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Papers by Robert Wolfe

Sleep, Apr 1, 2019

Introduction: Consuming calories later in the day is associated with obesity and metabolic syndro... more Introduction: Consuming calories later in the day is associated with obesity and metabolic syndrome. We hypothesized that eating a late dinner alters metabolic function during sleep in a manner that promotes obesity. Methods: We compared metabolic effects of routine dinnertime (RD, 18:00) versus late dinnertime (LD, 22:00) with a fixed sleep period (23:00-07:00) on the daily metabolic profile of healthy volunteers in a randomized crossover study. An isocaloric diet was administered at 8:00, 13:00, 18:00, or 22:00. For RD, dinner (35% daily kcal) was given at 18:00 and a snack (10% kcal) was given at 22:00; for LD, these meals were reversed. Peripheral venous blood samples were collected at 1-hour intervals from 17:00 to 12:00 the next day on both visits. We assessed plasma triglycerides (TG), free fatty acids (FFAs), glucose, insulin, cortisol, and sleep architecture. Participants ingested a lipid tracer, [ 2 H 31 ]palmitate with dinner to measure fatty acid oxidation. Time series data was analyzed using mixed effects regression models. Results: To date, eight participants (5 male and 3 females) aged 26.4 ± 0.7 years old, with a BMI of 24.1 ± 1.2 kg/m 2 completed the study. During sleep, LD increased plasma glucose (β=16.8 mg/dl, P<0.001), insulin (β=15.4 μU/ml, P<0.001), cortisol (β=1.5 μg/dl, P=0.017), and decreased plasma FFA (β=-0.1 mmol/l, P<0.001). Morning glucose, insulin, cortisol and FFA levels were not significantly different between two visits. Morning TG were increased by RD (β=17.4 mg/dl, P<0.001). The evening postprandial period following LD was characterized by higher glucose and lower FFA as compared to RD (P<0.05). Fatty acid oxidation will be measured by serial enrichment of plasma 2 H 2 0 (pending). Dinner time did not affect sleep architecture. Conclusion: LD increases nocturnal glucose, insulin, cortisol, and decreases FFA. The inhibition of nocturnal lipolysis with LD may lower morning TG. Overall, LD leads to an anabolic state during sleep that might promote the development of obesity.

Journal of Burn Care & Research, Apr 28, 2021

Loss of muscle mass in response to injury or immobilization impairs functional capacity and metab... more Loss of muscle mass in response to injury or immobilization impairs functional capacity and metabolic health, thus hindering rehabilitation. Stable isotope techniques are powerful in determining skeletal muscle protein fluxes. Traditional tracer incorporation methods to measure muscle protein synthesis and breakdown are cumbersome and invasive to perform in vulnerable populations such as children. To circumvent these issues, a two-bolus stable isotope amino acid method has been developed; although, measured rates of protein synthesis and breakdown have not been validated simultaneously against an accepted technique such as the arterial-venous balance method. The purpose of the current analysis was to provide preliminary data from the simultaneous determination of the arteriovenous balance and two-bolus tracer incorporation methods on muscle fractional synthesis and breakdown rates in children with burns. Five were administered a primed-constant infusion of L-[15N]Threonine for 180 minutes (Prime: 8 µmol/kg; constant: 0.1 µmol·kg-1·minute-1). At 120 and 150 minutes, bolus injections of L-[ring-13C6]Phenylalanine and L-[15N]Phenylalanine (50 µmol/kg each) were administered, respectively. Blood and muscle tissue samples were collected to assess mixed muscle protein synthesis and breakdown rates. The preliminary results from this study indicate that there is no difference in either fractional synthesis rate (mean ± SD; arteriovenous balance: 0.19 ± 0.17 %/h; tracer incorporation: 0.14 ± 0.08 %/h; P = .42) or fractional breakdown rate (arteriovenous balance: 0.29 ± 0.22 %/h; tracer incorporation: 0.23 ± 0.14 %/h; P = .84) between methods. These data support the validity of both methods in quantifying muscle amino acid kinetics; however, the results are limited and adequately powered research is still required.

Medicine and Science in Sports and Exercise, May 1, 2006

The Journal of Nutrition, 2004

The rationale for the use of nutritional supplements to enhance exercise capacity is based on the... more The rationale for the use of nutritional supplements to enhance exercise capacity is based on the assumption that they will confer an ergogenic effect above and beyond that afforded by regular food ingestion alone. The proposed or advertised ergogenic effect of many supplements is based on a presumptive metabolic pathway and may not necessarily translate to quantifiable changes in a variable as broadly defined as exercise performance. L-arginine is a conditionally essential amino acid that has received considerable attention due to potential effects on growth hormone secretion and nitric oxide production. In some clinical circumstances (e.g., burn injury, sepsis) in which the demand for arginine cannot be fully met by de novo synthesis and normal dietary intake, exogenous arginine has been shown to facilitate the maintenance of lean body mass and functional capacity. However, the evidence that supplemental arginine may also confer an ergogenic effect in normal healthy individuals is less compelling. In contrast to arginine, numerous studies have reported that supplementation with the arginine metabolite creatine facilitates an increase in anaerobic work capacity and muscle mass when accompanied by resistance training programs in both normal and patient populations. Whereas improvement in the rate of phosphocreatine resynthesis is largely responsible for improvements in acute work capacity, the direct effect of creatine supplementation on skeletal muscle protein synthesis is less clear. The purpose of this review is to summarize the role of arginine and its metabolite creatine in the context of a nutrition supplement for use in conjunction with an exercise stimulus in both healthy and patient populations.

International Journal of Sport Nutrition and Exercise Metabolism, 2004

This study tests the hypotheses that (a) a mixture of whey protein, amino acids (AA), and carbohy... more This study tests the hypotheses that (a) a mixture of whey protein, amino acids (AA), and carbohydrates (CHO) stimulates net muscle protein synthesis to a greater extent than isoenergetic CHO alone after resistance exercise; and (b) that the stimulatory effect of a protein, AA, and CHO mixture will last beyond the 1 st hour after intake. Eight subjects participated in 2 trials. In one (PAAC), they ingested 77.4 g CHO, 17.5 g whey protein, and 4.9 g AA 1 hr after resistance exercise. In the other (CON), 100 g CHO was ingested instead. They received a primed constant infusion of L-[2H5]-phenylalanine, and samples from femoral artery and vein, and biopsies from vastus lateralis were obtained. The area under the curve for net uptake of phenylalanine into muscle above pre-drink value was 128 ±42 mg • leg-1 (PAAC) versus 32 ± 10 mg - leg-1 (CON) for the 3 hr after the drink (p = .04). The net protein balance response to the mixture consisted of two components, one rapid immediate response...

Journal of Biological Chemistry, 2015

Background: Insulin is known as an anabolic agent; however, its effect on skin protein metabolism... more Background: Insulin is known as an anabolic agent; however, its effect on skin protein metabolism is not well understood. Results: Hyperaminoacidemia alters the effect of hyperinsulinemia on skin protein metabolism in pigs. Conclusion: Hyperinsulinemia itself was not anabolic but rather affected skin amino acid cycling. Significance: Knowing the effect of hyperinsulinemia on skin protein metabolism will help with understanding the pathophysiology of skin conditions. The effects of amino acid supply and insulin infusion on skin protein kinetics (fractional synthesis rate (FSR), fractional breakdown rate (FBR), and net balance (NB)) in pigs were investigated. Four-month-old pigs were divided into four groups as follows: control, insulin (INS), amino acid (AA), and INS ؉ AA groups based on the nutritional and hormonal conditions. L-[ring-13 C 6 ]Phenylalanine was infused. FBR was estimated from the enrichment ratio of arterial phenylalanine to intracellular free phenylalanine. Plasma INS was increased (p < 0.05) in the INS and INS ؉ AA groups. Plasma glucose was maintained by infusion of glucose in the groups receiving INS. The interventions did not change the NB of skin protein. However, the interventions affected the FSR and FBR differently. An infusion of INS significantly increased both FSR and FBR, although AA infusion did not. When an AA infusion was added to the infusion of insulin (INS ؉ AA group), FSR and FBR were both lower when compared with the INS group. Our data demonstrate that in anesthetized pigs INS infusion did not exert an anabolic effect, but rather it increased AA cycling into and out of skin protein. Because co-infusion of AAs with INS ameliorated this effect, it is likely that the increased AA cycling during INS infusion was related to AA supply. Although protein kinetics were affected by both INS and AAs, none of the interventions affected the skin protein deposition. Thus, skin protein content is closely regulated under normal circumstances and is not subject to transient changes in AAs or hormonal concentrations.

The American journal of clinical nutrition, 2005

Previous evidence suggests that aging in healthy persons does not result in decreased incorporati... more Previous evidence suggests that aging in healthy persons does not result in decreased incorporation of muscle proteins after a bolus ingestion of 15 g essential amino acids (EAAs). We sought to examine whether ingestion of a smaller bolus of EAAs is associated with diminished accretion of muscle proteins in the elderly when compared with the young. Eleven elderly subjects (mean +/- SEM: 68 +/- 2 y) and 8 young control subjects (mean +/- SEM: 31 +/- 2 y) were studied in the postabsorptive state and for 3.5 h after a bolus ingestion of approximately 7 g EAAs. Muscle protein accretion and synthesis were measured with the femoral arteriovenous phenylalanine net balance technique during a constant infusion of L-[ring-(2)H5]phenylalanine. Similar to previous observations, no significant differences in the postabsorptive phenylalanine net balance were observed between the groups. However, the mean (+/-SEM) net phenylalanine uptake after EAA ingestion was significantly less in the elderly (...

The American journal of clinical nutrition, 2003

Nutritional supplementation may be used to treat muscle loss with aging (sarcopenia). However, if... more Nutritional supplementation may be used to treat muscle loss with aging (sarcopenia). However, if physical activity does not increase, the elderly tend to compensate for the increased energy delivered by the supplements with reduced food intake, which results in a calorie substitution rather than supplementation. Thus, an effective supplement should stimulate muscle anabolism more efficiently than food or common protein supplements. We have shown that balanced amino acids stimulate muscle protein anabolism in the elderly, but it is unknown whether all amino acids are necessary to achieve this effect. We assessed whether nonessential amino acids are required in a nutritional supplement to stimulate muscle protein anabolism in the elderly. We compared the response of muscle protein metabolism to either 18 g essential amino acids (EAA group: n = 6, age 69 +/- 2 y; +/- SD) or 40 g balanced amino acids (18 g essential amino acids + 22 g nonessential amino acids, BAA group; n = 8, age 71 ...

American journal of physiology. Endocrinology and metabolism, 2003

We have examined the effect of a hemodialysis-induced 40% reduction in plasma amino acid concentr... more We have examined the effect of a hemodialysis-induced 40% reduction in plasma amino acid concentrations on rates of muscle protein synthesis and breakdown in normal swine. Muscle protein kinetics were measured by tracer methodology using [(2)H(5)]phenylalanine and [1-(13)C]leucine and analysis of femoral arterial and venous samples and tissue biopsies. Net amino acid release by muscle was accelerated during dialysis. Phenylalanine utilization for muscle protein synthesis was reduced from the basal value of 45 +/- 8 to 25 +/- 6 nmol x min(-1) x 100 ml leg(-1) between 30 and 60 min after start of dialysis and was stimulated when amino acids were replaced while dialysis continued. Muscle protein breakdown was unchanged. The signal for changes in synthesis appeared to be changes in plasma amino acid concentrations, as intramuscular concentrations remained constant throughout. The changes in muscle protein synthesis were accompanied by a reduction or stimulation, respectively, in the gua...

Nutrition, 2009

Objective-Hypertriglyceridemia is a risk factor for coronary heart disease. The aim of this study... more Objective-Hypertriglyceridemia is a risk factor for coronary heart disease. The aim of this study was to determine the effect of AA supplementation on plasma, liver and muscle lipid concentrations and insulin sensitivity in elderly. Methods-Twelve impaired glucose tolerant elderly (67.0 ± 5.6 (SD) years, 7 females, 5 males) ingested 11 g of essential AA + arginine twice a day for 16 weeks, after a 7 week control run in. Diet and activity were not otherwise modified. Plasma lipid concentrations and oral glucose tolerance were measured every 4 th week, and tissue lipid concentrations (magnetic resonance spectroscopy) every 8 th week. Results-No changes in plasma lipids were observed during the control run-in. AA supplementation lowered plasma triglyceride (TG) (P < 0.001), total cholesterol (P = 0.048) and very low density lipoprotein (VLDL)-cholesterol (P < 0.001) concentrations. Plasma TG dropped ~20% from the initial value of 1.45 ± 0.18 (SE) mmol/l (128 ± 16 mg/dl), with greatest decrease in the subjects starting out with highest concentrations (r = −0.83).

Medicine & Science in Sports & Exercise, 2006

Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for Medicine & Sc... more Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for Medicine & Science in Sports & Exercise. Enter your Email address: Wolters Kluwer Health may email you for journal alerts and information, but ...

Archives of Physical Medicine and Rehabilitation, 2007

Plasma amino acid concentrations during late rehabilitation in patients with traumatic brain inju... more Plasma amino acid concentrations during late rehabilitation in patients with traumatic brain injury. Arch Phys Med Rehabil 2007;88: 234-8. Objectives: To investigate whether the basal plasma amino acid concentrations in patients with traumatic brain injury (TBI) have returned to levels found in healthy controls at about 17 months postinjury and to determine the effect of intake of a mixture of essential amino acids (EAA) on plasma amino acid concentrations in TBI versus healthy controls. Design: Peripheral venous amino acid concentrations in subjects with TBI were compared with concentrations in healthy controls both at rest and for 1 hour after intake of 7g of EAA. Setting: Postacute brain injury rehabilitation center. Participants: Six men with TBI (age Ϯ standard deviation, 27Ϯ6y; months postinjury, 17Ϯ4) and 6 healthy men (age, 43Ϯ7y). Intervention: Intake of a drink consisting of 7g of EAA. Main Outcome Measures: Individual and total plasma amino acid concentrations. Results: Total amino acid concentration was about 12% lower in TBI versus controls (Pϭ.022). Valine was reduced by 33% in the TBI group versus controls (Pϭ.003), whereas the other EAA did not differ between groups. After intake of the EAA drink, plasma non-EAA increased to a significantly higher level in controls versus TBI subjects (Pϭ.017). Conclusions: Plasma total amino acid concentration is still reduced 17 months postinjury in patients with TBI versus healthy controls, mainly because of a lower valine level. This may be of importance for both brain and muscle metabolic functions, and warrant further study. Further, ingested EAA are apparently not as readily converted to non-EAA in TBI patients as in healthy controls, suggesting that in recovery from TBI, certain non-EAA may become provisionally essential.

American Journal of Physiology-Endocrinology and Metabolism, 2005

We describe a method based on the traditional arteriovenous balance technique in conjunction with... more We describe a method based on the traditional arteriovenous balance technique in conjunction with muscle biopsies for the determination of leg muscle protein balance during the nonsteady state in blood amino acid concentrations. Six young, healthy individuals were studied in the postabsorptive state (pre-Phe) and after a bolus ingestion of ∼0.5 g phenylalanine (post-Phe). Post-Phe free phenylalanine concentrations in blood and muscle increased ( P < 0.05), but the respective concentrations of the amino acid threonine did not change. The average post-Phe leg net balance (NB) for threonine decreased from basal ( P < 0.05), but that for phenylalanine did not change. A volume of distribution for free phenylalanine in the leg was calculated based on the leg lean mass and the relative muscle water content and used to estimate the rate of accumulation of free phenylalanine in the leg. When the post-Phe NB for phenylalanine was corrected for the rate of accumulation of free phenylalan...

American Journal of Physiology-Endocrinology and Metabolism, 2005

The intracellular concentrations of essential amino acids (EAA) in muscle are maintained relative... more The intracellular concentrations of essential amino acids (EAA) in muscle are maintained relatively constant under a variety of conditions. However, the effect of a decrease in blood amino acid concentrations on intracellular concentrations is not clear. Similarly, the relation between intracellular and interstitial concentrations has not been determined in this circumstance. Thus the aim of this study was to determine the effect of hypoaminoacidemia on intracellular, interstitial, and plasma concentrations of EAA and the mechanisms responsible for the respective changes. Twelve normal pigs were investigated before and during 120 min of hemodialysis by use of stable-isotope tracer methodology, microdialysis technique, and muscle biopsies. During hemodialysis, there was a decrease in the interstitial fluid concentrations of phenylalanine, leucine, alanine, and lysine that corresponded to their decrease in plasma concentration. Nonetheless, the intracellular concentrations of these am...

American Journal of Physiology-Endocrinology and Metabolism, 2006

This study was designed to evaluate the effects of enriching an essential amino acid (EAA) mixtur... more This study was designed to evaluate the effects of enriching an essential amino acid (EAA) mixture with leucine on muscle protein metabolism in elderly and young individuals. Four (2 elderly and 2 young) groups were studied before and after ingestion of 6.7 g of EAAs. EAAs were based on the composition of whey protein [26% leucine (26% Leu)] or were enriched in leucine [41% leucine (41% Leu)]. A primed, continuous infusion of l-[ ring-2H5]phenylalanine was used together with vastus lateralis muscle biopsies and leg arteriovenous blood samples for the determinations of fractional synthetic rate (FSR) and balance of muscle protein. FSR increased following amino acid ingestion in both the 26% (basal: 0.048 ± 0.005%/h; post-EAA: 0.063 ± 0.007%/h) and the 41% (basal: 0.036 ± 0.004%/h; post-EAA: 0.051 ± 0.007%/h) Leu young groups ( P < 0.05). In contrast, in the elderly, FSR did not increase following ingestion of 26% Leu EAA (basal: 0.044 ± 0.003%/h; post-EAA: 0.049 ± 0.006%/h; P >...

Clinical Nutrition, 2008

Background & Aims-With advancing age there is a gradual decline in muscle mass, strength and func... more Background & Aims-With advancing age there is a gradual decline in muscle mass, strength and function. The aim of this study was to determine if regular intake of a nutritional supplement containing essential amino acids (EAA) + arginine could reverse these responses in elderly subjects. Methods-Twelve glucose intolerant subjects (67.0 ± 5.6 (SD) years, 7 females, 5 males) ingested 11 g of EAA + arginine two times a day, between meals for 16 weeks. Diet and activity were not otherwise modified. Lean body mass (DEXA) was measured every 4 th week. Maximal leg strength was tested and functional tests were performed at week 0, 8, 12, and 16. Results-Lean body mass (LBM) increased during the study (p = 0.038). At week 12, the average increase in LBM was 1.14 ± 0.36 kg (p < 0.05 vs baseline), whereas at week 16, the increase was 0.60 ± 0.38 kg (NS vs baseline). The lower extremity strength measure score (sum of individual knee flexors and extensors 1-repetition maximum, n = 10) was 127.5 ± 21.8 kg at baseline, and average increase during the study was 22.2 ± 6.1% (p < 0.001). Improvements were also observed in usual gait speed (p = 0.002), timed 5-step test (p = 0.007), and timed floor-transfer test (p = 0.022). Conclusion-Supplementation of the diet with EAA + arginine improves lean body mass, strength and physical function compared to baseline values in glucose intolerant elderly individuals.

Clinical Nutrition, 2008

Background & Aims-With advancing age there is a gradual decline in muscle mass, strength and func... more Background & Aims-With advancing age there is a gradual decline in muscle mass, strength and function. The aim of this study was to determine if regular intake of a nutritional supplement containing essential amino acids (EAA) + arginine could reverse these responses in elderly subjects.

Sleep, Apr 1, 2019

Introduction: Consuming calories later in the day is associated with obesity and metabolic syndro... more Introduction: Consuming calories later in the day is associated with obesity and metabolic syndrome. We hypothesized that eating a late dinner alters metabolic function during sleep in a manner that promotes obesity. Methods: We compared metabolic effects of routine dinnertime (RD, 18:00) versus late dinnertime (LD, 22:00) with a fixed sleep period (23:00-07:00) on the daily metabolic profile of healthy volunteers in a randomized crossover study. An isocaloric diet was administered at 8:00, 13:00, 18:00, or 22:00. For RD, dinner (35% daily kcal) was given at 18:00 and a snack (10% kcal) was given at 22:00; for LD, these meals were reversed. Peripheral venous blood samples were collected at 1-hour intervals from 17:00 to 12:00 the next day on both visits. We assessed plasma triglycerides (TG), free fatty acids (FFAs), glucose, insulin, cortisol, and sleep architecture. Participants ingested a lipid tracer, [ 2 H 31 ]palmitate with dinner to measure fatty acid oxidation. Time series data was analyzed using mixed effects regression models. Results: To date, eight participants (5 male and 3 females) aged 26.4 ± 0.7 years old, with a BMI of 24.1 ± 1.2 kg/m 2 completed the study. During sleep, LD increased plasma glucose (β=16.8 mg/dl, P<0.001), insulin (β=15.4 μU/ml, P<0.001), cortisol (β=1.5 μg/dl, P=0.017), and decreased plasma FFA (β=-0.1 mmol/l, P<0.001). Morning glucose, insulin, cortisol and FFA levels were not significantly different between two visits. Morning TG were increased by RD (β=17.4 mg/dl, P<0.001). The evening postprandial period following LD was characterized by higher glucose and lower FFA as compared to RD (P<0.05). Fatty acid oxidation will be measured by serial enrichment of plasma 2 H 2 0 (pending). Dinner time did not affect sleep architecture. Conclusion: LD increases nocturnal glucose, insulin, cortisol, and decreases FFA. The inhibition of nocturnal lipolysis with LD may lower morning TG. Overall, LD leads to an anabolic state during sleep that might promote the development of obesity.

Journal of Burn Care & Research, Apr 28, 2021

Loss of muscle mass in response to injury or immobilization impairs functional capacity and metab... more Loss of muscle mass in response to injury or immobilization impairs functional capacity and metabolic health, thus hindering rehabilitation. Stable isotope techniques are powerful in determining skeletal muscle protein fluxes. Traditional tracer incorporation methods to measure muscle protein synthesis and breakdown are cumbersome and invasive to perform in vulnerable populations such as children. To circumvent these issues, a two-bolus stable isotope amino acid method has been developed; although, measured rates of protein synthesis and breakdown have not been validated simultaneously against an accepted technique such as the arterial-venous balance method. The purpose of the current analysis was to provide preliminary data from the simultaneous determination of the arteriovenous balance and two-bolus tracer incorporation methods on muscle fractional synthesis and breakdown rates in children with burns. Five were administered a primed-constant infusion of L-[15N]Threonine for 180 minutes (Prime: 8 µmol/kg; constant: 0.1 µmol·kg-1·minute-1). At 120 and 150 minutes, bolus injections of L-[ring-13C6]Phenylalanine and L-[15N]Phenylalanine (50 µmol/kg each) were administered, respectively. Blood and muscle tissue samples were collected to assess mixed muscle protein synthesis and breakdown rates. The preliminary results from this study indicate that there is no difference in either fractional synthesis rate (mean ± SD; arteriovenous balance: 0.19 ± 0.17 %/h; tracer incorporation: 0.14 ± 0.08 %/h; P = .42) or fractional breakdown rate (arteriovenous balance: 0.29 ± 0.22 %/h; tracer incorporation: 0.23 ± 0.14 %/h; P = .84) between methods. These data support the validity of both methods in quantifying muscle amino acid kinetics; however, the results are limited and adequately powered research is still required.

Medicine and Science in Sports and Exercise, May 1, 2006

The Journal of Nutrition, 2004

The rationale for the use of nutritional supplements to enhance exercise capacity is based on the... more The rationale for the use of nutritional supplements to enhance exercise capacity is based on the assumption that they will confer an ergogenic effect above and beyond that afforded by regular food ingestion alone. The proposed or advertised ergogenic effect of many supplements is based on a presumptive metabolic pathway and may not necessarily translate to quantifiable changes in a variable as broadly defined as exercise performance. L-arginine is a conditionally essential amino acid that has received considerable attention due to potential effects on growth hormone secretion and nitric oxide production. In some clinical circumstances (e.g., burn injury, sepsis) in which the demand for arginine cannot be fully met by de novo synthesis and normal dietary intake, exogenous arginine has been shown to facilitate the maintenance of lean body mass and functional capacity. However, the evidence that supplemental arginine may also confer an ergogenic effect in normal healthy individuals is less compelling. In contrast to arginine, numerous studies have reported that supplementation with the arginine metabolite creatine facilitates an increase in anaerobic work capacity and muscle mass when accompanied by resistance training programs in both normal and patient populations. Whereas improvement in the rate of phosphocreatine resynthesis is largely responsible for improvements in acute work capacity, the direct effect of creatine supplementation on skeletal muscle protein synthesis is less clear. The purpose of this review is to summarize the role of arginine and its metabolite creatine in the context of a nutrition supplement for use in conjunction with an exercise stimulus in both healthy and patient populations.

International Journal of Sport Nutrition and Exercise Metabolism, 2004

This study tests the hypotheses that (a) a mixture of whey protein, amino acids (AA), and carbohy... more This study tests the hypotheses that (a) a mixture of whey protein, amino acids (AA), and carbohydrates (CHO) stimulates net muscle protein synthesis to a greater extent than isoenergetic CHO alone after resistance exercise; and (b) that the stimulatory effect of a protein, AA, and CHO mixture will last beyond the 1 st hour after intake. Eight subjects participated in 2 trials. In one (PAAC), they ingested 77.4 g CHO, 17.5 g whey protein, and 4.9 g AA 1 hr after resistance exercise. In the other (CON), 100 g CHO was ingested instead. They received a primed constant infusion of L-[2H5]-phenylalanine, and samples from femoral artery and vein, and biopsies from vastus lateralis were obtained. The area under the curve for net uptake of phenylalanine into muscle above pre-drink value was 128 ±42 mg • leg-1 (PAAC) versus 32 ± 10 mg - leg-1 (CON) for the 3 hr after the drink (p = .04). The net protein balance response to the mixture consisted of two components, one rapid immediate response...

Journal of Biological Chemistry, 2015

Background: Insulin is known as an anabolic agent; however, its effect on skin protein metabolism... more Background: Insulin is known as an anabolic agent; however, its effect on skin protein metabolism is not well understood. Results: Hyperaminoacidemia alters the effect of hyperinsulinemia on skin protein metabolism in pigs. Conclusion: Hyperinsulinemia itself was not anabolic but rather affected skin amino acid cycling. Significance: Knowing the effect of hyperinsulinemia on skin protein metabolism will help with understanding the pathophysiology of skin conditions. The effects of amino acid supply and insulin infusion on skin protein kinetics (fractional synthesis rate (FSR), fractional breakdown rate (FBR), and net balance (NB)) in pigs were investigated. Four-month-old pigs were divided into four groups as follows: control, insulin (INS), amino acid (AA), and INS ؉ AA groups based on the nutritional and hormonal conditions. L-[ring-13 C 6 ]Phenylalanine was infused. FBR was estimated from the enrichment ratio of arterial phenylalanine to intracellular free phenylalanine. Plasma INS was increased (p < 0.05) in the INS and INS ؉ AA groups. Plasma glucose was maintained by infusion of glucose in the groups receiving INS. The interventions did not change the NB of skin protein. However, the interventions affected the FSR and FBR differently. An infusion of INS significantly increased both FSR and FBR, although AA infusion did not. When an AA infusion was added to the infusion of insulin (INS ؉ AA group), FSR and FBR were both lower when compared with the INS group. Our data demonstrate that in anesthetized pigs INS infusion did not exert an anabolic effect, but rather it increased AA cycling into and out of skin protein. Because co-infusion of AAs with INS ameliorated this effect, it is likely that the increased AA cycling during INS infusion was related to AA supply. Although protein kinetics were affected by both INS and AAs, none of the interventions affected the skin protein deposition. Thus, skin protein content is closely regulated under normal circumstances and is not subject to transient changes in AAs or hormonal concentrations.

The American journal of clinical nutrition, 2005

Previous evidence suggests that aging in healthy persons does not result in decreased incorporati... more Previous evidence suggests that aging in healthy persons does not result in decreased incorporation of muscle proteins after a bolus ingestion of 15 g essential amino acids (EAAs). We sought to examine whether ingestion of a smaller bolus of EAAs is associated with diminished accretion of muscle proteins in the elderly when compared with the young. Eleven elderly subjects (mean +/- SEM: 68 +/- 2 y) and 8 young control subjects (mean +/- SEM: 31 +/- 2 y) were studied in the postabsorptive state and for 3.5 h after a bolus ingestion of approximately 7 g EAAs. Muscle protein accretion and synthesis were measured with the femoral arteriovenous phenylalanine net balance technique during a constant infusion of L-[ring-(2)H5]phenylalanine. Similar to previous observations, no significant differences in the postabsorptive phenylalanine net balance were observed between the groups. However, the mean (+/-SEM) net phenylalanine uptake after EAA ingestion was significantly less in the elderly (...

The American journal of clinical nutrition, 2003

Nutritional supplementation may be used to treat muscle loss with aging (sarcopenia). However, if... more Nutritional supplementation may be used to treat muscle loss with aging (sarcopenia). However, if physical activity does not increase, the elderly tend to compensate for the increased energy delivered by the supplements with reduced food intake, which results in a calorie substitution rather than supplementation. Thus, an effective supplement should stimulate muscle anabolism more efficiently than food or common protein supplements. We have shown that balanced amino acids stimulate muscle protein anabolism in the elderly, but it is unknown whether all amino acids are necessary to achieve this effect. We assessed whether nonessential amino acids are required in a nutritional supplement to stimulate muscle protein anabolism in the elderly. We compared the response of muscle protein metabolism to either 18 g essential amino acids (EAA group: n = 6, age 69 +/- 2 y; +/- SD) or 40 g balanced amino acids (18 g essential amino acids + 22 g nonessential amino acids, BAA group; n = 8, age 71 ...

American journal of physiology. Endocrinology and metabolism, 2003

We have examined the effect of a hemodialysis-induced 40% reduction in plasma amino acid concentr... more We have examined the effect of a hemodialysis-induced 40% reduction in plasma amino acid concentrations on rates of muscle protein synthesis and breakdown in normal swine. Muscle protein kinetics were measured by tracer methodology using [(2)H(5)]phenylalanine and [1-(13)C]leucine and analysis of femoral arterial and venous samples and tissue biopsies. Net amino acid release by muscle was accelerated during dialysis. Phenylalanine utilization for muscle protein synthesis was reduced from the basal value of 45 +/- 8 to 25 +/- 6 nmol x min(-1) x 100 ml leg(-1) between 30 and 60 min after start of dialysis and was stimulated when amino acids were replaced while dialysis continued. Muscle protein breakdown was unchanged. The signal for changes in synthesis appeared to be changes in plasma amino acid concentrations, as intramuscular concentrations remained constant throughout. The changes in muscle protein synthesis were accompanied by a reduction or stimulation, respectively, in the gua...

Nutrition, 2009

Objective-Hypertriglyceridemia is a risk factor for coronary heart disease. The aim of this study... more Objective-Hypertriglyceridemia is a risk factor for coronary heart disease. The aim of this study was to determine the effect of AA supplementation on plasma, liver and muscle lipid concentrations and insulin sensitivity in elderly. Methods-Twelve impaired glucose tolerant elderly (67.0 ± 5.6 (SD) years, 7 females, 5 males) ingested 11 g of essential AA + arginine twice a day for 16 weeks, after a 7 week control run in. Diet and activity were not otherwise modified. Plasma lipid concentrations and oral glucose tolerance were measured every 4 th week, and tissue lipid concentrations (magnetic resonance spectroscopy) every 8 th week. Results-No changes in plasma lipids were observed during the control run-in. AA supplementation lowered plasma triglyceride (TG) (P < 0.001), total cholesterol (P = 0.048) and very low density lipoprotein (VLDL)-cholesterol (P < 0.001) concentrations. Plasma TG dropped ~20% from the initial value of 1.45 ± 0.18 (SE) mmol/l (128 ± 16 mg/dl), with greatest decrease in the subjects starting out with highest concentrations (r = −0.83).

Medicine & Science in Sports & Exercise, 2006

Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for Medicine & Sc... more Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for Medicine & Science in Sports & Exercise. Enter your Email address: Wolters Kluwer Health may email you for journal alerts and information, but ...

Archives of Physical Medicine and Rehabilitation, 2007

Plasma amino acid concentrations during late rehabilitation in patients with traumatic brain inju... more Plasma amino acid concentrations during late rehabilitation in patients with traumatic brain injury. Arch Phys Med Rehabil 2007;88: 234-8. Objectives: To investigate whether the basal plasma amino acid concentrations in patients with traumatic brain injury (TBI) have returned to levels found in healthy controls at about 17 months postinjury and to determine the effect of intake of a mixture of essential amino acids (EAA) on plasma amino acid concentrations in TBI versus healthy controls. Design: Peripheral venous amino acid concentrations in subjects with TBI were compared with concentrations in healthy controls both at rest and for 1 hour after intake of 7g of EAA. Setting: Postacute brain injury rehabilitation center. Participants: Six men with TBI (age Ϯ standard deviation, 27Ϯ6y; months postinjury, 17Ϯ4) and 6 healthy men (age, 43Ϯ7y). Intervention: Intake of a drink consisting of 7g of EAA. Main Outcome Measures: Individual and total plasma amino acid concentrations. Results: Total amino acid concentration was about 12% lower in TBI versus controls (Pϭ.022). Valine was reduced by 33% in the TBI group versus controls (Pϭ.003), whereas the other EAA did not differ between groups. After intake of the EAA drink, plasma non-EAA increased to a significantly higher level in controls versus TBI subjects (Pϭ.017). Conclusions: Plasma total amino acid concentration is still reduced 17 months postinjury in patients with TBI versus healthy controls, mainly because of a lower valine level. This may be of importance for both brain and muscle metabolic functions, and warrant further study. Further, ingested EAA are apparently not as readily converted to non-EAA in TBI patients as in healthy controls, suggesting that in recovery from TBI, certain non-EAA may become provisionally essential.

American Journal of Physiology-Endocrinology and Metabolism, 2005

We describe a method based on the traditional arteriovenous balance technique in conjunction with... more We describe a method based on the traditional arteriovenous balance technique in conjunction with muscle biopsies for the determination of leg muscle protein balance during the nonsteady state in blood amino acid concentrations. Six young, healthy individuals were studied in the postabsorptive state (pre-Phe) and after a bolus ingestion of ∼0.5 g phenylalanine (post-Phe). Post-Phe free phenylalanine concentrations in blood and muscle increased ( P < 0.05), but the respective concentrations of the amino acid threonine did not change. The average post-Phe leg net balance (NB) for threonine decreased from basal ( P < 0.05), but that for phenylalanine did not change. A volume of distribution for free phenylalanine in the leg was calculated based on the leg lean mass and the relative muscle water content and used to estimate the rate of accumulation of free phenylalanine in the leg. When the post-Phe NB for phenylalanine was corrected for the rate of accumulation of free phenylalan...

American Journal of Physiology-Endocrinology and Metabolism, 2005

The intracellular concentrations of essential amino acids (EAA) in muscle are maintained relative... more The intracellular concentrations of essential amino acids (EAA) in muscle are maintained relatively constant under a variety of conditions. However, the effect of a decrease in blood amino acid concentrations on intracellular concentrations is not clear. Similarly, the relation between intracellular and interstitial concentrations has not been determined in this circumstance. Thus the aim of this study was to determine the effect of hypoaminoacidemia on intracellular, interstitial, and plasma concentrations of EAA and the mechanisms responsible for the respective changes. Twelve normal pigs were investigated before and during 120 min of hemodialysis by use of stable-isotope tracer methodology, microdialysis technique, and muscle biopsies. During hemodialysis, there was a decrease in the interstitial fluid concentrations of phenylalanine, leucine, alanine, and lysine that corresponded to their decrease in plasma concentration. Nonetheless, the intracellular concentrations of these am...

American Journal of Physiology-Endocrinology and Metabolism, 2006

This study was designed to evaluate the effects of enriching an essential amino acid (EAA) mixtur... more This study was designed to evaluate the effects of enriching an essential amino acid (EAA) mixture with leucine on muscle protein metabolism in elderly and young individuals. Four (2 elderly and 2 young) groups were studied before and after ingestion of 6.7 g of EAAs. EAAs were based on the composition of whey protein [26% leucine (26% Leu)] or were enriched in leucine [41% leucine (41% Leu)]. A primed, continuous infusion of l-[ ring-2H5]phenylalanine was used together with vastus lateralis muscle biopsies and leg arteriovenous blood samples for the determinations of fractional synthetic rate (FSR) and balance of muscle protein. FSR increased following amino acid ingestion in both the 26% (basal: 0.048 ± 0.005%/h; post-EAA: 0.063 ± 0.007%/h) and the 41% (basal: 0.036 ± 0.004%/h; post-EAA: 0.051 ± 0.007%/h) Leu young groups ( P < 0.05). In contrast, in the elderly, FSR did not increase following ingestion of 26% Leu EAA (basal: 0.044 ± 0.003%/h; post-EAA: 0.049 ± 0.006%/h; P >...

Clinical Nutrition, 2008

Background & Aims-With advancing age there is a gradual decline in muscle mass, strength and func... more Background & Aims-With advancing age there is a gradual decline in muscle mass, strength and function. The aim of this study was to determine if regular intake of a nutritional supplement containing essential amino acids (EAA) + arginine could reverse these responses in elderly subjects. Methods-Twelve glucose intolerant subjects (67.0 ± 5.6 (SD) years, 7 females, 5 males) ingested 11 g of EAA + arginine two times a day, between meals for 16 weeks. Diet and activity were not otherwise modified. Lean body mass (DEXA) was measured every 4 th week. Maximal leg strength was tested and functional tests were performed at week 0, 8, 12, and 16. Results-Lean body mass (LBM) increased during the study (p = 0.038). At week 12, the average increase in LBM was 1.14 ± 0.36 kg (p < 0.05 vs baseline), whereas at week 16, the increase was 0.60 ± 0.38 kg (NS vs baseline). The lower extremity strength measure score (sum of individual knee flexors and extensors 1-repetition maximum, n = 10) was 127.5 ± 21.8 kg at baseline, and average increase during the study was 22.2 ± 6.1% (p < 0.001). Improvements were also observed in usual gait speed (p = 0.002), timed 5-step test (p = 0.007), and timed floor-transfer test (p = 0.022). Conclusion-Supplementation of the diet with EAA + arginine improves lean body mass, strength and physical function compared to baseline values in glucose intolerant elderly individuals.

Clinical Nutrition, 2008

Background & Aims-With advancing age there is a gradual decline in muscle mass, strength and func... more Background & Aims-With advancing age there is a gradual decline in muscle mass, strength and function. The aim of this study was to determine if regular intake of a nutritional supplement containing essential amino acids (EAA) + arginine could reverse these responses in elderly subjects.