Kwon, Lee, and Cho: Conventional Western Medicine and Complementary and Alternative Medicine on Leg Cramps: A Literature Review

Abstract

Objectives

The objective of this review is to investigate the use of conventional Western medicine (WM) and complementary and alternative medicine (CAM) on leg cramps. Leg cramps are the occurrence of muscular spasm in the leg muscles which occur frequently in the elderly and are frequently observed in the clinical field.

Methods

Relevant clinical studies were searched from five medical databases including PubMed, KISS, RISS, OASIS, and J-STAGE. Systematic review, clinical studies, and clinical practice guideline were included in this review.

Results

In total, 27 clinical studies, 9 systematic review and meta-analysis, and 1 clinical practice guideline met the inclusion criteria. Included studies were classified and analyzed according to the type of intervention. Studies on quinine and magnesium have been most studied in WM and CAM, respectively. Although quinine shows some clinical effects on leg cramps, however, the risk of side effects are suggested. In addition, magnesium failed to improve the clinically significant effects in most studies. Five case reports using Oriental herbal medicine (OHM) were included and OHMs were effective in improving leg cramps without side effects, however, the quality of evidence was low. Clinical studies on other interventions were lacking.

Conclusions

The results of this study indicate that there is no definite treatment standard for leg cramps until now, and there are limitations such as low level of evidence and side effects for each treatment. OHM can be an effective alternative to conventional intervention on leg cramps, therefore, related clinical studies are needed.

Fig. 1
PRISMA flow diagram of studies included in this review
jkm-38-3-13f1.gif
Table 1
Clinical Studies on Leg Cramps
Study Design Population Intervention Duration Results
Pharmacological intervention in WM
(1) Quinine
Jones, 198314) Double-blind RCT, Cross-over design Nocturnal leg cramp, elderly, n=9 TG: Quinine sulphate 300mg/day
CG: Placebo
2 weeks for each intervention 2 weeks for washout Number of cramps: +
Severity of cramps: +
Duration of cramps: −
Sleep disturbance: −
No adverse event was reported.
Lim, 198615) Double-blind RCT, Parallel design Nocturnal leg cramp, n=25 TG: Quinine sulphate 300mg/day
CG: Placebo
2 weeks for each intervention Number of cramps: −
Severity of cramps: −
No adverse event was reported.
Warburton, 198716) Double-blind RCT, Cross-over design Nocturnal leg cramp, elderly, n=22 TG: Quinine bisulphate 300mg/day
CG: Placebo
3 weeks for each intervention
3 weeks for washout
Number of cramps: −
Severity of cramps: −
No adverse event was reported.
Note. They reported that they found a significant relationship between serum quinine concentration and attenuation of cramps.
Fung, 198917) Double-blind RCT, Cross-over design Nocturnal leg cramp, elderly, n=9 TG: Quinine sulphate 200mg/day
CG: Placebo
4 weeks for each intervention
1 week for washout
Number of cramps: +
Duration of cramps: +
Severity of cramps: +
2 participants who received quinine reported side effects; ‘tinnitus’ and ‘blurred vision’, respectively.
Connolly, 199218) Double-blind RCT, Cross-over design Nocturnal leg cramp, male, n=30 TG: Quinine sulphate 500mg/day
CG1: Vitamin E 800U/day
CG2: Placebo
4 weeks for each intervention
4 weeks for washout
Number of cramps: +
Severity of cramps: −
Sleep disturbance: +
1 participant who received quinine reported side effect; ‘pruritus with bruising’.
Note. Vitamin E was not effective in reducing leg cramp frequency, severity, or sleep disturbance.
Dunn, 199319) Double-blind RCT, Cross-over design Patients receiving quinine regularly, n=28 TG: Quinine sulphate 300mg/day
CG: Placebo
30 days for each intervention
3 days for washout
Number of cramps: +
No adverse event was reported.
Note. They reported that quinine is more effective for night cramps at a higher dose, but this runs the risk of more side effects.
Sidorov, 199320) Double-blind RCT, Cross-over design Nocturnal leg cramp, male, n=19 TG: Quinine bisulphate 200mg/day
CG: Placebo
3 weeks for each intervention
No washout period but 2 weeks for run-in period
Number of cramps: −
Intensity of cramps: −
Duration of cramps: −
2 participants who received quinine reported side effects; ‘dizziness’ and ‘nausea, myalgia, leukopenia and thrombocytopenia’, respectively.
Diener, 200221) Double-blind RCT, Parallel design Nocturnal leg cramp, n=94 TG: Quinine sulphate 400mg/day
CG: Placebo
2 weeks for each intervention Number of cramps: +
Intensity of cramps: +
Intensity of pain: +
Global efficacy(by physician): +
Global efficacy(by patient): −
6 participants who received quinine reported side effect; ‘tinnitus’, ‘vomiting’, ‘diarrhea’, ‘epicondylitis’, ‘allergic exanthem’ and ‘bronchitis’, respectively.
Note. They reported that only the observed tinnitus was interpreted as being related with quinine.
Woodfield, 200522) Double-blind RCT, N-of-1 design Leg cramp, elderly, n=10 TG: Quinine sulphate 200~300mg/day
CG: Placebo
2 weeks for each intervention
2 weeks for washout
Number of cramps: ±
Days of cramps: ±
No adverse event was reported.
Note. Number and days of cramps were significantly reduced in 3 participants, but not in the other 7 participants.
Jansen, 199423) Double-blind RCT, Parallel design Leg cramp, n=20 TG: Hydroquinine hydrobromide 300mg/day
CG: Placebo
2 weeks for each intervention Number of cramps: +
Severity of cramps: −
Duration of cramps: −
4 participants who received quinine reported side effect; 3 for ‘bitter taste’, and 1 for ‘mild obstipation’.
Note. All women participants were assigned to hydroquinine group while all men participants were assigned to placebo group, randomly.
Jansen, 199724) Double-blind RCT, Parallel design Leg cramp, n=106 TG: Hydroquinine hydrobromide 300mg/day
CG: Placebo
2 weeks for each intervention Number of cramps: +
Severity of cramps: −
Duration of cramps: −
11 participants who received quinine reported side effect; 10 for ‘bitter taste or dry mouth’, and 1 for ‘tinnitus’.
Note. They reported that hydroquinine-group participants who reported side-effects were slightly heavier than those who did not, and also had a higher body-mass index.
(2) Verapamil
Baltodano, 198825) Single-arm study, Open-label trial Treatment resistant nocturnal leg cramp who were taking quinine sulfate 260mg daily, elderly, n=8 Verapamil hydrochloride 120mg/day 8 weeks Seven of eight patients had improvement.
No adverse event was reported.
(3) Naftidrofuryl
Young, 199326) Double-blind RCT, Cross-over design Nocturnal leg cramp, n=14 TG: Naftidrofuryl oxalate 600mg/day
CG: Placebo
4 weeks for each intervention
2 weeks for washout
Number of cramps: −
5 participants who received quinine reported side effect; ‘mild gastrointestinal upset’.
Note. They reported that naftidrofuryl is an effective alternative to quinine in the treatment of this painful condition.
Non-pharmacological intervention in WM
(1) Injection on trigger point
Prateepavanich, 199927) Single-blind RCT, Parallel design Nocturnal leg cramp, n=24 TG: Xylocaine injection at the gastrocnemius
CG: Quinine sulfate 300mg/day
4 weeks for each intervention Number of cramps: +
Duration of cramps: +
Intensity of pain: +
Cramp index: +
Pain threshold of the gastocnemius TrPs: +
No adverse event was reported.
Note. They reported that the benefit of both strategies lasted up to four weeks following cessation of the treatment but the outcome of all measures (except pain threshold) were found to be significantly better in the group treated with TrP injection.
Kim, 201528) Single-arm study Nocturnal leg cramp, n=12 1~2mL of 0.25% lidocaine into each of the TrPs on the gastrocnemius muscles 4 weeks Number of cramps: +
Pain threshold of the gastrocnemius TrPs: +
Sleep disturbance: +
No adverse event was reported.
Diet and dietary supplement in CAM
(1) Magnesium
Frusso, 199931) Double-blind RCT, Cross-over design Nocturnal leg cramp, n=93 TG: Magnesium citrate 1800mg/day
CG: Placebo
4 weeks for each intervention
4 weeks for washout
Number of cramps: −
Severity of cramps: −
Duration of cramps: −
Sleep disturbance: −
Note. They reported that no differences in the percentage of common side effects(diarrhea, nausea, vomiting) between magnesium(10.7%) and placebo(10.1%) were.
Roffe, 200232) Double-blind RCT, Cross-over design Chronic nocturnal leg cramp, n=73 TG: Magnesium citrate 300mg/day
CG: Placebo
4 weeks for each intervention
2 weeks for washout
Number of cramps: −
Severity of cramps: −
Duration of cramps: −
Global efficacy(by patient): +
22 participants who received quinine reported side effect; 14 for ‘diarrhea’, 6 for ‘constipation’, and 2 for ‘nausea, indigestion or flatulence’.
Garrison, 201133) Double-blind RCT, Parallel design Nocturnal leg cramp, n=46 TG: 4 hour intravenous infusions of 250ml D5W with 20mmol of magnesium sulfate
CG: 4 hour intravenous infusions of 250ml D5W
5 days for each intervention Number of cramps: −
No adverse event was reported.
(2) Caffeine
Molema, 200734) Double-blind, Single-case study Nocturnal leg cramp, n=1 2 capsules containing 500 mg paracetamol 3 times a day during 1 week; 2 capsules containing 500 mg paracetamol/50 mg caffeine 3 times a day during the other week. Note. Number of cramps increased according to rise of serum caffeine concentration. They reported that caffeine can increase susceptibility to muscle cramps in humans.
Exercise and physical therapy in CAM
(1) Stretching exercise
Coppin, 200535) RCT, Parallel design Nocturnal leg cramp who were taking quinine sulfate routinely, elderly, n=111 TG: Stretching exercise
CG: No stretching exercise
12 weeks Number of cramps: −
Symptom burden: −
Severity of cramps: −
No adverse event was reported.
Hallegraeff, 201236) Single-blind RCT, Parallel design Nocturnal leg cramp, older adults, n=55 TG: Stretching exercise
CG: No stretching exercise
6 weeks Number of cramps: +
Severity of cramps: +
No adverse event was reported.
Note. The stretching exercise was consisted of calf stretching in standing, hamstring stretch in standing, and hamstring and calf stretch in sitting.
(2) Physical therapy
Choi, 201037) Case reports Nocturnal leg cramp, n=2 Muscle energy technique 1 time The numbers of cramps during 1 week were reduced in the 2 patients.
No adverse event was reported.
Note. The muscle energy technique was a manipulation on articulation sacroiliaca.
(3) Oriental herbal medicine
Tahara, 201138) Case reports Treatment resistant leg cramp who were taking Jakyakgamcho-tang, n=1 Sokyungwhalhyul-tang 2 months The number of cramps was reduced.
No adverse event was reported.
Ishida, 201439) Case reports Nocturnal leg cramp, n=5 Uchashinki-hwan 8~18 weeks The cramps disappeared in 3 patients, but no improvement was observed in the other patients.
No adverse event was reported.
Ito, 201540) Case reports Chronic leg cramp, n=7 Samul-tang 14~609 days Seven cases showed improvement of the symptoms, but 3 cases showed no improvement.
No adverse event was reported.
Kimura, 201541) Case reports Leg cramp, n=2 Jinmu-tang 4 weeks~6 months The number and severity of cramps were reduced in the 2 patients.
No adverse event was reported.
Dokura, 201742) Case reports Leg cramp, n=33 Sokyungwhalhyul-tang 1 month In 96.95% (32 cases), symptoms of the cramps were improved by more than half, and 69.6% (23 cases) reported that the symptoms disappeared.
No adverse event was reported.
Note. In particular, 36.4% (12 cases) showed no occurrence of the cramps immediately after taking Sokyungwhalhyul-tang.

Abbreviation: CAM, complementary and alternative medicine; CG, control group; RCT, randomized controlled trial; TG, treatment group; TrPs, trigger points; WM, conventional Western medicine. Note. ‘+’ means that the intervention used for treatment group showed significant clinical effects; ‘−’ means that the intervention used for treatment group had no significant effect; ‘±’ means that the intervention used for treatment group had conflicting effects according to participants.

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