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Title:
Is the restricted ketogenic diet a viable alternative to the standard of care for managing malignant brain cancer?
Authors:
Seyfried, Thomas N.; Marsh, Jeremy; Shelton, Laura M.; Huysentruyt, Leanne C.; Mukherjee, Purna
Abstract:
Malignant brain cancer persists as a major disease of morbidity and mortality. The failure to recognize brain cancer as a disease of energy metabolism has contributed in large part to the failure in management. As long as brain tumor cells have access to glucose and glutamine, the disease will progress. The current standard of care provides brain tumors with access to glucose and glutamine. The high fat low carbohydrate ketogenic diet (KD) will target glucose availability and possibly that of glutamine when administered in carefully restricted amounts to reduce total caloric intake and circulating levels of glucose. The restricted KD (RKD) targets major signaling pathways associated with glucose and glutamine metabolism including the IGF-1/PI3K/Akt/Hif pathway. The RKD is anti-angiogenic, anti-invasive, anti-inflammatory, and pro-apoptotic when evaluated in mice with malignant brain cancer. The therapeutic efficacy of the restricted KD can be enhanced when combined with drugs that also target glucose and glutamine. Therapeutic efficacy of the RKD was also seen against malignant gliomas in human case reports. Hence, the RKD can be an effective non-toxic therapeutic option to the current standard of care for inhibiting the growth and invasive properties of malignant brain cancer.
Published:
2012-07
Title:
Long-term monitoring of the ketogenic diet: Do's and Don'ts. [Review]
Authors:
Bergqvist, A. G. Christina
Abstract:
The ketogenic diet (KD) is an effective treatment for epilepsy and like other treatments it is not without side effects. The side effects encountered are related to the diet composition and the radical metabolic changes that results from a high fat, low carbohydrate and protein diet. Short-term side effects are well documented. Long-term side effects are not as well documented but since the last "international symposium on dietary therapies for epilepsy and other neurological disorders", there are now more prospective and longitudinal data. Monitoring practices and treatments will be discussed and compared to the International Ketogenic Diet Consensus Statement (IKDCS) from 2008. Copyright © 2011 Elsevier B.V. All rights reserved.
Published:
2012-07
Title:
Low-carbohydrate ketogenic diets, glucose homeostasis, and nonalcoholic fatty liver disease
Authors:
Schugar, Rebecca C.; Crawford, Peter A.
Abstract:
PURPOSE OF REVIEW: Obesity-associated nonalcoholic fatty liver disease (NAFLD) is highly prevalent, for which weight loss is the generally recommended clinical management. Low-carbohydrate ketogenic diets have been successful in promoting weight loss, but variations in the range of metabolic responses to these diets indicate that the effects of altering macronutrient content are not completely understood. This review focuses on the most recent findings that reveal the relationship between low-carbohydrate diets and NAFLD in rodent models and humans. RECENT FINDINGS: Low-carbohydrate diets have been shown to promote weight loss, decrease intrahepatic triglyceride content, and improve metabolic parameters of patients with obesity. These ketogenic diets also provoke weight loss in rodents. However, long-term maintenance on a ketogenic diet stimulates the development of NAFLD and systemic glucose intolerance in mice. The relationship between ketogenic diets and systemic insulin resistance in both humans and rodents remains to be elucidated. SUMMARY: Because low-carbohydrate ketogenic diets are increasingly employed for treatment of obesity, NAFLD, and neurological diseases such as epilepsy, understanding the long-term systemic effects of low-carbohydrate diets is crucial to the development of efficacious and safe dietary interventions.
Published:
2012-07
Title:
Modulation of oxidative stress and mitochondrial function by the ketogenic diet
Authors:
Milder, Julie; Patel, Manisha
Abstract:
The ketogenic diet (KD) is a high-fat, low carbohydrate diet that is used as a therapy for intractable epilepsy. However, the mechanism(s) by which the KD achieves neuroprotection and/or seizure control are not yet known. The broad efficacy of the KD in diverse epilepsies coupled with its profound influence on metabolism suggests that mitochondrial functions may be critical in its mechanism(s) of seizure control. Mitochondria subserve important cellular functions that include the production of cellular ATP, control of apoptosis, maintenance of calcium homeostasis and the production and elimination of reactive oxygen species (ROS). This review will focus on recent literature reporting the regulation of mitochondrial functions and redox signaling by the KD. The review highlights a potential mechanism of the KD involving the production of low levels of redox signaling molecules such as H(2)O(2) and electrophiles e.g. 4-hydroxynonenal (4-HNE), which in turn activate adaptive pathways such as the protective transcription factor, NF E2-related factor 2 (Nrf2). This can ultimately result in increased production of antioxidants (e.g. GSH) and detoxification enzymes which may be critical in mediating the protective effects of the KD.
Published:
2012-07
Title:
Neuroprotection in metabolism-based therapy
Authors:
Hartman, Adam L.
Abstract:
Metabolism-based therapy has been used successfully in the treatment of seizures but study of its use in other neurodegenerative disorders is growing. Data demonstrating the use of different forms of metabolism-based therapy in human trials of Alzheimer disease and Parkinson disease are discussed. Animal and in vitro studies have shed light on metabolism-based therapy's mechanisms in these diseases, as well as ALS, aging, ischemia, trauma and mitochondrial cytopathies. Additional insights may be obtained by considering the role of metabolism-based therapy in cell disability and death (specifically apoptosis, excitotoxicity, and autophagy).
Published:
2012-07
Title:
Plasma inflammatory and vascular homeostasis biomarkers increase during human pregnancy but are not affected by oily fish intake
Authors:
García-Rodríguez, Cruz E.; Olza, Josune; Aguilera, Concepción M.; Mesa, María D.; Miles, Elizabeth A.; Noakes, Paul S.; Vlachava, Maria; Kremmyda, Lefkothea-Stella; Diaper, Norma D.; Godfrey, Keith M.; Calder, Philip C.; Gil, Angel
Abstract:
The Salmon in Pregnancy Study investigated whether the increased consumption of (n-3) long-chain PUFA (LC-PUFA) from farmed Atlantic salmon affects immune function during pregnancy and atopic disease in neonates compared with a habitual diet low in oily fish. In this context, because the ingestion of (n-3) LC-PUFA may lower the concentrations of inflammatory biomarkers, we investigated whether the consumption of oily fish affects the levels of inflammatory cytokines and vascular adhesion factors during pregnancy. Pregnant women (n = 123) were randomly assigned to continue their habitual diet (control group, n = 61), which was low in oily fish, or to consume two 150-g salmon portions/wk (salmon group, n = 62; providing 3.45 g EPA plus DHA) from 20 wk of gestation until delivery. Plasma inflammatory cytokines and vascular adhesion factors were measured in maternal plasma samples. Inflammatory biomarkers, including IL-8, hepatocyte growth factor, and monocyte chemotactic protein, increased over the course of pregnancy (P < 0.001), whereas plasma matrix metalloproteinase 9, IL-6, TNFα, and nerve growth factor concentrations were not affected. Vascular homeostasis biomarkers soluble E-selectin, soluble vascular adhesion molecule-1, soluble intercellular adhesion molecule (sICAM)-1, and total plasminogen activator inhibitor-1 increased as pregnancy progressed (P
Published:
2012-07
Title:
Soy Food Intake and Circulating Levels of Inflammatory Markers in Chinese Women
Authors:
Wu, Sheng Hui; Shu, Xiao Ou; Chow, Wong-Ho; Xiang, Yong-Bing; Zhang, Xianglan; Li, Hong-Lan; Cai, Qiuyin; Ji, Bu-Tian; Cai, Hui; Rothman, Nathaniel; Gao, Yu-Tang; Zheng, Wei; Yang, Gong
Abstract:
Soy and some of its constituents, such as isoflavones, have been shown to affect the inflammatory process in animal studies. The association between soy food intake and inflammatory markers has not been evaluated adequately in humans. Our aim was to evaluate whether higher intake of soy foods was inversely associated with inflammatory markers in 1,005 middle-aged Chinese women. In this cross-sectional study, dietary intake of soy foods was assessed by a validated food frequency questionnaire and by a 24-hour recall when biospecimens were procured. A general linear model was used to estimate the geometric means of selected inflammatory markers, including interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNFα), soluble IL-6 receptor, soluble GP130, soluble TNF receptors 1 and 2, and C-reactive protein, across categories of soy food intake after adjusting for age, lifestyle and dietary factors, and history of infectious or inflammation-related diseases. We found that multivariable-adjusted geometric mean concentrations of IL-6 and TNFα were inversely associated with quintiles of soy food intake, with a difference between the highest and lowest quintiles of 25.5% for IL-6 (P for trend=0.008) and 14% for TNFα (P for trend=0.04). Similar inverse associations were found for TNFα (P for trend=0.003), soluble TNF receptor 1 (P for trend=0.01), soluble TNF receptor 2 (P for trend=0.02), IL-1β (P for trend=0.05), and IL-6 (P for trend=0.04) when soy food consumption was assessed by the frequency of consumption in the preceding 24 hours. No significant associations were found for other markers studied. This study suggests that soy food consumption is related to lower circulating levels of IL-6, TNFα, and soluble TNF receptors 1 and 2 in Chinese women.
Published:
2012-07
Title:
Soy food intake after diagnosis of breast cancer and survival: an in-depth analysis of combined evidence from cohort studies of US and Chinese women
Authors:
Nechuta, Sarah J.; Caan, Bette J.; Chen, Wendy Y.; Lu, Wei; Chen, Zhi; Kwan, Marilyn L.; Flatt, Shirley W.; Zheng, Ying; Zheng, Wei; Pierce, John P.; Shu, Xiao Ou
Abstract:
BACKGROUND: Soy isoflavones have antiestrogenic and anticancer properties but also possess estrogen-like properties, which has raised concern about soy food consumption among breast cancer survivors. OBJECTIVE: We prospectively evaluated the association between postdiagnosis soy food consumption and breast cancer outcomes among US and Chinese women by using data from the After Breast Cancer Pooling Project. DESIGN: The analysis included 9514 breast cancer survivors with a diagnosis of invasive breast cancer between 1991 and 2006 from 2 US cohorts and 1 Chinese cohort. Soy isoflavone intake (mg/d) was measured with validated food-frequency questionnaires. HRs and 95% CIs were estimated by using delayed-entry Cox regression models, adjusted for sociodemographic, clinical, and lifestyle factors. RESULTS: After a mean follow-up of 7.4 y, we identified 1171 total deaths (881 from breast cancer) and 1348 recurrences. Despite large differences in soy isoflavone intake by country, isoflavone consumption was inversely associated with recurrence among both US and Chinese women, regardless of whether data were analyzed separately by country or combined. No heterogeneity was observed. In the pooled analysis, consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of all-cause (HR: 0.87; 95% CI: 0.70, 1.10) and breast cancer-specific (HR: 0.83; 95% CI: 0.64, 1.07) mortality and a statistically significant reduced risk of recurrence (HR: 0.75; 95% CI: 0.61, 0.92). CONCLUSION: In this large study of combined data on US and Chinese women, postdiagnosis soy food consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of breast cancer-specific mortality and a statistically significant reduced risk of recurrence.
Published:
2012-07
Title:
The ketogenic diet: what has science taught us?
Authors:
Rho, Jong M.; Stafstrom, Carl E.
Abstract:
Despite intense and growing interest in studying the mechanisms of ketogenic diet (KD) action, and recently published studies implicating novel molecular interactions with metabolic substrates, there nevertheless remains the pragmatic and scientific challenge of sustaining continued research in this field. This is in part a consequence of limited research funding and perhaps skepticism regarding the ultimate need to understand underlying mechanisms, particularly when clinical studies have increasingly validated the efficacy of the KD and its variants. After a decade and a half of more concerted laboratory efforts to understand KD mechanisms, it would be prudent to ask - what has all this scientific research really taught us? In this regard, it is instructive to compare and contrast laboratory research in dietary approaches for epilepsy with that traditionally used to screen for potential antiepileptic drugs (AEDs). In this review, lessons learned from AED development are applied to the more recent experimental findings and approaches attempting to link metabolic changes induced by the KD to neuronal and network excitability in the brain.
Published:
2012-07
Title:
Brain-Derived Neurotrophic Factor Val66Met Allele Impairs Basal and Ketamine-Stimulated Synaptogenesis in Prefrontal Cortex
Authors:
Liu, Rong-Jian; Lee, Francis S.; Li, Xiao-Yuan; Bambico, Francis; Duman, Ronald S.; Aghajanian, George K.
Abstract:
Background: Knock-in mice with the common human brain-derived neurotrophic factor (BDNF) Val66Met polymorphism have impaired trafficking of BDNF messenger RNA to dendrites. It was hypothesized, given evidence that local synapse formation is dependent on dendritic translation of BDNF messenger RNA, that loss-of-function Met allele mice would show synaptic deficits both at baseline and in response to ketamine, an N-methyl-D-aspartate antagonist that stimulates synaptogenesis in prefrontal cortex (PFC). Methods: Whole-cell recordings from layer V medial PFC pyramidal cells in brain slices were combined with two-photon laser scanning for analysis of wildtype, Val/Met, and Met/Met mice both at baseline and in response to a low dose of ketamine. Results: Val/Met and Met/Met mice were found to have constitutive atrophy of distal apical dendrites and decrements in apically targeted excitatory postsynaptic currents in layer V pyramidal cells of PFC. In addition, spine density and diameter were decreased, indicative of impaired synaptic formation/maturation (synaptogenesis). In Met/Met mice the synaptogenic effect of ketamine was markedly impaired, consistent with the idea that synaptogenesis is dependent on dendritic translation/release of BDNF. In parallel behavioral studies, we found that the antidepressant response to ketamine in the forced swim test was blocked in Met/Met mice. Conclusions: The results demonstrate that expression of the BDNF Met allele in mice results in basal synaptic deficits and blocks synaptogenic and antidepressant actions of ketamine in PFC, suggesting that the therapeutic response to this drug might be attenuated or blocked in depressed patients who carry the loss of function Met allele.
Published:
2012-06
Title:
Breath analysis as a potential diagnostic tool for tuberculosis
Authors:
Kolk, A. H. J.; van Berkel, J. J. B. N.; Claassens, M. M.; Walters, E.; Kuijper, S.; Dallinga, J. W.; van Schooten, F. J.
Abstract:
SETTING: Cape Town, South Africa. OBJECTIVES: We investigated the potential of breath analysis by gas chromatography-mass spectrometry (GC-MS) to discriminate between samples collected prospectively from patients with suspected tuberculosis (TB). DESIGN: Samples were obtained in a TB-endemic setting in South Africa, where 28% of culture-proven TB patients had Ziehl-Neelsen (ZN) negative sputum smear. A training set of breath samples from 50 sputum culture-proven TB patients and 50 culture-negative non-TB patients was analysed using GC-MS. We used support vector machine analysis for classification of the patient samples into TB and non-TB. RESULTS: A classification model with seven compounds had a sensitivity of 72%, a specificity of 86% and an accuracy of 79% compared with culture. The classification model was validated with breath samples from a different set of 21 TB and 50 non-TB patients from the same area, giving a sensitivity of 62%, a specificity of 84% and an accuracy of 77%. CONCLUSION: This study shows that GC-MS breath analysis is able to differentiate between TB and non-TB breath samples even among patients with a negative ZN sputum smear but a positive culture for Mycobacterium tuberculosis. We conclude that breath analysis by GC-MS merits further research.
Published:
2012-06
Title:
Childhood serum cholesterol ester fatty acids are associated with blood pressure 27 y later in the Cardiovascular Risk in Young Finns Study
Authors:
Kaikkonen, Jari E.; Jula, Antti; Mikkila, Vera; Viikari, Jorma Sa; Moilanen, Teemu; Nikkari, Tapio; Kahonen, Mika; Lehtimaki, Terho; Raitakari, Olli T.
Abstract:
CONCLUSION: Our findings suggest that fat quality as reflected in the serum cholesterol ester fraction in childhood is independently associated with adulthood BP particularly in men but also, to some extent, in women.
Published:
2012-06
Title:
Chinese lacto-vegetarian diet exerts favorable effects on metabolic parameters, intima-media thickness, and cardiovascular risks in healthy men
Authors:
Yang, Shu-Yu; Li, Xue-Jun; Zhang, Wei; Liu, Chang-Qin; Zhang, Hui-Jie; Lin, Jin-Rong; Yan, Bing; Yu, Ya-Xin; Shi, Xiu-Lin; Li, Can-Dong; Li, Wei-Hua
Abstract:
BACKGROUND: To investigate whether the Chinese lacto-vegetarian diet has protective effects on metabolic and cardiovascular disease (CVD). METHODS: One hundred sixty-nine healthy Chinese lacto-vegetarians and 126 healthy omnivore men aged 21-76 years were enrolled. Anthropometric indexes, lipid profile, insulin sensitivity, pancreatic β cell function, and intima-media thickness (IMT) of carotid arteries were assessed and compared. Cardiovascular risk points and probability of developing CVD in 5-10 years in participants aged 24-55 years were calculated. RESULTS: Compared with omnivores, lacto-vegetarians had remarkably lower body mass index, systolic and diastolic blood pressure, and serum levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, γ-glutamyl transferase, serum creatinine, uric acid, fasting blood glucose, as well as lower total cholesterol/high-density lipoprotein cholesterol ratio. Vegetarians also had higher homeostasis model assessment β cell function and insulin secretion index and thinner carotid IMT than the omnivores did. These results corresponded with lower cardiovascular risk points and probability of developing CVD in 5-10 years in vegetarians 24-55 years old. CONCLUSIONS: In healthy Chinese men, the lacto-vegetarian diet seems to exert protective effects on blood pressure, lipid profiles, and metabolic parameters and results in significantly lower carotid IMT. Lower CVD risks found in vegetarians also reflect the beneficial effect of the Chinese lacto-vegetarian diet.
Published:
2012-06
Title:
Chinese lacto-vegetarian diet exerts favorable effects on metabolic parameters, intima-media thickness, and cardiovascular risks in healthy men
Authors:
Yang, Shu-Yu; Li, Xue-Jun; Zhang, Wei; Liu, Chang-Qin; Zhang, Hui-Jie; Lin, Jin-Rong; Yan, Bing; Yu, Ya-Xin; Shi, Xiu-Lin; Li, Can-Dong; Li, Wei-Hua
Abstract:
BACKGROUND: To investigate whether the Chinese lacto-vegetarian diet has protective effects on metabolic and cardiovascular disease (CVD). METHODS: One hundred sixty-nine healthy Chinese lacto-vegetarians and 126 healthy omnivore men aged 21-76 years were enrolled. Anthropometric indexes, lipid profile, insulin sensitivity, pancreatic β cell function, and intima-media thickness (IMT) of carotid arteries were assessed and compared. Cardiovascular risk points and probability of developing CVD in 5-10 years in participants aged 24-55 years were calculated. RESULTS: Compared with omnivores, lacto-vegetarians had remarkably lower body mass index, systolic and diastolic blood pressure, and serum levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, γ-glutamyl transferase, serum creatinine, uric acid, fasting blood glucose, as well as lower total cholesterol/high-density lipoprotein cholesterol ratio. Vegetarians also had higher homeostasis model assessment β cell function and insulin secretion index and thinner carotid IMT than the omnivores did. These results corresponded with lower cardiovascular risk points and probability of developing CVD in 5-10 years in vegetarians 24-55 years old. CONCLUSIONS: In healthy Chinese men, the lacto-vegetarian diet seems to exert protective effects on blood pressure, lipid profiles, and metabolic parameters and results in significantly lower carotid IMT. Lower CVD risks found in vegetarians also reflect the beneficial effect of the Chinese lacto-vegetarian diet.
Published:
2012-06
Title:
Cytomegalovirus localization in atherosclerotic plaques is associated with acute coronary syndromes: report of 105 patients
Authors:
Izadi, Morteza; Fazel, Mozhgan; Saadat, Seyed Hassan; Nasseri, Mohammad Hassan; Ghasemi, Mojtaba; Dabiri, Hossein; Aryan, Reza Safi; Esfahani, Ali Akbar; Ahmadi, Ali; Kazemi-Saleh, Davood; Kalantar-Motamed, Mohammad Hassan; Taheri, Saeed
Abstract:
It has been shown that cytomegalovirus (CMV) is present in coronary atherosclerotic plaques, but the clinical relevance of this presence remains to be elucidated. In this study we sought to examine CMV infection in atherosclerosis patients defined by different methods and to identify the clinical significance of CMV replication in the atherosclerotic plaques. The study included 105 consecutive patients who were admitted to our department and underwent coronary artery bypass grafting (CABG) surgical interventions. Coronary atherosclerotic specimens as well as 53 specimens from the mamillary artery of these same patients were analyzed. Enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) methods were used for evaluations. The CMV PCR test result was positive for 28 (26.7%) of patients with coronary artery atherosclerosis. After adjusting for other risk factors, coronary artery disease patients with a history of acute coronary syndrome were more likely to be positive for CMV PCR test (P=0.027; odds ratio: 4.2; 95% CI: 1.18-15.0). They were also more likely to have a positive family history for cardiovascular diseases (CVD). This study confirms previous evidence about the replication of CMV virus in the atherosclerotic plaques of coronary arteries and brings clinical significance to this observation by showing a higher prevalence of acute coronary syndromes in those patients with CMV-infected plaques. Our study also suggests a familial vulnerability to CMV replication in the coronary artery walls.
Published:
2012-06
Title:
Dietary methods and biomarkers of omega 3 fatty acids: a systematic review
Authors:
Serra-Majem, Lluis; Nissensohn, Mariela; Øverby, Nina C.; Fekete, Katalin
Abstract:
The aims of the present study were to review the validity of dietary methods used to measure the usual long chain (LC) omega-3 polyunsaturated fatty acid (n-3 PUFA) intake of a population and to assess the usefulness of different biomarkers of n-3 PUFA in healthy humans. Two systematic literature searches were conducted until May 2011 to update previous systematic reviews. The first literature search aimed to find studies validating the methodology used for measuring the dietary intake of n-3 PUFA. The second search aimed to find human intervention studies in which n-3 PUFA status changed after 2 weeks of n-3 PUFA supplementation. Sixteen studies were identified for inclusion in the first review. Correlation coefficients between fatty acids in subcutaneous fat or blood lipids and dietary intake of n-3 PUFA from different questionnaires were similar. Subcutaneous fat has been reported as the best reference method for some authors, and these studies showed moderate correlation coefficients with no dietary intake method being superior to any other. As for the evaluation of biomarkers of docosahexaenoic acid (DHA, 22 : 6 n-3) and eicosapentaenoic acid (EPA, 20 : 5n-3) status in response to supplementation, the new search reaffirmed and reinforced the evidence supporting that plasma phospholipid DHA, erythrocyte DHA, and platelet DHA were all effective and robust biomarkers of DHA status. Our findings only confirmed earlier studies and did not provide evidence for reaching new conclusions.
Published:
2012-06
Title:
Evolution of public attitudes about mental illness: a systematic review and meta-analysis: Evolution of public attitudes
Authors:
Schomerus, G.; Schwahn, C.; Holzinger, A.; Corrigan, P. W.; Grabe, H. J.; Carta, M. G.; Angermeyer, M. C.
Abstract:
Objective: To explore whether the increase in knowledge about the biological correlates of mental disorders over the last decades has translated into improved public understanding of mental illness, increased readiness to seek mental health care and more tolerant attitudes towards mentally ill persons. Method: A systematic review of all studies on mental illness-related beliefs and attitudes in the general population published before 31 March 2011, examining the time trends of attitudes with a follow-up interval of at least 2 years and using national representative population samples. A subsample of methodologically homogeneous studies was further included in a meta-regression analysis of time trends. Results: Thirty-three reports on 16 studies on national time trends met our inclusion criteria, six of which were eligible for a metaregression analysis. Two major trends emerged: there was a coherent trend to greater mental health literacy, in particular towards a biological model of mental illness, and greater acceptance of professional help for mental health problems. In contrast, however, no changes or even changes to the worse were observed regarding the attitudes towards people with mental illness. Conclusion: Increasing public understanding of the biological correlates of mental illness seems not to result in better social acceptance of persons with mental illness.
Published:
2012-06
Title:
Fatty acids in cardiovascular health and disease: a comprehensive update. [Review]
Authors:
Baum, Seth J.; Kris-Etherton, Penny M.; Willett, Walter C.; Lichtenstein, Alice H.; Rudel, Lawrence L.; Maki, Kevin C.; Whelan, Jay; Ramsden, Christopher E.; Block, Robert C.
Abstract:
Research dating back to the 1950s reported an association between the consumption of saturated fatty acids (SFAs) and risk of coronary heart disease. Recent epidemiological evidence, however, challenges these findings. It is well accepted that the consumption of SFAs increases low-density lipoprotein cholesterol (LDL-C), whereas carbohydrates, monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) do not. High-density lipoprotein (HDL)-C increases with SFA intake. Among individuals who are insulin resistant, a low-fat, high-carbohydrate diet typically has an adverse effect on lipid profiles (in addition to decreasing HDL-C, it also increases triglyceride and LDL particle concentrations). Consequently, a moderate fat diet in which unsaturated fatty acids replace SFAs and carbohydrates are not augmented is advised to lower LDL-C; compared with a low-fat diet, a moderate-fat diet will lower triglycerides and increase HDL-C. Now, there is some new evidence that is questioning the health benefits of even MUFAs and PUFAs. In addition, in a few recent studies investigators have also failed to demonstrate expected cardiovascular benefits of marine-derived omega-3 fatty acids. To clarify the clinical pros and cons of dietary fats, the National Lipid Association held a fatty acid symposium at the 2011 National Lipid Association Scientific Sessions. During these sessions, the science regarding the effects of different fatty acid classes on coronary heart disease risk was reviewed. Copyright © 2012 National Lipid Association. Published by Elsevier Inc. All rights reserved.
Published:
2012-06
Title:
Ketogenic diet: rapid onset of selenium deficiency-induced cardiac decompensation
Authors:
Sirikonda, Naga S.; Patten, William D.; Phillips, John R.; Mullett, Charles J.
Abstract:
Selenium-deficiency cardiomyopathy is a known secondary complication from long-term treatment with a ketogenic diet for medical refractory epilepsy. Our patient, a 5-year-old boy on a ketogenic diet for intractable seizures, had a normal selenium level before starting the diet, but he shortly thereafter developed acute reversible cardiomyopathy and ventricular tachycardia, which was unmasked during a hospitalization for an elective operative procedure. His cardiomyopathy was suspected to be secondary to a selenium-deficient state and was confirmed by way of a markedly low serum selenium level and supported by rapid improvement with the initiation of selenium supplementation and cessation of the ketogenic diet. For patients being initiated on a ketogenic diet, current screening guidelines call for baseline and follow-up selenium levels every 3 months during the first year along with RDA selenium supplementation, which is 30 mcg/day. Most of the new ketogenic diet formulas meet this requirement. Our patient underwent elective surgery before his planned 3-month selenium level check and had potentially preventable complications. Secondary to this experience, we suggest that all patients initiated on a ketogenic diet should have a preoperative electrocardiogram (EKG), an echocardiogram, and selenium level determined before any elective surgery. These steps would prevent unnecessary perioperative morbidity and mortality.
Published:
2012-06
Title:
Lipoprotein subfractions and dietary intake of n-3 fatty acid: the Genetics of Coronary Artery Disease in Alaska Natives study
Authors:
Annuzzi, Giovanni; Rivellese, Angela A.; Wang, Hong; Patti, Lidia; Vaccaro, Olga; Riccardi, Gabriele; Ebbesson, Sven Oe; Comuzzie, Anthony G.; Umans, Jason G.; Howard, Barbara V.
Abstract:
CONCLUSIONS: Dietary n-3 fatty acids, independent of the reciprocal changes in carbohydrate and sugar intakes, are associated with an overall favorable lipoprotein profile in terms of cardiovascular risk. Because there are no relations with total LDL particles, the benefit may be related to cardiovascular processes other than atherosclerosis.
Published:
2012-06
Title:
Long-term follow-up of children treated with the modified Atkins diet
Authors:
Chen, Wendy; Kossoff, Eric H.
Abstract:
The modified Atkins diet has been studied in mostly short-term clinical trials and case series. No studies have systematically examined the long-term benefits and side effects. The modified Atkins diet was started without prior ketogenic diet use in 87 children at the Johns Hopkins Hospital since 2002, of which 54 continued for more than 6 months. Children who had not been seen within the past 2 years were contacted by phone and email. At their most recent point during the modified Atkins diet (mean 19.9 months), 30 of 54 (55%) children with diet durations of more than 6 months achieved >50% improvement; 19 (35%) were seizure-free. Using an intent-to-treat analysis, at 12 months, 33 of 87 (38%) had >50% seizure reduction; 16 (18%) were seizure-free. These results are similar to published data for short-term modified Atkins diet and long-term ketogenic diet use. Side effects were predominantly elevations in lipid profile and gastrointestinal upset.
Published:
2012-06
Title:
Mitochondrial biogenesis and increased uncoupling protein 1 in brown adipose tissue of mice fed a ketone ester diet
Authors:
Srivastava, Shireesh; Kashiwaya, Yoshihiro; King, M. Todd; Baxa, Ulrich; Tam, Joseph; Niu, Gang; Chen, Xiaoyuan; Clarke, Kieran; Veech, Richard L.
Abstract:
We measured the effects of a diet in which D-β-hydroxybutyrate-(R)-1,3 butanediol monoester [ketone ester (KE)] replaced equicaloric amounts of carbohydrate on 8-wk-old male C57BL/6J mice. Diets contained equal amounts of fat, protein, and micronutrients. The KE group was fed ad libitum, whereas the control (Ctrl) mice were pair-fed to the KE group. Blood d-β-hydroxybutyrate levels in the KE group were 3-5 times those reported with high-fat ketogenic diets. Voluntary food intake was reduced dose dependently with the KE diet. Feeding the KE diet for up to 1 mo increased the number of mitochondria and doubled the electron transport chain proteins, uncoupling protein 1, and mitochondrial biogenesis-regulating proteins in the interscapular brown adipose tissue (IBAT). [(18)F]-Fluorodeoxyglucose uptake in IBAT of the KE group was twice that in IBAT of the Ctrl group. Plasma leptin levels of the KE group were more than 2-fold those of the Ctrl group and were associated with increased sympathetic nervous system activity to IBAT. The KE group exhibited 14% greater resting energy expenditure, but the total energy expenditure measured over a 24-h period or body weights was not different. The quantitative insulin-sensitivity check index was 73% higher in the KE group. These results identify KE as a potential antiobesity supplement.
Published:
2012-06
Title:
Modelling the health impact of environmentally sustainable dietary scenarios in the UK
Authors:
Scarborough, P.; Allender, S.; Clarke, D.; Wickramasinghe, K.; Rayner, M.
Abstract:
BACKGROUND/OBJECTIVES: Food is responsible for around one-fifth of all greenhouse gas (GHG) emissions from products consumed in the UK, the largest contributor of which is meat and dairy. The Committee on Climate Change have modelled the impact on GHG emissions of three dietary scenarios for food consumption in the UK. This paper models the impact of the three scenarios on mortality from cardiovascular disease and cancer. SUBJECTS/METHODS: A previously published model (DIETRON) was used. The three scenarios were parameterised by fruit and vegetables, fibre, total fat, saturated fat, monounsaturated fatty acids, polyunsaturated fatty acids, cholesterol and salt using the 2008 Family Food Survey. A Monte Carlo simulation generated 95% credible intervals. RESULTS: Scenario 1 (50% reduction in meat and dairy replaced by fruit, vegetables and cereals: 19% reduction in GHG emissions) resulted in 36,910 (30,192 to 43,592) deaths delayed or averted per year. Scenario 2 (75% reduction in cow and sheep meat replaced by pigs and poultry: 9% reduction in GHG emissions) resulted in 1999 (1739 to 2389) deaths delayed or averted. Scenario 3 (50% reduction in pigs and poultry replaced with fruit, vegetables and cereals: 3% reduction in GHG emissions) resulted in 9297 (7288 to 11,301) deaths delayed or averted. CONCLUSION: Modelled results suggest that public health and climate change dietary goals are in broad alignment with the largest results in both domains occurring when consumption of all meat and dairy products are reduced. Further work in real-life settings is needed to confirm these results.
Published:
2012-06
Title:
Postprandial platelet aggregation: effects of different meals and glycemic index
Authors:
Ahuja, K. D. K.; Thomas, G. A.; Adams, M. J.; Ball, M. J.
Abstract:
CONCLUSION: In healthy individuals platelet aggregation is reduced postprandially but this decrease is similar between meals of different GI that induce different glucose and insulin responses.
Published:
2012-06
Title:
Regulation of respiration in muscle cells in vivo by VDAC through interaction with the cytoskeleton and MtCK within Mitochondrial Interactosome
Authors:
Guzun, Rita; Gonzalez-Granillo, Marcela; Karu-Varikmaa, Minna; Grichine, Alexei; Usson, Yves; Kaambre, Tuuli; Guerrero-Roesch, Karen; Kuznetsov, Andrey; Schlattner, Uwe; Saks, Valdur
Abstract:
This review describes the recent experimental data on the importance of the VDAC-cytoskeleton interactions in determining the mechanisms of energy and metabolite transfer between mitochondria and cytoplasm in cardiac cells. In the intermembrane space mitochondrial creatine kinase connects VDAC with adenine nucleotide translocase and ATP synthase complex, on the cytoplasmic side VDAC is linked to cytoskeletal proteins. Applying immunofluorescent imaging and Western blot analysis we have shown that β2-tubulin coexpressed with mitochondria is highly important for cardiac muscle cells mitochondrial metabolism. Since it has been shown by Rostovtseva et al. that αβ-heterodimer of tubulin binds to VDAC and decreases its permeability, we suppose that the β-tubulin subunit is bound on the cytoplasmic side and α-tubulin C-terminal tail is inserted into VDAC. Other cytoskeletal proteins, such as plectin and desmin may be involved in this process. The result of VDAC-cytoskeletal interactions is selective restriction of the channel permeability for adenine nucleotides but not for creatine or phosphocreatine that favors energy transfer via the phosphocreatine pathway. In some types of cancer cells these interactions are altered favoring the hexokinase binding and thus explaining the Warburg effect of increased glycolytic lactate production in these cells. This article is part of a Special Issue entitled: VDAC structure, function, and regulation of mitochondrial metabolism.
Published:
2012-06
Title:
The Mediterranean diet pattern and its main components are associated with lower plasma concentrations of tumor necrosis factor receptor 60 in patients at high risk for cardiovascular disease
Authors:
Urpi-Sarda, Mireia; Casas, Rosa; Chiva-Blanch, Gemma; Romero-Mamani, Edwin Saul; Valderas-Martinez, Palmira; Salas-Salvado, Jordi; Covas, Maria Isabel; Toledo, Estefania; Andres-Lacueva, Cristina; Llorach, Rafael; Garcia-Arellano, Ana; Bullo, Monica; Ruiz-Gutierrez, Valentina; Lamuela-Raventos, Rosa M.; Estruch, Ramon
Abstract:
Adherence to a Mediterranean diet (MD) is associated with a reduced risk of coronary heart disease. However, the molecular mechanisms involved are not fully understood. The aim of this study was to compare the effects of 2 MD with those of a low-fat-diet (LFD) on circulating inflammatory biomarkers related to atherogenesis. A total of 516 participants included in the Prevention with Mediterranean Diet Study were randomized into 3 intervention groups [MD supplemented with virgin olive oil (MD-VOO); MD supplemented with mixed nuts (MD-Nuts); and LFD]. At baseline and after 1 y, participants completed FFQ and adherence to MD questionnaires, and plasma concentrations of inflammatory markers including intercellular adhesion molecule-1(ICAM-1), IL-6, and 2 TNF receptors (TNFR60 and TNFR80) were measured by ELISA. At 1 y, the MD groups had lower plasma concentrations of IL-6, TNFR60, and TNFR80 (P < 0.05), whereas ICAM-1, TNFR60, and TNFR80 concentrations increased in the LFD group (P < 0.002). Due to between-group differences, participants in the 2 MD groups had lower plasma concentrations of ICAM-1, IL-6, TNFR60, and TNFR80 compared to those in the LFD group (P <= 0.028). When participants were categorized in tertiles of 1-y changes in the consumption of selected foods, those in the highest tertile of virgin olive oil (VOO) and vegetable consumption had a lower plasma TNFR60 concentration compared with those in tertile 1 (P
Published:
2012-06
Title:
The production of p-cresol sulfate and indoxyl sulfate in vegetarians versus omnivores
Authors:
Patel, Kajal P.; Luo, Frank J.-G.; Plummer, Natalie S.; Hostetter, Thomas H.; Meyer, Timothy W.
Abstract:
CONCLUSIONS: PCS and IS production rates are markedly lower in vegetarians than in individuals consuming an unrestricted diet.
Published:
2012-06
Title:
Tolerance and safety evaluation of N,N-dimethylglycine, a naturally occurring organic compound, as a feed additive in broiler diets
Authors:
Kalmar, Isabelle D.; Verstegen, Martin W. A.; Maenner, Klaus; Zentek, Jurgen; Meulemans, Godelieve; Janssens, Geert P. J.
Abstract:
N,N-Dimethylglycine (DMG) is a tertiary amino acid that naturally occurs as an intermediate metabolite in choline-to-glycine metabolism. The objective of the present trial was to evaluate tolerance, safety and bioaccumulation of dietary DMG in broilers when supplemented at 1 g and 10 g Na-DMG/kg. A feeding trial was conducted using 480 1-d-old broiler chicks that were randomly allocated to twenty-four pens and fed one of three test diets added with 0, 1 or 10 g Na-DMG/kg during a 39 d growth period. Production performance was recorded to assess tolerance and efficacy of the supplement. At the end of the trial, toxicity was evaluated by means of haematology, plasma biochemistry and histopathology of liver, kidney and heart (n 12), whereas bioaccumulation was assessed on breast meat, liver, blood, kidney and adipose tissue (n 8). Carcass traits were similar between the control and 1 g Na-DMG/kg feed groups (P>0.05), but the feed:gain ratio was significantly improved at 1 g Na-DMG/kg feed compared with the control or the 10-fold dose (P=0.008). Histological examinations showed no pathological effects and results of haematology and plasma biochemistry revealed similar values between the test groups (P>0.05). Bioaccumulation occurred at the 10-fold dose, but the resulting DMG content in breast meat was comparable with, for instance, wheat bran and much lower than uncooked spinach. In conclusion, DMG at 1 g Na-DMG/kg improved the feed:gain ratio in broilers without DMG being accumulated in consumer parts. Furthermore, dietary supplementation with DMG up to 10 g Na-DMG/kg did not induce toxicity or impaired performance in broilers.
Published:
2012-06
Title:
Will the real vegetarian please stand up? An investigation of dietary restraint and eating disorder symptoms in vegetarians versus non-vegetarians
Authors:
Timko, C. Alix; Hormes, Julia M.; Chubski, Janice
Abstract:
Adherence to a vegetarian diet has been hypothesized to be a factor in the onset and maintenance of disordered eating behavior; however, evidence to support this assumption has been largely mixed. The two studies presented here sought to address the causes of inconsistent findings in previous research, including: small samples of true vegetarians, lack of appropriate operational definitions of "vegetarianism", and uncertainty about the appropriateness of existing assessments of eating behaviors for semi-vegetarians. Study 1 assessed eating behaviors in the largest samples of confirmed true vegetarians and vegans surveyed to date, and compared them to semi-vegetarians and omnivores. Semi-vegetarians reported the highest levels of eating-related pathology; true vegetarians and vegans appeared to be healthiest in regards to weight and eating. Study 2 examined differences between semi-vegetarians and omnivores in terms of restraint and disordered eating and found little evidence for more eating-related pathology in semi-vegetarians, compared to omnivores. Semi-vegetarians' higher scores on traditional assessments of eating behaviors appeared artificially inflated by ratings of items assessing avoidance of specific food items which should be considered normative in the context of a vegetarian diet. Findings shed light on the sources of inconsistencies in prior research on eating behaviors in vegetarians and suggest that semi-vegetarianism - as opposed to true vegetarianism or veganism - is the most likely related to disordered eating.
Published:
2012-06
Title:
A role for the Warburg effect in preimplantation embryo development: metabolic modification to support rapid cell proliferation
Authors:
Krisher, Rebecca L.; Prather, Randall S.
Abstract:
In this essay, we propose that embryos express a metabolic phenotype necessarily different from that of differentiated somatic cells and more like that of rapidly proliferating cancer cells. This metabolic adaptation, known as the Warburg effect, supports rapid cell proliferation. One of the hallmarks of the Warburg effect is that pyruvate is directed away from the tri-carboxylic acid cycle and metabolized to lactate, resulting in a buildup of glycolytic intermediates. Although this is a comparatively inefficient way to generate ATP, this adaptation allows the cell to meet other critical metabolic requirements, including biomass production and redox regulation. Thus, utilization of WE gives proliferating cells a selective growth advantage. This model represents a completely new understanding of embryo metabolism in the context of a broad, interconnected network of metabolic mechanisms that influence viability, versus the current dogma of carbohydrate metabolism via oxidative phosphorylation. A more complete understanding of embryo metabolism is critical to better support embryo viability in vitro, and to avoid forcing embryos to adapt to suboptimal culture conditions at a significant cost to future growth and development.
Published:
2012-05
Title:
How do patients with rare diseases experience the medical encounter? Exploring role behavior and its impact on patient-physician interaction
Authors:
Budych, Karolina; Helms, Thomas M.; Schultz, Carsten
Abstract:
Objectives: Empirical research shows that patients with severe illnesses prefer the physician to dominate decision processes and provide the information needed. However, in rare diseases, due to the low prevalence and the lack of expertise, the patient is forced to become knowledgeable about his own disease state. Objectives of this study were to describe the experiences of patient-physician interaction in rare diseases, to develop an empirically derived typology of interaction patterns and to explore the antecedents of these interaction patterns, with a special focus on role behavior. Building on these results, implications for health care policy are made. Methods: We designed an exploratory study as a series of semi-standardized interviews with patients suffering from rare diseases. We extracted the following six rare diseases: amyotrophic lateral sclerosis, Duchenne muscular dystrophy, epidermolysis bullosa, Marfan syndrome, neurodegeneration with brain iron accumulation and Wilson's disease. A total of 107 interviews were recorded, transcribed and analyzed thematically in accordance with the grounded theory tradition. Results: As suggested, insufficient expertise of the healthcare providers proved to be a major problem in the highly specialized treatment process of rare diseases. Here, the patient often becomes an expert in his disease. Therefore, we identified the patient-directed interaction as a widely experienced communication pattern among patients with rare diseases. Our study also showed that role discrepancies have a major impact on communication processes in this context. Conclusions: People with rare diseases often face challenges, due to the low prevalence and the resulting lack of knowledge of their healthcare providers. Communication processes in this context are mainly affected by the role behavior of both the patient and provider. The present study showed the relevance of the provider's ability to acknowledge the active role of the patient as an informed, involved and interactive partner in the treatment process. However, allowing the patient to control therapy may require a change of mind-set with some long-standing traditional roles in healthcare. © 2012 Elsevier Ireland Ltd.
Published:
2012-05
Title:
Influence of dairy product and milk fat consumption on cardiovascular disease risk: a review of the evidence. [Review]
Authors:
Huth, Peter J.; Park, Keigan M.
Abstract:
Although evidence has linked the consumption of saturated fat (SF) to increased LDL levels and an increased risk of the development of cardiovascular disease (CVD), recent findings have indicated that the link between CVD and SF may be less straightforward than originally thought. This may be due to the fact that some food sources high in SF contain an array of saturated and unsaturated fatty acids, each of which may differentially affect lipoprotein metabolism, as well as contribute significant amounts of other nutrients, which may alter CVD risk. The purpose of this review is to examine the published research on the relationship between milk fat containing dairy foods and cardiovascular health. The findings indicate that the majority of observational studies have failed to find an association between the intake of dairy products and increased risk of CVD, coronary heart disease, and stroke, regardless of milk fat levels. Results from short-term intervention studies on CVD biomarkers have indicated that a diet higher in SF from whole milk and butter increases LDL cholesterol when substituted for carbohydrates or unsaturated fatty acids; however, they may also increase HDL and therefore might not affect or even lower the total cholesterol:HDL cholesterol ratio. The results from the review also indicate that cheese intake lowers LDL cholesterol compared with butter of equal milk fat content. In addition, the review highlights some significant gaps in the research surrounding the effects of full-fat dairy on CVD outcomes, pointing to the need for long-term intervention studies.
Published:
2012-05
Title:
New insights into the health effects of dietary saturated and omega-6 and omega-3 polyunsaturated fatty acids. [Review]
Authors:
de Lorgeril, Michel; Salen, Patricia
Abstract:
Cardiovascular diseases and cancers are leading causes of morbidity and mortality. Reducing dietary saturated fat and replacing it with polyunsaturated fat is still the main dietary strategy to prevent cardiovascular diseases, although major flaws have been reported in the analyses supporting this approach. Recent studies introducing the concept of myocardial preconditioning have opened new avenues to understand the complex interplay between the various lipids and the risk of cardiovascular diseases. The optimal dietary fat profile includes a low intake of both saturated and omega-6 fatty acids and a moderate intake of omega-3 fatty acids. This profile is quite similar to the Mediterranean diet. On the other hand, recent studies have found a positive association between omega-6 and breast cancer risk. In contrast, omega-3 fatty acids do have anticancer properties. It has been shown that certain (Mediterranean) polyphenols significantly increase the endogenous synthesis of omega-3 whereas high intake of omega-6 decreases it. Finally, epidemiological studies suggest that a high omega-3 to omega-6 ratio may be the optimal strategy to decrease breast cancer risk. Thus, the present high intake of omega-6 in many countries is definitely not the optimal strategy to prevent cardiovascular disease and cancers. A moderate intake of plant and marine omega-3 in the context of the traditional Mediterranean diet (low in saturated and omega-6 fatty acids but high in plant monounsaturated fat) appears to be the best approach to reduce the risk of both cardiovascular diseases and cancers, in particular breast cancer.
Published:
2012-05
Title:
Aromatic DNA adducts and risk of gastrointestinal cancers: a case-cohort study within the EPIC-Spain
Authors:
Agudo, Antonio; Peluso, Marco; Munnia, Armelle; Luján-Barroso, Leila; Sánchez, María-José; Molina-Montes, Esther; Sánchez-Cantalejo, Emilio; Navarro, Carmen; Tormo, María-José; Chirlaque, María-Dolores; Barricarte, Aurelio; Ardanaz, Eva; Amiano, Pilar; Dorronsoro, Miren; Quirós, J. Ramón; Piro, Sara; Bonet, Catalina; Sala, Núria; González, Carlos A.
Abstract:
BACKGROUND: Colorectal (CRC) and gastric cancer (GC) are associated with meat intake and tobacco smoke, maybe because of aromatic compounds occurring in tobacco smoking and formed during cooking meat. Activated metabolites of these compounds may bind to DNA forming bulky adducts. METHODS: Forty-eight subjects diagnosed of GC and 154 of CRC during a 7-year follow-up period in the European Prospective Investigation into Cancer and Nutrition-Spain cohort were compared with a sample of 296 subjects using a case-cohort approach. Aromatic adducts to DNA from leukocytes collected at recruitment were measured by means of the (32)P-postlabeling technique. The relative risk (RR) and 95% confidence interval (CI), adjusted by relevant confounders were estimated by a modified version of Cox regression. RESULTS: Using the log(2)-transformed adduct concentration, we observed a RR = 1.57 (CI: 1.25-1.97) for CRC, which means a 57% increased risk associated with doubling the level of adducts, and 47% (RR = 1.47, CI: 1.07-2.00) increase in risk of GC. The association was more marked for colon than for rectal tumors. CONCLUSIONS: The level of aromatic adducts in the DNA is independently associated with an increased risk of gastric and CRCs. This effect could be due to aromatic compounds present in tobacco smoke or formed in meat, but they could be also due to genotoxic compounds from other sources. IMPACT: Sources of aromatic compounds should be taken into account, in addition to known risk factors, in the research and prevention of tumors of the stomach, colon, and rectum.
Published:
2012-04
Title:
Blood cells as a source of transcriptional biomarkers of childhood obesity and its related metabolic alterations: results of the IDEFICS study
Authors:
Sánchez, Juana; Priego, Teresa; Picó, Catalina; Ahrens, Wolfgang; De Henauw, Stefaan; Fraterman, Arno; Mårild, Staffan; Molnár, Dénes; Moreno, Luis A.; Peplies, Jenny; Russo, Paola; Siani, Alfonso; Tornaritis, Michael; Veidebaum, Toomas; Palou, Andreu; IDEFICS Consortium
Abstract:
BACKGROUND: IDEFICS (Identification and Prevention of Dietary- and Lifestyle-Induced Health Effects in Children and Infants Project) is a European multicenter study on childhood obesity. One of its goals is to define early biomarkers of risk associated with obesity and its comorbid conditions. OBJECTIVE: We considered blood cells as a new potential source of transcriptional biomarkers for these metabolic disorders and examined whether blood cell mRNA levels of some selected genes (LEPR, INSR, CPT1A, SLC27A2, UCP2, FASN, and PPARα) were altered in overweight children and whether their expression levels could be defined as markers of the insulin-resistant or dyslipidemic state associated with overweight. DESIGN: Blood samples were obtained from 306 normal-weight and overweight children, aged 2-9 yr, from eight different European countries. Whole-blood mRNA levels were assessed by quantitative RT-PCR. RESULTS: LEPR, INSR, and CPT1A mRNA levels were higher in overweight compared with normal-weight children (the two latter only in males), whereas SLC27A2 mRNA levels were lower in overweight children. Significant associations were also found between expression levels of LEPR, INSR, CPT1A, SLC27A2, FASN, PPARα, and different parameters, including body mass index, homeostasis model assessment index, and plasma triglycerides and cholesterol levels. These associations showed that high expression levels of CPT1A, SLC27A2, INSR, FASN, or PPARα may be indicative of a lower risk for the insulin-resistant or dyslipidemic state associated with obesity, whereas low LEPR mRNA levels appear as a marker of high low-density lipoprotein cholesterol, independently of body mass index. CONCLUSIONS: These findings point toward the possibility of using the expression levels of these genes in blood cells as markers of metabolic status and can potentially provide an early warning of a future disorder.
Published:
2012-04
Title:
E-mail management of the modified Atkins Diet for adults with epilepsy is feasible and effective
Authors:
Cervenka, Mackenzie C.; Terao, Natalie N.; Bosarge, Jennifer L.; Henry, Bobbie J.; Klees, Angela A.; Morrison, Peter F.; Kossoff, Eric H.
Abstract:
PURPOSE: The modified Atkins Diet (MAD) is an effective dietary treatment for children with epilepsy. However, adults may have limited access to this therapy because of lack of availability of dietitian or nutrition support or familiarity with the diet by their treating neurologist. This study was designed to investigate the tolerability and efficacy of the MAD administered solely via e-mail to adults with pharmacoresistant epilepsy. METHODS: A prospective, open-label, proof-of-principle 3-month study design was employed. Adults were enrolled, instructed on how to self-administer a 20 g carbohydrate per day MAD, and followed by the investigators only via e-mail. There were no clinic visits or dietitian contacts during the study period. KEY FINDINGS: Twenty-five participants (median age 30 years [range 18-66 years], 68% female) consented and 22 started the MAD. The median prior anticonvulsants was 5 (range 2-10) and seizure frequency was 5 per week (range 1-140). Urinary ketosis was achieved in 21 participants (95%), of which 16 (76%) reported at least 40 mg/dl (moderate). Twenty-one participants (95%) remained on the MAD at 1 month and 14 (64%) at 3 months. After 1 month, 9 (41%) had >50% seizure reduction including one (5%) with >90% seizure reduction using intent-to-treat analysis. After 3 months, 6 (27%) had >50% seizure reduction including 3 (14%) with >90% seizure reduction. The mean ketogenic ratio was 1.1:1 (fat:carbohydrates and protein) for those who provided a MAD food record at follow-up. Over the study period, the median number of e-mails sent by the participants was 6 (range 1-19). The most frequent side effect was weight loss. SIGNIFICANCE: E-mail administration of the MAD to adults with refractory epilepsy appears to be feasible and effective. Therefore, when dietitian or physician support is limited for adult patients with epilepsy, remote access via telemedicine could provide an alternative.
Published:
2012-04
Title:
Evidence-based pharmacotherapy of panic disorder: an update
Authors:
Batelaan, Neeltje M.; Van Balkom, Anton J. L. M.; Stein, Dan J.
Abstract:
The evidence-based pharmacotherapy of panic disorder continues to evolve. This paper reviews data on first-line pharmacotherapy, evidence for maintenance treatment, and management options for treatmentrefractory patients. A Medline search of research on pharmacotherapy was undertaken, and a previous systematic review on the evidence-based pharmacotherapy of panic disorder was updated. Selective serotonin reuptake inhibitors remain a first-line pharmacotherapy of panic disorder, with the serotonin noradrenaline reuptake inhibitor venlafaxine also an acceptable early option. Temporary co-administration of benzodiazepines can be considered. Maintenance treatment reduces relapse rates, but further research to determine optimal duration is needed. For patients not responding to first-line agents several pharmacotherapy options are available, but there is a notable paucity of data on the optimal choice.
Published:
2012-04
Title:
Increased visceral adipose tissue is associated with increased resting heart rate in patients with manifest vascular disease
Authors:
Bemelmans, Remy H. H.; van der Graaf, Yolanda; Nathoe, Hendrik M.; Wassink, Annemarie M. J.; Vernooij, Joris W. P.; Spiering, Wilko; Visseren, Frank L. J.; SMART Study Group
Abstract:
Abdominal obesity is characterized by sympathetic nerve activation (SNA), probably mediated by elevated insulin and leptin levels. Resting heart rate (RHR) is a marker of sympathetic tone, and independently associated with cardiovascular events and death in various populations. We investigated and quantified the relation between visceral adipose tissue (VAT) and RHR in patients with vascular disease. In 3,723 patients with manifest vascular disease, visceral and subcutaneous fat tissue was measured with ultrasonography. RHR was obtained from an electrocardiogram (ECG). The association between quartiles of VAT and RHR was quantified using linear regression analysis with adjustments for potential confounding factors. Separate analyses were performed for men and women and for location of vascular disease. Visceral fat was categorized into sex-pooled quartiles (Q) ranging from 2.7-8.0 cm in Q1 (reference) to 9.4-20.6 cm in Q4. High visceral fat thickness was associated with increased RHR, in men (Q4 vs. Q1, β = 4.36; 95% confidence interval (CI) = 3.11-5.61) and women (β = 1.48; 95% CI = -0.70 to 3.66), after full adjustment. Waist circumference and BMI had a significant relation with RHR in men (β = 3.51; 95% CI = 2.21-4.81 and β = 2.80; 95% CI = 1.51-4.08, respectively) but these relations were smaller and not significant in women (β = 0.71; 95% CI = -1.44 to 2.85 and β = 0.24; 95% CI = -1.90 to 2.37, respectively). There was no relation between subcutaneous fat and RHR in men and women. The relation between visceral fat and RHR was similar in patients with different locations of vascular diseases. Increased visceral fat is associated with increased RHR in male and female patients with vascular disease, independent of the location.
Published:
2012-04
Title:
Ketone bodies in epilepsy
Authors:
McNally, Melanie A.; Hartman, Adam L.
Abstract:
Seizures that are resistant to standard medications remain a major clinical problem. One underutilized option for patients with medication-resistant seizures is the high-fat, low-carbohydrate ketogenic diet. The diet received its name based on the observation that patients consuming this diet produce ketone bodies (e.g., acetoacetate, β-hydroxybutyrate, and acetone). Although the exact mechanisms of the diet are unknown, ketone bodies have been hypothesized to contribute to the anticonvulsant and antiepileptic effects. In this review, anticonvulsant properties of ketone bodies and the ketogenic diet are discussed (including GABAergic and glutamatergic effects). Because of the importance of ketone body metabolism in the early stages of life, the effects of ketone bodies on developing neurons in vitro also are discussed. Understanding how ketone bodies exert their effects will help optimize their use in treating epilepsy and other neurological disorders.
Published:
2012-04
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