Shanon L. Casperson

Amino acid supplementation increases lean body mass, basal muscle protein synthesis, and insulin-like growth factor-I expression in older women.

CONTEXT Inadequate dietary protein intake has been implicated in sarcopenia. OBJECTIVE AND DESIGN The objectives of this study were to determine whether: 1) chronic essential amino acid (EAA) supplementation improves postabsorptive muscle protein fractional synthesis rate (FSR), lean body mass (LBM), and one-repetition maximum muscle strength, and androgen receptor and IGF-I muscle protein expression; and 2) the acute anabolic response to EAA ingestion is preserved after a 3-month supplementation period. Using a randomized, double-blinded, placebo-controlled design, older women (68 +/- 2 yr) were assigned to receive either placebo (n = 7), or 15 g EAA/d [supplemented treatment group (SUP)] (n = 7) for 3 months. Metabolic outcomes were assessed in association with stable isotope studies conducted at 0 and 3 months. SETTING The study was performed at The University of Texas Medical Branch General Clinical Research Center. RESULTS Ingestion of 7.5 g EAA acutely stimulated FSR in both groups at 0 months (P < 0.05). Basal FSR at 3 months was increased in SUP only. The magnitude of the acute response to EAA was unaltered after 3 months in SUP. LBM increased in SUP only (P < 0.05). One-repetition maximum strength remained unchanged in both groups. Basal IGF-I protein expression increased in SUP after 3 months (P = 0.05), with no changes in androgen receptor or total and phosphorylated Akt, mammalian target of rapamycin, S6 kinase, and 4E-binding protein. CONCLUSIONS EAA improved LBM and basal muscle protein synthesis in older individuals. The acute anabolic response to EAA supplementation is maintained over time and can improve LBM, possibly offsetting the debilitating effects of sarcopenia.

Dietary Protein Distribution Positively Influences 24-h Muscle Protein Synthesis in Healthy Adults

The RDA for protein describes the quantity that should be consumed daily to meet population needs and to prevent deficiency. Protein consumption in many countries exceeds the RDA; however, intake is often skewed toward the evening meal, whereas breakfast is typically carbohydrate rich and low in protein. We examined the effects of protein distribution on 24-h skeletal muscle protein synthesis in healthy adult men and women (n = 8; age: 36.9 ± 3.1 y; BMI: 25.7 ± 0.8 kg/m2). By using a 7-d crossover feeding design with a 30-d washout period, we measured changes in muscle protein synthesis in response to isoenergetic and isonitrogenous diets with protein at breakfast, lunch, and dinner distributed evenly (EVEN; 31.5 ± 1.3, 29.9 ± 1.6, and 32.7 ± 1.6 g protein, respectively) or skewed (SKEW; 10.7 ± 0.8, 16.0 ± 0.5, and 63.4 ± 3.7 g protein, respectively). Over 24-h periods on days 1 and 7, venous blood samples and vastus lateralis muscle biopsy samples were obtained during primed (2.0 μmol/kg) constant infusion [0.06 μmol/(kg⋅min)] of l-[ring-13C6]phenylalanine. The 24-h mixed muscle protein fractional synthesis rate was 25% higher in the EVEN (0.075 ± 0.006%/h) vs. the SKEW (0.056 ± 0.006%/h) protein distribution groups (P = 0.003). This pattern was maintained after 7 d of habituation to each diet (EVEN vs. SKEW: 0.077 ± 0.006 vs. 0.056 ± 0.006%/h; P = 0.001). The consumption of a moderate amount of protein at each meal stimulated 24-h muscle protein synthesis more effectively than skewing protein intake toward the evening meal.

Leucine supplementation chronically improves muscle protein synthesis in older adults consuming the RDA for protein

BACKGROUND & AIM Protein-energy supplementation is routinely employed to combat muscle loss. However, success is often compromised by increased satiety, poor palatability, high costs and low compliance. METHODS For 2-weeks we supplemented meals of older individuals with leucine (4 g/meal; 3 meals/day; days 2-14). Metabolic studies were performed prior to (Day 1) and following (Day 15) supplementation. Leucine was not provided on metabolic study days. Venous blood and vastus lateralis muscle biopsies were obtained during a primed constant infusion of L-[ring-(13)C(6)] phenylalanine. Mixed muscle fractional synthesis rate (FSR), body composition and markers of nutrient signaling (mTOR, 4E-BP1 and p70S6K1 phosphorylation) were measured before and after a low protein/carbohydrate simulated meal. RESULTS The meal modestly increased FSR on Day 1 (postabsorptive: 0.063 ± 0.004 vs. postprandial: 0.075 ± 0.006%/h; p = 0.03), however, two weeks of leucine supplementation increased postabsorptive FSR (p = 0.004) and the response to the meal (p = 0.01) (postabsorptive: 0.074 ± 0.007 vs. postprandial: 0.10 ± 0.007%/h). Changes in FSR were mirrored by increased phosphorylation of mTOR, 4E-BP1 and p70S6K1 (p ≤ 0.1). No change in fat free mass was observed (p > 0.05). CONCLUSIONS In older adults, leucine supplementation may improve muscle protein synthesis in response to lower protein meals.

Age-related anabolic resistance after endurance-type exercise in healthy humans

Age‐related skeletal muscle loss is thought to stem from suboptimal nutrition and resistance to anabolic stimuli. Impaired microcirculatory (nutritive) blood flow may contribute to anabolic resistance by reducing delivery of amino acids to skeletal muscle. In this study, we employed contrast‐enhanced ultrasound, microdialysis sampling of skeletal muscle interstitium, and stable isotope methodology, to assess hemodynamic and metabolic responses of older individuals to endurance type (walking) exercise during controlled amino acid provision. We hypothesized that older individuals would exhibit reduced microcirculatory blood flow, interstitial amino acid concentrations, and amino acid transport when compared with younger controls. We report for the first time that aging induces anabolic resistance following endurance exercise, manifested as reduced (by ∼40%) efficiency of muscle protein synthesis. Despite lower (by ∼40–45%) microcirculatory flow in the older than in the younger participants, circulating and interstitial amino acid concentrations and phenylalanine transport into skeletal muscle were all equal or higher in older individuals than in the young, comprehensively refuting our hypothesis that amino acid availability limits postexercise anabolism in older individuals. Our data point to alternative mediators of age‐related anabolic resistance and importantly suggest correction of these impairments may reduce requirements for, and increase the efficacy of, dietary protein in older individuals. Durham, W. J., Casperson, S. L., Dillon, E. L., Keske, M. A., Paddon‐Jones, D., Sanford, A. P., Hickner, R. C., Grady, J. J., Sheffield‐Moore, M. Age‐related anabolic resistance after endurance‐type exercise in healthy humans. FASEB J. 24, 4117–4127 (2010). www.fasebj.org

A Randomized Pilot Study of Monthly Cycled Testosterone Replacement or Continuous Testosterone Replacement Versus Placebo in Older Men

CONTEXT Cycling androgens has been reported by athletes to improve physical performance by enhancing muscle mass and strength, a paradigm that has not been studied, and may have clinical value in older men being treated with testosterone. OBJECTIVE We investigated the efficacy of a monthly cycled testosterone regimen that uses half the testosterone dose as the current standard of care continuous therapy on body composition and muscle strength in older men. DESIGN, SETTING, AND PATIENTS Twenty-four community-dwelling older men 70 ± 2 yr of age with total testosterone levels below 500 ng/dl were randomized at the Institute for Translational Sciences-Clinical Research Center into a 5-month double-blind placebo-controlled trial. INTERVENTION Subjects were dosed weekly for 5 months, receiving continuous testosterone (TE, n = 8; 100 mg testosterone enanthate, im injection), monthly cycled testosterone (MO, n = 8; alternating months of testosterone and placebo), or placebo (PL, n = 8). MAIN OUTCOME MEASURES Main outcomes included body composition by dual-energy x-ray absorptiometry and upper and lower body muscle strength. Secondary outcomes included body weight, serum hormones, and mixed-muscle protein fractional synthesis rate (FSR). RESULTS Total lean body mass was increased and percent fat was reduced after 5 months in TE and MO (P < 0.05). Upper body muscle strength increased in TE, and lower body muscle strength increased in TE and MO (P < 0.05). FSR increased in TE and MO (P < 0.05) but not in PL. CONCLUSIONS Cycled testosterone improved body composition and increased muscle strength compared with placebo and increased FSR similarly to continuous testosterone.

Muscle Protein Metabolism Responds Similarly to Exogenous Amino Acids in Healthy Younger and Older Adults during NO-Induced Hyperemia

The combination of increasing blood flow and amino acid (AA) availability provides an anabolic stimulus to the skeletal muscle of healthy young adults by optimizing both AA delivery and utilization. However, aging is associated with a blunted response to anabolic stimuli and may involve impairments in endothelial function. We investigated whether age-related differences exist in the muscle protein anabolic response to AAs between younger (30 ± 2 yr) and older (67 ± 2 yr) adults when macrovascular and microvascular leg blood flow were similarly increased with the nitric oxide (NO) donor, sodium nitroprusside (SNP). Regardless of age, SNP+AA induced similar increases above baseline (P ≤ 0.05) in macrovascular flow (4.3 vs. 4.4 ml·min(-1)·100 ml leg(-1) measured using indocyanine green dye dilution), microvascular flow (1.4 vs. 0.8 video intensity/s measured using contrast-enhanced ultrasound), phenylalanine net balance (59 vs. 68 nmol·min(-1)·100 ml·leg(-1)), fractional synthetic rate (0.02 vs. 0.02%/h), and model-derived muscle protein synthesis (62 vs. 49 nmol·min(-1)·100 ml·leg(-1)) in both younger vs. older individuals, respectively. Provision of AAs during NO-induced local skeletal muscle hyperemia stimulates skeletal muscle protein metabolism in older adults to a similar extent as in younger adults. Our results suggest that the aging vasculature is responsive to exogenous NO and that there is no age-related difference per se in AA-induced anabolism under such hyperemic conditions.

A Mobile Phone Food Record App to Digitally Capture Dietary Intake for Adolescents in a Free-Living Environment: Usability Study

Background Mobile technologies are emerging as valuable tools to collect and assess dietary intake. Adolescents readily accept and adopt new technologies; thus, a food record app (FRapp) may be a useful tool to better understand adolescents’ dietary intake and eating patterns. Objective We sought to determine the amenability of adolescents, in a free-living environment with minimal parental input, to use the FRapp to record their dietary intake. Methods Eighteen community-dwelling adolescents (11-14 years) received detailed instructions to record their dietary intake for 3-7 days using the FRapp. Participants were instructed to capture before and after images of all foods and beverages consumed and to include a fiducial marker in the image. Participants were also asked to provide text descriptors including amount and type of all foods and beverages consumed. Results Eight of 18 participants were able to follow all instructions: included pre- and post-meal images, a fiducial marker, and a text descriptor and collected diet records on 2 weekdays and 1 weekend day. Dietary intake was recorded on average for 3.2 (SD 1.3 days; 68% weekdays and 32% weekend days) with an average of 2.2 (SD 1.1) eating events per day per participant. A total of 143 eating events were recorded, of which 109 had at least one associated image and 34 were recorded with text only. Of the 109 eating events with images, 66 included all foods, beverages and a fiducial marker and 44 included both a pre- and post-meal image. Text was included with 78 of the captured images. Of the meals recorded, 36, 33, 35, and 39 were breakfasts, lunches, dinners, and snacks, respectively. Conclusions These data suggest that mobile devices equipped with an app to record dietary intake will be used by adolescents in a free-living environment; however, a minority of participants followed all directions. User-friendly mobile food record apps may increase participant amenability, increasing our understanding of adolescent dietary intake and eating patterns. To improve data collection, the FRapp should deliver prompts for tasks, such as capturing images before and after each eating event, including the fiducial marker in the image, providing complete and accurate text information, and ensuring all eating events are recorded and should be customizable to individuals and to different situations. Trial Registration Clinicaltrials.gov NCT01803997. http://clinicaltrials.gov/ct2/show/NCT01803997 (Archived at: http://www.webcitation.org/6WiV1vxoR).

Novel Noninvasive Breath Test Method for Screening Individuals at Risk for Diabetes

OBJECTIVE—Diagnosis of pre-diabetes and early-stage diabetes occurs primarily by means of an oral glucose tolerance test (OGTT), which requires invasive blood sampling. The aim of this study was to determine whether differences exist in breath 13CO2 excretion during a 13C-labeled OGTT between individuals with normal glucose tolerance (NGT) and individuals with pre-diabetes and early-stage diabetes (PDED) and whether these differences correlated with blood glucose kinetics. RESEARCH DESIGN AND METHODS—Blood and breath samples were collected at baseline and every 30 min for a 10-h period after ingestion of 75 g glucose isotopically labeled with 150 mg [U-13C6]d-glucose. RESULTS—Age (56 ± 5 vs. 47 ± 3 years) and BMI (31 ± 2 vs. 31 ± 2 kg/m2) were not different between individuals with NGT (n = 10) and PDED (n = 7), respectively. Blood glucose concentrations were significantly higher in those with PDED compared with those with NGT from baseline to 4.5 h after glucose ingestion (P ≤ 0.05). Glucose-derived breath 13CO2 was significantly lower in individuals with PDED compared with those with NGT from 1 to 3.5 h after glucose (P ≤ 0.05). Peak breath 13CO2 abundance occurred at 4.5 and 3.5 h in individuals with PDED and NGT, respectively (36.87 ± 3.15 vs. 41.36 ± 1.56‰ delta over baseline). CONCLUSIONS—These results suggest that this novel breath test method may assist in recognition of pre-diabetes or early-stage diabetes in at-risk persons without the need for invasive blood sampling, thus making it an attractive option for large-scale testing of at-risk populations, such as children.

The emerging role of carbon isotope ratio determination in health research and medical diagnostics

Variations in the isotopic signature of carbon in biological samples (e.g. breath, blood and tissues) can be used to monitor shifts in whole body metabolism. As a conservative recorder of our diet, changes in the isotopic signature of carbon in biological samples provide an objective means to distinguish dietary patterns and the relationship with diseases. In addition, metabolic discrimination of carbon within the body can be informative regarding changes in the bodys metabolic fuel usage during situations where shifts in the macronutrient oxidation ratio are expected. Therefore, changes in the isotopic signature over time have proven to be a tremendously powerful and sensitive means of detecting and measuring changes in steady-state systems. As such, this review focuses on how a naturally occurring ratio of stable isotopes of carbon (13C/12C) can be used as a biomarker for nutritional and metabolic status, altered macronutrient metabolism, and health and disease.

Impact of Dietary Protein and Gender on Food Reinforcement

Recent evidence suggests that increasing dietary protein may alter reward-driven eating behavior. However, the link between protein and food reinforcement is not known. We sought to determine the extent to which increasing dietary protein alters food reinforcement in healthy adults. In a randomized crossover study, 11 women (age = 25 ± 7 years; Body Mass Index (BMI) = 21 ± 2 kg/m2) and 10 men (age = 22 ± 2 years; BMI = 24 ± 2 kg/m2) consumed normal (15%) and high (30%) protein meals. Food reinforcement was assessed using a computer-based choice task (operant responding with concurrent log2(x) reinforcement schedules) 4 h after lunch. We found that food reinforcement was greater in men than women (p < 0.05) and greater for sweet than savory snack foods (p < 0.02). Gender interacted with dietary protein level (p = 0.03) and snack food type (p < 0.0001). Specifically, we found that increasing dietary protein decreased the reinforcing value of savory foods in women. The reinforcing value for sweet foods did not interact with dietary protein or gender. These results demonstrate the differential effects of dietary protein on the reinforcing value for energy-dense, highly palatable snack foods.