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Effects of Meldonium on Athletes Are Hazy

By ANDREW POLLACKMARCH 10, 2016

Meldonium at the production plant of the Grindeks pharmaceutical company in Riga, Latvia. Credit Ints Kalnins/Reuters

The drug that caused Maria Sharapova’s failed doping test sounds almost like a miracle potion.

Published studies say the drug, meldonium, may be effective in treating heart ailments, strokes, diabetes and Alzheimer’s disease, as well as in improving people’s moods. It even increases the sexual performance and sperm motility of boars.

But some experts said that the evidence for such claims was scant and that it was not even clear if the drug improves athletic performance. And they said there was little reason for someone like Sharapova to have taken it to treat her medical conditions, as she says she did.

“The evidence around whether it is a performance-enhancing drug is quite thin,” said Mark Stuart, a pharmacist in London who is on the medical and antidoping commission of the European Olympic Committees.

But the fact that multiple athletes have used it suggests that they believe it improves performance, he said. “I can’t see how so many athletes — young, quite fit and healthy — would really have a need for this particular drug.”

Meldonium is sold under the brand name Mildronate by Grindeks, a company in Latvia, where the drug was invented in the 1970s, and has been one of the country’s major exported products. It is now made by other companies as well.

The compound was originally envisioned as a “growth stimulator for animals and fowl,” according to a United States patent granted in 1984.

Instead, it has been sold in Russia and former states of the Soviet Union mainly to treat conditions, like angina and heart attacks, in which the heart is not getting enough oxygen.

Grindeks said it had not applied for approval of the drug in the United States because that would require costly clinical trials. It would not pay for the company to do that because the patent on the drug has expired, and Grindeks could face generic competition.

One question is how Sharapova, who lives mainly in Florida, has been getting the drug.

A spokeswoman for the Food and Drug Administration said it was illegal to import unapproved drugs into the United States. But the agency will allow imports for personal use in certain situations, such as if a drug is used for a serious condition for which effective treatment is unavailable in the United States. Generally, only a three-month supply is allowed in those cases.

Sharapova’s lawyer, John Haggerty, said she had always complied with the F.D.A.’s guidelines on the personal importation of drugs.

Sharapova said she had been prescribed the drug for conditions including a magnesium deficiency, irregular electrocardiograms and prediabetes. Some experts said they did not see how meldonium would necessarily help those conditions (although there are at least two studies in rats showing that the compound might help with diabetes). The F.D.A. has approved many drugs for heart conditions and diabetes.

Meldonium appears to work by inhibiting the synthesis of a substance called carnitine, which the cells in the body need to burn fat to produce energy. But when cells are not getting enough oxygen, they can switch to burning glucose instead of fat. Glucose produces more energy for a given amount of oxygen than fat.

“Glucose is more efficient when you have limited oxygen,” said Dr. William R. Hiatt, a cardiologist and professor at the University of Colorado School of Medicine.

That could explain why the drug would help people whose heart cells were not getting enough oxygen. One randomized controlled trial showed that the use of meldonium increased how long patients with angina, or chest pains from inadequate blood flow to the heart, could ride an exercise bike.

That might also, in theory, suggest why the drug would help athletes. At maximum exertion, their cells might not be getting enough oxygen. Use of the drug might help switch the cells to burning glucose instead.

“In general, if one is involved in short-duration, sprint-type activity, one tends to use glucose because it is more available and it is an efficient way to generate energy quickly,” said Dr. Eric Brass, a professor of medicine at U.C.L.A. who has studied the effects of carnitine.

Still, Brass said it was not clear if that was what was really happening in athletes. “The science behind many of these performance-enhancing compounds is limited, biased and subject to misinterpretation,” he said. Several of the studies on meldonium were done on rats and published only in Russian.

Complicating the picture is that some athletes think it helps their performance to increase their carnitine levels by taking supplements. But if increasing carnitine is good, that would imply that decreasing carnitine, as meldonium presumably does, could impair athletic performance.

“I can only see a downside to inhibiting carnitine in a healthy athlete,” Hiatt said.

Still, it is possible that enhancing carnitine might be good for certain activities while depleting it might be better for sudden energy bursts.

Grindeks said it did not believe meldonium’s use should be banned for athletes. It said the drug worked mainly by reducing damage to cells that can be caused by certain byproducts of carnitine.

Meldonium “is used to prevent death of ischemic cells and not to increase performance of normal cells,” it said in a statement. “Meldonium cannot improve athletic performance, but it can stop tissue damage in the case of ischemia,” which is lack of blood flow to the heart.

Still, one of the drug’s inventors, Ivars Kalvins, told a newspaper in 2009 that the drug had been used to increase the endurance of Soviet troops lugging heavy equipment in Afghanistan. And Grindeks’s website says that in addition to its use for cardiovascular disease, the drug is used “for the improvement of work capacity of healthy people at physical and mental overloads and during rehabilitation period.”

http://www.nytimes.com/2016/03/11/sports/tennis/effects-of-meldonium-on-athletes-are-hazy.html?ref=sports&_r=1

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