Creatine, an over-the-counter supplement popular among athletes (including major league baseball MVP Sammy Sosa) works twice as well in diseased mice as the only approved prescription drug available for treating Lou Gehrig's disease (ALS or amyotrophic lateral sclerosis), researchers funded by the Muscular Dystrophy Association announced today.

The metabolic supplement, which has previously shown therapeutic benefit in animal models for Huntington's, Parkinson's, other neurologic diseases and Duchenne muscular dystrophy, warrants additional study according to lead researcher and MDA grantee M. Flint Beal of the Cornell University Medical Center in New York City. "Clinical trials are now being planned," said Beal, "as our study of mice with a genetic form of ALS shows creatine to be at least twice as effective as riluzole, the only currently approved drug for people with ALS."
Dr. Leon Charash, chairman of the MDA Medical Advisory Committee, said, "Creatine is well tolerated by man, and harnessing its apparent ability to buffer and stabilize the production and transportation of energy within cells could yield important health benefits for people with ALS and other progressive diseases. MDA is eager to fund the human trials necessary to determine what this elegant animal study may mean to the tens of thousands affected by inherited and sporadic forms of ALS."

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Creatine works by an entirely different mechanism than riluzole. The fact that the mechanism is different suggests that the two drugs could be used together to achieve a beneficial, additive effect, researchers say. Riluzole works by blocking a body chemical called glutamate, while creatine works by affecting the energy-producing mechanisms of cells. MDA research has focused on both strategies, as well as others, for the treatment of ALS. Charash underscored that this research must be done quickly, as "it will be difficult to keep ALS patients off creatine until safe and effective dosage levels can be determined. The findings in mice were dosage dependent and if creatine is found to be beneficial in treating human ALS, two-percent creatine in drinking water. Researchers suspect that creatine is able to increase survival time in mice with ALS because it protects the muscle-controlling nerve cells (motor neurons) normally damaged in the disease. The motor neurons of the ALS mice are depleted by the time the mice are four months old. However, Beal and colleagues found that four-month-old mice with ALS that had received creatine in their diets had the same number of motor neurons as healthy mice of that age.
Beal suggests that there are two possibilities to explain how creatine may protect neurons against the effects of ALS. The first possibility is that taking creatine increases the energy levels in the brain - levels that may be compromised in ALS by damage to the main powerhouses of the cells, the mitochondria. "The second possibility," said Beal, "is that creatine may have direct effects on the mitochondria by inhibiting the mechanism by which some types of cell death are triggered. Recent data indicates that mitochondria play a pivotal role in maintaining the health of motor neurons and other cells." Beal and colleagues are currently doing more studies to try to understand the mechanism by which creatine protects nerve cells.

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Los Angeles Times, March 10 1999
Creatine Studied as Dystrophy Drug
By THOMAS H. MAUGH, LA TIMES MEDICAL WRITER

The food supplement creatine, used by many athletes to increase their strength, can also increase the strength of patients with muscular dystrophy and other wasting diseases, researchers report in a study to be released today.
The new finding comes on the heels of an animal study suggesting that creatine is twice as effective in controlling symptoms of amyotrophic lateral sclerosis, more commonly known as Lou Gehrig's disease, as the only drug now marketed for treating it. The results hint that creatine could be useful for large numbers of people who suffer muscular weakness caused by disease or aging, said Dr. Leon Charash, chairman of the Muscular Dystrophy Association's Medical Advisory Committee. Because creatine is widely available in health food stores and is "essentially nontoxic" in recommended doses, he predicts that hundreds of thousands of people may rush out to try it, and "It would be hard for a physician to discourage it." "If a family called me and asked if they should try it, I would be hard- pressed to say 'don't.'" Already, he notes, the MDA is organizing a large clinical trial of creatine at Johns Hopkins University, Massachusetts General Hospital, and Cornell University.

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That study will compare it against a placebo to determine if it is truly beneficial. But other experts urged caution, noting that the drug has only been studied in a small number of patients, for a short period of time. "I'm basically skeptical" Dr Audrey Penn of the National Institute of Neurological Disease and Stroke told the Associated Press. "I have a feeling that over the longer term it might not be such an exciting result." Penn noted that creatine - a naturally occurring chemical that the body uses to store energy in muscles - had been tried in children with muscular dystrophy in the 1950s and abandoned. But Charash said that researchers then did not measure muscular strength and did not compare results to those with a placebo. Such studies would not have observed the relatively modest effects seen in the current studies," he said. "But a small gain for a person who doesn't have much to work with can be very important," he noted.

In the study reported today in the journal of Neurology, Dr Mark Tarnopolsky of McMasters University in Canada gave 81 patients with muscular dystrophy and other neurological diseases 10 grams of creatine daily for 5 days and then 5 grams daily for 5 more days. The researchers measured such factors as hand gripping strength and knee strength and found an average of 10 percent to 15 percent improvement. "The improvements are as encouraging as many of the treatments people are now using for these diseases," Tarnopolsky said. "Creatine is inexpensive, it's nontoxic, and it has few side effects." That study follows another reported in the March issue of Nature Medicine by Dr M. Flint Beal, of Cornell University Medical Center. He was studying mice with a genetic form of ALS. Beal found that mice given creatine in their water at a solution of one percent or two percent lived an average of 26 days longer than those given the drug, and that their muscles remained healthy longer. That was twice the benefit observed with riluzole, the only drug now approved for treating ALS in humans. Riluzole, moreover, costs as much as $10,000 a year. The MDA will also fund clinical trials of creatine in ALS patients, Charash said. Creatine has been popular with professional athletes, such as home run sluggers Mark McGwire and Sammy Sosa, quarterback Troy Aikman, and Olympic track medallists Linford Christie and Michael the correct dose needs to be determined before patients should take the supplement."

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Creatine is a small molecule that can be turned into the high-energy compound phosphocreatine by the body. Because it creates bursts of energy, it is especially popular among athletes. Phosphocreatine is important for the rapid generation of energy in tissues that are very metabolically active such as the brain and muscle. Beal and colleagues at Massachusetts medical research centers in Boston, Bedford and Cambridge say initial trials will study the effectiveness of creatine in treating ALS in humans. Subsequent trials in both mice and humans will study the effects of combining creatine with riluzole.

ALS is a rapidly progressive disorder that causes degeneration of the neurons that control the voluntary muscles. Affecting some 35,000 Americans, ALS results in total paralysis and death usually within five years from the time of diagnosis.

The current findings reported in the March issue of Nature Medicine show that creatine supplementation in the diet of mice engineered to have an ALS-causing mutation extended their lives by an average of 26 days longer than such mice that didn't get the supplement. The effect of the orally administered creatine was dosage-dependant, with significant improvements in survival achieved with both one- and ...!---!

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Muscle supplement might help muscular dystrophy-type diseases
Date : Wed, 10 Mar 1999
By Lauran Neergaard AP Medical Writer WASHINGTON --

A dietary supplement that athletes use to build muscle might offer help to patients whose muscles are wasting away from such diseases as muscular dystrophy, a new study suggests. Taking very large doses of creatine daily seemed to increase the strength of patients' muscles by about 10 percent, concludes the small study published Tuesday in the journal Neurology. Independent scientists urged caution.

The study was far too small and too short, lasting only a few weeks, to show if creatine offers lasting benefit or if high doses for long periods can cause side effects. Plus, doctors actually tried to treat similar neuromuscular diseases with creatine in the 1950s, and it failed, said Dr. Audrey Penn of the National Institute of Neurological Disease and Stroke. So creatine was abandoned. "I'm basically skeptical," Penn said. "I have a feeling that over the longer term it might not be such an exciting result." But those 1950s studies only looked at whether creatine could cure or slow the disease, not if it had a smaller benefit like improving muscle strength and thus quality of life, Dr. Leon Charash of the Muscular Dystrophy Association said.

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The new study suggests creatine might do that, so Charash's association asked researchers Tuesday to start larger studies quickly and promised to help pay for them. "If somebody can hold a glass up and not have somebody give it to them, that's a small gain -- but it's very important to that person," Charash said. Creatine is an amino acid found naturally in healthy muscles. It has become one of the biggest-selling dietary supplements, thanks to athletes who hope it will build muscles. There are no data that confirm the safety of taking extra creatine for long periods or at high doses, because the government allows dietary supplements to sell largely unregulated. Some athletes have reported muscle cramps, muscle tears and dehydration.

Because creatine is so widely sold, neuromuscular patients probably will race to try it for themselves, Charash said. Separate research published last week in Nature Medicine already had patients of Lou Gehrig's disease excited. It was only a study in rodents, but it suggested that creatine might be more potent than the only prescription therapy for the disease, a killer neurological disorder that also attacks muscles. In the study published Tuesday, Dr. Mark Tarnopolsky of Ontario's McMaster University gave 81 patients with a variety of neuromuscular diseases 10 daily grams of creatine for five days, followed by 5 grams a day for another week. When patients exercised their legs, hands and feet, they were a little stronger after the creatine than before. Tarnopolsky noted that such patients naturally have lower creatine levels than healthy people and hypothesized that boosting their levels helped their muscle cells hang onto cellular energy supplies for a little longer.