Published Science

Objective The gut microbiota, which is considered a causal factor in metabolic diseases as shown best in animals, is under the dual influence of the host genome and nutritional environment. This study investigated whether the gut microbiota per se, aside from changes in genetic background and diet, could sign different metabolic phenotypes in mice. Methods The unique animal model of metabolic adaptation was used, whereby C57Bl/6 male mice fed a high-fat carbohydrate-free diet (HFD) became either diabetic (HFD diabetic, HFD-D) or resisted diabetes (HFD diabetes-resistant, HFD-DR). Pyrosequencing of the gut microbiota was carried out to profile the gut microbial community of different metabolic phenotypes. Inflammation, gut permeability, features of white adipose tissue, liver and skeletal muscle were studied. Furthermore, to modify the gut microbiota directly, an additional group of mice was given a gluco-oligosaccharide (GOS)-supplemented HFD (HFD+GOS). Results Despite the mice having the same genetic background and nutritional status, a gut microbial profile specific to each metabolic phenotype was identified. The HFD-D gut microbial profile was associated with increased gut permeability linked to increased endotoxaemia and to a dramatic increase in cell number in the stroma vascular fraction from visceral white adipose tissue. Most of the physiological characteristics of the HFD-fed mice were modulated when gut microbiota was intentionally modified by GOS dietary fibres. Conclusions The gut microbiota is a signature of the metabolic phenotypes independent of differences in host genetic background and diet.

Background Although fat deposition is a defining clinical characteristic of lymphedema, the cellular mechanisms that regulate this response remain unknown. The goals of this two-part study were to determine the effect of lymphatic fluid stasis on adipogenesis and inflammation (part 1) and how these changes regulate the temporal and spatial expression of fat differentiation genes (part 2). Methods Adult female mice underwent tail lymphatic ablation and were sacrificed 6 weeks after surgery (n=20). Fat deposition, fibrosis, and inflammation were then analyzed in the regions of the tail exposed to lymphatic fluid stasis as compared with normal lymphatic flow. Results Lymphatic fluid stasis in the tail resulted in significant subcutaneous fat deposition with a 2-fold increase in fat thickness (p<0.01). In addition, lymphatic stasis was associated with subcutaneous fat fibrosis and collagen deposition. Adipogenesis in response to lymphatic fluid stasis was associated with a marked mononuclear cell inflammatory response (5-fold increase in CD45+ cells; p<0.001). In addition, we noted a significant increase in the number of monocytes/macrophages as identified by F4/80 immunohistochemistry (p

Background Although fat deposition is a defining clinical characteristic of lymphedema, the cellular mechanisms that regulate this response remain unknown. The goal of this study was to determine how lymphatic fluid stasis regulates adipogenic gene activation and fat deposition. Methods Adult female mice underwent tail lymphatic ablation and sacrifice at 1, 3, or 6 weeks post-operatively (n=8/group). Samples were analyzed by immunohistochemistry and western blot. An alternative group of mice underwent axillary dissections or sham incisions and limb tissues were harvested 3 weeks post-operatively (n=8/group). Results Lymphatic fluid stasis resulted in significant subcutaneous fat deposition and fibrosis in lymphedematous tail regions (p

Cardiovascular disease (CVD) mortality rates are lower in Asian countries where dietary patterns are very different from Western diet. A number of studies have linked these lower rates to the inclusion of soy products as a staple food in those countries. Soy is the richest dietary source of isoflavones, a type of phytoestrogen associated with many potentially beneficial effects. Isoflavone-containing soy protein consumption has been linked to reduced levels of LDL cholesterol in hypercholesterolemic patients. This effect is increased with the concomitant administration of isoflavones, and seems to be also complemented by the isoflavone capacity to restore the endothelial function in patients with weak and moderated endothelial dysfunction. The effects are variable depending on individuals� � � metabolism and in particular to their ability to convert daidzein to equol that seems to be restricted to approximately 1/3 of the population. Equol production has been indeed linked to a decreased arterial stiffness and antiatherosclerotic effects via NO production. Because the relevance of isoflavones consumption on the modulation of cardiovascular risk still remains unclear, this paper aims to review the existing knowledge on the biological activity of the isoflavones on the human cardiovascular system from an epidemiological, clinical and -omics point of view.

Dietary and metabolic therapies have been attempted in a wide variety of neurological diseases, including epilepsy, headache, neurotrauma, Alzheimer disease, Parkinson disease, sleep disorders, brain cancer, autism, pain, and multiple sclerosis. The impetus for using various diets to treat – or at least ameliorate symptoms of – these disorders stems from both a lack of effectiveness of pharmacological therapies, and also the intrinsic appeal of implementing a more “natural” treatment. The enormous spectrum of pathophysiological mechanisms underlying the aforementioned diseases would suggest a degree of complexity that cannot be impacted universally by any single dietary treatment. Yet, it is conceivable that alterations in certain dietary constituents could affect the course and impact the outcome of these brain disorders. Further, it is possible that a final common neurometabolic pathway might be influenced by a variety of dietary interventions. The most notable example of a dietary treatment with proven efficacy against a neurological condition is the high-fat, low-carbohydrate ketogenic diet (KD) used in patients with medically intractable epilepsy. While the mechanisms through which the KD works remain unclear, there is now compelling evidence that its efficacy is likely related to the normalization of aberrant energy metabolism. The concept that many neurological conditions are linked pathophysiologically to energy dysregulation could well provide a common research and experimental therapeutics platform, from which the course of several neurological diseases could be favorably influenced by dietary means. Here we provide an overview of studies using the KD in a wide panoply of neurologic disorders in which neuroprotection is an essential component.

We have studied the prevalence of fibromyalgia syndrome (FMS) in patients with type 1 and type 2 diabetes mellitus (DM). Relationship with disease control of DM and the presence of FMS was also evaluated. We have studied 93 consecutive patients with DM (85 with type 2 DM and 8 patients with type 1 DM) followed in Diabetes Center. Single researcher took the history and did physical examination including manual tender point examination according to Manual Tender Point Survey instructions. For the diagnosis of FMS, 1990 American College of Rheumatology Classification Criteria for FMS was used. We measured patients' fasting blood sugar levels and HbA1c levels around the same time period. Patients were excluded from the study if they had any other serious disease, and if there was any history of drug use that interferes with the symptoms of FMS. Patients with rheumatoid arthritis (RA) were accepted as controls. FMS was found in 18% of patients with DM type 2 (no patients with FMS in type 1 DM group), in 34% of patients with RA. Female patients with DM type 2 had significantly higher FMS rates. Mean fasting blood sugar levels and mean HbA1c levels were not significantly different between type 2 DM patients with FMS and DM patients without FMS. In RA group, in RA patients without FMS, the use of steroids was significantly higher. We have found an increased prevalence rate of FMS in patients with DM type 2 and RA. There was no correlation between the prevalence rate of FMS and good DM disease control.

BACKGROUND Mitochondrial respiratory chain disorders are the most prevalent group of inherited neurometabolic diseases. They present with central and peripheral neurological features usually in association with other organ involvement including the eye, the heart, the liver, and kidneys, diabetes mellitus and sensorineural deafness. Current treatment is largely supportive and the disorders progress relentlessly causing significant morbidity and premature death. Vitamin supplements, pharmacological agents and exercise therapy have been used in isolated cases and small clinical trials, but the efficacy of these interventions is unclear. The first review was carried out in 2003, and identified six clinical trials. This major update was carried out to identify new studies and grade the original studies for potential bias in accordance with revised Cochrane Collaboration guidelines. OBJECTIVES To determine whether there is objective evidence to support the use of current treatments for mitochondrial disease. SEARCH METHODS We searched the Cochrane Neuromuscular Disease Group Specialized Register (4 July 2011), CENTRAL (2011, Issue 2, MEDLINE (1966 to July 2011), and EMBASE (January 1980 to July 2011), and contacted experts in the field. SELECTION CRITERIA We included randomised controlled trials (including cross-over studies). Two of the authors independently selected abstracts for further detailed review. Further review was performed independently by all five authors to decide which trials fit the inclusion criteria and graded risk of bias. Participants included males and females of any age with a confirmed diagnosis of mitochondrial disease based upon muscle histochemistry, respiratory chain complex analysis of tissues or cell lines or DNA studies. Interventions included any pharmacological agent, dietary modification, nutritional supplement, exercise therapy or other treatment. The review authors excluded studies at high risk of bias in any category. The primary outcome measures included an change in muscle strength and/or endurance, or neurological clinical features. Secondary outcome measures included quality of life assessments, biochemical markers of disease and negative outcomes. DATA COLLECTION AND ANALYSIS Two of the authors (GP and PFC) independently identified studies for further evaluation from all abstracts within the search period. For those studies identified for further review, all five authors then independently assessed which studies met the entry criteria. For the included studies, we extracted details of the number of randomised participants, treatment, study design, study category, allocation concealment and other risk of bias criteria, and participant characteristics. Analysis was based on intention-to-treat data. We planned to use meta-analysis, but this did not prove necessary. MAIN RESULTS The authors reviewed 1335 abstracts, and from these identified 21 potentially eligible abstracts. Upon detailed review, 12 studies fulfilled the entry criteria. Of these, eight were new studies that had been published since the previous version of this review. Two studies which were included in the previous version of this review were excluded because of potential for bias. The comparability of the included studies is extremely low because of differences in the specific diseases studied, differences in the therapeutic agents used, dosage, study design, and outcomes. The methodological quality of included studies was generally high, although risk of bias was unclear in random sequence generation and allocation concealment for most studies. Otherwise, the risk of bias was low for most studies in the other categories. Serious adverse events were uncommon, except for peripheral nerve toxicity in a long-term trial of dichloroacetate (DCA) in adults.One trial studied high-dose coenzyme Q10 without clinically meaningful improvement (although there were multiple biochemical, physiologic, and neuroimaging outcomes, in 30 participants). Three trials used creatine monohydrate alone, with one reporting evidence of improved measures of muscle strength and post-exercise lactate, but the other two reported no benefit (total of 38 participants). One trial studied the effects of a combination of coenzyme Q10, creatine monohydrate, and lipoic acid and reported a statistically significant improvement in biochemical markers and peak ankle dorsiflexion strength, but overall no clinical improvement in 16 participants. Five trials studied the effects of DCA: three trials in children showed a statistically significant improvement in secondary outcome measures of mitochondrial metabolism (venous lactate in three trials, and magnetic resonance spectroscopy (MRS) in one trial; total of 63 participants). One trial of short-term DCA in adults demonstrated no clinically relevant improvement (improved venous lactate but no change in physiologic, imaging, or questionnaire findings, in eight participants). One longer-term DCA trial in adults was terminated prematurely due to peripheral nerve toxicity without clinical benefit (assessments included the GATE score, venous lactate and MRS, in 30 participants). One trial using dimethylglycine showed no significant effect (measurements of venous lactate and oxygen consumption (VO(2)) in five participants). One trial using a whey-based supplement showed statistically significant improvement in markers of free radical reducing capacity but no clinical benefit (assessments included the Short Form 36 Health Survey (SF-36) questionnaire and UK Medical Research Council (MRC) muscle strength, in 13 participants). AUTHORS' CONCLUSIONS Despite identifying eight new trials there is currently no clear evidence supporting the use of any intervention in mitochondrial disorders. Further research is needed to establish the role of a wide range of therapeutic approaches. We suggest further research should identify novel agents to be tested in homogeneous study populations with clinically relevant primary endpoints.

Biological systems are increasingly being studied in a holistic manner, using omics approaches, to provide quantitative and qualitative descriptions of the diverse collection of cellular components. Among the omics approaches, metabolomics, which deals with the quantitative global profiling of small molecules or metabolites, is being used extensively to explore the dynamic response of living systems, such as organelles, cells, tissues, organs and whole organisms, under diverse physiological and pathological conditions. This technology is now used routinely in a number of applications, including basic and clinical research, agriculture, microbiology, food science, nutrition, pharmaceutical research, environmental science and the development of biofuels. Of the multiple analytical platforms available to perform such analyses, nuclear magnetic resonance and mass spectrometry have come to dominate, owing to the high resolution and large datasets that can be generated with these techniques. The large multidimensional datasets that result from such studies must be processed and analyzed to render this data meaningful. Thus, bioinformatics tools are essential for the efficient processing of huge datasets, the characterization of the detected signals, and to align multiple datasets and their features. This paper provides a state-of-the-art overview of the data processing tools available, and reviews a collection of recent reports on the topic. Data conversion, pre-processing, alignment, normalization and statistical analysis are introduced, with their advantages and disadvantages, and comparisons are made to guide the reader.

INTRODUCTION: This paper combines information from the book, Cool Cuisine-Taking the Bite Out of Global Warming (Gibbs Smith, 2008) with notes from the World of Healthy Flavors Conference (Culinary Institute of America, St. Helena, CA, USA, 2011). Cool Cuisine reports on connections between food choices and global warming, (what we termed the Global Warming Diet), both from a culinary and science point of view. METHOD: World of Healthy Flavors brought food industry professionals together to discuss ways the industry can collaborate on solutions to some of the most pressing health problems in the USA. RESULTS AND DISCUSSION: Science now supports the fact that dietary choices that adversely effect human health have an equally detrimental effect on the health of the environment and our livestock. Therefore, eating a more diverse, plant-based, whole grain, and sodium-reduced diet not only improves human health, but also the health of the environment. What is good for humans to eat is the same food that is best for the environment to grow and manufacture. Understanding and then teaching the connection between the two is one more tool toward effective behavior change, especially in children. Easy suggestions on ways to cook healthfully and "fight the global warming diet with a cool cuisine" close out this work.

OBJECTIVE: This study was conducted to assess the relation of major dietary patterns identified by factor analysis to attention-deficit/hyperactivity disorder (ADHD) in a group of Iranian school-age children. METHODS: This cross-sectional study was conducted in 375 school-age children in Tehran, Iran. We assessed usual dietary intakes by a semiquantitative food-frequency questionnaire. The presence of ADHD was diagnosed using the questionnaire of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Major dietary patterns were identified by factor analysis. RESULTS: The prevalence of ADHD was 9.7% in this population. We identified four major dietary patterns: "healthy," "Western," "sweet," and "fast food." After controlling for potential confounders, children in the top quintile of the sweet dietary pattern score had greater odds for having ADHD compared with those in the lowest quintile (odds ratio 3.95, 95% confidence interval 1.16-15.31, P for trend = 0.03). Greater adherence to the fast-food dietary pattern was significantly associated with a higher risk of having ADHD (odds ratio 3.21, 95% confidence interval 1.05-10.90, P for trend = 0.03). No overall significant associations were seen between the healthy or Western dietary pattern and ADHD. CONCLUSION: We found significant independent associations between the sweet and fast-food dietary patterns and the prevalence of ADHD. Prospective studies are required to confirm these findings.

The relationship between obesity and ketonuria is not well-established. We conducted a retrospective observational study to evaluate whether their body weight reduction response differed by the presence of ketonuria after fasting in the healthy obese. We used the data of 42 subjects, who had medical records of initial urinalysis at routine health check-up and follow-up urinalysis in the out-patient clinic, one week later. All subjects in the initial urinalysis showed no ketonuria. However, according to the follow-up urinalysis after three subsequent meals fasts, the patients were divided into a non-ketonuria group and ketonuria group. We compared the data of conventional low-calorie diet programs for 3 months for both groups. Significantly greater reduction of body weight (-8.6 ± 3.6 kg vs -1.1 ± 2.2 kg, P < 0.001), body mass index (-3.16 ± 1.25 kg/m(2) vs -0.43 ± 0.86 kg/m(2), P < 0.001) and waist circumference (-6.92 ± 1.22 vs -2.32 ± 1.01, P

Background and Aim: Increased levels of C-reactive protein (CRP), common in aging populations, are associated with higher risk for chronic diseases, including diabetes and coronary heart disease. The aim of this study was to investigate associations between lifestyle factors and high CRP among middle-aged men living in Shanghai, China.Methods and Results: In this cross-sectional study, 3978 urban Chinese men aged 40-74 years who were free of type-2 diabetes at baseline provided fasting blood samples, anthropometric measurements and information on lifestyle factors and disease history. Dietary patterns were assessed by factor analysis. Participants were categorised into two groups according to CRP level: normal (≤ 3 mg/L) and high (> 3 mg/L). Associations between CRP categories and lifestyle factors were investigated by using logistic regression. Obesity, weight gain, cigarette smoking and alcohol intake were positively associated with high CRP levels, while physical activity and a dietary pattern with high consumption of fruit were inversely related to high CRP levels. A positive trend of marginal significance between quintiles of a dietary pattern with high consumption of meat and high CRP levels was also observed. No association between tea intake and CRP level was observed.Conclusions: Components of an adverse lifestyle were associated with high CRP levels. Obesity, smoking and alcohol intake were associated with high CRP, a biomarker of low-grade inflammation in middle-aged men, while a dietary pattern rich in fruit and high physical activity were inversely associated with the prevalence of high CRP.

Glucagon is traditionally thought of as an antihypoglycemic hormone, for example in response to starvation. However, it actually increases energy expenditure and has other actions not in line with protection from hypoglycemia. Furthermore, it is often found to be elevated when glucose is also raised, for example in circumstances of psychological and metabolic stress. These findings seem more in keeping with glucagon having some role as a hormone enhancing the response to stress.

OBJECTIVE: To identify the nutritional status and food intake of individuals with systemic psoriasis and psoriatic arthritis associated. METHODS: This is an exploratory and cross-sectional study with 34 men aged between 19 and 60 years seen at a Psoriasis Center. Participants were divided into systemic psoriasis group and arthritic-systemic psoriasis associated group. For nutritional assessment we used anthropometry, bioelectrical impedance analysis and whole-body plethysmography. Clinical and nutritional information were assessed using the clinical and nutritional history-taking, and the 24-hour dietary recall. For statistics the general linear model test (p 25%) and a high risk for metabolic complications according to the waist circumference and the obesity index, however, there were no statistically significant differences between groups. The mean food intake, total fat, calories and protein were above recommended levels, being 58.8% for lipids (319.17 +/- 241.02 mg of cholesterol and 17.42 +/- 11.4 g saturated fatty acids); 29.4% for calories and 67.6% for proteins. Thus, regardless of the psoriasis type, an excessive consumption of calories, lipids, fatty acids, cholesterol and a higher incidence of overweight were found. CONCLUSION: The sample showed an abnormal nutritional condition, an increased risk for chronic diseases related to obesity, worsening of the psoriatic lesions, and poor quality of life.

Paraoxonase 1 (PON 1) has antioxidant and cardioprotective properties and is abnormally low in type 2 diabetic serum. This study aimed to determine the effect of type 2 diabetes and meals rich in saturated fat and oleic acid on PON1 activity in chylomicrons and very low density lipoproteins (VLDL). PON1 arylesterase activity was measured in chylomicrons and VLDL that were isolated in serum from 20 patients with type 2 diabetes and 20 age- and gender-matched, overweight controls 3 h after meals rich in cream or olive oil in a randomized, cross-over study. Chylomicron-PON1 activity (45%, P = 0.02), ratio chylomicron-PON1/chylomicron-triacylglycerides (TAG) (42%, P = 0.03) and chylomicron-protein content (46%, P < 0.001) were significantly lower in patients with type 2 diabetes compared with controls after the olive oil meal with comparable findings after the meal rich in cream. After ingestion of olive oil, chylomicron-PON1 activity was significantly higher in controls (P = 0.01) and marginally higher (P = 0.06) in diabetic patients and chylomicron-TAG were significantly (P < 0. 05) higher in both groups of subjects, compared with values after ingestion of cream. VLDL-PON1 increased (two-fold) significantly (P < 0.003) during both meals. Chylomicron-PON1 activity was correlated significantly with chylomicron-protein (P 

Vascular dysfunction is recognised as an integrative marker of CVD. While dietary strategies aimed at reducing CVD risk include reductions in the intake of SFA, there are currently no clear guidelines on what should replace SFA. The purpose of this review was to assess the evidence for the effects of total dietary fat and individual fatty acids (SFA, MUFA and n-6 PUFA) on vascular function, cellular microparticles and endothelial progenitor cells. Medline was systematically searched from 1966 until November 2010. A total of fifty-nine peer-reviewed publications (covering fifty-six studies), which included five epidemiological, eighteen dietary intervention and thirty-three test meal studies, were identified. The findings from the epidemiological studies were inconclusive. The limited data available from dietary intervention studies suggested a beneficial effect of low-fat diets on vascular reactivity, which was strongest when the comparator diet was high in SFA, with a modest improvement in measures of vascular reactivity when high-fat, MUFA-rich diets were compared with SFA-rich diets. There was consistent evidence from the test meal studies that high-fat meals have a detrimental effect on postprandial vascular function. However, the evidence for the comparative effects of test meals rich in MUFA or n-6 PUFA with SFA on postprandial vascular function was limited and inconclusive. The lack of studies with comparable within-study dietary fatty acid targets, a variety of different study designs and different methods for determining vascular function all confound any clear conclusions on the impact of dietary fat and individual fatty acids on vascular function.

We randomly assigned 23 older adults with mild cognitive impairment to either a high carbohydrate or very low carbohydrate diet. Following the 6-week intervention period, we observed improved verbal memory performance for the low carbohydrate subjects (p = 0.01) as well as reductions in weight (p < 0.0001), waist circumference (p

Oily fish intake during pregnancy may reduce the risk of allergic diseases in infancy possibly by shifts in the fatty acid balance and subsequent altered prostaglandin (PG) formation. This intervention is the first study to evaluate if increased oily fish intake affects in vivo PGF(2α) formation during pregnancy. British pregnant women were randomised to two portions of farmed salmon weekly (n=47), or maintenance of their normal diet low in fish (n=41), from pregnancy week 20 until parturition. The concentrations of eicosapentaenoic and docosahexaenoic acids in plasma phosphatidylcholine (PC) were higher and the concentration of arachidonic acid in plasma PC was lower in the salmon group than the control group at weeks 34 and 38 of pregnancy. PGF(2α) formation was evaluated by urinary measurement of 15-keto-dihydro-PGF(2α), a major PGF(2α) metabolite, at 20, 34 and 38 weeks. In both the salmon and control groups urinary 15-keto-dihydro-PGF(2α) concentrations increased significantly during pregnancy, which may be of physiological importance. Oily fish intervention altered fatty acid concentrations but did not affect urinary 15-keto-dihydro-PGF(2α) concentrations in pregnant women.

Increased gluconeogenesis (GNG) has been suggested to contribute to protein-induced satiety via modulation of glucose homoeostasis. The objective was to determine GNG and appetite in healthy human subjects after a high-protein v. a normal-protein diet and to assess whether GNG contributes to protein-induced satiety. A total of twenty-two healthy subjects (ten men and twelve women: age 23 (sem 1) years, BMI 22·1 (sem 0·5) kg/m2) received an isoenergetic high-protein (30/0/70 % of energy from protein/carbohydrate/fat) or normal-protein diet (12/55/33 % of energy from protein/carbohydrate/fat) for 1·5 d in a randomised cross-over design. Appetite ratings were measured using visual analogue scales (VAS); endogenous glucose production and GNG were measured via infusion of [6,6-2H2]glucose and ingestion of 2H2O. Moreover, fasting glucose and β-hydroxybutyrate concentrations were measured. Glycogen stores were lowered at the start with a glycogen-lowering exercise test. During the high-protein compared with the normal-protein diet, GNG was increased and appetite was suppressed (GNG: 148 (sem 7) v. 133 (sem 6) g/24 h, P < 0·05; and 24 h area under the curve for hunger: 694 (sem 46) v. 1055 (sem 52) mm VAS × 24 h, P < 0·001; fullness: 806 (sem 59) v. 668 (sem 64) mm VAS × 24 h, P < 0·05; desire to eat: 762 (sem 48) v. 1004 (sem 66) mm VAS × 24 h, P < 0·001). There was no correlation between appetite ratings and GNG. Glucose concentration was lower (4·09 (sem 0·10) v. 4·89 (sem 0·06) mmol/l, P < 0·001) and β-hydroxybutyrate concentration was higher (1349 (sem 139) v. 234 (sem 25) μmol/l, P 

RATIONALE, AIMS AND OBJECTIVES: Many clinical guidelines for cardiovascular disease (CVD) prevention contain risk estimation charts/calculators. These have shown a tendency to overestimate risk, which indicates that there might be theoretical flaws in the algorithms. Total cholesterol is a frequently used variable in the risk estimates. Some studies indicate that the predictive properties of cholesterol might not be as straightforward as widely assumed. Our aim was to document the strength and validity of total cholesterol as a risk factor for mortality in a well-defined, general Norwegian population without known CVD at baseline. METHODS: We assessed the association of total serum cholesterol with total mortality, as well as mortality from CVD and ischaemic heart disease (IHD), using Cox proportional hazard models. The study population comprises 52 087 Norwegians, aged 20-74, who participated in the Nord-Trøndelag Health Study (HUNT 2, 1995-1997) and were followed-up on cause-specific mortality for 10 years (510 297 person-years in total). RESULTS: Among women, cholesterol had an inverse association with all-cause mortality [hazard ratio (HR): 0.94; 95% confidence interval (CI): 0.89-0.99 per 1.0 mmol L(-1) increase] as well as CVD mortality (HR: 0.97; 95% CI: 0.88-1.07). The association with IHD mortality (HR: 1.07; 95% CI: 0.92-1.24) was not linear but seemed to follow a 'U-shaped' curve, with the highest mortality

Background Lithium is a widely used and effective treatment for mood disorders. There has been concern about its safety but no adequate synthesis of the evidence for adverse effects. We aimed to undertake a clinically informative, systematic toxicity profile of lithium.

CONCLUSIONS: These results suggest that an increase in dietary rTFAs equivalent to ~1% of daily energy has no significant effect on LDL but may be associated with a reduction in plasma HDL-cholesterol concentrations, particularly in overweight women. This trial is registered at clinicaltrials.gov as NCT00930137.

Rare adipose disorders (RADs) including multiple symmetric lipomatosis (MSL), lipedema and Dercum's disease (DD) may be misdiagnosed as obesity. Lifestyle changes, such as reduced caloric intake and increased physical activity are standard care for obesity. Although lifestyle changes and bariatric surgery work effectively for the obesity component of RADs, these treatments do not routinely reduce the abnormal subcutaneous adipose tissue (SAT) of RADs. RAD SAT likely results from the growth of a brown stem cell population with secondary lymphatic dysfunction in MSL, or by primary vascular and lymphatic dysfunction in lipedema and DD. People with RADs do not lose SAT from caloric limitation and increased energy expenditure alone. In order to improve recognition of RADs apart from obesity, the diagnostic criteria, histology and pathophysiology of RADs are presented and contrasted to familial partial lipodystrophies, acquired partial lipodystrophies and obesity with which they may be confused. Treatment recommendations focus on evidence-based data and include lymphatic decongestive therapy, medications and supplements that support loss of RAD SAT. Associated RAD conditions including depression, anxiety and pain will improve as healthcare providers learn to identify and adopt alternative treatment regimens for the abnormal SAT component of RADs. Effective dietary and exercise regimens are needed in RAD populations to improve quality of life and construct advanced treatment regimens for future generations.

Given the large social impact of dietary advice, it is important that the advice have a solid scientific basis. Evidence-based dietary advice should be built on results from all studies available, according to a given methodology. Conclusions should be a valid representation of the summarized results. The association between saturated fat intake and cardiovascular disease was examined. Results from three reports of leading U.S. and European advisory committees were compared with results as they were presented in the articles referred to. Findings were put into perspective with results not included in these reports. Different lines of evidence were included in the different reports. No overlap whatsoever was found in the articles included. Most results from the scientific literature were lacking for most different lines of evidence in all reports. All three reports included the effect of saturated fat on low-density lipoprotein cholesterol in the evidence linking saturated fat to cardiovascular disease, but the effect on high-density lipoprotein cholesterol was systematically ignored. Both U.S. reports failed to correctly describe the results from the prospective studies. Results and conclusions about saturated fat intake in relation to cardiovascular disease, from leading advisory committees, do not reflect the available scientific literature. Copyright © 2012 Elsevier Inc. All rights reserved.

The purpose of this study was to test the effect of a 3-week strength training program of knee extensor muscles on cycling delta efficiency in master endurance athletes. Nine master (age 51.5 ± 5.5 years) and 8 young (age 25.6 ± 5.9 years) endurance athletes with similar training levels participated in this study. During three consecutive weeks, all the subjects were engaged in a strength training program of the knee extensor muscles. Every week, they performed three training sessions consist of 10 × 10 knee extensions at 70% of maximal repetition with 3 min rest between in a leg extension apparatus. Maximal voluntary contraction torque (MVC torque) and force endurance (End) were assessed before, after every completed week of training, and after the program. Delta efficiency (DE) in cycling was evaluated before and after the training period. Before the training period, MVC torque, End, and DE in cycling were significantly lower in masters than in young. The strength training induced a significant improvement in MVC torque in all the subjects, more pronounced in masters (+17.8% in masters vs. +5.9% in young, P < 0.05). DE in cycling also significantly increased after training in masters, whereas it was only a trend in young. A significant correlation (r = 0.79, P

This article is intended to provide a comprehensive overview of the role of dietary methods for treatment of children with attention-deficit/hyperactivity disorder (ADHD) when pharmacotherapy has proven unsatisfactory or unacceptable. Results of recent research and controlled studies, based on a PubMed search, are emphasized and compared with earlier reports. The recent increase of interest in this form of therapy for ADHD, and especially in the use of omega supplements, significance of iron deficiency, and the avoidance of the "Western pattern" diet, make the discussion timely. Diets to reduce symptoms associated with ADHD include sugar-restricted, additive/preservative-free, oligoantigenic/elimination, and fatty acid supplements. Omega-3 supplement is the latest dietary treatment with positive reports of efficacy, and interest in the additive-free diet of the 1970s is occasionally revived. A provocative report draws attention to the ADHD-associated "Western-style" diet, high in fat and refined sugars, and the ADHD-free "healthy" diet, containing fiber, folate, and omega-3 fatty acids. The literature on diets and ADHD, listed by PubMed, is reviewed with emphasis on recent controlled studies. Recommendations for the use of diets are based on current opinion of published reports and our practice experience. Indications for dietary therapy include medication failure, parental or patient preference, iron deficiency, and, when appropriate, change from an ADHD-linked Western diet to an ADHD-free healthy diet. Foods associated with ADHD to be avoided and those not linked with ADHD and preferred are listed. In practice, additive-free and oligoantigenic/elimination diets are time-consuming and disruptive to the household; they are indicated only in selected patients. Iron and zinc are supplemented in patients with known deficiencies; they may also enhance the effectiveness of stimulant therapy. In patients failing to respond or with parents opposed to medication, omega-3 supplements may warrant a trial. A greater attention to the education of parents and children in a healthy dietary pattern, omitting items shown to predispose to ADHD, is perhaps the most promising and practical complementary or alternative treatment of ADHD.

The pathological consequences of traumatic head injury result largely from the opening of the mitochondrial permeability transition pore (mPTP). The mPTP opens due to a decrease in brain phosphorylation energy resulting in a further decrease in brain ATP production and a measurable increase in brain heat generation and temperature. The increase in brain temperature can be measured transcranially by near infrared spectroscopy which can be used to diagnose traumatic brain injury (TBI) and to monitor treatment. Effective therapy of TBI can be achieved by closure of the mPTP by administration of cyclosporine A or by oral administration of ketone body esters. While ketosis has previously been known to prevent damage from TBI, the availability of oral ketone esters presents the first practical modality of achieving therapeutic levels of ketone bodies.

BACKGROUND/OBJECTIVES: Consisting of ≈10(14) microbial cells, the intestinal microbiota represents the largest and the most complex microbial community inhabiting the human body. However, the influence of regular diets on the microbiota is widely unknown. SUBJECTS/METHODS: We examined faecal samples of vegetarians (n=144), vegans (n=105) and an equal number of control subjects consuming ordinary omnivorous diet who were matched for age and gender. We used classical bacteriological isolation, identification and enumeration of the main anaerobic and aerobic bacterial genera and computed absolute and relative numbers that were compared between groups. RESULTS: Total counts of Bacteroides spp., Bifidobacterium spp., Escherichia coli and Enterobacteriaceae spp. were significantly lower (P=0.001, P=0.002, P=0.006 and P=0.008, respectively) in vegan samples than in controls, whereas others (E. coli biovars, Klebsiella spp., Enterobacter spp., other Enterobacteriaceae, Enterococcus spp., Lactobacillus spp., Citrobacter spp. and Clostridium spp.) were not. Subjects on a vegetarian diet ranked between vegans and controls. The total microbial count did not differ between the groups. In addition, subjects on a vegan or vegetarian diet showed significantly (P=0.0001) lower stool pH than did controls, and stool pH and counts of E. coli and Enterobacteriaceae were significantly correlated across all subgroups. CONCLUSIONS: Maintaining a strict vegan or vegetarian diet results in a significant shift in the microbiota while total cell numbers remain unaltered.

Fish proteins have been reported to be more satiating than meat proteins. The objective was to determine the effect of different animal protein pre-meals on satiety. A total of ten intact female hounds were fed pork loin, beef loin, chicken breast, salmon fillet or pollock fillet. Each pre-meal was fed to contain 100 g protein. Blood was collected at 0, 5, 15, 30, 60, 90 and 120 min postprandially and analysed for glucose, insulin, total ghrelin, active glucagon-like peptide-1 (GLP-1) and plasma amino acids (AA). Dogs were fed 2 x metabolisable energy, 3 h following the pre-meal, and intake was determined 30, 60, 180 and 1440 min after food presentation. Glucose decreased over time (P < 0.001), but was lowest (P = 0.01) when dogs consumed pollock or chicken. Insulin increased (P < 0.0001) over time, and was greater (P = 0.09) when dogs consumed salmon. GLP-1 increased (P < 0.001) over time, and was greatest (P = 0.04) when dogs consumed beef. Ghrelin decreased (P

In our previous study, we demonstrated that abstaining from meat, for 1 month, by healthy omnivores (lacto-ovovegetarian model) resulted in a statistical decrease in pancreatic secretion as measured by faecal elastase-1 output. However, no correlation between relative and non-relative changes of energy and nutrient consumption and pancreatic secretion was documented. Therefore, in the present study, we aimed to assess the changes of exocrine pancreatic secretion with a more restrictive dietetic modification, by applying a vegan diet. A total of twenty-one healthy omnivores (sixteen females and five males) participated in the prospective study lasting for 6 weeks. The nutrient intake and faecal output of pancreatic enzymes (elastase-1, chymotrypsin and lipase) were assessed twice during the study. Each assessment period lasted for 7 d: the first before the transition to the vegan diet (omnivore diet) and the second during the last week of the study (vegan diet). The dietary modification resulted in a significant decrease in faecal elastase-1 (P < 0·05) and chymotrypsin output (P < 0·04). The lipase excretion remained unchanged. The decrease in proteolytic enzymes was documented to be positively correlated with a decreased protein intake (P < 0·05). In addition, elastase-1 and chymotrypsin outputs were also related to the changes of protein type, plant v. animal (P < 0·04 and P 

Background sounds, such as narration, music with prominent staccato passages, and office noise impair verbal short-term memory even when these sounds are irrelevant. This irrelevant sound effect (ISE) is evoked by so-called changing-state sounds that are characterized by a distinct temporal structure with varying successive auditory-perceptive tokens. However, because of the absence of an appropriate psychoacoustically based instrumental measure, the disturbing impact of a given speech or nonspeech sound could not be predicted until now, but necessitated behavioral testing. Our database for parametric modeling of the ISE included approximately 40 background sounds (e.g., speech, music, tone sequences, office noise, traffic noise) and corresponding performance data that was collected from 70 behavioral measurements of verbal short-term memory. The hearing sensation fluctuation strength was chosen to model the ISE and describes the percept of fluctuations when listening to slowly modulated sounds (f(mod)

CONCLUSIONS: Low-SFA, heart-healthy dietary patterns that contain lean beef elicit favorable effects on cardiovascular disease (CVD) lipid and lipoprotein risk factors that are comparable to those elicited by a DASH dietary pattern. These results, in conjunction with the beneficial effects on apolipoprotein CVD risk factors after consumption of the BOLD and BOLD+ diets, which were greater with the BOLD+ diet, provide support for including lean beef in a heart-healthy dietary pattern. This trial was registered at clinicaltrials.gov as NCT00937898.

Background As obesity levels increase, opportunistic behaviour change counselling from primary care clinicians in consultations about healthy eating is ever more important. However, little is known about the approaches clinicians take with patients. Aim To describe the content of simulated consultations on healthy eating in primary care, and compare this with the content of smoking cessation consultations. Design and setting Qualitative study of 23 audiotaped simulated healthy eating and smoking cessation consultations between an actor and primary care clinicians (GPs and nurses) within a randomised controlled trial looking at behaviour change counselling. Method Consultations were audiotaped and transcribed verbatim, then analysed inductively using thematic analysis. A thematic framework was developed by all authors and applied to the data. The content of healthy eating consultations was contrasted with that given for smoking cessation. Results There was a lack of consistency and clarity when clinicians discussed healthy eating compared with smoking; in smoking cessation consultations, the content was clearer to both the clinician and patient. There was a lack of specificity about what dietary changes should be made, how changes could be achieved, and how progress could be monitored. Barriers to change were addressed in more depth within the smoking cessation consultations than within the healthy eating encounters. Conclusion At present, dietary counselling by clinicians in primary care does not typically contain consistent, clear suggestions for specific change, how these could be achieved, and how progress would be monitored. This may contribute to limited uptake and efficacy of dietary counselling in primary care.

BACKGROUND: Oxidative stress is associated with the pathogenesis of cardiovascular diseases. The process of deep-fat frying in dietary cooking oil plays a role in the generation of free radicals. In this study, palm olein heated to 180 °C was tested for its effect on the activity of blood pressure-regulating enzymes and lipid peroxidation. METHODS: Forty-two adult male Sprague-Dawley rats were equally assigned into 6 groups.The first group was fed with normal rat chow as the control group, and the subsequent groups were fed with rat chow fortified with 15% weight/weight of the following: fresh palm olein, palm olein heated once, palm olein heated twice, palm olein heated 5 times, or palm olein heated 10 times. The duration of feeding was 6 months. Fatty acid analyses of oil were performed using gas chromatography. Peroxide values were determined using standard titration. Plasma was collected for biochemical analyses. RESULTS: Repeatedly heated palm olein increased the levels of peroxide, angiotensin-converting enzyme, and lipid peroxidation as well as reduced the level of heme oxygenase. Fresh palm olein and palm olein heated once had lesser effects on lipid peroxidation and a better effect on the activity of blood pressure-regulating enzymes than repeatedly heated palm olein. CONCLUSION: Repeatedly heated palm olein may negatively affect the activity of blood pressure-regulating enzymes and increase lipid peroxidation.

Urinary 3-hydroxy-benzo[a]pyrene (3-OHBaP) is considered as an exposure marker for assessing carcinogenic risks as it is a metabolite of benzo[a]pyrene (BaP). A controlled human study was conducted to examine the kinetics of urinary 3-OHBaP after consuming charcoal-barbecued meat. Two feeding experiments were performed, with meat doses of 15 and 30 g/kg (experiments 1 and 2, respectively). All voided urine over 7 days was collected and analyzed. The background urinary 3-OHBaP concentration was 0.002-0.085 ng/g creatinine, with large inter-individual (80-100%) and intra-individual of (90-100%) variations. The background amount of 3-OHBaP excreted by the current subjects was 40-50 pg/day. The amounts of urinary 3-OHBaP excreted within 12 h post-exposure increased significantly (P

This study was conducted to evaluate the association of single serum total cholesterol (TC) measurement with cardiovascular diseases (CVD) deaths in Korean adults. The study subjects were taken from the multi-site collaborative dynamic prospective cohort for epidemiologic investigation on cancer risk in residents nearby nuclear power plants in Korea. A total of 12,740 adults aged 40 to 69 yr who underwent a mass screening examination were followed up from 1993 to 2008. Occurring CVD deaths were confirmed by the death certificates in the National Statistical Office, Korea. Groups with the lowest group having TC = 240 mg/dL were associated with higher CVD mortality in Cox proportional hazards analysis adjusting for age, sex, smoking and drinking status, body mass index, level of blood pressure, triglyceride and high density lipoprotein cholesterol. The distribution of adjusted hazard ratios showed the U-shaped curve. Based on the results of this study, caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk in Korean adults.

In mammalian cells, the autophagy-dependent degradation of mitochondria (mitophagy) is thought to maintain mitochondrial quality by eliminating damaged mitochondria. However, the physiological importance of mitophagy has not been clarified in yeast. Here, we investigated the physiological role of mitophagy in yeast using mitophagy-deficient atg32- or atg11-knock-out cells. When wild-type yeast cells in respiratory growth encounter nitrogen starvation, mitophagy is initiated, excess mitochondria are degraded, and reactive oxygen species (ROS) production from mitochondria is suppressed; as a result, the mitochondria escape oxidative damage. On the other hand, in nitrogen-starved mitophagy-deficient yeast, excess mitochondria are not degraded and the undegraded mitochondria spontaneously age and produce surplus ROS. The surplus ROS damage the mitochondria themselves and the damaged mitochondria produce more ROS in a vicious circle, ultimately leading to mitochondrial DNA deletion and the so-called "petite-mutant" phenotype. Cells strictly regulate mitochondrial quantity and quality because mitochondria produce both necessary energy and harmful ROS. Mitophagy contributes to this process by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production.