top of page
Published Science
Click Search to Filter.
Total Entries: 10690
Title:
Role of diet and nutritional management in non-alcoholic fatty liver disease
Authors:
Fan, Jian-Gao; Cao, Hai-Xia
Abstract:
Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum ranging from simple steatosis to non-alcoholic steatohepatitis, which causes an increased risk of cirrhosis, type 2 diabetes, and cardiovascular complications. With the worldwide growing incidence of obesity, sedentary lifestyle, and unhealthy dietary pattern, NAFLD has currently been recognized as a major health burden. Dietary patterns and nutrients are the important contributors to the development, progression, and treatment of NAFLD and associated metabolic comorbidities. Generally, hypercaloric diet, especially rich in trans/saturated fat and cholesterol, and fructose-sweetened beverages seem to increase visceral adiposity and stimulate hepatic lipid accumulation and progression into non-alcoholic steatohepatitis, whereas reducing caloric intake, increasing soy protein and whey consumption, and supplement of monounsaturated fatty acids, omega-3 fatty acids, and probiotics have preventive and therapeutic effects. In addition, choline, fiber, coffee, green tea, and light alcohol drinking might be protective factors for NAFLD. Based on available data, at least 3-5% of weight loss, achieved by hypocaloric diet alone or in conjunction with exercise and behavioral modification, generally reduces hepatic steatosis, and up to 10% weight loss may be needed to improve hepatic necroinflammation. A sustained adherence to diet rather than the actual diet type is a major predictor of successful weight loss. Moreover, a healthy diet has benefits beyond weight reduction on NAFLD patients whether obese or of normal weight. Therefore, nutrition serves as a major route of prevention and treatment of NAFLD, and patients with NAFLD should have an individualized diet recommendation.
Published:
2013-12
Title:
Self-inserted foreign body and attention-deficit/hyperactivity disorder: evaluated by the Conners' Parent Rating Scales-Revised
Authors:
Özcan, Kemal; Özcan, Özlem; Muluk, Nuray Bayar; Cingi, Cemal; Durukan, Kübra
Abstract:
OBJECTIVES: We aimed to evaluate the relationship between attention-deficit/hyperactivity disorder (ADHD) and self-inserted foreign bodies (SIFBs) in children by the Conners' Parent Rating Scales-Revised (CPRS-R). METHODS: Forty-five children (31 males and 14 females) with self-inserted foreign body of ear/nose and 37 healthy children (22 males and 15 females) included into the study. They were all between 3 and 9 years old. The parents filled the socio-demographic information form including age, gender, demographic data, previous medical history of the child and features of the family; and completed the Conners' Parent Rating Scales-Revised (CPRS-R) questionnaire. RESULTS: In the SIFB group (study), 55.6% of the children were not attending to the school, 31.1% of them were attending to the primary school and 13.3% of them were the pre-school student. These rates were 37.8%, 32.4% and 29.7%, respectively, in the control group. The all CPRS-R subscale values (CG/I, H, ADHD-I, CGI-DI, DSMIV SS-I, DSM-IV SS-HI and DSM-IV SS-T) were significantly higher in the study group than the control group. There was no significant correlation between gender of the children and CPRS-R subscales. Children with lower school success, and having previous psychiatric problems were related to higher CPRS-R values in all subscales. In older children, hyperactivity scores were lower; and in younger children and the children, not going to the school, hyperactivity scores were higher. CPRS-R scores decreased as the child grown. CONCLUSION: It was concluded that children with ADHD were more likely to have conditions that might damage himself/herself such as self-inserted foreign body or trauma than normal children. To avoid this condition, these families should closely observe the child; and the child should be provided to participate in activities such as group games and activities that contribute to the development of the child. Warning the children properly and close follow-up of the young children are required to prevent this unwanted condition.
Published:
2013-12
Title:
The uncertain significance of low vitamin D levels in African descent populations: a review of the bone and cardiometabolic literature
Authors:
O'Connor, Michelle Y.; Thoreson, Caroline K.; Ramsey, Natalie L. M.; Ricks, Madia; Sumner, Anne E.
Abstract:
Vitamin D levels in people of African descent are often described as inadequate or deficient. Whether low vitamin D levels in people of African descent lead to compromised bone or cardiometabolic health is unknown. Clarity on this issue is essential because if clinically significant vitamin D deficiency is present, vitamin D supplementation is necessary. However, if vitamin D is metabolically sufficient, vitamin D supplementation could be wasteful of scarce resources and even harmful. In this review vitamin D physiology is described with a focus on issues specific to populations of African descent such as the influence of melanin on endogenous vitamin D production and lactose intolerance on the willingness of people to ingest vitamin D fortified foods. Then data on the relationship of vitamin D to bone and cardiometabolic health in people of African descent are evaluated.
Published:
2013-12
Title:
Thought for food: Clinical evidence for the dietary prevention strategy in cardiovascular disease. [Review]
Authors:
Lewis, Barry; Sullivan, David R.; Watts, Gerald F.
Abstract:
A modified diet has been advocated for the past 50 years for prevention of cardiovascular disease. The evidence has in the past been largely epidemiological and experimental, with relatively limited support from clinical trials. However a major element of this strategy, reduction in intake of saturated fats, has recently been called into question; the evidence for and against this view is critically reviewed. A Cochrane review, and recent trials, have advanced our understanding of the role of diet and of optimal dietary recommendation strategy. Here we consider these advances in the light of established knowledge. Copyright © 2013 The Authors. International Journal of Evidence-Based Healthcare © 2013 The Joanna Briggs Institute.
Published:
2013-12
Title:
[Chrono-nutrition and chrono-exercise]
Authors:
Shibata, Shigenobu; Sasaki, Hiroyuki; Ikeda, Yuko
Abstract:
The circadian rhythm controls many physiological functions, such as feeding, motor activity, endocrine secretion and autonomic nerve. Regular feeding pattern can entrain the peripheral circadian clock, whereas peripheral clock systems can control the absorption distribution, metabolism and excretion of nutrients, suggesting mutual interactions between circadian clocks and nutrition/food. The interactions were so-called by "chrono-nutrition", and bigger meals for breakfast were good for entrainment of peripheral clock and protection of obesity. Similar to chrono-nutrition the timing of exercise ("chrono-exercise") is important for both entrainment signals and energy expenditure. Evening exercise and/or feeding then exercise was good timing exercise for protection of obesity. Taken all, it is suggested that timing of feeding and exercise is now one of key factors for metabolic syndrome.
Published:
2013-12
Title:
A positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: implications for ADHD and its treatment
Authors:
del Campo, Natalia; Fryer, Tim D.; Hong, Young T.; Smith, Rob; Brichard, Laurent; Acosta-Cabronero, Julio; Chamberlain, Samuel R.; Tait, Roger; Izquierdo, David; Regenthal, Ralf; Dowson, Jonathan; Suckling, John; Baron, Jean-Claude; Aigbirhio, Franklin I.; Robbins, Trevor W.; Sahakian, Barbara J.; Müller, Ulrich
Abstract:
Through the combined use of (18)F-fallypride positron emission tomography and magnetic resonance imaging this study examined the neural mechanisms underlying the attentional deficits associated with attention deficit/hyperactivity disorder and their potential reversal with a single therapeutic dose of methylphenidate. Sixteen adult patients with attention deficit/hyperactivity disorder and 16 matched healthy control subjects were positron emission tomography and magnetic resonance imaging scanned and tested on a computerized sustained attention task after oral methylphenidate (0.5 mg/kg) and placebo administration in a within-subject, double-blind, cross-over design. Although patients with attention deficit/hyperactivity disorder as a group showed significant attentional deficits and reduced grey matter volume in fronto-striato-cerebellar and limbic networks, they had equivalent D2/D3 receptor availability and equivalent increases in endogenous dopamine after methylphenidate treatment to that observed in healthy control subjects. However, poor attentional performers drawn from both the attention deficit/hyperactivity disorder and the control groups had significantly reduced left caudate dopamine activity. Methylphenidate significantly increased dopamine levels in all nigro-striatal regions, thereby normalizing dopamine levels in the left caudate in low performers. Behaviourally, methylphenidate improved sustained attention in a baseline performance-dependent manner, irrespective of diagnosis. This finding was accompanied by an equally performance-dependent effect of the drug on dopamine release in the midbrain, whereby low performers showed reduced dopamine release in this region. Collectively, these findings support a dimensional model of attentional deficits and underlying nigro-striatal dopaminergic mechanisms of attention deficit/hyperactivity disorder that extends into the healthy population. Moreover, they confer midbrain dopamine autoreceptors a hitherto neglected role in the therapeutic effects of oral methylphenidate in attention deficit/hyperactivity disorder. The absence of significant case-control differences in D2/D3 receptor availability (despite the observed relationships between dopamine activity and attention) suggests that dopamine dysregulation per se is unlikely to be the primary cause underlying attention deficit/hyperactivity disorder pathology in adults. This conclusion is reinforced by evidence of neuroanatomical changes in the same set of patients with attention deficit/hyperactivity disorder.
Published:
2013-11
Title:
Alterations in thyroid function among the different polycystic ovary syndrome phenotypes
Authors:
Morgante, Giuseppe; Musacchio, Maria Concetta; Orvieto, Raoul; Massaro, Maria Giulia; De Leo, Vincenzo
Abstract:
The study evaluates the prevalence of subclinical thyroid dysfunction in infertile PCOS patients, according to the different PCOS phenotypes and to examine whether insulin sensitizers in insulin resistant (IR) PCOS patients may improve thyroid function. The study population consisted of all PCOS patients, attending the infertility and IVF unit of Department of Pediatrics, Obstetrics and Reproductive Medicine of University of Siena, Italy, and compared them to regularly cycling, healthy, infertile controls. Upon admission, blood was drawn from all patients during the early follicular phase, for complete hormonal and metabolic profiles. In IR-PCOS patients treated with insulin sensitizers, blood was drawn again after 6 months. PCOS patients had a significantly higher prevalence of subclinical thyroid dysfunction compared to infertile controls. While no significant association was detected between TSH value and the presence of hyperandrogenism, overweight and obese PCOS patients, as well as IR PCOS patients showed significantly higher prevalence of subclinical thyroid dysfunction. Moreover, among IR PCOS patients, 6 months treatment with insulin sensitizers significantly reduces TSH levels. Infertile PCOS patients have a high prevalence of subclinical thyroid dysfunction, which may be successfully treated in IR PCOS patients by insulin sensitizers.
Published:
2013-11
Title:
Calcium and α-tocopherol suppress cured-meat promotion of chemically induced colon carcinogenesis in rats and reduce associated biomarkers in human volunteers
Authors:
Pierre, Fabrice H. F.; Martin, Océane C. B.; Santarelli, Raphaelle L.; Taché, Sylviane; Naud, Nathalie; Guéraud, Françoise; Audebert, Marc; Dupuy, Jacques; Meunier, Nathalie; Attaix, Didier; Vendeuvre, Jean-Luc; Mirvish, Sidney S.; Kuhnle, Gunter C. G.; Cano, Noel; Corpet, Denis E.
Abstract:
BACKGROUND: Processed meat intake has been associated with increased colorectal cancer risk. We have shown that cured meat promotes carcinogen-induced preneoplastic lesions and increases specific biomarkers in the colon of rats. OBJECTIVES: We investigated whether cured meat modulates biomarkers of cancer risk in human volunteers and whether specific agents can suppress cured meat-induced preneoplastic lesions in rats and associated biomarkers in rats and humans. DESIGN: Six additives (calcium carbonate, inulin, rutin, carnosol, α-tocopherol, and trisodium pyrophosphate) were added to cured meat given to groups of rats for 14 d, and fecal biomarkers were measured. On the basis of these results, calcium and tocopherol were kept for the following additional experiments: cured meat, with or without calcium or tocopherol, was given to dimethylhydrazine-initiated rats (47% meat diet for 100 d) and to human volunteers in a crossover study (180 g/d for 4 d). Rat colons were scored for mucin-depleted foci, putative precancer lesions. Biomarkers of nitrosation, lipoperoxidation, and cytotoxicity were measured in the urine and feces of rats and volunteers. RESULTS: Cured meat increased nitroso compounds and lipoperoxidation in human stools (both P < 0.05). Calcium normalized both biomarkers in rats and human feces, whereas tocopherol only decreased nitro compounds in rats and lipoperoxidation in feces of volunteers (all P
Published:
2013-11
Title:
Dietary carbohydrate restriction improves insulin sensitivity, blood pressure, microvascular function, and cellular adhesion markers in individuals taking statins
Authors:
Ballard, Kevin D.; Quann, Erin E.; Kupchak, Brian R.; Volk, Brittanie M.; Kawiecki, Diana M.; Fernandez, Maria Luz; Seip, Richard L.; Maresh, Carl M.; Kraemer, William J.; Volek, Jeff S.
Abstract:
Statins positively impact plasma low-density lipoprotein cholesterol, inflammation and vascular endothelial function (VEF). Carbohydrate restricted diets (CRD) improve atherogenic dyslipidemia, and similar to statins, have been shown to favorably affect markers of inflammation and VEF. No studies have examined whether a CRD provides additional benefit beyond that achieved by habitual statin use. We hypothesized that a CRD (<50 g carbohydrate/d) for 6 weeks would improve lipid profiles and insulin sensitivity, reduce blood pressure, decrease cellular adhesion and inflammatory biomarkers, and augment VEF (flow-mediated dilation and forearm blood flow) in statin users. Participants (n = 21; 59.3 ± 9.3 y, 29.5 ± 3.0 kg/m(2)) decreased total caloric intake by approximately 415 kcal at 6 weeks (P < .001). Daily nutrient intakes at baseline (46/36/17% carb/fat/pro) and averaged across the intervention (11/58/28% carb/fat/pro) demonstrated dietary compliance, with carbohydrate intake at baseline nearly 5-fold greater than during the intervention (P < .001). Compared to baseline, both systolic and diastolic blood pressure decreased after 3 and 6 weeks (P < .01). Peak forearm blood flow, but not flow-mediated dilation, increased at week 6 compared to baseline and week 3 (P ≤ .03). Serum triglyceride, insulin, soluble E-Selectin and intracellular adhesion molecule-1 decreased (P
Published:
2013-11
Title:
Dolastatin, along with Celecoxib, stimulates apoptosis by a mechanism involving oxidative stress, membrane potential change and PI3-K/AKT pathway down regulation
Authors:
Piplani, Honit; Rana, Chandan; Vaish, Vivek; Vaiphei, Kim; Sanyal, S. N.
Abstract:
BACKGROUND: Phosphoinositide 3-kinase (PI3-K) is an important regulator of oncogenesis and apoptosis in various types of cancers including colon cancer. A combinatorial strategy of using Cyclooxygenase-2 inhibitor, Celecoxib and Dolastatin, a linear peptide from marine mollusks of Indian Ocean origin has shown anti-neoplastic effects in colon cancer in a rat model. METHODS: The signal transduction pathway of PI3-K/AKT and the downstream signaling proteins had been studied in an early stage of colon carcinogenesis (DMH induced) by gene and protein expression, apoptotic studies by colonocyte apoptotic bleb assay, intracellular calcium level by fluorescence spectrometry, mitochondrial membrane potential by Rhodamine 123 flow cytometry and Reactive oxygen species measurement. Molecular docking analysis was employed to study the interaction of oncogenic proteins and the ligand, Celecoxib and Dolastatin. RESULTS: Apoptotic cell index was lowered with DMH while both the drugs increased it and inhibited PI3-K and AKT expression. Docking studies revealed both the proteins targeted by the drugs via an ATP binding site. An increased expression of GSK-3β, pro-apoptotic protein Bad, transcription factor Egr-1, tumor suppressor protein PTEN while a downregulation of G1-associated cell cycle protein, Cyclin D1 and increased intracellular calcium as well as reactive oxygen species were observed. Also, the number of cells having a higher mitochondrial membrane potential was lowered. CONCLUSION: Celecoxib and Dolastatin inhibited the tumor development through regulation of the PI3-K/AKT pathway which can act as a novel target for these drugs. GENERAL SIGNIFICANCE: The anti-cancer properties of Dolastatin, a peptide isolated from marine mollusks in colorectal cancer is shown.
Published:
2013-11
Title:
Evaluation of Oral Glucose Tolerance Test in Children With Epilepsy
Authors:
Varlamis, Sotirios; Vavatsi, Norma; Pavlou, Evangelos; Kotsis, Vasileios; Spilioti, Martha; Kavga, Maria; Varlamis, George; Sotiriadou, Foteini; Agakidou, Eleni; Voutoufianakis, Spyridon; Evangeliou, Athanasios E.
Abstract:
Glucose metabolism of children with drug-resistant epilepsy, controlled by antiepileptic drugs epilepsy, and first-time nonfebrile seizures was studied through the performance of an oral glucose tolerance test and through insulin, C-peptide, and glycosylated hemoglobin measurements. In the refractory epilepsy group, there were more abnormal oral glucose tolerance test results (62.07%) in comparison to the controlled epilepsy group (25%) and the group of first-time seizures (21.21%). There was a significant difference between the group of refractory epilepsy and every other group concerning the abnormality of the oral glucose tolerance test (P
Published:
2013-11
Title:
Is fatty acid intake a predictor of arterial stiffness and blood pressure in men? Evidence from the Caerphilly Prospective Study
Authors:
Livingstone, K. M.; Givens, D. I.; Cockcroft, J. R.; Pickering, J. E.; Lovegrove, J. A.
Abstract:
CONCLUSION: This study suggests that consumption of SFA and PUFA have opposing effects on arterial stiffness and blood pressure. Importantly, this study suggests that consumption of FA is an important risk factor for arterial stiffness and CVD. Copyright © 2012 Elsevier B.V. All rights reserved.
Published:
2013-11
Title:
Mitochondrial DNA genetics and the heteroplasmy conundrum in evolution and disease.
Authors:
Wallace, Douglas C; Chalkia, Dimitra
Abstract:
The unorthodox genetics of the mtDNA is providing new perspectives on the etiology of the common "complex" diseases. The maternally inherited mtDNA codes for essential energy genes, is present in thousands of copies per cell, and has a very high mutation rate. New mtDNA mutations arise among thousands of other mtDNAs. The mechanisms by which these "heteroplasmic" mtDNA mutations come to predominate in the female germline and somatic tissues is poorly understood, but essential for understanding the clinical variability of a range of diseases. Maternal inheritance and heteroplasmy also pose major challengers for the diagnosis and prevention of mtDNA disease.
Published:
2013-11
Title:
Randomized cross-over trial of short-term water-only fasting: metabolic and cardiovascular consequences
Authors:
Horne, B. D.; Muhlestein, J. B.; Lappé, D. L.; May, H. T.; Carlquist, J. F.; Galenko, O.; Brunisholz, K. D.; Anderson, J. L.
Abstract:
BACKGROUND AND AIMS: Routine, periodic fasting is associated with a lower prevalence of coronary artery disease (CAD). Animal studies show that fasting may increase longevity and alter biological parameters related to longevity. We evaluated whether fasting initiates acute changes in biomarker expression in humans that may impact short- and long-term health. METHODS AND RESULTS: Apparently-healthy volunteers (N = 30) without a recent history of fasting were enrolled in a randomized cross-over trial. A one-day water-only fast was the intervention and changes in biomarkers were the study endpoints. Bonferroni correction required p ≤ 0.00167 for significance (p
Published:
2013-11
Title:
Targeted alteration of dietary n-3 and n-6 fatty acids for the treatment of chronic headaches: A randomized trial
Authors:
Ramsden, Christopher E.; Faurot, Keturah R.; Zamora, Daisy; Suchindran, Chirayath M.; MacIntosh, Beth A.; Gaylord, Susan; Ringel, Amit; Hibbeln, Joseph R.; Feldstein, Ariel E.; Mori, Trevor A.; Barden, Anne; Lynch, Chanee; Coble, Rebecca; Mas, Emilie; Palsson, Olafur; Barrow, David A.; Mann, J. Douglas
Abstract:
Omega-3 and n-6 fatty acids are biosynthetic precursors to lipid mediators with antinociceptive and pronociceptive properties. We conducted a randomized, single-blinded, parallel-group clinical trial to assess clinical and biochemical effects of targeted alteration in dietary n-3 and n-6 fatty acids for treatment of chronic headaches. After a 4-week preintervention phase, ambulatory patients with chronic daily headache undergoing usual care were randomized to 1 of 2 intensive, food-based 12-week dietary interventions: a high n-3 plus low n-6 (H3-L6) intervention, or a low n-6 (L6) intervention. Clinical outcomes included the Headache Impact Test (HIT-6, primary clinical outcome), Headache Days per month, and Headache Hours per day. Biochemical outcomes included the erythrocyte n-6 in highly unsaturated fatty acids (HUFA) score (primary biochemical outcome) and bioactive n-3 and n-6 derivatives. Fifty-six of 67 patients completed the intervention. Both groups achieved targeted intakes of n-3 and n-6 fatty acids. In intention-to-treat analysis, the H3-L6 intervention produced significantly greater improvement in the HIT-6 score (−7.5 vs −2.1; P < 0.001) and the number of Headache Days per month (−8.8 vs −4.0; P = 0.02), compared to the L6 group. The H3-L6 intervention also produced significantly greater reductions in Headache Hours per day (−4.6 vs −1.2; P = 0.01) and the n-6 in HUFA score (−21.0 vs −4.0%; P < 0.001), and greater increases in antinociceptive n-3 pathway markers 18-hydroxy-eicosapentaenoic acid (+118.4 vs +61.1%; P < 0.001) and 17-hydroxy-docosahexaenoic acid (+170.2 vs +27.2; P
Published:
2013-11
Title:
The human milk metabolome reveals diverse oligosaccharide profiles
Authors:
Smilowitz, Jennifer T; O'Sullivan, Aifric; Barile, Daniela; German, J Bruce; Lönnerdal, Bo; Slupsky, Carolyn M
Abstract:
Breast milk delivers nutrition and protection to the developing infant. There has been considerable research on the high-molecular-weight milk components; however, low-molecular-weight metabolites have received less attention. To determine the effect of maternal phenotype and diet on the human milk metabolome, milk collected at day 90 postpartum from 52 healthy women was analyzed by using proton nuclear magnetic resonance spectroscopy. Sixty-five milk metabolites were quantified (mono-, di-, and oligosaccharides; amino acids and derivatives; energy metabolites; fatty acids and associated metabolites; vitamins, nucleotides, and derivatives; and others). The biological variation, represented as the percentage CV of each metabolite, varied widely (4-120%), with several metabolites having low variation (
Published:
2013-11
Title:
Up-regulation of p53 and mitochondrial signaling pathway in apoptosis by a combination of COX-2 inhibitor, Celecoxib and Dolastatin 15, a marine mollusk linear peptide in experimental colon carcinogenesis
Authors:
Piplani, Honit; Vaish, Vivek; Rana, Chandan; Sanyal, Sankar N.
Abstract:
Programmed cell death, also known as apoptosis, is an active process occurring in eukaryotic cells and it depends on various sets of pro and anti-apoptotic proteins. Chemoprevention of colorectal cancer can be achieved by inducing apoptosis using synthetic compound, Celecoxib and natural peptide, Dolastatin 15 in an effective manner. But the apoptotic signaling by these two drugs remain unclear. The present study was thus focused on the role of Bcl2 family of proteins and their interplay with p53 in rats during the chemoprevention by these two drugs. After treatment for 6 wk with 1, 2-dimethylhydrazine (DMH), animals showed a marked occurrence of multiple plaque lesions. However, a simultaneous treatment with Celecoxib and Dolastatin 15 decreases such number to a significant level. DMH treatment also decreases the number of apoptotic cells in the colonic enterocytes which were corrected to the normal level by Celecoxib and Dolastatin 15. An increased expression of Bcl2 while other proteins like Bax, Apaf-1, cyt c, and caspases in the apoptotic pathway, and the tumor suppressor proteins, p53 and p21 get down-regulated after DMH treatment which were reverted back to normal with Celecoxib and Dolastatin 15. Also, cells having high mitochondrial membrane potential had been seen to increase to significant levels which were reduced after the administration of these anti-inflammatory drugs. In silico molecular docking studies also showed that Dolastatin 15 and Celecoxib may bind to the active site pocket of Bcl2 , thus revealing the direct target of Dolastatin 15 and Celecoxib apart from binding to COX-2.
Published:
2013-11
Title:
2-Aminoadipic acid is a biomarker for diabetes risk
Authors:
Wang, Thomas J; Ngo, Debby; Psychogios, Nikolaos; Dejam, Andre; Larson, Martin G; Vasan, Ramachandran S; Ghorbani, Anahita; O'Sullivan, John; Cheng, Susan; Rhee, Eugene P; Sinha, Sumita; McCabe, Elizabeth; Fox, Caroline S; O'Donnell, Christopher J; Ho, Jennifer E; Florez, Jose C; Magnusson, Martin; Pierce, Kerry A; Souza, Amanda L; Yu, Yi
Abstract:
Improvements in metabolite-profiling techniques are providing increased breadth of coverage of the human metabolome and may highlight biomarkers and pathways in common diseases such as diabetes. Using a metabolomics platform that analyzes intermediary organic acids, purines, pyrimidines, and other compounds, we performed a nested case-control study of 188 individuals who developed diabetes and 188 propensity-matched controls from 2,422 normoglycemic participants followed for 12 years in the Framingham Heart Study. The metabolite 2-aminoadipic acid (2-AAA) was most strongly associated with the risk of developing diabetes. Individuals with 2-AAA concentrations in the top quartile had greater than a 4-fold risk of developing diabetes. Levels of 2-AAA were not well correlated with other metabolite biomarkers of diabetes, such as branched chain amino acids and aromatic amino acids, suggesting they report on a distinct pathophysiological pathway. In experimental studies, administration of 2-AAA lowered fasting plasma glucose levels in mice fed both standard chow and high-fat diets. Further, 2-AAA treatment enhanced insulin secretion from a pancreatic β cell line as well as murine and human islets. These data highlight a metabolite not previously associated with diabetes risk that is increased up to 12 years before the onset of overt disease. Our findings suggest that 2-AAA is a marker of diabetes risk and a potential modulator of glucose homeostasis in humans.
Published:
2013-10
Title:
A Comparison of the Risk of QT Prolongation Among SSRIs
Authors:
Funk, Kylee A.; Bostwick, Jolene R.
Abstract:
Objective: To report QT prolongation potential in selective serotonin reuptake inhibitors (SSRIs) in order to advise clinicians on safe use of SSRIs other than citalopram in light of citalopram warnings. Data Sources: Primary literature and case reports were identified through a systematic search. Data from drug manufacturers, package inserts, and the ArizonaCERT database were also utilized. Study Selection and Data Extraction: English-language studies and case reports were included. Data Synthesis: Studies demonstrate possible dose-related clinically significant QT prolongation with escitalopram. Fluoxetine, fluvoxamine, and sertraline at traditional doses demonstrate a lack of clinically significant increases in QTc in the majority of studies. Further, paroxetine monotherapy shows a lack of clinically significant QTc prolongation in all studies. However, case reports or reporting tools still link these SSRIs with QTc prolongation. Fluoxetine, escitalopram, and sertraline used in post–acute coronary syndrome patients did not demonstrate risk of QTc prolongation. Conclusion: For clinicians who choose not to use citalopram due to recent Food and Drug Administration (FDA) recommendations, other antidepressants within this class may be considered. When citalopram is not utilized based on risk factors for TdP, use of escitalopram is not likely the safest alternative. Based on current literature, fluoxetine, fluvoxamine, and sertraline appear to have similar, low risk for QT prolongation, and paroxetine appears to have the lowest risk. However, there are significant limitations in interpreting the studies, including varying definitions of significant QT prolongation. Therefore, choice of an alternative SSRI should be based on individual risk factors for arrhythmias and other patient-specific factors.
Published:
2013-10
Title:
Comparison of immune and health markers in intact and neonatally castrated male pigs
Authors:
Merlot, E.; Thomas, F.; Prunier, A.
Abstract:
Stress and sex hormones are known to regulate immune function. Castration of male piglets is used to avoid boar taint in the meat, but its consequences on immunity and health of male pigs are poorly known. In this study, intact and neonatally surgically castrated male pigs (n=20 per group) were compared along puberty for some immune parameters and hormone receptor expression in lymphoid organs. Pigs were immunised with keyhole limpet haemocyanin (KLH) at 113 and 133 days of age. Blood lymphocyte numbers and proliferation, immunoglobulin titres, haptoglobin and hormone levels at 89, 119 and 152 days and the mRNA expression of androgen, alpha-oestrogen, glucocorticoid and beta2-adrenergic receptors in liver, spleen and thymus at 160 days were assessed. Blood lymphocyte numbers were lower (at 119 and 152 days) and total IgG and haptoglobin concentrations were higher (at 152 days) in castrated than intact males. The concanavalin A and KLH proliferation responses and anti-KLH IgG titres were not altered. At slaughter, intact pigs presented a heavier thymus and a lower hepatic expression of beta2-adrenergic receptor. In conclusion, the effects of neonatal castration were moderate. Other studies are needed to clarify the possible detrimental outcomes of castration on lymphocyte numbers and thymic growth.
Published:
2013-10
Title:
Effects of carbohydrate restriction and dietary cholesterol provided by eggs on clinical risk factors in metabolic syndrome
Authors:
Blesso, Christopher N.; Andersen, Catherine J.; Barona, Jacqueline; Volk, Brittanie; Volek, Jeff S.; Fernandez, Maria Luz
Abstract:
BACKGROUND: There are a limited number of clinical interventions evaluating the effects of dietary cholesterol in individuals at elevated risk for type 2 diabetes and cardiovascular disease. OBJECTIVE: To investigate the effects of whole egg intake in adults with metabolic syndrome (MetS). METHODS: Men (n = 12) and women (n = 25) with MetS were instructed to follow a moderate carbohydrate-restricted diet (<30% energy) and randomly assigned to consume either three whole eggs (EGG, n = 20) or egg substitute (SUB, n = 17)/d for 12 weeks. Dietary intake, MetS parameters, and body composition were assessed at baseline and post-intervention. RESULTS: Total carbohydrate (P < .001) intake decreased in all participants over time. The EGG group consumed more dietary cholesterol (P < .001) and choline (P < .001) than the SUB group. MetS was reduced in both groups, with improvements noted in dyslipidemia and decreases in waist circumference (P < .01), weight (P < .001), and percent body fat (P < .001). Reductions in plasma tumor necrosis factor-α (P < .001) and serum amyloid A (P
Published:
2013-10
Title:
Effects of sea buckthorn and bilberry on serum metabolites differ according to baseline metabolic profiles in overweight women: a randomized crossover trial
Authors:
Larmo, Petra S.; Kangas, Antti J.; Soininen, Pasi; Lehtonen, Henna-Maria; Suomela, Jukka-Pekka; Yang, Baoru; Viikari, Jorma; Ala-Korpela, Mika; Kallio, Heikki P.
Abstract:
Background: Berries are associated with health benefits. Little is known about the effect of baseline metabolome on the overall metabolic responses to berry intake. Objective: We studied the effects of berries on serum metabolome. Design: Eighty overweight women completed this randomized crossover study. During the interventions of 30 d, subjects consumed dried sea buckthorn berries (SBs), sea buckthorn oil (SBo), sea buckthorn phenolics ethanol extract mixed with maltodextrin (SBe+MD) (1:1), or frozen bilberries. Metabolic profiles were quantified from serum samples by using H nuclear magnetic resonance spectroscopy. Results: All interventions induced a significant (P < 0.001-0.003) effect on the overall metabolic profiles. The effect was observed both in participants who had a metabolic profile that rejected higher cardiometabolic risk at baseline (group B: P = 0.001-0.008) and in participants who had a lower-risk profile (group A: P
Published:
2013-10
Title:
Favourable metabolic effects of a eucaloric lower-carbohydrate diet in women with PCOS
Authors:
Gower, Barbara A.; Chandler-Laney, Paula C.; Ovalle, Fernando; Goree, Laura Lee; Azziz, Ricardo; Desmond, Renee A.; Granger, Wesley M.; Goss, Amy M.; Bates, G. Wright
Abstract:
Objective Diet-induced reduction in circulating insulin may be an attractive nonpharmacological treatment for women with polycystic ovary syndrome (PCOS) among whom elevated insulin may exacerbate symptoms by stimulating testosterone synthesis. This study was designed to determine whether a modest reduction in dietary carbohydrate (CHO) content affects β-cell responsiveness, serum testosterone concentration and insulin sensitivity in women with PCOS. Design In a crossover design, two diets (‘Standard,’ STD, 55:18:27% energy from carbohydrate/protein/fat; lower-carbohydrate, 41:19:40) were provided for 8 weeks in random order with a 4-week washout between. Patients Thirty women with PCOS. Measurements β-cell responsiveness assessed as the C-peptide response to glucose during a liquid meal test; insulin sensitivity from insulin and glucose values throughout the test; insulin resistance (HOMA-IR); and total testosterone by immunoassay. Results Paired t-test indicated that the lower-CHO diet induced significant decreases in basal β-cell response (PhiB), fasting insulin, fasting glucose, HOMA-IR, total testosterone and all cholesterol measures, and significant increases in insulin sensitivity and dynamic (‘first-phase’) β-cell response. The STD diet induced a decrease in HDL-C and an increase in the total cholesterol- to-HDL-C ratio. Across all data combined, the change in testosterone was positively associated with the changes in fasting insulin, PhiB and insulin AUC (P
Published:
2013-10
Title:
Food addiction: detox and abstinence reinterpreted?
Authors:
Shriner, Richard L.
Abstract:
The senior patient and/or the geriatrician are confronted with a confusing literature describing how patients interested in combating metabolic syndrome, diabesity (diabetes plus obesity) or simple obesity might best proceed. The present paper gives a brief outline of the basic disease processes that underlie metabolic pro-inflammation, including how one might go about devising the most potent and practical detoxification from such metabolic compromise. The role that dietary restriction plays in pro-inflammatory detoxification (detox), including how a modified fast (selective food abstinence) is incorporated into this process, is developed. The unique aspects of geriatric bariatric medicine are elucidated, including the concepts of sarcopenia and the obesity paradox. Important caveats involving the senior seeking weight loss are offered. By the end of the paper, the reader will have a greater appreciation for the challenges and opportunities that lie ahead for geriatric patients who wish to overcome food addiction and reverse pro-inflammatory states of ill-heath. This includes the toxic metabolic processes that create obesity complicated by type 2 diabetes mellitus (T2DM) which collectively we call diabesity. In that regard, diabesity is often the central pathology that leads to the evolution of the metabolic syndrome. The paper also affords the reader a solid review of the neurometabolic processes that effectuate anorexigenic versus orexigenic inputs to obesity that drive food addiction. We argue that these processes lead to either weight gain or weight loss by a tripartite system involving metabolic, addictive and relational levels of organismal functioning. Recalibrating the way we negotiate these three levels of daily functioning often determines success or failure in terms of overcoming metabolic syndrome and food addiction.
Published:
2013-10
Title:
Ketone esters increase brown fat in mice and overcome insulin resistance in other tissues in the rat
Authors:
Veech, Richard L.
Abstract:
Brown adipose tissue (BAT) is classically activated by sympathetic nervous stimulation resulting from exposure to cold. Feeding a high-fat diet also induces development of brown fat, but is decreased by caloric restriction. Blood ketone bodies, which function as alternative energy substrates to glucose, are increased during caloric restriction. Here we discuss the unexpected observation that feeding an ester of ketone bodies to the mouse, which increases blood ketone body concentrations, results in an activation of brown fat. The mechanism of this activation of brown fat is similar to that occurring from cold exposure in that cyclic adenosine monophosphate (AMP) levels are increased as are levels of the transcription factor cyclic AMP-responsive element-binding protein, which is also increased by ketone ester feeding. Other effects of feeding ketone esters, in addition to their ability to induce brown fat, are discussed such as their ability to overcome certain aspects of insulin resistance and to ameliorate the accumulation of amyloid and phosphorylated tau protein in brain, and improve cognitive function, in a triple transgenic mouse model of Alzheimer's disease.
Published:
2013-10
Title:
Marine n-3 fatty acids in adipose tissue and development of atrial fibrillation: a Danish cohort study
Authors:
Rix, Thomas Andersen; Joensen, Albert Marni; Riahi, Sam; Lundbye-Christensen, Søren; Overvad, Kim; Schmidt, Erik Berg
Abstract:
OBJECTIVE: Consumption of fish and marine n-3 polyunsaturated fatty acids (PUFA) may be associated with a lower risk of atrial fibrillation (AF), but results have been inconsistent. The aim was to investigate this further by measurements of marine n-3 PUFA in adipose tissue. DESIGN: Cohort study. SETTING: A total of 57 053 Danish participants 50-64 years of age were enrolled into the Diet, Cancer and Health Cohort Study. PATIENTS: A randomly drawn subcohort of 3440 participants with available data from baseline adipose tissue biopsies. INTERVENTIONS: Exposure was the adipose tissue content of marine n-3 PUFA, which reflects the endogenous exposure and is also an objective marker of the long-term dietary intake. MAIN OUTCOME MEASURES: Incident AF during follow-up. RESULTS: 179 cases of AF occurred over 13.6 years. Multivariate, sex-stratified Cox proportional hazards regression analyses using cubic splines showed a monotonic, negative, dose-response trend, but not statistically significant association, between total marine n-3 PUFA in adipose tissue and incident AF. A similar trend towards a lower risk of AF was seen in the second (HR 0.87, 95% CI 0.60 to 1.24) and third tertiles (HR 0.77, 95% CI 0.53 to 1.10) of marine n-3 PUFA compared with the lowest tertile. Similar trends, but also not statistically significant, were found separately for eicosapentaenoic, docosahexaenoic and docosapentaenoic acids. CONCLUSIONS: There was no statistically significant association between the content of marine n-3 PUFA in adipose tissue and the development of AF; however, data showed a monotonic, negative dose-response trend suggestive of a negative association.
Published:
2013-10
Title:
Markers for nutrition studies: review of criteria for the evaluation of markers
Authors:
de Vries, Jan; Antoine, Jean-Michel; Burzykowski, Tomasz; Chiodini, Alessandro; Gibney, Mike; Kuhnle, Gunter; Méheust, Agnès; Pijls, Loek; Rowland, Ian
Abstract:
INTRODUCTION: Markers are important tools to assess the nutrition status and effects of nutrition interventions. There is currently insufficient consensus in nutrition sciences on how to evaluate markers, despite the need for properly evaluating them. OBJECTIVES: To identify the criteria for the evaluation of markers related to nutrition, health and disease and to propose generic criteria for evaluation. METHOD: The report on "Evaluation of Biomarker and Surrogate Endpoints in Chronic Disease" from the Institute of Medicine was the starting point for the literature search. Additionally, specific search strategies were developed for Pubmed. RESULTS: In nutrition, no set of criteria or systematic approach to evaluate markers is currently available. There is a reliance on the medical area where statistical methods have been developed to quantify the evaluation of markers. Even here, a systematic approach is lacking-markers are still evaluated on a case-by-case basis. The review of publications from the literature search resulted in a database with definitions, criteria for validity and the rationale behind the criteria. It was recognized that, in nutrition, a number of methodological aspects differ from medical research. CONCLUSIONS: The following criteria were identified as essential elements in the evaluation of markers: (1) the marker has a causal biological link with the endpoint, (2) there is a significant association between marker and endpoint in the target population, (3) marker changes consistently with the endpoint, e.g., in response to an intervention, and (4) change in the marker explains a substantial proportion of the change in the endpoint in response to the intervention.
Published:
2013-10
Title:
Meat intake and cause-specific mortality: a pooled analysis of Asian prospective cohort studies
Authors:
Lee, Jung Eun; McLerran, Dale F.; Rolland, Betsy; Chen, Yu; Grant, Eric J.; Vedanthan, Rajesh; Inoue, Manami; Tsugane, Shoichiro; Gao, Yu-Tang; Tsuji, Ichiro; Kakizaki, Masako; Ahsan, Habibul; Ahn, Yoon-Ok; Pan, Wen-Harn; Ozasa, Kotaro; Yoo, Keun-Young; Sasazuki, Shizuka; Yang, Gong; Watanabe, Takashi; Sugawara, Yumi; Parvez, Faruque; Kim, Dong-Hyun; Chuang, Shao-Yuan; Ohishi, Waka; Park, Sue K.; Feng, Ziding; Thornquist, Mark; Boffetta, Paolo; Zheng, Wei; Kang, Daehee; Potter, John; Sinha, Rashmi
Abstract:
BACKGROUND: Total or red meat intake has been shown to be associated with a higher risk of mortality in Western populations, but little is known of the risks in Asian populations. OBJECTIVE: We examined temporal trends in meat consumption and associations between meat intake and all-cause and cause-specific mortality in Asia. DESIGN: We used ecological data from the United Nations to compare country-specific meat consumption. Separately, 8 Asian prospective cohort studies in Bangladesh, China, Japan, Korea, and Taiwan consisting of 112,310 men and 184,411 women were followed for 6.6 to 15.6 y with 24,283 all-cause, 9558 cancer, and 6373 cardiovascular disease (CVD) deaths. We estimated the study-specific HRs and 95% CIs by using a Cox regression model and pooled them by using a random-effects model. RESULTS: Red meat consumption was substantially lower in the Asian countries than in the United States. Fish and seafood consumption was higher in Japan and Korea than in the United States. Our pooled analysis found no association between intake of total meat (red meat, poultry, and fish/seafood) and risks of all-cause, CVD, or cancer mortality among men and women; HRs (95% CIs) for all-cause mortality from a comparison of the highest with the lowest quartile were 1.02 (0.91, 1.15) in men and 0.93 (0.86, 1.01) in women. CONCLUSIONS: Ecological data indicate an increase in meat intake in Asian countries; however, our pooled analysis did not provide evidence of a higher risk of mortality for total meat intake and provided evidence of an inverse association with red meat, poultry, and fish/seafood. Red meat intake was inversely associated with CVD mortality in men and with cancer mortality in women in Asian countries.
Published:
2013-10
Title:
Meldonium decreases the diet-increased plasma levels of trimethylamine N-oxide, a metabolite associated with atherosclerosis
Authors:
Dambrova, Maija; Skapare-Makarova, Elina; Konrade, Ilze; Pugovics, Osvalds; Grinberga, Solveiga; Tirzite, Dace; Petrovska, Ramona; Kalvins, Ivars; Liepins, Edgars
Abstract:
Published:
2013-10
Title:
Plasma triglyceride/HDL-cholesterol ratio, insulin resistance, and cardiometabolic risk in young adults
Authors:
MurguÃa-Romero, Miguel; Jiménez-Flores, J. Rafael; Sigrist-Flores, Santiago C.; Espinoza-Camacho, Miguel A.; Jiménez-Morales, Mayra; Piña, Enrique; Méndez-Cruz, A. René; Villalobos-Molina, Rafael; Reaven, Gerald M.
Abstract:
Studies in mature adults suggest that the plasma concentration ratio of triglyceride (TG)/HDL-cholesterol (HDL-C) provides a simple way to identify apparently healthy individuals who are insulin resistant (IR) and at increased cardiometabolic risk. This study extends these observations by examining the clinical utility of the TG/HDL-C ratio and the metabolic syndrome (MetS) in 2,244 healthy college students (17-24 years old) of Mexican Mestizo ancestry. The TG/HDL-C ratio separating the 25% with the highest value was used to identify IR and increased cardiometabolic risk. Cardiometabolic risk factors were more adverse in men and women whose TG/HDL-C ratios exceeded 3.5 and 2.5, respectively, and approximately one third were identified as being IR. The MetS identified fewer individuals as being IR, but their risk profile was accentuated. In conclusion, both a higher TG/HDL-C ratio and a diagnosis of the MetS identify young IR individuals with an increased cardiometabolic risk profile. The TG/HDL-C ratio identified a somewhat greater number of "high risk" subjects, whereas the MetS found a group whose risk profile was somewhat magnified. These findings suggest that the TG/HDL-C ratio may serve as a simple and clinically useful approach to identify apparently healthy, young individuals who are IR and at increased cardiometabolic risk.
Published:
2013-10
Title:
Short-term calorie and protein restriction provide partial protection from chemotoxicity but do not delay glioma progression
Authors:
Brandhorst, Sebastian; Wei, Min; Hwang, Saewon; Morgan, Todd E.; Longo, Valter D.
Abstract:
Short-term starvation (STS) protects normal cells while simultaneously sensitizing malignant cells to high-dose chemotherapeutic drugs in mice and possibly patients. The fasting-dependent protection of normal cells and sensitization of malignant cells depends, in part, on reduced levels of insulin-like growth factor-1 (IGF-1) and glucose. Calorie restricted diets with defined macronutrient (carbohydrate, protein, fat) ratios were evaluated for the effects on stress sensitization markers and protection in mice treated with high-dose chemotherapy. We show that short-term CR significantly reduced both glucose and IGF-1 levels, but when specific macronutrient deficiencies were tested, only the complete lack of proteins reduced IGF-1 levels. Short-term 50% CR combined with either severe protein-deficiency or ketogenic diets improved chemotoxicity resistance similarly to the standard 50% CR, but did not result in the high protection caused by STS. Notably, a high protein diet reversed the beneficial effects of short-term CR. In a subcutaneous mouse model of glioma, feeding a low protein (4% calories from protein) diet for more than 20 days did not delay tumor progression once the tumor became palpable. Also, cycles of short-term (3 days) 50% CR did not augment the chemotherapy efficacy of cisplatin in a murine breast cancer model. These results indicate that the protection from chemotoxicity and retardation of the progression of certain tumors achieved with fasting is not obtained with shortterm calorie and/or macronutrient restriction.
Published:
2013-10
Title:
Sugar, uric acid, and the etiology of diabetes and obesity
Authors:
Johnson, Richard J.; Nakagawa, Takahiko; Sanchez-Lozada, L. Gabriela; Shafiu, Mohamed; Sundaram, Shikha; Le, Myphuong; Ishimoto, Takuji; Sautin, Yuri Y.; Lanaspa, Miguel A.
Abstract:
The intake of added sugars, such as from table sugar (sucrose) and high-fructose corn syrup has increased dramatically in the last hundred years and correlates closely with the rise in obesity, metabolic syndrome, and diabetes. Fructose is a major component of added sugars and is distinct from other sugars in its ability to cause intracellular ATP depletion, nucleotide turnover, and the generation of uric acid. In this article, we revisit the hypothesis that it is this unique aspect of fructose metabolism that accounts for why fructose intake increases the risk for metabolic syndrome. Recent studies show that fructose-induced uric acid generation causes mitochondrial oxidative stress that stimulates fat accumulation independent of excessive caloric intake. These studies challenge the long-standing dogma that "a calorie is just a calorie" and suggest that the metabolic effects of food may matter as much as its energy content. The discovery that fructose-mediated generation of uric acid may have a causal role in diabetes and obesity provides new insights into pathogenesis and therapies for this important disease.
Published:
2013-10
Title:
Tumor necrosis factor alpha increases aerobic glycolysis and reduces oxidative metabolism in prostate epithelial cells
Authors:
Vaughan, Roger A.; Garcia-Smith, Randi; Trujillo, Kristina A.; Bisoffi, Marco
Abstract:
BACKGROUND: Chronic inflammation promotes prostate cancer formation and progression. Furthermore, alterations in energy metabolism are a hallmark of prostate cancer cells. However, the actions of inflammatory factors on the energy metabolism of prostate epithelial cells have not been previously investigated. This is the first study to report on the effect of the inflammatory cytokine tumor necrosis factor alpha (TNFα) on the glycolytic and oxidative metabolism, and the mitochondrial function of widely used prostate epithelial cells. METHODS: Pre-malignant RWPE-1 and cancerous LNCaP and PC-3 cells were treated with low-dose TNFα. Glycolytic and oxidative metabolism was quantified by measuring extracellular acidification and oxygen consumption rates, respectively. ATP content and lactate export were measured by luminescence and fluorescence, respectively. Mitochondrial content and the expression of glucose transporter 1 (GLUT1), peroxisome proliferator-activated receptor co-activator 1 alpha (PGC-1α), and Cytochrome C were measured by flow cytometry. RESULTS: Our data suggest that TNFα increases glycolysis, ATP production, and lactate export, while it reduces oxidative metabolism and mitochondrial function in prostate epithelial cells. The highly aggressive PC-3 cells tend to be less responsive to the actions of TNFα than the pre-malignant RWPE-1 and the non-aggressive LNCaP cells. CONCLUSIONS: Cellular energetics, that is, glycolytic and oxidative metabolism is significantly influenced by low-level inflammation in prostate epithelial cells. In widely used prostate epithelial cell models, the micro-environmental inflammatory cytokine TNFα induces aerobic glycolysis while inhibiting oxidative metabolism. This supports the hypothesis that low-level inflammation can induce Warburg metabolism in prostate epithelial cells, which may promote cancer formation and progression.
Published:
2013-10
Title:
Variation of serum metabolites related to habitual diet: a targeted metabolomic approach in EPIC-Potsdam
Authors:
Floegel, A; von Ruesten, A; Drogan, D; Schulze, M B; Prehn, C; Adamski, J; Pischon, T; Boeing, H
Abstract:
Background/objective: Serum metabolites have been linked to higher risk of chronic diseases but determinants of serum metabolites are not clear. We aimed to investigate the association between habitual diet as a modifiable risk factor and relevant serum metabolites.Subjects/methods: This cross-sectional study comprised 2380 EPIC-Potsdam participants. Intake of 45 food groups was assessed by food frequency questionnaire and concentrations of 127 serum metabolites were measured by targeted metabolomics. Reduced rank regression was used to find dietary patterns that explain the maximum variation of metabolites.Results: In the multivariable-adjusted model, the proportion of explained variation by habitual diet was ranked as follows: acyl-alkyl-phosphatidylcholines (5.7%), sphingomyelins (5.1%), diacyl-phosphatidylcholines (4.4%), lyso-phosphatidylcholines (4.1%), acylcarnitines (3.5%), amino acids (2.2%) and hexose (1.6%). A pattern with high intake of butter and low intake of margarine was related to acylcarnitines, acyl-alkyl-phosphatidylcholines, lyso-phosphatidylcholines and hydroxy-sphingomyelins, particularly with saturated and monounsaturated fatty acid side chains. A pattern with high intake of red meat and fish and low intake of whole-grain bread and tea was related to hexose and phosphatidylcholines. A pattern consisting of high intake of potatoes, dairy products and cornflakes particularly explained methionine and branched chain amino acids. Dietary patterns related to type 2 diabetes-relevant metabolites included high intake of red meat and low intake of whole-grain bread, tea, coffee, cake and cookies, canned fruits and fish.Conclusions: Dietary patterns characterized by intakes of red meat, whole-grain bread, tea and coffee were linked to relevant metabolites and could be potential targets for chronic disease prevention.
Published:
2013-10
Title:
A Trial of Prazosin for Combat Trauma PTSD With Nightmares in Active-Duty Soldiers Returned From Iraq and Afghanistan
Authors:
Raskind, Murray A.; Peterson, Kris; Williams, Tammy; Hoff, David J.; Hart, Kimberly; Holmes, Hollie; Homas, Dallas; Hill, Jeffrey; Daniels, Colin; Calohan, Jess; Millard, Steven P.; Rohde, Kirsten; O’Connell, James; Pritzl, Denise; Feiszli, Kevin; Petrie, Eric C.; Gross, Christopher; Mayer, Cynthia L.; Freed, Michael C.; Engel, Charles; Peskind, Elaine R.
Abstract:
Published:
2013-09
Title:
Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis
Authors:
Leucht, Stefan; Cipriani, Andrea; Spineli, Loukia; Mavridis, Dimitris; Örey, Deniz; Richter, Franziska; Samara, Myrto; Barbui, Corrado; Engel, Rolf R; Geddes, John R; Kissling, Werner; Stapf, Marko Paul; Lässig, Bettina; Salanti, Georgia; Davis, John M
Abstract:
Background The question of which antipsychotic drug should be preferred for the treatment of schizophrenia is controversial, and conventional pairwise meta-analyses cannot provide a hierarchy based on the randomised evidence. We aimed to integrate the available evidence to create hierarchies of the comparative efficacy, risk of all-cause discontinuation, and major side-effects of antipsychotic drugs.
Published:
2013-09
Title:
Identification of biomarkers for intake of protein from meat, dairy products and grains: a controlled dietary intervention study
Authors:
Altorf-van der Kuil, Wieke; Brink, Elizabeth J.; Boetje, Martine; Siebelink, Els; Bijlsma, Sabina; Engberink, Marielle F.; van 't Veer, Pieter; Tome, Daniel; Bakker, Stephan J. L.; van Baak, Marleen A.; Geleijnse, Johanna M.
Abstract:
In the present controlled, randomised, multiple cross-over dietary intervention study, we aimed to identify potential biomarkers for dietary protein from dairy products, meat and grain, which could be useful to estimate intake of these protein types in epidemiological studies. After 9 d run-in, thirty men and seventeen women (22 (SD 4) years) received three high-protein diets (aimed at approximately 18% of energy (en%)) in random order for 1 week each, with approximately 14 en% originating from either meat, dairy products or grain. We used a two-step approach to identify biomarkers in urine and plasma. With principal component discriminant analysis, we identified amino acids (AA) from the plasma or urinary AA profile that were distinctive between diets. Subsequently, after pooling total study data, we applied mixed models to estimate the predictive value of those AA for intake of protein types. A very good prediction could be made for the intake of meat protein by a regression model that included urinary carnosine, 1-methylhistidine and 3-methylhistidine (98% of variation in intake explained). Furthermore, for dietary grain protein, a model that included seven AA (plasma lysine, valine, threonine, alpha-aminobutyric acid, proline, ornithine and arginine) made a good prediction (75% of variation explained). We could not identify biomarkers for dairy protein intake. In conclusion, specific combinations of urinary and plasma AA may be potentially useful biomarkers for meat and grain protein intake, respectively. These findings need to be cross-validated in other dietary intervention studies.
Published:
2013-09
Title:
Ingestion of thermally oxidized sunflower oil decreases postprandial lipemia mainly in younger individuals
Authors:
Manning, Patrick J.; Sutherland, Wayne H. F.; Manning, Anna E.; de Jong, Sylvia A.; Berry, Elizabeth A.
Abstract:
Animal studies have shown that diets rich in thermally oxidized fat increase glucose and decrease insulin and triglyceride (TG) concentrations in the blood. We hypothesized that ingestion of a potato meal rich in thermally oxidized sunflower oil (TOSO) would decrease postprandial concentrations of insulin, incretins, and TG and increase plasma glucose concentrations. Twenty healthy subjects aged 22 to 70 years consumed meals rich in TOSO or unheated sunflower oil and containing paracetamol (1.5 g) in a randomized, crossover trial. Blood samples were taken at baseline and 10, 20, 30, 60, 90, and 120 minutes after the meals and glucose, insulin, TG, nonesterified fatty acids, glucagon-like polypeptide-1, glucose-independent polypeptide, and paracetamol (as a marker of gastric emptying) were measured in plasma or serum. The incremental areas under the curve of glucose, insulin, nonesterified fatty acid, incretins, and paracetamol levels were not significantly different between the meals. Plasma TG incremental area under the curve was 44% lower after the TOSO meal at a marginal level of significance (P = .06) in the total study population and was significantly (P = .04) and 61% lower in those of median age and younger (n = 11). These data suggest that ingestion of TOSO may acutely decrease plasma TG mainly in younger individuals and does not acutely affect glucose and insulin metabolism or gastric emptying in healthy subjects.
Published:
2013-09
Title:
Molecular Analysis and Differentiation Capacity of Adipose-Derived Stem Cells from Lymphedema Tissue
Authors:
Levi, Benjamin; Glotzbach, Jason P.; Sorkin, Michael; Hyun, Jeong; Januszyk, Michael; Wan, Derrick C.; Li, Shuli; Nelson, Emily R.; Longaker, M.D. Michael T.; Gurtner, Geoffrey C.
Abstract:
Background Many breast cancer patients are plagued by the disabling complication of upper limb lymphedema after axillary surgery. Conservative treatments using massage and compression therapy do not offer a lasting relief, as they fail to address the chronic transformation of edema into excess adipose tissue. Liposuction to address the adipose nature of the lymphedema has provided an opportunity for a detailed analysis of the stromal fraction of lymphedema-associated fat to clarify the molecular mechanisms for this adipogenic transformation. Methods Adipose-derived stem cells were harvested from human lipoaspirate of the upper extremity from age-matched patients with lymphedema (n = 3) or subcutaneous adipose tissue from control patients undergoing cosmetic procedures (n = 3). Immediately after harvest, adipose-derived stem cells were analyzed using single-cell transcriptional profiling techniques. Osteogenic, adipogenic, and vasculogenic gene expression and differentiation were assessed by quantitative real-time polymerase chain reaction and standard in vitro differentiation assays. Results Differential transcriptional clusters of adipose-derived stem cells were found between lymphedema and subcutaneous fat. Interestingly, lymphedema-associated stem cells had a much higher adipogenic gene expression and enhanced ability to undergo adipogenic differentiation. Conversely, they had lower vasculogenic gene expression and diminished capability to form tubules in vitro, whereas the osteogenic differentiation capacity was not significantly altered. Conclusions Adipose-derived stem cells from extremities affected by lymphedema appear to exhibit transcriptional profiles similar to those of abdominal adipose-derived stem cells; however, their adipogenic differentiation potential is strongly increased and their vasculogenic capacity is compromised. These results suggest that the underlying pathophysiology of lymphedema drives adipose-derived stem cells toward adipogenic differentiation.
Published:
2013-09
Title:
The "vegetarian brain": chatting with monkeys and pigs?
Authors:
Filippi, Massimo; Riccitelli, Gianna; Meani, Alessandro; Falini, Andrea; Comi, Giancarlo; Rocca, Maria A.
Abstract:
An array of brain regions in the fronto-parietal and temporal lobes cooperates to process observation and execution of actions performed by other individuals. Using functional MRI, we hypothesized that vegetarians and vegans might show brain responses to mouth actions performed by humans, monkeys, and pigs different from omnivores. We scanned 20 omnivores, 19 vegetarians, and 21 vegans while watching a series of silent videos, which presented a single mouth action performed by a human, a monkey, and a pig. Compared to omnivores, vegetarians and vegans have increased functional connectivity between regions of the fronto-parietal and temporal lobes versus the cerebellum during observation of mouth actions performed by humans and, to the same degree, animals. Vegans also had increased connectivity with the supplementary motor area. During human mouth actions, increased amygdala activity in vegetarians and vegans was found. More critically, vegetarians recruited the right middle frontal gyrus and insula, which are involved in social mirroring, whereas vegans activated the left inferior frontal gyrus and middle temporal gyrus, which are part of the mirror neuron system. Monkey mouth actions triggered language network activity in both groups, which might be due to the attempt to decode monkey mouth gesture, with an additional recruitment of associative temporo-occipital areas in vegans, whereas pig mouth actions activated empathy-related regions, including the anterior cingulum. These results support the role of the action observation-execution matching system in social cognition, which enables us to interact not only with our conspecifics but also with species in phylogenetic proximity to humans.
Published:
2013-09
Title:
An update on diets in clinical practice
Authors:
Zupec-Kania, Beth; Neal, Elizabeth; Schultz, Rebecca; Roan, Marian E.; Turner, Zahava; Welborn, Michelle
Abstract:
Ketogenic diet therapies involve a collaborative healthcare team and therefore are typically offered in tertiary care centers. Centers that utilize these therapies with frequency gain valuable experience and become skilled in their practice. This chapter is a summary from the presentations of 5 practitioners including a nurse, pharmacist, and 3 dietitians who shared their expertise during the clinical session of the 2012 International Symposium.
Published:
2013-08
Title:
Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets
Authors:
Paoli, A.; Rubini, A.; Volek, J. S.; Grimaldi, K. A.
Abstract:
Very-low-carbohydrate diets or ketogenic diets have been in use since the 1920s as a therapy for epilepsy and can, in some cases, completely remove the need for medication. From the 1960s onwards they have become widely known as one of the most common methods for obesity treatment. Recent work over the last decade or so has provided evidence of the therapeutic potential of ketogenic diets in many pathological conditions, such as diabetes, polycystic ovary syndrome, acne, neurological diseases, cancer and the amelioration of respiratory and cardiovascular disease risk factors. The possibility that modifying food intake can be useful for reducing or eliminating pharmaceutical methods of treatment, which are often lifelong with significant side effects, calls for serious investigation. This review revisits the meaning of physiological ketosis in the light of this evidence and considers possible mechanisms for the therapeutic actions of the ketogenic diet on different diseases. The present review also questions whether there are still some preconceived ideas about ketogenic diets, which may be presenting unnecessary barriers to their use as therapeutic tools in the physician's hand.
Published:
2013-08
bottom of page