N-3 Fatty Acid Supplementation Impacts Protein Metabolism Faster Than it Lowers Proinflammatory Cytokines in Advanced Breast Cancer Patients: Natural 15N/14N Variations during a Clinical Trial.

While clinical evidence remains limited, an extensive amount of research suggests a beneficial role of n-3 polyunsaturated fatty acid supplementation in cancer treatment. One potential benefit is an improvement of protein homeostasis, but how protein metabolism depends on proinflammatory cytokines in this context remains unclear. Here, using the natural abundance of the stable isotopes of nitrogen as a marker of changes in protein metabolism during a randomized, double-blind, controlled clinical trial, we show that protein homeostasis is affected way faster than proinflammatory cytokines in metastatic breast cancer patients supplemented with n-3 polyunsaturated fatty acids. We provide some evidence that this response is unrelated to major changes in whole-body substrate oxidation. In addition, we demonstrate that more fatty acids were impacted by metabolic regulations than by differences in their intake levels during the supplementation. This study documents that the percentage of patients that complied with the supplementation decreased with time, making compliance assessment crucial for the kinetic analysis of the metabolic and inflammatory responses. Our results highlight the time-dependent nature of metabolic and inflammatory changes during long-chain n-3 fatty acid supplementation.

Clinical Nutrition and Human Rights. An International Position Paper.

The International Working Group for Patients' Right to Nutritional Care presents its position paper regarding nutritional care as a human right intrinsically linked to the right to food and the right to health. All people should have access to food and evidence-based medical nutrition therapy including artificial nutrition and hydration. In this regard, the hospitalized malnourished ill should mandatorily have access to screening, diagnosis, nutritional assessment, with optimal and timely nutritional therapy in order to overcome malnutrition associated morbidity and mortality, while reducing the rates of disease-related malnutrition. This right does not imply there is an obligation to feed all patients at any stage of life and at any cost. On the contrary, this right implies, from an ethical point of view, that the best decision for the patient must be taken and this may include, under certain circumstances, the decision not to feed. Application of the human rights-based approach to the field of clinical nutrition will contribute to the construction of a moral, political, and legal focus to the concept of nutritional care. Moreover, it will be the cornerstone to the rationale of political and legal instruments in the field of clinical nutrition.

Clinical nutrition and human rights. An international position paper.

The International Working Group for Patients' Right to Nutritional Care presents its position paper regarding nutritional care as a human right intrinsically linked to the right to food and the right to health. All people should have access to food and evidence-based medical nutrition therapy including artificial nutrition and hydration. In this regard, the hospitalized malnourished ill should mandatorily have access to screening, diagnosis, nutritional assessment, with optimal and timely nutritional therapy in order to overcome malnutrition associated morbidity and mortality, while reducing the rates of disease-related malnutrition. This right does not imply there is an obligation to feed all patients at any stage of life and at any cost. On the contrary, this right implies, from an ethical point of view, that the best decision for the patient must be taken and this may include, under certain circumstances, the decision not to feed. Application of the human rights-based approach to the field of clinical nutrition will contribute to the construction of a moral, political and legal focus to the concept of nutritional care. Moreover, it will be the cornerstone to the rationale of political and legal instruments in the field of clinical nutrition.

Religious dietary rules and their potential nutritional and health consequences.

BACKGROUND: The vast majority of the world population declares affiliation to a religion, predominantly Christianity and Islam. Many religions have special dietary rules, which may be more or less strictly adhered to. METHODS: Religious food rules were collected from holy books and religious websites as well as their translation into dietary practices. The literature was searched for potential associations between these rules and potential nutritional consequences. RESULTS: Jewish, Islamic and Indian religions support prolonged breastfeeding. Religious avoidance of alcohol is probably beneficial to health. When strictly applied, a few rules may lead to nutritional inadequacies, mainly in populations living in unfavourable socio-economic or environmental conditions. In Jewish and Muslim observants, animal slaughtering procedures may increase the risk of iron deficiency. Jews may be at risk of excess sodium intake related to home-prepared foods. A vegan diet, as observed by some believers, often by drifting from original precepts, or by some Hindus or Buddhists, may result in vitamin B12, calcium, iron, zinc, selenium and n-3 fatty acids deficiencies. CONCLUSION: When implemented in accordance with the rules, most religious food precepts are not detrimental to health, as suggested by the fact that they have more or less been followed for millennia. Nevertheless, some practices may lead to nutritional inadequacies, such as iron, calcium, vitamin D and vitamin B12 deficiencies. Patients with low socio-economic status, children and women of childbearing age are of particular risk of such deficiencies. Being aware of them should help health professionals to take an individualized approach to decide whether to supplement or not.

Role of Young Child Formulae and Supplements to Ensure Nutritional Adequacy in U.K. Young Children.

The European Food Safety Authority (EFSA) states that young child formulae (YCFs) "cannot be considered as a necessity to satisfy the nutritional requirements" of children aged 12-36 months. This study quantifies the dietary changes needed to ensure nutritional adequacy in U.K. young children who consume YCFs and/or supplements and in those who do not. Dietary data from 1147 young children (aged 12-18 months) were used to identify, using linear programming models, the minimum changes needed to ensure nutritional adequacy: (i) by changing the quantities of foods initially consumed by each child (repertoire-foods); and (ii) by introducing new foods (non-repertoire-foods). Most of the children consumed neither YCFs, nor supplements (61.6%). Nutritional adequacy with repertoire-foods alone was ensured for only one child in this group, against 74.4% of the children consuming YCFs and supplement. When access to all foods was allowed, smaller food changes were required when YCFs and supplements were initially consumed than when they were not. In the total sample, the main dietary shifts needed to ensure nutritional adequacy were an increase in YCF and a decrease in cow's milk (+226 g/day and -181 g/day, respectively). Increasing YCF and supplement consumption was the shortest way to cover the EFSA nutrient requirements of U.K. children.

Effect of glutamine on glucose metabolism in children with Duchenne muscular dystrophy.

BACKGROUND & AIMS: Glutamine is a potent gluconeogenic precursor and stimulates insulin secretion. Glutamine's effect on glucose metabolism in Duchenne muscular dystrophy (DMD) has never been studied. To determine plasma glucose and insulin concentrations measured during and after glutamine administration in DMD boys. We hypothesized that glutamine can modulate whole body glutamine-glucose metabolism in DMD, a genetically determined disease. METHODS: As secondary endpoints of a randomized crossover trial in 30 prepubertal DMD boys, we measured fasting blood glucose, insulin and the Homeostasis Model Assessment (HOMA) index after daily oral glutamine (0.5 g kg(-1) d(-1)) for 4 months versus placebo. In a separate time series trial in 6 prepubertal DMD boys, we measured the same endpoints as well as plasma glutamine and whole body glucose turnover (Ra,glc) (primed continuous i.v. infusion of d-[6,6-(2)D]glucose), while participants received acute oral glutamine (0.5 g kg(-1) d(-1)) continuously for 5 h. RESULTS: In the randomized trial, baseline measurements of HOMA correlated with age (r = 0,51, p = 0.007) and percent fat estimated by bioelectrical impedance analysis (BIA) (r = 0.39, p = 0.047). After 4 months glutamine supplementation, we observed no treatment or order effect on HOMA or insulin. During acute glutamine for 5 h (time series trial), plasma glutamine doubled and was associated with increased plasma insulin concentration (10.42 ± 2.54 vs 7.32 ± 1.86, p = 0.05) with no effect on plasma glucose, HOMA or Ra,glc. CONCLUSIONS: Acute glutamine transiently stimulates insulin secretion in DMD boys, which could be mediated by plasma glutamine concentrations. Fasting insulin concentration and HOMA might provide quantifiable indices of disease progression.

Glutamine supplementation in sick children: is it beneficial?

The purpose of this review is to provide a critical appraisal of the literature on Glutamine (Gln) supplementation in various conditions or illnesses that affect children, from neonates to adolescents. First, a general overview of the proposed mechanisms for the beneficial effects of Gln is provided, and subsequently clinical studies are discussed. Despite safety, studies are conflicting, partly due to different effects of enteral and parenteral Gln supplementation. Further insufficient evidence is available on the benefits of Gln supplementation in pediatric patients. This includes premature infants, infants with gastrointestinal disease, children with Crohn's disease, short bowel syndrome, malnutrition/diarrhea, cancer, severe burns/trauma, Duchenne muscular dystrophy, sickle cell anemia, cystic fibrosis, and type 1 diabetes. Moreover, methodological issues have been noted in some studies. Further mechanistic data is needed along with large randomized controlled trials in select populations of sick children, who may eventually benefit from supplemental Gln.

Lack of functional benefit with glutamine versus placebo in Duchenne muscular dystrophy: a randomized crossover trial.

BACKGROUND: Oral glutamine decreases whole body protein breakdown in Duchenne muscular dystrophy (DMD). We evaluated the functional benefit of 4 months oral glutamine in DMD. METHODOLOGY/PRINCIPAL FINDINGS: 30 ambulant DMD boys were included in this double-blind, randomized crossover trial with 2 intervention periods: glutamine (0.5 g/kg/d) and placebo, 4 months each, separated by a 1-month wash-out, at 3 outpatient clinical investigation centers in France. Functional benefit was tested by comparing glutamine versus placebo on change in walking speed at 4 months. Secondary outcome measures were: 2-minute walk test, work, power, muscle mass (urinary creatinine), markers of myofibrillar protein breakdown (urinary 3-methyl-histidine/creatinine), serum creatine phospho-kinase, body composition (fat free mass, fat mass percentage), safety and oral nutrient intake. There was no improvement in the primary end point (walking speed) or in secondary measures of muscle function (2-minute walk test, work, power) in the glutamine group compared with placebo. However, subjects receiving glutamine or placebo showed no deterioration in functional measures over the course of the 9-month trial. No differences in muscle mass, markers of protein breakdown or serum creatine phosho-kinase were observed, except for a blunted increase in fat free mass in the glutamine group which led to a greater increase in fat mass percentage. Glutamine was safe and well-tolerated. CONCLUSIONS: This trial did not identify additional benefit of 4 months oral glutamine over placebo on muscle mass or function in ambulatory DMD boys. Although apparently safe, current data cannot support routine supplementation in this population as a whole, until further research proves otherwise. TRIAL REGISTRATION: (ClinicalTrials.gov) NCT00296621.

l-Glutamine administration reduces oxidized glutathione and MAP kinase signaling in dystrophic muscle of mdx mice.

To determine whether glutamine (Gln) reduces the ratio of oxidized to total glutathione (GSSG/GSH) and extracellular signal-regulated kinase (ERK1/2) activation in dystrophic muscle. Four-week old mdx mice, an animal model for Duchenne muscular dystrophy and control (C57BL/10) received daily intraperitoneal injections of l-Gln (500 mg/kg/d) or 0.9% NaCl for 3 d. GSH and GSSG concentrations in gastrocnemius were measured using a standard enzymatic recycling procedure. Free amino acid concentrations in gastrocnemius were determined by ion exchange chromatography. Phosphorylated protein levels of ERK1/2 in quadriceps were examined using Western Blot. l-Gln decreased GSSG and GSSG/GSH (an indicator of oxidative stress). This was associated with decreased ERK1/2 phosphorylation. Muscle free Gln, glutamate (Glu), and the sum (Gln + Glu) were higher in mdx versus C57BL/10, at the basal level. Exogenous Gln decreased muscle free Glu and Gln + Glu in mdx only, whereas Gln was not affected. In conclusion, exogenous Gln reduces GSSG/GSH and ERK1/2 activation in dystrophic skeletal muscle of young mdx mice, which is associated with decreased muscle free Glu and Gln + Glu. This antioxidant protective mechanism provides a molecular basis for Gln's antiproteolytic effect in Duchenne muscular dystrophy children.

Oral glutamine and amino acid supplementation inhibit whole-body protein degradation in children with Duchenne muscular dystrophy.

BACKGROUND: Glutamine has been shown to acutely decrease whole-body protein degradation in Duchenne muscular dystrophy (DMD). OBJECTIVE: To improve nutritional support in DMD, we tested whether oral supplementation with glutamine for 10 d decreased whole-body protein degradation significantly more than did an isonitrogenous amino acid control mixture. DESIGN: Twenty-six boys with DMD were included in this randomized, double-blind parallel study; they received an oral supplement of either glutamine (0.5 g . kg(-1) . d(-1)) or an isonitrogenous, nonspecific amino acid mixture (0.8 g . kg(-1) . d(-1)) for 10 d. The subjects in each group were not clinically different at entry. Leucine and glutamine metabolisms were estimated in the postabsorptive state by using a primed continuous intravenous infusion of [1-(13)C]leucine and [2-(15)N]glutamine before and 10 d after supplementation. RESULTS: A significant effect of time was observed on estimates of whole-body protein degradation. A significant (P < 0.05) decrease in the rate of leucine appearance (an index of whole-body protein degradation) was observed after both glutamine and isonitrogenous amino acid supplementation [x +/-SEM: 136 +/- 9 to 124 +/- 6 micromol . kg fat-free mass (FFM)(-1) . h(-1) for glutamine and 136 +/- 6 to 131 +/- 8 micromol . kg FFM(-1) . h(-1) for amino acids]. A significant (P < 0.05) decrease in endogenous glutamine due to protein breakdown was also observed (91 +/- 6 to 83 +/- 4 micromol . kg FFM(-1) . h(-1) for glutamine and 91 +/- 4 to 88 +/- 5 micromol . kg FFM(-1) . h(-1) for amino acids). The decrease in the estimates of whole-body protein degradation did not differ significantly between the 2 supplemental groups. CONCLUSION: Oral glutamine or amino acid supplementation over 10 d equally inhibits whole-body protein degradation in DMD.

Nutrition and growth in cystic fibrosis.

Malnutrition is a common complication of chronic diseases in children and may lead to growth impairment (stunting). Malnutrition in cystic fibrosis (CF) results from increased energy expenditure, decreased energy intakes, malabsorption of ingested nutrients because of pancreatic insufficiency and chronic inflammation. Malnutrition and high levels of inflammatory cytokines affect IGF-1 production through interrelated mechanisms. Nutritional support was shown to improve both nutritional status and outcome in CF. However, some nutrients have a direct effect on the disease. n-3 fatty acids supplementation is able to correct lipid abnormalities resulting from a primary mechanism. Moreover, n-3 fatty acids have a direct effect on the inflammatory response, decreasing eicosanoid synthesis and modulating nuclear transcriptional factors nuclear factor kappaB and peroxisome proliferator-activated receptors gamma. Nutritional support may be considered part of the care of the CF patient together with antibiotics, pancreatic enzymes and physiotherapy, influencing significantly the evolution of the disease.