Until not very long ago, quinine -- a bitter-tasting substance sometimes associated with tonic water that was once the world's mainstay treatment for malaria -- was also the drug of choice for treatment of muscle cramps. But in 2006, the Food and Drug Administration warned against the use of quinine for this purpose, not because it was utterly ineffective but because of accumulating anecdotal evidence of adverse effects.

A thorough literature review conducted by researchers at the Stanford University School of Medicine, to be published Feb. 23 in Neurology, confirms the FDA's concerns. The resulting guidelines urge caution in the use of quinine, suggest the exploration of other possible treatments and encourage patients and physicians to pay closer attention to the manifestation of muscle cramps, which are usually benign but can sometimes signal more significant medical problems.

"Our recommendation is that quinine should be avoided for general use in treating muscle cramps," said the study's first author, Hans Katzberg, MD, who has a fellowship in neuromuscular medicine at the medical school. Although available data suggests that quinine can reduce the symptoms by one-third to one-half, serious adverse effects, including blood irregularities, arise as often as one in 25 cases, Katzberg said. Still, if muscle cramps are disabling, other attempted therapies fail and the patient's condition can be actively monitored by a physician, then the use of quinine may be in order. Once sold over the counter, quinine is no longer easily available. It is still a key ingredient in tonic water, but a self-medicating Dr. Schweppes would have to ingest at least a few liters of the stuff a day to get a therapeutic dose. That's a bit of a stretch.

There is no solid formal evidence that either drinking water (tonic or otherwise) or stretching, two frequently cited non-drug approaches to reducing muscle cramps, effectively counters them. Still, neither method is likely to cause much harm if practiced in moderation.

Other muscle-cramp treatments reviewed in this study include vitamin B complex, calcium-channel blocking agents often prescribed for hypertension, and anti-epileptic drugs. But the investigators concluded that more research is needed to assess the efficacy of these alternatives. "The relative lack of data on many of these compounds came as a surprise," said Katzberg.

The review covered only studies of muscle cramps that were unrelated to any underlying disease. Muscle cramps -- typically in the calves, usually more noticeable in the still of the night and frequently experienced by pregnant women -- often occur independently of any underlying serious condition. But they can be indicators of kidney or liver disease as well as neurological conditions, such as Lou Gehrig's disease and peripheral neuropathy associated with late-stage type-2 diabetes. For this reason, people experiencing significant cramping are encouraged to consult a physician.

While breakthrough treatments for muscle cramps remain elusive, the prescription for getting them is no secret: Try sitting and reading 500 journal articles. Katzberg initially sifted through 563 studies on the subject, deeming 24 suitable for analysis. Then he and two colleagues -- senior author Yuen So, MD, PhD, professor of neurology and neurological sciences, and Ahmir Khan, MD, a clinical fellow at the medical school now practicing neurology in Chicago -- carefully read the studies in order to draw their conclusions about different therapies' effectiveness and safety.

Note: If no author is given, the source is cited instead.

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