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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.

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.

It is a truth universally acknowledged that every ambitious twenty-first century trade agreement is in want of a chapter on electronic commerce. One of the most politically sensitive and technically challenging issues is personal privacy, including cross-border transfer of information by electronic means, use and location of computing facilities, and personal information protection. States are learning to solve the problem of state responsibility for something that does not respect their borders while still allowing twenty-first century commerce to develop. A comparison of the Canada–European Union Comprehensive Economic and Trade Agreement (CETA) and the Trans-Pacific Partnership (TPP) allows us to see the evolution of the issues thought necessary for an e-commerce chapter, since both include Canada, and to see the differing priorities of the US and the EU, since they are each signatory to one of the agreements, but not of the other. I conclude by seeking generalizations about why we see a mix of aspirational and obligatory provisions in free trade agreements. I suggest that the reasons are that governments are learning how to work with each other in a new domain, and learning about the trade implications of these issues.

Using trade policy to achieve foreign policy objectives, such as stable international relations, has a long history, from Kant to the founders of the GATT. Punishing enemies and rewarding ‘friends’ by granting or withholding market access is also not new, and sanctions or blockades are a venerable form of trade policy used as foreign policy. A more recent form is influencing the domestic policy of another country with non-commercial provisions in trade agreements. All these tools are based on linkage, on the assumption that a desired outcome can be achieved by interventions that would increase or decrease trade. The latest instance is so-called ‘friend-shoring’, which would in principle isolate enemies, although it will be difficult in practice and risks undermining multilateralism. The cost of these interventions is susceptible to economic analysis, even if the conclusion is that it is worth paying. Influenced by Alan Winters who referred to national security as a motivation for agriculture protection as a ‘so-called non-economic objective’ or SNO, I argue that using a trade policy tool for a foreign policy purpose as if there is no cost is a SNO job, an attempt to justify an intervention aimed at one objective by framing it as being valuable for another.

Nutritional status is a strong predictor of postoperative outcomes and is recognized as an important component of surgical recovery programs. Adequate nutritional consumption is essential for addressing the surgical stress response and mitigating the loss of muscle mass, strength, and functionality. Especially in older patients, inadequate protein can lead to significant muscle atrophy, leading to a loss of independence and increased mortality risk. Current nutritional recommendations for surgery primarily focus on screening and prevention of malnutrition, pre-surgical fasting protocols, and combating post-surgical insulin resistance, while recommendations regarding macronutrient composition and timing around surgery are less established. The goal of this review is to highlight oral nutrition strategies that can be implemented leading up to and following major surgery to minimize atrophy and the resultant loss of functionality. The role of carbohydrate and especially protein/essential amino acids in combating the surgical stress cascade and supporting recovery are discussed. Practical considerations for nutrient timing to maximize oral nutritional intake, especially during the immediate pre- and post- surgical periods, are also be discussed.

AbstractObjectiveTo determine the effects of diets varying in carbohydrate to fat ratio on total energy expenditure.DesignRandomized trial.SettingMulticenter collaboration at US two sites, August 2014 to May 2017.Participants164 adults aged 18-65 years with a body mass index of 25 or more.InterventionsAfter 12% (within 2%) weight loss on a run-in diet, participants were randomly assigned to one of three test diets according to carbohydrate content (high, 60%, n=54; moderate, 40%, n=53; or low, 20%, n=57) for 20 weeks. Test diets were controlled for protein and were energy adjusted to maintain weight loss within 2 kg. To test for effect modification predicted by the carbohydrate-insulin model, the sample was divided into thirds of pre-weight loss insulin secretion (insulin concentration 30 minutes after oral glucose).Main outcome measuresThe primary outcome was total energy expenditure, measured with doubly labeled water, by intention-to-treat analysis. Per protocol analysis included participants who maintained target weight loss, potentially providing a more precise effect estimate. Secondary outcomes were resting energy expenditure, measures of physical activity, and levels of the metabolic hormones leptin and ghrelin.ResultsTotal energy expenditure differed by diet in the intention-to-treat analysis (n=162, P=0.002), with a linear trend of 52 kcal/d (95% confidence interval 23 to 82) for every 10% decrease in the contribution of carbohydrate to total energy intake (1 kcal=4.18 kJ=0.00418 MJ). Change in total energy expenditure was 91 kcal/d (95% confidence interval −29 to 210) greater in participants assigned to the moderate carbohydrate diet and 209 kcal/d (91 to 326) greater in those assigned to the low carbohydrate diet compared with the high carbohydrate diet. In the per protocol analysis (n=120, P<0.001), the respective differences were 131 kcal/d (−6 to 267) and 278 kcal/d (144 to 411). Among participants in the highest third of pre-weight loss insulin secretion, the difference between the low and high carbohydrate diet was 308 kcal/d in the intention-to-treat analysis and 478 kcal/d in the per protocol analysis (P<0.004). Ghrelin was significantly lower in participants assigned to the low carbohydrate diet compared with those assigned to the high carbohydrate diet (both analyses). Leptin was also significantly lower in participants assigned to the low carbohydrate diet (per protocol).ConclusionsConsistent with the carbohydrate-insulin model, lowering dietary carbohydrate increased energy expenditure during weight loss maintenance. This metabolic effect may improve the success of obesity treatment, especially among those with high insulin secretion.Trial registrationClinicalTrials.gov NCT02068885.

State-owned enterprises (SOEs) are a major force in the Chinese economy and a growing presence in international trade and investment. The challenge to the WTO legal regime is commercial, given the size of SOEs and their share of Chinese output, and political, given worries that trade and investment by SOEs may be driven by public policy goals. And both challenges may be exacerbated by the murky world of Chinese SOEs. In this article, I first review whether Chinese SOEs are a problem for the WTO, and whether more sunshine on their operations might be a useful discipline. I then ask what we know about SOEs inside the WTO, including in the Trade Policy Review Mechanism. Since the answer is, not much, I consider whether mega-regional trade negotiations offer a better approach. My answer being negative, I finally consider whether an attempt to negotiate a WTO Reference Paper on SOEs might help. I conclude that transparency is likely to be a better discipline on the spillovers associated with SOEs than a search for binding rules, while also helping everyone better understand the efficiency effects.

Abstract Context Consuming calories later in the day is associated with obesity and metabolic syndrome. We hypothesized that eating a late dinner alters substrate metabolism during sleep in a manner that promotes obesity. Objective The objective of this work is to examine the impact of late dinner on nocturnal metabolism in healthy volunteers. Design and Setting This is a randomized crossover trial of late dinner (LD, 22:00) vs routine dinner (RD, 18:00), with a fixed sleep period (23:00-07:00) in a laboratory setting. Participants Participants comprised 20 healthy volunteers (10 male, 10 female), age 26.0 ± 0.6 years, body mass index 23.2 ± 0.7 kg/m2, accustomed to a bedtime between 22:00 and 01:00. Interventions An isocaloric macronutrient diet was administered on both visits. Dinner (35% daily kcal, 50% carbohydrate, 35% fat) with an oral lipid tracer ([2H31] palmitate, 15 mg/kg) was given at 18:00 with RD and 22:00 with LD. Main Outcome Measures Measurements included nocturnal and next-morning hourly plasma glucose, insulin, triglycerides, free fatty acids (FFAs), cortisol, dietary fatty acid oxidation, and overnight polysomnography. Results LD caused a 4-hour shift in the postprandial period, overlapping with the sleep phase. Independent of this shift, the postprandial period following LD was characterized by higher glucose, a triglyceride peak delay, and lower FFA and dietary fatty acid oxidation. LD did not affect sleep architecture, but increased plasma cortisol. These metabolic changes were most pronounced in habitual earlier sleepers determined by actigraphy monitoring. Conclusion LD induces nocturnal glucose intolerance, and reduces fatty acid oxidation and mobilization, particularly in earlier sleepers. These effects might promote obesity if they recur chronically.

Since Rudolf Schoenheimer’s pioneering metabolic tracing work in the 1930s1, it is currently well appreciated that all constituents of living matter (e.g., DNAs, RNAs, proteins, lipids, and metabolites) are in a constant state of turnover at varying rates to achieve overall “dynamic” homeostasis. Furthermore, metabolic systems are highly complex, connected, and interactive, and consequently, one’s metabolic fluxes (“motion pictures”) should not be understood as individual components but as a whole system2. Unfortunately, most modern metabolic studies heavily depend on the measurements of static, snapshot information, so-called “statomics” (e.g., transcriptomics, proteomics, metabolomics, and cellular signaling cascades) of individual components of the whole system, which often fail to reflect actual metabolic status3,4. Without simultaneous considerations of metabolic flux, sole dependence on “statomics” can lead to incorrect conclusions regarding metabolic status. In this Special Feature, experts in the field of tracer methodology or fluxomics provide the basic principles and applications of the methodologies determining metabolic fluxes to various metabolic conditions. The incorporation of these state-of-the-art methodologies into metabolic research will guide researchers to a better understanding of dynamic metabolic systems with which to better dissect underlying molecular mechanisms of physiology or pathophysiology. KCI Citation Count: 0