Published Science

Modern diets are largely heat-processed and as a result contain high levels of advanced glycation end products (AGEs). Dietary advanced glycation end products (dAGEs) are known to contribute to increased oxidant stress and inflammation, which are linked to the recent epidemics of diabetes and cardiovascular disease. This report significantly expands the available dAGE database, validates the dAGE testing methodology, compares cooking procedures and inhibitory agents on new dAGE formation, and introduces practical approaches for reducing dAGE consumption in daily life. Based on the findings, dry heat promotes new dAGE formation by >10- to 100-fold above the uncooked state across food categories. Animal-derived foods that are high in fat and protein are generally AGE-rich and prone to new AGE formation during cooking. In contrast, carbohydrate-rich foods such as vegetables, fruits, whole grains, and milk contain relatively few AGEs, even after cooking. The formation of new dAGEs during cooking was prevented by the AGE inhibitory compound aminoguanidine and significantly reduced by cooking with moist heat, using shorter cooking times, cooking at lower temperatures, and by use of acidic ingredients such as lemon juice or vinegar. The new dAGE database provides a valuable instrument for estimating dAGE intake and for guiding food choices to reduce dAGE intake.

BACKGROUND: Excess visceral adipose tissue (VAT) is considered to be a component in metabolic syndrome, an accumulation of cardiovascular risk factors that includes increased blood pressure; however, there are no previous data showing an association between increases in the VAT-subcutaneous adipose tissue (SAT) ratio and difficult-to-treat hypertension. METHODS: In 572 patients who had cardiovascular risk factors and who were under stable antihypertensive treatment, we evaluated whether the VAT-SAT ratio, as assessed by abdominal computed tomography, predicted difficult-to-treat hypertension, which we defined as an elevation of clinic blood pressure (i.e., clinic blood pressure >or=140/90 mmHg) during treatment with at least three antihypertensive drugs. RESULTS: In men, an elevated VAT-SAT ratio [odds ratio (OR) 1.44 per 1 SD (0.52), 95% confidence interval (CI) 1.08-1.92] and alcohol drinking habit (OR 2.16, 95% CI 1.07-4.36) were significant predictors of difficult-to-treat hypertension, independently of the presence of metabolic syndrome or the insulin level. However, when we included diuretic use in the diagnosis of difficult-to-treat hypertension (i.e., resistant hypertension), the significance of the VAT-SAT ratio disappeared (P = 0.06), and a decreased estimated glomerular filtration rate (OR 0.74 per 10 ml/min per 1.73 m, 95% CI 0.58-0.94) and alcohol drinking habit (OR 4.31, 95% CI 1.74-10.68) were the significant predictors. In contrast, in women, the VAT-SAT ratio did not predict difficult-to-treat hypertension (P = 0.18). CONCLUSION: An increased VAT-SAT ratio was associated with difficult-to-treat hypertension in men, but not with resistant hypertension, suggesting that diuretic use may partly affect the relationship between the VAT-SAT ratio and difficult-to-treat hypertension.

Recent dietary guidelines emphasize micronutrient sufficiency by giving importance to consumption of whole grains and a variety of fruits and vegetables. The objective of this study was to identify a measure of micronutrient quality of diets in adolescent girls consuming a lacto-vegetarian diet. Data were collected on the nutritional status of 630 schoolgirls (ages 10 to 16 years) from Pune city, India, in a cross-sectional survey during 2006-2007. Dietary intakes were assessed by 24-hour recall on 3 nonconsecutive days. Nutrient intakes were calculated from the Indian nutritive value databases. Micronutrient adequacy was expressed as a ratio of observed intake to reference intake. An Adolescent Micronutrient Quality Index (AMQI) was formulated using the Indian and the recent US dietary guidelines. Fasting blood samples were analyzed for plasma levels of vitamin C, beta carotene, and zinc. The average energy intake of the majority of the girls was below the Indian recommended dietary intakes, whereas micronutrient intakes were 50% to 70% lower than recommended dietary intakes. The mean AMQI score was 41.5+/-9.4. The age of subjects as well as mother's education and occupation were significantly associated with the AMQI. The AMQI was correlated with nutrient intakes and the ratio of observed intake to reference intake (P

Attention-deficit hyperactivity disorder (ADHD) is recognized to exist in males and females although the literature supports a higher prevalence in males. However, when girls are diagnosed with ADHD, they are more often diagnosed as predominantly inattentive than boys with ADHD. This article provides a review of gender differences noted across the lifespan. Males and females with ADHD are more similar than different, and generally ADHD profiles are not sex specific. Small gender differences have been found: adolescent girls with ADHD have lower self-efficacy and poorer coping strategies than adolescent boys with ADHD; rates of depression and anxiety may be higher, and physical aggression and other externalizing behaviors lower in girls and women with ADHD. Men with ADHD seem to be incarcerated more often than women with ADHD. However, many studies suffer from small sample sizes, referral biases, differences in diagnostic procedures, and possible rater influences. Treatments are reviewed and discussed with reference to the reported gender differences in functioning and the global deficits noted in all samples. The data available so far suggest that treatments are likely to be equally effective in males and females. However, referral bias is a problem, in that females with ADHD are less likely to be referred for treatment than males with ADHD. Future research should include equal representation of both sexes in samples such that sex by treatment analyses can be routinely conducted.

PURPOSE OF REVIEW: HDL is a cardioprotective lipoprotein, at least in part, because of its ability to mediate reverse cholesterol transport (RCT). It is becoming increasingly clear that the antiatherogenic effects of HDL are not only dependent on its concentration in circulating blood but also on its biological 'quality'. This review summarizes our current understanding of how the biological activities of individual subclasses of HDL particles contribute to overall HDL performance in RCT. RECENT FINDINGS: Recent work indicates that apolipoprotein A-I-containing nascent HDL particles are heterogeneous and that such particles exert different effects on the RCT pathway. RCT from macrophages has been examined in detail in mice and the roles of plasma factors (lecithin-cholesterol acyltransferase, cholesterol ester transfer protein, phospholipid transfer protein) and cell factors (ATP-binding cassette transporter A1, ATP-binding cassette transporter G1, scavenger receptor class B type 1) have been evaluated. Manipulation of such factors has consistent effects on RCT and atherosclerosis, but the level of plasma HDL does not reliably predict the degree of RCT. Furthermore, HDL cholesterol or apolipoprotein A-I levels do not necessarily correlate with the magnitude of cholesterol efflux from macrophages; more understanding of the contributions of specific HDL subspecies is required. SUMMARY: The antiatherogenic quality of HDL is defined by the functionality of HDL subspecies. In the case of RCT, the rate of cholesterol movement through the pathway is critical and the contributions of particular types of HDL particles to this process are becoming better defined.

Nutrient digestion and absorption is necessary for the survival of living organisms and has evolved into the complex and specific task of the gastrointestinal (GI) system. While most people simply assume that their GI tract will work properly to use nutrients, provide energy, and release wastes, few nonscientists know the details about how various nutrients are digested and how the breakdown products traverse the cells lining the small intestine to reach the blood stream and to be used by the other cells of the body. There have been several recent discoveries of new transporters that likely contribute to the absorption of oligopeptides and fatty acids. In addition, details are being clarified about how transporters work and in what forms nutrients can be absorbed. The enzymes that digest basic carbohydrates, proteins, and fats have been identified in various segments of the GI tract, and details are becoming clearer about what types of bonds they hydrolyze. Usually, detailed information about the digestion of basic nutrients is presented and learned in biochemistry courses and detailed information about absorption via transepithelial transport of the breakdown products of digestion is studied in physiology courses. The goal of this Staying Current article is to combine the details of the biochemistry of digestion with the updated information about the physiology of nutrient absorption into one source for teachers of physiology. Insights are included about some of the diseases and conditions that can bring about malabsorption of food in the GI tract and their consequences.

Previous studies on coffee examined absorption of phenolic acids (PA) in the small intestine, but not the contribution of the colon to absorption. Nine healthy volunteers ingested instant soluble coffee ( approximately 335 mg total chlorogenic acids (CGAs)) in water. Blood samples were taken over 12 h, and at 24 h to assess return to baseline. Many previous studies, which used glucuronidase and sulfatase, measured only PA and did not rigorously assess CGAs. To improve this, plasma samples were analyzed after full hydrolysis by chlorogenate esterase, glucuronidase and sulfatase to release aglycone equivalents of PA followed by liquid-liquid extraction and ESI-LC-ESI-MS/MS detection. Ferulic, caffeic and isoferulic acid equivalents appeared rapidly in plasma, peaking at 1-2 h. Dihydrocaffeic and dihydroferulic acids appeared in plasma 6-8 h after ingestion (T(max=)8-12 h). Substantial variability in maximum plasma concentration and T(max) was also observed between individuals. This study confirms that the small intestine is a significant site for absorption of PA, but shows for the first time that the colon/microflora play the major role in absorption and metabolism of CGAs and PA from coffee.

Diabetes type 1 seems to be more prevalent in epilepsy, and low-carbohydrate diets improve glycemic control in diabetes type 2, but data on the use of the classic ketogenic diet (KD) in epilepsy and diabetes are scarce. We present 15 months of follow-up of a 3 years and 6 months old girl with diabetes type 1 (on the KD), right-sided hemiparesis, and focal epilepsy due to a malformation of cortical development. Although epileptiform activity on electroencephalography (EEG) persisted (especially during sleep), clinically overt seizures have not been reported since the KD. An improved activity level and significant developmental achievements were noticed. Glycosylated hemoglobin (HbA1c) levels improved, and glycemic control was excellent, without severe side effects. Our experience indicates that diabetes does not preclude the use of the KD.

This report summarises a workshop convened by the UK Food Standards Agency (FSA) on 14 October 2008 to discuss current FSA-funded research on carbohydrates and cardiovascular health. The objective of this workshop was to discuss the results of recent research and to identify any areas which could inform future FSA research calls. This workshop highlighted that the FSA is currently funding some of the largest, well-powered intervention trials investigating the type of fat and carbohydrate, whole grains and fruit and vegetables, on various CVD risk factors. Results of these trials will make a substantive contribution to the evidence on diet and cardiovascular risk.

Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases worldwide, mostly due to the dramatic increase in obesity rates. This disease presents mainly as simple liver steatosis, whereas 10-20% of patients exhibit an inflammatory phenotype referred to as non-alcoholic steatohepatitis (NASH). Advanced liver disease affects a smaller group of patients including fibrosis, cirrhosis and hepatocellular carcinoma. Higher age, extensive overweight, and number of features of the metabolic syndrome are associated with NAFLD severity. In most cases, NAFLD is associated with insulin resistance and insulin resistance is therefore a major target for all NAFLD treatment modalities. Various treatments into this direction, such as the use of thiazolidinediones have recently failed and did not lead to an improvement in liver histology parameters. Successful weight loss either achieved via bariatric surgery or subsequent to lifestyle modification/behavior therapy, however, has been demonstrated to improve both metabolic parameters and liver histology including inflammatory changes. The first recently reported randomized controlled trial in NASH patients testing the effects of weight loss showed that a one year period of lifestyle adjustment resulted in a 7-10% weight loss with significant histological improvement of liver disease. Orlistat, the only available obesity drug treatment on the market, failed to improve insulin resistance or histopathology in NAFLD. Therefore, new weight-loss inducing agents are eagerly awaited to increase the percentage of obese people to benefit from weight reduction.

N-3 polyunsaturated fatty acids have been associated with reduced colon tumorigenesis. However, their association with colorectal cancer incidence is not conclusive. We investigated the influence of isocaloric replacement of red meat with fatty fish on endogenous nitrosation, inflammation and genotoxicity of faecal water in apparently healthy human volunteers on controlled diets. Fourteen volunteers consumed a high red meat, a combined red meat/fish and a high fish diet for 8 days each. Faecal homogenates were analysed for haem, nitroso compounds (NOC) and calprotectin and associated supernatants for genotoxicity. Both faecal NOC and haem excretion decreased with more fish and less meat in the diet. Nitrosyl iron (FeNO) was the main contributor to total NOC on all diets. The proportion of other NOC increased with more fish and less meat in the diet (P = 0.01), resulting in a non-statistically significant decrease in the proportion of FeNO on the fish diet. There was no statistically significant difference in faecal calprotectin (P = 0.54) and faecal water-induced DNA strand breaks and oxidized purines and pyrimidines between the diets (P > 0.36). Increasing fish intake and reducing the intake of red meat does not seem to have an effect on inflammation and faecal water-induced (oxidative) DNA damage; however, it does reduce the formation of mutagenic and potentially carcinogenic NOC and may as such beneficially affect colorectal risk.

We evaluated a community-based 12-week healthy lifestyle program in Moloka‘i, HI, called Ke ‘Ano Ola, which was developed to decrease chronic disease risk through health education emphasizing weight loss, exercise, and risk factor reduction. Program leaders' strong commitment and positive role modeling, along with social and group support and community involvement, were key elements. A pre–post evaluation of weight, blood pressure, total cholesterol, and blood sugar showed significant improvements for weight (mean change [Δ] = −7.4 lbs; P < .001), systolic blood pressure (Δ = –3.8 mm Hg; P = .027), diastolic blood pressure (Δ = –4.6 mm Hg; P < .001), and total cholesterol (Δ = –9.7 mg/dL; P

BACKGROUND: Comorbidity of personality disorder (PD) and attention-deficit/hyperactivity disorder (ADHD) has been suggested in several reports. However, assessment of PD is problematic, and studies have over-relied on baseline evaluations. METHODS: Forty-seven patients entered a double-blind trial of osmotic release oral system (OROS) methylphenidate (MPH). Patients were assessed at baseline with the Wisconsin Personality Inventory IV (WISPI-IV) and the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II). Following the study, all information-including tests, family reports, and extended clinical observations-produced a final PD diagnosis. Three post hoc categories were created: PD-negative (no PD), PD-positive (1 PD), and PD-plus (2 or more PDs). RESULTS: Twenty-one (45%) patients had a PD on the final assessment vs 62% using SCID-II and 33% using WISPI-IV; final PD diagnosis revealed 9% cluster A, 17% cluster B, and 28% cluster C. Twenty-one percent of patients experienced multiple disorders. Using a weighted kappa, the number of PDs on the final assessment correlated with the WISPI-IV (kappa=.53; P > .001) and the SCID-II (kappa =.70; P

BACKGROUND: This study explored the relationship between personality disorder (PD) and treatment response in a randomized, double-blind, clinical trial of osmotic release oral system (OROS) methylphenidate (MPH). METHODS: Forty-seven patients entered a crossover trial using the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) to assess outcome. A final personality diagnosis was made using staff consensus and information from the Wisconsin Personality Inventory IV (WISPI-IV) and the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II). Three post hoc categories were created: PD-negative (no PD; n = 26), PD-positive (patients with 1 PD; n = 11), and PD-plus (patients with 2 or more PDs; n = 10). Improvement in attention-deficit/hyperactivity disorder (ADHD) symptoms was assessed using a mixed-model analysis with treatment and personality categories as fixed variables. Average z scores on the WISPI-IV and items endorsed on SCID-II provided dimensional measures of PD severity. RESULTS: Different treatment effects were observed for the PD subgroups (P

BACKGROUND: This study explored the relationship between the dimensions of adult attention-deficit/hyperactivity disorder (ADHD), personality disorder (PD), and adverse social adjustment. METHODS: In a controlled trial of osmotic release oral system methylphenidate, PD was assessed using the Wisconsin Personality Disorders Inventory IV (WISPI-IV), the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II), and a final consensus diagnosis. Participants were categorized 2 ways: (1) ADHD alone, ADHD with emotional dysregulation (ADHD + ED), and ADHD plus emotional dysregulation plus oppositional symptoms (ADHD + ED + ODD); and (2) those with no PD (PD-negative), 1 (PD-positive), and 2 or more (PD-plus) PDs. RESULTS: None of the ADHD-alone patients had a PD compared with 33% of ADHD + ED patients and 68% of ADHD + ED + ODD patients. The level of ADHD-related emotional and oppositional symptoms correlated significantly with the severity of PD dimensions as assessed by WISPI-IV z scores and the number of items endorsed on the SCID-II screening questionnaire. Complex presentations (define by both ADHD and personality categories) were associated with high childhood ADHD ratings and problems in work, extended family, and economic functioning. CONCLUSION: The ADHD symptoms of emotional dysregulation and oppositional symptoms were associated with increased Axis II disorders. Adverse outcomes were concentrated in patients with ADHD combined with emotional and oppositional symptoms, and in those with comorbid PDs.

The increased prevalence of childhood overweight and obesity is not unique to industrialized societies; dramatic increases are occurring in urbanized areas of developing countries. In light of the consensus that obesity is a significant public health concern and that many weight-loss interventions have been unsuccessful in the long term, an exploration of food patterns that are beneficial in the primary prevention of obesity is warranted. The focus of this article is to review the relation between vegetarian diets and obesity, particularly as they relate to childhood obesity. Epidemiologic studies indicate that vegetarian diets are associated with a lower body mass index (BMI) and a lower prevalence of obesity in adults and children. A meta-analysis of adult vegetarian diet studies estimated a reduced weight difference of 7.6 kg for men and 3.3 kg for women, which resulted in a 2-point lower BMI (in kg/m(2)). Similarly, compared with nonvegetarians, vegetarian children are leaner, and their BMI difference becomes greater during adolescence. Studies exploring the risk of overweight and food groups and dietary patterns indicate that a plant-based diet seems to be a sensible approach for the prevention of obesity in children. Plant-based diets are low in energy density and high in complex carbohydrate, fiber, and water, which may increase satiety and resting energy expenditure. Plant-based dietary patterns should be encouraged for optimal health and environmental benefits. Food policies are warranted to support social marketing messages and to reduce the cultural and economic forces that make it difficult to promote plant-based dietary patterns.

A well-balanced vegetarian diet can provide for the needs of children and adolescents. However, appropriate caloric intake should be ensured and growth monitored. Particular attention should be paid to adequate protein intake and sources of essential fatty acids, iron, zinc, calcium, and vitamins B₁₂ and D. Supplementation may be required in cases of strict vegetarian diets with no intake of any animal products. Pregnant and nursing mothers should also be appropriately advised to ensure that the nutritional needs of the fetus and infant are adequately met. Recommendations are provided. Adolescents on restricted vegetarian or other such diets should be screened for eating disorders.

Attention deficit/hyperactivity disorder (ADHD) is a frequent and disabling condition in school children, with cognitive and behavioral symptoms persisting into adulthood in a majority of patients. Etiology of ADHD is considered multifactorial and heterogenous, with an important contribution of genetic factors. Apart from genetic risk factors, emphasis has been put on the early environment, and prenatal exposure to nicotine, alcohol, prematurity and low birth weight have been associated with subsequent ADHD symptoms. This article reviews recent findings in neurobiology, genetics and neuroimaging of ADHD. Despite their clinical heterogeneity and frequent comorbidities, key symptoms of ADHD, such as impulsivity, hyperactivity and inattention are regularly improved by dopaminergic agonists, leading to consider dopaminergic dysfunction a possibly contributing factor in ADHD. Norepinephrine agonists also have clinical efficacy on ADHD symptoms and several other neurotransmission systems are likely involved in the etiology of ADHD. Dysfunction of neurotransmitter systems have been related to impairments of sustained attention, inhibitory control and working memory. Cognitive tasks focusing on reaction time and verbal working memory fit certain criteria for ADHD endophenotypes, offering a pathway to bridge the gap between observed traits and genetic vulnerability. Despite ADHD being a highly heritable disorder, most candidate genes with replicated findings across association studies only account for a small proportion of genetic variance. Neuroimaging studies using treatment effect or cognitive tasks show differential activation patterns in ADHD patients, with trends towards normalization under treatment. Further insight into neurobiological mechanisms involved in ADHD will arise from collaborative networks and combination of imaging, genetic and neurobiological techniques with consideration of the developmental aspects of ADHD.

Coenzyme Q10 (CoQ(10)) is an effective natural antioxidant with a fundamental role in cellular bioenergetics and numerous known health benefits. Reports of its natural occurrence in various food items are comprehensively reviewed and critically evaluated. Meat, fish, nuts, and some oils are the richest nutritional sources of CoQ(10), while much lower levels can be found in most dairy products, vegetables, fruits, and cereals. Large variations of CoQ(10) content in some foods and food products of different geographical origin have been found. The average dietary intake of CoQ(10) is only 3-6 mg, with about half of it being in the reduced form. The intake can be significantly increased by the fortification of food products but, due to its lipophilicity, until recently this goal was not easily achievable particularly with low-fat, water-based products. Forms of CoQ(10) with increased water-solubility or dispersibility have been developed for this purpose, allowing the fortification of aqueous products, and exhibiting improved bioavailability; progress in this area is described briefly. Three main fortification strategies are presented and illustrated with examples, namely the addition of CoQ(10) to food during processing, the addition of this compound to the environment in which primary food products are being formed (i.e. animal feed), or with the genetic modification of plants (i.e. cereal crops).

We previously reported that carbohydrate restriction (CR) (10-15% en) during a weight loss intervention lowered plasma triglycerides (TG) by 45% in male subjects (P<.001). However, those subjects with a higher intake of cholesterol provided by eggs (640 mg additional cholesterol, EGG group) had higher concentrations of high-density lipoprotein (HDL) cholesterol (P<.0001) than the individuals consuming lower amounts (0 mg of additional cholesterol, SUB group). The objectives of the present study were to evaluate whether CR and egg intake (1) modulate circulating carotenoids and (2) affect the concentrations of plasma apolipoproteins (apo), lipoprotein size and subfraction distribution. CR decreased the number of large and medium very low-density lipoprotein cholesterol subclasses (P<.001), while small low-density lipoprotein (LDL) were reduced (P<.001). In agreement with these observations, a decrease in apo B (P<.01) was observed. In addition, CR resulted in a 133% increase in apo C-II and a 65% decrease in apo C-III (P<.0001). Although an increase of the larger LDL subclass was observed for all subjects, the EGG group had a greater increase (P<.05). The EGG group also presented a higher number of large HDL particles (P<.01) compared to the SUB group. Regarding carotenoids, CR resulted in no changes in dietary or plasma alpha- or beta-carotene and beta-cryptoxanthin, while there was a significant reduction in both dietary and plasma lycopene (P<.001). In contrast, dietary lutein and zeaxanthin were increased during the intervention (P

We previously reported that carbohydrate restriction (CR) (10-15% en) during a weight loss intervention lowered plasma triglycerides (TG) by 45% in male subjects (P<.001). However, those subjects with a higher intake of cholesterol provided by eggs (640 mg additional cholesterol, EGG group) had higher concentrations of high-density lipoprotein (HDL) cholesterol (P<.0001) than the individuals consuming lower amounts (0 mg of additional cholesterol, SUB group). The objectives of the present study were to evaluate whether CR and egg intake (1) modulate circulating carotenoids and (2) affect the concentrations of plasma apolipoproteins (apo), lipoprotein size and subfraction distribution. CR decreased the number of large and medium very low-density lipoprotein cholesterol subclasses (P<.001), while small low-density lipoprotein (LDL) were reduced (P<.001). In agreement with these observations, a decrease in apo B (P<.01) was observed. In addition, CR resulted in a 133% increase in apo C-II and a 65% decrease in apo C-III (P<.0001). Although an increase of the larger LDL subclass was observed for all subjects, the EGG group had a greater increase (P<.05). The EGG group also presented a higher number of large HDL particles (P<.01) compared to the SUB group. Regarding carotenoids, CR resulted in no changes in dietary or plasma alpha- or beta-carotene and beta-cryptoxanthin, while there was a significant reduction in both dietary and plasma lycopene (P<.001). In contrast, dietary lutein and zeaxanthin were increased during the intervention (P

Ketones have previously shown beneficial effects in models of neurodegenerative disorders, particularly against associated mitochondrial dysfunction and cognitive impairment. However, evidence of a synaptic protective effect of ketones remains lacking. We tested the effects of ketones on synaptic impairment induced by mitochondrial respiratory complex (MRC) inhibitors using electrophysiological, reactive oxygen species (ROS) imaging and biochemical techniques. MRC inhibitors dose-dependently suppressed both population spike (PS) and field potential amplitudes in the CA1 hippocampus. Pre-treatment with ketones strongly prevented changes in the PS, whereas partial protection was seen in the field potential. Rotenone (Rot; 100 nmol/L), a MRC I inhibitor, suppressed synaptic function without altering ROS levels and PS depression by Rot was unaffected by antioxidants. In contrast, antioxidant-induced PS recovery against the MRC II inhibitor 3-nitropropionic acid (3-NP; 1 mmol/L) was similar to the synaptic protective effects of ketones. Ketones also suppressed ROS generation induced by 3-NP. Finally, ketones reversed the decreases in ATP levels caused by Rot and 3-NP. In summary, our data demonstrate that ketones can preserve synaptic function in CA1 hippocampus induced by MRC dysfunction, likely through an antioxidant action and enhanced ATP generation. © 2010 International Society for Neurochemistry.

CONCLUSIONS: The replacement of 7-8% of fat intake with complex carbohydrates over 6 y was not associated with clinically adverse effects on triglycerides, HDL cholesterol, or lipoprotein subclasses. Diabetic white women with higher triglyceride concentrations may have greater increases in triglycerides.

A frequently cited concern of very-low-carbohydrate diets is the potential for increased risk of renal disease associated with a higher protein intake. However, to date, no well-controlled randomized studies have evaluated the long-term effects of very-low-carbohydrate diets on renal function. To study this issue, renal function was assessed in 68 men and women with abdominal obesity (age 51.5+/-7.7 years, body mass index [calculated as kg/m(2)] 33.6+/-4.0) without preexisting renal dysfunction who were randomized to consume either an energy-restricted ( approximately 1,433 to 1,672 kcal/day), planned isocaloric very-low-carbohydrate (4% total energy as carbohydrate [14 g], 35% protein [124 g], 61% fat [99 g]), or high-carbohydrate diet (46% total energy as carbohydrate [162 g], 24% protein [85 g], 30% fat [49 g]) for 1 year. Body weight, serum creatinine, estimated glomerular filtration rate and urinary albumin excretion were assessed before and after 1 year (April 2006-July 2007). Repeated measures analysis of variance was conducted. Weight loss was similar in both groups (very-low-carbohydrate: -14.5+/-9.7 kg, high-carbohydrate: -11.6+/-7.3 kg; P=0.16). By 1 year, there were no changes in either group in serum creatinine levels (very-low-carbohydrate: 72.4+/-15.1 to 71.3+/-13.8 mumol/L, high-carbohydrate: 78.0+/-16.0 to 77.2+/-13.2 mumol/L; P=0.93 time x diet effect) or estimated glomerular filtration rate (very-low-carbohydrate: 90.0+/-17.0 to 91.2+/-17.8 mL/min/1.73 m(2), high-carbohydrate: 83.8+/-13.8 to 83.6+/-11.8 mL/min/1.73 m(2); P=0.53 time x diet effect). All but one participant was classified as having normoalbuminuria at baseline, and for these participants, urinary albumin excretion values remained in the normoalbuminuria range at 1 year. One participant in high-carbohydrate had microalbuminuria (41.8 microg/min) at baseline, which decreased to a value of 3.1 microg/min (classified as normoalbuminuria) at 1 year. This study provides preliminary evidence that long-term weight loss with a very-low-carbohydrate diet does not adversely affect renal function compared with a high-carbohydrate diet in obese individuals with normal renal function.

BACKGROUND: Soyfoods provide healthful options for school breakfasts and lunches that are lower in saturated fat, cholesterol, fat, and calories and can help meet demands for vegetarian choices. Researchers tested acceptance of soy-based options substituted for popular lunch items with a diverse student population. METHODS: Researchers conducted a plate waste study in 5 middle schools in Montgomery County, Maryland, to test the comparability of soy-based alternatives to 4 popular meat-based menu items. Initially, students ranked taste, appearance, and texture of 15 soyfoods to narrow to "hybrid" beef patties, soy-based nuggets, soy-based chicken-less slices, and soy macaroni and cheese. After the meal, trained observers randomly tagged and collected trays with and without test items and weighed leftover entrées. Researchers used a proportional odds model to compare amounts and proportions of food consumed, and a mixed model to account for differences between schools. RESULTS: Students consumed the same amount of soy-based and traditional patties, nuggets, and pasta, and less soy than regular chicken in the salad (odds ratio 0.122, p value < .0001). Students consumed higher proportions (p value

As patent protection ends for the next generation of antiepileptic drugs (AEDs), a complex debate continues over generic substitution of AEDs. On one hand, generic drug formulations provide cost savings for patients and society. On the other hand, patients with epilepsy and physicians are wary about the adequacy and efficacy of the Food and Drug Administration's (FDA) standards for generics. This article reviews current and proposed bioequivalence test procedures, summarizes new generic AED formulations and their costs, and discusses potential pitfalls in the current standards. These shortcomings include certain pharmacokinetic factors and clinical pharmacologic factors that may affect bioequivalence of generic AEDs, and statistical limitations of the standards. While the drug concentration differences between the brand name drug and each generic formulation are unlikely to be substantial, the differences with generic-to-generic switches will be greater and potentially clinically significant. Conversely, owing to their more favorable pharmacokinetic profile, newer AEDs may be less prone to problems with generic substitution than older ones. Unfortunately, very few data are available to guide decisions regarding what is best for an individual patient. Based on new prediction methods, generic substitution should be safe for many patients but identifying them ultimately requires more rigorous study.

BACKGROUND: A long-term vegetarian diet is generally poor in vitamin B group. The lack of vitamin B(12) together with vitamin B(6) and folate deficiency is closely related to homocysteine metabolism. Hyperhomocysteinemia was found to be associated with increased bone turnover markers and increased fracture risk. Thus, hyperhomocysteinemia, vitamin B(12) and folate deficiency may be regarded as novel risk factors for micronutrient deficiency-related osteoporosis. AIM OF THE STUDY: To assess the possible impact of a vegetarian diet on bone mineral density in cohort of Slovak vegetarian women. METHODS: Fasting serum glucose, albumin, calcium, phosphorous and creatinine as well as bone markers, serum vitamin B(12), folate and plasma levels of total homocysteine were assessed in two nutritional groups (vegetarians vs. nonvegetarians) of apparently healthy women (age range 20-70 years). Bone mineral density of the femoral neck, trochanter, total femur and lumbar spine was measured in all subjects. RESULTS: Vegetarians had a significantly lower weight (p < 0.05), higher PTH (p < 0.01) and homocysteine (p < 0.001). Vitamin B(12) was significantly higher in nonvegetarians (p < 0.001). No differences were observed in folate levels. Univariate analysis showed significant association between homocysteine and B(12) (p < 0.01), folate (p < 0.001), creatinine (p < 0.001), total proteins (p < 0.049), age (p < 0.001) and vegetarian food intake (p < 0.001). Vegetarians had a significantly lower TrFBMD (p < 0.05) and ToFBMD (p < 0.05). Age and CTx were significant predictors in all sites of measured BMD and PTH. A strong correlation between homocysteine and FNBMD (r = -0.2009, p < 0.002), TrFBMD (r = -0.1810, p < 0.004) and ToFBMD (r = -0.2225, p

Significant benefits for diabetes prevention and management have been observed with vegetarian and especially vegan diets. This article reviews observational studies and intervention trials on such diets, and discusses their efficacy, nutritional adequacy, acceptability, and sustainability. Research to date has demonstrated that a low-fat, plant-based nutritional approach improves control of weight, glycemia, and cardiovascular risk. These studies have also shown that carefully planned vegan diets can be more nutritious than diets based on more conventional diet guidelines, with an acceptability that is comparable with that of other therapeutic regimens. Current intervention guidelines from professional organizations offer support for this approach. Vegetarian and vegan diets present potential advantages in managing type 2 diabetes that merit the attention of individuals with diabetes and their caregivers.

Dietary fats have long been associated with human health, and especially cardiovascular disease (CVD). Some observational studies have shown that reduction in dietary fats, and particularly cholesterol is associated with lower cardiovascular risk; however, other prospective studies or randomized controlled trials of dietary fat reduction or modification have shown varying results on CVD morbidity and mortality. In this work we evaluated the relationships between dietary fats and a cluster of CVD risk factors (i.e., diabetes, obesity, hypercholesterolemia, hypertension), among elderly individuals without known CVD. In particular, dietary and clinical data from 1486 elderly (aged 65 to 100 years) men and women living in Cyprus, Mitilini, Samothraki, Cephalonia, Crete, Lemnos, Syros, Naxos, Corfu and Zakynthos islands, and participated in the MEDIS study, were analysed. Data analysis revealed that 18.5% of males and 33.3% of females had three or four cardiovascular disease risk factors; the major source of fat was olive oil (mean intake for men and women 50.0 +/- 19.3 g/day and 46.0 +/- 16.8 g/day, p

Circulating numbers of endothelial microparticles (EMP) are an index of endothelial injury and dysfunction; and microparticles positive to CD31 antibody increase acutely after cooked, fatty fast-food meals that are rich in saturated fatty acids (SAFA) and lipid oxidation products. The aim of this study was to determine the acute effect of meals rich in SAFA and native and thermally oxidized polyunsaturated vegetable oil on circulating numbers of EMP positive to CD144 antibody, a more specific marker of EMP. Twenty-two apparently healthy subjects received isocaloric meals rich in cream (CR), unheated sunflower oil, or heated sunflower oil in a randomized crossover study design. Circulating numbers of CD144-EMP and plasma lipids and Svedberg unit of flotation (S(f)) greater than 400 triglyceride content were measured before and 1 and 3 hours after the meals. Triglycerides in the plasma S(f) greater than 400 fraction increased significantly (P < .001) after the meals, with a significantly (P < .05) larger increase after the CR meal. Plasma CD144-EMP increased significantly (20%, P

BACKGROUND: A reduction in dietary saturated fat has generally been thought to improve cardiovascular health. OBJECTIVE: The objective of this meta-analysis was to summarize the evidence related to the association of dietary saturated fat with risk of coronary heart disease (CHD), stroke, and cardiovascular disease (CVD; CHD inclusive of stroke) in prospective epidemiologic studies. DESIGN: Twenty-one studies identified by searching MEDLINE and EMBASE databases and secondary referencing qualified for inclusion in this study. A random-effects model was used to derive composite relative risk estimates for CHD, stroke, and CVD. RESULTS: During 5-23 y of follow-up of 347,747 subjects, 11,006 developed CHD or stroke. Intake of saturated fat was not associated with an increased risk of CHD, stroke, or CVD. The pooled relative risk estimates that compared extreme quantiles of saturated fat intake were 1.07 (95% CI: 0.96, 1.19; P = 0.22) for CHD, 0.81 (95% CI: 0.62, 1.05; P = 0.11) for stroke, and 1.00 (95% CI: 0.89, 1.11; P = 0.95) for CVD. Consideration of age, sex, and study quality did not change the results. CONCLUSIONS: A meta-analysis of prospective epidemiologic studies showed that there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD or CVD. More data are needed to elucidate whether CVD risks are likely to be influenced by the specific nutrients used to replace saturated fat.

BACKGROUND: A reduction in dietary saturated fat has generally been thought to improve cardiovascular health. OBJECTIVE: The objective of this meta-analysis was to summarize the evidence related to the association of dietary saturated fat with risk of coronary heart disease (CHD), stroke, and cardiovascular disease (CVD; CHD inclusive of stroke) in prospective epidemiologic studies. DESIGN: Twenty-one studies identified by searching MEDLINE and EMBASE databases and secondary referencing qualified for inclusion in this study. A random-effects model was used to derive composite relative risk estimates for CHD, stroke, and CVD. RESULTS: During 5-23 y of follow-up of 347,747 subjects, 11,006 developed CHD or stroke. Intake of saturated fat was not associated with an increased risk of CHD, stroke, or CVD. The pooled relative risk estimates that compared extreme quantiles of saturated fat intake were 1.07 (95% CI: 0.96, 1.19; P = 0.22) for CHD, 0.81 (95% CI: 0.62, 1.05; P = 0.11) for stroke, and 1.00 (95% CI: 0.89, 1.11; P = 0.95) for CVD. Consideration of age, sex, and study quality did not change the results. CONCLUSIONS: A meta-analysis of prospective epidemiologic studies showed that there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD or CVD. More data are needed to elucidate whether CVD risks are likely to be influenced by the specific nutrients used to replace saturated fat.

During the past century, treatments for the diseases of youth and middle age have helped raise life expectancy significantly. However, cognitive decline has emerged as one of the greatest health threats of old age, with nearly 50% of adults over the age of 85 afflicted with Alzheimer's disease. Developing therapeutic interventions for such conditions demands a greater understanding of the processes underlying normal and pathological brain ageing. Recent advances in the biology of ageing in model organisms, together with molecular and systems-level studies of the brain, are beginning to shed light on these mechanisms and their potential roles in cognitive decline. © 2010 Macmillan Publishers Limited. All rights reserved.

PURPOSE: To evaluate research on the vegetarian diet for its safety, effectiveness in reducing heart disease, special considerations, contraindications, and its association with decreased cardiovascular disease risk. DATA SOURCES: Selected research and evidence-based dietary guidelines found by searching CINAHL, PubMed, Ovid databases, and the World Wide Web. CONCLUSIONS: A carefully planned vegetarian diet with adequate supplementation may be effective for primary prevention of heart disease. The vegetarian diet is cost effective, safe, and relatively easy to implement. IMPLICATIONS FOR PRACTICE: Improved dietary choices can help improve many chronic conditions. Guidelines for proper nutrition within a vegetarian lifestyle are readily accessible to patients and professionals alike. Referral to a dietitian is an appropriate option in primary care settings.

A focus of dietary recommendations for cardiovascular disease (CVD) prevention and treatment has been a reduction in saturated fat intake, primarily as a means of lowering LDL-cholesterol concentrations. However, the evidence that supports a reduction in saturated fat intake must be evaluated in the context of replacement by other macronutrients. Clinical trials that replaced saturated fat with polyunsaturated fat have generally shown a reduction in CVD events, although several studies showed no effects. An independent association of saturated fat intake with CVD risk has not been consistently shown in prospective epidemiologic studies, although some have provided evidence of an increased risk in young individuals and in women. Replacement of saturated fat by polyunsaturated or monounsaturated fat lowers both LDL and HDL cholesterol. However, replacement with a higher carbohydrate intake, particularly refined carbohydrate, can exacerbate the atherogenic dyslipidemia associated with insulin resistance and obesity that includes increased triglycerides, small LDL particles, and reduced HDL cholesterol. In summary, although substitution of dietary polyunsaturated fat for saturated fat has been shown to lower CVD risk, there are few epidemiologic or clinical trial data to support a benefit of replacing saturated fat with carbohydrate. Furthermore, particularly given the differential effects of dietary saturated fats and carbohydrates on concentrations of larger and smaller LDL particles, respectively, dietary efforts to improve the increasing burden of CVD risk associated with atherogenic dyslipidemia should primarily emphasize the limitation of refined carbohydrate intakes and a reduction in excess adiposity. [References: 132]

The female hormones, oestrogen and progesterone, fluctuate predictably across the menstrual cycle in naturally cycling eumenorrhoeic women. Other than reproductive function, these hormones influence many other physiological systems, and their action during exercise may have implications for exercise performance. Although a number of studies have found exercise performance - and in particular, endurance performance - to vary between menstrual phases, there is an equal number of such studies reporting no differences. However, a comparison of the increase in the oestrogen concentration (E) relative to progesterone concentration (P) as the E/P ratio (pmol/nmol) in the luteal phase in these studies reveals that endurance performance may only be improved in the mid-luteal phase compared with the early follicular phase when the E/P ratio is high in the mid-luteal phase. Furthermore, the late follicular phase, characterized by the pre-ovulatory surge in oestrogen and suppressed progesterone concentrations, tends to promote improved performance in a cycling time trial and future studies should include this menstrual phase. Menstrual phase variations in endurance performance may largely be a consequence of changes to exercise metabolism stimulated by the fluctuations in ovarian hormone concentrations. The literature suggests that oestrogen may promote endurance performance by altering carbohydrate, fat and protein metabolism, with progesterone often appearing to act antagonistically. Details of the ovarian hormone influences on the metabolism of these macronutrients are no longer only limited to evidence from animal research and indirect calorimetry but have been verified by substrate kinetics determined with stable tracer methodology in eumenorrhoeic women. This review thoroughly examines the metabolic perturbations induced by the ovarian hormones and, by detailed comparison, proposes reasons for many of the inconsistent reports in menstrual phase comparative research. Often the magnitude of increase in the ovarian hormones between menstrual phases and the E/P ratio appear to be important factors determining an effect on metabolism. However, energy demand and nutritional status may be confounding variables, particularly in carbohydrate metabolism. The review specifically considers how changes in metabolic responses due to the ovarian hormones may influence exercise performance. For example, oestrogen promotes glucose availability and uptake into type I muscle fibres providing the fuel of choice during short duration exercise; an action that can be inhibited by progesterone. A high oestrogen concentration in the luteal phase augments muscle glycogen storage capacity compared with the low oestrogen environment of the early follicular phase. However, following a carbo-loading diet will super-compensate muscle glycogen stores in the early follicular phase to values attained in the luteal phase. Oestrogen concentrations of the luteal phase reduce reliance on muscle glycogen during exercise and although not as yet supported by human tracer studies, oestrogen increases free fatty acid availability and oxidative capacity in exercise, favouring endurance performance. Evidence of oestrogen's stimulation of 5'-AMP-activated protein kinase may explain many of the metabolic actions of oestrogen. However, both oestrogen and progesterone suppress gluconeogenic output during exercise and this may compromise performance in the latter stages of ultra-long events if energy replacement supplements are inadequate. Moreover, supplementing energy intake during exercise with protein may be more relevant when progesterone concentration is elevated compared with menstrual phases favouring a higher relative oestrogen concentration, as progesterone promotes protein catabolism while oestrogen suppresses protein catabolism. Furthermore, prospective research ideas for furthering the understanding of the impact of the menstrual cycle on metabolism and exercise performance are highlighted. [PUBLICATION ABSTRACT]

PURPOSE: The purpose of this review is to provide educators with the knowledge and tools to utilize plant-based nutrition education as an intervention for type 2 diabetes. Scientific support for the efficacy, acceptability, and nutritional adequacy of a plant-based diet for people with type 2 diabetes is presented, and practical considerations such as medication adjustment and risk of hypoglycemia are reviewed. CONCLUSIONS: Plant-based meal planning is an acceptable and effective strategy that educators can use to improve diabetes management and reduce risk of complications. Studies show that dietary changes that are effective for reducing cardiac risk may also be helpful for management of type 2 diabetes. A low-fat, plant-based diet reduces body weight and improves glycemic control, and has been shown to be remarkably well accepted by patients.

Objective dietary intake markers for meat would be useful to assess meat intake in observational studies and as compliance markers in dietary intervention studies. A number of compounds are specific to meat compared with most other dietary items but there is some overlap between protein rich foods. A number of single compounds have been analysed in urine, plasma, serum or hair samples in studies of their relationship to meat or total protein intake. Among potential markers of dietary meat intake are urea, creatine, creatinine, carnitine, carnosine, anserine, ophidine, 1- and 3-methylhistidine, and sulphate or sulphite. Anserine and 1-methylhistidine come close to being meat-specific markers but true quantitative biomarker may not exist. Modern profiling techniques are increasingly used to look for useful biomarkers or for constructing them from latent information in complex profiles. Metabolomics by NMR spectroscopy of urine has also been applied to search for meat intake markers. Studies on single compounds or metabolomics markers are shortly reviewed here.

Postprandial hyperlipidaemia has been recognised to be a risk factor for atherosclerosis development. Epidemiological and animal studies have shown that Mg intake is inversely associated with some risk factors of atherosclerosis, including lipid metabolism. The present study was performed to determine the effects of Mg supplementation on postprandial responses in serum lipid levels. We used bittern (Nigari, in Japanese), a natural MgCl(2) solution from sea or salt lake water, for Mg supplementation. In a two-way, randomised, crossover study, sixteen healthy male volunteers consumed 30 g butter with or without 5 ml bittern containing 500 mg of Mg. Fasting and postprandial blood samples were taken 2, 3, 4 and 6 h after ingestion. Postprandial lipid responses were evaluated by serum TAG, chylomicron TAG, apo-B48, remnant-like particle cholesterol (RLP-C) and NEFA concentrations. We found that the serum and the chylomicron TAG responses after the fat load were reduced and delayed by Mg supplementation. The concentrations of apo-B48 (P < 0.05), RLP-C (P < 0.05) and NEFA (P

Several hydroxyproline (Hyp)-containing food-derived collagen peptides were identified in human blood after oral ingestion of gelatin hydrolysates. However, these types of peptides were not quantified in human plasma. In this report, a sensitive LC-MS/MS method was introduced for simultaneous quantitative analysis of Hyp-containing peptides. All peptide concentrations were determined accurately, with all coefficients of determination (r(2)) >0.999. The method achieved detection and quantification limits of 0.01 pmol/ml and 12.5-1,000 pmol/ml in plasma, respectively. Concentrations were quantified for nine Hyp-containing peptides in human plasma by this method, identifying Pro-Hyp (C(max) = 60.65 +/- 5.74 nmol/ml) as the major constituent of food-derived collagen peptides, while the minor components were Ala-Hyp-Gly, Ser-Hyp-Gly, Ala-Hyp, Phe-Hyp, Leu-Hyp, Ile-Hyp, Gly-Pro-Hyp, and Pro-Hyp-Gly (C(max) from 23.84 to 0.67 nmol/ml). Thus a total of nine Hyp-containing peptides in human plasma were successfully quantified by this approach. The concentration of Hyp-containing peptides is substantially higher than that following oral administration of other peptides.