Efficacy of calcium glycerophosphate vs conventional mineral salts for total parenteral nutrition in low-birth-weight infants: a randomized clinical trial

To test the efficacy of calcium glycerophosphate (CaGlyP) vs the conventional mineral salts, calcium gluconate plus KH2PO4 + K2HPO4 (CaGluc + P), in promoting mineral retention, 72-h mineral balance, biochemical status, net acid excretion, and growth were assessed in 16 low-birth-weight infants receiving total parenteral nutrition (TPN) containing approximately 1.5 mmol Ca and P.kg-1.d-1 for 5 d. Net retentions of calcium (1.2 +/- 0.2 vs 1.0 +/- 0.2 mmol.kg-1.d-1, means +/- SD) and phosphorus (1.1 +/- 0.3 vs 0.8 +/- 0.3 mmol.kg-1.d-1) from CaGluc + P vs CaGlyP, respectively, were similar, as were retentions of magnesium and sodium, urinary pH, and net acid excretion. Plasma ionized calcium, inorganic phosphorus, alkaline phosphatase, and osteocalcin were normal and not different between groups. CaGlyP is as effective as CaGluc + P in promoting mineral retention and normal mineral homeostasis. However, at intakes of less than or equal to 1.5 mmol Ca and P.kg-1.d-1 from either mineral salt, retention represented only 60% and 45%, respectively, of the predicted intrauterine accretion for calcium and phosphorus. Larger intakes permitted by the more-soluble CaGlyP may be desirable for infants receiving TPN.     

Glutamine and smooth muscle morphology of the gut in rats on total parenteral nutrition

The purpose of this study was to assess the effects of addition of L-glutamine to an IV nutritional solution on the urinary excretion of 3-methylhistidine (3-MeH) and the morphology of the musculature of the gut in rats. Two experiments were run. In experiment 1 glutamine was added to a mildly hypocaloric IV solution which contained no other amino acids. For experiment 2 glutamine was added to an isocaloric balanced amino acid mixture. In both experiments L-alanine was added in equimolar amounts in place of the L-glutamine for the control groups. Providing glutamine in an IV diet without other amino acids significantly decreased urinary 3-MeH excretion (p less than 0.05). Electron microscopy and morphometric analysis of the jejunum showed an approximate 50% loss of musculature from the gut wall in alanine-treated animals. Glutamine supplementation of a balanced amino acid regime had no effect on urinary 3-MeH excretion or the musculature of the jejunum. We concluded that (1) glutamine is a preferred fuel for jejunal smooth muscle as well as for mucosal cells of the jejunum and (2) only when amino acids are limiting does exogenous glutamine prevent atrophy of the gut musculature.     

Nitrogen balance of healthy Dutch women before and during pregnancy

BACKGROUND: Experimental studies including longitudinal nitrogen balance studies could provide insight into protein metabolism in pregnancy. OBJECTIVE: Our aim was to determine the development of nitrogen balance during pregnancy compared with nitrogen balance before pregnancy in women consuming imposed constant diets. We also tracked changes in muscle mass and lean body mass by measuring urinary 3-methylhistidine (3-MeH) and urinary creatinine. DESIGN: Nitrogen balance was determined over 8 d in 12 healthy Dutch women before pregnancy and at weeks 12, 23, and 34 of gestation. Complete daily diets were supplied during each balance period so that each subject's energy, protein, and macronutrient intakes were similar in amount and composition in all 4 balance periods. RESULTS: Throughout pregnancy there was no significant change in loss of nitrogen in feces and therefore no change in protein digestibility. The amount of nitrogen excreted in urine in late pregnancy (11.0 +/- 1.4 g/d) was significantly (P < 0.01) less than in early pregnancy (12.6 +/- 1.3 g/d). Nitrogen retention increased toward term, even though energy balance became progressively negative. The difference between the first (-0.4 +/- 1.7 g N/d) and third (1.2 +/- 1.6 g N/d) trimester was significant (P < 0.05). No differences were found in either 3-MeH or creatinine excretion between trimesters. CONCLUSIONS: These urinary nitrogen excretion and nitrogen retention data show that when the dietary supply remains constant, nitrogen balance increases toward the end of pregnancy, suggesting a more efficient use of dietary protein later in pregnancy. Urinary 3-MeH and creatinine excretion indicated no change in protein metabolism.     

Book Review

The purpose of this study was to assess the effects of addition of L-glutamine to an IV nutritional solution on the urinary excretion of 3-methylhistidine (3-MeH) and the morphology of the musculature of the gut in rats. Two experiments were run. In experiment 1 glutamine was added to a mildly hypocaloric IV solution which contained no other amino acids. For experiment 2 glutamine was added to an isocaloric balanced amino acid mixture. In both experiments L-alanine was added in equimolar amounts in place of the L-glutamine for the control groups. Providing glutamine in an IV diet without other amino acids significantly decreased urinary 3-MeH excretion (p less than 0.05). Electron microscopy and morphometric analysis of the jejunum showed an approximate 50% loss of musculature from the gut wall in alanine-treated animals. Glutamine supplementation of a balanced amino acid regime had no effect on urinary 3-MeH excretion or the musculature of the jejunum. We concluded that (1) glutamine is a preferred fuel for jejunal smooth muscle as well as for mucosal cells of the jejunum and (2) only when amino acids are limiting does exogenous glutamine prevent atrophy of the gut musculature.     

Amino acid intake and urinary zinc excretion in newborn infants receiving total parenteral nutrition

Zinc deficiency is well described in infants on total parenteral nutrition (TPN). Urinary Zn excretion is the major source of Zn loss in the parenterally fed infant; factors causing increased zincuria will predispose the infant to Zn deficiency and affect the recommended Zn intake dosage. Histidine, threonine, and lysine have been shown to bind Zn increasing its renal ultrafilterability. The effect of the infusion of high and low lysine (206 +/- 34 vs 158 +/- 38 mg.kg-1.d-1; means +/- SD), threonine (147 +/- 24 vs 113 +/- 27), and histidine (124 +/- 34 vs 85 +/- 15) on urinary Zn excretion were determined in 23 newborns on TPN who received similar Zn intakes (6.8 +/- 1.4 mumol.kg-1.d-1). After a 72-h adaptation period each infant had urine collected for two 24-h periods. Despite the significant difference in amino acid intakes, mean urinary Zn excretion was identical (1.58 +/- 0.73 vs 1.56 +/- 0.63 mumol.kg-1.d-1). Hyperzincuria, therefore, does not occur when amino acids are infused at rates appropriate for the safety and nutritional maintenance of neonates.     

Branched chain amino acid therapy in liver disease.

Patients with hepatic cirrhosis often are malnourished and wasted. If portal-systemic encephalopathy (PSE) develops, restriction of dietary protein in an attempt to treat encephalopathy may further promote negative nitrogen balance. There is considerable interest in providing nutritional supplements to patients with cirrhosis and PSE which would lead to improvement in nitrogen balance while improving or at least not worsening PSE. Amino acid supplements designed to correct the abnormal amino acid pattern characteristically found in patients with cirrhosis and PSE are under investigation as potential therapeutic agents. The levels of the branched chain amino acids (BCAAs) are decreased in almost all patients with cirrhosis and PSE. The exact mechanism for the reductions in BCAA concentrations is unknown. Furthermore, aromatic amino acids (AAA) and methionine (MET) concentrations are usually increased in these patients. It has been suggested that BCAAs and neutral amino acids compete for transport across the blood-brain barrier and that a decrease in BCAA concentrations promotes entrance of neutral amino acids into the brain. Aromatic amino acids, MET, and their derivatives may have a role in the production of PSE. These observations have increased interest in the potential therapeutic benefit of administering BCAAs to patients with cirrhosis and PSE in order to decrease the entrance of putative toxins into the brain. Treatment trials using BCAAs alone or in solutions containing other amino acids in patients with cirrhosis and PSE have given conflicting results. In one trial, there appeared to be less PSE induced by a BCAA-enriched solution when compared to equinitrogenous dietary protein. However, other controlled studies have not demonstrated any advantage to the addition of BCAAs as compared to placebo with regards to reducing mortality or improving cerebral function in patients with acute cirrhosis and PSE. Some of the differences in study outcomes may relate to the patient population evaluated; the type, amount, and duration of treatment; and whether other therapy was administered. BCAA supplements may also be useful in minimizing or reversing the catabolic state characteristic of patients with cirrhosis. A reduction of increased urinary 3-methylhistidine excretion by infusions of BCAAs in cirrhotic patients suggests an anticatabolic effect. These potential anticatabolic effects of BCAAs are most interesting and deserve further study.     

Branched chain amino acid therapy in liver disease

Patients with hepatic cirrhosis often are malnourished and wasted. If portal-systemic encephalopathy (PSE) develops, restriction of dietary protein in an attempt to treat encephalopathy may further promote negative nitrogen balance. There is considerable interest in providing nutritional supplements to patients with cirrhosis and PSE which would lead to improvement in nitrogen balance while improving or at least not worsening PSE. Amino acid supplements designed to correct the abnormal amino acid pattern characteristically found in patients with cirrhosis and PSE are under investigation as potential therapeutic agents. The levels of the branched chain amino acids (BCAAs) are decreased in almost all patients with cirrhosis and PSE. The exact mechanism for the reductions in BCAA concentrations is unknown. Furthermore, aromatic amino acids (AAA) and methionine (MET) concentrations are usually increased in these patients. It has been suggested that BCAAs and neutral amino acids compete for transport across the blood-brain barrier and that a decrease in BCAA concentrations promotes entrance of neutral amino acids into the brain. Aromatic amino acids, MET, and their derivatives may have a role in the production of PSE. These observations have increased interest in the potential therapeutic benefit of administering BCAAs to patients with cirrhosis and PSE in order to decrease the entrance of putative toxins into the brain. Treatment trials using BCAAs alone or in solutions containing other amino acids in patients with cirrhosis and PSE have given conflicting results. In one trial, there appeared to be less PSE induced by a BCAA-enriched solution when compared to equinitrogenous dietary protein. However, other controlled studies have not demonstrated any advantage to the addition of BCAAs as compared to placebo with regards to reducing mortality or improving cerebral function in patients with acute cirrhosis and PSE. Some of the differences in study outcomes may relate to the patient population evaluated; the type, amount, and duration of treatment; and whether other therapy was administered. BCAA supplements may also be useful in minimizing or reversing the catabolic state characteristic of patients with cirrhosis. A reduction of increased urinary 3-methylhistidine excretion by infusions of BCAAs in cirrhotic patients suggests an anticatabolic effect. These potential anticatabolic effects of BCAAs are most interesting and deserve further study.     

Total parenteral nutrition in the newborn: impact of the quality of infused energy on nitrogen metabolism

To separate the respective influence of the level and source of infused energy on nitrogen metabolism, 32 studies were performed in 16 appropriate-for-gestational-age newborn infants (birth weight 2150 +/- 115 g, means +/- SEM). In a cross-over design, each patient received two 6-d periods of isocaloric and isonitrogenous (450 mg.kg-1.d-1) infusions, differing only by the source of calories (high or low fat intakes). Half of the patients were studied at 60 kcal.kg-1.d-1, the other half at 80 kcal.kg-1.d-1. Nitrogen balance, urinary 3-methylhistidine excretion, glycemia, and insulin were compared. The results suggest that for an intravenous energy intake ranging from 60 to 80 kcal.kg-1.d-1, glucose and fat provide an equivalent nitrogen sparing effect in the newborn infant. At an energy level covering maintenance requirements, it is the infant's clinical condition rather than the source of energy which affects most the magnitude of amino acids participation in energy metabolism.     

The effect of solutions of varying branched-chain concentration on the plasma amino acid pattern and metabolism in intensive care patients

30 intensive care surgical patients were investigated over a period of five days following trauma or major surgery. They were randomised by card into two groups, Group I received an amino acid solution containing 45 per cent branched-chain amino acids (BCAA), and group II an amino acid solution with a 10 per cent content of BCAAs. After 24 hours of infusion, the total amino acid concentration and branched-chain amino acid concentration in the plasma of Group I patients already clearly exceeded the normal range, and continued to increase during the period of study. In Group II these parameters rapidly returned to normal where they remained. Cumulative negative nitrogen balance and nitrogen excretion on each day of investigation were significantly less in Group II. These results indicate that after severe trauma or major surgery amino acid solutions containing high concentrations of BCAAs may be an unphysiological load on the already stressed metabolism, rather than a benefit.     

High-protein intake alters the response of fasting in normal human subjects.

Two groups of normal volunteers were studied for 5 d of dietary control followed by 3 d of fasting. One group (n = 5) was given a control diet of 0.9 g protein.kg-1.d-1 and the other group (n = 7) was given a high-protein (HP) diet (2.5 g protein.kg-1.d-1). Both groups received 175.56 kJ.kg-1.d-1 (42 kcal.kg-1.d-1). The HP diet but not the control diet caused a significant retention of nitrogen. Postabsorptive leucine kinetics as assessed with [1,2-13C]leucine were similar in the two groups. In the control subjects, the rate of nitrogen excretion did not change in response to fasting, but leucine oxidation increased. In contrast, nitrogen excretion progressively decreased with fasting after the HP diet. Leucine rate of appearance was increased after fasting after the HP diet but oxidation was not increased, meaning that the calculated rate of whole-body protein synthesis was higher than in the control group. The response to a short period of food deprivation is dependent on prior protein intake.     

Effects of body size on kinetics of glucose metabolism and on nitrogen balance in growing cattle

Effects of body size on the kinetics of glucose metabolism were examined. In trial 1, steers were fed 6 kg of an 80:20 concentrate:roughage diet daily across a weight range of 226 to 470 kg. In trial 2, steers were fed 4.5 kg of a 45:55 concentrate:roughage diet daily across a weight range of 134 to 390 kg. Glucose irreversible loss averaged 820 +/- 32 and 461 +/- 13 mg/min for trials 1 and 2 and was not affected by body size. Thus, glucose irreversible loss seems to be regulated by feed intake when intake is above maintenance. Body size had no effect on glucose total entry rate, recycling or pool size. Blood glucose concentration and glucose space decreased at 0.004 mg X ml-1 X kg-1 and 0.002 fractional units body wt X kg-1 as body size increased. Digestible energy and nitrogen balance were measured in trial 2. Digestibility of energy increased at 0.0054 Mcal X d-1 X kg-1 as body size increased. Nitrogen retention averaged 28.2 g X d-1 and was not influenced by body size even though energy intake approached maintenance amounts at the end of the trial. On the basis of urinary nitrogen excretion data, we conclude that the maximum net contribution of amino acid carbon to glucose synthesis was 8% of glucose carbon.     

Effects of branched-chain amino acid supplementation on plasma concentrations of free amino acids, insulin, and energy substrates in young men

The present study was conducted to examine alterations in the concentrations of plasma free amino acids, glucose, insulin, free fatty acids (FFAs), and urea nitrogen induced by branched-chain amino acid (BCAA) supplementation in young men. Overnight-fasted subjects ingested drinks containing 1 or 5 g of a BCAA mixture (weight ratio of 1 : 2.3 : 1.2 for isoleucine : leucine : valine), and blood was intermittently collected for 3 h after ingestion. Ingestion of the BCAA mixture resulted in significant increases in the plasma concentrations of individual BCAAs, corresponding to the amounts of amino acids ingested. On the other hand, plasma concentrations of methionine and aromatic amino acids tended to decrease in the trial with 5 g BCAAs, suggesting that BCAA ingestion affects the metabolism of these amino acids. The ingestion of BCAAs temporarily increased plasma insulin levels and affected plasma concentrations of FFAs, but had almost no effect on glucose or urea nitrogen.     

Variations in plasma amino acids in septic patients subjected to parenteral nutrition with a high proportion of branched-chain amino acids.

Sepsis is characterized by an increase in the plasma concentration of aromatic amino acids (AAAs) and those containing sulfur and a decrease in the branched-chain amino acids (BCAAs). We studied changes in the plasma aminogram of septic patients given different types of total parenteral nutrition (TPN), analyzing variations in accordance with the type of TPN used and the importance that the use of BCAA may have in these patients. We studied 80 patients with peritonitis divided into two groups of 40 patients each: group 1 was given a solution with 22.5% BCAA and group 2 a solution with 45% BCAA. High BCAA content caused an increase in the plasma concentrations of these amino acids and in the BCAA/AAA quotient and a decrease in AAAs. Plasma concentrations of leucine and valine reached high, potentially toxic levels at 15 days when solutions with high BCAA content were used. Glycine increased in group 1, which may be important because of its tendency to produce hyperammonemia. BCAAs are of unquestioned nutritional importance in view of the evidence of changes that take place in muscle protein catabolism and in plasma amino acids. In the phase of increased protein catabolism, we saw a plasma amino acid pattern in keeping with the existing metabolic situation. The need for BCAA diminishes when the hypercatabolic state disappears.     

单能源与双能源全营养液对急性肝衰竭大鼠氮代谢影响的比较

目的　探讨含有高 BCAA的复方氨基酸、脂肪乳、糖、维生素、无机盐的混合营养液 (TNA)对急性肝衰竭大鼠氮代谢的影响。方法　应用 D-半乳糖胺腹腔注射诱导 Wistar大鼠呈急性肝脏衰竭。 72 h后随机分为富含 BCAA双能源 TNA组、富含 BCAA单能源 TNA组、普通饲料组、无氮饲料组观察其血浆总蛋白、白蛋白、前白蛋白、血浆氨基酸谱、氨平衡、肝肾功能的改变。结果　双能源组血浆氨基酸谱恢复接近正常 (P<0 .0 5)。普通饲料组、单能源组氨基酸谱恢复与无氮饲料组也有明显的差别 (P<0 .0 5)。双能源组血浆总蛋白、白蛋白、前白蛋白恢复较快。双能源组好于正常饲料组、单能源组 ,其中前白蛋白恢复更明显 (P<0 .0 5)。除无氮饲料组为负氮平衡 ,其余三组均为正氮平衡。肝功能 ALT、AST、ALP、Bil均以双能源组和普通饲料组恢复优于其他两组。肾功能以单能源组损害明显。结论　本研究设计的双能源 TNA对急性肝衰大鼠有较好的治疗效果 :提供了合理的能源底物 ,可改善血浆氨基酸谱至基本恢复正常 ,维持氮平衡 ,总蛋白、白蛋白明显回升。可能是葡萄糖、脂肪双能源 TNA供给的结构比例符合于肝衰竭代谢特点 ,促进了合成代谢 ,使损伤的肝细胞得以再生     

Protein-energy requirements of prepubertal school-age boys determined by using the nitrogen-balance response to a mixed-protein diet

Short-term nitrogen-balance response to a vegetable-protein mixed diet and to a milk-egg protein diet was tested in eight healthy male children 8-10 y old. They received 96, 128, 160, and 192 mg N.kg body wt-1.d-1 for 10 d while on the mixed diet and 160 mg N.kg-1.d-1 on the milk-egg diet. The mean regression equation was nitrogen balance = 0.52 (nitrogen intake) -68.3, all in mg N.kg-1.d-1. Apparent nitrogen digestibility was 82% and 86% for the mixed and milk-egg diets, respectively, when the subjects received 160 mg N.kg-1.d-1. Mean nitrogen intake for satisfactory nitrogen retention on the mixed diet was 150 mg N.kg-1.d-1; the suggested protein recommended allowance to cover 97.5% of the population was derived by using a CV of 12.5% is 1.2 g protein.kg-1.d-1. We conclude that present recommendations are adequate for short-term nitrogen retention; long-term studies are needed to evaluate the chronic safety of this protein allowance.     

Evaluation of an infusion solution enriched with branched chain amino acid in parenteral nutrition of rats

Nutritional effects of an infusion solution enriched with branched chain amino acids (BCAAs) were investigated with young adult rats. Continuous infusion through a central venous cannula was carried out for 7 days with three kinds of solutions: 1) 21.8% glucose (S-1); 2) 18.6% glucose plus 2.50% amino acids based on human milk pattern (S-2), and 3) 18.6% glucose plus 2.58% amino acids enriched with BCAAs (S-3). Rats received daily 50 ml of the solution, containing 45 kcal and 200 mg N in S-2 and S-3. The body weights of rats in the S-2 and S-3 groups were only slightly reduced, while those of the S-1 group were extremely reduced. The rats were in positive nitrogen balance in the S-2 and S-3 groups on days 2-7. Its value was somewhat, but not significantly, larger in the S-3 group than in the S-2 group. The plasma BCAA levels determined 15 minutes after the end of infusion were higher in the S-3 group than in the S-2 group, but there was no significant difference except for the leucine level. The urinary levels of creatinine and 3-methylhistidine, the plasma levels of urea and glucose, and liver lipid content were similar in the S-2 and S-3 groups. The plasma albumin level was somewhat higher in the S-3 group than in the S-2 group. The present data suggest that an infusion solution enriched with BCAAs served to maintain the normal rats in desirable nutritional status.     

Prior protein intake may affect phenylalanine kinetics measured in healthy adult volunteers consuming 1 g protein. kg-1. d-1

Study of the amino acid metabolism of vulnerable groups, such as pregnant women, children and patients, is needed. Our existing protocol is preceded by 2 d of adaptation to a low 13C formula diet at a protein intake of 1 g. kg-1. d-1 to minimize variations in breath 13CO2 enrichment and protein metabolism. To expand on our potential study populations, a less invasive protocol needs to be developed. We have already established that a stable background 13CO2 enrichment can be achieved on the study day without prior adaptation to the low 13C formula. Therefore, this study investigates phenylalanine kinetics in response to variations in prior protein intake. Healthy adult subjects were each fed nutritionally adequate mixed diets containing 0.8, 1.4 and 2.0 g protein. kg-1. d-1 for 2 d. On d 3, subjects consumed an amino acid-based formula diet containing the equivalent of 1 g protein. kg-1. d-1 hourly for 10 h and primed hourly oral doses of L-[1-13C]phenylalanine for the final 6 h. Phenylalanine kinetics were calculated from plasma-free phenylalanine enrichment and breath 13CO2 excretion. A significant quadratic response of prior protein intake on phenylalanine flux (P = 0.012) and oxidation (P = 0.009) was identified, such that both variables were lower following adaptation to a protein intake of 1.4 g. kg-1. d-1. We conclude that variations in protein intake, between 0.8 and 2.0 g. kg-1. d-1, prior to the study day may affect amino acid kinetics and; therefore, it is prudent to continue to control protein intake prior to an amino acid kinetics study.     

Protein-energy requirements of boys 12-14 y old determined by using the nitrogen-balance response to a mixed-protein diet.

Short-term nitrogen-balance response to graded intakes of a vegetable mixed-protein diet and to a milk-egg protein diet was tested in eight healthy male children aged 12-14 y. They received 72, 104, 136, and 168 mg N.kg body wt-1.d-1 for 10 d while on the mixed diet, and 160 mg N.kg-1.d-1 on the milk-egg diet. The mean regression equation was nitrogen balance = 0.64 (nitrogen intake)-74, all values are in mg N.kg-1.d-1. Apparent digestibility was 86% and 85% for the mixed and milk-egg diets when the subjects received 168 and 160 mg N.kg-1.d-1, respectively. Mean nitrogen intake for satisfactory nitrogen retention for growth on the mixed diet was 147 mg N.kg-1.d-1; the recommended protein allowance to cover 97.5% of the population, which was derived by using a CV of 12.5%, is 1.15 g protein.kg-1.d-1. We conclude that FAO/WHO/UNU recommendations are adequate, at least for short-term nitrogen retention; long-term studies are needed to evaluate the chronic safety of this protein allowance.     

A Novel Dietary Intervention Reduces Circulatory Branched-Chain Amino Acids by 50%: A Pilot Study of Relevance for Obesity and Diabetes

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.     

The effect of dietary protein intake on glutamine and glutamate nitrogen metabolism in humans.

The response of glutamine and glutamate kinetics were studied in five healthy young adult men on diets containing deficient (0.1), adequate (0.8), or surfeit (2.2 g.kg-1.d-1) amounts of protein. Glutamate, glutamine, and phenylalanine kinetics were measured in the postabsorptive state at the end of each diet period. Urinary urea and ammonia excretion correlated with protein intake (the sum of the two was 2.1 +/- 0.2, 5.7 +/- 0.3, and 11.9 +/- 1.2 g N g.kg-1.d-1 for the respective 0.1, 0.8, and 2.2 g.kg-1.d-1 protein intakes). Glutamate and glutamine concentrations varied inversely with protein intake. Phenylalanine concentrations and phenylalanine flux did not change significantly with the changing protein intake. Both glutamate and glutamine fluxes varied inversely with protein intake (glutamate flux was 177 +/- 15, 120 +/- 10, and 125 +/- 11 mumol.kg-1.h-1 and glutamine flux was 373 +/- 29, 343 +/- 26, and 318 +/- 15 mumol.kg-1.h-1 at the respective 0.1, 0.8, and 2.2 g.kg-1.d-1 protein intakes). These changes in glutamine or glutamate flux in response to alterations in dietary protein intake were attributable to changes in de novo production.