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A tennis lesson: sharp practice in the science behind the Sharapova case
  1. Arduino Arduini1,
  2. Victor A Zammit2
  1. 1CoreQuest, Manno, Switzerland
  2. 2Translational and Experimental Medicine, Warwick Medical School, Coventry, UK
  1. Correspondence to Professor Victor A Zammit, Translational Medicine, Warwick Medical School, Coventry CV4 7AL, UK; v.a.zammit{at}

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Maria Sharapova (and hundreds of other elite athletes) took meldonium, a drug developed at the time of the USSR for the treatment of heart attack and stroke, though it has never been approved for use anywhere outside of the former Soviet Union. Meldonium is an inhibitor of γ-butyrobetaine hydroxylase, an enzyme involved in the carnitine biosynthetic pathway.1 Intake results in a reduction of tissue carnitine content, including the heart and skeletal muscles. Carnitine plays a critical role in transferring long-chain fatty acids across mitochondrial inner membrane into the mitochondrial matrix, to enable entry of the fatty acid moiety into the oxidation pathway, to synthesise ATP aerobically.2 In cases when intracellular carnitine availability is compromised, such as in neonatal primary carnitine deficiency,3 those affected experience hypoglycaemia, fatigue, seizures and cardiomyopathy.3 Carnitine-deficient individuals are sensitive to prodrugs containing the pivaloyl moiety, as pivalic acid is a prodrug able to induce carnitine deficiency (like meldonium); this results in lethal cardiac arrhythmias.4 Meldonium administered orally at ‘recommended’ doses (500 mg, twice daily)5 would …

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