Peter Hespel

Creatine supplementation in Huntington’s disease A placebo-controlled pilot trial

Objective: To evaluate the effect of creatine (Cr) supplementation (5 g/day) in Huntington’s disease (HD). Methods: A 1-year double-blind placebo-controlled study was performed in 41 patients with HD (stage I through III). At baseline and after 6 and 12 months, the functional, neuromuscular, and cognitive status of the patients was assessed by a test battery that consisted of 1) the Unified Huntington’s Disease Rating Scale (UHDRS), 2) an exercise test on an isokinetic dynamometer to assess strength of the elbow flexor muscles, 3) a maximal exercise test on a bicycle ergometer to evaluate cardiorespiratory fitness, and 4) a test to assess bimanual coordination ability. Following the baseline measurements, the subjects were assigned to either a creatine (n = 26) or a placebo group (n = 15). Results: Scores on the functional checklist of the UHDRS (p < 0.05), maximal static torque (p < 0.05), and peak oxygen uptake (p < 0.05) decreased from the start to the end of the study, independent of the treatment received. Cognitive functioning, bimanual coordination ability, and general motor function (total motor scale, UHDRS) did not change from baseline to 1 year in either group. Conclusion: One year of Cr intake, at a rate that can improve muscle functional capacity in healthy subjects and patients with neuromuscular disease (5 g/day), did not improve functional, neuromuscular, and cognitive status in patients with stage I to III HD.

Glucose uptake and transport in contracting, perfused rat muscle with different pre-contraction glycogen concentrations

1. Glucose uptake and transport, muscle glycogen, free glucose and glucose‐6‐phosphate concentrations were studied in perfused resting and contracting rat skeletal muscle with different pre‐contraction glycogen concentrations. Rats were pre‐conditioned by a combination of swimming exercise and diet, resulting in either low (glycogen‐depleted rats), normal (control rats) or high (supercompensated rats) muscle glycogen concentrations at the time their hindlimbs were perfused. 2. Compared with control rats, pre‐contraction muscle glycogen concentration was approximately 40% lower in glycogen‐depleted rats, whereas it was 40% higher in supercompensated rats. Muscle glycogen break‐down correlated positively (r = 0.76; P less than 0.001) with pre‐contraction muscle glycogen concentration. 3. Glucose uptake during contractions was approximately 50% higher in glycogen‐depleted hindquarters than in control hindquarters; in supercompensated hindquarters it was 30% lower. When rats with similar muscle glycogen concentrations were compared, glucose uptake in hindquarters from rats that had exercised on the preceding day was approximately 20% higher than in hindquarters from rats that had not exercised on the preceding day. 4. Muscle membrane glucose transport, as measured by the rate of accumulation of 14C‐3‐O‐methylglucose in the contracting muscles, was 25% lower in supercompensated than in glycogen‐depleted muscles at the onset as well as at the end of the 15 min contraction period. 5. Intracellular concentrations of free glucose and glucose‐6‐phosphate were higher at rest and during the entire 15‐min stimulation period in supercompensated muscles than in glycogen‐depleted muscles, and glucose uptake during contractions correlated negatively with free glucose (r = ‐0.52; P less than 0.01) as well as with glucose‐6‐phosphate (r = ‐0.49; P less than 0.01) concentrations. 6. It is concluded that: (a) The rate of glucose uptake in contracting skeletal muscle is dependent on the pre‐contraction muscle glycogen concentration. Regulating mechanisms include limitations of membrane glucose transport as well as of glucose metabolism. (b) Contractions on the preceding day have a stimulating effect on glucose uptake during contractions of the same muscles on the next day.

Effect of training in the fasted state on metabolic responses during exercise with carbohydrate intake.

Skeletal muscle gene response to exercise depends on nutritional status during and after exercise, but it is unknown whether muscle adaptations to endurance training are affected by nutritional status during training sessions. Therefore, this study investigated the effect of an endurance training program (6 wk, 3 day/wk, 1-2 h, 75% of peak Vo(2)) in moderately active males. They trained in the fasted (F; n = 10) or carbohydrate-fed state (CHO; n = 10) while receiving a standardized diet [65 percent of total energy intake (En) from carbohydrates, 20%En fat, 15%En protein]. Before and after the training period, substrate use during a 2-h exercise bout was determined. During these experimental sessions, all subjects were in a fed condition and received extra carbohydrates (1 g.kg body wt(-1) .h(-1)). Peak Vo(2) (+7%), succinate dehydrogenase activity, GLUT4, and hexokinase II content were similarly increased between F and CHO. Fatty acid binding protein (FABPm) content increased significantly in F (P = 0.007). Intramyocellular triglyceride content (IMCL) remained unchanged in both groups. After training, pre-exercise glycogen content was higher in CHO (545 +/- 19 mmol/kg dry wt; P = 0.02), but not in F (434 +/- 32 mmol/kg dry wt; P = 0.23). For a given initial glycogen content, F blunted exercise-induced glycogen breakdown when compared with CHO (P = 0.04). Neither IMCL breakdown (P = 0.23) nor fat oxidation rates during exercise were altered by training. Thus short-term training elicits similar adaptations in peak Vo(2) whether carried out in the fasted or carbohydrate-fed state. Although there was a decrease in exercise-induced glycogen breakdown and an increase in proteins involved in fat handling after fasting training, fat oxidation during exercise with carbohydrate intake was not changed.

Effect of endurance training on blood pressure at rest, during exercise and during 24 hours in sedentary men

The effect of 4 months of physical training on resting, exercise and 24-hour blood pressure (BP) was studied using a randomized crossover design in 26 healthy, sedentary men, with an average age of 39 +/- 10 (standard deviation) years. Peak oxygen uptake increased by 14% (p less than 0.001) and the physical working capacity at a heart rate of 130 beats/min by 25% (p less than 0.001). The heart rate was reduced by 7 beats/min at night (p less than 0.01) and by 6 beats/min during the day (p less than 0.001). Training-induced changes of BP varied according to measuring conditions. A decrease in BP at rest while sitting in the morning in the laboratory was significant for diastolic (-5 mm Hg, p less than 0.01) but not for systolic BP. During exercise, systolic BP was significantly lower after training, when measured at the same submaximal workloads. However, when workload was expressed as a percentage of peak oxygen uptake, systolic BP was not different before and after training. When measured during 24 hours, the training-induced change in BP was not significant at night either for systolic or diastolic BP. During the day the decrease in diastolic BP was significant (-5 mm Hg, p less than 0.001), but the change in systolic BP was not.

Creatine supplementation in health and disease: What is the evidence for long-term efficacy?

Creatine supplementation is an established ergogenic aid in sports and is now claimed to have therapeutical applications in a variety of diseases. The available literature mainly covers the short-term (one to several weeks) effects of creatine supplementation on skeletal muscle function in health and disease, which is of little help to evaluate the long-term (two or more months) potential of creatine as a drug in chronic disorders, such as neurodegenerative diseases or muscular dystrophies. Recent findings in healthy humans indicate that the beneficial effect on muscle function and muscle total creatine content may disappear when creatine is continuously ingested for more than two or three months. The mechanism for this habituation to chronic creatine exposure is poorly understood. The primary purpose of the present review article is to critically evaluate the available evidence for long-term efficacy of creatine administration and to hypothesize about ways to optimize creatine administration regimens.

Effect of prolonged physical exercise on intra-erythrocyte and plasma potassium

SummaryThe intracellular concentrations of sodium [Na+] and potassium [K+] and the water content in human erythrocytes were investigated in 21 male runners before and after a marathon. From 2 to 5 min after the race, the intra-erythrocyte [K+] was significantly decreased (p<0.001) by 7% whereas the plasma [K+], intra-erythrocyte [Na+] and the erythrocyte water content were unchanged. The change in the intra-erythrocyte [K+] observed immediately after the marathon, was negatively correlated with the race time (r=−0.44;p<0.05). Furthermore, the change in the plasma [K+] (r=−0.64;p<0.001) and the amount of K+ excreted in the urine during the race (r=0.54;p<0.05) were also, respectively, negatively and positively correlated with the race time. It is concluded that during prolonged physical exercise the erythrocytes could serve as a kind of K+ reservoir that is drained with increasing magnitude of body K+ loss. This might explain why in the faster marathon runners, in whom the urinary K+ loss is smaller and the K+ intake is greater than in the slower runners during race, the intra-erythrocyte [K+] is unchanged after a marathon whereas in the slower runners it is decreased.

Effects of Training On the Serum-lipid Profile in Normal Men

SummaryCross-sectional studies have demonstrated in the past that endurance-trained persons are characterised by a less atherogenic lipid profile than their sedentary counterparts: the former have clearly higher HDL-cholesterol and lower serum triglyceride concentrations than the latter, and also their LDL-cholesterol and total cholesterol concentrations are slightly lower. In a longitudinal intervention study in previously sedentary men, the effect of moderate short term physical training on the serum lipid profile was investigated. 30 healthy male volunteers were trained for 16 weeks, 3 hours weekly. After training their physical working capacity was increased on average by 29%. This was accompanied by an increment in the HDL-cholesterol fraction of 26%; the relative increase was greater for HDL2-(+32%) than for HDL3-cholesterol (+24%). VLDL-cholesterol was reduced by 21% at the end of the training period. On average, plasma total cholesterol, total triglycerides and LDL-cholesterol were not significantly changed at the end of the training period. Negative associations were, however, found between the training-induced increase in exercise capacity and the concomitant changes in plasma triglycerides and LDL-cholesterol. In conclusion, these longitudinal observations show that short term moderate endurance training improves the serum lipid profile in previously sedentary men.