Body Protein Breakdown Research Articles

Effects of improved amino acid balance diet on lysine mammary utilization, whole body protein turnover and muscle protein breakdown on lactating sows

BackgroundThe study objective was to test the hypothesis that low crude protein (CP) diet with crystalline amino acids (CAA) supplementation improves Lys utilization efficiency for milk production and reduces protein turnover and muscle protein breakdown. Eighteen lactating multiparous Yorkshire sows were allotted to 1 of 2 isocaloric diets (10.80 MJ/kg net energy): control (CON; 19.24% CP) and reduced CP with “optimal” AA profile (OPT; 14.00% CP). Sow body weight and backfat were recorded on d 1 and 21 of lactation and piglets were weighed on d 1, 14, 18, and 21 of lactation. Between d 14 and 18, a subset of 9 sows (CON = 4, OPT = 5) was infused with a mixed solution of 3-[methyl-2H3]histidine (bolus injection) and [13C]bicarbonate (priming dose) first, then a constant 2-h [13C]bicarbonate infusion followed by a 6-h primed constant [1-13C]lysine infusion. Serial blood and milk sampling were performed to determine plasma and milk Lys enrichment, Lys oxidation rate, whole body protein turnover, and muscle protein breakdown.ResultsOver the 21-d lactation period, compared to CON, sows fed OPT had greater litter growth rate (P < 0.05). Compared to CON, sows fed OPT had greater efficiency of Lys (P < 0.05), Lys mammary flux (P < 0.01) and whole-body protein turnover efficiency (P < 0.05). Compared to CON, sows fed OPT tended to have lower whole body protein breakdown rate (P = 0.069). Muscle protein breakdown rate did not differ between OPT and CON (P = 0.197).ConclusionFeeding an improved AA balance diet increased efficiency of Lys and reduced whole-body protein turnover and protein breakdown. These results imply that the lower maternal N retention observed in lactating sows fed improved AA balance diets in previous studies may be a result of greater partitioning of AA towards milk rather than greater body protein breakdown.

Sex related differences in muscle health and metabolism in chronic obstructive pulmonary disease

Sex differences in muscle function and mass, dyspnea, and clinical outcomes have been observed in patients with Chronic Obstructive Pulmonary Disease (COPD) despite a similar level of airflow obstruction. Protein and amino acid metabolism is altered in COPD, however, it remains unclear whether a difference in metabolic signature exists between males and females with COPD that may explain the observed differences in muscle health and clinical outcomes. In 234 moderate to severe COPD patients (males/females: 113/121) and 182 healthy controls (males/females: 77/105), we assessed, besides presence of comorbidities and clinical features, muscle function by handgrip and leg dynamometry, and body composition by dual-energy x-ray absorptiometry. In the postabsorptive state, a mixture of 18 stable isotopes of amino acids was administered by pulse and arterialized blood was sampled for 2h. Amino acid concentrations and enrichments were analyzed by LC-MS/MS to calculate whole body (net) protein breakdown (WBnetPB) and whole body production (WBP) rates (μmol/hour) of the amino acids playing a known role in muscle health. Statistics was done by ANCOVA to examine the effects of sex, COPD, and sex-by-COPD interaction with as covariates age and lean mass. Significance was set as p<0.05. Lung function was comparable between males and females with COPD. Being a female and presence of COPD were independently associated with lower appendicular lean mass, muscle strength, and WBnetPB (p<0.05). Being a male was associated with higher visceral adipose tissue, C-reactive protein (CRP) (p<0.05), and higher prevalence of heart failure and obstructive sleep apnea. Sex-by-COPD interactions were found indicating lower fat mass (p=0.0005) and WBPs of phenylalanine (measure of whole body protein turnover) and essential amino acids (p<0.05), particularly in COPD females. Higher visceral adipose tissue (p=0.025), CRP (p<0.0001), and WBP of tau-methylhistidine (p=0.010) (reflecting enhanced myofibrillar protein breakdown) were observed in COPD males. Presence of sex specific changes in protein and amino acid metabolism and cardiometabolic health in COPD need to be considered when designing treatment regimens to restore muscle health in males and females with COPD. www. gov, NCT01787682, NCT01624792, NCT02157844, NCT02065141, NCT02770092, NCT02780219, NCT03327181, NCT03796455, NCT01173354, NCT01154400.

Females have a different metabolic response to critical illness, measured by comprehensive amino acid flux analysis

BackgroundThe trajectory from healthy to critical illness is influenced by numerous factors, including metabolism, which differs substantially between males and females. Whole body protein breakdown is substantially increased in critically ill patients, but it remains unclear whether there are sex differences that could explain the different health outcomes. Hence, we performed a secondary analysis of a study, where we used a novel pulse isotope method in critically ill and matched healthy males and females. MethodsIn 51 critically ill ICU patients (26 males, 15 females) and 49 healthy controls (36 males and 27 females), we assessed their general and disease characteristics and collected arterial(ized) blood in the postabsorptive state after pulse administration of 8 ml of a solution containing 18 stable AA tracers. In contrast to the original study, we now fitted the decay curves and calculated non-compartmental whole body amino acid production (WBP) and compartmental measurements of metabolism, including intracellular amino acid production. We measured amino acid enrichments and concentrations by LC-MS/MS and derived statistics using AN(C)OVA. ResultsCritically ill males and females showed an increase in the WBP of many amino acids, including those related to protein breakdown, but females showed greater elevations, or in the event of a reduction, attenuated reductions. Protein breakdown-independent WBP differences remained between males and females, notably increased glutamine and glutamate WBP. Only severely ill females showed a lower increase in WBP of many amino acids in comparison to moderately ill females, suggesting a suppressed metabolism. Compartmental analysis supported the observations. ConclusionsThe present study shows that females have a different response to critical illness in the production of several amino acids and changes in protein breakdown, observations made possible using our innovative stable tracer pulse approach. Clinical trial registryData are from the baseline measurements of study NCT02770092 (URL: https://clinicaltrials.gov/ct2/show/NCT02770092) and NCT03628365 (URL: https://clinicaltrials.gov/ct2/show/NCT03628365).

Randomized controlled phase I trial for a novel peripheral parenteral nutrition formula containing dextrose, amino acids, fat emulsion, electrolytes, and FDA2000 recommendation-based vitamins

We developed the world's first all-in-one type peripheral parenteral nutrition product containing dextrose, amino acids, fat emulsion, electrolytes and vitamins, according to the FDA 2000 recommendation. This phase I trial examined the safety and changes in nutritional parameters in healthy participants. A single-center, randomized, open-label, active-controlled trial was performed in single ascending dose (SAD: Step 1-3) and multiple dose (Step 4) studies. Participants were administered a single dose of OPF-105 (test solution: 150g of dextrose, 60g of amino acids, 40g of fat, 1240kcal of total energy per 2200mL, and 106 NPC/N ratio, with multivitamins, n=17) or BFI (control solution: 150g of dextrose, 60g of amino acids, 840kcal of total energy per 2000mL, and 64 NPC/N ratio, with vitamin B1, n=18) with three ascending doses (Step 1: 550mL, Step 2: 1100mL, and Step 3: 2200mL) in the SAD study, or received multiple doses with Step 3 amount of OPF-105 (n=5) or BFI (n=6) for 3 days (Step 4) via peripherally inserted venous catheters. The safety and nutritional parameters were assessed. There were no serious adverse events or events requiring discontinuation of the solution administration in either group. Blood urea nitrogen (BUN) levels remained within the normal range in both groups (Step 1-4). However, they gradually increased during the time course of the study in the BFI group but not in the OPF group (Step 4), suggesting the prevention of body protein breakdown. Blood triglyceride (TG) levels increased after administration in the OPF group but promptly returned to the pre-administration level (Step 1-4). Blood total ketone body levels increased the day after administration in both groups, which may imply a lower degree of starvation (Step 1-3), but the increase in the OPF group was milder than that in the BFI group (Step 4). Blood vitamin B6 and folic acid levels were maintained within the normal ranges in the OPF group but were near the lower limit in the BFI group (Step 1-4). Blood vitamin C levels showed almost lower limit in the two groups (Step 1-3), but increased only in the OPF group (Step 4). Blood vitamin K levels in the BFI group remained near the lower limit of the normal range, but those in the OPF group were higher than the upper limit at the end of administration and quickly returned to the pre-administration level (Step 1-4). This trial suggests that the newly developed formula (OPF-105) improves fat metabolism, maintains vitamin profiles, and may prevent body protein and fat breakdown and can be safely administered to healthy participants. Registration number of Clinical Trial: UMIN000046915; https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000053479.

A low postabsorptive whole body protein balance is associated with markers of poor daily physical functioning in Chronic Obstructive Pulmonary Disease

Postabsorptive whole body protein kinetics are related to age, gender, body mass index (BMI), and habitual protein intake level. It is unclear how protein synthesis, breakdown, and postabsorptive protein balance rates are affected in Chronic Obstructive Pulmonary Disease (COPD)) and whether these relate to disease severity, lifestyle characteristics and poor daily functioning. We studied 91 COPD (GOLD 1-4) and 56 age matched control subjects without COPD or other chronic or acute health disease/condition in the postabsorptive state and measured body composition by Dual-energy X-ray Absorptiometry, and disease severity and comorbidities by medical screening, blood analysis and questionnaires. We assessed whole body production rates of phenylalanine and tyrosine by pulse stable isotope tracer infusion to calculate whole body protein breakdown (PB) and hydroxylation of phenylalanine to tyrosine, representative of postabsorptive protein balance. We measured muscle and cognitive function, and physical performance by isokinetic dynamometry, cognitive assessments, and 6-min walk test. We assessed physical activity level, mood and dietary protein intake by questionnaires. We measured plasma enrichments by LC-MS/MS and statistics by Fisher's exact test or analysis of covariance. Data are mean [95% CI]. The COPD patients had moderate to severe airflow obstruction, multiple comorbidities, and elevated values for plasma high sensitivity c-reactive protein (hs-CRP) and glucose. Although PB (3630 [3361, 3900] vs 3504 [3297, 3711] umol/h, p=0.1649) was not different, postabsorptive protein balance was lower in COPD patients (274.2 [242.4, 306.1] vs 212.9 [194.7, 231.0] umol/h, p<0.0001), both compared to control subjects. A lower postabsorptive protein balance was associated with age (p<0.0001) and higher levels for systolic blood pressure (p=0.0051) and hs-CRP (p=0.0046) but not with lung function. Furthermore, a lower postabsorptive protein balance level was associated with a lower intake of total calories and protein (p<0.0001) and lower muscle strength (p=0.0248), while only in COPD with a lower physical performance (p=0.0343). We found no association with cognitive function or mood. For all subjects, a cumulative model that included group, gender, age, BMI, systolic blood pressure, hs-CRP, caloric intake, protein intake, and leg strength was able to explain 55% of the variation in postabsorptive protein balance. These data suggest that systemic inflammation, high blood pressure and low protein intake are risk factors of a lower postabsorptive protein balance in COPD patients. A lower postabsorptive protein balance is associated with markers of poor daily physical functioning.

β-hydroxy β-methylbutyric acid (hmb) supplementation reduced whole body protein breakdown in the early recovery phase of sepsis in the pig

Rationale: Optimal feeding in patients recovering from sepsis is critical to preserve muscle mass. β-Hydroxy β-methylbutyric acid (HMB) supplementation potentially attenuates whole body protein breakdown (WbPB) in healthy subjects, but it is unclear whether HMB reduces WbPB during the recovery phase of sepsis. Therefore, we studied WbPB and untargeted amino acid productions (WBP) during a HMB intervention in the early recovery phase of sepsis in the pig.

Serum creatinine is a poor marker of a predicted change in muscle mass in lactating sows.

Serum creatinine (SCr) in humans has proven to be a reliable biomarker of body protein breakdown and/or muscle mass change. This study set out to investigate the potential of SCr to indicate a loss in sow muscle mass over lactation, validated against 3methyl histidine (3MH) and blood urea nitrogen (BUN), markers of dietary and/or body protein breakdown. A total of 40sows were allocated to four treatment groups aimed to induce body weight changes by restrictively feeding sows using a stepwise percentage reduction model. Data were pooled and reallocated into three groups representing the 25th , 50th and 75th percentiles based on body weight change over lactation in the range -22.3 to -4.1% (treatment 25), -4.0 to 6.2% (Treatment 50), and 6.3-15.2% (Treatment 75). Indirect measures for the prediction of protein (3MH, BUN) or fat change (caliper, P2) were taken on entry into the farrowing house, day 5 of lactation, and at weaning. Serum was collected on these days, and SCr, 3MH and BUN were analysed. Piglet weaning weight and average daily feed intake did not differ between treatments (p > .05). There were no changes (p > .05) in indirect measures of body composition (sow caliper score, P2) and analytes (SCr, 3MH, BUN) over lactation. By day 20, those sows in treatment 25had higher (p < .05) 3MH concentrations whilst changes from day 5 to 20 were not different (p > .05) and did not correlate with SCr change (p > .05) but were highly correlated to BUN change (R2 = 0.691, p < .001). The data suggested that concentrations of SCr and BUN may have been the result of dietary and/or body protein breakdown and/or changes in muscle mass. In the current testing conditions, SCr was not a reliable marker of changes in muscle mass.

Anemic hypoxemia reduces myoblast proliferation and muscle growth in late-gestation fetal sheep.

Fetal skeletal muscle growth requires myoblast proliferation, differentiation, and fusion into myofibers in addition to protein accretion for fiber hypertrophy. Oxygen is an important regulator of this process. Therefore, we hypothesized that fetal anemic hypoxemia would inhibit skeletal muscle growth. Studies were performed in late-gestation fetal sheep that were bled to anemic and therefore hypoxemic conditions beginning at ∼125 days of gestation (term = 148 days) for 9 ± 0 days (n = 19) and compared with control fetuses (n = 16). A metabolic study was performed on gestational day ∼134 to measure fetal protein kinetic rates. Myoblast proliferation and myofiber area were determined in biceps femoris (BF), tibialis anterior (TA), and flexor digitorum superficialis (FDS) muscles. mRNA expression of muscle regulatory factors was determined in BF. Fetal arterial hematocrit and oxygen content were 28% and 52% lower, respectively, in anemic fetuses. Fetal weight and whole body protein synthesis, breakdown, and accretion rates were not different between groups. Hindlimb length, however, was 7% shorter in anemic fetuses. TA and FDS muscles weighed less, and FDS myofiber area was smaller in anemic fetuses compared with controls. The percentage of Pax7+ myoblasts that expressed Ki67 was lower in BF and tended to be lower in FDS from anemic fetuses indicating reduced myoblast proliferation. There was less MYOD and MYF6 mRNA expression in anemic versus control BF consistent with reduced myoblast differentiation. These results indicate that fetal anemic hypoxemia reduced muscle growth. We speculate that fetal muscle growth may be improved by strategies that increase oxygen availability.

Measuring Protein Turnover in the Field: Implications for Military Research

Protein turnover reflects the continual synthesis and breakdown of body proteins, and can be measured at a whole-body (i.e. aggregated across all body proteins) or tissue (e.g. skeletal muscle only) level using stable isotope methods. Evaluating protein turnover in free-living environments, such as military training, can help inform protein requirements. We undertook a narrative review of published literature with the aim of reviewing the suitability of, and advancements in, stable isotope methods for measuring protein turnover in field research. The 2 primary approaches for measuring protein turnover are based on precursor- and end-product methods. The precursor method is the gold-standard for measuring acute (over several hours) skeletal muscle protein turnover, whereas the end-product method measures chronic (over several weeks) skeletal muscle protein turnover and provides the opportunity to monitor free-living activities. Both methods require invasive procedures such as the infusion of amino acid tracers and muscle biopsies to assess the uptake of the tracer into tissue. However, the end-product method can also be used to measure acute (over 9-24 h) whole-body protein turnover noninvasively by ingesting 15N-glycine, or equivalent isotope tracers, and collecting urine samples. The end-product method using 15N-glycine is a practical method for measuring whole-body protein turnover in the field over short (24 h) time frames and has been used effectively in recent military field research. Application of this method may improve our understanding of protein kinetics during conditions of high physiological stress in free-living environments such as military training.

Branched-Chain Amino Acid Oxidation Is Elevated in Adults with Morbid Obesity and Decreases Significantly after Sleeve Gastrectomy

Plasma concentrations of branched-chain amino acids (BCAAs) are elevated in obese individuals with insulin resistance (IR) and decrease after bariatric surgery. However, the metabolic mechanisms are unclear. Our objectives are to compare leucine kinetics between morbidly obese and healthy-weight individuals cross-sectionally, and to prospectively evaluate changes in the morbidly obese after sleeve gastrectomy. We hypothesized that leucine oxidation is slower in obese individuals and increases after surgery. Ten morbidly obese [BMI (in kg/m2)≥32.5, age 21-50 y] and 10 healthy-weight participants (BMI <25), matched for age (median ∼30 y) but not gender, were infused with [U-13C6] leucine and [2H5] glycerol to quantify leucine and glycerol kinetics. Morbidly obese participants were studied again 6 mo postsurgery. Primary outcomes were kinetic parameters related to BCAA metabolism. Data were analyzed by nonparametric methods and presented as median (IQR). Participants with obesity had IR with an HOMA-IR (4.89; 4.36-8.76) greater than that of healthy-weight participants (1.32; 0.99-1.49; P <0.001) and had significantly faster leucine flux [218; 196-259 compared with 145; 138-149 μmol · kg fat-free mass (FFM)-1 · h-1], oxidation (24.0; 17.9-29.8 compared with 16.1; 14.3-18.5 μmol · kg FFM-1 · h-1), and nonoxidative disposal (204; 190-247 compared with 138; 129-140 μmol · kg FFM-1 · h-1) (P <0.017 for all). After surgery, the morbidly obese had a marked improvement in IR (3.54; 3.06-6.08; P=0.008) and significant reductions in BCAA concentrations (113; 95-157 μmol/L) and leucine oxidation (9.37; 6.85-15.2 μmol · kg FFM-1 · h-1) (P=0.017 for both). Further, leucine flux in this group correlated significantly with IR (r=0.78, P <0.001). BCAA oxidation is not impaired but elevated in individuals with morbid obesity. Plasma BCAA concentrations are lowered after surgery owing to slower breakdown of body proteins as insulin's ability to suppress proteolysis is restored. These findings suggest that IR is the underlying cause and not the consequence of elevated BCAAs in obesity.

Varying Postprandial, Postexercise Nutrient Timing: Effects On Substrate Oxidation And Protein Retention In Resistance-trained Men

Dietary protein and/or carbohydrate consumption augments postexercise recovery by facilitating the rebuilding of damaged contractile tissues and restoring energy reserves, particularly in a postabsorptive state. It is unclear how altering postexercise nutrient timing when in a postprandial state affects the shift towards fat utilization and changes in net protein retention after a resistance training bout. PURPOSE: To examine the effects of immediate versus delayed postexercise nutrient intake on substrate oxidation and protein retention during recovery. METHODS: In a single-blinded, crossover design, resistance trained (≥1 y) men (n=10, 22±2 y, 83±10 kg) consumed a mixed, eucaloric meal 2 hours before performing resistance exercise (3 sets of 6 whole body exercises, 2-3 minutes rest). Participants then consumed one of three postexercise beverages: immediate consumption of a whey protein concentrate (0.35 g/kg) and dextrose (1.0 g/kg) beverage (IMM), delayed consumption (2 h) of a whey and dextrose beverage (+2H), or placebo (flavoring with water) (PLA). Participants recovered (3 h) while expired carbon dioxide and oxygen were analyzed. Carbohydrate and fat oxidation was determined and body protein breakdown was investigated via analyses of salivary cortisol and urinary nitrogen excretion. RESULTS: Nitrogen balance in PLA (-0.02±0.01 g) was significantly lower than +2H (5.21±0.63 g, p=<0.001, ES=11.61) and IMM (5.21±0.64 g) (p=<0.001, ES=11.59) during the three-hour recovery. There were no significant differences in nitrogen balance between IMM and +2H (p=1.0). Carbohydrate oxidation in IMM was significantly higher than +2H at 60 minutes postexercise (0.21±0.13 g/min vs. 0.11±0.12 g/min, respectively; p=0.014). Fat oxidation was higher in +2H than IMM at minute 90 (p>0.05, ES=0.60), minute 120 (p>0.05, ES=0.40), and minute 150 (p>0.05, ES=0.50). There were no significant differences in salivary cortisol among groups (all p=1.0). CONCLUSION: In the postprandial state, +2H promoted higher fat utilization than IMM, whereas IMM promoted greater carbohydrate oxidation earlier in the recovery period. Both interventions resulted in similar net protein retention. Thus, postponing postexercise nutrient intake when in a postprandial state may be implicated in body composition improvements.

Superior Influence of Reindeer compared to Beef Ingestion on Protein Metabolism in Humans

Wild game consumption has been associated with health benefits, but the immediate influence on protein metabolism remains unknown. In order to address the direct effects on protein kinetics, we compared the feeding‐induced response to free‐range reindeer versus commercial beef using stable isotope methodology in humans. Eight male and female participants (age: 38±12 years; body mass index: 24±3 kg/m2) completed two studies using a randomized, crossover design in which they ingested reindeer or beef. L‐[2H5]phenylalanine &amp; L‐[2H2]tyrosine were delivered via primed, continuous intravenous infusion. Blood samples were collected during a 3‐hour basal period and for 4 hrs after consumption of reindeer and beef. A priming dose of L‐[2H4]tyrosine was also delivered. Feeding‐induced changes in whole body protein synthesis (PS), protein breakdown (PB), and net protein balance (NB) were determined via analysis of plasma samples by liquid chromatography‐electrospray ionization‐tandem mass spectrometry (LC‐ESI‐MS). Post‐prandial essential amino acid (EAA) concentrations were higher with reindeer ingestion (P=0.02). PS was not different but PB was reduced with reindeer compared to beef ingestion (P=0.02), contributing to superior level of NB (P=0.001). Reindeer promoted higher plasma EAA levels and NB compared to beef. The amino acid and fatty acid profiles of reindeer may have an immediate and greater benefit on protein metabolism as compared to beef. These data support the potential health benefits of wild game in the preservation of whole‐body protein.Support or Funding InformationResearch reported in this publication was supported by an Institutional Development Award (IDeA) under grant number P20GM103395 and the Biomedical Learning and Student Training Program (UL1GM118991, TL4GM118992, or RL5GM118990) from the National Institute of General Medical Sciences from the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

RELATIONSHIP BETWEEN MALIGNANT TUMOR METABOLISM AND TUMOR-BEARING ORGANISM

For a long time, the attention of researchers has primarily focused to the molecular−genetic aspects of the oncogenesis regulation, while quite a logical question remained unclear: where does the cancer cell get an energy for accelerated division? Today the studies have emerged and they prove that specific oncogenes control many other genes, including those responsible for metabolism, which not only maintain high energy levels of their own metabolism, but also alter the supply of glucose and amino acids from healthy microenvironment cells to their advantage. Metabolic disorders are accompanied with a progressive protein−energy deficiency. A feature of this process is the discrepancy between the amount of energy received and that required. There is a sharp rise in energy needs and a pronounced breakdown of body proteins, a decrease in the rate of glucose oxidation with a simultaneous increase in lipid oxidation. Nutrient deficiency leads to a release of its own reserves as a result of the destruction of body tissues. In this regard, the development of ways to block the energy sources and plastic material to enter a cancer cell is being actively discussed in order to improve the effectiveness of treatment of cancer patients. Key words: malignant tumor, metabolism, tumor carrier.

Advances in stable isotope tracer methodology part 2: new thoughts about an “old” method—measurement of whole body protein synthesis and breakdown in the fed state

Whole-body protein turnover (protein synthesis, breakdown, and net balance) model enables quantification of the response to a variety of circumstances, including the response to meal feeding. In the fed state,...

Potential benefits of arginine formulation in oral health care products

AbstractArginine (Arg) is derived from dietary intake, body protein breakdown, and endogenous Arg production, and is also present in saliva. Arg has been introduced as an additive in toothpaste and other fluoride‐containing dental care products and is now being promoted as more efficacious than conventional fluoride‐only toothpaste for the prevention of dental caries. Arg inclusion in dentifrice could potentially inhibit oral biofilm formation and destabilize dental plaque. Arg is expected to inhibit oral biofilm formation and destabilize complex aggregates in dental plaque and its inclusion in mouth rinse could facilitate oral biofilm removal. The destabilization of the oral biofilm by Arg may facilitate the removal of dental plaque during routine oral care. Since removing this solid biological plaque from tooth surfaces by water rinsing or brushing can be difficult, Arg metabolism in oral biofilms leading to an increase in pH decreases the risk for caries development. Moreover, clinical data have shown that Arg‐containing toothpaste increased benefits leading to the prevention of dental caries. However, there are concerns regarding the use of Arg dentifrice in caries progression or regression and some studies contradict the claims of Arg benefits in caries progression or regression.

The Effect of Dietary Protein on Protein Metabolism and Performance in Endurance-trained Males.

This study aimed to determine how varying protein intakes, including a new tracer-derived safe intake, alter whole body protein metabolism and exercise performance during training. Using a double-blind randomized crossover design, 10 male endurance-trained runners (age, 32 ± 8 yr; V˙O2peak, 65.9 ± 7.9 mL O2·kg·min) performed three trials consisting of 4 d of controlled training (20, 5, 10, and 20 km·d, respectively) while consuming diets providing 0.94 (LOW), 1.20 (MOD), and 1.83 (HIGH) g protein·kg·d. Whole body protein synthesis, breakdown, and net balance were determined by oral [N]glycine on the first and last day of the 4-d controlled training period, whereas exercise performance was determined from maximum voluntary isometric contraction, 5-km time trial, and countermovement jump impulse (IMP) and peak force before and immediately after the 4-d intervention. Synthesis and breakdown were not affected by protein intake, whereas net balance showed a dose-response (HIGH > MOD > LOW, P < 0.05) with only HIGH being in positive balance (P < 0.05). There was a trend (P = 0.06) toward an interaction in 5-km Time Trial with HIGH having a moderate effect over LOW (effect size = 0.57) and small effect over MOD (effect size = 0.26). IMP decreased with time (P < 0.01) with no effect of protein (P = 0.56). There was no effect of protein intake (P ≥ 0.06) on maximum voluntary isometric contraction, IMP, or peak force performance. Our data suggest that athletes who consume dietary protein toward the upper end of the current recommendations by the American College of Sports Medicine (1.2-2 g·kg) would better maintain protein metabolism and potentially exercise performance during training.

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

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. Eight older (67±2), obese (35±2kg/m2) female and male participants completed two studies using a randomized, crossover design in which they ingested each meal replacement. The isotopic tracers L-[2H5]phenylalanine & L-[2H2]tyrosine were delivered via primed, continuous intravenous infusion throughout a basal period and following consumption of EMR or BA. We determined changes in whole body protein synthesis (PS), protein breakdown (PB), and net protein balance (NB) from fasted states via analysis of plasma samples by LC-ESI-MS. PS was higher (P=0.03) and PB was less (P=0.005) with EMR in comparison to BA. As a result, NB was much greater (P=0.00003) following the ingestion of EMR as compared to BA. In comparison with BA, which has a higher amount of intact protein that any other meal replacement, EMR promoted a greater increment in NB. These data support the potential efficacy of EMR as a meal replacement for the preservation of lean tissue mass during weight loss in older, overweight individuals.

Whole body protein anabolism in COPD patients and healthy older adults is not enhanced by adding either carbohydrates or leucine to a serving of protein

Carbohydrates (CHO) and leucine (LEU) both have insulinotropic properties, and could therefore enhance the protein anabolic capacity of dietary proteins, which are important nutrients in preventing muscle loss in patients with Chronic Obstructive Pulmonary Disease (COPD). LEU is also known to activate protein anabolic signaling pathways independent of insulin. Based on our previous findings in COPD, we hypothesized that whole body protein anabolism is enhanced to a comparable extent by the separate and combined co-ingestion of CHO and LEU with protein. To disentangle the protein anabolic effects of CHO and/or free LEU when co-ingested with a high-quality protein, we studied 10 patients with moderate to very severe COPD and dyspnea (GOLD: II-IV, mMRC dyspnea scale≥2), at risk for muscle loss, and 10 healthy age- and gender-matched controls. On four occasions, in a single-blind randomized crossover design, each subject ingested a drink containing 0.6g/kg fat-free mass (ffm) hydrolyzed casein protein with, a) no add-ons (protein), b) 0.3g/kg ffm CHO (protein+CHO), c) 0.095g/kg ffm leucine (protein+LEU), d) both add-ons (protein+CHO+LEU). Whole body protein breakdown (PB), protein synthesis (PS), and net protein balance (= PS - PB) were measured by IV primed and continuous infusion of L-[ring-2H5]-phenylalanine and L-[13C9,15N]-tyrosine. L-[15N]-phenylalanine was added to the protein drinks to measure splanchnic extraction. In both groups, whole body PS, PB and net protein balance responses were comparable between the four protein drinks, despite higher postprandial plasma LEU concentrations for the LEU supplemented drinks (P<0.05), and higher insulin concentrations for the CHO supplemented drinks as compared to the protein only drink (P<0.05). Adding CHO and/or LEU to a serving of high-quality protein does not further augment whole body protein anabolism in dyspneic COPD patients at risk for muscle loss or healthy older adults. ClinicalTrials.gov; No. NCT01734473; URL: www.clinicaltrials.gov.

Preserved anabolic threshold and capacity as estimated by a novel stable tracer approach suggests no anabolic resistance or increased requirements in weight stable COPD patients

Assessing the ability to respond anabolic to dietary protein intake during illness provides important insight in the capacity of lean body mass maintenance. We applied a newly developed stable tracer approach to assess in one session in patients with chronic obstructive pulmonary disease (COPD) and healthy older adults both the minimal amount of protein intake to obtain protein anabolism (anabolic threshold) and the efficiency of dietary protein to promote protein anabolism (anabolic capacity). We studied 12 clinically and weight stable patients with moderate to very severe COPD (mean±SE forced expiratory volume in 1s: 36±3% of predicted) and 10 healthy age-matched older adults. At 2-h intervals and in consecutive order, all participants consumed a mixture of 0.0, 0.04, 0.10 and 0.30g hydrolyzed casein protein×kg ffm-1×2h-1 and carbohydrates (2:1). We assessed whole body protein synthesis (PS), breakdown (PB), net PS (PS-PB) and net protein balance (phenylalanine (PHE) intake - PHE to tyrosine (TYR) hydroxylation) by IV primed and continuous infusion of L-[ring-2H5]PHE and L-[13C9,15N]-TYR. Anabolic threshold (net protein balance=0) and capacity (slope) were determined on an individual basis from the assumed linear relationship between protein intake and net protein balance. We confirmed a linear relationship between protein intake and net protein balance for all participants (R2 range: 0.9988-1.0, p≤0.0006). On average, the anabolic threshold and anabolic capacity were comparable between the groups (anabolic threshold COPD vs. healthy: 3.82±0.31 vs. 4.20±0.36μmol PHE×kg ffm-1×hr-1; anabolic capacity COPD vs. healthy: 0.952±0.007 and 0.954±0.004). At protein intake around the anabolic threshold (0.04 and 0.10g protein×kg ffm-1×2h-1), the increase in net PS resulted mainly from PB reduction (p<0.0001) whereas at a higher protein intake (0.30g protein×kg ffm-1×2h-1) PS was also stimulated (p<0.0001). The preserved anabolic threshold and capacity in clinically and weight stable COPD patients suggests no disease related anabolic resistance and/or increased protein requirements. ClinicalTrials.gov; No. NCT01734473; URL: www.clinicaltrials.gov.

Arginine enzymatic deprivation and diet restriction for cancer treatment

Recent findings in amino acid metabolism and the differences between normal, healthy cells and neoplastic cells have revealed that targeting single amino acid metabolic enzymes in cancer therapy is a promising strategy for the development of novel therapeutic agents. Arginine is derived from dietary protein intake, body protein breakdown, or endogenous de novo arginine production and several studies have revealed disturbances in its synthesis and metabolism which could enhance or inhibit tumor cell growth. Consequently, there has been an increased interest in the arginine-depleting enzymes and dietary deprivation of arginine and its precursors as a potential antineoplastic therapy. This review outlines the most recent advances in targeting arginine metabolic pathways in cancer therapy and the different chemo- and radio-therapeutic approaches to be co-applied.