Defining malnutrition: a plea to rethink

In a recent consensus report in Clinical Nutrition the undernourished category of malnutrition was proposed to be defined and diagnosed on the basis of a low BMI or unintentional weight loss combined with low BMI or FFMI with certain cut off points. The definition was endorsed by ESPEN despite recent endorsement of a very different definition. The approach aims to assess whether nutritional intake is sufficient but is imprecise because a low BMI does not always indicate malnutrition and individuals with increasing BMI's may have decreasing FFM's. The pathophysiology of individuals, considered to be malnourished in rich countries and in areas with endemic malnutrition, results predominantly from deficient nutrition combined with infection/inflammation. Both elements jointly determine body composition and function and consequently outcome of disease, trauma or treatment. When following the consensus statement only an imprecise estimate is acquired of nutritional intake without knowing the impact of inflammation. Most importantly, functional abilities are not assessed. Consequently it will remain uncertain how well the individual can overcome stressful events, what the causes are of dysfunction, how to set priorities for treatment and how to predict the effect of nutritional support. We therefore advise to consider the pathophysiology of malnourished individuals leading to inclusion of the following elements in the definition of malnutrition: a disordered nutritional state resulting from a combination of inflammation and a negative nutrient balance, leading to changes in body composition, function and outcome. A precise diagnosis of malnutrition should be based on assessment of these element

Prognostic value of simple frailty and malnutrition screening tools in patients with acute heart failure due to left ventricular systolic dysfunction

Background: Frailty and malnutrition are common in patients with heart failure (HF), and are associated with adverse outcomes. We studied the prognostic value of three malnutrition and three frailty indices in patients admitted acutely to hospital with HF. Methods: 265 consecutive patients [62% males, median age 80 (interquartile range (IQR): 72–86) years, median NTproBNP 3633 (IQR: 2025–6407) ng/l] admitted with HF between 2013 and 2014 were enrolled. Patients were screened for frailty using the Derby frailty index (DFI), acute frailty network (AFN) frailty criteria, and clinical frailty scale (CFS) and for malnutrition using the geriatric nutritional risk index (GNRI), controlling nutritional status (CONUT) score and prognostic nutritional index (PNI). Results: According to the CFS (> 4), DFI, and AFN, 53, 50, and 53% were frail, respectively. According to the GNRI (≤ 98), CONUT score (> 4), and PNI (≤ 38), 46, 46, and 42% patients were malnourished, respectively. During a median follow-up of 598 days (IQR 319–807 days), 113 patients died. One year mortality was 1% for those who were neither frail nor malnourished; 15% for those who were either malnourished or frail; and 65% for those who were both malnourished and frail. Amongst the malnutrition scores, PNI, and amongst the frailty scores, CFS increased model performance most compared with base model. A final model, including CFS and PNI, increased c-statistic for mortality prediction from 0.68 to 0.84. Conclusion: Worsening frailty and malnutrition indices are strongly related to worse outcome in patients hospitalised with HF

Features, Causes and Consequences of Splanchnic Sequestration of Amino Acid in Old Rats

RATIONALE: In elderly subjects, splanchnic extraction of amino acids (AA) increases during meals in a process known as splanchnic sequestration of amino acids (SSAA). This process potentially contributes to the age-related progressive decline in muscle mass via reduced peripheral availability of dietary AA. SSAA mechanisms are unknown but may involve an increased net utilization of ingested AA in the splanchnic area. OBJECTIVES: Using stable isotope methodology in fed adult and old rats to provide insight into age-related SSAA using three hypotheses: 1) an increase in protein synthesis in the gut and/or the liver, 2) an increase in AA oxidation related to an increased ureagenesis, and 3) Kupffer cell (KC) activation consequently to age-related low-grade inflammation. FINDINGS: Splanchnic extraction of Leu (SPELeu) was doubled in old rats compared to adult rats and was not changed after KC inactivation. No age-related effects on gut and liver protein synthesis were observed, but urea synthesis was lower in old rats and negatively correlated to liver Arg utilization. Net whole-body protein synthesis and arterial AA levels were lower in old rats and correlated negatively with SPELeu. CONCLUSION: SSAA is not the consequence of age-related alterations in ureagenesis, gut or liver protein synthesis or of KC activity. However, SSAA may be related to reduced net whole-body protein synthesis and consequently to the reduced lean body mass that occurs during aging

Is glutamine the cornerstone of sarcopenia in very old individuals ?

National audienceIntroduction: Glutamine is the most abundant free amino acid in the body and has its primary source in skeletal muscle, from where it is released into the bloodstream and transported to a variety of tissues such the gut. The size of the muscle glutamine pool may be related to lean body mass and so, to sarcopenia Objectives: Because glutamine is known to have a specific role in very old rats (up to 25 months of age), the aim of this study is to demonstrate that glutamine is the cornerstone of sarcopenia with advanced age. For this reason, we have orally supplemented female rats (27 months) with glutamine (20% of diet protein) intermittently, before animals became very old (named long-term treatment with glutamine). Rats were studied after the last glutamine cure Material and methods: Skeletal muscle (tibialis anterior) and gut were dissected and weighed. A 2-cm length of the proximal part of the jejunum was removed for measurements of intestinal histomorphometry Results: Muscle mass decreased by ~ 20 % with advanced age. No difference was observed in skeletal muscle mass with glutamine supplementation. However, glutamine synthesis was enhanced in skeletal muscle from very old female rat as previously reported. Glutamine played a role in maintaining mass of splanchnic tissues. Total intestine mass was significantly higher in glutamine supplemented very old rats than in controls (~15%). By histomorphometry, we demonstrated that villus height increased with glutamine supplementation in very old female rats; this increase was similar to that measured in gut mass Discussion: Long-term treatment with glutamine had positive effects on very old rats: 1) it prevented the loss of body weight, but, 2) it did not prevent the inevitable sarcopenia because of its inefficiency to limit the loss of muscle mass due to aging and, 3) it maintained or improved the gut mass. Long-term treatment with glutamine essentially played a role in maintaining intestine integrity and intestinal immune function. Indeed, villus height was improved by this treatment Consequently, the observed increase in glutamine requirements can be explained by the increased use of glutamine by the gut. Glutamine may play a role in repairing possible gut mucosal deterioration due to aging by increasing mucosal protein synthesis and decreasing ubiquitin-dependent proteolysis, as previously reported in healthy humans. Conclusion: Glutamine is not the cornerstone of sarcopenia in very old individuals even if a very high synthesis capacity is maintained in aging atrophied-muscl

Long-term intermittent glutamine supplementation repairs intestinal damage (structure and functional mass) with advanced age: Assessment with plasma citrulline in a rodent model

International audienceGlutamine is the preferred fuel for the rat small intestine and promotes the growth of intestinal mucosa, especially in the event of gut injury. Quantitatively, glutamine is one important precursor for intestinal citrulline release. The aim of this study was to determine whether the effect of glutamine on the increase in intestinal villus height is correlated with an increase in both gut mass and citrulline plasma level in very old rats. We intermittently supplemented very old (27-mo) female rats with oral glutamine (20% of diet protein). Intestinal histomorphometric analysis of the small bowel was performed. Amino acids, in particular citrulline, were measured in the plasma, liver and jejunum. Markers of renal (creatinine, urea) and liver (alanine aminotransferase [ALT]) and aspartate aminotransferase (AST) functions were measured to evaluate renal and liver functions in relation to aging and to glutamine supplementation. Liver glutathione was also determined to evaluate cellular redox state. Glutamine supplementation maintains the body weight of very old rats, not by limiting sarcopenia but rather by increasing the organ mass of the splanchnic area. Total intestine mass was significantly higher in glutamine-supplemented rats than in controls (15%). Measurement of villus height and crypt depth demonstrated that the difference between villus and crypt was significantly improved in glutamine pre-treated rats compared to controls (similar to 11%). Plasma citrulline also increased by 15% in glutamine-supplemented rats compared to controls. Citrulline appears as a biomarker of enterocyte mass in villous atrophy associated with advanced age. Non-invasive measurement of this metabolite may be useful in following the state of the gastrointestinal tract in very old people, whose numbers are increasing worldwide and the care of whom is a major public health issue. The gut may contribute to the malnutrition caused by malabsorption frequently observed in the elderly