507241)
21 19 and 20 (100)
Appendix 5. WHO International Clinical Trials Registry Platform
This source was not available for search on 17 May 2020.
(Muscle Cramp OR Contracture) AND (Leg OR Calf OR Foot OR Thigh OR Hamstring OR Gastrocnemius OR Quadricep OR Lower Limb OR Lower Extremities) in the Condition
Recruitment status is ALL
Appendix 6. ClinicalTrials.gov search
Advanced Search
Condition or disease: (Muscle Cramp OR Contracture) AND (Leg OR Calf OR Foot OR Thigh OR Hamstring OR Gastrocnemius OR Quadricep OR Lower Limb OR Lower Extremities)
Study type: Interventional Studies (Clinical Trials)
24 Studies
Data and analyses
Comparison 1. Calf and hamstring stretching versus no intervention for lower limb muscle cramps.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1.1 Change in cramp severity after 6 weeks (0 to 10; higher = worse pain) | 1 | 80 | Mean Difference (IV, Fixed, 95% CI) | ‐1.30 [‐1.74, ‐0.86] |
Comparison 2. Calf, quadriceps, and hamstring stretching versus no intervention for leg cramps.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 2.1 Cramp frequency after 6 weeks | 1 | 24 | Mean Difference (IV, Fixed, 95% CI) | ‐0.75 [‐1.40, ‐0.10] |
| 2.2 Cramp severity after 6 weeks | 1 | 24 | Mean Difference (IV, Fixed, 95% CI) | ‐3.42 [‐4.33, ‐2.51] |
Characteristics of studies
Characteristics of included studies [ordered by study ID]
Coppin 2005.
| Study characteristics | ||
| Methods | Factorial design randomised control trial for the first 6 weeks. After 6 weeks, participants were told that they could continue the exercises if they wished, and also decide themselves whether or not to continue, or resume taking quinine tablets. | |
| Participants | Participants were recruited through 28 general practices in southern England. Database searching at each practice identified potential participants, who were then contacted by letter. Inclusion criteria: people aged 60 years and over who had been given a repeat prescription by their GP of quinine for nocturnal (night) cramps in the previous 3 months. Cramp was not defined in the published report. Exclusion criteria: people with conditions significantly limiting their ability to undertake the stretching exercises (for example, severe osteoarthritis); leg pain that might be confused with cramp (e.g. severe peripheral vascular disease); inability to reliably report on symptoms (e.g. dementia); and people who described being previously taught leg exercises aimed at preventing cramps. This review includes only the 97 participants who were advised to continue taking quinine. Of these participants, 49 (51%) were male, the mean age was 74.3 years (standard error of the mean (SEM 0.6)), and at baseline, the recalled number of cramps in the previous 4 weeks was 10.4 (SEM 1.76). |
|
| Interventions | Participants were given advice to either continue or discontinue taking quinine tablets (this review only includes data from participants who were allocated to continue quinine use) and to undertake a daily programme of either stretching or sham exercises, for which they received training. The sham exercise was devised to be of comparable duration and simplicity to the intervention stretching exercise, but was passive and involved negligible stretching of the muscles of the calf and foot. An attempt was made to minimise intervention contamination by terming the stretching as 'standing' and sham exercises as 'lying' exercises. Participants were then shown how to complete a 6‐week diary record. Participants were also given an instruction sheet describing the exercise programme and confirming the advice. One week later, the nurse telephoned the participant to check that they were coping with the diary recording; intervention advice was not repeated. Stretching (N = 48) For the stretching exercise, the nurse gave participants the following instruction, "First remove your shoes, then stand facing a wall 2 to 3 feet away, so that the tips of your fingers are just touching the wall. Lean forward, keeping your heels in contact with the floor, keep your body straight and use your arms to control your forward tilt until you feel a moderately intense, but not painful, 'pulling sensation' in your calf muscles. This stretching position should be held for 10 seconds (count 1 elephant, 2 elephants, etc). Stand upright and relax for 5 seconds, then repeat the stretch for a further 10 seconds. Carry out this sequence three times spread through each day". Sham stretching (N = 46) For the non‐stretching exercise, the nurse advised participants as follows; "First, lie face up on your bed or on the floor, so that your legs are out straight. Gently bend your knees up and move them towards your chest, keeping your feet flat on the bed or floor. When your feet are as near your bottom as you can get them without causing discomfort, hold that position for 10 seconds (count 1 elephant, 2 elephants, etc.). Straighten your legs out and relax for 5 seconds, then repeat the exercise for a further 10 seconds. Carry out this sequence three times spread through each day". |
|
| Outcomes | A 6‐week diary was used by participants to record daily cramp symptoms (presumably number of cramps per day), intervention compliance, and weekly symptom burden scores. Symptom burden scores were calculated using the mean of three Likert scale scores assessing ‘disrupted activity’, ‘sleep
quality’ (sleep disturbance is a recognised consequence of night cramps), and ‘overall problems with cramp in the past week’ — all reported on a seven‐point Likert scale following the same format as the MYMOP (Measure Yourself Medical Outcome Profile). Six‐week data were not reported in the published study. It is not clear from the published report methods whether adverse effects were measures formally as an outcome. The online protocol (ISRCTN26051665) states that outcomes would include duration of leg cramps and subsequent GP attendance. Data for these outcomes are not provided in the published paper. Outcomes not eligible for inclusion in this review: All 12 week outcomes data were not eligible for inclusion, as, after six weeks, participants were told that they could continue the stretching exercises if they wished and also themselves decide whether or not to continue taking quinine sulphate tablets. 12 week outcome data were: symptom burden score; number of night cramps in previous 4 weeks; problems with cramps; number of quinine tablets used in the previous week; number of patients stopping quinine treatment. Note: In an attempt to avoid the confounding effects of changing interventions and to exclude participants who were advised to discontinue taking quinine sulphate, we contacted trial authors to provide six‐week follow‐up data for the participants who were advised to continue taking quinine sulphate in the stretching and sham stretching groups. They provided only 12 weeks' follow‐up data for the primary outcome 'number of cramps in the last four weeks'. |
|
| Funding | NHS Executive SE Project Grant SPGS787/SW | |
| Conflicts of interest | Authors declared no conflicts of interest. | |
| Date study conducted | Data collected between January 1999 and September 2001 | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "Randomised by the research assistant using random number tables" |
| Allocation concealment (selection bias) | Low risk | "Randomisation to the trial took place when the nurse opened a sealed, numbered, opaque envelope containing intervention instructions" |
| Blinding of participants (performance bias) | Low risk | Quote: "The placebo exercise was devised to be of comparable duration and simplicity to the intervention stretching exercise, but was passive and involved negligible stretching of the muscles of the calf and foot. We sought to minimise intervention contamination by terming the stretching and placebo exercises as 'standing' and 'lying' exercises, respectively." "By 12 weeks, people performed the exercises 3 to 4 times per week, and although the non‐stretch group did them slightly more frequently, this was not significant (placebo = 3.79 times per week, stretch = 3.07 times per week, t = 1.71; P = 0.09)." Comment: this may indicate successful blinding. However, after 6 weeks of intervention, participants could choose whether to continue their allocated placebo/stretching exercises, or to swap to placebo/stretching exercises of the other group. It is not clear how many people swapped exercises. |
| Blinding of personnel who administered the intervention (performance bias) | High risk | Not blinded do to the nature of the intervention. |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | 12‐week data included in this review: participant‐completed postal questionnaire |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Missing data at 12 weeks (from data provided by authors for analysis): Data missing for two participants, one from each group. Reasons for missing data not explained |
| Selective reporting (reporting bias) | High risk | The online trial registration (ISRCTN26051665) states that outcomes would include duration of leg cramps and "subsequent GP attendance". Outcome data were not provided in the published paper |
| Other bias | High risk | Participants were allowed to discontinue or swap treatments after 6 weeks. Results of outcomes measures for each group after 12 weeks might not reflect the effect of the intervention allocated at baseline. Only the 12 week data were provided by the authors for analysis in this review. After 12 weeks, participants were asked to recall how many night cramps they had experienced in the preceding 4 weeks. Participants may have been subject to recall bias |
Gholizadeh 2017.
| Study characteristics | ||
| Methods | Randomised controlled trial of 6 weeks' duration, conducted in 2016 | |
| Participants | Females with metabolic syndrome recruited from GP clinics in the city of Fuman, Gilan Province, Iran. Inclusion criteria: physically inactive women aged between 50 and 60 years with metabolic syndrome, who took no medications except for those controlling the risks associated with metabolic syndrome. Exclusion criteria: not provided Mean age in years (SD): stretching 55.83 (9.35); control 57.91 (1.06) Sex; n, females (%): stretching 12 (100); control 12 (100) |
|
| Interventions |
Stretching (N = 12) 10 days prior to the intervention, participants were instructed on how to complete the stretching exercises during a face‐to‐face session. Target muscles were gastrocnemius, quadriceps femoris, and hamstrings. Participants were instructed to stretch the muscles until they felt the stretch and slight pain or discomfort. Each stretch was held for 10 to 15 seconds and repeated 3 to 6 times. This set was done 3 times per day, 5 days per week, for 6 weeks. The number of repetitions and holding time were increased from the 1st week to the final week. Control (N = 12): The control group was instructed to follow their daily routines and not to change their diet, medication dosages, or their level of activity over the study period. For all participants Participants were asked not to change the dosage of their medications or their diet during their participation in the study. Participants' performance was checked in week 4. |
|
| Outcomes |
Included in this review ‐ Self‐reported average frequency of muscle cramps per week was recorded 1 week before the intervention and after 6 weeks of intervention. ‐ Self‐reported average severity of pain experienced per week was recorded 1 week before the intervention and after 6 weeks of intervention. VAS 0 to 10. Not included in this review ‐ Anthropometric measures: body mass index, waist circumference ‐ Triglycerides, high density lipoprotein, glucose, calcium and magnesium levels in fasting blood samples ‐ Blood pressure ‐ McGill pain questionnaire ‐ Calorie intake was recorded using the 5‐day food intake questionnaire before intervention and after 6 weeks, to monitor diet |
|
| Funding | None stated | |
| Conflicts of interest | None stated | |
| Date study conducted | 2016 | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomisation was accomplished by taking participant names out of a box. The first 12 names were placed in the control group. This is a predictable sequence rather than a random sequence. |
| Allocation concealment (selection bias) | High risk | Due to the method used for randomisation, trialists had access to information that would allow them to alter the allocation, e.g. by putting a name back in the hat. There is no evidence this was done, but the risk was present. |
| Blinding of participants (performance bias) | High risk | Not done |
| Blinding of personnel who administered the intervention (performance bias) | High risk | Not done |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | All outcomes included in this review from this study are participant self‐reported. Participants were not blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | The abstract states all 24 participants completed the study. |
| Selective reporting (reporting bias) | Unclear risk | There is no reference to a published protocol. |
| Other bias | High risk | Recall bias: participants retrospectively reported frequency and severity of cramps. |
Hallegraeff 2012.
| Study characteristics | ||
| Methods | Randomised controlled trial of 6 weeks' duration | |
| Participants |
Inclusion criteria: aged over 55 years; nocturnal leg cramps at least once per week Cramps were not defined in the published report Exclusion criteria: use of quinine or medication to assist with sleep; orthopaedic problems; severe medical conditions; comorbidities known to cause muscular spasms or cramps. Participants were recruited through advertisements in local newspapers in the northern part of the Netherlands. The study was set in a physical therapy clinic in Groningen, The Netherlands. Mean age in years (SD): stretching 67 (7); control 72 (7) Sex, n, males (%): stretching 20 (50); control 26 (65) |
|
| Interventions |
Stretching group (N = 40) Participants in the experimental group attended a 45‐minute visit, at which they were taught a program of daily stretching exercises for the hamstring and calf muscles by one physiotherapist, who was specially trained in the study procedure. For each stretch, the participant was advised to adopt the position shown, move to the comfortable limit of motion, move beyond this until a moderately intense stretch was felt, and sustain it for 10 seconds, and then return to the starting position. Participants were instructed to remain calm and never to hold their breath during the stretch. Each stretch was completed a total of 3 times, with 10 seconds of relaxation between each stretch. Stretching of both legs was done within 3 minutes. The physiotherapist demonstrated the stretches first, and then observed the participant performing the stretches, correcting the technique if necessary. If a participant found stretching while standing difficult, the participant was shown how to stretch in a sitting position. Calf stretch in standing Starting position: standing facing a wall with the elbows extended and both palms on the wall at chest height. One leg is forward with the knee flexed and the other leg is back with the knee extended. Both feet are in full contact with the floor. Motion to apply stretch: flex the front knee so that the trunk moves forward, keeping the trunk straight and the heels in contact with the floor. Hamstring stretch in standing Starting position:standing facing a chair that is placed against a wall. Place one heel on the chair with the knee of that leg fully extended. Motion to apply stretch: flex at the hips so that the trunk tilts forward, keeping the trunk straight. The foot on the floor should maintain full contact and the other heel remains in contact with the chair. Hamstring and calf stretch in sitting Starting position: sit on the floor or a firm bed with both legs extended. Grasp toes with both hands. Motion to apply stretch: flex at the hips so that the trunk tilts forward, keeping the trunk as straight as possible. Dorsiflex the ankles. Control group (N = 40) Participants in the control group were not taught any sham stretches and were advised not to commence stretches. Instructions for all participants Participants were strongly encouraged not to make any changes to their typical daily routine of work and leisure activity. All participants were encouraged to maintain and not change all other usual activity. At week 4, all participants received a home visit to assess and encourage adherence to the study protocol. |
|
| Outcomes |
Primary outcome: "change in the average number of nocturnal leg cramps per day over a one‐week period. This was assessed in the week prior to starting the 6‐week stretching program (Week 0) and again in the final week of the stretching program (Week 6)." Secondary outcome: severity of nocturnal leg cramps, measured using "a 10 cm visual analogue scale, with 0 cm representing no pain and 10 cm representing the worst pain the participant could imagine. Recordings were again made in the daily diary over the same 1‐week periods." Adverse events: "If adverse events were present, they were recorded daily in the diary card throughout the trial" |
|
| Funding | No funding source was reported | |
| Conflicts of interest | The authors declare no competing interests | |
| Date study conducted | Study dates were not reported | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "computer‐generated assignment schedule that was coded and concealed until after the study" |
| Allocation concealment (selection bias) | Low risk | "computer‐generated assignment schedule that was coded and concealed until after the study. An independent researcher assigned each patient to either the experimental group or the control group" |
| Blinding of participants (performance bias) | High risk | Participants were not blinded to group allocation |
| Blinding of personnel who administered the intervention (performance bias) | High risk | The physiotherapist who delivered the intervention was not blinded to group allocation |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Cramp outcomes were self‐reported by participants, who were not blinded to group allocation |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | "All participants completed their diary cards at Weeks 0 and 6" |
| Selective reporting (reporting bias) | Unclear risk | Insufficient detail to permit judgment |
| Other bias | Low risk | The study appears free of other sources of bias. |
GP: general practitioner; SEM: standard error of the mean; VAS: visual analogue scale;
Characteristics of excluded studies [ordered by study ID]
| Study | Reason for exclusion |
|---|---|
| Abdel‐Aziem 2010 | Presence of lower limb cramps was not measured at baseline. |
| Aguilar‐Ferrándiz 2013 | All participants did not report cramps at baseline and randomisation was not stratified for cramps. |
| Aguilar‐Ferrándiz 2014 | All participants did not report cramps at baseline and randomisation was not stratified for cramps. |
| Atik 2016 | All participants did not report cramps at baseline and randomisation was not stratified for cramps. |
| Atik 2016B | Not a randomised trial |
| Backus 2016 | Presence of lower limb cramps was not measured at baseline. |
| Behringer 2015 | Laboratory study exploring cramp susceptibility |
| Beyaz 2011 | Pregnancy |
| Dodd 2011 | Presence of lower limb cramps was not measured at baseline. |
| Fard 2016 | Pregnancy |
| Hidaka 2012 | Drug therapy |
| Holmes 2014 | All participants did not report cramps at baseline and randomisation was not stratified for cramps. |
| ISRCTN10576209 | All participants did not report cramps at baseline and randomisation was not stratified for cramps. |
| Jung 2005 | Laboratory study exploring cramp susceptibility |
| Kudo 2013 | Presence of lower limb cramps was not measured at baseline. |
| Leung 2014 | Presence of lower limb cramps was not measured at baseline. |
| Maas 2014 | Not a randomised trial to treat cramps. Cramps were reported as an adverse effect by one participant. |
| Macias‐Rodriguez 2014 | It is unclear if presence of lower limb cramps was measured at baseline. Authors did not respond to requests for more information. |
| Mansouri 2017 | Drug therapy |
| Maor 2017 | Drug therapy |
| Mastnardo 2016 | Randomised trial of only 2 weeks duration |
| Nishant 2014 | Not a randomised trial |
| Ozdemir 2013 | Reflexology |
| Sebo 2014 | Drug therapy |
| Simó 2015 | All participants did not report cramps at baseline and randomisation was not stratified for cramps. |
| Sung 2016 | Presence of lower limb cramps was not measured at baseline. |
| Supakatisant 2015 | Drug therapy |
Characteristics of ongoing studies [ordered by study ID]
NCT03864770.
| Study name | Extracorporeal shock wave therapy treatment for nocturnal leg cramps |
| Methods | RCT, parallel design |
| Participants | 30 participants. Inclusion criteria:
Exclusion criteria:
|
| Interventions | Experimental: extracorporeal shock wave therapy and general physical therapy 3 times per week for 2 weeks Control: general physical therapies 3 times a week for 2 weeks General physical therapies include thermotherapy, straight leg raise (SLR), transcutaneous electrical nerve stimulation (TENS) for treatment on calf muscle |
| Outcomes | Measured after 1 and 2 weeks of intervention Primary:
Secondary:
|
| Starting date | 5 March 2019 |
| Contact information | LI‐Wei Chou, PhD chouliwe@gmail.com China Medical University Hospital Taichung, Taiwan, 999079 +886‐4‐22052121 ext 2381 |
| Notes | We contacted the authors. The study is completed and data are being analysed. Professor Chou will email Fiona Hawke the report once it has been published. |
RCT: randomised controlled trial
Differences between protocol and review
We revised the following methods in accordance with Cochrane guidance (Higgins 2011; MECIR):
updated the 'Risk of bias' assessment;
included a PRISMA flow chart and a 'Summary of findings' table;
included an Assessment of reporting bias section, based in part on text from the Cochrane Neuromuscular standard protocol;
searched trials registries for ongoing studies; and
specified that quasi‐RCTs were eligible.
We also amended the methods to:
exclude studies of interventions for leg cramps in pregnancy, as these are included in the Cochrane review Interventions for leg cramps in pregnancy (Zhou 2015);
include outcome 'proportion of participants with lower limb muscle cramps' to separate these data from cramp frequency data.
clarify handling of cramp frequency data;
separate the 'cramp severity' outcome from 'cramp pain severity' and 'cramp duration';
clarify eligibility of studies in which not all participants reported cramps at baseline; and
clarify handling of data from multi‐arm studies.
Sean Sadler, Hans Dieter Katzberg, and Fereshteh Pourkazemi replaced Kate Walter as authors for this review update.
Contributions of authors
FH was responsible for selecting trials; contacting authors of studies; assessing risk of bias; extracting, entering and analysing data; interpreting results; and writing the review. HK was responsible for selecting trials when the search was updated in 2018. SS was responsible for selecting trials when the search was updated in 2020, assessing risk of bias, checking data extraction. VC was responsible for checking data entry. FP was responsible for translating an included trial from Farsi to English and helping interpret results and determine risk of bias for that study. SS, JB, VC, HK, and FP were responsible for providing comments on the draft review. All authors agreed on the final text.
Sources of support
Internal sources
-
Fiona Hawke, Sean Sadler, Vivienne Chuter, Australia
The University of Newcastle School of Health Sciences Faculty of Health and Medicine, Ourimbah, Australia
-
Fereshteh Pourkazemi, Australia
University of Sydney School of Health Sciences, Faculty of Medicine and Health, Sydney, Australia
-
Hans Katzberg, Other
University of Toronto Toronto General Hospital / UHN, Toronto, Canada
-
Joshua Burns, Australia
University of Sydney School of Health Sciences, Faculty of Medicine and Health & Children's Hospital at Westmead, Sydney, Australia
External sources
No sources of support provided
Declarations of interest
FH: none known; FH is a podiatrist and manages people with muscle cramps.
SS: none known; SS is a podiatrist and manages people with muscle cramps.
HK: non known; HK is a neurologist and manages people with muscle cramps.
VC: none known; VC is a podiatrist and manages people with muscle cramps.
JB receives research funding from NIH (National Institute of Neurological Diseases and Stroke and National Center for Advancing Translational Sciences, Inherited Neuropathies Consortium, Rare Disease Clinical Research Network #2U54NS065712), Charcot‐Marie Tooth Association of Australia, Charcot‐Marie Tooth Association (USA), Diabetes Australia, Multiple Sclerosis Research Australia, Sydney Southeast Asia Centre, New Zealand Neuromuscular Research Foundation Trust, Elizabeth Lottie May Rosenthal Bone Bequest and Perpetual Limited. JB is a podiatrist and manages people with muscle cramps.
New search for studies and content updated (no change to conclusions)
References
References to studies included in this review
Coppin 2005 {published and unpublished data}
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References to ongoing studies
NCT03864770 {published data only (unpublished sought but not used)}
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