Effects of different protein sources on amino acid absorption and plasma appearance of tryptophan, large neutral amino acids, and tryptophan metabolites in pigs.

BACKGROUND: Absorption of tryptophan (TRP) across the gut epithelium is potentially modulated by competing large neutral amino acids (LNAAs), which could affect the appearance of TRP and its metabolites in the bloodstream. OBJECTIVES: This study aimed to determine, in a growing pig model of an adult human, the absorption of TRP and other LNAAs from the gastrointestinal tract, and plasma appearance of TRP, LNAAs and TRP metabolites , in response to dietary proteins varying in TRP content. METHODS: Pigs were adapted for seven days to each of four diets that differed in their protein source and TRP content: 1) alpha-lactalbumin (AL; 9.95mg TRP/g diet DM), 2) whey protein (6.59mg TRP/g), 3) casein (3.73mg TRP/g), or 4) zein (0.14mg TRP/g). On day 8, after a 12h fast, pigs received a test meal consisting of 45g protein, or a protein-free meal, and were euthanized 0 (baseline), 1, 2, 3, 4, or 6h later (n=6 pigs at each time in each meal group). Tryptophan and LNAA absorption from the small intestine, and appearance of TRP, LNAAs and TRP metabolites (melatonin, serotonin, kynurenine pathway metabolites), in the portal vein and systemic circulation, were determined. RESULTS: AL intake resulted in sustained elevated plasma TRP concentrations after an overnight fast. The amount of TRP absorbed was dose-dependently related to protein TRP content (p=0.028), with fastest rates for pigs fed AL (371mg/h). Portal and systemic plasma TRP, TRP/LNAA and the TRP metabolites were highest (p≤0.05) after AL intake , and remained above baseline levels for ∼4h postprandially. Absorption rates of TRP correlated with postprandial plasma TRP and TRP metabolites(p≤0.05). CONCLUSIONS: In adult humans, postprandial plasma TRP and TRP metabolite concentrations can likely be modulated by the TRP content of the meal.

Monosodium Glutamate in the Diet Does Not Raise Brain Glutamate Concentrations or Disrupt Brain Functions.

The non-essential amino acid glutamate participates in numerous metabolic pathways in the body. It also performs important physiologic functions, which include a sensory role as one of the basic tastes (as monosodium glutamate [MSG]), and a role in neuronal function as the dominant excitatory neurotransmitter in the central nervous system. Its pleasant taste (as MSG) has led to its inclusion as a flavoring agent in foods for centuries. Glutamate's neurotransmitter role was discovered only in the last 60 years. Its inclusion in foods has necessitated its safety evaluation, which has raised concerns about its transfer into the blood ultimately increasing brain glutamate levels, thereby causing functional disruptions because it is a neurotransmitter. This concern, originally raised almost 50 years ago, has led to an extensive series of scientific studies to examine this issue, conducted primarily in rodents, non-human primates, and humans. The key findings have been that (a) the ingestion of MSG in the diet does not produce appreciable increases in glutamate concentrations in blood, except when given experimentally in amounts vastly in excess of normal intake levels; and (b) the blood-brain barrier effectively restricts the passage of glutamate from the blood into the brain, such that brain glutamate levels only rise when blood glutamate concentrations are raised experimentally via non-physiologic means. These and related discoveries explain why the ingestion of MSG in the diet does not lead to an increase in brain glutamate concentrations, and thus does not produce functional disruptions in brain. This article briefly summarizes key experimental findings that evaluate whether MSG in the diet poses a threat to brain function.

Introduction and Summary of the 2018 Dietary Glutamate Workshop.

The 2018 Dietary Glutamate Workshop was organized and sponsored by the International Glutamate Technical Committee to provide a platform for a broad expert discussion on all relevant aspects of glutamate metabolism and safety in human nutrition. The participants reached a consensus with previous safety evaluations conducted by the global expert bodies, but contradicted the 2017 re-evaluation of dietary glutamates by the European Food Safety Authority, which proposed a group acceptable daily intake (ADI) of 30 mg/kg body weight per day. The participants of the Workshop concluded that the present knowledge on metabolism, kinetics, developmental and general toxicity of dietary glutamates did not warrant a change in the previous ADI of "not specified."

A Perspective on the Safety of Supplemental Tryptophan Based on Its Metabolic Fates.

Over the past 50 y, tryptophan has been ingested in amounts well in excess of its dietary requirement. This use is based on extensive findings that ingesting tryptophan increases brain tryptophan concentrations, which stimulates the synthesis and release of the neurotransmitter serotonin, from which it is derived. Such increases in serotonin function may improve mood and sleep. However, tryptophan ingestion has other effects, such as increasing serotonin production in the gut, increasing serotonin concentrations in blood, stimulating the production of the hormone melatonin (a tryptophan metabolite), stimulating tryptophan metabolism via the kynurenine pathway, and possibly stimulating the production of tryptophan metabolites in the gut microbiome. Several of the kynurenine metabolites have actions on excitatory glutamate receptors in the gut and brain and on cells of the immune system. In addition, metabolites of tryptophan produced by colonic bacteria are reported to cause adverse effects in some species. This review examines each of these tryptophan pathways to determine if any of the metabolites increase after tryptophan ingestion, and if so, whether effects are seen on target body functions. In this regard, recent research suggests that it may be useful to examine kynurenine pathway metabolites and some microbial tryptophan metabolites to determine whether supplemental tryptophan consumption increases their concentrations in the body and amplifies their actions.

Large neutral amino acids: dietary effects on brain neurochemistry and function.

The ingestion of large neutral amino acids (LNAA), notably tryptophan, tyrosine and the branched-chain amino acids (BCAA), modifies tryptophan and tyrosine uptake into brain and their conversion to serotonin and catecholamines, respectively. The particular effect reflects the competitive nature of the transporter for LNAA at the blood-brain barrier. For example, raising blood tryptophan or tyrosine levels raises their uptake into brain, while raising blood BCAA levels lowers tryptophan and tyrosine uptake; serotonin and catecholamine synthesis in brain parallel the tryptophan and tyrosine changes. By changing blood LNAA levels, the ingestion of particular proteins causes surprisingly large variations in brain tryptophan uptake and serotonin synthesis, with minimal effects on tyrosine uptake and catecholamine synthesis. Such variations elicit predictable effects on mood, cognition and hormone secretion (prolactin, cortisol). The ingestion of mixtures of LNAA, particularly BCAA, lowers brain tryptophan uptake and serotonin synthesis. Though argued to improve physical performance by reducing serotonin function, such effects are generally considered modest at best. However, BCAA ingestion also lowers tyrosine uptake, and dopamine synthesis in brain. Increasing dopamine function in brain improves performance, suggesting that BCAA may fail to increase performance because dopamine is reduced. Conceivably, BCAA administered with tyrosine could prevent the decline in dopamine, while still eliciting a drop in serotonin. Such an LNAA mixture might thus prove an effective enhancer of physical performance. The thoughtful development and application of dietary proteins and LNAA mixtures may thus produce treatments with predictable and useful functional effects.

Oral branched-chain amino acid supplements that reduce brain serotonin during exercise in rats also lower brain catecholamines.

Exercise raises brain serotonin release and is postulated to cause fatigue in athletes; ingestion of branched-chain amino acids (BCAA), by competitively inhibiting tryptophan transport into brain, lowers brain tryptophan uptake and serotonin synthesis and release in rats, and reputedly in humans prevents exercise-induced increases in serotonin and fatigue. This latter effect in humans is disputed. But BCAA also competitively inhibit tyrosine uptake into brain, and thus catecholamine synthesis and release. Since increasing brain catecholamines enhances physical performance, BCAA ingestion could lower catecholamines, reduce performance and thus negate any serotonin-linked benefit. We therefore examined in rats whether BCAA would reduce both brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Sedentary and exercising rats received BCAA or vehicle orally; tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis rates were measured 1 h later in brain. BCAA reduced brain tryptophan and tyrosine concentrations, and serotonin and catecholamine synthesis. These reductions in tyrosine concentrations and catecholamine synthesis, but not tryptophan or serotonin synthesis, could be prevented by co-administering tyrosine with BCAA. Complete essential amino acid mixtures, used to maintain or build muscle mass, were also studied, and produced different effects on brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Since pharmacologically increasing brain catecholamine function improves physical performance, the finding that BCAA reduce catecholamine synthesis may explain why this treatment does not enhance physical performance in humans, despite reducing serotonin synthesis. If so, adding tyrosine to BCAA supplements might allow a positive action on performance to emerge.

Effects and side effects associated with the non-nutritional use of tryptophan by humans.

The daily nutritional requirement for L-tryptophan (Trp) is modest (5 mg/kg). However, many adults choose to consume much more, up to 4-5 g/d (60-70 mg/kg), typically to improve mood or sleep. Ingesting L-Trp raises brain tryptophan levels and stimulates its conversion to serotonin in neurons, which is thought to mediate its actions. Are there side effects from Trp supplementation? Some consider drowsiness a side effect, but not those who use it to improve sleep. Though the literature is thin, occasional side effects, seen mainly at higher doses (70-200 mg/kg), include tremor, nausea, and dizziness, and may occur when Trp is taken alone or with a drug that enhances serotonin function (e.g., antidepressants). In rare cases, the "serotonin syndrome" occurs, the result of too much serotonin stimulation when Trp is combined with serotonin drugs. Symptoms include delirium, myoclonus, hyperthermia, and coma. In 1989 a new syndrome appeared, dubbed eosinophilia myalgia syndrome (EMS), and was quickly linked to supplemental Trp use. Key symptoms included debilitating myalgia (muscle pain) and a high peripheral eosinophil count. The cause was shown not to be Trp but a contaminant in certain production batches. This is not surprising, because side effects long associated with Trp use were not those associated with the EMS. Over 5 decades, Trp has been taken as a supplement and as an adjunct to medications with occasional modest, short-lived side effects. Still, the database is small and largely anecdotal. A thorough, dose-related assessment of side effects remains to be conducted.

Mechanisms for sweetness.

A remarkable amount of information has emerged in the past decade regarding sweet taste physiology. This article reviews these data, with a particular focus on the elucidation of the sweet taste receptor, its location and actions in taste transduction in the mouth, its nontaste functions in the gastrointestinal tract (e.g., in enteroendocrine cells), and the brain circuitry involved in the sensory processing of sweet taste. Complications in the use of rodents to model human sweet taste perception and responses are also considered. In addition, information relating to low-calorie sweeteners (LCS) is discussed in the context of these issues. Particular consideration is given to the known effects of LCS on enteroendocrine cell function.

Imaged based estimation of food volume using circular referents in dietary assessment.

Measuring food volume (portion size) is a critical component in both clinical and research dietary studies. With the wide availability of cell phones and other camera-ready mobile devices, food pictures can be taken, stored or transmitted easily to form an image based dietary record. Although this record enables a more accurate dietary recall, a digital image of food usually cannot be used to estimate portion size directly due to the lack of information about the scale and orientation of the food within the image. The objective of this study is to investigate two novel approaches to provide the missing information, enabling food volume estimation from a single image. Both approaches are based on an elliptical reference pattern, such as the image of a circular pattern (e.g., circular plate) or a projected elliptical spotlight. Using this reference pattern and image processing techniques, the location and orientation of food objects and their volumes are calculated. Experiments were performed to validate our methods using a variety of objects, including regularly shaped objects and food samples.

The chronic ingestion of diets containing different proteins produces marked variations in brain tryptophan levels and serotonin synthesis in the rat.

Serotonin (5HT) synthesis in brain is influenced by precursor (tryptophan (TRP)) concentrations, which are modified by food ingestion. Hence, in rats, a carbohydrate meal raises brain TRP and 5HT; a protein-containing meal does not, but little attention has focused on differences among dietary proteins. Recently, single meals containing different proteins have been shown to produce marked changes in TRP and 5HT. The present studies evaluate if such differences persist when rats ingest such diets chronically. Male rats were studied that ingested diets for 9 days containing zein, wheat gluten, soy protein, casein, or α-lactalbumin (17% dry weight). Brain TRP varied up to eightfold, and 5HT synthesis fivefold among the different protein groups. TYR and LEU concentrations, and catecholamine synthesis rate in brain varied much less. The effects of dietary protein on brain TRP and 5HT previously noted after single meals thus continue undiminished when such diets are consumed chronically.

Effect of chronic protein ingestion on tyrosine and tryptophan levels and catecholamine and serotonin synthesis in rat brain.

OBJECTIVES: Previous studies have shown that brain tyrosine (TYR) levels and catecholamine synthesis rate increase in rats as chronic dietary protein content increases from 2 to 10% (% weight). A single protein, casein, was examined. The present study explores how TYR levels and catecholamine synthesis (and tryptophan (TRP) levels and serotonin synthesis) change when different proteins are ingested chronically over the same range of dietary protein contents. METHODS: Male rats ingested for 8 days diets contain 2 or 10% protein (zein, gluten, casein, soy protein, or alpha-lactalbumin). On the last day, they were killed 2.5 hours into the dark period, 30 minutes after receiving an injection of m-hydroxybenzylhydrazine, an inhibitor of aromatic l-amino acid decarboxylase. Brain samples were analyzed for amino acids, including 5-hydroxytryptophan (index of serotonin synthesis rate) and dihydroxyphenylalanine (index of catecholamine synthesis rate), by HPLC-electrochemical detection. RESULTS: TYR levels and catecholamine synthesis rate in brain were unaffected by the particular protein ingested. However, TRP levels and serotonin synthesis rate varied markedly, depending on the protein ingested, with effects being most prominent in the 10% protein groups. The effect of dietary protein on brain TRP correlated very highly with its effect on serotonin synthesis. DISCUSSION: The results indicate that the protein ingested can chronically modify TRP levels and serotonin synthesis in brain, but not TYR levels or catecholamine synthesis, with effects most distinct at an adequate level of protein intake (10%).

Physical Activity Recognition Based on Motion in Images Acquired by a Wearable Camera.

A new technique to extract and evaluate physical activity patterns from image sequences captured by a wearable camera is presented in this paper. Unlike standard activity recognition schemes, the video data captured by our device do not include the wearer him/herself. The physical activity of the wearer, such as walking or exercising, is analyzed indirectly through the camera motion extracted from the acquired video frames. Two key tasks, pixel correspondence identification and motion feature extraction, are studied to recognize activity patterns. We utilize a multiscale approach to identify pixel correspondences. When compared with the existing methods such as the Good Features detector and the Speed-up Robust Feature (SURF) detector, our technique is more accurate and computationally efficient. Once the pixel correspondences are determined which define representative motion vectors, we build a set of activity pattern features based on motion statistics in each frame. Finally, the physical activity of the person wearing a camera is determined according to the global motion distribution in the video. Our algorithms are tested using different machine learning techniques such as the K-Nearest Neighbor (KNN), Naive Bayesian and Support Vector Machine (SVM). The results show that many types of physical activities can be recognized from field acquired real-world video. Our results also indicate that, with a design of specific motion features in the input vectors, different classifiers can be used successfully with similar performances.

Perspective: Measuring Sweetness in Foods, Beverages, and Diets: Toward Understanding the Role of Sweetness in Health.

Various global public health agencies recommend minimizing exposure to sweet-tasting foods or beverages. The underlying rationale is that reducing exposure to the perception of sweet tastes, without regard to the source of sweetness, may reduce preferences for sweetness, added sugar intake, caloric intake, and body weight. However, the veracity of this sequence of outcomes has yet to be documented, as revealed by findings from recent systematic reviews on the topic. Efforts to examine and document the effects of sweetness exposure are needed to support evidence-based recommendations. They require a generally agreed-upon methodology for measuring sweetness in foods, beverages, and the overall diet. Although well-established sensory evaluation techniques exist for individual foods in laboratory settings, they are expensive and time-consuming, and agreement on the optimal approach for measuring the sweetness of the total diet is lacking. If such a measure could be developed, it would permit researchers to combine data from different studies and populations and facilitate the design and conduct of new studies to address unresolved research questions about dietary sweetness. This narrative review includes an overview of available sensory techniques, their strengths and limitations, recent efforts to measure the sweetness of foods and diets across countries and cultures, and a proposed future direction for improving methods for measuring sweetness toward developing the data required to support evidence-based recommendations around dietary sweetness.

The development of tolerance to drugs that suppress food intake.

Appetite suppressants have been available as weight-reducing aids for over 50 years. The first discovered was amphetamine, which was potent, but possessed undesirable side effects (it is a stimulant and elevates blood pressure). Subsequently, a variety of appetite drugs was developed, all structurally related to amphetamine, but mostly lacking unwanted side effects. Until recently, fenfluramine (FEN) was the most widely used; presently, sibutramine is the most commonly used appetite suppressant. While these appetite suppressants are effective at reducing hunger and food intake when given as a single dose or for short periods of time, their effectiveness diminishes when administered chronically. The biological mechanisms underlying this tolerance have not been carefully studied, but many possibilities have been identified, including the down-regulation in brain of neurotransmitter receptors that might mediate the action of these drugs and adaptive responses of the appetite control circuitry in brain. To date, however, few studies have examined these possibilities in any detail. This article focuses on the question of why appetite suppressants lose efficacy, when given chronically, because this issue is important to the development of the next generation of appetite suppressants. Chronic efficacy should be an issue studied relatively early in the drug development process. This issue is of particular relevance, since obesity treatment is now recognized as a long-term, not a short-term, process. If appetite suppressants are to become a more important tool in obesity treatment, agents that do not lose efficacy when administered for extended periods of time must be identified.

Applications for α-lactalbumin in human nutrition.

α-Lactalbumin is a whey protein that constitutes approximately 22% of the proteins in human milk and approximately 3.5% of those in bovine milk. Within the mammary gland, α-lactalbumin plays a central role in milk production as part of the lactose synthase complex required for lactose formation, which drives milk volume. It is an important source of bioactive peptides and essential amino acids, including tryptophan, lysine, branched-chain amino acids, and sulfur-containing amino acids, all of which are crucial for infant nutrition. α-Lactalbumin contributes to infant development, and the commercial availability of α-lactalbumin allows infant formulas to be reformulated to have a reduced protein content. Likewise, because of its physical characteristics, which include water solubility and heat stability, α-lactalbumin has the potential to be added to food products as a supplemental protein. It also has potential as a nutritional supplement to support neurological function and sleep in adults, owing to its unique tryptophan content. Other components of α-lactalbumin that may have usefulness in nutritional supplements include the branched-chain amino acid leucine, which promotes protein accretion in skeletal muscle, and bioactive peptides, which possess prebiotic and antibacterial properties. This review describes the characteristics of α-lactalbumin and examines the potential applications of α-lactalbumin for human health.

Effect of chronic infusion of olanzapine and clozapine on food intake and body weight gain in male and female rats.

Many antipsychotics cause weight gain in humans, but usually not in rats, when injected once or twice daily. Since blood antipsychotic half-lives are short in rats, compared to humans, chronic administration by constant infusion may be necessary to see consistent weight gain in rats. Male and female rats were implanted with mini-pumps for constant infusion of olanzapine (5 mg/kg/day), clozapine (10 mg/kg/day) or vehicle for 11 days. Food intake and body weight were measured; blood drug levels were measured by HPLC. Olanzapine increased food intake and body weight in female, but not male rats. Serum olanzapine concentrations were 30-35 ng/ml. Clozapine had no effect on food intake or body weight in female or male rats. Serum clozapine concentrations were about 75 ng/ml. Single-dose pharmacokinetic analysis revealed a serum terminal half-life of 1.2-1.5 h for each drug, with no sex differences. Despite the fact that olanzapine and clozapine promote weight gain in humans, these drugs appear to have minimal effects on body weight and food intake in rats, except for a modest effect of olanzapine in female rats, even though therapeutic levels of olanzapine are achieved in serum during chronic infusion. Hence, the rapid clearance of drug following single administration in previous studies cannot explain the weak or absent effects of antipsychotics on weight gain in this species. The rat thus appears to be an inadequate model of weight gain produced by some antipsychotics in humans.

Long-term changes in blood pressure in extremely obese patients who have undergone bariatric surgery.

HYPOTHESIS: Systolic and diastolic pressure and the incidence of hypertension in very obese patients decline after bariatric surgery and do not rebound. DESIGN: Chart review. SETTING: Surgical practice in a university medical center. PATIENTS: Women and men, 18 years or older, with a body mass index (BMI) (calculated as weight in kilograms divided by the square of height in meters) of 40 or greater, having no previous surgical intervention for extreme obesity. INTERVENTION: Vertical-banded gastroplasty or Roux-en-Y gastric bypass. MAIN OUTCOME MEASURES: Systolic and diastolic blood pressure, BMI, and antihypertensive medications. RESULTS: Patients underwent Roux-en-Y gastric bypass (n = 285; mean initial BMI, 55.7) or vertical banded gastroplasty (n = 62; mean initial BMI, 48.5); half of each group was hypertensive at evaluation. The BMI dropped in both groups after surgery and stabilized at about 35 within 18 months. Systolic pressure changes were generally modest, although diastolic pressure declined significantly after surgery. In patients with untreated stage 1 hypertension, marked reductions in systolic and diastolic pressures occurred after surgery. Many patients taking antihypertensive medications before surgery discontinued them after surgery and remained normotensive. CONCLUSIONS: Blood pressure reductions that occur after bariatric surgery and substantial weight loss depend on the blood pressure status of patients before surgery: normotensive patients and hypertensive patients taking antihypertensive medications show small postsurgical pressure reductions, while patients with elevated blood pressure before surgery show notable postsurgical pressure drops. The overall incidence of hypertension after bariatric surgery declines substantially and remains low.

Effects of chronic fenfluramine administration on hypothalamic neuropeptide mRNA expression.

Appetite suppressants lose efficacy when given chronically; the mechanisms are unknown. We gave male rats once-daily dl-fenfluramine (dl-FEN, 5 mg/kg, i.p.) injections for 15 days and measured mRNA expression of corticotropin releasing factor (CRF), neuropeptide Y (NPY) and proopiomelanocortin (POMC) in hypothalamic neurons on days 1, 2 and 15. dl-FEN decreased food intake on days 1-2 but not on day 15. The drug increased CRF mRNA and decreased NPY mRNA on days 1-2; on day 15, NPY mRNA was normal, but CRF mRNA remained elevated. No changes occurred in POMC mRNA. Thus, only the NPY mRNA response to dl-FEN correlated with changes in food intake over time in a manner consistent with the known effects of NPY on food intake.