1.
From mitochondria to healthy aging: The role of branched-chain amino acids treatment: MATeR a randomized study.
Buondonno, I, Sassi, F, Carignano, G, Dutto, F, Ferreri, C, Pili, FG, Massaia, M, Nisoli, E, Ruocco, C, Porrino, P, et al
Clinical nutrition (Edinburgh, Scotland). 2020;39(7):2080-2091
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Despite the increase in life expectancy, there is no corresponding increase in healthy life expectancy. Lifestyle changes appear to be fundamental in increasing healthy life expectancy, and adequate nutrition is enormously important, given that malnutrition (i.e., undernutrition), particularly as protein-energy deficit is very common amongst the elderly population. It has been suggested that the aging process significantly affects protein metabolism and enhances the muscle wastage that accompanies undernutrition and sarcopenia. The aim of this study was to evaluate the efficacy of a specific branched-chain amino acids enriched mixtures (BCAAem) compared to diet advice to promote mitochondrial function and improve clinical outcomes, particularly muscle and cognitive performance, in malnourished elderly community-dwelling subjects. This study is a parallel, randomised, controlled, open-label trial. One hundred and fifty-five malnourished elderly patients were enrolled. The participants were randomly assigned to one of the two groups: diet advice, summarised in an easy-to-use brochure for lay persons or BCAAem supplements. Results show that amelioration of nutritional status is associated with improvement in general health status, muscle and cognitive performances in old, malnourished patients. In fact, the diagnosis of malnutrition and its treatment, albeit using different approaches, is fundamental in improving the patients’ general health and nutritional status. Authors conclude that BCAAem treatment in old, malnourished patients may be a good strategy to ameliorate the bioenergetic capacity of peripheral blood mononuclear cells.
Abstract
RATIONALE Malnutrition often affects elderly patients and significantly contributes to the reduction in healthy life expectancy, causing high morbidity and mortality. In particular, protein malnutrition is one of the determinants of frailty and sarcopenia in elderly people. METHODS To investigate the role of amino acid supplementation in senior patients we performed an open-label randomized trial and administered a particular branched-chain amino acid enriched mixture (BCAAem) or provided diet advice in 155 elderly malnourished patients. They were followed for 2 months, assessing cognitive performance by Mini Mental State Examination (MMSE), muscle mass measured by anthropometry, strength measure by hand grip and performance measured by the Timed Up and Go (TUG) test, the 30 s Chair Sit to Stand (30-s CST) test and the 4 m gait speed test. Moreover we measured oxidative stress in plasma and mitochondrial production of ATP and electron flux in peripheral blood mononuclear cells. RESULTS Both groups improved in nutritional status, general health and muscle mass, strength and performance; treatment with BCAAem supplementation was more effective than simple diet advice in increasing MMSE (1.2 increase versus 0.2, p = 0.0171), ATP production (0.43 increase versus -0.1, p = 0.0001), electron flux (0.50 increase versus 0.01, p < 0.0001) and in maintaining low oxidative stress. The amelioration of clinical parameters as MMSE, balance, four meter walking test were associated to increased mitochondrial function. CONCLUSIONS Overall, our findings show that sustaining nutritional support might be clinically relevant in increasing physical performance in elderly malnourished patients and that the use of specific BCAAem might ameliorate also cognitive performance thanks to an amelioration of mitochondria bioenergetics.
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Insulin-like growth factor I response during nutritional rehabilitation of persistent diarrhoea.
Bhutta, ZA, Bang, P, Karlsson, E, Hagenäs, L, Nizami, SQ, Söder, O
Archives of disease in childhood. 1999;80(5):438-42
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Persistent diarrhoea in childhood causes severe malnutrition, and morbidity in 15%+ cases. Treatment includes nutritional rehabilitation for weight gain and diarrheal recovery. This study evaluates nutritional recovery (defined as weight gain (> 5 g/kg/day) with a resolution of diarrhea by day 7 of treatment), intestinal permeability and insulin-like growth factor I (IGF-I) response in malnourished children with faltering growth (aged 6-36 months) with persistent diarrhoea ((>/= 14 days) and their relation to concomitant systemic infection(s) (as indicated by serum C reactive protein (CRP)). For a minimum of 7 days, 63 children were fed a previously validated dietary regimen (data not available) of rice–lentil (khitchri) and yogurt aimed at providing at least 100 kcal/kg/day by day 3, with ad libitum feeds thereafter. Children were nursed on a research ward throughout. 49 children were treatment successes. They had a significant increase in serum IGF-I and IGF-I% correlated with weight gain. 14 children did not meet the criteria for nutritional recovery. They had higher serum CRP concentrations and sepsis at admission. They had lower mean (SD) weight gain in spite of overall mean energy intake being comparable with treatment successes. This may indicate malabsoption. Admission CRP concentration and IGF-I were negatively correlated. CRP concentrations at admission and corresponding individual IGF-I values over the 7 days treatment were significantly correlated. Significantly raised CRP concentrations in children with a correspondingly low IGF-I response may indicate a continued inflammatory or infected state in these children. Small but opposing trends of urinary excretion of the oral lactulose dose were seen in both groups over the seven days of treatment, indicating worsening enteropathy (mucosal injury) among treatment failures. None of the permeability parameters correlated with IGF-I at baseline or recovery. The study confirms that a traditional rice–lentil (khitchri) and yogurt diet can be used successfully for enteral nutritional rehabilitation in malnourished children with persistent diarrhoea and leads to adequate weight gain; Serum IGF-I levels correlates closely with weight gain and reduction in stool output; recovery is delayed with sepsis and raised blood CRP concentrations at admission; IGF-I is depressed at admission in children with persistent diarrhoea. The data provide evidence that serum IGF-I response in recovering malnourished children with persistent diarrhoea may provide a sensitive measure of nutritional and diarrhoeal recovery. Further studies are needed to evaluate factors regulating the IGF-I response in such children, especially the effect of intercurrent infections. Arbitrary definition of treatment failure is a study limitation.
Abstract
OBJECTIVE Evaluation of nutritional recovery, intestinal permeability, and insulin-like growth factor I (IGF-I) response in malnourished children with persistent diarrhoea and their relation to concomitant systemic infection(s). STUDY DESIGN Open study of severely malnourished children (aged 6-36 months) with persistent diarrhoea (≥ 14 days) admitted for nutritional rehabilitation with a standardised rice-lentil and yogurt diet. Successful recovery was defined prospectively as overall weight gain (> 5 g/kg/day) with a reduction in stool output by day 7 of treatment. Data on coexisting infections and serum C reactive protein (CRP) were collected at admission. RESULTS Of 63 children, 48 (group A) recovered within seven days of dietary treatment. These children had a significant increase in serum IGF-I (DeltaIGF-I%) and, in contrast to serum prealbumin and retinol binding protein, DeltaIGF-I% correlated with weight gain (r = 0.41). There was no correlation between the IGF-I response and intestinal permeability as assessed by urinary lactulose/rhamnose excretion. Treatment failures (group B) included more children with clinical (relative risk, 4.8; 95% confidence interval, 1.2 to 19.7) and culture proven sepsis at admission and higher concentrations of serum CRP (median (range), 36 (0-182) v 10 (0-240) mg/l) at admission. There was a negative correlation between admission CRP concentration and DeltaIGF-I% (r = -0.45). CONCLUSIONS In comparison with serum albumin, prealbumin, and retinol binding protein, serum IGF-I increment is a better marker of nutritional recovery in malnourished children with persistent diarrhoea. The possible association of systemic infections, serum IGF-I response, and mucosal recovery needs evaluation in future studies.