Sanne Stegen

Influence of combined aerobic and resistance training on metabolic control, cardiovascular fitness and quality of life in adolescents with type 1 diabetes: a randomized controlled trial

Objective: To evaluate the effect of combined exercise training on metabolic control, physical fitness and quality of life in adolescents with type 1 diabetes. Design: A double-blind randomized controlled trial with patients receiving combined aerobic and strength or no training. Setting: University Hospital Ghent (Belgium). Subjects: Sixteen children with type 1 diabetes were randomized into a control group (n = 8) and an intervention group (n = 8). Interventions: Patients participated twice a week for 20 weeks in the combined aerobic and strength group. The control group continued their normal daily activities. Main measures: Before and after the intervention anthropometric variables (weight, length, BMI, body composition), metabolic control (glycaemia, HbA1c, daily insulin injected), aerobic capacity (peak V o 2, peak power, peak heart rate, 6-minute walk distance), strength (1 repetition maximum of upper and lower limb, hand grip strength, muscle fatigue resistance, sit-to-stand) and quality of life (SF-36) were assessed. Results: At baseline, none of the measured parameters differed significantly between the two groups. There was no significant evolution in the groups concerning anthropometric indices, glycaemia and HbA1c. However, the daily doses of insulin injected were significantly lowered in the training group (0.96 IU/kg.day pre versus 0.90 IU/kg.day post; P < 0,05), while it was increased in the control group. Physical fitness increased significantly in the training group. General health, vitality and role emotional had a tendency to improve. Conclusion: Combined exercise training seemed to lower daily insulin requirement and improve physical fitness, together with better well-being.

Effect of beta-alanine and carnosine supplementation on muscle contractility in mice

PURPOSE Enhanced carnosine levels have been shown to be ergogenic for high-intensity exercise performances, although the role of carnosine in the control of muscle function is poorly understood. Therefore, the aim of this study was to investigate the effect of long-term supplementation with increasing doses of carnosine and beta-alanine on muscle carnosine, anserine, and taurine levels and on in vitro contractility and fatigue in mice. METHODS Male Naval Medical Research Institute mice (n = 66) were control fed or supplemented with either carnosine (0.1%, 0.5%, or 1.8%) or beta-alanine (0.6 or 1.2%) in their drinking water for 8-12 wk. Soleus and extensor digitorum longus (EDL) were tested for in vitro contractile properties, and carnosine, anserine, and taurine content were measured in EDL and tibialis anterior by high-performance liquid chromatography. RESULTS Only supplementation with 1.8% carnosine and 1.2% beta-alanine resulted in markedly higher carnosine (up to +160%) and anserine levels (up to +46%) compared with control mice. Beta-alanine supplementation (1.2%) resulted in increased fatigue resistance in the beginning of the fatigue protocol in soleus (+2%-4%) and a marked leftward shift of the force-frequency relation in EDL (10%-31% higher relative forces). CONCLUSION Comparable with humans, beta-alanine availability seems to be the rate-limiting step for synthesis of muscle histidine-containing dipeptides in mice. Moreover, muscle histidine-containing dipeptides loading in mice moderately and muscle dependently affects excitation-contraction coupling and fatigue.

Muscle carnosine loading by beta-alanine supplementation is more pronounced in trained vs. untrained muscles

Carnosine occurs in high concentrations in human skeletal muscle and assists working capacity during high-intensity exercise. Chronic beta-alanine (BA) supplementation has consistently been shown to augment muscle carnosine concentration, but the effect of training on the carnosine loading efficiency is poorly understood. The aim of the present study was to compare muscle carnosine loading between trained and untrained arm and leg muscles. In a first study (n = 17), reliability of carnosine quantification by proton magnetic resonance spectroscopy ((1)H-MRS) was evaluated in deltoid and triceps brachii muscles. In a second study, participants (n = 35; 10 nonathletes, 10 cyclists, 10 swimmers, and 5 kayakers) were supplemented with 6.4 g/day of slow-release BA for 23 days. Carnosine content was evaluated in soleus, gastrocnemius medialis, and deltoid muscles by (1)H-MRS. All the results are reported as arbitrary units. In the nonathletes, BA supplementation increased carnosine content by 47% in the arm and 33% in the leg muscles (not significant). In kayakers, the increase was more pronounced in arm (deltoid) vs. leg (soleus + gastrocnemius) muscles (0.089 vs. 0.049), whereas the reverse pattern was observed in cyclists (0.065 vs. 0.084). Swimmers had significantly higher increase in carnosine in both deltoid (0.107 vs. 0.065) and gastrocnemius muscle (0.082 vs. 0.051) compared with nonathletes. We showed that 1) carnosine content can be reliably measured by (1)H-MRS in deltoid muscle, 2) carnosine loading is equally effective in arm vs. leg muscles of nonathletes, and 3) carnosine loading is more pronounced in trained vs. untrained muscles.

β-Alanine dose for maintaining moderately elevated muscle carnosine levels.

INTRODUCTION Chronic β-alanine (BA) supplementation is an increasingly popular nutritional strategy, because it can elevate muscle carnosine content and thereby enhance high-intensity exercise performance. The current study investigated 1) whether sex and body mass are determinants of BA-induced muscle carnosine loading and 2) the optimal maintenance dose for ensuring constantly elevated muscle carnosine stores. METHODS During the loading phase, 34 participants (men and women) were supplemented with 3.2 g (4 × 800 mg) BA per day for 46 d (slightly different loading strategies were applied concerning the effect of meal timing and supplementation form). Thereafter, 19 participants (men and women) continued taking free-powder BA for six more weeks (maintenance phase). The participants were matched and redivided into three groups receiving 0.4, 0.8, and 1.2 g·d(-1) BA, respectively. Muscle carnosine content was measured in the soleus and gastrocnemius muscles using proton magnetic resonance spectroscopy. RESULTS Body mass and sex had only minimal effect on the absolute increase in muscle carnosine. Given the lower baseline values in women, the relative increase for women was higher, indicating that women required less BA for the same relative increase. In addition, a significant negative correlation was observed between body mass and the relative increase in muscle carnosine (r = -0.45, P = 0.007). A maintenance dose of ∼1.2 g·d(-1) BA was the most effective in keeping muscle carnosine content elevated at the postsupplementation level. CONCLUSIONS Sex and body mass did not markedly affect the absolute increase during muscle carnosine loading, although they are determinants for the relative increase. In addition, we established for the first time an effective maintenance dose of ∼1.2 g·d(-1) BA to keep muscle carnosine content elevated at 30%-50% above baseline for a prolonged period.

Meal and beta-alanine coingestion enhances muscle carnosine loading.

INTRODUCTION Beta-alanine (BA) is a popular ergogenic supplement because it can induce muscle carnosine loading. We hypothesize that, by analogy with creatine supplementation, 1) an inverse relationship between urinary excretion and muscle loading is present, and 2) the latter is stimulated by carbohydrate- and protein-induced insulin action. METHODS In study A, the effect of a 5-wk slow-release BA (SRBA) supplementation (4.8 g · d(-1)) on whole body BA retention was determined in seven men. We further determined whether the coingestion of carbohydrates and proteins with SRBA would improve retention. In study B (34 subjects), we explored the effect of meal timing on muscle carnosine loading (3.2 g · d(-1) during 6-7 wk). One group received pure BA (PBA) in between the meals; the other received PBA at the start of the meals, to explore the effect of meal-induced insulin release. Further, we compared with a third group receiving SRBA at the start of the meals. RESULTS AND CONCLUSION Orally ingested SRBA has a very high whole body retention (97%-98%) that is not declining throughout the 5-wk supplementation period, nor is it influenced by the coingestion of macronutrients. Thus, a very small portion (1%-2%) is lost through urinary excretion, and equally only a small portion is incorporated into muscle carnosine (≈ 3%), indicating that most ingested BA is metabolized (possibly through oxidation). Second, in soleus muscles, the efficiency of carnosine loading is significantly higher when PBA is coingested with a meal (+64%) compared with in between the meals (+41%), suggesting that insulin stimulates muscle carnosine loading. Finally, the chronic supplementation of SRBA versus PBA seems equally effective.

The Effect of Combined Exercise Training in Adolescents Who Are Overweight Or Obese With Intellectual Disability: The Role of Training Frequency

Elmahgoub, SS, Calders, P, Lambers, S, Stegen, SM, Van Laethem, C, and Cambier, DC. The effect of combined exercise training in Adolescents Who Are Overweight or Obese with intellectual disability: the role of training frequency. J Strength Cond Res 25(8): 2274-2282, 2011—Data about effects of exercise training in adolescents with intellectual disability (ID) are very limited. This study investigated the effect of 2 different frequencies of the same intensity and total training volume of combined exercise training on indices of body composition, physical fitness, and lipid profile in overweight and obese adolescents with ID. A total of 45 overweight and obese adolescents with ID aged 14-22 years with a total IQ 45-70 received combined exercise training 3 times a week (CET3) for 30 sessions (10 weeks; n = 15), twice a week (CET2) for 30 sessions (15 weeks; n = 15), or no training (10 weeks; n = 15). Groups were matched for age, sex, and education form. Before and after the intervention period, indices of body composition, physical fitness and lipid profile have been evaluated. Compared to the control group, CET3 resulted in a significant improvement of physical fitness, obesity indices, and lipid profile of the participants. Comparing CET2 with CET3, no significantly different evolutions were noticed, except for lower limb strength in favor of exercising 3 times a week. In conclusion, exercising 2 times a week, which is more feasible and practical for participants and guidance, has the same health beneficial effects as 3 times per week in overweight and obese adolescents with ID in short-term training.

Muscle Histidine-Containing Dipeptides Are Elevated by Glucose Intolerance in Both Rodents and Men

Objective Muscle carnosine and its methylated form anserine are histidine-containing dipeptides. Both dipeptides have the ability to quench reactive carbonyl species and previous studies have shown that endogenous tissue levels are decreased in chronic diseases, such as diabetes. Design and Methods Rodent study: Skeletal muscles of rats and mice were collected from 4 different diet-intervention studies, aiming to induce various degrees of glucose intolerance: 45% high-fat feeding (male rats), 60% high-fat feeding (male rats), cafeteria feeding (male rats), 70% high-fat feeding (female mice). Body weight, glucose-tolerance and muscle histidine-containing dipeptides were assessed. Human study: Muscle biopsies were taken from m. vastus lateralis in 35 males (9 lean, 8 obese, 9 prediabetic and 9 newly diagnosed type 2 diabetic patients) and muscle carnosine and gene expression of muscle fiber type markers were measured. Results Diet interventions in rodents (cafeteria and 70% high-fat feeding) induced increases in body weight, glucose intolerance and levels of histidine-containing dipeptides in muscle. In humans, obese, prediabetic and diabetic men had increased muscle carnosine content compared to the lean (+21% (p>0.1), +30% (p<0.05) and +39% (p<0.05), respectively). The gene expression of fast-oxidative type 2A myosin heavy chain was increased in the prediabetic (1.8-fold, p<0.05) and tended to increase in the diabetic men (1.6-fold, p = 0.07), compared to healthy lean subjects. Conclusion Muscle histidine-containing dipeptides increases with progressive glucose intolerance, in male individuals (cross-sectional). In addition, high-fat diet-induced glucose intolerance was associated with increased muscle histidine-containing dipeptides in female mice (interventional). Increased muscle carnosine content might reflect fiber type composition and/or act as a compensatory mechanism aimed at preventing cell damage in states of impaired glucose tolerance.

Effects of Histidine and β-alanine Supplementation on Human Muscle Carnosine Storage.

Purpose Carnosine is a dipeptide composed of &bgr;-alanine and L-histidine and is present in skeletal muscle. Chronic oral &bgr;-alanine supplementation can induce muscle carnosine loading and is therefore seen as the rate-limiting factor for carnosine synthesis. However, the effect of L-histidine supplementation on carnosine levels in humans is never established. This study aims to investigate whether 1) L-histidine supplementation can induce muscle carnosine loading and 2) combined supplementation of both amino acids is more efficient than &bgr;-alanine supplementation alone. Methods Fifteen male and 15 female participants were equally divided in three groups. Each group was supplemented with either pure &bgr;-alanine (BA) (6 g·d−1), L-histidine (HIS) (3.5 g·d−1), or both amino acids (BA + HIS). Before (D0), after 12 d (D12), and after 23 d (D23) of supplementation, carnosine content was evaluated in soleus and gastrocnemius medialis muscles by 1H-MRS, and venous blood samples were collected. Muscle biopsies were taken at D0 and D23 from the vastus lateralis. Plasma and muscle metabolites (&bgr;-alanine, histidine, and carnosine) were measured by high-performance liquid chromatography. Results Both BA and BA + HIS groups showed increased carnosine concentrations in all investigated muscles, with no difference between these groups. By contrast, carnosine levels in the HIS group remained unaltered. Histidine levels were significantly decreased in plasma (−30.6%) and muscle (−31.6%) of the BA group, and this was prevented when &bgr;-alanine and L-histidine were supplemented simultaneously. Conclusion We confirm that &bgr;-alanine, and not L-histidine, is the rate-limiting precursor for carnosine synthesis in human skeletal muscle. Yet, although L-histidine is not rate limiting, its availability is not unlimited and gradually declines upon chronic &bgr;-alanine supplementation. The significance of this decline still needs to be determined, but may affect physiological processes such as protein synthesis.

Carnosine and anserine homeostasis in skeletal muscle and heart is controlled by β-alanine transamination.

Using recombinant DNA technology, the present study provides the first strong and direct evidence indicating that β‐alanine is an efficient substrate for the mammalian transaminating enzymes 4‐aminobutyrate‐2‐oxoglutarate transaminase and alanine‐glyoxylate transaminase. The concentration of carnosine and anserine in murine skeletal and heart muscle depends on circulating availability of β‐alanine, which is in turn controlled by degradation of β‐alanine in liver and kidney. Chronic oral β‐alanine supplementation is a popular ergogenic strategy in sports because it can increase the intracellular carnosine concentration and subsequently improve the performance of high‐intensity exercises. The present study can partly explain why the β‐alanine supplementation protocol is so inefficient, by demonstrating that exogenous β‐alanine can be effectively routed toward oxidation.

Plasma carnosine, but not muscle carnosine, attenuates high-fat diet-induced metabolic stress

There is growing in vivo evidence that the dipeptide carnosine has protective effects in metabolic diseases. A critical unanswered question is whether its site of action is tissues or plasma. This was investigated using oral carnosine versus β-alanine supplementation in a high-fat diet rat model. Thirty-six male Sprague-Dawley rats received a control diet (CON), a high-fat diet (HF; 60% of energy from fat), the HF diet with 1.8% carnosine (HFcar), or the HF diet with 1% β-alanine (HFba), as β-alanine can increase muscle carnosine without increasing plasma carnosine. Insulin sensitivity, inflammatory signaling, and lipoxidative stress were determined in skeletal muscle and blood. In a pilot study, urine was collected. The 3 HF groups were significantly heavier than the CON group. Muscle carnosine concentrations increased equally in the HFcar and HFba groups, while elevated plasma carnosine levels and carnosine-4-hydroxy-2-nonenal adducts were detected only in the HFcar group. Elevated plasma and urine N(ε)-(carboxymethyl)lysine in HF rats was reduced by ∼50% in the HFcar group but not in the HFba group. Likewise, inducible nitric oxide synthase mRNA was decreased by 47% (p < 0.05) in the HFcar group, but not in the HFba group, compared with HF rats. We conclude that plasma carnosine, but not muscle carnosine, is involved in preventing early-stage lipoxidation in the circulation and inflammatory signaling in the muscle of rats.