New insights into the anorexia of ageing: from prevention to treatment.

PURPOSE OF REVIEW: Undernutrition in older adults is associated with frailty, functional decline, and mortality. The 'anorexia of ageing' is the age-related appetite and weight loss underpinning such undernutrition. This review examines the latest evidence for its prevention and treatment. RECENT FINDINGS: Existing nutritional therapies for the anorexia of ageing include supporting nutritional intake with fortified food or supplements, including protein, omega-3 fatty acids, multivitamins, and vitamin D. The Mediterranean diet provides high fat intake and nutrient density in a moderate volume of colourful and flavoursome food and is strengthening in evidence for healthy ageing. Studies of the gut microbiome, which potentially regulates normal appetite by acting on the brain-gut communication axis, are pertinent. Utilisation of the genetic profile of individuals to determine nutritional needs is an exciting advancement of the past decade and may become common practice. SUMMARY: Prevention or early treatment of the anorexia of ageing in older adults is critical. Latest evidence suggests that once significant weight loss has occurred, aggressive nutritional support may not result in improved outcomes.

Mechanisms and treatment of cancer cachexia.

According to a recent consensus, cachexia is a complex metabolic syndrome associated with underlying illness and characterised by loss of muscle with or without loss of fat mass. The prominent clinical feature of cachexia is weight loss. Cachexia occurs in the majority of terminal cancer patients and it is responsible for the deaths of 22% of cancer patients. Although body weight is, indeed, an important factor to be taken into consideration in any cachexia treatment, body composition, physical performance and quality of life should be monitored. From the results presented here, one can speculate that a single therapy may not be completely successful in the treatment of cachexia. From this point of view, treatments involving different combinations are more likely to be successful. The objectives of any therapeutical combination are two: an anticatabolic aim directed towards both fat and muscle catabolism and an anabolic objective leading to the synthesis of macromolecules such as contractile proteins.

The use of herbal medicine in cancer-related anorexia/ cachexia treatment around the world.

Cancer-related cachexia, a condition in which the body is consumed by deranged carbohydrate, lipid and protein metabolism that is induced by inflammatory cytokines. Cachexia is associated with poor treatment outcome, fatigue and poor quality of life. Pharmacological intervention in the treatment and/or prevention of cachexia has been mainly aimed at the use of appetite enhancers to increase oral nutritional intake so far. Herbal remedies are part of traditional and folk healing methods with long histories of use. In this report, we have assessed which herbal approaches have had associated cancer cachexia case reports. Commonly used herbal medicines in western countries include essiac, iscador, pau d'arco tea, cannabinoids and so on. Some Kampo herbs and formulations are commonly used by cancer patients reduce the side effects and complications during the antitumor therapy. The relevant herbal medicines include ginseng, C. rhizome and radix astragali, and the related herbal remedies, such as TJ-48, TJ-41, PHY906 and Rikkunshito. However, there still have some adverse effects caused or amplified by herb and drug interactions that are difficult to separate. However, randomized effectiveness of herbal medicines shall be further identified in controlled clinical trials involving cancer patients with cachexia.

Decreased glutamate, glutamine and citrulline concentrations in plasma and muscle in endotoxemia cannot be reversed by glutamate or glutamine supplementation: a primary intestinal defect?

Endotoxemia affects intestinal physiology. A decrease of circulating citrulline concentration is considered as a reflection of the intestinal function. Citrulline can be produced in enterocytes notably from glutamate and glutamine. The aim of this work was to determine if glutamate, glutamine and citrulline concentrations in blood, intestine and muscle are decreased by endotoxemia, and if supplementation with glutamate or glutamine can restore normal concentrations. We induced endotoxemia in rats by an intraperitoneal injection of 0.3 mg kg(-1) lipopolysaccharide (LPS). This led to a rapid anorexia, negative nitrogen balance and a transient increase of the circulating level of IL-6 and TNF-α. When compared with the values measured in pair fed (PF) animals, almost all circulating amino acids (AA) including citrulline decreased, suggesting a decrease of intestinal function. However, at D2 after LPS injection, most circulating AA concentrations were closed to the values recorded in the PF group. At that time, among AA, only glutamate, glutamine and citrulline were decreased in gastrocnemius muscle without change in intestinal mucosa. A supplementation with 4% monosodium glutamate (MSG) or an isomolar amount of glutamine failed to restore glutamate, glutamine and citrulline concentrations in plasma and muscle. However, MSG supplementation led to an accumulation of glutamate in the intestinal mucosa. In conclusion, endotoxemia rapidly but transiently decreased the circulating concentrations of almost all AA and more durably of glutamate, glutamine and citrulline in muscle. Supplementation with glutamate or glutamine failed to restore glutamate, glutamine and citrulline concentrations in plasma and muscles. The implication of a loss of the intestinal capacity for AA absorption and/or metabolism in endotoxemia (as judged from decreased citrulline plasma concentration) for explaining such results are discussed.

Beyond anorexia -cachexia. Nutrition and modulation of cancer patients' metabolism: supplementary, complementary or alternative anti-neoplastic therapy?

Anorexia and muscle wasting are frequently observed in cancer patients and influence their clinical outcome. The better understanding of the mechanisms underlying behavioral changes and altered metabolism yielded to the development of specialized nutritional support, which enhances utilization of provided calories and proteins by counteracting some of the metabolic derangements occurring during tumor growth. Inflammation appears to be a key factor determining the cancer-associated biochemical abnormalities eventually leading to anorexia and cachexia. Interestingly, inflammation is also involved in carcinogenesis, cancer progression and metastasis by impairing immune surveillance, among other mechanisms. Therefore, nutritional interventions aiming at modulating inflammation to restore nutritional status may also result in improved response to pharmacological anti-cancer therapies. Recent clinical data show that supplementation with nutrients targeting inflammation and immune system increases response rate and survival in cancer patients. This suggests that nutrition therapy should be considered as an important adjuvant strategy in the multidimensional approach to cancer patients.

Consequences of protein supplementation for anorexia, expression of immunity and plasma leptin concentrations in parasitized ewes of two breeds.

The periparturient relaxation of immunity (PPRI) against parasites in ewes has a nutritional basis. We investigated whether ewes experience a reduction in food intake (anorexia) during PPRI and if the magnitude of anorexia is affected by host production potential and dietary protein supplementation. We also investigated whether nematode infection is linked to plasma leptin concentrations in periparturient ewes. The experiment was a 2 x 2 x 2 factorial design. Two breeds of twin-bearing/lactating ewes (Greyface cross, G (n 32) and Scottish Blackface, B (n 32)) were used. Half of the ewes were trickle infected with 30,000 larvae of the abomasal parasite Teladorsagia circumcincta per week and the other half were not. During the experiment, all ewes had ad libitum access to a low-protein diet that provided less protein than the recommended allowance. In addition, half of the ewes received a protein supplement that resulted in protein intakes that exceeded recommendations. Nematode infection resulted in a breakdown of immunity to parasites and a reduction in food intake in both breeds. The breeds differed in the extent of PPRI (G ewes having higher faecal egg counts than B ewes), but not in the magnitude of anorexia. Protein supplementation resulted in a reduction in faecal egg counts, but had no effect on the magnitude of anorexia. Plasma leptin concentrations changed significantly over time, but were not affected by protein supplementation or infection. It is concluded that infection with T. circumcincta in periparturient ewes results in anorexia that is not alleviated by protein supplementation and seems unrelated to plasma leptin concentrations.

Anorexia-cachexia syndrome: a systematic review of the role of dietary polyunsaturated Fatty acids in the management of symptoms, survival, and quality of life.

To provide a systematic review on the clinical utility of anti-inflammatory polyunsaturated fatty acids (PUFAs) in cancer-associated anorexia-cachexia syndrome (ACS), clinical trials involving eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for the management of ACS were identified in the medical literature using MEDLINE (1966 to October 2006) and EMBASE (1980 to October 2006). Review Manager 4.1 was used to compare trials based on outcome measures of interest, including weight change, lean muscle mass change, survival, and quality of life (QoL). Seven randomized controlled trials (RCTs) were identified. Various outcome measures were used in each study. Variability in study populations, dose of EPA and DHA, and standardized scales did not allow for analysis using Review Manager 4.1. Therefore, trials were summarized based on their individual outcomes. Except for one trial showing a positive effect on weight, none of the trials found a clinically or statistically significant difference in outcome measures reviewed. EPA and DHA alone have not shown significant clinical effect in altering weight, lean muscle mass, survival, or QoL in patients with ACS associated with cancer.

Criterios de intervención nutricional: objetivos, indicaciones y evidencias / No disponible

No disponible

[Use of new synbiotics in treatment of the intestinal infections among children].

The article deals with the findings of the complex estimate of the new synbiotic product "Life Harmony" to treat acute intestinal infection among children. The authors show that application of this product, containing B. bifidum, B. longum and L. casei strains, in the diet therapy of the acute intestinal infections of "the watery" type among children contributes to the reduction of the duration of anorexia, flabbiness and diarrhea syndrome, as well as provides a complete recovery of the intestinal microflora balance.

A phase II study with antioxidants, both in the diet and supplemented, pharmaconutritional support, progestagen, and anti-cyclooxygenase-2 showing efficacy and safety in patients with cancer-related anorexia/cachexia and oxidative stress.

PURPOSE: To test the efficacy and safety of an integrated treatment based on a pharmaconutritional support, antioxidants, and drugs, all given orally, in a population of advanced cancer patients with cancer-related anorexia/cachexia and oxidative stress. PATIENTS AND METHODS: An open early-phase II study was designed according to the Simon two-stage design. The integrated treatment consisted of diet with high polyphenols content (400 mg), antioxidant treatment (300 mg/d alpha-lipoic acid + 2.7 g/d carbocysteine lysine salt + 400 mg/d vitamin E + 30,000 IU/d vitamin A + 500 mg/d vitamin C), and pharmaconutritional support enriched with 2 cans per day (n-3)-PUFA (eicosapentaenoic acid and docosahexaenoic acid), 500 mg/d medroxyprogesterone acetate, and 200 mg/d selective cyclooxygenase-2 inhibitor celecoxib. The treatment duration was 4 months. The following variables were evaluated: (a) clinical (Eastern Cooperative Oncology Group performance status); (b) nutritional [lean body mass (LBM), appetite, and resting energy expenditure]; (c) laboratory [proinflammatory cytokines and leptin, reactive oxygen species (ROS) and antioxidant enzymes]; (d) quality of life (European Organization for Research and Treatment of Cancer QLQ-C30, Euro QL-5D, and MFSI-SF). RESULTS: From July 2002 to January 2005, 44 patients were enrolled. Of these, 39 completed the treatment and were assessable. Body weight increased significantly from baseline as did LBM and appetite. There was an important decrease of proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha, and a negative relationship worthy of note was only found between LBM and IL-6 changes. As for quality of life evaluation, there was a marked improvement in the European Organization for Research and Treatment of Cancer QLQ-C30, Euro QL-5D(VAS), and multidimensional fatigue symptom inventory-short form scores. At the end of the study, 22 of the 39 patients were "responders" or "high responders." The minimum required was 21; therefore, the treatment was effective and more importantly was shown to be safe. CONCLUSION: The efficacy and safety of the treatment have been shown by the study; therefore, a randomized phase III study is warranted.

Contribución del soporte nutricional a combatir la caquexia cancerosa / Contribution of nutritional support to fight cancer cachexia

Habitualmente para incrementar la ingesta de alimentos y combatir la anorexia se adoptan medidas encaminadas a controlar los síntomas que la disminuyen o a administrar los nutrientes por las vías más adecuadas a las alteraciones patológicas existentes. Sin embargo en el caso de la anorexia-caquexia que presentan los pacientes neoplásicos no siempre ello resulta tan lineal ni efectivo. El tratamiento nutritivo debería enfocarse en función de los diversos mecanismos patogénicos implicados en su desarrollo. El análisis del soporte nutricional como parte del tratamiento de estos pacientes a partir de una revisión sobe la evidencia científica pone de manifiesto que no existe ningún estudio bien diseñado que investigue el impacto de los suplementos orales en un grupo específico de pacientes y que ninguno evalúa resultados funcionales. Existe una mejoría en la ingesta energética total y en la ingesta de comida que, no obstante, a largo plazo no se mantiene. Los efectos observados sobre el peso y la composición corporal son variables y, o bien existen pocas diferencias entre los grupos suplementados y los grupos control, o son confusos por la heterogeneidad de los pacientes, los tipos de cáncer analizados y la falta de información sobre la existencia o no de edemas. Se observan algunos datos que orientan hacia una mejor respuesta inmunológica. No se han observado suficientes mejoras significativas en cambios funcionales ni en la evolución clínica. El análisis del uso de los suplementos nutritivos por vía enteral permite concluir que ello comporta incrementos en la ingesta total de nutrientes, puede ayudar a ganar peso o a reducir la pérdida el mismo y pueden comportar beneficios funcionales y de la evolución clínica pero se requieren estudios aleatorios más amplios en pacientes con distintos tipos de cáncer y distintos tratamientos antineoplásicos. A pesar de la poca disponibilidad de datos, los resultados existentes con el uso de suplementos nutricionales enriquecidos con EPA son muy prometedores. Con dosis mínimas de 2 g de EPA adicionados a los suplementos nutricionales además de aportar calorías y proteínas para cubrir las necesidades energéticas del huésped y del tumor, se contribuye a revertir las anormalidades metabólicas asociadas a la anorexia-caquexia del cáncer. Ello permite vislumbrar la posibilidad de frenar este proceso devastador de los tejidos que se observa en los pacientes neoplásicos que presentan anorexia-caquexia (AU)

To increase dietary intake and to fight anorexia several measures to treat symptoms and administer the most adequate diet according to composition, texture and flavour are proposed. However, in the anorexiacaquexia present in cancer patients not always these measures are effective. Now a day it seems more reasonable to approach this problem with different strategies directed to modulate the pathologic alterations associated. The analysis of specific nutritional support as part as the treatment of these patients from a systematic review conclude that no high methodological quality studies to analyze the impact of oral supplementation on a specific group of patients, neither the study of functional effects are done. However, an increase in the total energy intake, not maintained over the time, was observed. The effects on weight and corporal composition are variable, with small differences between groups with o without supplementation and confuse due to, mainly, the heterogeneity of the patients included in the different studies analyzed. The analysis of the effects of nutritional supplements administered by enteral feeding shown an increase in the energy intake with an increase in body weight or a lack of decrease it, and with some functional and clinical beneficial effects. Despite the results and conclusions obtained, a strong recommendation to conduct clinical trials in specific group of cancer patients with different antineoplasic treatment seems necessary. N-3 fatty acids, especially eicosapentaenoic acid may have anticachectic properties. Although further trials are necessary the limited results available suggests that nutritional supplements enriched with EPA may reverse cachexia in cancer patients (AU)

Omega-3 fatty acids and anorexia.

PURPOSE OF REVIEW: To review the mechanisms of action of omega-3 fatty acids and their role in the brain, as well as their therapeutic implications in anorexia. RECENT FINDINGS: Recent studies have demonstrated that omega-3 fatty acids modulate changes in the concentrations and actions of several orexigenic and anorexigenic neuropeptides in the brain, including neuropeptide Y, alpha-melanocyte stimulating hormone and the neurotransmitters serotonin and dopamine. In patients with acute and chronic inflammatory conditions, low tissue concentrations of omega-3 fatty acids and high concentrations of proinflammatory cytokines are found, in association with anorexia and decreased food intake. The data suggest that omega-3 fatty acid supplementation suppresses proinflammatory cytokine production and improves food intake by normalizing hypothalamic orexigenic peptides and neurotransmitters. SUMMARY: Based on current data, omega-3 fatty acid supplementation has a role in the treatment of anorexia by stimulating the production and release of orexigenic neurotransmitters in food intake regulatory nuclei in the hypothalamus.

Cancer-related anorexia/cachexia syndrome and oxidative stress: an innovative approach beyond current treatment.

OBJECTIVE: Cancer-related anorexia/cachexia syndrome and oxidative stress play a key role in the progression and outcome of neoplastic disease. PATIENTS AND METHODS: On the basis of our previously published studies and clinical experience, we have developed an innovative approach consisting of diet with high polyphenol content (400 mg), p.o. pharmaconutritional support enriched with n - 3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) 2 cans (237 mL each) per day, medroxiprogesterone acetate 500 mg/d, antioxidant treatment with alpha-lipoic acid 300 mg/d plus carbocysteine lysine salt 2.7 g/d plus vitamin E 400 mg/d plus vitamin A 30,000 IU/d plus vitamin C 500 mg/d, and selective cyclooxygenase-2 inhibitor Celecoxib 200 mg/d. The treatment is administered for 16 weeks. The following variables are evaluated: (a) clinical variables (stage and Eastern Cooperative Oncology Group performance status); (b) nutritional variables (lean body mass, appetite, and resting energy expenditure); (c) laboratory variables (serum levels of proinflammatory cytokines, C-reactive protein, and leptin and blood levels of reactive oxygen species and antioxidant enzymes); and (d) quality of life variables (European Organization for Research and Treatment of Cancer QLQ-C30, EQ-5Dindex, and EQ-5DVAS). A phase II nonrandomized study has been designed to enroll 40 patients with advanced cancer at different sites with symptoms of cancer-related anorexia/cachexia syndrome and oxidative stress. RESULTS: As of January 2004, 28 patients have been enrolled: 25 patients were evaluable and 14 of them have completed the treatment (20 patients have completed 2 months of treatment). As for clinical response, five patients improved, three patients remained unchanged, and six patients worsened. The Eastern Cooperative Oncology Group performance status (grade) 1 remained unchanged. As for nutritional/functional variables, the lean body mass increased significantly at 2 and 4 months. As for laboratory variables, reactive oxygen species decreased significantly and proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha decreased significantly. As for quality of life, it comprehensively improved after treatment. CONCLUSIONS: The treatment has been shown to be effective for clinical response, increase of lean body mass, decrease of reactive oxygen species and proinflammatory cytokines, and improvement of quality of life. The treatment has been shown to be safe with good compliance of patients. The study is in progress (14 further patients will be included).

Alzheimer y la alimentación / Alzheimer´s disease and nutrition

La enfermedad de Alzheimer es la demencia senil de mayor prevalencia en la población occidental. Aunque de origen multifactorial, a medida que se profundiza en su fisiopatología, gana fuerza la hipótesis de la implicación de factores de riesgo nutricionales, como son bajos niveles de antioxidantes y de las vitaminas folato, B6 y B12, implicadas en el ciclo metabólico de la homocisteína. El diagnóstico precoz es esencial para mantener al paciente en un estado funcional el mayor tiempo posible. Hay que garantizar el aporte de energía y nutrientes, bien mediante alimentos, suplementos o alimentación enteral. Aunque es prematuro hablar de una prevención nutricional de la demencia, puede estar indicada la suplementación de vitaminas a dosis fisiológicas en los mayores de 60 años con una buena relación coste-beneficio (AU)

Institutional feeding of the elderly.

Not only is there a high prevalence of malnutrition among the elderly admitted to hospital and other institutions, but nutritional status seems to decline during admission, not only as a result of disease but also problems with catering and feeding policies, which are not well-geared to the needs of the sick. This results in high food wastage rates and inadequate macro- and micronutrient intakes to meet requirements. In the elderly, decreased portion size and increased energy, protein and micronutrient density have been shown to be effective in decreasing wastage and improving intake. Other strategies for improving intake are reviewed, including a better environment, a reduction in drugs causing anorexia, help with eating, and less interruption of meals by procedures and ward rounds. Targets for nutritional intake and aims of feeding are reviewed.