Elliot M. Berry

Effect of an Indo-Mediterranean diet on progression of coronary artery disease in high risk patients (Indo-Mediterranean Diet Heart Study): a randomised single-blind trial.

BACKGROUND The rapid emergence of coronary artery disease (CAD) in south Asian people is not explained by conventional risk factors. In view of cardioprotective effects of a Mediterranean style diet rich in alpha-linolenic acid, we assessed the benefits of this diet for patients at high risk of CAD. METHODS We did a randomised, single-blind trial in 1000 patients with angina pectoris, myocardial infarction, or surrogate risk factors for CAD. 499 patients were allocated to a diet rich in whole grains, fruits, vegetables, walnuts, and almonds. 501 controls consumed a local diet similar to the step I National Cholesterol Education Program (NCEP) prudent diet. FINDINGS The intervention group consumed more fruits, vegetables, legumes, walnuts, and almonds than did controls (573 g [SD 127] vs 231 g [19] per day p<0.001). The intervention group had an increased intake of whole grains and mustard or soy bean oil. The mean intake of alpha-linolenic acid was two-fold greater in the intervention group (1.8 g [SD 0.4] vs 0.8 g [0.2] per day, p<0.001). Total cardiac end points were significantly fewer in the intervention group than the controls (39 vs 76 events, p<0.001). Sudden cardiac deaths were also reduced (6 vs 16, p=0.015), as were non-fatal myocardial infarctions (21 vs 43, p<0.001). We noted a significant reduction in serum cholesterol concentration and other risk factors in both groups, but especially in the intervention diet group. In the treatment group, patients with pre-existing CAD had significantly greater benefits compared with such patients in the control group. INTERPRETATION An Indo-Mediterranean diet that is rich in alpha-linolenic acid might be more effective in primary and secondary prevention of CAD than the conventional step I NCEP prudent diet.

Food and emotion

The relationship between eating and emotion has always interested researchers of human behavior. This relationship varies according to the particular characteristics of the individual and according to the specific emotional state. We consider findings on the reciprocal interactions between, on the one hand, emotions and food intake, and, on the other, the psychological and emotional consequences of losing weight and dieting. Theories on the relationship between emotions and eating behaviors have their origin in the literature on obesity. The psychosomatic theory of obesity proposes that eating may reduce anxiety, and that the obese overeat in order to reduce discomfort. The internal/external theory of obesity hypothesizes that overweight people do not recognize physiological cues of hunger or satiety because of faulty learning. It thus predicts that normal weight people will alter (either increase or decrease) their eating when stressed, while obese people will eat regardless of their physiological state. The restraint hypothesis postulates that people who chronically restrict their food intake overeat in the presence of disinhibitors such as the perception of having overeaten, alcohol or stress. These theories are examined in the light of present research and their implications on eating disorders are presented.

Low dose anandamide affects food intake, cognitive function, neurotransmitter and corticosterone levels in diet-restricted mice

This investigation reports the possible role of the endocannabinoid anandamide on modulating the behavioral and neurochemical consequences of semi-starvation. We studied the effect of very low dose anandamide (0.001 mg/kg) administration on food intake, cognitive function and catecholaminergic and serotonergic pathways in two murine brain areas concerned with appetite (hypothalamus) and learning (hippocampus), and the peripheral corticosterone response to the stress of 40% diet restriction. Anandamide-treated mice consumed 44% more food (P<0.05) during 1 week of 2.5-h feeding each day. In the hypothalamus, there were significantly increased concentrations of norepinephrine (P<0.01), dopamine (P<0.05) and 5-hydroxytryptamine (5-HT) (P<0.001). In the hippocampus, anandamide increased significantly norepinephrine and dopamine, but decreased 5-HT (all at P<0.001). Diet restriction was accompanied in both areas by a significant decrease in all neurotransmitter concentrations that were partially restored by anandamide for dopamine and 5-HT, but not for norepinephrine. In animals on diet restriction, anandamide significantly improved impaired maze performance. Norepinephrine turnover and plasma corticosterone levels were also raised significantly by anandamide. The fact that low dose anandamide improved food intake, cognitive function and reversed some of the neurotransmitter changes caused by diet restriction, might have implications for the treatment of cachexia associated with acquired immunodeficiency syndrome (AIDS) and cancer, for mood changes sometimes associated with dieting, and in the extreme case, of patients with anorexia.

Tetrahydrocannabinol and endocannabinoids in feeding and appetite

The physiological control of appetite and satiety, in which numerous neurotransmitters and neuropeptides play a role, is extremely complex. Here we describe the involvement of endocannabinoids in these processes. These endogenous neuromodulators enhance appetite in animals. The same effect is observed in animals and in humans with the psychotropic plant cannabinoid Delta(9)-tetrahydrocannabinol, which is an approved appetite-enhancing drug. The CB(1) cannabinoid receptor antagonist SR141716A blocks the effects on feeding produced by the endocannabinoids. If administered to mice pups, this antagonist blocks suckling. In obese humans, it causes weight reduction. Very little is known about the physiological and biochemical mechanisms involved in the effects of Delta(9)-tetrahydrocannabinol and the cannabinoids in feeding and appetite.

EVALUATION OF PLASMA LOW MOLECULAR WEIGHT ANTIOXIDANT CAPACITY BY CYCLIC VOLTAMMETRY

The low molecular weight antioxidants (LMWA) of biological samples include many compounds and contribute to the total antioxidant capacity of the system. They act as direct chemical scavengers neutralizing, reactive oxygen-derived species (ROS), and contribute to the ability of the sample to cope with oxidative stress. We propose cyclic voltammetry (CV) as a new method for evaluating the antioxidant capacity of plasma-LMWA and the severity of oxidative stress exerted on the plasma. It is based on the reducing properties of these molecules. CV has been proven to be a simple, sensitive and reliable method. Its tracing does not change during storage of frozen plasma for up to six months. We analyzed the CV tracings by the oxidation potential E1/2, and the current heights Ia of its anodic wave(s). E1/2 indicates the specific component of the LMWA and its ability to donate electron(s); Ia indicates the concentration of this component. Two anodic waves have been identified in human plasma, at E1/2 = 420 +/- 25 and 920 +/- 25 mV. Ascorbate (AA) and urate (UA) were identified as major LMWA components of the first anodic wave, and were confirmed by HPLC-electrochemical detection. Ia was shown to depend linearly on the concentration of either of these LMWA, both in buffer and in plasma. Oxidative stress exerted by exposure to peroxyl radicals, copper ions and ionizing irradiation caused marked changes in the CV tracing. These changes represent corresponding alterations particularly in la, rather than in E1/2. The Ia and E1/2 values reflect the antioxidant capacity of the plasma, while the change of Ia value represents the severity of the oxidative stress induced.

Psychosocial predictors of weight loss and psychological adjustment following bariatric surgery and a weight-loss program: the mediating role of emotional eating.

OBJECTIVE To examine a structural equation model of the effects of personal and interpersonal factors on treatment outcome of bariatric surgery and weight-loss program. METHOD Forty-four participants of the surgery group and 47 participants of the diet group completed questionnaires before treatment and 1 year afterward. Predictor measures are as follows: social support, motivation for control, sense of control, self-esteem, neuroticism, fear of intimacy, and emotional eating (EE). OUTCOME MEASURES Weight loss, quality of life, and mental health. RESULTS Neurotic predisposition (NP), a latent variable indicated by neuroticism, low self-esteem, and fear of intimacy, had an effect on weight loss that was fully mediated by EE. NP also had an effect on quality of life improvement that was fully mediated by EE and weight loss in both treatment groups. DISCUSSION Both NP and EE predict outcome of obesity treatments, but EE is the more proximal variable that mediates the effect of NP.

Short-term fasting and prolonged semistarvation have opposite effects on 2-AG levels in mouse brain

2-Arachidonoyl glycerol (2-AG) levels in whole mouse brain and two of its regions-hippocampus and hypothalamus-were determined after diet restriction (between 60 and 40%) lasting 12 days. The diet restriction lowered the level of 2-AG, which in the hypothalamus depended on the severity of the diet restriction, while the level in the hippocampus was not dependent on the diet regimen. As these observations differ from previously published data showing elevation of 2-AG levels in rat brain after 24 h of severe food restriction, we measured 2-AG levels in whole mouse brain after a comparable period of full starvation (fasting). We confirmed the elevation of 2-AG levels. It seems possible that these time-dependent variations of 2-AG levels may be of importance as a general coping strategy by animals during periods of starvation.

Association study of cannabinoid receptor gene (CNR1) alleles and anorexia nervosa: Differences between restricting and bingeing/purging subtypes

Anorexia nervosa (AN) is a severe and disabling psychiatric disorder, characterized by profound weight loss and body image disturbance. Family and twin studies indicate a significant genetic contribution to this disorder although no genetic mutation has yet been identified. The endocannabinoid system has recently been implicated in many physiological functions including appetite regulation. We, therefore, undertook a family based study to test the hypothesis whether a polymorphism of the CNR1 gene, which encodes human CB1 receptor, a subclass of the central cannabinoid receptor, contributes to the susceptibility to AN. Fifty two families (parents with one or two affected siblings) were genotyped for the (AAT) trinucleotide repeat of CNR1 gene. Using the haplotype relative risk (HRR) method, the distribution of alleles transmitted to the patients was not found to be significantly different from the non‐transmitted parental alleles. However, upon dividing the samples to restricting and bingeing/purging subtypes of AN, the extended transmission disequilibrium test (ETDT) revealed that there is preferential transmission of different alleles in each of the subtypes. The 14 repeat allele was preferentially transmitted in the bingeing/purging AN group (P = 0.05) but not in the restricting AN group, whereas the 13 repeat allele was preferentially transmitted in the restricting AN group (almost significant, P = 0.07) but not in the bingeing/purging AN group. Our study suggests that restricting AN and bingeing/purging AN may be associated with different alleles of the CNR1 gene.

Dietary fatty acids in the management of diabetes mellitus.

Dietary fatty acid recommendations for patients with diabetes mellitus may be neither similar to, nor extrapolated from, those for the normal population; some evidence suggests that diabetes prevalence may be correlated with the dietary ratio of n-6 to n-3 fatty acids. In human experiments, n-3 fatty acids may improve many of the metabolic sequelae of insulin resistance by lowering blood pressure and triacylglycerol concentrations. In animals, n-3 fatty acids may cause less weight gain than other fats; however, they may raise low-density-lipoprotein concentrations, increase hepatic glucose output, and decrease insulin secretion in non-insulin-dependent diabetes mellitus. In a minority of patients with insulin-dependent diabetes mellitus, glycemic control may be adversely affected n-6 Fatty acids lower plasma cholesterol but may increase lipoprotein oxidation. Glucose in the presence of transition metals may produce free radicals and result in pancreatic damage and the formation of glycosylation products that inhibit nitric oxide-mediated smooth muscle relaxation; fish oil may counter these effects. High-carbohydrate, low-fat diets, once recommended for diabetes mellitus, appear to aggravate hypertriglyceridemia and are inferior to diets high in monounsaturated fatty acids (MUFAs) if saturated fats are kept to a minimum. MUFA-rich diets improve lipid profiles and may also have antioxidant properties. However, high-fat diets-whatever their composition-promote obesity. Current advice individualizes carbohydrate and fat requirements to optimize blood glucose and lipid concentrations in a lifestyle program to control obesity, exercise, smoking, and blood pressure. Fatty acid modifications may fine-tune the diet if proper balance is kept between the different long-chain polyunsaturated fatty acids and antioxidant requirements.

Polymyxin B reduces cecal flora, TNF production and hepatic steatosis during total parenteral nutrition in the rat

Hepatic complications are common in patients receiving total parental nutrition (TPN) and who have no underlying liver disease. In the present study we examined the hypothesis that endotoxin (LPS) or possibly TNF derived from the overgrowth of intestinal gram-negative bacteria is responsible for TPN-associated hepatic steatosis, and that bowel decontamination and specific anti-LPS activity of polymyxin B will reduce fatty infiltration of the liver during TPN. Forty-five male Sabra rats underwent jugular vein cannulation, were placed in metabolic cages, and were randomized into five groups. Group I was continuously infused with normal saline and allowed food ad lib, while group II-V were continuously infused with a TPN formula containing 4.25% amino acids and 25% dextrose for a total of 36 calories and 3.0 g protein per 100 g body weight/day. In addition, groups III-IV were also treated by oral polymyxin B while Groups IV and V received a combination of neomycin, metronidazole, and vancomycin (NMV). Thus, Group III received polymyxin B, Group IV received both polymyxin B and NMV, while Group V received NMV only. On Days 7-8 of the study, all animals were sacrificed and spontaneous production of TNF by peritoneal macrophages, bacterial translocation to mesenteric lymph nodes, culture of the cecum, and fat, triglyceride, and cholesterol contents of the liver were determined. All groups infused with TPN exhibited higher levels of total fat, triglycerides, and cholesterol compared to the free feeding control group (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)