The branched chain amino acids (BCAAs) are leucine, valine and isoleucine. A multi-million dollar industry of nutritional supplements has grown around the concept that dietary supplements of BCAAs ...alone produce an anabolic response in humans driven by a stimulation of muscle protein synthesis. In this brief review the theoretical and empirical bases for that claim are discussed. Theoretically, the maximal stimulation of muscle protein synthesis in the post-absorptive state in response to BCAAs alone is the difference between muscle protein breakdown and muscle protein synthesis (about 30% greater than synthesis), because the other EAAs required for synthesis of new protein can only be derived from muscle protein breakdown. Realistically, a maximal increase in muscle protein synthesis of 30% is an over-estimate because the obligatory oxidation of EAAs can never be completely suppressed. An extensive search of the literature has revealed no studies in human subjects in which the response of muscle protein synthesis to orally-ingested BCAAs alone was quantified, and only two studies in which the effect of intravenously infused BCAAs alone was assessed. Both of these intravenous infusion studies found that BCAAs decreased muscle protein synthesis as well as protein breakdown, meaning a decrease in muscle protein turnover. The catabolic state in which the rate of muscle protein breakdown exceeded the rate of muscle protein synthesis persisted during BCAA infusion. We conclude that the claim that consumption of dietary BCAAs stimulates muscle protein synthesis or produces an anabolic response in human subjects is unwarranted.
Muscle plays a central role in whole-body protein metabolism by serving as the principal reservoir for amino acids to maintain protein synthesis in vital tissues and organs in the absence of amino ...acid absorption from the gut and by providing hepatic gluconeogenic precursors. Furthermore, altered muscle metabolism plays a key role in the genesis, and therefore the prevention, of many common pathologic conditions and chronic diseases. Nonetheless, the maintenance of adequate muscle mass, strength, and metabolic function has rarely, if ever, been targeted as a relevant endpoint of recommendations for dietary intake. It is therefore imperative that factors directly related to muscle mass, strength, and metabolic function be included in future studies designed to demonstrate optimal lifestyle behaviors throughout the life span, including physical activity and diet.
Hypoalbuminemia: Pathogenesis and Clinical Significance Soeters, Peter B.; Wolfe, Robert R.; Shenkin, Alan
JPEN, Journal of parenteral and enteral nutrition/JPEN. Journal of parenteral and enteral nutrition,
February 2019, Letnik:
43, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Hypoalbuminemia is associated with inflammation. Despite being addressed repeatedly in the literature, there is still confusion regarding its pathogenesis and clinical significance. Inflammation ...increases capillary permeability and escape of serum albumin, leading to expansion of interstitial space and increasing the distribution volume of albumin. The half‐life of albumin has been shown to shorten, decreasing total albumin mass. These 2 factors lead to hypoalbuminemia despite increased fractional synthesis rates in plasma. Hypoalbuminemia, therefore, results from and reflects the inflammatory state, which interferes with adequate responses to events like surgery or chemotherapy, and is associated with poor quality of life and reduced longevity. Increasing or decreasing serum albumin levels are adequate indicators, respectively, of improvement or deterioration of the clinical state. In the interstitium, albumin acts as the main extracellular scavenger, antioxidative agent, and as supplier of amino acids for cell and matrix synthesis. Albumin infusion has not been shown to diminish fluid requirements, infection rates, and mortality in the intensive care unit, which may imply that there is no body deficit or that the quality of albumin “from the shelf” is unsuitable to play scavenging and antioxidative roles. Management of hypoalbuminaemia should be based on correcting the causes of ongoing inflammation rather than infusion of albumin. After the age of 30 years, muscle mass and function slowly decrease, but this loss is accelerated by comorbidity and associated with decreasing serum albumin levels. Nutrition support cannot fully prevent, but slows down, this chain of events, especially when combined with physical exercise.
The determination of whether increased dietary protein can positively affect health outcomes is hindered by the absence of prospective, randomized trials directly addressing this issue in which all ...pertinent variables are controlled. Consequently, we can only address the question deductively by considering the support for the rationale underlying the notion of a beneficial effect of increased dietary protein intake. With regard to health outcomes, we have focused on older individuals. Muscle mass and function are progressively lost with aging, so that by the age of 60 many individuals have reached a threshold where function begins to be affected. An association between reduced muscle mass and strength and unfavourable health outcomes is more likely to be revealed in individuals who have significant decrements in muscle mass and strength. In this article support for the rationale underlying the notion of a beneficial effect of increased dietary protein intake is considered. Dietary protein intake, and the resulting increased availability of plasma amino acids, stimulates muscle protein synthesis. If all other variables are controlled, increased muscle protein synthesis leads to improved muscle mass, strength and function over time. Increased muscle mass, strength and function are related to improved health outcomes in older individuals. Since adverse effects of reasonable increases in protein intake above the recommended dietary allowance (RDA) of 0·8 g protein/kg/day have not been reported, it is reasonable to conclude that the optimal protein intake for an older individual is greater than the RDA.
Abstract Purpose The aims of this article were to systematically review the literature about the mechanism of action of colchicine in the multimodal pathology of acute inflammation associated with ...gout and to consider the clinical utility of colchicine in other chronic inflammatory diseases. Methods The English-language literature on PubMed was searched for articles published between 1990 and October 2013, with a cross-reference to citations across all years. Relevant articles pertaining to the mechanism of action of colchicine and the clinical applications of colchicine in gout and other inflammatory conditions were identified and reviewed. Findings The molecular pathology of acute inflammation associated with gouty arthritis involves several concurrent pathways triggered by a variety of interactions between monosodium urate crystals and the surface of cells. Colchicine modulates multiple pro- and antiinflammatory pathways associated with gouty arthritis. Colchicine prevents microtubule assembly and thereby disrupts inflammasome activation, microtubule-based inflammatory cell chemotaxis, generation of leukotrienes and cytokines, and phagocytosis. Many of these cellular processes can be found in other diseases involving chronic inflammation. The multimodal mechanism of action of colchicine suggests potential efficacy of colchicine in other comorbid conditions associated with gout, such as osteoarthritis and cardiovascular disease. Implications Colchicine has multiple mechanisms of action that affect inflammatory processes and result in its utility for treating and preventing acute gout flare. Other chronic inflammatory diseases that invoke these molecular pathways may represent new therapeutic applications for colchicine.
The epidemiology of mucormycosis in the era of modern diagnostics is relatively under-explored.
To examine the contemporary epidemiology, clinical manifestations, diagnosis and causative pathogens of ...mucormycosis.
Ovid MEDLINE and Ovid EMBASE from January 2000 to January 2017.
Published case reports/series of proven/probable mucormycosis.
Patients ≥18 years old.
Patient characteristics, disease manifestations and causative pathogens were summarized descriptively. Categorical variables were assessed by chi-square test or Fischer's exact test, and continuous variables by the Wilcoxon–Mann–Whitney or Kruskal–Wallis test. Risk factors for the different clinical manifestations of mucormycosis were identified using multivariate logistic regression.
Initial database searches identified 3619 articles of which 600 (851 individual patient cases) were included in the final analysis. Diabetes mellitus was the commonest underlying condition (340/851, 40%) and was an independent risk for rhino-orbital-cerebral mucormycosis (odds ratio (OR) 2.49; 95% CI 1.77–3.54; p < 0.001). Underlying haematological malignancy was associated with disseminated infection (OR 3.86; 95% CI 1.78–8.37; p 0.001), whereas previous solid organ transplantation was associated with pulmonary (OR 3.19; 95% CI 1.50–6.82; p 0.003), gastrointestinal (OR 4.47; 95% CI 1.69–11.80; p 0.003), or disseminated (OR 4.20; 95% CI 1.68–10.46; p 0.002) mucormycosis. Eight genera (24 species) of Mucorales organisms were identified in 447/851 (53%) cases, of which Rhizopus spp. (213/447, 48%) was the most common. Compared with other genera, Rhizopus spp. was predominantly observed in patients with rhino-orbital-cerebral mucormycosis (75/213, 35% versus 34/234, 15%; p < 0.001). Death was reported in 389/851 (46%) patients. Mortality associated with Cunninghamella infections was significantly higher than those caused by other Mucorales (23/30, 71% versus 185/417, 44%; p < 0.001). However, Cunninghamella spp. were isolated primarily in patients with pulmonary (17/30, 57%) or disseminated disease (10/30, 33%).
Findings from the current review have helped ascertain the association between various manifestations of mucormycosis, their respective predisposing factors and causative organisms.
In this short review, our current understanding of key aspects of the catabolic response are presented in the context of the seminal contributions of Sir David Cuthbertson.
Studies have confirmed ...that an increase in resting energy expenditure occurs in almost all forms of critical illness and injury. However, meeting the resulting increase in caloric requirement is not an insurmountable problem. The primary focus of nutritional support should be the net loss of body protein. Increased intake of dietary protein may ameliorate, but usually will not entirely reverse, the accelerated loss of body protein because of anabolic resistance. Anabolic resistance is due, at least in part, to impaired inward transport efficiency of amino acids from blood into muscle. Simultaneous consumption of excess non-protein calories in an anabolic resistant state provides minimal additional benefit, and may cause potentially adverse effects, including accumulation of liver fat and excess production of carbon dioxide. Because of the limited effectiveness of dietary protein and non-protein caloric intake, it is likely that traditional nutritional support alone will not reverse the net loss of body protein in the catabolic state. The reversal of the catabolic response can only be accomplished in many patients by combining reasonable nutritional support with appropriate metabolic control. Metabolic control may be achieved with the use of a number of pharmacological approaches, including propranolol, insulin or testosterone. Regardless of the approach, ensuring an adequate availability of dietary essential amino acids is necessary for pharmacologic therapy to result in an increased rate of protein synthesis.
Protein is a macronutrient essential for growth, muscle function, immunity and overall tissue homeostasis. Suboptimal protein intake can significantly impact physical function and overall health in ...older adults.
This article reviews the literature on the recommendations for protein intake in older adults in light of the new evidence linking protein intake with sarcopenia and physical function. Challenges and opportunities for optimal protein nutrition in older persons are discussed.
Recent metabolic and epidemiological studies suggest that the current recommendations of protein intake may not be adequate for maintenance of physical function and optimal health in older adults. Methodological limitations and novel concepts in protein nutrition are also discussed.
We conclude that new research and novel research methodologies are necessary to establish the protein needs and optimal patterns of protein intake for older persons.
The exact relationship between the bed rest-induced loss of skeletal muscle and reductions in muscle strength and physical performance in the older individuals is still unclear.
We examined the ...effect of 10 days of bed rest on changes in regional body composition, muscle strength, and functional status, and the relationship between these variables in older individuals.
Regional body composition was measured using dual energy x-ray absorptiometry. We also determined changes in leg strength and several indices of functional status, including walking speed.
Body weight, body mass index, and total and lower extremity lean mass decreased with bed rest. There were also significant reductions in knee extension one repetition maximum, isometric knee extension, knee extension 60° concentric, stair ascent time, stair ascent power, stair descent time, VO2 max, floor transfer test, 5-minute walk time, and chair stand. The overall change in total and lower extremity lean mass was also directly related to bed rest-induced reductions in one repetition maximum knee extension.
Bed rest promoted overall declines in muscle mass, muscle strength, and physical function in older individuals. The changes in lean tissue were closely correlated with the bed rest-induced decline of muscle strength.
Loss of lean body mass that occurs with aging is the primary endpoint with which sarcopenia is defined. Furthermore, loss of muscle mass is central to the development of many adverse health issues in ...the elderly. Consequently, the response of lean body mass to nutritional interventions, particularly to dietary protein, has been a commonly measured endpoint. However, increased protein intake has been associated with improved markers for cardiovascular health, improved bone health, management of weight and metabolic diseases, and reduced all-cause mortality. Strength, rather than lean body mass, may be a more accurate indicator of health, especially in the elderly. The recommended dietary allowance for protein has been set at 0.8 g/kg/day. Because the average protein intake in the United States is approximately 1.2 g/kg/day, it appears that the average protein intake is above the recommended dietary allowance but below the low end of the acceptable macronutrient distribution range recommended by expert committees of the National Academy of Sciences and below the dietary intake levels suggested by the US Department of Agriculture in the Dietary Guidelines.
PDF
