Nutritional interventions to preserve skeletal muscle mass

Muscle mass is the main predictor for muscle strength and physical function. The amount of muscle mass can decline rapidly during periods of reduced physical activity or during periods of energy intake restriction. For athletes, it is important to maintain muscle mass, since the loss of muscle is associated with decreased muscle strength, decreased physical performance and a longer recovery period. In the older and more clinically compromised populations, the consequences of muscle loss can substantially impact metabolic health, physical functioning, quality of life and mortality rates. In this thesis, the effects of different nutritional interventions on the preservation of muscle mass are being evaluated. Vitamin D deficiency (serum 25-hydroxyvitamin D or 25(OH)D) has been associated with increased muscle loss and reduced muscle strength. In chapter 2, we identified seasonal changes in 25(OH)D concentration in elite athletes. We observed that 25(OH)D concentrations were highest at the end of summer (113±26 nmol/L), and lowest at the end of winter (78±30 nmol/L). Athletes that had a sufficient 25(OH)D concentration (>75 nmol/L) at the start of the study, still had a high risk (20%) of being deficient (chapter 3, we assessed 25(OH)D concentrations in 128 highly-trained athletes and found that 70% had a deficient or insufficient 25(OH)D concentration at the end of the winter season. Supplementation with 2200 IU/d vitamin D resulted in a sufficient 25(OH)D concentration in 80% of the athletes after 12 months and was therefore a better dosage to improve 25(OH)D concentration than 400 or 1100 IU/d. In the following chapters, we assessed the effects of creatine supplementation (chapter 4), leucine supplementation (chapter 5) and nandrolone administration (chapter 6) on the preservation of muscle mass during a short period of muscle disuse. For all of these compounds there is prior evidence for their efficacy in augmenting muscle mass and strength gains in combination with resistance-type exercise training and all have been suggested to attenuate the loss of muscle mass during a period of muscle disuse. During 7 days of single-leg immobilization, muscle mass decreased by ~6% and muscle strength decreased by ~8%. Surprisingly, none of the tested compounds attenuated the loss of muscle mass during 7 days of single-leg immobilization in healthy, young men. In chapter 7, we performed a fully controlled dietary intervention to assess the impact of a high protein intake on the preservation of lean body mass during 12 weeks of energy intake restriction. Sixty-one overweight and obese men and women were randomly assigned to either a high protein diet (1.7 g/kg/d) or a normal protein diet (0.9 g/kg/d) during 12 weeks of 25% energy intake restriction. During the dietary intervention, subjects lost 9±3 kg body weight with a concomitant 2±2 kg decline in lean body mass with no differences between the two intervention groups. Thus, increasing protein intake above habitual intake levels (0.9 g/kg/d) did not preserve lean body mass during a period of energy intake restriction. Finally, in chapter 8 we reflected on the main findings described in this thesis. In this chapter, we point out that the populations studied were all healthy and well-nourished. We conclude that in these populations, additional creatine, leucine and protein beyond habitual intakes did not preserve muscle mass. Older and/or malnourished individuals might be more responsive to these nutritional interventions. Future research could also focus on the combined effects of two or more nutritional compounds during disuse that are known to affect different mechanisms. Moreover, we speculate that the tested nutritional compounds could be effective in accelerating the regain of muscle mass and strength after a period of muscle loss. However, it should be noted that muscle loss during disuse occurs at a rate that is several-fold greater than muscle (re)gain during resistance type exercise training. Therefore, it is imperative that we continue our endeavors to identify nutritional or pharmaceutical compounds or exercise mimetics that may help to prevent or attenuate disuse atrophy.</p

Coordinated regulation of skeletal muscle mass and metabolic plasticity during recovery from disuse

Skeletal muscle regeneration after disuse is essential for muscle maintenance and involves the regulation of both mass‐ and metabolic plasticity–related processes. However, the relation between these processes during recovery from disuse remains unclear. In this study, we explored the potential interrelationship between the molecular regulation of muscle mass and oxidative metabolism during recovery from disuse. Molecular profiles were measured in biopsies from the vastus lateralis of healthy men after 1‐leg cast immobilization and after 1 wk reloading, and in mouse gastrocnemius obtained before and after hindlimb suspension and during reloading (RL‐1, ‐2, ‐3, ‐5, and ‐8 d). Cluster analysis of the human recovery response revealed correlations between myogenesis and autophagy markers in 2 clusters, which were distinguished by the presence of markers of early myogenesis, autophagosome formation, and mitochondrial turnover vs. markers of late myogenesis, autophagy initiation, and mitochondrial mass. In line with these findings, an early transient increase in B‐cell lymphoma‐2 interacting protein‐3 and sequestosome‐1 protein, and GABA type A receptor‐associated protein like‐1 protein and mRNA and a late increase in myomaker and myosin heavy chain‐8 mRNA, microtubule‐associated protein 1 light chain 3‐II:I ratio, and FUN14 domain‐containing‐1 mRNA and protein were observed in mice. In summary, the regulatory profiles of protein, mitochondrial, and myonuclear turnover are correlated and temporally associated, suggesting a coordinated regulation of muscle mass‐ and oxidative metabolism‐related processes during recovery from disus

Seasonal variation in vitamin D status in elite athletes: a longitudinal study

Studies monitoring vitamin D status in athletes are seldom conducted for a period of 12 months or longer, thereby lacking insight into seasonal fluctuations. The objective of the cur-rent study was to identify seasonal changes in total 25-hydroxyvitamin D (25(OH)D) concen-tration throughout the year. Fifty-two, mainly Caucasian athletes with a sufficient 25(OH)D concentration (>75 nmol/L) in June were included in this study. Serum 25(OH)D concentra-tion was measured every three months (June, September, December, March, June). Addition-ally, vitamin D intake and sun exposure were assessed by questionnaires at the same time points. Highest total 25(OH)D concentrations were found at the end of summer (113±26 nmol/L), whereas lowest concentrations were observed at the end of winter (78±30 nmol/L). Although all athletes had a sufficient 25(OH)D concentration at the start of the study, nearly 20% of the athletes were deficient (<50 nmol/L) in late winter

Leucine Supplementation Does Not Attenuate Skeletal Muscle Loss during Leg Immobilization in Healthy, Young Men

Background: Short successive periods of physical inactivity occur throughout life and contribute considerably to the age-related loss of skeletal muscle mass. The maintenance of muscle mass during brief periods of disuse is required to prevent functional decline and maintain metabolic health. Objective: To assess whether daily leucine supplementation during a short period of disuse can attenuate subsequent muscle loss in vivo in humans. Methods: Thirty healthy (22 &plusmn; 1 y) young males were exposed to a 7-day unilateral knee immobilization intervention by means of a full leg cast with (LEU, n = 15) or without (CON, n = 15) daily leucine supplementation (2.5 g leucine, three times daily). Prior to and directly after immobilization, quadriceps muscle cross-sectional area (computed tomography (CT) scan) and leg strength (one-repetition maximum (1-RM)) were assessed. Furthermore, muscle biopsies were taken in both groups before and after immobilization to assess changes in type I and type II muscle fiber CSA. Results: Quadriceps muscle cross-sectional area (CSA) declined in the CON and LEU groups (p &lt; 0.01), with no differences between the two groups (from 7712 &plusmn; 324 to 7287 &plusmn; 305 mm2 and from 7643 &plusmn; 317 to 7164 &plusmn; 328 mm2; p = 0.61, respectively). Leg muscle strength decreased from 56 &plusmn; 4 to 53 &plusmn; 4 kg in the CON group and from 63 &plusmn; 3 to 55 &plusmn; 2 kg in the LEU group (main effect of time p &lt; 0.01), with no differences between the groups (p = 0.052). Type I and II muscle fiber size did not change significantly over time, in both groups (p &gt; 0.05). Conclusions: Free leucine supplementation with each of the three main meals (7.5 g/d) does not attenuate the decline of muscle mass and strength during a 7-day limb immobilization intervention

The impact of protein quantity during energy restriction on genome-wide gene expression analysis in human adipose tissue

Overweight is a growing health problem worldwide. The most effective strategy to reduce weight is energy restriction (ER): restriction of food intake without malnutrition. ER has been shown to be beneficial in disease prevention, healthy aging, and inflammation. Recent studies suggest that reducing the protein content of a diet contributes to the beneficial effects by ER. The first objective of our study was to assess the effect of energy restriction on changes in gene expression in adipose tissue. Secondly, the changes in gene expression were compared between a high protein diet and a normal protein diet during energy restriction. In a parallel double-blinded study, overweight older subjects adhered to a 25% ER diet, either combined with high protein intake (HP-ER, 1.7 g/kg per day), or with normal protein intake (NP-ER, 0.9 g/kg per day) for 12 weeks. From 10 HP-ER subjects and 12 NP-ER subjects subcutaneous adipose tissue biopsies were collected before and after the diet. Adipose tissue was used to isolate total RNA and to evaluate whole genome gene expression changes upon a HP-ER and NP-ER diet. Upon 25% ER, clusters of gene sets in energy metabolism, such as lipid metabolism and PPARα targets, NRF2 targets, glucose metabolism, and TCA cycle, as well as gene sets in oxidative phosphorylation, adaptive immune response, immune cell infiltration, and cell cycle were decreased, and RNA translation and processing gene sets were increased. A different gene expression response between HP-ER and NP-ER was observed for 530 genes. Pathway analysis revealed that after NP-ER a downregulation in expression of genes involved in adaptive immune response was present. HP-ER resulted in an upregulation of pathways involved in cell cycle, GPCR signalling, olfactory signalling and nitrogen metabolism. Based on the gene expression changes, we concluded that HP seems to be less beneficial for ER’s effect on immune-related gene expression in adipose tissue

Seasonal variation in vitamin D status in elite athletes: a longitudinal study

Studies monitoring vitamin D status in athletes are seldom conducted for a period of 12 months or longer, thereby lacking insight into seasonal fluctuations. The objective of the cur-rent study was to identify seasonal changes in total 25-hydroxyvitamin D (25(OH)D) concen-tration throughout the year. Fifty-two, mainly Caucasian athletes with a sufficient 25(OH)D concentration (>75 nmol/L) in June were included in this study. Serum 25(OH)D concentra-tion was measured every three months (June, September, December, March, June). Addition-ally, vitamin D intake and sun exposure were assessed by questionnaires at the same time points. Highest total 25(OH)D concentrations were found at the end of summer (113±26 nmol/L), whereas lowest concentrations were observed at the end of winter (78±30 nmol/L). Although all athletes had a sufficient 25(OH)D concentration at the start of the study, nearly 20% of the athletes were deficient (<50 nmol/L) in late winter

Seasonal Variation in Vitamin D Status in Elite Athletes: A Longitudinal Study

Studies monitoring Vitamin D status in athletes are seldom conducted for a period of 12 months or longer, thereby lacking insight into seasonal fluctuations. The objective of the current study was to identify seasonal changes in total 25-hydroxyVitamin D (25(OH)D) concentration throughout the year. Fifty-Two, mainly Caucasian athletes with a sufficient 25(OH)Dconcentration ( > 75 nmol/L) in June were included in this study. Serum 25(OH)D concentration was measured every three months (June, September, December, March, June). In addition, Vitamin D intake and sun exposure were assessed by questionnaires at the same time points. Highest total 25(OH)D concentrations were found at the end of summer (113 ± 26 nmol/L), whereas lowest concentrations were observed at the end of winter (78 ± 30 nmol/L). Although all athletes had a sufficient 25(OH)D concentration at the start of the study, nearly 20% of the athletes were deficient ( < 50 nmol/L) in late winter

Creatine Loading Does Not Preserve Muscle Mass or Strength During Leg Immobilization in Healthy, Young Males:A Randomized Controlled Trial

<p>Background: A short period of leg immobilization leads to rapid loss of muscle mass and strength. Creatine supplementation has been shown to increase lean body mass in active individuals and can be used to augment gains in muscle mass and strength during prolonged resistance-type exercise training. Objective: Our objective was to investigate whether creatine loading can attenuate the loss of muscle mass and strength during short-term leg immobilization. Methods: Healthy young men (n = 30; aged 23 ± 1 years; body mass index [BMI] 23.3 ± 0.5 kg/m⁻²) were randomly assigned to either a creatine or a placebo group. Subjects received placebo or creatine supplements (20 g/d) for 5 days before one leg was immobilized by means of a full-leg cast for 7 days. Muscle biopsies were taken before creatine loading, prior to and immediately after leg immobilization, and after 7 days of subsequent recovery. Quadriceps cross-sectional area (CSA) (computed tomography [CT] scan) and leg muscle strength (one-repetition maximum [1-RM] knee extension) were assessed before and immediately after immobilization and after 1 week of recovery. Data were analyzed using repeated measures analysis of variance (ANOVA). Data are presented consistently as mean ± standard error of the mean (SEM). Results: There was a significant overall increase in muscle total creatine content following the 5-day loading phase (p = 0.049), which appeared driven by an increase in the creatine group (from 90 ± 9 to 107 ± 4 mmol/kg⁻¹ dry muscle) with no apparent change in the placebo group (from 88 ± 4 to 90 ± 3 mmol/kg⁻¹; p = 0.066 for time × treatment interaction). Quadriceps muscle CSA had declined by 465 ± 59 and 425 ± 69 mm² (p &lt;0.01) in the creatine and placebo group, respectively, with no differences between groups (p = 0.76). Leg muscle strength decreased from 56 ± 4 to 53 ± 4 kg in the creatine and from 59 ± 3 to 53 ± 3 kg in the placebo group, with no differences between groups (p = 0.20). Muscle fiber size did not change significantly over time in either group (p &gt; 0.05). When non-responders to creatine loading were excluded (n = 6), responders (n = 8; total creatine content increasing from 70 to 106 mmol/kg⁻¹) showed similar findings, with no signs of preservation of muscle mass or strength during immobilization. During the subsequent recovery phase, no differences in muscle mass or strength were found between the two groups (p &gt; 0.05). Conclusion: Creatine supplementation prior to and during leg immobilization does not prevent or attenuate the loss of muscle mass or strength during short-term muscle disuse. </p

Nandrolone decanoate administration does not attenuate muscle atrophy during a short period of disuse

BACKGROUND: A few days of bed rest or immobilization following injury, disease, or surgery can lead to considerable loss of skeletal muscle mass and strength. It has been speculated that such short, successive periods of muscle disuse may be largely responsible for the age-related loss of muscle mass throughout the lifespan. OBJECTIVE: To assess whether a single intramuscular injection of nandrolone decanoate prior to immobilization can attenuate the loss of muscle mass and strength in vivo in humans. DESIGN, SETTING AND PARTICIPANTS: Thirty healthy (22 ± 1 years) men were subjected to 7 days of one-legged knee immobilization by means of a full leg cast with (NAD, n = 15) or without (CON, n = 15) prior intramuscular nandrolone decanoate injection (200 mg). MEASURES: Before and immediately after immobilization, quadriceps muscle cross-sectional area (CSA) (by means of single-slice computed tomography (CT) scans of the upper leg) and one-legged knee extension strength (one-repetition maximum [1-RM]) were assessed for both legs. Furthermore, muscle biopsies from the immobilized leg were taken before and after immobilization to assess type I and type II muscle fiber cross-sectional area. RESULTS: Quadriceps muscle CSA decreased during immobilization in both CON and NAD (-6 ± 1% and -6 ± 1%, respectively; main effect of time P<0.01), with no differences between the groups (time × treatment interaction, P = 0.59). Leg muscle strength declined following immobilization (-6 ± 2% in CON and -7 ± 3% in NAD; main effect of time, P<0.05), with no differences between groups (time × treatment interaction, P = 0.55). CONCLUSIONS: This is the first study to report that nandrolone decanoate administration does not preserve skeletal muscle mass and strength during a short period of leg immobilization in vivo in humans.</p