Published Science

Differences in allometric scaling of physiological characters have the appeal to explain species diversification and niche differentiation along a body mass (BM) gradient - because they lead to different combinations of physiological properties, and thus may facilitate different adaptive strategies. An important argument in physiological ecology is built on the allometries of gut fill (assumed to scale to BM(1.0)) and energy requirements/intake (assumed to scale to BM(0.75)) in mammalian herbivores. From the difference in exponents, it has been postulated that the mean retention time (MRT) of digesta should scale to BM(1.0-0.75)=BM(0.25). This has been used to argue that larger animals have an advantage in digestive efficiency and hence can tolerate lower-quality diets. However, empirical data does not support the BM(0.25) scaling of MRT, and the deduction of MRT scaling implies, according to physical principles, no scaling of digestibility; basing assumptions on digestive efficiency on the thus-derived MRT scaling amounts to circular reasoning. An alternative explanation considers a higher scaling exponent for food intake than for metabolism, allowing larger animals to eat more of a lower quality food without having to increase digestive efficiency; to date, this concept has only been explored in ruminants. Here, using data for 77 species in which intake, digestibility and MRT were measured (allowing the calculation of the dry matter gut contents (DMC)), we show that the unexpected shallow scaling of MRT is common in herbivores and may result from deviations of other scaling exponents from expectations. Notably, DMC have a lower scaling exponent than 1.0, and the 95% confidence intervals of the scaling exponents for intake and DMC generally overlap. Differences in the scaling of wet gut contents and dry matter gut contents confirm a previous finding that the dry matter concentration of gut contents decreases with body mass, possibly compensating for the less favorable volume-surface ratio in the guts of larger organisms. These findings suggest that traditional explanations for herbivore niche differentiation along a BM gradient should not be based on allometries of digestive physiology. In contrast, they support the recent interpretation that larger species can tolerate lower-quality diets because their intake has a higher allometric scaling than their basal metabolism, allowing them to eat relatively more of a lower quality food without having to increase digestive efficiency.

Fatigue is commonly reported in the primary care setting; however, its cause is often unclear. This article presents 3 cases involving patients with chronic fatigue syndrome who responded poorly to treatment. After clinical evaluation, all patients were found to meet criteria for attention-deficit/hyperactivity disorder (ADHD) and underwent a standard regimen of a psychostimulant medication. After treatment with psychostimulants, the 3 patients reported improved symptoms of fatigue and pain, and cognitive and core ADHD symptoms. These cases suggest that ADHD and chronic fatigue syndrome (and possibly fibromyalgia) share a common underlying mechanism. This article presents a model suggesting that over time, ADHD (predominantly inattentive type) develops into a syndrome of chronic fatigue and pain. These cases indicate that fatigue may be an important presenting symptom of adult ADHD. These cases also suggest the need for additional research to determine the prevalence of ADHD in patients who present with fatigue, and, in those meeting criteria for ADHD, the responsiveness of fatigue to psychostimulant treatment.

The modern Western diet bears little resemblance to the diet which forged the human genome over many million years. The change in basic food structure is operating to distort biology even before conception and into late years, with the epidemic of obesity and diabetes likely to lead to stroke, heart disease, and now dementia, being flagged as a consequence. In addition, mental ill health is overtaking all other burdens of ill health, and almost certainly has its roots in early disturbance of brain development. Whilst lifestyle will be playing its part, there can be little doubt that the common denominator is the aberrations in food development, predominantly in the last century. It seems it is time to reassess food policy. The principle of food production should be nutrition and human health. The globalisation of a food structure linked to such disorders and their appearance globally in response asks that steps be taken to protect other countries from making the same mistakes.

Background: Limited data exist on the contribution of dietary sources of arsenic to an individual's total exposure, particularly in populations with exposure via drinking water. Here, the association between diet and toenail arsenic concentrations (a long-term biomarker of exposure) was evaluated for individuals with measured household tap water arsenic. Foods known to be high in arsenic, including rice and seafood, were of particular interest.Methods: Associations between toenail arsenic and consumption of 120 individual diet items were quantified using general linear models that also accounted for household tap water arsenic and potentially confounding factors (e.g., age, caloric intake, sex, smoking) (n = 852). As part of the analysis, we assessed whether associations between log-transformed toenail arsenic and each diet item differed between subjects with household drinking water arsenic concentrations

BACKGROUND/OBJECTIVES Cardiovascular disease (CVD) is the leading cause of death in the United States and the world. Clinical trials have suggested that soybean protein lowers lipids and blood pressure. The effect of soybean protein on novel CVD risk factors has not been well studied. The objective of this study was to examine the effect of soybean protein on biomarkers of inflammation, endothelial dysfunction and adipocytokines. SUBJECTS/METHODS The effect of 8 weeks of 40 g of soybean protein supplement (89.3 mg isoflavones), 40 g of milk protein supplement and 40 g of complex carbohydrate placebo was examined in a randomized, placebo-controlled, double-blind, three-phase crossover trial among adults in New Orleans, Louisiana and Jackson, Mississippi. Plasma levels of inflammation biomarkers (C-reactive protein, interleukin-6, tumor necrosis factor-α), endothelial dysfunction biomarkers (E-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, thrombomodulin) and adipocytokines (high-molecular weight adiponectin, leptin, resistin) were measured at baseline and at the end of each intervention using immunoturbidimetric and enzyme-linked immunosorbent assay techniques. RESULTS Soy protein supplementation resulted in a significant mean net change (95% confidence interval) in plasma E-selectin of −3.93 ng/ml (−7.05 to −0.81 ng/ml; P = 0.014) compared with milk protein, and in plasma leptin of −2089.8 pg/ml (−3689.3 to −490.3pg/ml; P = 0.011) compared with carbohydrate. There were no significant changes in any other risk factors. CONCLUSIONS Soy protein supplementation may reduce levels of E-selectin and leptin. Further research is warranted to investigate the mechanisms through which protein may confer protective effects on novel CVD risk factors.

Knowledge of the effects of training volume on upper limb muscular strength and hypertrophy is rather limited. In this study, both arms of the same subject were trained in a crossover-like design with different training volumes (1 or 3 sets) to eliminate the effects of genetic variation and other individual differences. The purpose of this study was to investigate the effects of training volume on muscular strength and hypertrophy in sedentary, untrained young Japanese men. Eight subjects (age, 25.0 ± 2.1 years; body mass, 64.2 ± 7.9 kg; height, 171.7 ± 5.1 cm) were recruited. The subjects trained their elbow flexor muscles twice per week for 12 consecutive weeks using a seated dumbbell preacher curl. The arms were randomly assigned to training with 1 or 3 sets. The training weight was set at 80% of 1 repetition maximum for all sets. The 3-set protocol increased cross-sectional area significantly more than did 1 set (1 set, 8.0 ± 3.7%; 3 sets, 13.3 ± 3.6%, p

CONCLUSIONS: This meta-analysis provides consistent evidence that low GI diets reduce total and LDL-cholesterol and have no effect on HDL-cholesterol or triglycerides. Copyright © 2012 Elsevier B.V. All rights reserved.

Malnutrition affects the oral health and a poor oral health in turn, may lead to malnutrition. This interdependent relationship sees good nutritional health, thus promoting good oral health and vice versa. Malnutrition may alter the homeostasis, which can lead to disease progression of the oral cavity, reduce the resistance to the microbial biofilm and reduce the capacity of tissue healing. It may even affect the development of the oral cavity. Protein-energy malnutrition occurs when there is a deficiency of protein, energy foods or both, which are relative to a body’s need. Studies have suggested that enamel hypoplasia, salivary gland hypofunction and saliva compositional changes may be the mechanisms through which the malnutrition is associated with caries, while an altered eruption timing may create a challenge in the analysis of the age specific caries rates. This paper gives an insight on the relationship of the malnutrition and the protein-energy malnutrition with the oral health status.

BACKGROUND AND AIMS: Vegan diet excludes all foodstuffs of animal origin and leads to cholesterol lowering and possibly reduction of cardiovascular disease risk. The aim was to investigate whether vegan diet improves the metabolic pathway of triglyceride-rich lipoproteins, consisting in lipoprotein lipolysis and removal from circulation of the resulting remnants and to verify whether the diet alters HDL metabolism by changing lipid transfers to this lipoprotein. METHODS AND RESULTS: 21 vegan and 29 omnivores eutrophic and normolipidemic subjects were intravenously injected triglyceride-rich emulsions labeled with (14)C-cholesterol oleate and (3)H-triolein: fractional clearance rates (FCR, in min(-1)) were calculated from samples collected during 60 min for radioactive counting. Lipid transfer to HDL was assayed by incubating plasma samples with a donor nanoemulsion labeled with radioactive lipids; % lipids transferred to HDL were quantified in supernatant after chemical precipitation of non-HDL fractions and nanoemulsion. Serum LDL cholesterol was lower in vegans than in omnivores (2.1 ± 0.8, 2.7 ± 0.7 mmol/L, respectively, p < 0,05), but HDL cholesterol and triglycerides were equal. Cholesteryl ester FCR was greater in vegans than in omnivores (0.016 ± 0.012, 0.003 ± 0.003, p < 0.01), whereas triglyceride FCR was equal (0.024 ± 0.014, 0.030 ± 0.016, N.S.). Cholesteryl ester transfer to HDL was lower in vegans than in omnivores (2.7 ± 0.6, 3.5 ± 1.5%, p

Epidemiological data indicate that atopic eczema (AE) in infancy significantly increases the risk for attention deficit/hyperactivity disorder (ADHD) in later life. The underlying pathophysiological mechanisms of this comorbidity are unknown. We propose that the release of inflammatory cytokines caused by the allergic inflammation and/or elevated levels of psychological stress as a result of the chronic disease interfere with the maturation of prefrontal cortex regions and neurotransmitter systems involved ADHD pathology. Alternatively, increased stress levels in ADHD patients may trigger AE via neuroimmunological mechanisms. In a third model, AE and ADHD may be viewed as two separate disorders with one or more shared risk factors (e.g., genetics, prenatal stress) that increase the susceptibility for both disorders leading to the co-occurrence of AE and ADHD. Future investigation of these three models may lead to a better understanding of the mechanisms underlying the observed comorbidity between AE and ADHD and further, to targeted interdisciplinary primary prevention and treatment strategies.

The pathways of mitophagy for quality control and clearance of mitochondria

Psychological stress is a major provocative factor of symptoms in chronic inflammatory conditions. In recent years, interest in addressing stress responsivity through meditation training in health-related domains has increased astoundingly, despite a paucity of evidence that reported benefits are specific to meditation practice. We designed the present study to rigorously compare an 8-week Mindfulness-Based Stress Reduction (MBSR) intervention to a well-matched active control intervention, the Health Enhancement Program (HEP) in ability to reduce psychological stress and experimentally-induced inflammation. The Trier Social Stress Test (TSST) was used to induce psychological stress and inflammation was produced using topical application of capsaicin cream to forearm skin. Immune and endocrine measures of inflammation and stress were collected both before and after MBSR training. Results show those randomized to MBSR and HEP training had comparable post-training stress-evoked cortisol responses, as well as equivalent reductions in self-reported psychological distress and physical symptoms. However, MBSR training resulted in a significantly smaller post-stress inflammatory response compared to HEP, despite equivalent levels of stress hormones. These results suggest behavioral interventions designed to reduce emotional reactivity may be of therapeutic benefit in chronic inflammatory conditions. Moreover, mindfulness practice, in particular, may be more efficacious in symptom relief than the well-being promoting activities cultivated in the HEP program. © 2012 Elsevier Inc.

There is increasing evidence that dietary saturated fatty acids (SAFA) have not only an indirect atherogenic effect due to increasing LDL-cholesterol concentration but also a direct effect by activating the inflammation process. This review summarizes several recent publications in this field. The effect of SAFA on the inflammation process mediated by Toll-like receptor 4/NF-kappaB pathway has been well documented in various in vitro culture studies of macrophages and adipocytes or in their co-culture. In contrast to these in vitro data, in vivo epidemiological studies or clinical experiments in men are less consistent. Well controlled cross-over studies in volunteers might enlighten the differences between saturated and unsaturated fatty acids dietary intake and proatherogenic inflammation effects.

In humans, essential amino acids (EAAs) stimulate muscle protein synthesis (MPS) with no effect on muscle protein breakdown (MPB). Insulin can stimulate MPS, and carbohydrates (CHOs) and insulin decrease MPB. Net protein balance (NB; indicator of overall anabolism) is greatest when MPS is maximized and MPB is minimized. To determine whether adding CHO or a gluconeogenic amino acid to EAAs would improve NB compared with EAA alone, young men and women (n = 21) ingested 10 g EAA alone, with 30 g sucrose (EAA+CHO), or with 30 g alanine (EAA+ALA). The fractional synthetic rate and phenylalanine kinetics (MPS, MPB, NB) were assessed by stable isotopic methods on muscle biopsies at baseline and 60 and 180 min following nutrient ingestion. Insulin increased 30 min postingestion in all groups and remained elevated in the EAA+CHO and EAA+ALA groups for 60 and 120 min, respectively. The fractional synthetic rate increased from baseline at 60 min in all groups (P \textless 0.05; EAA = 0.053 ± 0.018 to 0.090 ± 0.039% · h(-1); EAA+ALA = 0.051 ± 0.005 to 0.087 ± 0.015% · h(-1); EAA+CHO = 0.049 ± 0.006 to 0.115 ± 0.024% · h(-1)). MPS and NB peaked at 30 min in the EAA and EAA+CHO groups but at 60 min in the EAA+ALA group and NB was elevated above baseline longer in the EAA+ALA group than in the EAA group (P \textless 0.05). Although responses were more robust in the EAA+CHO group and prolonged in the EAA+ALA group, AUCs were similar among all groups for fractional synthetic rate, MPS, MPB, and NB. Because the overall muscle protein anabolic response was not improved in either the EAA+ALA or EAA+CHO group compared with EAA, we conclude that protein nutritional interventions to enhance muscle protein anabolism do not require such additional energy.

It is widely accepted that Hebbian forms of plasticity mediate selective modifications in synaptic strength underlying information encoding in response to experience and circuit formation or refinement throughout development. Several complementary forms of homeostatic plasticity coordinate to keep Hebbian plasticity in check, frequently through the actions of conserved regulatory molecules. Recent evidence suggests that this may be the case for adenosine, which is ubiquitous in the brain and is released by both neurons and glial cells via constitutive and activity-dependent mechanisms. Through A1 and A2A receptor activation, adenosine modulates neuronal homeostasis and tunes the ability of synapses to undergo and/or sustain plasticity. Here, we review how adenosine equilibrates neuronal activity and sets the stage for synaptic plasticity. © 2012 Elsevier Ltd.

Objective Increased sensitivity to alcohol after gastric bypass has been described. The aim of this study was to investigate whether bariatric surgery is associated with alcohol problems. Design and Methods The prospective, controlled Swedish Obese Subjects (SOS) study enrolled 2,010 obese patients who underwent bariatric surgery (68% vertical banded gastroplasty (VBG), 19% banding, and 13% gastric bypass) and 2,037 matched controls. Patients were recruited between 1987 and 2001. Data on alcohol abuse diagnoses, self-reported alcohol consumption, and alcohol problems were obtained from the National Patient Register and questionnaires. Follow-up time was 8-22 years. Results During follow-up, 93.1% of the surgery patients and 96.0% of the controls reported alcohol consumption classified as low risk by the World Health Organization (WHO). However, compared to controls, the gastric bypass group had increased risk of alcohol abuse diagnoses (adjusted hazard ratio [adjHR] = 4.97), alcohol consumption at least at the WHO medium risk level (adjHR = 2.69), and alcohol problems (adjHR = 5.91). VBG increased the risk of these conditions with adjHRs of 2.23, 1.52, and 2.30, respectively, while banding was not different from controls. Conclusions Alcohol consumption, alcohol problems, and alcohol abuse are increased after gastric bypass and VBG.

Nutritional research is undergoing a remarkable transformation driven by new technological tools. Because of the complexity of the components present in food and how they may interact with the biochemical networks of living organisms, nutrition cannot be considered a reductionist discipline. More holistic approaches, which are capable of gathering comprehensive, high-throughput amounts of data, appear to best enhance our understanding of the role of food in health and disease. In this context, global metabolite analysis, or 'metabolomics', is becoming an appealing research tool for nutrigenomics and nutrigenetics scientists. The purpose of the present review is to highlight some potential applications of metabolomics in nutrition research.

Several studies have found an association between sleep duration and morbidity and mortality, but no previous studies have examined the association between sleep disturbances and semen quality. We conducted a cross-sectional study among 953 young Danish men from the general population who were recruited in Copenhagen at the time of determination of fitness for military service between January 2008 and June 2011. All of the men delivered a semen sample, had a blood sample drawn, underwent a physical examination, and answered a questionnaire including information about sleep disturbances. Sleep disturbances were assessed on the basis of a modified 4-item version of the Karolinska Sleep Questionnaire, which includes questions on sleep patterns during the past 4 weeks. Sleep disturbances showed an inverse U-shaped association with sperm concentration, total sperm count, percent motile and percent morphologically normal spermatozoa, and testis size. Men with a high level of sleep disturbance (score \textgreater50) had a 29% (95% confidence interval: 2, 48) lower adjusted sperm concentration and 1.6 (95% confidence interval: 0.3, 3.0) percentage points' fewer morphologically normal spermatozoa than men with a sleep score of 11-20. This appears to be the first study to find associations between sleep disturbances and semen quality. In future studies, investigators should attempt to elucidate mechanistic explanations and prospectively assess whether semen quality improves after interventions restoring a normal sleeping pattern. © The Author 2013. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved.

Meat-eating was a game changer for human evolution. We suggest that the limiting factors for expanding brains earlier were scarcities of nicotinamide and tryptophan. In humans and some other omnivores, lack of meat causes these deficiencies. Nicotinamide adenine dinucleotide (NADH) is necessary to synthesize adenosine triphosphate (ATP) via either glycolysis or via the mitochondrial respiratory chain. NAD consumption is also necessary for developmental and repair circuits. Inadequate supplies result in "de-evolutionary" brain atrophy, as seen with pellagra. If trophic nicotinamide/tryptophan was a "prime mover" in building bigger brains, back-up mechanisms should have evolved. One strategy may be to recruit extra gut symbionts that produce NADH precursors or export nicotinamide (though this may cause diarrhea). We propose a novel supplier TB that co-evolved early, which did not originally and does not now inevitably cause disease. TB has highly paradoxical immunology for a pathogen, and secretes and is inhibited by nicotinamide and its analogue, isoniazid. Sharp declines in TB and diarrhea correlated with increased meat intake in the past, suggesting that dietary vitamin B3 and tryptophan deficiencies (also associated with poor cognition and decreased lifespans) are still common where meat is unaffordable.

Background: The Daniel Fast involves dietary modification similar to a purified vegan diet. Although improvements in several health-specific biomarkers have been noted with this plan, the removal of animal products results in a significant reduction in both dietary protein and saturated fatty acid intake, which results in a loss of lean body mass and a reduction in HDL-cholesterol. Methods. We assigned 29 men and women to either a traditional or modified Daniel Fast for 21 days and measured anthropometric and biochemical markers of health pre and post intervention. The modified Daniel Fast was otherwise identical to the traditional plan but included one serving per day of lean meat and dairy (skim milk), providing approximately 30 grams per day of additional protein. Results: Compared to baseline, both plans resulted in similar and significant improvements in blood lipids, as well as a reduction in inflammation. Conclusions: Modification of dietary intake in accordance with either a traditional or modified Daniel Fast may improve risk factors for cardiovascular and metabolic disease. © 2013 Alleman, Jr et al.; licensee BioMed Central Ltd.

Gillman Mound, on the Adelaide Plains, South Australia, was excavated in 1970 after human remains were discovered during redevelopment. Twenty-two individuals were recovered, along with a further 16 from the Wingfield area. In collaboration with the Kaurna Nation Cultural Heritage Association, these remains were recently analysed and dated. This paper analyses the burial practices in order to identify temporal and spatial continuities and discontinuities, both within the site, and in a more regional context. One of the major issues with burial sites is their interpretation in terms of a temporal scale. The burials at Gillman date to between 1100 and 600 BP. Given that on at least two occasions a single grave was used for the burial of two people, the time frame suggests approximately one burial per generation (or potentially a more episodic use of the site). This points to the existence of multiple places in use for burial at the same time and raises the question of which people were buried at particular places. While some of the burial practices in the mound are congruent with ethnohistoric accounts of Kaurna burials, others point to discontinuities in time or space

OBJECTIVE: Adequate calcium and vitamin D intakes are critical during all life cycle stages. This study aimed to characterize usual intakes of calcium and vitamin D from food and dietary supplements in specific subpopulations of Americans so that fortification/enrichment and supplementation efforts may be targeted toward populations who are truly in need. METHODS: The National Cancer Institute method was used to estimate usual intakes of calcium and vitamin D by source and compared usual intakes to the established Dietary Reference Intakes for U.S. residents aged ≥4 years using National Health and Nutrition Examination Survey 2001-2002, 2003-2004, 2005-2006, and 2007-2008 data sets. RESULTS: These results showed for the first time that low-income, overweight, and/or obese minority populations may be at greater risk of calcium and vitamin D insufficiency. Children aged 4-8 years were more likely to obtain recommended dairy intakes compared with older children and adults of all ages. Food intakes of calcium decreased with age in adults. Adults who used supplemental calcium showed a lower prevalence of insufficiency. Calcium and vitamin D intakes from food and dietary supplements were not related to vegetarian status. Excessive intakes of calcium and vitamin D above the tolerable upper intake level were low among all studied populations and "overnutrification" was not widely present across these analyses. CONCLUSIONS: Age- and gender-specific supplementation and modest use of fortification with calcium and vitamin D may be warranted for targeting certain subpopulations, particularly older adults, teenagers, minorities, and those who are low income and overweight and/or obese. PRACTICAL APPLICATION: This study aimed to characterize usual intakes of calcium and vitamin D from food and dietary supplements in specific subpopulations of Americans so that fortification/enrichment and supplementation efforts may be better targeted. Low-income, overweight, and/or obese minority populations may be at a greater risk of calcium and vitamin D insufficiency.

OBJECTIVE: To investigate whether glycosylated hemoglobin (HbA1c) and 1-hour glucose level in oral glucose tolerance test (OGTT) are useful parameters for evaluation of glucose homeostasis in childhood. METHODS: The medical records of 106 obese/overweight children aged from 7 to 18 years who underwent OGTT were evaluated retrospectively. The subjects were divided into 2 groups according to their one-hour glucose concentration. Group 1 consisted of subjects whose one-hour glucose level was <155 mg/dL, and Group 2 consisted of subjects whose one-hour glucose level was ≥155 mg/dL. The fasting and 2-hour glucose concentrations of the groups were compared. The sensitivity and specificity levels were determined using the ROC curve to assess the predictive value of HbA1c for impaired glucose tolerance (IGT). RESULTS: The mean 2-hour glucose concentration of the subjects in Group 2 was significantly higher than that of the subjects in Group 1 (137.8±35.5 mg/dL versus 113.1±21.2 mg/dL, p<0.05). If a 5.5% cut-off value for HbA1c was accepted as predictor of IGT, the sensitivity was 63% and specificity was 70%. 31% of the subjects with HbA1c levels at or above 5.5% had IGT. This rate was significantly lower in subjects who had HbA1c levels below 5.5% (p

Satellite cells, the quintessential skeletal muscle stem cells, reside in a specialized local environment whose anatomy changes dynamically during tissue regeneration. The plasticity of this niche is attributable to regulation by the stem cells themselves and to a multitude of functionally diverse cell types. In particular, immune cells, fibrogenic cells, vessel-associated cells and committed and differentiated cells of the myogenic lineage have emerged as important constituents of the satellite cell niche. Here, we discuss the cellular dynamics during muscle regeneration and how disease can lead to perturbation of these mechanisms. To define the role of cellular components in the muscle stem cell niche is imperative for the development of cell-based therapies, as well as to better understand the pathobiology of degenerative conditions of the skeletal musculature.

Objective: It is believed that monocyte isolation methods and maturation factors affect the phenotypic and functional characteristics of resultant dendritic cells (DC). In the present study, we compared two monocyte isolation methods, including plastic adherence-dendritic cells (Adh-DC) and magnetic activated cell sorting- dendritic cells (MACS-DC), and their effects on phagocytic activity of differentiated immature DCs (immDCs). Materials and Methods: : In this experimental study, immDCs were generated from plastic adherence and MACS isolated monocytes in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4) in five days. The phagocytic activity of immDCs was analyzed by fluorescein isothiocyanate (FITC)-conjugated latex bead using flow cytometry. One way ANOVA test was used for statistical analysis of differences among experimental groups, including Adh-DC and MACS-DC groups. Results: We found that phagocytic activity of Adh-DC was higher than MACS-DC, whereas the mean fluorescence intensity (MFI) of phagocytic cells was higher in MACS-DC (p

Dietary fat plays an important role in the primary prevention of cardiovascular disease, but long-term (≥12 months) effects of different percentages of fat in the diet on blood lipid levels remain to be established. Our systematic review and meta-analysis focused on randomized controlled trials assessing the long-term effects of low-fat diets compared with diets with high amounts of fat on blood lipid levels. Relevant randomized controlled trials were identified searching MEDLINE, EMBASE, and the Cochrane Trial Register until March 2013. Thirty-two studies were included in the meta-analysis. Decreases in total cholesterol (weighted mean difference -4.55 mg/dL [-0.12 mmol/L], 95% CI -8.03 to -1.07; P=0.01) and low-density lipoprotein (LDL) cholesterol (weighted mean difference -3.11 mg/dL [-0.08 mmol/L], 95% CI -4.51 to -1.71; P\textless0.0001) were significantly more pronounced following low-fat diets, whereas rise in high-density lipoprotein (HDL) cholesterol (weighted mean difference 2.35 mg/dL [0.06 mmol/L], 95% CI 1.29 to 3.42; P\textless0.0001) and reduction in triglyceride levels (weighted mean difference -8.38 mg/dL [-0.095 mmol/L], 95% CI -13.50 to -3.25; P=0.001) were more distinct in the high-fat diet groups. Including only hypocaloric diets, the effects of low-fat vs high-fat diets on total cholesterol and LDL cholesterol levels were abolished. Meta-regression revealed that lower total cholesterol level was associated with lower intakes of saturated fat and higher intakes of polyunsaturated fat, and increases in HDL cholesterol levels were related to higher amounts of total fat largely derived from monounsaturated fat (of either plant or animal origin) in high-fat diets (composition of which was ∼17% of total energy content in the form of monounsaturated fatty acids, ∼8% of total energy content in the form of polyunsaturated fatty acids), whereas increases in triglyceride levels were associated with higher intakes of carbohydrates. In addition, lower LDL cholesterol level was marginally associated with lower saturated fat intake. The results of our meta-analysis do not allow for an unequivocal recommendation of either low-fat or high-fat diets in the primary prevention of cardiovascular disease. © 2013 Academy of Nutrition and Dietetics.

Purpose: To examine the association of red meat and whole-grain bread consumption with plasma levels of biomarkers related to glucose metabolism, oxidative stress, inflammation and obesity. Methods: Our cross-sectional study was based on 2,198 men and women who were selected as a sub-cohort for an investigation of biological predictors of diabetes and cardiovascular diseases from the European Prospective Investigation into Cancer and Nutrition-Potsdam study. Circulating levels of glycated hemoglobin, adiponectin, hs-CRP, gamma-glutamyltransferase, alanine-aminotransferase, fetuin-A, HDL-cholesterol and triglycerides were measured from random blood samples. Diet and lifestyle data were assessed by questionnaires, and anthropometric data were measured. Results: After multivariable adjustment, higher consumption of whole-grain bread was significantly (P trend

A recent advertisement on the back cover of a special health issue of the New York Times Magazine section read “Ironic that a plumber came to us to help him remove a clog.”1 The ad referred to doctors in the cardiac catheterization laboratory as “one kind of pipe specialist,” and noted that the patient in the ad returned to work “just 2 days after having his own pipes cleaned out.” Although the image of coronary arteries as kitchen pipes clogged with fat is simple, familiar, and evocative, it is also wrong. Conceptual models help us to make sense of a complex world. In both research and clinical practice, our conceptual models inform our decisions about which outcomes to measure, which confounders to adjust for, and which patients are likely to benefit from a particular treatment. For example, the model of cervical cancer as the consequence of infection with certain strains of human papilloma virus has led to the development of a vaccine to prevent cancer. However, when a conceptual model is flawed, as in the case of the clogged pipes analogy, we are supposed to discard it and replace it with a more accurate one. In Structure of Scientific Revolutions, Kuhn observed that such paradigm shifts do not occur easily.2 Instead, scientists cling tenaciously to the old, accepted model, despite its inability to explain observed phenomena. In medicine, too, misconceptions embedded in an outdated model may linger for years, influencing physicians' practice and patients' expectations. Simple models, especially those we have worked for years to get the public to understand, may be the hardest to abandon. Previous Section Next Section Misconception Number 1: Arterial Narrowing Is the Problem The clogged pipe analogy of stable coronary heart disease has been particularly difficult to dislodge. This representation had its origins in the 1970s, when researchers observed that the degree of coronary obstruction correlated with subsequent risk of myocardial infarction.3 According to this model, cholesterol plaques in the arterial walls slowly encroach on the lumen, causing silent ischemia first, then angina, and eventually infarction. Diagnosis begins with physiologic stress testing, looking for supply–demand mismatch, and progresses to angiography to find blockages. Treatments based on this theory include both coronary bypass and angioplasty, the latter often explained to patients as a Roto-Rooter or in the case of the magazine ad, as a Rotablator. Results of such revascularization procedures are visually striking and, in stable disease, may lead to the erroneous conclusion that the plumbing problem has been fixed and the risk of myocardial infarction ameliorated. Indeed, early proponents of coronary artery bypass were so convinced by the angiographic evidence of success that they questioned the need to conduct randomized trials to assess the impact on myocardial infarction or mortality.4 Four decades later, we know that the interactions between dietary fat, serum cholesterol, and arterial endothelium are complex and dynamic.5 Although high-grade stenoses can cause chronic angina, most cardiac events occur at lesions that appeared mild on previous angiography.6 These plaques contain a lipid-rich core covered by a thin fibromatous cap. Inflammatory cells (eg, macrophages and mast cells) within the plaque may become activated by microbes, autoantigens, or inflammatory molecules (activated plaque model). The activated cells secrete cytokines and proteases that weaken the fibrous cap, causing it to erode or rupture. The newly exposed subendothelium and procoagulant factors precipitate platelet aggregation and local thrombus formation, sometimes leading to infarction. Before rupture, these plaques often do not limit flow and may be invisible to angiography and stress tests. They are therefore not amenable to percutaneous coronary intervention (PCI). To add to the confusion, in the setting of myocardial infarction, the model of an obstructed pipe is accurate, and interventions aimed at eliminating the thrombus, either thrombolytics or angioplasty, can be lifesaving. But for patients with stable disease, local interventions can only relieve symptoms; they cannot prevent future myocardial infarctions. Indeed, at least 12 randomized trials conducted between 1987 and 2007 and involving \textgreater5 000 patients have found no reduction in myocardial infarction attributable to angioplasty in any of its forms.7,8 Despite this overwhelming evidence, the plumbing model, complete with blockages that can be fixed, continues to be used to explain stable coronary disease to patients, who understandably assume that PCI will prevent heart attacks.9 Cardiologists also cling to the belief that for patients with stable coronary disease, an open artery is beneficial,10 and the approach to stable coronary artery disease continues to be a search for ischemia. Not surprisingly, a substantial minority of cardiologists also believe that elective angioplasty and stenting can prevent heart attacks.9 These beliefs translate into practice: As many as half of all elective PCIs may be inappropriate.11 Previous Section Next Section Misconception Number 2: Fat Clogs Arteries The plumbing model—in which dietary fat or cholesterol is slowly deposited in arterial walls, leading to blockages—also perpetuates misconceptions about fat consumption. Although atheromatous plaques contain lipids, they are not composed of fat directly from the diet. Low-density lipoprotein is produced primarily in the liver and may infiltrate vascular endothelium, where it can initiate a complex inflammatory response, especially at sites of hemodynamic strain.5 This inflammatory response can lead to arterial remodeling, in which plaque growth within the vessel walls is accommodated by outward enlargement of the vessel. In that case, large plaques may not encroach on the lumen and are therefore hidden from angiography. These plaques are particularly dangerous both because they are prone to rupture and because before rupture they do not limit flow and therefore do not induce formation of protective collaterals. High-density lipoprotein removes low-density lipoprotein from peripheral tissues through reverse cholesterol transport to the liver and may have antiinflammatory properties.12 Although saturated fat increases low-density lipoprotein cholesterol, it also increases high-density lipoprotein, so the net effect on cardiac risk is neutral. The American Heart Association's (AHA's) early diet recommendations reflected beliefs about fat in the 1980s. They recommended limiting total dietary fat to 30% of calories and saturated fat to 10% on the basis of the caloric density of fat and the association of saturated fat with coronary heart disease across countries.13 The interpretation of this evidence was selective and ignored the low rates of heart disease in Crete and among the Inuit, as well as the notorious French Paradox, wherein the French were noted to consume a diet high in both fat and saturated fat yet had low levels of heart disease.14,15 From these recommendations, low-fat diets became synonymous with heart-healthy diets and gave birth to a generation of low-fat, high-sugar substitutes. More recent observational studies do not support the use of low-fat diets. In 1997, the Nurses' Health Study demonstrated that after proper adjustment neither total fat consumption nor saturated fat was associated with heart disease and that polyunsaturated fat was actually protective.16 Subsequent studies have also found no link between saturated fat and heart disease.17,18 In keeping with the new evidence, the AHA changed its diet recommendations, eliminating restrictions on total fat and acknowledging that low-fat diets had adverse effects on high-density lipoprotein cholesterol.19 But for patients with elevated low-density lipoprotein, they have tightened restrictions on saturated fats and now recommend that consumption not exceed 7% of total calories. Although it may be argued that reducing saturated fat will increase consumption of polyunsaturated fat, in many products, fat is simply replaced by sugar. More recently, the AHA recommended that people limit their intake of sugar, which now appears to contribute to obesity, hypertension, and subsequently coronary heart disease.20 However, patients and many doctors have not gotten this message. The AHA's heart-healthy label still appears on a number of low-fat, high-sugar foods, including fruit juices and sugary cereals,21 whereas patients continue to believe that dietary fat, especially the saturated fat found in cheese and bacon, is the cause of heart disease. A recent survey revealed that 73% of patients believed eating fried food increased the risk of heart attack, the same proportion that believed smoking did.22 A Google search of “artery-clogging saturated fat” returns 195 000 hits, many offering advice about a healthy diet. Previous Section Next Section Promoting Evidence to Doctors and Patients How do we end the misconceptions? First, institutions like the AHA should be more proactive in educating doctors about the inflammatory disease model and how to communicate it to patients. The 2011 American College of Cardiology Foundation/AHA/Society for Cardiovascular Angiography and Interventions guideline for PCI23 is a step in the right direction, stating that patients considering PCI “should understand when the procedure is being performed in an attempt to improve symptoms, survival, or both.” The guideline points out that “evaluation of 61 trials of PCI conducted over several decades shows that despite improvements in PCI technology and pharmacotherapy, PCI has not been demonstrated to reduce the risk of death or [myocardial infarction] in patients without recent [acute coronary syndrome]” but makes no mention of pathophysiology. Few medical questions have engendered 61 randomized trials, yet the authors of the guideline still rate the Level of Evidence as “B”

Island archipelagos of the tropical coast of central Queensland include the most distant offshore islands used by Aboriginal Australians. Excavations on Collins, Otterbourne and High Peak Islands, located up to 40 km from the mainland, reveal evidence of offshore voyaging and marine specialisation in the Shoalwater Bay region for at least 5200 years. A time lag of up to 3000 years between island formation and systematic island use may reflect delayed development of key marine resources. Expansion of island use commencing around 3000–3500 years ago is linked to population increases sustained by synchronous increases in marine resources. Occupational hiatuses variously between 1000 and 3000 years ago are associated with increased ENSO activity. Intensified island use within the past 1000 years is primarily a social phenomenon associated with continuing demographic pressures and the development of more coastally and marine-focused mainland groups, with settlement patterns increasingly encompassing adjacent islands. The viability of risky offshore canoe voyaging was underwritten by two key high-return subsistence pursuits – hunting green turtles and collecting turtle eggs. In addition to subsistence and quartz quarrying, a key motivation for island visitation may have been socially restricted (e.g. ceremonial) practices.

The ketogenic diet is a high-fat, low-carbohydrate diet long used to treat refractory epilepsy; ketogenesis (ketone body formation) is a physiological phenomenon also observed in patients following lowcarbohydrate, low-calorie diets prescribed for rapid weight loss. We report the case of a pair of twin sisters, whose high-frequency migraine improved during a ketogenic diet they followed in order to lose weight. The observed time-lock between ketogenesis and migraine improvement provides some insight into how ketones act to improve migraine.

It is well established that diet influences the health of an individual and that a diet rich in plant-based foods has many advantages in relation to the health and well-being of an individual. What has been unclear until recently is the large contribution of the gut microbiota to this effect. As well as providing basic nutritional requirements, the long-term diet of an animal modifies its gut microbiota. In adults, diets that have a high proportion of fruit and vegetables and a low consumption of meat are associated with a highly diverse microbiota and are defined by a greater abundance of Prevotella compared to Bacteroides, while the reverse is associated with a diet that contains a low proportion of plant-based foods. Furthermore, it is becoming increasingly clear that the effect of the microbial ecology of the gut goes beyond the local gut immune system and is implicated in immune-related disorders, such as IBS, diabetes and inflamm-ageing. In this review, we investigate the evidence that a balanced diet leads to a balanced, diverse microbiota with significant consequences for healthy ageing by focusing on conditions of interest. © 2013 by the authors; licensee MDPI, Basel, Switzerland.

Prostate cancer is the most common non-cutaneous cancer in men in the United States. Several studies have examined the relationship between prostate cancer and antioxidants; however, the results of these studies are inconsistent. This article provides a systematic review of studies on prostate cancer and antioxidant intake from diet and supplements. Tea and coffee appear to offer protection against advanced prostate cancer. Different forms of vitamin E appear to exert different effects on prostate cancer, with alpha-tocopherol potentially increasing and gamma-tocopherol potentially decreasing risk of the disease. There is no strong evidence for a beneficial effect of selenium, vitamin C, or beta-carotene, while lycopene appears to be negatively associated with risk of the disease. The effect of dietary antioxidants on prostate cancer remains undefined and inconclusive, with different antioxidants affecting prostate cancer risk differentially. Further studies are needed to clarify the relationship between antioxidants and prostate cancer risk and to delineate the underlying mechanisms.

Black compared with non-Hispanic white Americans have higher systolic and diastolic blood pressure and rates of prehypertension/hypertension. Reasons for these adverse findings remain obscure. Analyses here focused on relations of foods/nutrients/urinary metabolites and higher black blood pressure for 369 black compared with 1190 non-Hispanic white Americans aged 40 to 59 years from 8 population samples. Multiple linear regression, standardized data from four 24-hour dietary recalls per person, two 24-hour urine collections, and 8 blood pressure measurements were used to quantitate the role of foods, nutrients, and metabolites in higher black blood pressure. Compared with non-Hispanic white Americans, blacks' average systolic/diastolic pressure was higher by 4.7/3.4 mm Hg (men) and 9.0/4.8 mm Hg (women). Control for higher body mass index of black women reduced excess black systolic/diastolic pressure to 6.8/3.8 mm Hg. Lesser intake of vegetables, fruits, grains, vegetable protein, glutamic acid, starch, fiber, minerals, and potassium, and higher intake of processed meats, pork, eggs, and sugar-sweetened beverages, along with higher cholesterol and higher Na/K ratio, related to in higher black blood pressure. Control for 11 nutrient and 10 non-nutrient correlates reduced higher black systolic/diastolic pressure to 2.3/2.3 mm Hg (52% and 33% reduction in men) and to 5.3/2.8 mm Hg (21% and 27% reduction in women). Control for foods/urinary metabolites had little further influence on higher black blood pressure. Less favorable multiple nutrient intake by blacks than non-Hispanic white Americans accounted, at least in part, for higher black blood pressure. Improved dietary patterns can contribute to prevention/control of more adverse black blood pressure levels. © 2013 American Heart Association, Inc.

The purpose of the present literature review was to investigate and summarize the current evidence on associations between dietary patterns and biomarkers of inflammation, as derived from epidemiological studies. A systematic literature search was conducted using PubMed, Web of Science, and EMBASE, and a total of 46 studies were included in the review. These studies predominantly applied principal component analysis, factor analysis, reduced rank regression analysis, the Healthy Eating Index, or the Mediterranean Diet Score. No prospective observational study was found. Patterns identified by reduced rank regression as being statistically significantly associated with biomarkers of inflammation were almost all meat-based or "Western" patterns. Studies using principal component analysis or a priori-defined diet scores found that meat-based or "Western-like" patterns tended to be positively associated with biomarkers of inflammation, predominantly C-reactive protein, while vegetable- and fruit-based or "healthy" patterns tended to be inversely associated. While results of the studies were inconsistent, interventions with presumed healthy diets resulted in reductions of almost all investigated inflammatory biomarkers. In conclusion, prospective studies are warranted to confirm the reported findings and further analyze associations, particularly by investigating dietary patterns as risk factors for changes in inflammatory markers over time. © 2013 International Life Sciences Institute.

Analysis of dietary patterns has been used to examine the impact of diet on chronic diseases. The objectives of this study were to identify the dietary pattern among diabetic patients and to investigate the association between patterns and the metabolic risk factors i.e. anthropometric, glucose and lipid abnormalities. In a cross-sectional survey, 170 diabetic patients, both genders were randomly enrolled from Elnoor Hospital. Information about diet was obtained using a 74-item FFQ. Principal components analysis was applied to extract dietary patterns. Linear regression analysis evaluated the associations between the extracted dietary patterns and the metabolic risks. Six components were derived explaining 73.34% of the total variation. The components explained, 22.64, 16.63, 12.38, 10.41, 8.66 and 2.61 % of the variation. Component 1 "Transitional pattern" was positively associated with risk factors (r-range 0.556-0.784, p-range 0.022-0.0001). An inverse association was found for Healthy and Traditional patterns (r-range-0.468 to-0.709, p-range 0.05-0.0001, r-range-0.466 to-0.673, p-range 0.05-0.0001), respectively. "Desirable fat pattern" was associated with modestly reduced risks of diabetes. No association was found between miscellanies and snacks patterns and metabolic risk factors. A dietary pattern that includes meat, refined cereals, was associated with increased levels of risk biomarkers, whereas fish, legumes, vegetables, fruits and nuts intake showed the inverse results.

Associations between individual foods or nutrients and oxidative markers have been reported. Comprehensive measures of food intake may be uniquely informative, given the complexity of oxidative systems and the possibility of antioxidant synergies. We quantified associations over a 20-year history between three food-based dietary patterns (summary measures of whole diet) and a plasma biomarker of lipid peroxidation, F2-isoprostanes, in a cohort of Americans ages 18-30 at year 0 (1985-1986). We assessed diet at years 0, 7, and 20 through a detailed history of past-month food consumption and supplement use and measured plasma F2-isoprostanes at years 15 and 20. We created three dietary patterns: (1) a priori (a priori diet quality score) based on hypothesized healthfulness of foods, (2) an empirical pattern reflecting high fruit and vegetable intake (fruit-veg), and (3) an empirical pattern reflecting high meat intake (meat). We used linear regression to estimate associations between each dietary pattern and plasma F2-isoprostanes cross-sectionally (at year 20, n=2736) and prospectively (year 0/7 average diet and year 15/20 average F2-isoprostanes, n=2718), adjusting for age, sex, race, total energy intake, education, smoking, body mass index, waist circumference, physical activity, and supplement use. In multivariable-adjusted cross-sectional analysis, the a priori diet quality score and the fruit-veg diet pattern were negatively, and the meat pattern was positively, associated with F2-isoprostanes (all p values <0.001). These associations remained statistically significant in prospective analysis. Our findings suggest that long-term adherence to a diet rich in fruits and vegetables and low in red meat may decrease lipid peroxidation. © 2012 Elsevier Inc.

Over the last few years, the concept of food addiction has become a common feature in the scientific literature, as well as the popular press. Nevertheless, the use of the term addiction to describe pathological aspects of food intake in humans remains controversial, and even among those who affirm the validity of the concept, there is considerable disagreement about its utility for explaining the increasing prevalence of obesity throughout much of the world. An examination of the literature on food addiction indicates that mesolimbic and nigrostriatal dopamine systems often are cited as mechanisms that contribute to the establishment of food addiction. However, in reviewing this literature, it is important to have a detailed consideration of the complex nature of dopaminergic involvement in motivational processes. For example, although it is often stated that mesolimbic dopamine mediates reward, there is no standard or consistent technical meaning of this term. Moreover, there is a persistent tendency to link dopamine transmission with pleasure or hedonia, as opposed to other aspects of motivation or learning. The present article provides a critical discussion of some aspects of the food addiction literature, viewed through the lens of recent findings and current theoretical views of dopaminergic involvement in food motivation. Furthermore, compulsive food intake and binge eating will be considered from an evolutionary perspective, in terms of the motivational subsystems that are involved in adaptive patterns of food consumption and seeking behaviors and a consideration of how these could be altered in pathological conditions. © 2013 Society of Biological Psychiatry.

The aim of the present study was to investigate the effect of Finnish sauna bathing on a white blood cell profile, cortisol levels and selected physiological indices in athletes and non-athletes. The study evaluated 9 trained middle-distance runners and 9 male non-athletes. The subjects from both groups participated in 15-minute sauna sessions until their core temperature rose by 1.2°C (mean temperature in the sauna room was 96° ± 2°C; relative humidity was 15 ± 3%) with a 2 minute cool down with water at a temperature of 19-20°C. Body mass was measured before and after the session and blood samples were taken for tests. Rectal temperature was monitored at five-minute intervals during the whole session. Serum total protein, haematological indices and cortisol levels were determined. Sauna bathing caused higher body mass loss and plasma volume in the athletes compared to the group of non-athletes. After the sauna session, an increased number of white blood cells, lymphocyte, neutrophil and basophil counts was reported in the white blood cell profile. Higher increments in leukocyte and monocyte after the sauna bathing session were recorded in the group of athletes compared to untrained subjects. The obtained results indicated that sauna bathing stimulated the immune system to a higher degree in the group of athletes compared to the untrained subjects.

STUDY OBJECTIVES: Examine sleep restriction's effects on weight gain, daily caloric intake, and meal timing. DESIGN: Repeated-measures experiments assessing body weight at admittance and discharge in all subjects (N = 225) and caloric intake and meal timing across days following 2 baseline nights, 5 sleep restriction nights and 2 recovery nights or across days following control condition nights in a subset of subjects (n = 37). SETTING: Controlled laboratory environment. PARTICIPANTS: Two hundred twenty-five healthy adults aged 22-50 y (n = 198 sleep-restricted subjects; n = 31 with caloric intake data; n = 27 control subjects; n = 6 with caloric intake data). INTERVENTIONS: Approximately 8-to-1 randomization to an experimental condition (including five consecutive nights of 4 h time in bed [TIB]/night, 04:00-08:00) or to a control condition (all nights 10 h TIB/night, 22:00-08:00). MEASUREMENTS AND RESULTS: Sleep-restricted subjects gained more weight (0.97 ± 1.4 kg) than control subjects (0.11 ± 1.9 kg; d = 0.51, P = 0.007). Among sleep-restricted subjects, African Americans gained more weight than Caucasians (d = 0.37, P = 0.003) and males gained more weight than females (d = 0.38, P = 0.004). Sleep-restricted subjects consumed extra calories (130.0 ± 43.0% of daily caloric requirement) during days with a delayed bedtime (04:00) compared with control subjects who did not consume extra calories (100.6 ± 11.4%; d = 0.94, P = 0.003) during corresponding days. In sleep-restricted subjects, increased daily caloric intake was due to more meals and the consumption of 552.9 ± 265.8 additional calories between 22:00-03:59. The percentage of calories derived from fat was greater during late-night hours (22:00-03:59, 33.0 ± 0.08%) compared to daytime (08:00-14:59, 28.2 ± 0.05%) and evening hours (15:00-21:59, 29.4 ± 0.06%; Ps \textless 0.05). CONCLUSIONS: In the largest, most diverse healthy sample studied to date under controlled laboratory conditions, sleep restriction promoted weight gain. Chronically sleep-restricted adults with late bedtimes may be more susceptible to weight gain due to greater daily caloric intake and the consumption of calories during late-night hours. CITATION: Spaeth AM; Dinges DF; Goel N. Effects of experimental sleep restriction on weight gain, caloric intake, and meal timing in healthy adults. SLEEP 2013;36(7):981-990.

Context: Qualitative aspects of diet influence eating behavior and body weight, but the physiological mechanisms for these calorie-independent effects remain speculative. The postprandial rise in blood glucose as quantified by the glycemic index (GI) is of particular interest, as a high GI elicits hormonal and metabolic events that cause hunger and overeating. Thus, our aim was to examine the effects of GI on brain activity in the late postprandial period, after a typical inter-meal interval. Methods: Using a randomized, blinded, crossover design, 12 overweight or obese men age 18-35 years consumed high and low GI meals controlled for calorie content, macronutrient composition and palatability on two occasions. Frequent hunger ratings and blood samples were obtained. Functional neuroimaging was performed 4 hours after the test meals. Main outcome measures were cerebral blood flow as a measure of resting brain activity, assessed by arterial spin labelling MRI (the primary outcome), plasma glucose and insulin levels, and reported palatability and hunger. We hypothesized that brain activity would be greater after the high vs. low GI meal in areas involved in the regulation of eating behavior, reward and addiction, including the striatum, hypothalamus, amygdala, hippocampus, cingulate, orbitofrontal cortex and insular cortex. Results: Incremental plasma glucose (2hr area under the curve) was 2.4 fold greater after the high vs. low GI meal (P=0.0001). Plasma glucose was lower (83.9 mg/dL vs. 95.6 mg/dL, P=0.005) and reported hunger was greater (P=0.04) four hours after the high GI meal. At this time, the high GI meal elicited greater brain activity centered in the right nucleus accumbens (P\textless0.0001), spreading to other areas of the right striatum (caudate, putamen and globus pallidus) and to the olfactory area. Conclusion: Compared to an isocaloric low GI meal, a high GI meal decreased plasma glucose, increased hunger and selectively stimulated brain areas associated with addiction in the late postprandial period, a time with special significance to eating behavior at the next meal. These findings provide a possible mechanism for the previously described excess food intake after high GI meals, and a target for therapeutic interventions.