RESUMO
OBJECTIVE: To study if treatment with triheptanoin, a 7-carbon triglyceride, improves exercise tolerance in patients with McArdle disease. McArdle patients have a complete block in glycogenolysis and glycogen-dependent expansion of tricarboxylic acid cycle (TCA), which may restrict fat oxidation. We hypothesized that triheptanoin metabolism generates substrates for the TCA, which potentially boosts fat oxidation and improves exercise tolerance in McArdle disease. METHODS: Double-blind, placebo-controlled, crossover study in patients with McArdle disease completing two treatment periods of 14 days each with a triheptanoin or placebo diet (1 g/kg/day). Primary outcome was change in mean heart rate during 20 min submaximal exercise on a cycle ergometer. Secondary outcomes were change in peak workload and oxygen uptake along with changes in blood metabolites and respiratory quotients. RESULTS: Nineteen of 22 patients completed the trial. Malate levels rose on triheptanoin treatment versus placebo (8.0 ± SD2.3 vs. 5.5 ± SD1.8 µmol/L, P < 0.001), but dropped from rest to exercise (P < 0.001). There was no difference in exercise heart rates between triheptanoin (120 ± SD16 bpm) and placebo (121 ± SD16 bpm) treatments. Compared with placebo, triheptanoin did not change the submaximal respiratory quotient (0.82 ± SD0.05 vs. 0.84 ± SD0.03), peak workload (105 ± SD38 vs. 102 ± SD31 Watts), or peak oxygen uptake (1938 ± SD499 vs. 1977 ± SD380 mL/min). INTERPRETATION: Despite increased resting plasma malate with triheptanoin, the increase was insufficient to generate a normal TCA turnover during exercise and the treatment has no effect on exercise capacity or oxidative metabolism in patients with McArdle disease.
Assuntos
Tolerância ao Exercício , Doença de Depósito de Glicogênio Tipo V/dietoterapia , Doença de Depósito de Glicogênio Tipo V/metabolismo , Avaliação de Resultados em Cuidados de Saúde , Oxigênio/metabolismo , Triglicerídeos/farmacologia , Adulto , Idoso , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Triglicerídeos/administração & dosagem , Adulto JovemRESUMO
No effective treatment for McArdle disease exists.We report a Japanese patient with McArdle disease who was treated with vitamin B(6) supplementation (60-90 mg/day). After treatment, increased muscle phosphorylase activity was confirmed by follow-up muscle biopsy (3.8 times higher than pretreatment levels). Increased lactate levels were seen on the forearm exercise test, and regular work activities could be resumed. Vitamin B(6) supplementation can enhance residual phosphorylase activity and improve insufficient anaerobic glycolysis of skeletal muscle.
Assuntos
Suplementos Nutricionais , Doença de Depósito de Glicogênio Tipo V/dietoterapia , Doença de Depósito de Glicogênio Tipo V/patologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Ácido Pantotênico/farmacologia , Complexo Vitamínico B/farmacologia , Adulto , Biópsia , Terapia por Exercício , Seguimentos , Doença de Depósito de Glicogênio Tipo V/reabilitação , Humanos , Masculino , Ácido Pantotênico/administração & dosagem , Fosforilases/metabolismoRESUMO
Epidemiology of muscular dystrophies has been important in the prevention of these diseases. In fact the genetic counselling, after a preliminary epidemiological investigation, reduced the incidence rate of Duchenne muscular dystrophy in the Veneto Region. Furthermore the new biochemical data on dismetabolic muscular diseases revealed a future strategy in the early identification of muscular dystrophies for their epidemiology and genetic prevention as well as for the new systems of research used in the field of muscular dystrophies.