Muscle transcriptomic circuits linked to periarticular physiology in end-stage osteoarthritis.

The ability of individuals with end-stage osteoarthritis (OA) to functionally recover from total joint arthroplasty is highly inconsistent. The molecular mechanisms driving this heterogeneity have yet to be elucidated. Furthermore, OA disproportionately impacts females, suggesting a need for identifying female-specific therapeutic targets.

Perioperative assessment of muscle inflammation susceptibility in patients with end-stage osteoarthritis.

Many individuals with end-stage osteoarthritis (OA) undergo elective total hip/knee arthroplasty (THA/TKA) to relieve pain, improve mobility and quality of life. However, ∼30% suffer long-term mobility impairment following surgery. This may be in part due to muscle inflammation susceptibility (MuIS+), an overt proinflammatory pathology localized to skeletal muscle surrounding the diseased joint, present in some patients with TKA/THA.

Perioperative amino acid infusion reestablishes muscle net balance during total hip arthroplasty.

Surgery and anesthesia induce a catabolic response that leads to skeletal muscle protein loss. Previous investigations have observed positive effects of perioperative nutrition. Furthermore, the benefits of exogenous amino acids on muscle protein kinetics are well established.

Equivalent servings of free-range reindeer promote greater net protein balance compared to commercial beef.

Wild game consumption has been associated with health benefits but the acute influence on human protein metabolism remains unknown. We compared feeding-induced responses of equivalent amounts of free-range reindeer (FR) and commercial beef (CB) on protein kinetics using stable isotope methodology. Seven participants (age: 40 ± 14 years; body mass index: 24 ± 3 kg/m) completed two randomised studies, ingesting 2 oz of FR or CB.

Daily Consumption of a Specially Formulated Essential Amino Acid-Based Dietary Supplement Improves Physical Performance in Older Adults With Low Physical Functioning.

We have investigated the hypothesis that nutritional supplementation of the diet in low-physical-functioning older individuals with a specially formulated composition based on essential amino acids (EAAs) would improve physical function as compared to supplementation with the same amount of whey protein. A third group of comparable volunteers were given nutrition education but no supplementation of the diet. After 6 weeks of whey protein supplementation (n = 32), there was no effect on the distance walked in 6 minutes, but the distance walked improved significantly from the pre-value after 12 weeks of whey supplementation.

The Anabolic Response to Dietary Protein Is Not Limited by the Maximal Stimulation of Protein Synthesis in Healthy Older Adults: A Randomized Crossover Trial.

We have recently demonstrated in young adults that an anabolic response with mixed meal protein intake above ~35 g/meal, previously recognized as an "optimal" protein dose, was further stimulated. However, it is unknown if this applies to older adults. We therefore examined anabolic response to a mixed meal containing either 35 g (MOD, moderate amount of protein) or 70 g (HIGH, high amount of protein) in a randomized cross-over metabolic study in older adults ( = 8).

The impact of Hayward green kiwifruit on dietary protein digestion and protein metabolism.

Purpose: The purpose of the study was to determine if an actinidin protease aids gastric digestion and the protein anabolic response to dietary protein.

Methods: Hayward green kiwifruit (containing an actinidin protease) and Hort 16A gold kiwifruit (devoid of actinidin protease) were given in conjunction with a beef meal to healthy older subjects. Twelve healthy older males (N = 6) and females (N = 6) were studied with a randomized, double-blinded, crossover design to assess muscle and whole-body protein metabolism before and after ingestion of kiwifruit and 100 g of ground beef.

Effects of Fortetropin on the Rate of Muscle Protein Synthesis in Older Men and Women: A Randomized, Double-Blinded, Placebo-Controlled Study.

Background: Fortetropin is a proteo-lipid complex made from fertilized egg yolk and, in young men, has been shown to increase lean body mass.

Methods: The purpose of this study was to examine the effects of 21 days of Fortetropin supplementation on the fractional synthetic rate (FSR) of muscle protein in 10 healthy, older men and 10 women (66.4 ± 4.

Anabolic response to essential amino acid plus whey protein composition is greater than whey protein alone in young healthy adults.

Background: We have determined the acute response of protein kinetics to one or two servings (6.3 g and 12.6 g) of a proprietary composition containing free-form essential amino acids (EAA) (3.

Consumption of a Specially-Formulated Mixture of Essential Amino Acids Promotes Gain in Whole-Body Protein to a Greater Extent than a Complete Meal Replacement in Older Women with Heart Failure.

Heart failure in older individuals is normally associated with a high body mass index and relatively low lean body mass due to, in part, a resistance to the normal anabolic effect of dietary protein. In this study we have investigated the hypothesis that consumption of a specially-formulated composition of essential amino acids (HiEAAs) can overcome anabolic resistance in individuals with heart failure and stimulate the net gain of body protein to a greater extent than a commercially popular protein-based meal replacement beverage with greater caloric but lower essential amino acid (EAA) content (LoEAA). A randomized cross-over design was used.

Essential amino acid-enriched meal replacement promotes superior net protein balance in older, overweight adults.

Background & Aims: Older individuals are susceptible to the loss of muscle and accumulation of fat. To address this problem, we have compared protein kinetics following consumption of an essential amino acid (EAA)-enriched meal replacement (EMR) to consumption of a high-protein meal replacement beverage (Bariatric Advantage, BA) using stable isotope methodology.

Methods: Eight older (67 ± 2), obese (35 ± 2 kg/m) female and male participants completed two studies using a randomized, crossover design in which they ingested each meal replacement.

Skeletal Muscle Acute and Chronic Metabolic Response to Essential Amino Acid Supplementation in Hypertriglyceridemic Older Adults.

Supplementation with essential amino acids (EAAs) + arginine is a promising nutritional approach to decrease plasma triglyceride (TG) concentrations, which are an independent risk factor for ischemic heart disease. The objective of this study was to examine the effects of 8 wk of EAA supplementation on skeletal muscle basal metabolite concentrations and changes in metabolic response to acute EAA intake, with an emphasis on mitochondrial metabolism, in adults with elevated TGs to better understand the mechanisms of lowering plasma TGs. Older adults with elevated plasma TG concentrations were given 22 g EAAs to ingest acutely before and after an 8-wk EAA supplementation period.

Quality of meal protein determines anabolic response in older adults.

Background & Aims: It has been demonstrated that the relative content and profile of essential amino acids (EAA) play a determining role for stimulation of muscle protein synthesis (MPS) following intake of pure EAA or protein alone.

Methods: To test if this also holds in the context of mixed meals at both whole body and muscle levels, twelve older subjects (57-74 yrs) received primed continuous infusion of L-[ring-H]phenylalanine and L-[ring-H]tyrosine over a 9-h experimental period to determine whole body protein kinetics and MPS in the fasted state and following consumption of egg-based (EGG) or cereal-based (CEREAL) isocaloric and isonitrogenous breakfast. A standardized lunch, primarily consisting of beef protein was also consumed by each group.

Do anabolic nutritional supplements stimulate human growth hormone secretion in elderly women with heart failure?

Growth hormone treatment has gained attention over the past decade as a treatment for heart failure. Human growth hormone (HGH) must be administered by injections (usually daily), so there is considerable advantage to stimulation of endogenous secretion by amino acid-based nutritional supplementation. However, studies investigating the effect of amino acid (AA) supplementation show conflicting results.

Short term elevation in dietary protein intake does not worsen insulin resistance or lipids in older adults with metabolic syndrome: a randomized-controlled trial.

Background: There is a great deal of controversy as to whether higher protein intake improves or worsens insulin sensitivity in humans. The purpose of the study was to determine the influence of a short-term elevation in dietary protein on hepatic and peripheral insulin sensitivity in twelve older subjects (51-70 yrs) with metabolic syndrome.

Methods: Individuals were randomly assigned to one of the dietary groups: recommended protein intake (RPI, 10% of daily calorie intake) or elevated protein intake (EPI, 20% of daily calorie intake) for 4 weeks.

Protein intake distribution pattern does not affect anabolic response, lean body mass, muscle strength or function over 8 weeks in older adults: A randomized-controlled trial.

Background & Aims: In our recent acute metabolic study, we found no differences in the anabolic response to differing patterns of dietary protein intake. To confirm this in a chronic study, we investigated the effects of protein distribution pattern on functional outcomes and protein kinetics in older adults over 8 weeks.

Methods: To determine chronic effects of protein intake pattern at 1.

Nutritional Supplementation with Essential Amino Acids and Phytosterols May Reduce Risk for Metabolic Syndrome and Cardiovascular Disease in Overweight Individuals with Mild Hyperlipidemia.

Background: Hyperlipidemia and insulin resistance are risk factors for the development of metabolic syndrome and cardiovascular disease. We have previously observed that supplementation with essential amino acids (EAA) could lower plasma triglycerides, and may improve glucose metabolism.

Objective: We sought to determine whether EAA's combined with whey protein and phytosterols would facilitate improvements in plasma lipids and insulin sensitivity in adults with mild hypertriglyceridemia.

The anabolic response to a meal containing different amounts of protein is not limited by the maximal stimulation of protein synthesis in healthy young adults.

We have determined whole body protein kinetics, i.e., protein synthesis (PS), breakdown (PB), and net balance (NB) in human subjects in the fasted state and following ingestion of ~40 g [moderate protein (MP)], which has been reported to maximize the protein synthetic response or ~70 g [higher protein (HP)] protein, more representative of the amount of protein in the dinner of an average American diet.

Acute ingestion of citrulline stimulates nitric oxide synthesis but does not increase blood flow in healthy young and older adults with heart failure.

To determine if age-associated vascular dysfunction in older adults with heart failure (HF) is due to insufficient synthesis of nitric oxide (NO), we performed two separate studies: 1) a kinetic study with a stable isotope tracer method to determine in vivo kinetics of NO metabolism, and 2) a vascular function study using a plethysmography method to determine reactive hyperemic forearm blood flow (RH-FBF) in older and young adults in the fasted state and in response to citrulline ingestion. In the fasted state, NO synthesis (per kg body wt) was ∼ 50% lower in older vs. young adults and was related to a decreased rate of appearance of the NO precursor arginine.

Quantity of dietary protein intake, but not pattern of intake, affects net protein balance primarily through differences in protein synthesis in older adults.

To examine whole body protein turnover and muscle protein fractional synthesis rate (MPS) following ingestions of protein in mixed meals at two doses of protein and two intake patterns, 20 healthy older adult subjects (52-75 yr) participated in one of four groups in a randomized clinical trial: a level of protein intake of 0.8 g (1RDA) or 1.5 g·kg(-1)·day(-1) (∼2RDA) with uneven (U: 15/20/65%) or even distribution (E: 33/33/33%) patterns of intake for breakfast, lunch, and dinner over the day (1RDA-U, 1RDA-E, 2RDA-U, or 2RDA-E).

Acute lysine supplementation does not improve hepatic or peripheral insulin sensitivity in older, overweight individuals.

Context: Lysine supplementation may have a positive influence on the regulation of glucose metabolism but it has not been tested in the geriatric population.

Objective: We evaluated the impact of acute lysine supplementation using three randomized experimental scenarios: 1) oral glucose alone (control), 2) oral glucose and low-dose lysine (2 grams), and oral glucose and high dose lysine (5 grams) lysine in 7 older (66 ± 1 years/age), overweight/obese (BMI = 28 ± 2 kg/m(2)) individuals.

Methods: We utilized a dual tracer technique (i.

Whey protein and essential amino acids promote the reduction of adipose tissue and increased muscle protein synthesis during caloric restriction-induced weight loss in elderly, obese individuals.

Background: Excess adipose tissue and sarcopenia presents a multifaceted clinical challenge that promotes morbidity and mortality in the obese, elderly population. Unfortunately, the mortality risks of muscle loss may outweigh the potential benefits of weight loss in the elderly. We have previously demonstrated the effectiveness of whey protein and essential amino acids towards the preservation of lean tissue, even under the conditions of strict bedrest in the elderly.

Muscle protein synthesis in cancer patients can be stimulated with a specially formulated medical food.

Objective: Maintenance of muscle mass is crucial to improving outcome and quality of life in cancer patients. Stimulating muscle protein synthesis is the metabolic basis for maintaining muscle mass, but in cancer patients normal dietary intake has minimal effects on muscle protein synthesis. Adding leucine to high protein supplements stimulates muscle protein synthesis in healthy older subjects.