Scientific abstracts

 

Protein catabolism and requirements in severe illness.
SOURCE: Int J Vitam Nutr Res. 2011 Mar;81(2):143-52.
AUTHORS: Genton L, Pichard C.
AFFILIATION: Clinical Nutrition, Geneva University Hospital, Geneva, Switzerland.
 
ABSTRACT:
Reduced total body protein mass is a marker of protein-energy malnutrition and has been associated with numerous complications. Severe illness is characterized by a loss of total body protein mass, mainly from the skeletal muscle. Studies on protein turnover describe an increased protein breakdown and, to a lesser extent, an increased whole-body protein synthesis, as well as an increased flux of amino acids from the periphery to the liver. Appropriate nutrition could limit protein catabolism. Nutritional support limits but does not stop the loss of total body protein mass occurring in acute severe illness. Its impact on protein kinetics is so far controversial, probably due to the various methodologies and characteristics of nutritional support used in the studies. Maintaining calorie balance alone the days after an insult does not clearly lead to an improved clinical outcome. In contrast, protein intakes between 1.2 and 1.5 g/kg body weight/day with neutral energy balance minimize total body protein mass loss. Glutamine and possibly leucine may improve clinical outcome, but it is unclear whether these benefits occur through an impact on total body protein mass and its turnover, or through other mechanisms. Present recommendations suggest providing
20 - 25 kcal/kg/day over the first 72 - 96 hours and increasing energy intake to  target thereafter. Simultaneously, protein intake should be between 1.2 and 1.5 g/kg/day. Enteral immunonutrition enriched with arginine, nucleotides, and omega-3 fatty acids is indicated in patients with trauma, acute respiratory distress syndrome (ARDS), and mild sepsis. Glutamine (0.2 - 0.4 g/kg/day of L-glutamine) should be added to enteral nutrition in burn and trauma patients (ESPEN guidelines 2006) and to parenteral nutrition, in the form of dipeptides, in intensive care unit (ICU) patients in general (ESPEN guidelines 2009). 
 
 
Branched-chain amino acid levels are associated with improvement in insulin resistance with weight loss.
SOURCE: Diabetologia. 2011 Nov 8. 
AUTHORS: Shah SH, Crosslin DR, Haynes CS, Nelson S, Turer CB, Stevens RD, Muehlbauer MJ, Wenner BR, Bain JR, Laferrère B, Gorroochurn P, Teixeira J, Brantley PJ, Stevens  VJ, Hollis JF, Appel LJ, Lien LF, Batch B, Newgard CB, Svetkey LP.
AFFILIATION: Department of Medicine, DUMC, Duke University Medical Center, Box 3445, Durham, NC, 27710, USA
 
ABSTRACT:
Insulin resistance (IR) improves with weight loss, but this response is heterogeneous. We hypothesised that metabolomic profiling would identify biomarkers predicting changes in IR with weight loss. Targeted  mass spectrometry-based profiling of 60 metabolites, plus biochemical assays of NEFA, β-hydroxybutyrate, ketones, insulin and glucose were performed in baseline  and 6 month plasma samples from 500 participants who had lost ≥4 kg during Phase I of the Weight Loss Maintenance (WLM) trial. Homeostatic model assessment of insulin resistance (HOMA-IR) and change in HOMA-IR with weight loss (∆HOMA-IR) were calculated. Principal components analysis (PCA) and mixed models adjusted for race, sex, baseline weight, and amount of weight loss were used; findings were validated in an independent cohort of patients (n = 22). Mean weight loss was 8.67 ± 4.28 kg; mean ∆HOMA-IR was -0.80 ± 1.73, range -28.9 to 4.82). Baseline PCA-derived factor 3 (branched chain amino acids [BCAAs] and associated catabolites) correlated with baseline HOMA-IR (r = 0.50, p < 0.0001) and independently associated with ∆HOMA-IR (p < 0.0001). ∆HOMA-IR increased in a linear fashion with increasing baseline factor 3 quartiles. Amount of weight loss was only modestly correlated with ∆HOMA-IR (r = 0.24). These findings were validated in the independent cohort, with a factor composed of BCAAs and related metabolites predicting ∆HOMA-IR (p = 0.007). A cluster of metabolites comprising BCAAs and related analytes predicts improvement in HOMA-IR independent of the amount of weight lost. These results may help identify individuals most likely to benefit from moderate weight loss and elucidate novel mechanisms of IR in obesity.
 

 

 

Branched-chain amino acids prevent insulin-induced hepatic tumor cell proliferation by inducing apoptosis through mTORC1 and mTORC2-dependent mechanisms.

SOURCE: Journal of Cell physiology, July 18, 2011  doi: 10.1002/jcp.22941.

AUTHORS: Hagiwara A, Nishiyama M, Ishizaki S.

AFFILIATION: Pharmaceutical Research Center, Ajinomoto Pharmaceuticals Co., Ltd., Kawasaki, Japan

ABSTRACT:

Branched-chain amino acids (BCAA) supplementation has been reported to suppress the incidence of liver cancer in obese patients with liver cirrhosis or in obese and diabetic model animals of carcinogenesis. Whether BCAA directly suppresses cell proliferation of hepatic tumor cells under hyperinsulinemic condition remain to be defined. The aim of this study was to investigate the effects of BCAA on insulin-induced proliferation of hepatic tumor cells and de  

 termine the underlying mechanisms. BCAA suppressed insulin-induced cell proliferation of H4IIE, HepG2 cells. In H4IIE cells, BCAA did not affect cell cycle progression but increased apoptosis by suppressing expressions of anti-apoptotic genes and inducing pro-apoptotic gene via inactivation of PI3K/Akt and NF-κB signaling pathways. Further studies demonstrated that BCAA inhibited PI3K/Akt pathway not only by promoting negative feedback loop from mammalian target of rapamycin complex 1 (mTORC1)/S6K1 to PI3K/Akt pathway, but also by suppressing mTORC2 kinase activity toward Akt. Our findings suggest that BCAA supplementation is likely to suppress liver cancer progression by inhibiting insulin-induced PI3K/Akt and subsequent anti-apoptotic pathway, indicating that BCAA may be useful for the obese patients with advanced liver disease

Oral citrulline does not affect whole body protein metabolism in healthy human volunteers: Results of a prospective, randomized, double-blind, cross-over study.

AUTHORS: Thibault R, Flet L, Vavasseur F, Lemerle M, Ferchaud-Roucher V, Picot D, Darmaun D.

AFFILIATION: Service d'Hépato-gastro-entérologie et Assistance Nutritionnelle, CHU de Nantes, Nantes, France; UMR 1280 Physiologie des Adaptations Nutritionnelles, INRA, Université de Nantes Nantes, France; Centre d'Investigation Clinique, CRNH Nantes and Institut des Maladies de l'Appareil Digestif, CHU de Nantes, Nantes F-44093, France.

ABSTRACT:

Citrulline increases protein synthesis during refeeding in rodents with short bowel syndrome, aging and malnutrition, and improves nitrogen balance in fed healthy humans. The aim of the current study therefore was to determine whether citrulline had affected protein metabolism in healthy volunteers.

In a randomized, double-blind, cross-over study, 12 healthy adults received a 5-h intravenous infusion of L-[1-(13)C]-leucine in the post-absorptive state, after a 7-day oral supplementation with 0

 .18 g/kg/day citrulline, or an iso-nitrogenous placebo. Treatment order was randomized, treatment periods were separated by 13-day wash out. Leucine appearance rate (Ra) was determined from plasma [1-(13)C]-keto-iso-caproate enrichment and leucine oxidation from expired (13)CO(2), and nitrogen balance was estimated from 6-h urinary urea excretion.

Compared with placebo, oral citrulline supplementation increased plasma citrulline, arginine and ornithine concentrations, but failed to affect albumin, transthyretin, free insulin and insulin-like growth factor (IGF)-1 plasma concentrations, urinary nitrate excretion, or nitrogen balance. Citrulline supplementation did not alter leucine Ra, leucine oxidation, nor whole-body protein synthesis. In healthy, well nourished volunteers, oral citrulline increases plasma citrulline and arginine availability but does not affect whole-body protein kinetics in the post-absorptive state. 

 

 Parenteral administration of L-arginine enhances fetal survival and growth in sheep carrying multiple fetuses.

JOURNAL: J Nutr. 2011 May;141(5):849-55. Epub 2011 Mar 23.

AUTHORS: Lassala A, Bazer FW, Cudd TA, Datta S, Keisler DH, Satterfield MC, Spencer TE, Wu G.

AFFILIATION: Department of Animal Science, Texas A&M University, College Station, TX 77843.

ABSTRACT:
The frequency of multiple fetuses has increased in human pregnancies due to assisted reproductive technologies. This translates into a greater proportion of premature and low-birth weight infants in the United States and worldwide. In addition, improvements in sheep breeding have resulted in new breeds with increased litter size but reduced fetal survival and birth weight. Currently, there are no treatments for preventing fetal growth restriction in humans or sheep (an established model for studying human fetal physiology) carrying multiple fetuses. In this work, Booroola Rambouillet ewes (FecB+/-) with 2-4 fetuses were fed a diet providing 100% of NRC-recommended nutrient requirements. Between d 100 and 121 of gestation, ewes received an i.v. bolus injection of either saline solution or 345 μmol arginine-HCl/kg body weight 3 times daily. The arginine treatment reduced (P < 0.05) the percentage of lambs born dead by 23% while increasing (P = 0.05) the percentage of lambs born alive by 59%. The i.v. administration of arginine enhanced (P < 0.05) the birth weights of quadruplets by 23% without affecting maternal body weight. The improved pregnancy outcome was associated with an increase in maternal plasma concentrations of arginine, ornithine, cysteine, and proline, as well as a decrease in circulating levels of ammonia and β-hydroxybutyrate. These novel results indicate that parenteral administration of arginine to prolific ewes ameliorated fetal mortality and growth retardation. Our findings provide support for experiments to assess the clinical use of arginine to enhance fetal growth and survival in women gestating multiple fetuses.

 

Dose-dependent effects of leucine supplementation on preservation of muscle mass in cancer cachectic mice.

JOURNAL: Oncol Rep. 2011 Apr 18. doi: 10.3892/or.2011.1269.

AUTHORS: Peters SJ, van Helvoort A, Kegler D, Argilès JM, Luiking YC, Laviano A, van
Bergenhenegouwen J, Deutz NE, Haagsman HP, Gorselink M, van Norren K.

AFFILIATION: Advanced Medical Nutrition, Danone Research, Centre for Specialised Nutrition, Wageningen, The Netherlands.

ABSTRACT:
Cancer cachexia, which is characterized by muscle wasting, is associated with increased morbidity and mortality. Because muscle protein synthesis may be increased and protein breakdown reduced by leucine supplementation, we used the C26 tumor-bearing cachectic mouse model to assess the effects of dietary supplementation with leucine on muscle weight and the markers of muscle protein breakdown (mRNA of atrogin and murf). Male CD2F1 mice were subcutaneously inoculated with tumor cells (tumor-bearing mice; TB) or were sham injected (control; C). They were fed standard diets or diets supplemented with leucine [1  gr (TB1Leu) or 8 gr (TB8Leu) supplemented leucine per kg feed]; TB and C received

8.7% Leu/g protein, TB1Leu received 9.6% Leu/g protein and TB8Leu received 14.6 Leu/g protein. After 21 days, the following were determined: body weights, plasma amino-acid concentrations, tumor size and muscle mass of the gastrocnemius (mG),  tibialis anterior (mTA), extensor digitorum longus (mEDL) and soleus (mS) muscles. In tumor-bearing (TB) mice, carcass and skeletal muscle masses decreased, and levels of atrogin and murf mRNA in the mEDL increased. Muscle-mass loss was counteracted dose-dependently by leucine supplementation: relative to TB, the mass of the mG was +23% in TB8Leu, and +22% in mTA (p<0.05). However, leucine supplementation did not change atrogin and murf mRNA levels. Total plasma amino acid concentrations increased in TB, especially for taurine, lysine, arginine and alanine (p<0.05). Leucine supplementation attenuated the increase in total plasma amino-acid concentrations (p<0.05). Irrespective of changes in muscle protein breakdown markers, leucine supplementation reduced muscle wasting  in tumor-bearing cachectic mice and attenuated changes in plasma amino acids. 

Branched-chain amino acid supplementation before squat exercise and delayed-onset muscle soreness.
JOURNAL: Int J Sport Nutr Exerc Metab. 2010 Jun;20(3):236-44.
AUTHORS: Shimomura Y, Inaguma A, Watanabe S, Yamamoto Y, Muramatsu Y, Bajotto G, Sato J, Shimomura N, Kobayashi H, Mawatari K.
AFFILIATION: Dept. of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
ABSTRACT:   
The authors examined the effect of branched-chain amino acid (BCAA) supplementation on squat-exercise-induced delayed-onset muscle soreness (DOMS) using 12 young, healthy, untrained female participants. The experiment was conducted with a crossover double-blind design. In the morning on the exercise-session day, the participants ingested either BCAA (isoleucine:leucine:valine = 1:2.3:1.2) or dextrin at 100 mg/kg body weight before the squat exercise, which consisted of 7 sets of 20 squats/set with 3-min intervals between sets. DOMS showed a peak on Days 2 and 3 in both trials, but the level of soreness was significantly lower in the BCAA trial than in the placebo. Leg-muscle force during maximal voluntary isometric contractions was measured 2 d after exercise (Day 3), and the BCAA supplementation suppressed the muscle-force decrease (to ~80% of the value recorded under the control conditions) observed in the placebo trial. Plasma BCAA concentrations, which decreased after exercise in the placebo trial, were markedly elevated during the 2 hr postexercise in the BCAA trial. Serum myoglobin concentration was increased by exercise in the placebo but not in the BCAA trial. The concentration of plasma elastase as an index of neutrophil activation appeared to increase after the squat exercise in both trials, but the change in the elastase level was significant only in the placebo trial. These results suggest that muscle damage may be suppressed by BCAA supplementation.  

 

Amino acid composition in parenteral nutrition: what is the evidence?
JOURNAL: Curr Opin Clin Nutr Metab Care. 2010 Oct 30. [E-pub ahead of print]
AUTHORS: Yarandi SS, Zhao VM, Hebbar G, Ziegler TR.
AFFILIATION: Department of Medicine, Emory University School of Medicine, USA; Nutrition and Metabolic Support Service, Emory University Hospital, Emory University, Atlanta, Georgia, USA.
ABSTRACT:
PURPOSE OF REVIEW: Complete parenteral nutrition solutions contain mixed amino acid products providing all nine essential amino acids and a varying composition of nonessential amino acids. Relatively little rigorous comparative efficacy research on altered parenteral nutrition amino acid composition has been published in recent years.

RECENT FINDINGS: Limited data from randomized, double-blind, adequately powered clinical trials to define optimal doses of total or individual amino acids in parenteral nutrition are available. An exception is the growing number of studies on the efficacy of glutamine supplementation of parenteral nutrition or given as a single parenteral agent. Parenteral glutamine appears to confer benefit in selected patients; however, additional data to define optimal glutamine dosing and the patient subgroups who may most benefit from this amino acid are needed. Although some promising studies have been published, little data are available in the current era of nutrition support on the clinical efficacy of altered doses of arginine, branched chain amino acids, cysteine, or taurine supplementation of parenteral nutrition.

SUMMARY: Despite routine use of parenteral nutrition, surprisingly little clinical efficacy data are available to guide total or specific amino acid dosing in adult and pediatric patients requiring this therapy. This warrants increased attention by the research community and funding agencies to better define optimal amino acid administration strategies in patient subgroups requiring parenteral nutrition. 

 

Effect of lysine supplementation on health and morbidity in subjects belonging to poor peri-urban households in Accra, Ghana.

JOURNAL: Am J Clin Nutr. 2010 Oct;92(4):928-39
AUTHORS: Ghosh S, Smriga M, Vuvor F, Suri D, Mohammed H, Armah SM, Scrimshaw NS.
AFFILIATION: Nevin Scrimshaw International Nutrition Foundation, Boston, MA02111, USA; Ajinomoto Europe SAS, Paris, France; University of Ghana, Accra, Ghana

ABSTRACT:

BACKGROUND: Lysine affects diarrhea and anxiety via effects on serotonin receptors, enhanced intestinal repair, and sodium chloride-dependent opioid peptide transport.

OBJECTIVE: The objective was to investigate the effects of lysine supplementation on morbidity, growth, and anxiety in children and adults of peri-urban areas of Accra, Ghana.

DESIGN: In a double-blind randomized trial, the effect of lysine supplementation (1 g lysine/d) compared with that of placebo was examined in 2 groups of men, women, and children (n = 271). Primary outcomes included diarrheal and respiratory morbidity, growth, and anxiety and complement C3, C-reactive protein, serum cortisol, transferrin, and ferritin values. Independent-sample t tests, odds ratios, generalized estimating equations, 4-parameter sinusoid regression, and generalized linear models were used.

RESULTS: Thirty percent of men, 50% of women, and 15% of children were at risk of lysine inadequacy. Supplementation in children reduced diarrheal episodes [19 lysine, 35 placebo; odds ratio (OR): 0.52; 95% CI: 0.29, 0.92; P = 0.046] and the total number of days ill (21 lysine, 47 placebo; OR: 0.44; 95% CI: 0.26, 0.74; P = 0.034). Mean days ill per child per week (0.058 ± 0.039 lysine, 0.132 ± 0.063 placebo; P = 0.017) were negatively associated with weight gain with control for baseline weight and study group (P = 0.04). Men had fewer coryza episodes (23 lysine, 39 placebo; OR: 0.60; 95% CI: 0.36, 1.01; P = 0.05), total number of days ill (lysine: 130; placebo: 266; OR: 0.51; 95% CI: 0.28, 0.93; P = 0.03), and mean days ill per person per week (lysine: 0.21 ± 0.23; placebo: 0.41 ± 0.35; P = 0.04). Serum ferritin (P = 0.045) and C-reactive protein (P = 0.018) decreased in lysine-supplemented women but increased in placebo-supplemented women.

CONCLUSION: Lysine supplementation reduced diarrheal morbidity in children and respiratory morbidity in men in Ghana.

Image previewImage preview Small children in several developing regions with low intake of dietary lysine are the potential benefactors from long-term lysine food fortification