BACKGROUND: Weight loss is associated with a reduction in all body compartments, including muscle mass (MM), and this effect produces a decrease in function and muscle strength. Our objective was to assess the impact of protein or amino acid supplements on MM loss in middle-aged men (age < 65 years) with severe obesity (BMI > 35 kg/m2) during weight loss.
METHODS: We conducted a single-site randomized controlled trial (Clinicaltrials.gov NCT05143398) with 40 in-patient male subjects with severe obesity. Participants underwent an intervention program consisting of a low-calorie balanced diet and structured physical activity. They were randomly assigned to 4-week treatment groups: (1) control (CTR, N = 10), (2) protein (P, N = 10), (3) branched-chain amino acid (BCAA, N = 10), and (4) essential amino acid mixture with tricarboxylic acid cycle intermediates (PD-E07, N = 10) supplementation.
RESULTS: Following 4 weeks of intervention, all groups showed similar reductions in body weight compared to baseline. When examining the delta values, a notable increase in muscle mass (MM) was observed in the PD-E07 intervention group [MM (kg): 2.84 ± 3.57; MM (%): 3.63 ± 3.14], in contrast to the CTR group [MM (kg): -2.46 ± 3.04; MM (%): -0.47 ± 2.28], with a statistical significance of p = 0.045 and p = 0.023, respectively. However, the MM values for the P group [MM (kg): -2.75 ± 5.98, p = 0.734; MM (%): -0.44 ± 4.02, p = 0.990] and the BCAA group [MM (kg): -1 ± 3.3, p = 0.734; MM (%): 0.34 ± 2.85, p = 0.956] did not exhibit a statistically significant difference when compared to the CTR group.
CONCLUSIONS: Amino acid-based supplements may effectively mitigate the loss of MM typically observed during weight reduction. Further validation through large-scale studies is necessary.

Dietary protein intake is vital to life. Here we sought to characterize dietary sources of protein in eight Latin American countries. Survey data were collected for Estudio Latinoamericano de Nutrición y Salud (ELANS); participants were from Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, Peru, and Venezuela (n = 9218, 15-65 years old). The primary aim of this analysis was to quantify per-person daily protein consumption by country and sociodemographic factors. Secondary aims: to quantify proportional intake of proteins by source, amount and processing, and to determine the adequacy of protein/essential amino acid intake. Younger groups (adolescents 15-19 years, adults 20-33 years) had the highest intake of proteins; middle-aged adults (34-49 years) had a lower intake, and older adults (50-65 years) had a strikingly lower intake. Protein consumption was higher in men than women. Animal proteins comprised nearly 70% of total daily protein intake in Argentina and Venezuela, contrasting with <60% in Peru, Chile, and Costa Rica. Brazil and Venezuela showed the highest protein intake within the highest education level. The higher the socioeconomic level, the higher the protein intake, except for Argentina, Chile, and Peru. Proportional intake of animal- and plant-based protein generally reflected the food availability by country. This study presents a pre-pandemic regional baseline and offers a perspective for future studies of changes related to government policies, climate, and dietary practices.

The increasing number of dementia patients has become a global social problem. Amino acids are known to be used as precursors of neurotransmitters in the brain. Amino acid mixtures as a supplement may be used as a solution to Alzheimer\'s symptoms. This exploratory study evaluated the efficacy and safety of a mixture containing nine essential amino acids on behavioral and psychological symptoms of dementia (BPSD) and cognitive function in patients with Alzheimer\'s disease (AD).
We conducted a double-blind, randomized, placebo-controlled trial to evaluate the intervention effects of nine essential amino acid mixture for 28 days. A total of 36 patients with AD were enrolled in Japan. BPSD and cognitive function were evaluated by the Neuropsychiatric Inventory-12 item (NPI-12; the primary endpoint), Mini-Mental State Examination (MMSE), Trail Making Test A (TMT-A), Trail Making Test B (TMT-B), Frontal Assessment Battery (FAB), and Clinical Dementia Rating Scale (CDR).
Compared with placebo, the amino acid mixture did not improve NPI-12, MMSE, TMT-A and B or CDR scores. However, the analysis of covariance revealed improved FAB scores in the amino acid mixture group as a secondary endpoint. There were four subjects with adverse events in each group.
Our results did not show a beneficial effect of the mixture containing nine essential amino acids on BPSD as a primary endpoint; however, it may improve executive function in patients with AD.

Tea catechins (TCCs) have gained significant attention owing to their health effects. However, evidence is limited regarding the benefit of TCC and essential amino acids (EAAs) ingestion plus that of TCC ingestion after resistance exercise (RE) among older individuals with sarcopenia. We aimed to evaluate whether a 24-week nutritional program involving EAA and TCC supplementation after RE improved skeletal muscle mass (SMM) among older adults with sarcopenia.
We conducted an open-label, pilot, randomized controlled trial among older adults with sarcopenia at the Harima Care Center or community in Hyogo, Japan. Participants were allocated to RE (n = 18), RE with EAA supplementation (RE + EAA, n = 18), or RE with EAA and TCC supplementation (RE + EAA + TCC, n = 18) groups. Sarcopenia was defined using the Asian Working Group for Sarcopenia 2019 criteria. A 24-week resistance exercise program was carried out twice weekly, with an intake of 3,000 mg and 540 mg of EAA and TCC supplements, respectively. SMM was the primary outcome parameter.
The mean adherence rate to exercise and supplementation intake over the 24-week intervention period was 86.8% in the RE + EAA + TCC group, 86.4% in the RE + EAA group, and 85.4% in the RE group. A significant group-by-time interaction was identified for SMM (p = 0.010). The pre- to post-intervention increase in SMM was significantly higher in the RE + EAA + TCC group than in the RE group (p = 0.010).
These results suggest that supplementation with EAA and TCC after RE, compared to RE only, improves SMM in older people with sarcopenia. To the best of our knowledge, our study is the first pilot randomized controlled trial to evaluate the effect of TCC supplementation on SMM in older people with sarcopenia.
Supplemental data for this article is available online at http://dx.doi.org/10.1080/07315724.2022.2025546.

The Dietary Guidelines for Americans (DGAs) published an \"ounce equivalents\" recommendation to help consumers meet protein requirements with a variety of protein food sources. However, the metabolic equivalency of these varied protein food sources has not been established.
We have investigated the hypothesis that the anabolic responses to consumption of ounce equivalents of protein food sources would be directly related to the essential amino acid (EAA) content of the protein food source.
Following 3 d of dietary control, a total of 56 healthy young adults underwent an 8.5-h metabolic study using stable isotope tracer methodology. The changes from baseline following consumption of 1 of 7 different protein food sources were compared with the baseline value for that individual (n = 8 per group).
Consumption of ounce equivalents of animal-based protein food sources (beef sirloin, pork loin, eggs) resulted in a greater gain in whole-body net protein balance above baseline than the ounce equivalents of plant-based protein food sources (tofu, kidney beans, peanut butter, mixed nuts; P < 0.01). The improvement in whole-body net protein balance was due to an increase in protein synthesis (P < 0.05) with all the animal protein sources, whereas the egg and pork groups also suppressed protein breakdown compared with the plant protein sources (P < 0.01). The magnitude of the whole-body net balance (anabolic) response was correlated with the EAA content of the protein food source (P < 0.001).
The \"ounce equivalents\" of protein food sources as expressed in the DGAs are not metabolically equivalent in young healthy individuals. The magnitude of anabolic response to dietary proteins should be considered as the DGAs develop approaches to establish healthy eating patterns.

Elevated circulating branched-chain amino acids (BCAAs; isoleucine, leucine, and valine) are associated with obesity and type 2 diabetes (T2D). Reducing circulatory BCAAs by dietary restriction was suggested to mitigate these risks in rodent models, but this is a challenging paradigm to deliver in humans. We aimed to design and assess the feasibility of a diet aimed at reducing circulating BCAA concentrations in humans, while maintaining energy balance and overall energy/protein intake. Twelve healthy individuals were assigned to either a 7-day BCAA-restricted diet or a 7-day control diet. Diets were iso-nitrogenous and iso-caloric, with only BCAA levels differing between the two. The BCAA-restricted diet significantly reduced circulating BCAA concentrations by ~50% i.e., baseline 437 ± 60 to 217 ± 40 µmol/L (p < 0.005). Individually, both valine (245 ± 33 to 105 ± 23 µmol/L; p < 0.0001), and leucine (130 ± 20 to 75 ± 13 µmol/L; p < 0.05), decreased significantly in response to the BCAA-restricted diet. The BCAA-restricted diet marginally lowered Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) levels: baseline 1.5 ± 0.2 to 1.0 ± 0.1; (p = 0.096). We successfully lowered circulating BCAAs by 50% while maintaining iso-nitrogenous, iso-caloric dietary intakes, and while meeting the recommended daily allowances (RDA) for protein requirements. The present pilot study represents a novel dietary means by which to reduce BCAA, and as such, provides a blueprint for a potential dietary therapeutic in obesity/diabetes.

Background: To delay the onset of dementia, it is important for healthy adults to take preventive actions before the cognitive function clearly declines. Protein malnutrition is a potential risk factor for senile dementia, although the precise link between protein/amino acid nutrition and cognitive function is unknown. The purpose of this study was to examine the effect of the ingestion of seven selected essential amino acids as a granular powder, namely, leucine, phenylalanine, and lysine supplemented with isoleucine, histidine, valine, and tryptophan on cognitive and psychosocial functions in healthy adults. Methods: A double-blind, randomized, placebo-controlled trial was conducted. A total of 105 participants aged 55 years or older were randomly assigned to one of three groups: daily ingestion of 3 g (3gIG) or 6 g (6gIG) of the selected amino acids or daily ingestion of a placebo (PCG). Each group ingested the test powder for 12 weeks. As the main outcome, cognitive function was assessed before and after ingestion by a cognitive test battery. Psychosocial functions were also examined. Results: The numbers of participants excluding dropouts were 35 in PCG and 3gIG and 33 in 6gIG. Analysis of covariance revealed that the 6gIG showed significantly improved cognitive function (Trail Making Test B), social interaction and psychological health scores after ingestion compared to the PCG (multiplicity adjusted p < 0.05). Conclusions: Current findings suggested that ingestion of the seven essential amino acids led to improved attention and cognitive flexibility and psychosocial functioning, which is expected to prevent cognitive decline. Clinical Trial Registration: University Hospital Medical Information Network Clinical Trial Registry (URL: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000037779, Identifier: UMIN000033174).

Background: Intolerances to bovine dairy are a motivating factor in consumers seeking alternate-or replacement-dairy beverages and foods. Sheep milk (SM) is an alternate dairy source, with greater protein, although similar amino acid composition compared to cow milk (CM). Studies are yet to address the appearance of circulating amino acids following consumption of SM, relative to CM, in humans. Objective: To clinically determine the appearance of branched chain amino acids, and other amino acids, in circulation in response to equal servings of SM and CM, in females who avoid dairy products. Design: In a double-blinded, randomized, cross-over trial, 30 self-described dairy avoiding females (20-40 years) drank 650 mL of SM or CM that were reconstituted from the spray dried powders (30 and 25 g in 180 mL water, respectively) on separate occasions, following an overnight fast. After reconstitution, the energy and protein provided by SM was higher than for CM (2,140 vs. 1,649 kJ; 29.9 vs. 19.4 g protein); content of branched chain amino acids (BCAAs) were 10.5 and 6.5 mg·mL-1, respectively. Blood samples were collected at fasting and at regular intervals over 5 h after milk consumption. Plasma amino acids were measured by HPLC. Results: 80% of subjects self-identified as lactose intolerant, and the majority (47%) \"avoided drinking milk\" \"most of the time\". SM resulted in greater plasma appearance of BCAAs at 60 min (641.1 ± 16.3 vs. 563.5 ± 14.4 μmol·L-1; p < 0.001) compared with CM. SM similarly resulted in elevated postprandial concentrations of the amino acids lysine, methionine, and proline, particularly at 240 min (time × milk interactions p = 0.011, 0.017, and p = 0.002, respectively). Postprandial increases in plasma alanine concentrations were sustained to 120 min after CM (time × milk interaction p = 0.001) but not after SM, despite greater quantities provided by SM. Conclusions: SM is a rich source of protein, and relative to CM, provides a greater quantity of BCAAs, with a corresponding elevation of the postprandial circulating BCAA response. SM is therefore a possible dairy alternative of benefit to those who need to increase total protein intake or for individuals with heightened protein requirements. Unique Identifier and Registry: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375324, identifier U1111-1209-7768.

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 (n = 8). Primed continuous infusions of L-[2H5] phenylalanine and L-[2H2]tyrosine were performed to determine whole-body protein kinetics and muscle protein fractional synthesis rate (MPS) in basal fasted and fed states. Whole-body protein kinetics (NB, net protein balance; PS, protein synthesis; PB, protein breakdown) and MPS was expressed as changes from the baseline post-absorptive state. Consistent with our previous findings in young adults, both feedings resulted in a positive NB, with HIGH being more positive than MOD. Furthermore, NB (expressed as g protein∙240 min) increased linearly with an increasing amount of protein intake, expressed relative to lean body mass. The positive NB was achieved due mainly to the suppression of PB in both MOD and to a greater extent HIGH, while PS was only increased in HIGH. Consistent with the whole-body data, MPS was significantly higher in HIGH than MOD. Plasma concentrations of essential amino acids and insulin were greater in HIGH vs. MOD. We conclude that in the context of mixed meals, whole-body anabolic response linearly increases with increasing protein intake primarily through the suppression of PB, and MPS was further stimulated with protein intake above the previously considered \"optimal\" protein dose in older adults.

Consuming 0.10-0.14 g essential amino acids (EAA)/kg/dose (0.25-0.30 g protein/kg/dose) maximally stimulates muscle protein synthesis (MPS) during energy balance. Whether consuming EAA beyond that amount enhances MPS and whole-body anabolism following energy deficit is unknown. The aims of this study were to determine the effects of standard and high EAA ingestion on mixed MPS and whole-body protein turnover following energy deficit.
Nineteen males (mean ± SD; 23 ± 5 y; 25.4 ± 2.7 kg/m2) completed a randomized, double-blind crossover study consisting of two, 5-d energy deficits (-30 ± 4% of total energy requirements), separated by 14-d. Following each energy deficit, mixed MPS and whole-body protein synthesis (PS), breakdown (PB), and net balance (NET) were determined at rest and post-resistance exercise (RE) using primed, constant L-[2H5]-phenylalanine and L-[2H2]-tyrosine infusions. Beverages providing standard (0.1 g/kg, 7.87 ± 0.87 g) or high (0.3 g/kg, 23.5 ± 2.54 g) EAA were consumed post-RE. Circulating EAA were measured.
Postabsorptive mixed MPS (%/h) at rest was not different (P = 0.67) between treatments. Independent of EAA, postprandial mixed MPS at rest (standard EAA, 0.055 ± 0.01; high EAA, 0.061 ± 0.02) and post-RE (standard EAA, 0.055 ± 0.01; high EAA, 0.065 ± 0.02) were greater than postabsorptive mixed MPS at rest (P = 0.02 and P = 0.01, respectively). Change in (Δ postabsorptive) whole-body (g/180 min) PS and PB was greater for high than standard EAA [mean treatment difference (95% CI), 3.4 (2.3, 4.4); P = 0.001 and -15.6 (-17.8, -13.5); P = 0.001, respectively]. NET was more positive for high than standard EAA [19.0 (17.3, 20.7); P = 0.001]. EAA concentrations were greater in high than standard EAA (P = 0.001).
These data demonstrate that high compared to standard EAA ingestion enhances whole-body protein status during underfeeding. However, the effects of consuming high and standard EAA on mixed MPS are the same during energy deficit.
NCT03372928, https://clinicaltrials.gov.