TOTUM-63, a plant-based polyphenol-rich extract, improves glycaemic control in subjects with prediabetes or early stage newly-diagnosed type 2 diabetes in a randomized, double-blind, placebo-controlled trial.

AIM: The plant-based polyphenol-rich extract TOTUM-63 improves glucose homeostasis in various preclinical models of obesity and type 2 diabetes (T2D). A pilot exploratory study showed that TOTUM-63 has good safety and tolerability profiles, and beneficial effects on postprandial glucose control in healthy individuals with overweight. The aim of this study was to assess the effects of TOTUM-63 on glycaemic control in individuals with prediabetes or early stage newly-diagnosed T2D (which does not require pharmacological treatment). MATERIALS AND METHODS: This study was a multicentre, randomized, double-blind, placebo-controlled trial. Individuals with prediabetes or early stage newly-diagnosed T2D and with overweight/abdominal obesity received TOTUM-63 (5 g/day) or placebo for 6 months. The primary outcome was the change in fasting blood glucose. RESULTS: Fifty-one participants (age: 57.1 ± 10 years; body mass index: 31.3 ± 5.7 kg.m2 ; 35 women and 16 men) completed the study (n = 38 TOTUM-63, n = 13 placebo). After 6 months, blood glucose concentration after fasting and after the 2-h oral glucose tolerance test was reduced in the TOTUM-63-treated group compared with the placebo group (placebo-corrected difference between baseline and month 6: -0.71 mmol/L, p < .05, and -1.93 mmol/L, p < .05, respectively). TOTUM-63 was safe and well tolerated and significantly reduced body weight gain (-1.9 kg; p < .05), waist circumference (-4.5 cm; p < .001), circulating triglycerides (-0.54 mmol/L; p < .01) and low-density lipoprotein-cholesterol (-0.38 mmol/L; p < .05) compared with placebo. CONCLUSIONS: TOTUM-63 lowered fasting blood glucose in participants with impaired fasting glycaemia and glucose intolerance. Moreover, TOTUM-63 showed a good safety and tolerability profile and improved several metabolic syndrome features. Therefore, TOTUM-63 is a promising candidate for T2D prevention.

Beneficial Effects of Linseed Supplementation on Gut Mucosa-Associated Microbiota in a Physically Active Mouse Model of Crohn's Disease.

The Western diet, rich in lipids and in n-6 polyunsaturated fatty acids (PUFAs), favors gut dysbiosis observed in Crohn's disease (CD). The aim of this study was to assess the effects of rebalancing the n-6/n-3 PUFA ratio in CEABAC10 transgenic mice that mimic CD. Mice in individual cages with running wheels were randomized in three diet groups for 12 weeks: high-fat diet (HFD), HFD + linseed oil (HFD-LS-O) and HFD + extruded linseed (HFD-LS-E). Then, they were orally challenged once with the Adherent-Invasive Escherichia coli (AIEC) LF82 pathobiont. After 12 weeks of diet, total energy intake, body composition, and intestinal permeability were not different between groups. After the AIEC-induced intestinal inflammation, fecal lipocalin-2 concentration was lower at day 6 in n-3 PUFAs supplementation groups (HFD-LS-O and HFD-LS-E) compared to HFD. Analysis of the mucosa-associated microbiota showed that the abundance of Prevotella, Paraprevotella, Ruminococcus, and Clostridiales was higher in the HFD-LS-E group. Butyrate levels were higher in the HFD-LS-E group and correlated with the Firmicutes/Proteobacteria ratio. This study demonstrates that extruded linseed supplementation had a beneficial health effect in a physically active mouse model of CD susceptibility. Additional studies are required to better decipher the matrix influence in the linseed supplementation effect.

The Nutrition-Microbiota-Physical Activity Triad: An Inspiring New Concept for Health and Sports Performance.

The human gut microbiota is currently the focus of converging interest in many diseases and sports performance. This review presents gut microbiota as a real "orchestra conductor" in the host's physio(patho)logy due to its implications in many aspects of health and disease. Reciprocally, gut microbiota composition and activity are influenced by many different factors, such as diet and physical activity. Literature data have shown that macro- and micro-nutrients influence gut microbiota composition. Cumulative data indicate that gut bacteria are sensitive to modulation by physical activity, as shown by studies using training and hypoactivity models. Sports performance studies have also presented interesting and promising results. Therefore, gut microbiota could be considered a "pivotal" organ for health and sports performance, leading to a new concept: the nutrition-microbiota-physical activity triad. The next challenge for the scientific and medical communities is to test this concept in clinical studies. The long-term aim is to find the best combination of the three elements of this triad to optimize treatments, delay disease onset, or enhance sports performance. The many possibilities offered by biotic supplementation and training modalities open different avenues for future research.

Substrate metabolism during exercise: Sexual dimorphism and women's specificities.

The aim of this review is to discuss sexual dimorphism of energy metabolism, and to describe the impact of women's hormonal status on substrate oxidation during exercise. Many evidences indicate that sex steroids play a pivotal role in the sex-related differences of body composition and energy substrate storage. Compared with men, women rely more on fat and less on carbohydrates at the same relative exercise intensity. Scientific data suggest that 17-ß oestradiol is a key hormone for the regulation of body composition and substrate metabolism. However, in women, measurements with stable isotopic tracers did not highlight any difference in whole-body substrate oxidation rates between the follicular and luteal phases of the menstrual cycle during endurance exercise. The remaining discrepancies about the effect of menstrual cycle-related hormone fluctuations on substrate oxidation could be partly explained by the exercise intensity, which is an important regulator of substrate oxidation. Due to their specific nature and concentration, the synthetic ovarian hormones contained in oral contraceptives also influence substrate metabolism during endurance exercise. However, more studies are needed to confirm that oral contraceptives increase lipolytic activity during endurance exercise without any substantial (or detectable) effect on substrate utilization. Pregnancy and menopause also modify body composition and substrate utilization during exercise through specific hormonal fluctuations. This review highlights that the hormonal status is likely to affect substrate oxidation during exercise in women emphasizing the need to take it into consideration to optimize their health and performance.

Beneficial Effects of High Intensity Interval Training and/or Linseed Oil Supplementation to Limit Obesity-Induced Oxidative Stress in High Fat Diet-Fed Rats.

High-intensity interval training (HIIT) and linseed oil (LO) supplementation are effective strategies to reduce obesity-induced oxidative stress. Our aim was to determine whether the HIIT + LO combination prevents obesity-induced oxidative stress in high fat diet (HFD)-fed rats. HFD-fed 8-week-old, male, Wistar rats were subdivided in four groups: HFD, LO (2% of sunflower oil replaced with 2% of LO in the HFD), HIIT (4 days/week for 12 weeks), and HIIT + LO. Wistar rats fed a low-fat diet (LFD) were used as controls. Epididymal and subcutaneous adipose tissue, gastrocnemius muscle, liver, and plasma samples were collected to measure oxidative stress markers (AOPP, oxLDL), antioxidant (SOD, CAT, and GPx activities) and pro-oxidant (NOx and XO) enzyme activities. Compared with the LFD, the HFD altered the pro/antioxidant status in different tissues (increase of AOPP, oxLDL, SOD and catalase activities in plasma, and SOD activity increase in liver and decrease in adipose tissues) but not in gastrocnemius. LO upregulated CAT activity and decreased NOx in liver. HIIT alleviated HFD negative effects in liver by reducing SOD and NOx activities. Moreover, the HIIT + LO combination potentiated SOD activity upregulation in subcutaneous tissue. HIIT and LO supplementation have independent beneficial effects on the pro/antioxidant balance. Their association promotes SOD activity in subcutaneous adipose tissue.

The TOTUM-63 Supplement and High-Intensity Interval Training Combination Limits Weight Gain, Improves Glycemic Control, and Influences the Composition of Gut Mucosa-Associated Bacteria in Rats on a High Fat Diet.

Obesity and prediabetes are the two strongest risk factors of type 2 diabetes. It has been reported that TOTUM-63, a polyphenol-rich plant extract, has beneficial effects on body weight (BW) and insulin resistance in mice fed a high fat diet (HFD). The study aim was to determine whether high-intensity interval training (HIIT) and/or TOTUM-63 supplementation improved body composition and glycemic control and gut microbiota composition in a Western diet-induced obesity rat model. Wistar rats received a standard diet (CTRL; control; n = 12) or HFD (HFD; n = 48) for 16 weeks. Then, HFD rats were divided in four groups: HFD, HFD + TOTUM-63 (T63), HFD + HIIT (HIIT), and HFD + HIIT +T63 (HIIT + T63). Training was performed 4 days/week for 12 weeks. TOTUM-63 was included in diet composition (2%). The HIIT + T63 combination significantly limited BW gain, without any energy intake modulation, and improved glycemic control. BW variation was correlated with increased α-diversity of the colon mucosa microbiota in the HIIT + T63 group. Moreover, the relative abundance of Anaeroplasma, Christensenellaceae and Oscillospira was higher in the HIIT + T63 group. Altogether, these results suggest that the HIIT and TOTUM-63 combination could be proposed for the management of obesity and prediabetes.

Effects of Totum-63 on glucose homeostasis and postprandial glycemia: a translational study.

Global prevalence of type 2 diabetes (T2D) is rising and may affect 700 million people by 2045. Totum-63 is a polyphenol-rich natural composition developed to reduce the risk of T2D. We first investigated the effects of Totum-63 supplementation in high-fat diet (HFD)-fed mice for up to 16 wk and thereafter assessed its safety and efficacy (2.5 g or 5 g per day) in 14 overweight men [mean age 51.5 yr, body mass index (BMI) 27.6 kg·m-2] for 4 wk. In HFD-fed mice, Totum-63 reduced body weight and fat mass gain, whereas lean mass was unchanged. Moreover, fecal energy excretion was higher in Totum-63-supplemented mice, suggesting a reduction of calorie absorption in the digestive tract. In the gut, metagenomic analyses of fecal microbiota revealed a partial restoration of HFD-induced microbial imbalance, as shown by principal coordinate analysis of microbiota composition. HFD-induced increase in HOMA-IR score was delayed in supplemented mice, and insulin response to an oral glucose tolerance test was significantly reduced, suggesting that Totum-63 may prevent HFD-related impairments in glucose homeostasis. Interestingly, these improvements could be linked to restored insulin signaling in subcutaneous adipose tissue and soleus muscle. In the liver, HFD-induced steatosis was reduced by 40% (as shown by triglyceride content). In the subsequent study in men, Totum-63 (5 g·day-1) improved glucose and insulin responses to a high-carbohydrate breakfast test (84% kcal carbohydrates). It was well tolerated, with no clinically significant adverse events reported. Collectively, these data suggest that Totum-63 could improve glucose homeostasis in both HFD-fed mice and overweight individuals, presumably through a multitargeted action on different metabolic organs.NEW & NOTEWORTHY Totum-63 is a novel polyphenol-rich natural composition developed to reduce the risk of T2D. Totum-63 showed beneficial effects on glucose homeostasis in HFD-fed mice, presumably through a multitargeted action on different metabolic organs. Totum-63 was well tolerated in humans and improved postprandial glucose and insulin responses to a high-carbohydrate breakfast test.

Preventive Effect of Spontaneous Physical Activity on the Gut-Adipose Tissue in a Mouse Model That Mimics Crohn's Disease Susceptibility.

Crohn's disease is characterized by abnormal ileal colonization by adherent-invasive E. coli (AIEC) and expansion of mesenteric adipose tissue. This study assessed the preventive effect of spontaneous physical activity (PA) on the gut-adipose tissue in a mouse model that mimics Crohn's disease susceptibility. Thirty-five CEABAC10 male mice performed spontaneous PA (wheel group; n = 24) or not (controls; n = 11) for 12 weeks. At week 12, mice were orally challenged with the AIEC LF82 strain for 6 days. Body composition, glycaemic control, intestinal permeability, gut microbiota composition, and fecal short-chain fatty acids were assessed in both groups. Animals were fed a high fat/high sugar diet throughout the study. After exposure to AIEC, mesenteric adipose tissue weight was lower in the wheel group. Tight junction proteins expression increased with spontaneous PA, whereas systemic lipopolysaccharides were negatively correlated with the covered distance. Bifidobacterium and Lactobacillus decreased in controls, whereas Oscillospira and Ruminococcus increased in the wheel group. Fecal propionate and butyrate were also higher in the wheel group. In conclusion, spontaneous physical activity promotes healthy gut microbiota composition changes and increases short-chain fatty acids in CEABAC10 mice fed a Western diet and exposed to AIEC to mimic Crohn's disease.

Neuregulin 1 improves complex 2-mediated mitochondrial respiration in skeletal muscle of healthy and diabetic mice.

It has been reported that neuregulin1 (NRG1) improves glucose tolerance in healthy and diabetic rodents. In vitro studies also suggest that NRG1 regulates myocyte oxidative capacity. To confirm this observation in vivo, we evaluated the effect on mitochondrial function of an 8-week treatment with NRG1 in db/db diabetic mice and C57BL/6JRJ healthy controls. NRG1 treatment improved complex 2-mediated mitochondrial respiration in the gastrocnemius of both control and diabetic mice and increased mitochondrial complex 2 subunit content by 2-fold. This effect was not associated with an increase in mitochondrial biogenesis markers. Enhanced ERBB4 phosphorylation could mediate NRG1 effects on mitochondrial function through signalling pathways, independently of ERK1/2, AKT or AMPK.

Effects of high-intensity interval training and moderate-intensity continuous training on glycaemic control and skeletal muscle mitochondrial function in db/db mice.

Physical activity is known as an effective strategy for prevention and treatment of Type 2 Diabetes. The aim of this work was to compare the effects of a traditional Moderate Intensity Continuous Training (MICT) with a High Intensity Interval Training (HIIT) on glucose metabolism and mitochondrial function in diabetic mice. Diabetic db/db male mice (N = 25) aged 6 weeks were subdivided into MICT, HIIT or control (CON) group. Animals in the training groups ran on a treadmill 5 days/week during 10 weeks. MICT group ran for 80 min (0° slope) at 50-60% of maximal speed (Vmax) reached during an incremental test. HIIT group ran thirteen times 4 minutes (20° slope) at 85-90% of Vmax separated by 2-min-rest periods. HIIT lowered fasting glycaemia and HbA1c compared with CON group (p < 0.05). In all mitochondrial function markers assessed, no differences were noted between the three groups except for total amount of electron transport chain proteins, slightly increased in the HIIT group vs CON. Western blot analysis revealed a significant increase of muscle Glut4 content (about 2 fold) and higher insulin-stimulated Akt phosphorylation ratios in HIIT group. HIIT seems to improve glucose metabolism more efficiently than MICT in diabetic mice by mechanisms independent of mitochondrial adaptations.

Nutritional and exercise interventions variably affect estrogen receptor expression in the adipose tissue of male rats.

Energy-dense food consumption and lack of physical activity are implicated in the development of the current obesity epidemic. The role of estrogen in adiposity and fuel partitioning is mediated mainly though the estrogen receptor α (ERα) isoform. We hypothesized that nutritional adaptation and exercise training, either individually or combined, could impact ERα expression in adipose tissue relative to glucose tolerance. Seventy-two Wistar rats were submitted to a high-fat, high-sucrose (HF-HS) diet for 16weeks. The first phase of our study was to investigate the effect of an HF-HS diet on whole-body glucose tolerance, as well as on body composition and ERα expression in different adipose tissues. Second, we investigated the effect of switching to a well-balanced diet, with or without exercise training for 8 weeks, on those same parameters. After the first part of this study, HF-HS-fed rats were fatter (8%) than control rats. Despite a decrease in glucose tolerance, ERα expression in adipose tissues was not significantly altered by an HF-HS diet. The return to a well-balanced diet significantly increased ERα expression in perirenal and epididymal adipose tissue, but there was no effect of diet or exercise training on whole-body glucose tolerance. The present findings suggest that diet is a powerful modulator of ERα expression in adipose tissue, as nutritional modulation after an HF-HS diet strongly affects ERα expression, particularly in perirenal and epididymal adipose tissue. However, ERα expression in adipose tissue does not appear to be associated with whole-body glucose tolerance.

Neuregulin 1 Improves Glucose Tolerance in db/db Mice.

In vitro experiments using rodent skeletal muscle cells suggest that neuregulin 1 (NRG1) is involved in glucose metabolism regulation, although no study has evaluated the role of NRG1 in systemic glucose homeostasis. The purpose of this study was to investigate the effect of chronic and acute NRG1 treatment on glucose homeostasis in db/db mice. To this aim, glucose tolerance tests were performed in 8-week-old male db/db mice after treatment with NRG1 (50µg.kg-1) or saline 3 times per week for 8 weeks. In other experiments, glucose tolerance and pyruvate tolerance tests were performed in db/db mice 15 minutes after a single NRG1 (50µg.kg-1) or saline injection. Liver, adipose tissue, hypothalamus and skeletal muscle were also collected 30 minutes after acute NRG1 (50µg.kg-1) or saline treatment, and the phosphorylation status of the ERBB receptors, AKT (on Ser473) and FOXO1 (on Ser256) was assessed by western blotting. Chronic treatment (8 weeks) with NRG1 improved glucose tolerance in db/db mice. Acute treatment also lowered glycemia and insulinemia during glucose or pyruvate tolerance tests. NRG1 acute injection induced activation of ERBB3 receptors and phosphorylation of AKT and FOXO1 only in liver. Altogether, this study shows that acute and chronic NRG1 treatments improve glucose tolerance in db/db mice. This effect could be mediated through inhibition of hepatic gluconeogenesis.

Exercise training and return to a well-balanced diet activate the neuregulin 1/ErbB pathway in skeletal muscle of obese rats.

KEY POINTS: Some studies suggest that neuregulin 1 (NRG1) could be involved in the regulation of skeletal muscle energy metabolism in rodents. Here we assessed whether unbalanced diet is associated with alterations of the NRG1 signalling pathway and whether exercise and diet might restore NRG1 signalling in skeletal muscle of obese rats. We show that diet-induced obesity does not impair NRG1 signalling in rat skeletal muscle. We also report that endurance training and a well-balanced diet activate the NRG1 signalling in skeletal muscle of obese rats, possibly via a new mechanism mediated by the protease ADAM17. These results suggest that some beneficial effects of physical activity and diet in obese rats could be partly explained by stimulation of the NRG1 signalling pathway. ABSTRACT: Some studies suggest that the signalling pathway of neuregulin 1 (NRG1), a protein involved in the regulation of skeletal muscle metabolism, could be altered by nutritional and exercise interventions. We hypothesized that diet-induced obesity could lead to alterations of the NRG1 signalling pathway and that chronic exercise could improve NRG1 signalling in rat skeletal muscle. To test this hypothesis, male Wistar rats received a high fat/high sucrose (HF/HS) diet for 16 weeks. At the end of this period, NRG1 and ErbB expression/activity in skeletal muscle was assessed. The obese rats then continued the HF/HS diet or were switched to a well-balanced diet. Moreover, in both groups, half of the animals also performed low intensity treadmill exercise training. After another 8 weeks, NRG1 and ErbB expression/activity in skeletal muscle were tested again. The 16 week HF/HS diet induced obesity, but did not significantly affect the NRG1/ErbB signalling pathway in rat skeletal muscle. Conversely, after the switch to a well-balanced diet, NRG1 cleavage ratio and ErbB4 amount were increased. Chronic exercise training also promoted NRG1 cleavage, resulting in increased ErbB4 phosphorylation. This result was associated with increased protein expression and phosphorylation ratio of the metalloprotease ADAM17, which is involved in NRG1 shedding. Similarly, in vitro stretch-induced activation of ADAM17 in rat myoblasts induced NRG1 cleavage and ErbB4 activation. These results show that low intensity endurance training and well-balanced diet activate the NRG1-ErbB4 pathway, possibly via the metalloprotease ADAM17, in skeletal muscle of diet-induced obese rats.

Osteocyte apoptosis and lipid infiltration as mechanisms of alcohol-induced bone loss.

AIMS: We carried out an in vivo study to assess the relationship between increase in adiposity in the marrow and osteocyte apoptosis in the case of alcohol-induced bone loss. METHODS AND RESULTS: After alcohol treatment, the number of apoptotic osteocytes was increased and lipid droplets were accumulated within the osteocytes, the bone marrow and the cortical bone micro-vessels. At last, we found an inverse correlation between bone mineral density and osteocyte apoptosis and strong significant correlations between the osteocyte apoptotic number and lipid droplet accumulation in osteocyte and bone micro-vessels. CONCLUSION: These data show that alcohol-induced bone loss is associated with osteocyte apoptosis and lipid accumulation in the bone tissue. This lipid intoxication, or 'bone steatosis', is correlated with lipid accumulation in bone marrow and blood micro-vessels.

Influence of hormonal status on substrate utilization at rest and during exercise in the female population.

During exercise, substrate utilization plays a major role in performance and disease prevention. The contribution of fat and carbohydrates to energy expenditure during exercise is modulated by several factors, including intensity and duration of exercise, age, training and diet, but also gender. Because sex hormone levels change throughout a woman's lifetime (in connection with puberty, the menstrual cycle, use of oral contraceptives and menopause), the female population has to be considered specifically in terms of substrate utilization, and metabolic and hormonal responses to exercise. Before puberty, there is no difference between males and females when it comes to substrate oxidation during exercise. This is not the case during adulthood, since women are known to rely more on fat than men for the same relative intensity of exercise. Among adult women, the menstrual cycle and use of oral contraceptives may influence substrate oxidation. While some authors have noted that the luteal phase of the menstrual cycle is connected with greater lipid oxidation, compared with the follicular stage, other authors have found no difference. Among oral contraceptive users, fat oxidation is sometimes increased during prolonged exercise with a concomitant rise in lipolytic hormones, as well as growth hormone. If this result is not always observed, the type of oral contraceptive (monophasic vs triphasic) and hormone doses may be implicated. Menopause represents a hormonal transition in a woman's life, leading to a decline in ovarian hormone production. A decrease in fat oxidation is consequently observed, and some studies have demonstrated a similar respiratory exchange ratio during prolonged exercise in postmenopausal women and in men. As is the case during puberty, no sex difference should thus appear after menopause in the absence of hormonal replacement therapy (HRT). Results concerning women who take HRT remain conflicting. HRT may act on fat loss by increasing lipid metabolism, but this depends on how the treatment is administered (orally vs transdermally). To better understand the role of ovarian hormones in substrate oxidation, studies have made use of animal protocols to investigate cellular mechanisms. Estradiol and progesterone seem to have opposite effects, with greater lipid oxidation when estradiol is used alone. However, the concentrations used (physiological levels or pharmacological doses) may considerably modify fuel selection. In cases where conflicting data are observed in studies of substrate utilization and prolonged exercise in women, methodological reasons must be called into question. Too many parameters, which oftentimes are not specified, may modulate substrate utilization and metabolic and hormonal responses to prolonged exercise. Although information is generally provided about the type of exercise, its duration and the subjects' training level, detailed information is not always given about the subjects' nutritional state and, more specifically, the hormonal status of female subjects. The primary purpose of this review was to identify the impact of hormonal status on substrate oxidation among female subjects at rest and during exercise. A second aim was to describe gender differences in substrate utilization during exercise.

Cortical bone is more sensitive to alcohol dose effects than trabecular bone in the rat.

OBJECTIVE: While chronic alcohol consumption is known to decrease bone mineral content (BMC), bone mineral density (BMD), and negatively modify trabecular bone microarchitecture, the impact of alcohol on cortical microarchitecture is still unclear. The aim of this study was to investigate the effects of various doses of alcohol on bone density, trabecular and cortical parameters and bone strength in rats. METHODS: Forty-eight male Wistar rats were divided into four groups: control (C), alcohol 25% v/v (A25), alcohol 30% v/v (A30) and alcohol 35% v/v (A35). Rats in the alcohol groups were fed a solution composed of ethanol and water for 17 weeks while the control group drank only water. Bone quality and quantity were evaluated through the analysis of density, trabecular and cortical bone microarchitectural parameters, osteocalcin and N-Telopeptide concentrations and a 3-point bending test. RESULTS: Bone density along with trabecular and cortical thickness were lower in alcohol groups compared to C. BMD was lower in A35 vs. A30 and cortical thickness was lower in A35 vs. A25 and A30. Pore number was increased by alcohol and the porosity was greater in A35 compared to C. N-Telopeptide concentration was decreased in alcohol groups compared to control whereas no differences were observed in osteocalcin concentrations. Maximal energy to failure was lower in A25 and A35 compared to C. CONCLUSION: Chronic ethanol consumption increases cortical bone damage in rats and may have detrimental effects on bone strength. These effects were dose-dependent, with greater negative effects proportionate to greater alcohol doses.

Combined effects of chronic alcohol consumption and physical activity on bone health: study in a rat model.

Chronic alcohol consumption may be deleterious for bone tissue depending on the amount of ethanol consumed, whereas physical activity has positive effects on bone. This study was designed to analyze the effects of moderate alcohol consumption on bone in trained rats. 48 male Wistar rats were divided into four groups: control (C), alcohol (A), exercise (E) and alcohol + exercise (AE). A and AE groups drank a solution composed of water and ethanol. E and AE groups were trained for 2 months (treadmill: 40 min/day, 5 times/week). Body composition and bone mineral density (BMD) were assessed by dual X-ray absorptiometry and microarchitectural parameters using micro-computed tomography. Serum osteocalcin and CTx were determined by ELISA assays. The body weight and lean mass gain were lower in group A, while the fat mass gain was lower in exercised groups. BMD and BMC were higher with alcohol after body weight adjustment. Trabecular thickness was significantly higher in AE and A groups compared to C and E; cross-sectional area was larger in A and C groups compared to AE and E. CTx levels were higher in A compared to C and in AE and E versus C and A. Osteocalcin levels were significantly greater in AE and E groups versus C and A. In conclusion, the light to moderate alcohol consumption over a short period increased the trabecular thickness, BMC and BMD in A and AE groups. However, we observed alterations in bone remodeling and body composition with alcohol, at the end of the protocol, which did not appear when alcohol was combined to exercise.

No effect of creatine supplementation on human myofibrillar and sarcoplasmic protein synthesis after resistance exercise.

Muscle hypertrophy during resistance training is reportedly increased by creatine supplementation. Having previously failed to find an anabolic effect on muscle protein turnover at rest, either fed or fasted, we have now examined the possibility of a stimulatory effect of creatine in conjunction with acute resistance exercise. Seven healthy men (body mass index, 23 +/- 2 kg/m2, 21 +/- 1 yr, means +/- SE) performed 20 x 10 repetitions of leg extension-flexion at 75% one-repetition maximum in one leg, on two occasions, 4 wk apart, before and after ingesting 21 g/day creatine for 5 days. The subjects ate approximately 21 g maltodextrin + 6 g protein/h for 3 h postexercise. We measured incorporation of [1-13C]leucine into quadriceps muscle proteins in the rested and exercised legs. Leg protein breakdown (as dilution of [2H5]phenylalanine) was also assessed in the exercised and rested leg postexercise. Creatine supplementation increased muscle total creatine by approximately 21% (P < 0.01). Exercise increased the synthetic rates of myofibrillar and sarcoplasmic proteins by two- to threefold (P < 0.05), and leg phenylalanine balance became more positive, but creatine was without any anabolic effect.

Creatine supplementation has no effect on human muscle protein turnover at rest in the postabsorptive or fed states.

Dietary creatine supplementation is associated with increases in muscle mass, but the mechanism is unknown. We tested the hypothesis that creatine supplementation enhanced myofibrillar protein synthesis (MPS) and diminished muscle protein breakdown (MPB) in the fed state. Six healthy men (26 +/- 7 yr, body mass index 22 +/- 4 kg/m(2)) were studied twice, 2-4 wk apart, before and after ingestion of creatine (21 g/day, 5 days). We carried out two sets of measurements within 5.5 h of both MPS (by incorporation of [1-(13)C]leucine in quadriceps muscle) and MPB (as dilution of [1-(13)C]leucine or [(2)H(5)]phenylalanine across the forearm); for the first 3 h, the subjects were postabsorptive but thereafter were fed orally (0.3 g maltodextrin and 0.083 g protein. kg body wt(-1) x h(-1)). Creatine supplementation increased muscle total creatine by approximately 30% (P < 0.01). Feeding had significant effects, doubling MPS (P < 0.001) and depressing MPB by approximately 40% (P < 0.026), but creatine had no effect on turnover in the postabsorptive or fed states. Thus any increase in muscle mass accompanying creatine supplementation must be associated with increased physical activity.