title: Lipoic (thioctic) acid increases brain energy availability and skeletal muscle performance as shown by in vivo 31P-MRS in a patient with mitochondrial cytopathy.
abstract: A woman affected by chronic progressive external ophthalmoplegia and muscle mitochondrial DNA deletion was studied by phosphorus magnetic resonance spectroscopy (31P-MRS) prior to and after 1 and 7 months of treatment with oral lipoic acid. Before treatment a decreased phosphocreatine (PCr) content was found in the occipital lobes, accompanied by normal inorganic phosphate (Pi) level and cytosolic pH. Based on these findings, we found a high cytosolic adenosine diphosphate concentration [ADP] and high relative rate of energy metabolism together with a low phosphorylation potential. Muscle MRS showed an abnormal work-energy cost transfer function and a low rate of PCr recovery during the post-exercise period. All of these findings indicated a deficit of mitochondrial function in both brain and muscle. Treatment with 600 mg lipoic acid daily for 1 month resulted in a 55% increase of brain [PCr], 72% increase of phosphorylation potential, and a decrease of calculated [ADP] and rate of energy metabolism. After 7 months of treatment MRS data and mitochondrial function had improved further. Treatment with lipoate also led to a 64% increase in the initial slope of the work-energy cost transfer function in the working calf muscle and worsened the rate of PCr resynthesis during recovery. The patient reported subjective improvement of general conditions and muscle performance after therapy. Our results indicate that treatment with lipoate caused a relevant increase in levels of energy available in brain and skeletal muscle during exercise.
authors.affiliation: Cattedra di Biochimica Clinica, Istituto di Patologia Speciale Medica D. Campanacci, Universita' di Bologna, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Barbiroli
authors.forename: R
authors.initials: R
authors.lastname: Medori
authors.forename: H J
authors.initials: HJ
authors.lastname: Tritschler
authors.forename: T
authors.initials: T
authors.lastname: Klopstock
authors.forename: P
authors.initials: P
authors.lastname: Seibel
authors.forename: H
authors.initials: H
authors.lastname: Reichmann
authors.forename: S
authors.initials: S
authors.lastname: Iotti
authors.forename: R
authors.initials: R
authors.lastname: Lodi
authors.forename: P
authors.initials: P
authors.lastname: Zaniol
mesh_terms: D000244:Adenosine Diphosphate / Q000032:analysis; D000328:Adult; D001923:Brain Chemistry; D002908:Chronic Disease; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D015444:Exercise / Q000502:physiology; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D017240:Mitochondrial Myopathies / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D009778:Occipital Lobe / Q000378:metabolism*; D009886:Ophthalmoplegia / Q000209:etiology; D010758:Phosphorus; D010766:Phosphorylation / Q000187:drug effects; D008063:Thioctic Acid / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D010758:Phosphorus; D000244:Adenosine Diphosphate; D008063:Thioctic Acid