Published Science

BACKGROUND: Small-scale, short-term intervention studies have suggested that plasma alkylresorcinol (AR) concentrations may be biomarkers of whole grain (WG) wheat and rye intakes. OBJECTIVE: The objective was to determine whether plasma AR concentrations reflect self-reported WG food intake in a 16-wk WG intervention study and to establish which phenotypic characteristics influence plasma AR concentrations. DESIGN: In a randomized parallel-group dietary intervention study, 316 overweight and obese participants with a WG intake of

Cardiac complications have been rarely reported associated with the ketogenic diet. Prolonged QT interval in the electrocardiogram and torsades de pointes arrhythmias have been described in a few cases. The effect of the ketogenic diet on QT interval has not been systematically evaluated. We obtained serial electrocardiograms in our patients on the ketogenic diet to look for changes in the mean QT interval. Twenty seven children aged 6 months to 5 years with refractory epilepsy were enrolled. Classic ketogenic diet was introduced using a non-fasting gradual initiation protocol. All patients were supplemented with oral calcium and selenium. Electrocardiograms were obtained at baseline and after 1, 3, 6, and 12 months on the ketogenic diet. There was no statistically significant change in the corrected QT interval over time. There were no ST segment changes or dysrhythmias in any of the electrocardiograms. Copyright © 2011 Elsevier Ltd. All rights reserved.

Objectives. We examined the influence of vegetarian diet on the risk of developing anaemia among Indian women and suggest initiatives for addressing diet-related iron-deficiency anaemia. Methods. We analysed data on diet, social class, and haemoglobin levels from the nationally representative Indian National Family and Health Survey 2005/06 for a sample of 81,301 women aged 15–49 years using logistic regression models. Results. After controlling for individual-level factors and household level socioeconomic characteristics, daily consumption of meat, fish, and eggs was associated with lower odds of being moderately or severely anaemic. Our analysis also revealed that economic characteristics such as being from higher wealth quintiles, being in paid employment, and rural residence reduced the odds of having iron-deficiency anaemia among Indian women. Discussion. As a large proportion of Indians subsist on iron-poor vegetarian diets for religious, economic, and cultural reasons, large-scale iron supplementation and fortification of commonly consumed vegetarian foodstuffs constitute a feasible, culturally appropriate, and cost-effective strategy for addressing this major public health problem. Consumption of cheap iron-rich foodstuffs should be promoted. Effective poverty alleviation and hookworm prevention programs are also important. Large-scale cohort and intervention studies are urgently required to further define the influence of vegetarianism on iron deficiency anaemia in India.

Diabetic nephropathy is a major complication of diabetes and tubulointerstitial fibrosis is one of its manifestations. This study aimed to clarify the pathogenicity of advanced glycation endproducts (AGEs) toward NRK-52E, a tubular epithelial cell line. The AGE-exposed cells significantly increased gene expression of transforming growth factor beta, plasminogen activator inhibitor-1, and tissue transglutaminase, and a medium conditioned by them showed strong potential to recruit macrophages, partly through a chemokine, monocyte chemoattractant protein-1. Albumin denatured by maintenance at 37 °C for 120 d exhibited similar activities, but they were lower than those of the AGEs. Thus, AGEs generated in diabetic patients might exacerbate fibrosis in the kidneys directly through renal epithelial cell stimulation, and indirectly by recruitment of macrophages.

Abstract - Background Our systematic review has demonstrated that antioxidant supplements may increase mortality. We have now updated this review. Objectives To assess the beneficial and harmful effects of antioxidant supplements for prevention of mortality in adults. Search methods We searched The Cochrane Library , MEDLINE, EMBASE, LILACS, the Science Citation Index Expanded, and Conference Proceedings Citation Index‐Science to February 2011. We scanned bibliographies of relevant publications and asked pharmaceutical companies for additional trials. Selection criteria We included all primary and secondary prevention randomised clinical trials on antioxidant supplements (beta‐carotene, vitamin A, vitamin C, vitamin E, and selenium) versus placebo or no intervention. Data collection and analysis Three authors extracted data. Random‐effects and fixed‐effect model meta‐analyses were conducted. Risk of bias was considered in order to minimise the risk of systematic errors. Trial sequential analyses were conducted to minimise the risk of random errors. Random‐effects model meta‐regression analyses were performed to assess sources of intertrial heterogeneity. Main results Seventy‐eight randomised trials with 296,707 participants were included. Fifty‐six trials including 244,056 participants had low risk of bias. Twenty‐six trials included 215,900 healthy participants. Fifty‐two trials included 80,807 participants with various diseases in a stable phase. The mean age was 63 years (range 18 to 103 years). The mean proportion of women was 46%. Of the 78 trials, 46 used the parallel‐group design, 30 the factorial design, and 2 the cross‐over design. All antioxidants were administered orally, either alone or in combination with vitamins, minerals, or other interventions. The duration of supplementation varied from 28 days to 12 years (mean duration 3 years; median duration 2 years). Overall, the antioxidant supplements had no significant effect on mortality in a random‐effects model meta‐analysis (21,484 dead/183,749 (11.7%) versus 11,479 dead/112,958 (10.2%); 78 trials, relative risk (RR) 1.02, 95% confidence interval (CI) 0.98 to 1.05) but significantly increased mortality in a fixed‐effect model (RR 1.03, 95% CI 1.01 to 1.05). Heterogeneity was low with an I 2 ‐ of 12%. In meta‐regression analysis, the risk of bias and type of antioxidant supplement were the only significant predictors of intertrial heterogeneity. Meta‐regression analysis did not find a significant difference in the estimated intervention effect in the primary prevention and the secondary prevention trials. In the 56 trials with a low risk of bias, the antioxidant supplements significantly increased mortality (18,833 dead/146,320 (12.9%) versus 10,320 dead/97,736 (10.6%); RR 1.04, 95% CI 1.01 to 1.07). This effect was confirmed by trial sequential analysis. Excluding factorial trials with potential confounding showed that 38 trials with low risk of bias demonstrated a significant increase in mortality (2822 dead/26,903 (10.5%) versus 2473 dead/26,052 (9.5%); RR 1.10, 95% CI 1.05 to 1.15). In trials with low risk of bias, beta‐carotene (13,202 dead/96,003 (13.8%) versus 8556 dead/77,003 (11.1%); 26 trials, RR 1.05, 95% CI 1.01 to 1.09) and vitamin E (11,689 dead/97,523 (12.0%) versus 7561 dead/73,721 (10.3%); 46 trials, RR 1.03, 95% CI 1.00 to 1.05) significantly increased mortality, whereas vitamin A (3444 dead/24,596 (14.0%) versus 2249 dead/16,548 (13.6%); 12 trials, RR 1.07, 95% CI 0.97 to 1.18), vitamin C (3637 dead/36,659 (9.9%) versus 2717 dead/29,283 (9.3%); 29 trials, RR 1.02, 95% CI 0.98 to 1.07), and selenium (2670 dead/39,779 (6.7%) versus 1468 dead/22,961 (6.4%); 17 trials, RR 0.97, 95% CI 0.91 to 1.03) did not significantly affect mortality. In univariate meta‐regression analysis, the dose of vitamin A was significantly associated with increased mortality (RR 1.0006, 95% CI 1.0002 to 1.001, P = 0.002). Authors' conclusions We found no evidence to support antioxidant supplements for primary or secondary prevention. Beta‐carotene and vitamin E seem to increase mortality, and so may higher doses of vitamin A. Antioxidant supplements need to be considered as medicinal products and should undergo sufficient evaluation before marketing. Plain language summary Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases Previous research on animal and physiological models suggests that antioxidant supplements have beneficial effects that may prolong life. Some observational studies also suggest that antioxidant supplements may prolong life, whereas other observational studies demonstrate neutral or harmful effects. Our Cochrane review from 2008 demonstrated that antioxidant supplements seem to increase mortality. This review is now updated. The present systematic review included 78 randomised clinical trials. In total, 296,707 participants were randomised to antioxidant supplements (beta‐carotene, vitamin A, vitamin C, vitamin E, and selenium) versus placebo or no intervention. Twenty‐six trials included 215,900 healthy participants. Fifty‐two trials included 80,807 participants with various diseases in a stable phase (including gastrointestinal, cardiovascular, neurological, ocular, dermatological, rheumatoid, renal, endocrinological, or unspecified diseases). A total of 21,484 of 183,749 participants (11.7%) randomised to antioxidant supplements and 11,479 of 112,958 participants (10.2%) randomised to placebo or no intervention died. The trials appeared to have enough statistical similarity that they could be combined. When all of the trials were combined, antioxidants may or may not have increased mortality depending on which statistical combination method was employed; the analysis that is typically used when similarity is present demonstrated that antioxidant use did slightly increase mortality (that is, the patients consuming the antioxidants were 1.03 times as likely to die as were the controls). When analyses were done to identify factors that were associated with this finding, the two factors identified were better methodology to prevent bias from being a factor in the trial (trials with ‘low risk of bias’) and the use of vitamin A. In fact, when the trials with low risks of bias were considered separately, the increased mortality was even more pronounced (1.04 times as likely to die as were the controls). The potential damage from vitamin A disappeared when only the low risks of bias trials were considered. The increased risk of mortality was associated with beta‐carotene and possibly vitamin E and vitamin A, but was not associated with the use of vitamin C or selenium. The current evidence does not support the use of antioxidant supplements in the general population or in patients with various diseases.

Context—Antipsychotic drugs have been linked to QT-interval prolongation, a presumed marker of cardiac risk, and torsade de pointes.

The intake of large amounts of ω-6 polyunsaturated fatty acids (PUFAs) and foodswith a very high of ω-6/ω-3 PUFA ratio reportedly promotes cardiovascular diseaseassociated with atherosclerosis. Arachidonic acid (AA) is one example of an ω-6 PUFA.In unstable plaque of the human arterial wall, AA metabolites are involved inatherogenesis through lipid oxidation as well as inflammatory processes, and the ruptureof unstable coronary plaque is a key process in acute myocardial infarction (AMI). TheAA concentrations in adipose tissue, serum or plasma are significantly correlated with therisk of AMI. A recent study found that the plasma levels of a free radical oxidationproduct from AA, hydroxyeicosatetraenoic acid (HETE), were associated with coronaryartery disease (CAD). Furthermore, the serum AA level was reportedly correlated withthe serum levels of malondialdehyde (MDA)-modified low density lipoprotein (LDL),which is a major component of lipid-rich fragile atheromatous plaques, in CAD patients.The serum AA level was positively associated with the prevalence of major adversecardiac events after AMI. The identification of lipid-rich unstable plaque is clinicallyimportant with respect to coronary events. A significant correlation between the ratio ofserum levels of AA to eicosapentaenoic acid (EPA), one of the ω-3 PUFAs that generallycounteracts ω-6 PUFAs, and the volume and percentage of lipid-rich core component incoronary plaques was obtained using recent advanced intravascular ultrasound spectralanalyses. Regarding food intake, the AA content is correlated with the cholesterolcontents in food, including meats, fish, milk and egg products, and a cholesterol intake of less than 300 mg is recommended to reduce the risk of CAD. Reducing the cholesterolintake coincides with a reduction in the AA intake and may enable the excessive intake ofAA to be avoided. In conclusion, AA contributes to coronary atherogenesis and theclinical manifestations of CAD, specifically the instability of coronary artery plaques.Appropriate intake of AA is important for reducing the risk of CAD. © 2013 by Nova Science Publishers, Inc. All rights reserved.

For much of the 20th century, the predominant view of human evolutionary history was derived from the fossil record. Homo erectus was seen arising in Africa from an earlier member of the genus and then spreading throughout the Old World and into the Oceania. A regional continuity model of anagenetic change from H. erectus via various intermediate archaic species into the modern humans in each of the regions inhabited by H. erectus was labeled the multiregional model of human evolution (MRE). A contrasting model positing a single origin, in Africa, of anatomically modern H. sapiens with some populations later migrating out of Africa and replacing the local archaic populations throughout the world with complete replacement became known as the recent African origin (RAO) model. Proponents of both models used different interpretations of the fossil record to bolster their views for decades. In the 1980s, molecular genetic techniques began providing evidence from modern human variation that allowed not only the different models of modern human origins to be tested but also the exploration demographic history and the types of selection that different regions of the genome and even specific traits had undergone. The majority of researchers interpreted these data as strongly supporting the RAO model, especially analyses of mitochondrial DNA (mtDNA). Extrapolating backward from modern patterns of variation and using various calibration points and substitution rates, a consensus arose that saw modern humans evolving from an African population around 200,000 years ago. Much later, around 50,000 years ago, a subset of this population migrated out of Africa replacing Neanderthals in Europe and western Asia as well as archaics in eastern Asia and Oceania. mtDNA sequences from more than two-dozen Neanderthals and early modern humans re-enforced this consensus. In 2010, however, the complete draft genomes of Neanderthals and of heretofore unknown hominins from Siberia, called Denisovans, demonstrated gene flow between these archaic human species and modern Eurasians but not sub-Saharan Africans. Although the levels of gene flow may be very limited, this unexpected finding does not fit well with either the RAO model or MRE model. More thorough sampling of modern human diversity, additional fossil discoveries, and the sequencing of additional hominin fossils are necessary to throw light onto our origins and our history.

This book is first a story about Japanese modernization. Second, it considers the history of science and medicine in Japan; the story of this disease exemplifies the rise of scientific medicine and the shift from the clinic to the laboratory. It also focuses on the nexus between medicine and power in modern Japan.

It is increasingly accepted that metabolic changes in cancer cells can drive tumour formation. The finding that the SIRT6 protein suppresses tumour formation by regulating metabolism adds weight to this view.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and finally death. ALS patients suffer from asthenia and their progressive weakness negatively impacts quality of life, limiting their daily activities. They have impaired energy balance linked to lower activity of mitochondrial electron transport chain enzymes in ALS spinal cord, suggesting that improving mitochondrial function may present a therapeutic approach for ALS. When fed a ketogenic diet, the G93A ALS mouse shows a significant increase in serum ketones as well as a significantly slower progression of weakness and lower mortality rate. In this study, we treated SOD1-G93A mice with caprylic triglyceride, a medium chain triglyceride that is metabolized into ketone bodies and can serve as an alternate energy substrate for neuronal metabolism. Treatment with caprylic triglyceride attenuated progression of weakness and protected spinal cord motor neuron loss in SOD1-G93A transgenic animals, significantly improving their performance even though there was no significant benefit regarding the survival of the ALS transgenic animals. We found that caprylic triglyceride significantly promoted the mitochondrial oxygen consumption rate in vivo. Our results demonstrated that caprylic triglyceride alleviates ALS-type motor impairment through restoration of energy metabolism in SOD1-G93A ALS mice, especially during the overt stage of the disease. These data indicate the feasibility of using caprylic acid as an easily administered treatment with a high impact on the quality of life of ALS patients.

In 2009 the world celebrated the 150th anniversary of the publication of Charles Darwin's seminal work, the Origin of Species. While much was made of his evolutionary thinking, there was more to Darwin than merely challenging the way the Western World thought about the natural world. Gregarious by nature, Darwin also enjoyed the pleasures of the table. From his Glutton Club days at Cambridge University and throughout the voyage of the Beagle, Darwin not only collected specimens to develop his understanding of the natural world but he also ate them. He was never more satisfied than digesting species unknown to the human palate, at least the English palate. Darwin relished the culinary delights that different lands offered and approached the discovery of a new dish, and of the way it was cooked, with the same sense of curiosity and adventure he brought to collecting specimens.

Background: Meat, milk, and eggs have been inconsistently associated with the risk of advanced prostate cancer. These foods are sources of choline - a nutrient that may affect prostate cancer progression through cell membrane function and one-carbon metabolism. No study has examined dietary choline and the risk of lethal prostate cancer. Objective: Our objective was to examine whether dietary choline, choline-containing compounds, and betaine (a choline metabolite) increase the risk of lethal prostate cancer. Design: We prospectively examined the intake of these nutrients and the risk of lethal prostate cancer among 47,896 men in the Health Professionals Follow-Up Study. In a case-only survival analysis, we examined the postdiagnostic intake of these nutrients and the risk of lethal prostate cancer among 4282 men with an initial diagnosis of nonmetastatic disease during follow-up. Diet was assessed with a validated questionnaire 6 times during 22 y of follow-up. Results: In the incidence analysis, we observed 695 lethal prostate cancers during 879,627 person-years. Men in the highest quintile of choline intake had a 70% increased risk of lethal prostate cancer (HR: 1.70; 95% CI: 1.18, 2.45; P-trend = 0.005). In the case-only survival analysis, we observed 271 lethal cases during 33,679 person-years. Postdiagnostic choline intake was not statistically significantly associated with the risk of lethal prostate cancer (HR for quintile 5 compared with quintile 1: 1.69; 95% CI: 0.93, 3.09; P-trend = 0.20). Conclusion: Of the 47,896 men in our study population, choline intake was associated with an increased risk of lethal prostate cancer. © 2012 American Society for Nutrition.

Animal data indicates that dietary cottonseed oil (CSO) may lower cholesterol; however, the effects of a CSO-rich diet have not been evaluated in humans. Thirty-eight healthy adults (aged 18-40; 12 males, 26 females) consumed a CSO rich diet (95 g CSO daily) for one week. Anthropometric measurements were obtained, and blood was drawn pre- and post-intervention. Serum lipids (total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), triglyceride (TG), and free fatty acids (FFA)) were assayed. There was no change in weight or waist circumference among participants. There was no change in HDL (Pre: 1.27 +/- 0.4 mmol/L; Post: 1.21 +/- 0.3 mmol/L) or TG (Pre: 0.91 +/- 0.6 mmol/L; Post: 1.06 +/- 1.0 mmol/L). Total cholesterol and LDL were reduced (TC Pre: 4.39 +/- 0.9 mmol/L; Post: 4.16 +/- 0.8 mmol/L; LDL Pre: 2.70 +/- 0.8 mmol/L; Post: 2.47 +/- 0.6 mmol/L). When data were grouped by sex, total cholesterol was reduced in female participants (Pre: 4.34 +/- 0.9 mmol/L; Post: 4.09 +/- 0.8 mmol/L). Consumption of a high fat, CSO-rich diet for one week reduced total cholesterol in female participants without reducing HDL.

Introduction: Colorectal cancer is the third cause of death in industrialized countries. Genetic susceptibility and diet are determinant of cancer risk and tumor behavior. Variation in cancer incidence among and within populations with similar dietary patterns suggests that an individual response may reflect interactions with genetic factors, which may modify gene, protein, and metabolite expression patterns. Nutrigenomics, defined as the interaction between nutrition and an individual genome, will likely provide important clues about responders and non-responders to nutritional intervention. Discussion: Epidemiological and experimental studies suggest a protective role of some normal components of daily diet (fish oil, milk, and vegetables), estrogens, and phytoestrogens in colorectal cancer. The effect of estrogen seems to be mediated by their binding to estrogen receptor beta (ER-β), one of the two estrogen receptors with high affinity for these hormones. Very recently, the demonstration of an involvement of ER-β in the development of adenomatous polyps of the colon has also been documented, suggesting the use of selective ER-β agonists in primary colorectal cancer prevention. Phytoestrogens are plant-derived compounds that structurally and functionally act as estrogen agonists in mammals. They are characterized by a higher binding affinity to ER-β as compared to estrogen receptor alpha (ER-α), the other estrogen receptor subtype. These biological characteristics explain why the administration of phytoestrogens does not produce the classical side effects associated to estrogen administration (cerebro- and cardiovascular accidents, higher incidence of endometrial and breast cancer) and makes these substances potential candidates for colorectal cancer prevention. © 2011 Springer Science+Business Media, LLC.

The association between diet and CVD cannot be assigned to a single nutrient, but rather to a set of nutrients and non-nutrients, and eating pattern analyses have become an important tool in investigation of this relationship. Our objective was to investigate eating patterns in relation to nutrient intake and serum concentration of folate, vitamin B12 and TAG in ninety-five healthy adult participants. Dietary information was collected by an FFQ, and eating patterns were obtained by principal components analyses of thirty-three food groups. Three eating patterns were extracted, a sweet eating pattern identified by intakes of cakes, snacks, sugar-sweetened drinks and chocolates; a prudent eating pattern identified by vegetables, fruits and olive oil; and a traditional food pattern identified by red meat, lean fish and cheese. Blood samples were collected in the morning after an overnight fast. Linear regression analyses adjusted for age, BMI and smoking showed a negative association between the sweet eating pattern scores and the serum concentration of folate (ß = -2·31 (95 % CI -4·14, -0·45)) and a positive association with serum concentration of TAG (ß = 0·35 (95 % CI 0·12, 0·57)). The prudent eating pattern scores were positively associated with the serum concentration of folate (ß = 1·69 (95% CI 0·44, 2·92)). In conclusion, a sweet eating pattern was associated with risk factors for CVD, whereas a prudent eating pattern was associated with protective factors. © The Author(s) 2012.

Background: The response of status biomarkers to an increase in iron supply depends on several physiologic and environmental factors, which make it difficult to predict the outcome of an intervention. Objective: We assessed effects of baseline iron status, sex, menopausal status, duration of intervention, iron form, and daily dose on the change in iron status in response to iron supplementation. Design: A systematic review of randomized controlled trials (RCTs) of iron-supplementation and -fortification trials that assessed effects on hemoglobin, serum ferritin (SF), soluble transferrin receptor, or body iron was conducted. Subgrouping and straight-line and curved metaregression were used to describe the magnitude and dose-responsiveness of effect modifiers with respect to changes in status. Results: Forty-one RCTs were included; none of the RCTs were judged at low risk of bias. Random-effects meta-analyses showed that iron supplementation significantly improved iron status but with high levels of heterogeneity. Metaregression explained approximately one-quarter of between-study variance in effect size. There were clear effects on SF with study duration (increase in SF concentration/wk: 0.51 μg/L; 95% CI: 0.02, 1.00 μg/L; P = 0.04) and dose (increase in SF concentration/g Fe: 0.10 μg/L; 95% CI: 0.01, 0.20 μg/L; P = 0.036) and on hemoglobin concentrations with baseline iron status [-0.08 g/dL (95% CI: 0.15, 0.00 g/dL) per 10-μg/L increase in baseline SF concentration; P = 0.02]. Insufficient data were available to assess effects on body iron, sex, or menopausal status. Conclusion: Quantitative relations between baseline iron status, study duration, and iron dose on changes in iron-status biomarkers, which were generated from the meta-analyses, can be used to predict effects of trials of iron supplementation and fortification and to design iron-intervention programs. © 2012 American Society for Nutrition.

Repeated sauna treatment, known as Waon therapy, has been shown to improve cardiac function as well as exercise tolerance in patients with chronic heart failure. However, the underlying mechanisms of this therapy regarding these improvements remain to be elucidated. Forty-one patients with chronic heart failure (mean age 68.3 ± 13.5 years old) underwent Waon therapy 5 times a week for 3 weeks. Before and after treatment, a number of assessments were performed in all subjects: 6-minute walk test, echocardiography, determination of neurohumoral factors and number of circulating CD34 + cells, and a flow-mediated dilation (FMD) test of endothelial function. Cardiopulmonary exercise testing was also performed in 20 patients. Waon therapy increased the left ventricular ejection fraction (from 30.4 ± 12.6% to 32.5% ± 12.8%, p = 0.023) and reduced plasma levels of norepinephrine (from 400 ± 258 to 300 ± 187 pg/ml, p = 0.015) and brain natriuretic peptide (from 550 ± 510 to 416 ± 431 pg/ml, p = 0.035). Waon therapy increased the 6-minute walk distance (from 337 ± 120 to 379 ± 126 m, p \textless0.001) in association with an improvement in FMD (from 3.5 ± 2.3% to 5.5% ± 2.7%, p \textless0.001) and an increase in the number of circulating CD34 + cells (p = 0.025). Changes in 6-minute walk distance were correlated positively with those in the left ventricular ejection fraction and FMD and negatively with those in plasma levels of norepinephrine and brain natriuretic peptide levels. A multivariate analysis revealed that an increase in FMD was the only independent determinant of 6-minute walk distance improvement. Finally, Waon therapy significantly increased peak Vo 2, and this increase was also correlated with changes in FMD. In conclusion, repeated sauna therapy in patients with chronic heart failure improves exercise tolerance in association with improvement in endothelial function. © 2012 Elsevier Inc. All rights reserved.

There are close links among hyperglycaemia, oxidative stress and diabetic complications. Glutamine (GLN) is an amino acid with immunomodulatory properties. The present study investigated the effect of dietary GLN on oxidative stress-relative gene expressions and tissue oxidative damage in diabetes. There were one normal control (NC) and two diabetic groups in the present study. Diabetes was induced by an intraperitoneal injection of nicotinamide followed by streptozotocin (STZ). Rats in the NC group were fed a regular chow diet. In the two diabetic groups, one group (diabetes mellitus, DM) was fed a common semi-purified diet while the other group received a diet in which part of the casein was replaced by GLN (DM-GLN). GLN provided 25% of total amino acid N. The experimental groups were fed the respective diets for 8 weeks, and then the rats were killed for further analysis. The results showed that blood thioredoxin-interacting protein (Txnip) mRNA expression in the diabetic groups was higher than that in the NC group. Compared with the DM group, the DM-GLN group had lower glutamine fructose-6-phosphate transaminase 1, a receptor of advanced glycation end products, and Txnip gene expressions in blood mononuclear cells. The total antioxidant capacity was lower and antioxidant enzyme activities were altered by the diabetic condition. GLN supplementation increased antioxidant capacity and normalised antioxidant enzyme activities. Also, the renal nitrotyrosine level and Txnip mRNA expression were lower when GLN was administered. These results suggest that dietary GLN supplementation decreases oxidative stress-related gene expression, increases the antioxidant potential and may consequently attenuate renal oxidative damage in rats with STZ-induced diabetes.

One of the most common reasons for a nephrology consult is an elevated creatinine. An elevation in the serum creatinine concentration usually reflects a reduction in the glomerular filtration rate (GFR). Given the association of elevated creatinine and risk of cardiovascular mortality, it is important to keep in mind that at times the elevation of the creatinine is not representative of a true reduction in GFR. There are various causes of factitious elevation of creatinine. They can be broadly grouped into increased production of creatinine, interference with the assay and decreased tubular secretion of creatinine.

"There may be no greater source of anxiety for Americans today than the question of what to eat and drink. Are eggs the perfect protein, or are they cholesterol bombs? Is red wine good for my heart or bad for my liver? Will pesticides, additives, and processed foods kill me? Here with some very rare and very welcome advice is food historian Harvey Levenstein: Stop worrying! In "Fear of Food" Levenstein reveals the people and interests who have created and exploited these worries, causing an extraordinary number of Americans to allow fear to trump pleasure in dictating their food choices. He tells of the prominent scientists who first warned about deadly germs and poisons in foods and their successors who charged that processing foods robs them of life-giving vitamins and minerals. These include Nobel Prize-winner Eli Metchnikoff, who advised that yogurt would enable people to live to be 140, and Elmer McCollum, the "discoverer" of vitamins, who tailored his warnings about vitamin deficiencies to suit the food producers who funded him. Levenstein also highlights how large food companies have taken advantage of these concerns by marketing their products to combat the fear of the moment. Such examples include the co-opting of the "natural foods" movement, which grew out of the belief that inhabitants of a remote Himalayan Shangri-la enjoyed remarkable health by avoiding the very kinds of processed food these corporations produced, and the physiologist Ancel Keys, originator of the Mediterranean Diet, who provided the basis for a powerful coalition of scientists, doctors, food producers, and others to convince Americans that high-fat foods were deadly. In "Fear of Food", Levenstein offers a much-needed voice of reason; he expertly questions these stories of constantly changing advice to reveal that there are no hard-and-fast facts when it comes to eating. With this book, he hopes to free us from the fears that cloud so many of our food choices and allow us to finally rediscover the joys of guiltless eating."--Jacket.

Background: Chronic hyperglycemia has been hypothesized to contribute to coronary heart disease (CHD), but the extent to which hemoglobin A 1c (HbA 1c) level, a marker of long-term glycemic control, is independently related to CHD risk is uncertain.

1H-high resolution magic angle spinning-nuclear magnetic resonance spectroscopy was employed to gain the metabolic profile of longissimus dorsi and semitendinosus muscles of four different breeds: Chianina, Holstein Friesian, Maremmana and Buffalo.Principal component analysis, partial least squares projection to latent structure - discriminant analysis and orthogonal partial least squares projection to latent structure - discriminant analysis were used to build models capable of discriminating the muscle type according to the breed. Data analysis led to an excellent classification for Buffalo and Chianina, while for Holstein Friesian the separation was lower. In the case of Maremmana the use of intelligent bucketing was necessary due to some resonances shifting allowed improvement of the discrimination ability. Finally, by using the Variable Importance in Projection values the metabolites relevant for the classification were identified. © 2012 Elsevier Ltd.

Omega-6 (n-6) polyunsaturated fatty acids (PUFA) (e.g., arachidonic acid (AA)) and omega-3 (n-3) PUFA (e.g., eicosapentaenoic acid (EPA)) are precursors to potent lipid mediator signalling molecules, termed “eicosanoids,” which have important roles in the regulation of inflammation. In general, eicosanoids derived from n-6 PUFA are proinflammatory while eicosanoids derived from n-3 PUFA are anti-inflammatory. Dietary changes over the past few decades in the intake of n-6 and n-3 PUFA show striking increases in the (n-6) to (n-3) ratio (~15 : 1), which are associated with greater metabolism of the n-6 PUFA compared with n-3 PUFA. Coinciding with this increase in the ratio of (n-6) : (n-3) PUFA are increases in chronic inflammatory diseases such as nonalcoholic fatty liver disease (NAFLD), cardiovascular disease, obesity, inflammatory bowel disease (IBD), rheumatoid arthritis, and Alzheimer's disease (AD). By increasing the ratio of (n-3) : (n-6) PUFA in the Western diet, reductions may be achieved in the incidence of these chronic inflammatory diseases.

Omega-6 (n-6) polyunsaturated fatty acids (PUFA) (e.g., arachidonic acid (AA)) and omega-3 (n-3) PUFA (e.g., eicosapentaenoic acid (EPA)) are precursors to potent lipid mediator signalling molecules, termed “eicosanoids,” which have important roles in the regulation of inflammation. In general, eicosanoids derived from n-6 PUFA are proinflammatory while eicosanoids derived from n-3 PUFA are anti-inflammatory. Dietary changes over the past few decades in the intake of n-6 and n-3 PUFA show striking increases in the (n-6) to (n-3) ratio (~15 : 1), which are associated with greater metabolism of the n-6 PUFA compared with n-3 PUFA. Coinciding with this increase in the ratio of (n-6) : (n-3) PUFA are increases in chronic inflammatory diseases such as nonalcoholic fatty liver disease (NAFLD), cardiovascular disease, obesity, inflammatory bowel disease (IBD), rheumatoid arthritis, and Alzheimer's disease (AD). By increasing the ratio of (n-3) : (n-6) PUFA in the Western diet, reductions may be achieved in the incidence of these chronic inflammatory diseases.

Aims/hypothesis: The study aimed to compare the effects of a 2 year intervention with a low-fat diet (LFD) or a lowcarbohydrate diet (LCD), based on four group meetings to achieve compliance. Methods: This was a prospective randomised parallel trial involving 61 adults with type 2 diabetes consecutively recruited in primary care and randomised by drawing ballots. Patients that did not speak Swedish could not be recruited. The primary outcomes in this non-blinded study were weight and HbA\textlessinf\textgreater1c\textless/inf\textgreater. Patients on the LFD aimed for 55-60 energy per cent (E%) and those on LCD for 20 E% from carbohydrate. Results The mean BMI and HbA\textlessinf\textgreater1c\textless/inf\textgreater of the participants were 32.7+/-5.4 kg/m\textlesssup\textgreater2\textless/sup\textgreater and 57.0+/-9.2 mmol/mol, respectively. No patients were lost to follow-up. Weight loss did not differ between groups and was maximal at 6 months: LFD -3.99+/- 4.1 kg (n=31); LCD -4.31+/-3.6 kg (n030); p\textless0.001 within groups. At 24 months, patients on the LFD had lost -2.97+/- 4.9 kg and those on LCD -2.34+/-5.1 kg compared with baseline (p=0.002 and p=0.020 within groups, respectively). HbA\textlessinf\textgreater1c\textless/inf\textgreater fell in the LCD group only (LCD at 6 months -4.8+/- 8.3 mmol/mol, p=0.004, at 12 months -2.2+/-7.7 mmol/mol, p=0.12; LFD at 6 months -0.9+/-8.8 mmol/mol, p=0.56). At 6 months, HDL-cholesterol had increased with the LCD (from 1.13+/-0.33 mmol/l to 1.25+/-0.47 mmol/l, p=0.018) while LDL-cholesterol did not differ between groups. Insulin doses were reduced in the LCD group (0 months, LCD 42+/-65 E, LFD 39+/-51 E; 6 months, LCD 30+/-47 E, LFD 38+/-48 E; p=0.046 for between-group change). Conclusions/interpretation: Weight changes did not differ between the diet groups, while insulin doses were reduced significantly more with the LCD at 6 months, when compliance was good. Thus, aiming for 20% of energy intake from carbohydrates is safe with respect to cardiovascular risk compared with the traditional LFD and this approach could constitute a treatment alternative. © The Author(s) 2012.

The goal of this review was to summarize evidence supporting the view that insulin resistance/compensatory hyperinsulinemia play an important role in the pathogenesis of coronary heart disease (CHD) in nondiabetic individuals. Results of case-control and epidemiological studies in nondiabetic individuals will be reviewed to examine the link between insulin resistance/compensatory hyperinsulinemia, associated abnormalities, and CHD. The primary focus of the review will be on the central role that dyslipidemia plays in the link between insulin resistance/compensatory hyperinsulinemia and CHD. Additional issues to be addressed include the following: (1) the relationship among obesity, insulin resistance, and CHD; (2) a listing of other abnormalities that contribute to risk of CHD in insulin-resistant individuals; and (3) discussion of the importance of differential tissue insulin sensitivity in the development of abnormalities that increase CHD risk in insulin-resistant, nondiabetic individuals. The information will reflect the author's decision as to what issues are believed to be of particular relevance or less well appreciated concerning the complex relationship between insulin resistance and CHD. Resistance to insulin-mediated glucose disposal and hyperinsulinemia is a common finding in apparently healthy individuals and is associated with a number of abnormalities that greatly increase risk of CHD.

Intermittent fasting and caloric restriction have been shown to extend life expectancy and reduce inflammation and cancer promotion in animal models. It was hypothesized that intermittent prolonged fasting practiced during the month of Ramadan (RIF) could positively affect the inflammatory state. To investigate this hypothesis, a cross-sectional study was designed to investigate the impact of RIF on selected inflammatory cytokines and immune biomarkers in healthy subjects. Fifty (21 men and 29 women) healthy volunteers who practiced Ramadan fasting were recruited for the investigation of circulating proinflammatory cytokines (interleukin [IL]-1. β, IL-6, and tumor necrosis factor α), immune cells (total leukocytes, monocytes, granulocytes, and lymphocytes), and anthropometric and dietary assessments. The investigations were conducted 1 week before Ramadan fasting, at the end of the third week of Ramadan, and 1 month after the cessation of Ramadan month. The proinflammatory cytokines IL-1. β, IL-6, and tumor necrosis factor α; systolic and diastolic blood pressures; body weight; and body fat percentage were significantly lower (P \textless .05) during Ramadan as compared with before Ramadan or after the cessation of Ramadan fasting. Immune cells significantly decreased during Ramadan but still remained within the reference ranges. These results indicate that RIF attenuates inflammatory status of the body by suppressing proinflammatory cytokine expression and decreasing body fat and circulating levels of leukocytes. © 2012 Elsevier Inc.

Improvement in body condition was assessed in 40 cull ewes (>6 years), equally distributed in two groups and realimented with ad libitum roughage (gram straw) and two levels of concentrate feeding, i.e., 2.5 % (T1) of live weight (LW) and ad libitum (T2). Five representative animals from an initial 45 were slaughtered at the initiation of the study (0 day) and five animals from each treatment at 44, 67, and 90 days of experiment for carcass attributes. Improvement in body condition score (BCS), nutrient utilization, feed efficiency, and carcass traits were assessed at 44, 67, and 90 days. Metabolism trial of 6-day collection of feed, feces, and urine samples was conducted on five representative ewes from each group after 60 days of feeding. The level of concentrate feeding on LW gain and BCS was significant, and the duration of realimentation showed a linear improvement (P < 0.001). The digestibility and intake of dry matter, organic matter, and crude protein was higher (P < 0.05) in T2. The N intake, absorption, and balance showed a similar trend. Increase (P < 0.05) in total N, trichloroacetic acid precipitable N, and ammonia N was observed with extension of realimentation period. Blood metabolic profile also showed improvement (P < 0.05) from an undernourished state to normal after alimentation. Animals in T2 accumulated higher LW with minimal expenditure of metabolizable energy (73.4 vs 79.1 MJ) and higher efficiency of feed conversion during 68 to 90 days of realimentation. Linear improvement (P < 0.01) in carcass traits (preslaughter weight, empty live weight, hot carcass weight, dressing percentage, and amount of subcutaneous and intramuscular fat) and composition of longissimus dorsi muscle was observed. Ad lib concentrate supplementation for a period of 90 days may thus be considered appropriate for achieving desired efficiency of gain and improvement in body condition of cull ewes for quality mutton production. © 2012 Springer Science+Business Media B.V.

Lipedema is a disproportionate, symmetrical fatty swelling characterized by pain and bruising existing almost exclusively among women. We undertook a systematic review of the available literature about lipedema, given the lack of knowledge and little evidence about this disorder especially among obesity experts. Diagnosis of lipedema is usually based on clinical features. Symmetrical edema in the lower limbs with fatty deposits located to hips and thighs usually appears at puberty and often affects several members of the same family. Main disorders considered for differential diagnosis are lymphedema, obesity, lipohypertrophy and phlebedema. Treatment protocols comprise conservative (decongestive lymphatic therapy) and surgical (liposuction) approaches. Early diagnosis and treatment are mandatory for this disorder otherwise gradual enlargement of fatty deposition causes impaired mobility and further comorbidities like arthrosis and lymphatic insufficiency.

Yeasts are a convenient platform for many applications. They have been widely used as the expression hosts. There is a need to have a new yeast expression system to contribute the molecular cloning demands. Eight yeast isolates were screened from various environment sources and identified through ribosomal DNA (rDNA) Internal Transcribed Spacer (ITS). Full sequence of the rDNA ITS region for each isolate was BLASTed and phylogenetic study was constructed by using MEGA4. Among the isolates, isolate WB from 'ragi' (used to ferment carbohydrates) could be identified as a new species in order Saccharomycetales according to rDNA ITS region, morphology and biochemical tests. Isolate SO (from spoiled orange), RT (rotten tomato) and RG (different type of 'ragi') were identified as Pichia sp. Isolates R1 and R2, S4 and S5 (from the surrounding of a guava tree) were identified as Issatchenkia sp. and Hanseniaspora sp., respectively. Geneticin, 50 µg/mL, was determined to be the antibiotic marker for all isolates excepted for isolates RT and SO which used 500 µg/mL and 100 µg/mL Zeocin, respectively. Intra-extracellular proteins were screened for lipolytic activity at 30°C and 70°C. Thermostable lipase activity was detected in isolates RT and R1 with 0.6 U/mg and 0.1 U/mg, respectively. In conclusion, a new yeast-vector system for isolate WB can be developed by using phleomycin or geneticin as the drugs resistance marker. Moreover, strains RT and R1 can be investigated as a novel source of a thermostable lipase.

Objective To study the long term consequences of low carbohydrate diets, generally characterised by concomitant increases in protein intake, on cardiovascular health. Design Prospective cohort study. Setting Uppsala, Sweden. Participants From a random population sample, 43 396 Swedish women, aged 30-49 years at baseline, completed an extensive dietary questionnaire and were followed-up for an average of 15.7 years. Main outcome measures Association of incident cardiovascular diseases (ascertained by linkage with nationwide registries), overall and by diagnostic category, with decreasing carbohydrate intake (in tenths), increasing protein intake (in tenths), and an additive combination of these variables (low carbohydrate-high protein score, from 2 to 20), adjusted for intake of energy, intake of saturated and unsaturated fat, and several non-dietary variables. Results A one tenth decrease in carbohydrate intake or increase in protein intake or a 2 unit increase in the low carbohydrate-high protein score were all statistically significantly associated with increasing incidence of cardiovascular disease overall (n=1270)—incidence rate ratio estimates 1.04 (95% confidence interval 1.00 to 1.08), 1.04 (1.02 to 1.06), and 1.05 (1.02 to 1.08). No heterogeneity existed in the association of any of these scores with the five studied cardiovascular outcomes: ischaemic heart disease (n=703), ischaemic stroke (n=294), haemorrhagic stroke (n=70), subarachnoid haemorrhage (n=121), and peripheral arterial disease (n=82). Conclusions Low carbohydrate-high protein diets, used on a regular basis and without consideration of the nature of carbohydrates or the Department of Clinical and Experimental Medicine, University of Linköping, Cancer Registry of Norway, Folkhälsan Research Center, Samfundet source of proteins, are associated with increased risk of cardiovascular disease.

BACKGROUND: Experimental studies support the anti-neoplastic effect of apo(a), but several clinical studies have reported contradictory results. The purpose of this study was to determine whether a low lipoprotein(a) [Lp(a)] concentration is related to mortality from major causes of death, especially cancer. METHODS: The subjects were 10,413 participants (4,005 men and 6,408 women) from a multi-center population-based cohort study in Japan (The Jichi Medical School cohort study). The average age at registration was 55.0 years, and the median observation period was 4,559 days. As the estimated hazard ratio was high for both the low and very high Lp(a) levels, we defined two Lp(a) groups: a low Lp(a) group [Lp(a)<80 mg/L] and an intermediate-to-high Lp(a) group [Lp(a) ≥ 80]. Participants who died from malignant neoplasms (n = 316), cardiovascular disease (202), or other causes (312) during the observation period were examined. RESULTS: Cumulative incidence plots showed higher cumulative death rates for the low Lp(a) group than for the intermediate-to-high Lp(a) group for all-cause, cancer, and miscellaneous-cause deaths (p<0.001, p = 0.03, and p = 0.03, respectively). Cox proportional hazards analyses with the sex and age of the participants, body mass index, and smoking and drinking histories as covariates showed that a low Lp(a) level was a significant risk for all-cause, cancer, and miscellaneous-cause deaths (p

Long-term effects of carbohydrate-restricted diets are unclear. We examined a low-carbohydrate, high-protein (LCHP) score in relation to mortality.

Vascular calcification has severe clinical consequences and is considered an accurate predictor of future adverse cardiovascular events, including myocardial infarction and stroke. Previously vascular calcification was thought to be a passive process which involved the deposition of calcium and phosphate in arteries and cardiac valves. However, recent studies have shown that vascular calcification is a highly regulated, cell-mediated process similar to bone formation. In this article, we outline the current understanding of key mechanisms governing vascular calcification and highlight the clinical consequences. By understanding better the molecular pathways and genetic circuitry responsible for the pathological mineralization process novel drug targets may be identified and exploited to combat and reduce the detrimental effects of vascular calcification on human health.

Insulin resistance is a complex metabolic disorder that defies explanation by a single etiological pathway. Accumulation of ectopic lipid metabolites, activation of the unfolded protein response (UPR) pathway, and innate immune pathways have all been implicated in the pathogenesis of insulin resistance. However, these pathways are also closely linked to changes in fatty acid uptake, lipogenesis, and energy expenditure that can impact ectopic lipid deposition. Ultimately, these cellular changes may converge to promote the accumulation of specific lipid metabolites (diacylglycerols and/or ceramides) in liver and skeletal muscle, a common final pathway leading to impaired insulin signaling and insulin resistance. © 2012 Elsevier Inc.

BACKGROUND: The effects of carbohydrate-restricted (ketogenic) diets on metabolic parameters in children have been incompletely assessed. OBJECTIVE: To compare the efficacy and metabolic impact of ketogenic and hypocaloric diets in obese children and adolescents. SUBJECTS: Fifty-eight obese subjects were placed on one of the two diets for 6 months. METHODS: Anthropometric measurements, body composition, oral glucose/insulin tolerance test, lipidemic profile, high molecular weight (HMW) adiponectin, whole-body insulin sensitivity index (WBISI), and homeostatic model assessment-insulin resistance (HOMA-IR) were determined before and after each diet. RESULTS: Both groups significantly reduced their weight, fat mass, waist circumference, fasting insulin, and HOMA-IR (p = 0.009 for ketogenic and p = 0.014 for hypocaloric), but the differences were greater in the ketogenic group. Both groups increased WBISI significantly, but only the ketogenic group increased HMW adiponectin significantly (p = 0.025). CONCLUSIONS: The ketogenic diet revealed more pronounced improvements in weight loss and metabolic parameters than the hypocaloric diet and may be a feasible and safe alternative for children's weight loss.

SIGNIFICANCE: Mitochondrial dynamics and turnover are crucial for cellular homeostasis and differentiation. The removal of damaged mitochondria that could contribute to cellular dysfunction or death is achieved through the process of mitochondrial autophagy, i.e., mitophagy. Moreover, mitophagy is responsible for removal of mitochondria during terminal differentiation of red blood cells and T cells.$\backslash$n$\backslash$nRECENT ADVANCES: Recent work is elucidating how mitochondria are recognized for selective mitophagy either by PINK1 and Parkin or mitophagic receptors Nix and Bnip3 and their accompanying modulators. PINK1/Parkin-mediated mitophagy reveals their role of cargo recognition through polyubiquitination of mitochondrial proteins, while Nix functions as a regulated mitophagy receptor. These recognized modes of capture by the autophagy machinery operate at different efficiencies, from partial to complete elimination of mitochondria.$\backslash$n$\backslash$nCRITICAL ISSUES: It is critical to understand that the distinct regulatory mechanisms involve not only autophagy machinery, but also proteins associated with mitochondrial fusion and fission and therefore, regulation of mitochondrial morphology. The end result is either finely tuned quality control of damaged mitochondria, or mitochondrial clearance during development- induced mitophagy.$\backslash$n$\backslash$nFUTURE DIRECTIONS: In this article, known mechanisms and future directions for deciphering the challenge of mitophagy regulation will be discussed.