Use of nutritional supplements to increase the efficacy of fluoxetine in the treatment of anorexia nervosa.

OBJECTIVE: Selective serotonin reuptake inhibitor (SSRI) medication does not appear to be effective in ill, malnourished anorexia nervosa (AN) patients. However, it may be effective in preventing relapse after weight restoration. The purpose of this study was to determine whether nutritional supplements could potentiate the effects of fluoxetine in underweight AN subjects. METHOD: Twenty-six subjects with AN participated in a trial of fluoxetine. In a double-blind, placebo-controlled manner, subjects received either nutritional supplements or a nutritional placebo. The nutritional supplement included tryptophan (the precursor of serotonin), vitamins, minerals, and essential fatty acids believed to influence serotonin pathway function. RESULTS: There was no significant difference in weight gain between subjects treated with fluoxetine plus nutritional supplements versus fluoxetine plus a nutritional placebo. Moreover, there were no significant differences between groups on mean changes in anxiety or obsessive and compulsive symptoms. DISCUSSION: The results of this study suggest that supplement strategies are not a substitute for adequate nutrition and are ineffective in increasing the efficacy of fluoxetine in underweight AN subjects.

Cancer anorexia and cachexia.

Patients with cancer cachexia experience a profound wasting of adipose tissue and lean body mass. Anorexia, although often present, is insufficient to account for tissue wasting because 1) cachexia involves massive depletion of skeletal muscle that does not occur during anorexia, 2) nutritional supplementation cannot replenish the loss of lean body mass, 3) cachexia can occur without anorexia, and 4) food intake might be normal for the lower weight of the cancer patient. Anorexia can arise from 1) decreased taste and smell of food, 2) early satiety, 3) dysfunctional hypothalamic membrane adenylate cyclase, 4) increased brain tryptophan, and 5) cytokine production. Appetite stimulants such as cyproheptadine, medroxyprogesterone acetate, and megestrol acetate do not significantly improve lean body mass. Tumor products might be more important in the development of cachexia. Cachectic patients excrete in their urine a lipid-mobilizing factor that directly stimulates lipolysis in a cyclic AMP-dependent manner and increases energy expenditure. Loss of skeletal muscle in cachexia is caused by upregulation of the ubiquitin-proteasome catabolic pathway. Cachexia-inducing tumors elaborate a sulfated glycoprotein, which directly initiates protein catabolism in skeletal muscle. The action of this proteolysis-inducing factor is attenuated by the polyunsaturated fatty acid eicosapentaenoic acid, which is also effective in preventing loss of skeletal muscle in cancer patients. Antagonists of tumor catabolic factors will provide important new agents in the treatment of cancer cachexia.

Metabolic abnormalities in cachexia and anorexia.

An increased glucose requirement by many solid tumors produces an increased metabolic demand on the liver, resulting in an increased energy expenditure. In addition, several cytokines and tumor catabolic products have been suggested as being responsible for the depletion of adipose tissue and skeletal-muscle mass in cachexia. A sulphated glycoprotein of molecular mass 24 kDa, produced by cachexia-inducing tumors and present in the urine of cancer patients actively losing weight, has been shown to be capable of inducing direct muscle catabolism in vitro and a state of cachexia in vivo, with specific loss of the non-fat carcass mass. In vitro studies have shown the bioactivity of this proteolysis-inducing factor to be attenuated by the polyunsaturated fatty acid, eicosapentaenoic acid. Preliminary clinical studies have shown that eicosapentaenoic acid stabilizes body weight and protein and fat reserves in patients with pancreatic carcinoma. Further trials are required to confirm the efficacy of eicosapentaenoic acid and to determine the anticachectic activity in other types of cancer.

Effect of oral eicosapentaenoic acid on weight loss in patients with pancreatic cancer.

Eicosapentaenoic acid (EPA) has been shown to modulate aspects of the inflammatory response that may contribute to weight loss in cancer. This study aimed to evaluate the acceptability and effects of oral supplementation with high-purity EPA in weight-losing patients with advanced pancreatic cancer. Twenty-six patients were entered into the study. EPA (95% pure) was administered as free acid starting at 1 g/day; the dose was increased to 6 g/day over four weeks, and then a maintenance dose of 6 g/day was administered. Patients were assessed before EPA and at 4, 8, and 12 weeks while receiving EPA, for weight, body composition, hematologic and clinical chemistry variables, acute-phase protein response, and performance status. Overall survival was noted. Supplementation was well tolerated, with only five patients experiencing side effects possibly attributable to the EPA. Before starting EPA, all patients had been losing weight at a median rate of 2 kg/mo. In general, after EPA supplementation, weight was stable. After four weeks of EPA supplementation, patients had a median weight gain of 0.5 kg (p = 0.0009 vs. rate of weight loss at baseline), and this stabilization of weight persisted over the 12-week study period. Total body water as a percentage of body weight remained stable, as did the proportion of patients with an acute-phase protein response, patients' nutritional intake, and performance status. Overall median survival from diagnosis in this study was 203 days. This study suggests that EPA is well tolerated, may stabilize weight in cachectic pancreatic cancer patients, and should be tested as an anticachectic agent in controlled trials.

Efectos del enriquecimiento de los sucedaneos de leche materna con aceite de pescado rico en ácidos eicosapentaenoico y docosahexaenoico en la alimentación del prematuro / Effects of succedaneous maternal milk enrichment with fish oil rich in eicosapentanoic and decosahexaenoic acids in the feeding of preterm infants

En este trabajo estudiamos los efectos del suplemento en la alimentación de aceite de pescado o concentrados de derivados de A.G. n-3 que contienen ácido eicosapentaenoico (EPA) y decosahexaenoico (DHA) mediante determinaciones antropométricas, y de una manera indirecta, el crecimiento cerebral, usando el método de ecosonografía craneal. Además se estimaron las variaciones en la composición de los A.G. en los fosfolípidos de membranas de glóbulos rojos en niños prematuros. Estudiamos 13 niños recién nacidos pretérmino con edad gestacional menor de 37 semanas con un peso promedio al nacer de 1.600 g que hubieran nacido en buenas condiciones generales. Todos fueron alimentados con fórmula láctea diluida al 13% con un aporte nutricional de 20 calorías por onza. Un grupo recibió la fórmula láctea sola y el otro grupo se suplementó con mezcla de EPA y DHA a razón de 0,5 g por KG. de peso por día durante 15 días. En la evaluación antropométrica sólo observamos diferencias en la CBD (circunferencia de brazo derecho) y la relación CBD/CC, siendo mayor la de los niños suplementados; al no encontrar diferencias en mediciones de los cutáneos, probablemente el incremento de esas relaciones indiquen formación de nuevo tejido. En las mediciones del manto cerebral no hubo diferencias. Un aumento significativo en los A.G. 20:5 n-3 y 22:6 n-3 se encontró en el grupo suplementado. Además mostró que la administración de los ácidos grasos de la serie n-3 (EPA y DHA) pueden rápidamente incorporarse a los diferentes fosfolípidos de las membranas. Por último, se observaron variaciones en estos ácidos grasos en la leche materna de una madre de un niño prematuro alimentada con A.G poliinsaturados

Pharmacologic manipulation of the peripheral vasculature in shock: clinical and experimental approaches.

An improved understanding of the patho-physiological and biochemical changes that occur in shock states has led to new and innovative pharmacologic approaches to shock reversal. In this article, we review the actions of several pharmaceutical agents on the peripheral vasculature in shock states. Agents with known efficacy, probable utility, and possible usefulness are each discussed. A model of factors modulating alpha-1 adrenergic receptor action is presented.

Eicosanoids in health and in disease: an appraisal.

Oxygenation of the 20-carbon polyunsaturated fatty acid, arachidonic acid, which is found in most body cells of all domestic animals, leads to the formation of a group of compounds possessing biological activity. These compounds, collectively known was eicosanoids, currently receive considerable attention owing to their involvement in a wide variety of physiological and pathophysiological processes. Particular interest has been focussed in recent years on the role and control of prostanoids and leukotrienes in inflammatory and allergic conditions in animals and man. Arachidonic acid metabolites are also recognised to be intimately involved in reproductive and perinatal processes; with platelet aggregation and vascular homeostasis; kidney function; fever; certain tumours and many other normal and disease conditions. Eicosanoid research in veterinary medicine is still at a relatively early stage in many respects and in this review an attempt is given to highlight some of the functions of this important series of compounds both in health and in disease. As more evidence comes to light, it is possible that veterinary surgeons may have to consider revising their clinical approach to the treatment of certain disease states where eicosanoids are implicated or where chemotherapy may interfere with their normal physiological activities.

Dietary enrichment with the polyunsaturated fatty acid eicosapentaenoic acid prevents proteinuria and prolongs survival in NZB x NZW F1 mice.

Prostaglandins and related compounds are active mediators of inflammation, but data concerning their role in the pathogenesis of the glomerulonephritis of New Zealand Black x New Zealand White (NZB x NZW) F1 mice are conflicting. Dietary eicosapentaenoic acid (EPA, C20:5), a fatty acid analogue of arachidonic acid (C20:4), has been shown to impair platelet aggregation in humans, apparently through inhibition of the synthesis of prostaglandins and thromboxanes from arachidonic acid. We report here the effects of a diet high in EPA on the development of renal disease and survival in female NZB x NZW F1 mice. Animals from 4--5 wk of age were fed diets containing 25% lipid, supplied either as beef tallow or menhaden oil, with fatty acid analysis of less than 0.05 and 14.4% EPA, respectively. In the first experiment, by 13.5 mo of age, mice on the beef tallow diet had all (9/9) developed proteinuria and the majority (6/9) had died, with renal histologic examination revealing severe glomerulonephritis. In contrast, none of 10 menhaden oil-fed animals had developed proteinuria, and all were alive at this time (P less than 0.005 for both proteinuria and survival). In a second experiment using 50 mice in each dietary group, 56% of the beef tallow group vs. none of the menhaden oil group had developed proteinuria at 9 mo of age (P less than 0.005). Native DNA binding at 6 mo of age was 23.9 +/- 14.7 vs. 10.1 +/- 9.7% in the beef and menhaden oil groups, respectively (P less than 0.01). Weights were similar in all groups, and there was no evidence of essential fatty acid deficiency in any group. These results demonstrate that a diet high in EPA protects NZB x NZW F1 mice from the development of glomerulonephritis.