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Title:
Food Patterns and Framingham Risk Score in Iranian Adults: Tehran Lipid and Glucose Study: 2005-2011
Authors:
Ebrahimof, S.; Hosseini-Esfahani, F.; Mirmiran, P.; Fallah-Kezabi, M.; Azizi, F.
Abstract:
Background: Healthy dietary habits can prevent cardiovascular diseases (CVD). The aim of this study was to investigate the association between dietary patterns and predicted risk of CVD development using Framingham Risk Score (FRS) in Iranian population over 6 years of follow-up. Methods: In this prospective study, 2333 individuals aged 30-74 years with a 10-year predicted risk
Published:
2018
Title:
Food intake biomarkers for apple, pear, and stone fruit
Authors:
Ulaszewska, Marynka; Vázquez-Manjarrez, Natalia; Garcia-Aloy, Mar; Llorach, Rafael; Mattivi, Fulvio; Dragsted, Lars O.; Praticò, Giulia; Manach, Claudine
Abstract:
Fruit is a key component of a healthy diet. However, it is still not clear whether some classes of fruit may be more beneficial than others and whether all individuals whatever their age, gender, health status, genotype, or gut microbiota composition respond in the same way to fruit consumption. Such questions require further observational and intervention studies in which the intake of a specific fruit can be precisely assessed at the population and individual levels. Within the Food Biomarker Alliance Project (FoodBAll Project) under the Joint Programming Initiative "A Healthy Diet for a Healthy Life", an ambitious action was undertaken aiming at reviewing existent literature in a systematic way to identify validated and promising biomarkers of intake for all major food groups, including fruits. This paper belongs to a series of reviews following the same BFIRev protocol and is focusing on biomarkers of pome and stone fruit intake. Selected candidate biomarkers extracted from the literature search went through a validation process specifically developed for food intake biomarkers.
Published:
2018
Title:
Fructose metabolism, cardiometabolic risk, and the epidemic of coronary artery disease
Authors:
Mirtschink, Peter; Jang, Cholsoon; Arany, Zoltan; Krek, Wilhelm
Abstract:
Despite strong indications that increased consumption of added sugars correlates with greater risks of developing cardiometabolic syndrome (CMS) and cardiovascular disease (CVD), independent of the caloric intake, the worldwide sugar consumption remains high. In considering the negative health impact of overconsumption of dietary sugars, increased attention is recently being given to the role of the fructose component of high-sugar foods in driving CMS. The primary organs capable of metabolizing fructose include liver, small intestine, and kidneys. In these organs, fructose metabolism is initiated by ketohexokinase (KHK) isoform C of the central fructose-metabolizing enzyme KHK. Emerging data suggest that this tissue restriction of fructose metabolism can be rescinded in oxygen-deprived environments. In this review, we highlight recent progress in understanding how fructose metabolism contributes to the development of major systemic pathologies that cooperatively promote CMS and CVD, reference recent insights into microenvironmental control of fructose metabolism under stress conditions and discuss how this understanding is shaping preventive actions and therapeutic approaches.
Published:
2018
Title:
GSK3 suppression upregulates β-catenin and c-Myc to abrogate KRas-dependent tumors
Authors:
Kazi, Aslamuzzaman; Xiang, Shengyan; Yang, Hua; Delitto, Daniel; Trevino, José; Jiang, Rays H. Y.; Ayaz, Muhammad; Lawrence, Harshani R.; Kennedy, Perry; Sebti, Saïd M.
Abstract:
Mutant KRas is a significant driver of human oncogenesis and confers resistance to therapy, underscoring the need to develop approaches that disable mutant KRas-driven tumors. Because targeting KRas directly has proven difficult, identifying vulnerabilities specific for mutant KRas tumors is an important alternative approach. Here we show that glycogen synthase kinase 3 (GSK3) is required for the in vitro and in vivo growth and survival of human mutant KRas-dependent tumors but is dispensable for mutant KRas-independent tumors. Further, inhibiting phosphorylation of GSK3 substrates c-Myc on T58 and β-catenin on S33/S37/T41 and their subsequent upregulation contribute to the antitumor activity of GSK3 inhibition. Importantly, GSK3 blockade inhibits the in vivo growth of G12D, G12V, and G12C mutant KRas primary and metastatic patient-derived xenografts from pancreatic cancer patients who progressed on chemo- and radiation therapies. This discovery opens new avenues to target mutant KRas-dependent cancers.
Published:
2018
Title:
Genetic Variants in SGLT1, Glucose Tolerance, and Cardiometabolic Risk
Authors:
Yu, Bing; Boerwinkle, Eric; Selvin, Elizabeth; Franceschini, Nora; Ebeling, Tapani; Feofanova, Elena; Solomon, Scott D.; MacRae, Calum A.; Puolijoki, Hannu; Perola, Markus; Coresh, Josef; Seidelmann, Sara B.; Salomaa, Veikko; Cheng, Susan; Shah, Amil; Claggett, Brian; Kuokkanen, Mikko
Abstract:
Published:
2018
Title:
Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries
Authors:
Bray, Freddie; Ferlay, Jacques; Soerjomataram, Isabelle; Siegel, Rebecca L.; Torre, Lindsey A.; Jemal, Ahmedin
Abstract:
This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
Published:
2018
Title:
Guidelines for Biomarker of Food Intake Reviews (BFIRev): how to conduct an extensive literature search for biomarker of food intake discovery
Authors:
Praticò, Giulia; Gao, Qian; Scalbert, Augustin; Vergères, Guy; Kolehmainen, Marjukka; Manach, Claudine; Brennan, Lorraine; Pedapati, Sri Harsha; Afman, Lydia A.; Wishart, David S.; Vázquez-Fresno, Rosa; Andres-Lacueva, Cristina; Garcia-Aloy, Mar; Verhagen, Hans; Feskens, Edith J. M.; Dragsted, Lars O.
Abstract:
Identification of new biomarkers of food and nutrient intake has developed fast over the past two decades and could potentially provide important new tools for compliance monitoring and dietary intake assessment in nutrition and health science. In recent years, metabolomics has played an important role in identifying a large number of putative biomarkers of food intake (BFIs). However, the large body of scientific literature on potential BFIs outside the metabolomics area should also be taken into account. In particular, we believe that extensive literature reviews should be conducted and that the quality of all suggested biomarkers should be systematically evaluated. In order to cover the literature on BFIs in the most appropriate and consistent manner, there is a need for appropriate guidelines on this topic. These guidelines should build upon guidelines in related areas of science while targeting the special needs of biomarker methodology. This document provides a guideline for conducting an extensive literature search on BFIs, which will provide the basis to systematically validate BFIs. This procedure will help to prioritize future work on the identification of new potential biomarkers and on validating these as well as other biomarker candidates, thereby providing better tools for future studies in nutrition and health.
Published:
2018
Title:
Gut symbiotic microbes imprint intestinal immune cells with the innate receptor SLAMF4 which contributes to gut immune protection against enteric pathogens
Authors:
Cabinian, Allison; Sinsimer, Daniel; Tang, May; Jang, Youngsoon; Choi, Bongkum; Laouar, Yasmina; Laouar, Amale
Abstract:
BACKGROUND: Interactions between host immune cells and gut microbiota are crucial for the integrity and function of the intestine. How these interactions regulate immune cell responses in the intestine remains a major gap in the field. AIM: We have identified the signalling lymphocyte activation molecule family member 4 (SLAMF4) as an immunomodulator of the intestinal immunity. The aim is to determine how SLAMF4 is acquired in the gut and what its contribution to intestinal immunity is. METHODS: Expression of SLAMF4 was assessed in mice and humans. The mechanism of induction was studied using GFPtg bone marrow chimaera mice, lymphotoxin α and TNLG8A-deficient mice, as well as gnotobiotic mice. Role in immune protection was revealed using oral infection with Listeria monocytogenes and Cytobacter rodentium. RESULTS: SLAMF4 is a selective marker of intestinal immune cells of mice and humans. SLAMF4 induction occurs directly in the intestinal mucosa without the involvement of the gut-associated lymphoid tissue. Gut bacterial products, particularly those of gut anaerobes, and gut-resident antigen-presenting cell (APC) TNLG8A are key contributors of SLAMF4 induction in the intestine. Importantly, lack of SLAMF4 expression leads the increased susceptibility of mice to infection by oral pathogens culminating in their premature death. CONCLUSIONS: SLAMF4 is a marker of intestinal immune cells which contributes to the protection against enteric pathogens and whose expression is dependent on the presence of the gut microbiota. This discovery provides a possible mechanism for answering the long-standing question of how the intertwining of the host and gut microbial biology regulates immune cell responses in the gut.
Published:
2018
Title:
Healthy Plant-Based Diets Are Associated with Lower Risk of All-Cause Mortality in US Adults
Authors:
Kim, Hyunju; Caulfield, Laura E.; Rebholz, Casey M.
Abstract:
Background: Plant-based diets, often referred to as vegetarian diets, are associated with health benefits. However, the association with mortality is less clear. Objective: We investigated associations between plant-based diet indexes and all-cause and cardiovascular disease mortality in a nationally representative sample of US adults. Methods: Analyses were based on 11,879 participants (20-80 y of age) from NHANES III (1988-1994) linked to data on all-cause and cardiovascular disease mortality through 2011. We constructed an overall plant-based diet index (PDI), which assigns positive scores for plant foods and negative scores for animal foods, on the basis of a food-frequency questionnaire administered at baseline. We also constructed a healthful PDI (hPDI), in which only healthy plant foods received positive scores, and a less-healthful (unhealthy) PDI (uPDI), in which only less-healthful plant foods received positive scores. Cox proportional hazards models were used to estimate the association between plant-based diet consumption in 1988-1994 and subsequent mortality. We tested for effect modification by sex. Results: In the overall sample, PDI and uPDI were not associated with all-cause or cardiovascular disease mortality after controlling for demographic characteristics, socioeconomic factors, and health behaviors. However, among those with an hPDI score above the median, a 10-unit increase in hPDI was associated with a 5% lower risk in all-cause mortality in the overall study population (HR: 0.95; 95% CI: 0.91, 0.98) and among women (HR: 0.94; 95% CI: 0.88, 0.99), but not among men (HR: 0.95; 95% CI: 0.90, 1.01). There was no effect modification by sex (P-interaction > 0.10). Conclusions: A nonlinear association between hPDI and all-cause mortality was observed. Healthy plant-based diet scores above the median were associated with a lower risk of all-cause mortality in US adults. Future research exploring the impact of quality of plant-based diets on long-term health outcomes is necessary.
Published:
2018
Title:
High Glucose Induces VEGF-C Expression via the LPA1/3-Akt-ROS-LEDGF Signaling Axis in Human Prostate Cancer PC-3 Cells
Authors:
Huang, Yuan-Li; Lin, Yueh-Chien; Lin, Chu-Cheng; Chen, Wei-Min; Chen, Benjamin P. C.; Lee, Hsinyu
Abstract:
BACKGROUND/AIMS: Hyperglycemia has been shown to increase the incidence and metastasis in various types of cancers. However, the correlation between hyperglycemia and lymphatic metastasis in prostate cancer (PCa) remains unclear. Our previous study demonstrated that lysophosphatidic acid (LPA) enhances vascular endothelial growth factor-C (VEGF-C) expression, a lymphangiogenic factor, through activating it receptors LPA1/3 in prostate cancer (PCa) cells. Moreover, hyperglycemia up-regulates autotaxin (ATX) expression, a LPA-generating enzyme. Therefore, we propose that high glucose promotes VEGF-C expression through LPA signaling in PCa cells. METHODS: Pharmacological inhibitors and siRNAs were utilized to investigate the molecular mechanism of high glucose-induced VEGF-C expression. Real-time PCR and Western blot were used to determine the mRNA and protein expressions, respectively. Cellular bioenergetics analysis was performed to determine the glycolysis levels. RESULTS: We demonstrated that the expressions of VEGF-C, ATX, and calreticulin were increased upon high glucose treatments in PC-3 cells. Moreover, high glucose-induced VEGF-C expression was mediated through the LPA1/3, PLC, Akt, ROS and LEDGF-dependent pathways. Additionally, high glucose enhanced the aerobic glycolysis via LPA1/3. CONCLUSION: These results indicated that hyperglycemia leads to LPA synthesis, and subsequent promoting pathological consequence of PCa. These novel findings could potentially provide new strategies for PCa treatments.
Published:
2018
Title:
High-intensity interval training for patients with cardiovascular disease-is it safe? A systematic review
Authors:
Wewege, Michael A.; Ahn, Dohee; Yu, Jennifer; Liou, Kevin; Keech, Andrew
Abstract:
© 2018 The Authors. Background-Cardiac rehabilitation (CR) for patients with cardiovascular disease has traditionally involved low-to moderateintensity continuous aerobic exercise training (MICT). There is growing and robust evidence that high-intensity interval training (HIIT) shows similar or greater efficacy compared with MICT across a range of cardiovascular and metabolic measures, in both healthy populations and populations with a chronic illness. However, there is understandable concern about the safety aspects of applying HIIT in CR settings. This systematic review analyzed safety data drawn from recent proof-of-concept studies of HIIT during CR among patients with cardiovascular disease. Methods and Results-We included trials comparing HIIT with either MICT or usual care in patients with coronary artery disease or heart failure participating in tertiary care services, such as phase 2 (outpatient) CR. Adverse events occurring during or up to 4 hours after an exercise training session were collated. There were 23 studies included, which analyzed 1117 participants (HIIT=547; MICT=570). One major cardiovascular adverse event occurred in relation to an HIIT session, equating to 1 major cardiovascular event per 17 083 training sessions (11 333 training hours). One minor cardiovascular adverse events and 3 noncardiovascular adverse events (primarily musculoskeletal complaints) were also reported for HIIT. Two noncardiovascular events were reported in relation to MICT. Conclusions-HIIT has shown a relatively low rate of major adverse cardiovascular events for patients with coronary artery disease or heart failure when applied within CR settings.
Published:
2018
Title:
High-intensity interval training versus moderate-intensity continuous training within cardiac rehabilitation: a systematic review and meta-analysis
Authors:
Hannan, Amanda; Hing, Wayne; Simas, Vini; Climstein, Mike; Coombes, Jeff; Jayasinghe, Rohan; Byrnes, Joshua; Furness, James
Abstract:
Background Aerobic capacity has been shown to be inversely proportionate to cardiovascular mortality and morbidity and there is growing evidence that high-intensity interval training (HIIT) appears to be more effective than moderate-intensity continuous training (MICT) in improving cardiorespiratory fitness within the cardiac population. Previously published systematic reviews in cardiovascular disease have neither investigated the effect that the number of weeks of intervention has on cardiorespiratory fitness changes, nor have adverse events been collated. Objective We aimed to undertake a systematic review and meta-analysis of randomized controlled trials (RCTs) within the cardiac population that investigated cardiorespiratory fitness changes resulting from HIIT versus MICT and to collate adverse events. Methods A critical narrative synthesis and meta-analysis was conducted after systematically searching relevant databases up to July 2017. We searched for RCTs that compared cardiorespiratory fitness changes resulting from HIIT versus MICT interventions within the cardiac population. Results Seventeen studies, involving 953 participants (465 for HIIT and 488 for MICT) were included in the analysis. HIIT was significantly superior to MICT in improving cardiorespiratory fitness overall (SMD 0.34 mL/kg/min; 95% confidence interval [CI; 0.2-0.48]; p\textless0.00001; I2=28%). There were no deaths or cardiac events requiring hospitalization reported in any study during training. Overall, there were more adverse events reported as a result of the MICT (n=14) intervention than the HIIT intervention (n=9). However, some adverse events (n=5) were not classified by intervention group. Conclusion HIIT is superior to MICT in improving cardiorespiratory fitness in participants of cardiac rehabilitation (CR). Improvements in cardiorespiratory fitness are significant for CR programs of \textgreater6-week duration. Programs of 7-12 weeks' duration resulted in the largest improvements in cardiorespiratory fitness for patients with coronary artery disease. HIIT appears to be as safe as MICT for CR participants.
Published:
2018
Title:
Histone H3 lysine 4 methylation signature associated with human undernutrition
Authors:
Uchiyama, Robin; Kupkova, Kristyna; Shetty, Savera J.; Linford, Alicia S.; Pray-Grant, Marilyn G.; Wagar, Lisa E.; Davis, Mark M.; Haque, Rashidul; Gaultier, Alban; Mayo, Marty W.; Grant, Patrick A.; Petri, William A.; Bekiranov, Stefan; Auble, David T.
Abstract:
Chronically undernourished children become stunted during their first 2 years and thereafter bear burdens of ill health for the rest of their lives. Contributors to stunting include poor nutrition and exposure to pathogens, and parental history may also play a role. However, the epigenetic impact of a poor environment on young children is largely unknown. Here we show the unfolding pattern of histone H3 lysine 4 trimethylation (H3K4me3) in children and mothers living in an urban slum in Dhaka, Bangladesh. A pattern of chromatin modification in blood cells of stunted children emerges over time and involves a global decrease in methylation at canonical locations near gene start sites and increased methylation at ectopic sites throughout the genome. This redistribution occurs at metabolic and immune genes and was specific for H3K4me3, as it was not observed for histone H3 lysine 27 acetylation in the same samples. Methylation changes in stunting globally resemble changes that occur in vitro in response to altered methylation capacity, suggesting that reduced levels of one-carbon nutrients in the diet play a key role in stunting in this population. A network of differentially expressed genes in stunted children reveals effects on chromatin modification machinery, including turnover of H3K4me3, as well as posttranscriptional gene regulation affecting immune response pathways and lipid metabolism. Consistent with these changes, reduced expression of the endocytic receptor gene LDL receptor 1 (LRP1) is a driver of stunting in a mouse model, suggesting a target for intervention.
Published:
2018
Title:
Hormonal and dietary factors in acne vulgaris versus controls
Authors:
Stewart, Thomas Jonathan; Bazergy, Carl
Abstract:
Background: Acne vulgaris is an inflammatory skin disorder with not as yet fully understood pathogenesis. In this controlled study, we assessed acne vulgaris patients for several possible pathogenic factors such as vitamin D deficiency, vegan diet, increased body mass index (BMI) and positive anti-transglutaminase antibody. Methods: We screened 10 years of records at a family medicine clinic for patients diagnosed with acne vulgaris. In eligible subjects, we collected data regarding 25-hydroxylvitamin D levels, BMI, dietary preference and serum IgA tissue transglutaminase levels. Controls were age- (+/- 12 months) and sex-matched patients seen during the study period without a diagnosis of acne vulgaris. Results: 453 patients were given a diagnosis of acne vulgaris during the study period. Compared with controls, we found significant associations between vitamin D deficiency (4.0U/mL) and a diagnosis of acne vulgaris. Conclusions: Our study adds important information to the current body of literature in pursuit of elucidating the pathogenesis of this complex multifactorial disease.
Published:
2018
Title:
Hunter-gatherers as models in public health
Authors:
Pontzer, H.; Wood, B. M.; Raichlen, D. A.
Abstract:
Hunter-gatherer populations are remarkable for their excellent metabolic and cardiovascular health and thus are often used as models in public health, in an effort to understand the root, evolutionary causes of non-communicable diseases. Here, we review recent work on health, activity, energetics and diet among hunter-gatherers and other small-scale societies (e.g. subsistence farmers, horticulturalists and pastoralists), as well as recent fossil and archaeological discoveries, to provide a more comprehensive perspective on lifestyle and health in these populations. We supplement these analyses with new data from the Hadza, a hunter-gatherer population in northern Tanzania. Longevity among small-scale populations approaches that of industrialized populations, and metabolic and cardiovascular disease are rare. Obesity prevalence is very low (
Published:
2018
Title:
Hyperglycaemia and Survival in Solid Tumours: A Systematic Review and Meta-analysis
Authors:
Barua, R.; Templeton, A. J.; Seruga, B.; Ocana, A.; Amir, E.; Ethier, J. L.
Abstract:
Aims: Diabetes is associated with adverse cancer outcomes. However, the effect of hyperglycaemia in non-diabetic cancer patients is unclear. Materials and methods: A systematic search of electronic databases identified publications exploring the effect of hyperglycaemia on overall survival, disease-free survival (DFS) or progression-free survival (PFS). Data from studies reporting a hazard ratio and 95% confidence interval and/or a P-value were pooled in a meta-analysis using generic inverse-variance and random effects modelling. Subgroup analyses were conducted based on method of hyperglycaemia measurement (HbA1c, other) and stage (early, advanced, mixed). Meta-regression was performed to evaluate the influence of clinical characteristics including baseline diabetes status on the hazard ratio for overall survival. Results: Twelve studies comprising a total of 9872 patients were included. All studies reported hazard ratios for overall survival. Three studies reported DFS; two reported PFS outcomes. Definitions of hyperglycaemia and cut-offs varied between studies. Hyperglycaemia was associated with worse overall survival (hazard ratio 2.05, 95% confidence interval 1.67–2.51; P \textless 0.001) and DFS (hazard ratio 1.98, 95% confidence interval 1.20–3.27; P = 0.007), but did not affect PFS (hazard ratio 1.08, 95% confidence interval 0.72–1.62; P = 0.71). The association with worse overall survival was maintained in subgroups based on method of hyperglycaemia measurement (subgroup difference P = 0.46) and stage (P = 0.14). Meta-regression showed a significantly greater magnitude of association between hyperglycaemia and decreased overall survival in studies with higher proportions of women and diabetic patients. Conclusions: Hyperglycaemia is associated with adverse overall survival and DFS in patients with cancer. The therapeutic role of glycaemic control in cancer patients warrants further investigation.
Published:
2018
Title:
Impact of Statins on Cardiovascular Outcomes Following Coronary Artery Calcium Scoring
Authors:
Mitchell, Joshua D.; Fergestrom, Nicole; Gage, Brian F.; Paisley, Robert; Moon, Patrick; Novak, Eric; Cheezum, Michael; Shaw, Leslee J.; Villines, Todd C.
Abstract:
![Figure][1]\textless/img\textgreater Background Compared with traditional risk factors, coronary artery calcium (CAC) scores improve prognostic accuracy for atherosclerotic cardiovascular disease (ASCVD) outcomes. However, the relative impact of statins on ASCVD outcomes stratified by CAC scores is unknown. Objectives The authors sought to determine whether CAC can identify patients most likely to benefit from statin treatment. Methods The authors identified consecutive subjects without pre-existing ASCVD or malignancy who underwent CAC scoring from 2002 to 2009 at Walter Reed Army Medical Center. The primary outcome was first major adverse cardiovascular event (MACE), a composite of acute myocardial infarction, stroke, and cardiovascular death. The effect of statin therapy on outcomes was analyzed stratified by CAC presence and severity, after adjusting for baseline comorbidities with inverse probability of treatment weights based on propensity scores. Results A total of 13,644 patients (mean age 50 years; 71% men) were followed for a median of 9.4 years. Comparing patients with and without statin exposure, statin therapy was associated with reduced risk of MACE in patients with CAC (adjusted subhazard ratio: 0.76, 95% confidence interval: 0.60 to 0.95; p = 0.015), but not in patients without CAC (adjusted subhazard ratio: 1.00, 95% confidence interval: 0.79 to 1.27; p = 0.99). The effect of statin use on MACE was significantly related to the severity of CAC (p \textless 0.0001 for interaction), with the number needed to treat to prevent 1 initial MACE outcome over 10 years ranging from 100 (CAC 1 to 100) to 12 (CAC \textgreater100). Conclusions In a largescale cohort without baseline ASCVD, the presence and severity of CAC identified patients most likely to benefit from statins for the primary prevention of cardiovascular diseases. [1]: pending:yes
Published:
2018
Title:
Impact of a 3-Months Vegetarian Diet on the Gut Microbiota and Immune Repertoire
Authors:
Zhang, Chenchen; Björkman, Andrea; Cai, Kaiye; Liu, Guilin; Wang, Chunlin; Li, Yin; Xia, Huihua; Sun, Lijun; Kristiansen, Karsten; Wang, Jun; Han, Jian; Hammarström, Lennart; Pan-Hammarström, Qiang
Abstract:
The dietary pattern can influence the immune system directly, but may also modulate it indirectly by regulating the gut microbiota. Here, we investigated the effect of a 3-months lacto-ovo-vegetarian diet on the diversity of gut microbiota and the immune system in healthy omnivorous volunteers, using high-throughput sequencing technologies. The short-term vegetarian diet did not have any major effect on the diversity of the immune system and the overall composition of the metagenome. The prevalence of bacterial genera/species with known beneficial effects on the intestine, including butyrate-producers and probiotic species and the balance of autoimmune-related variable genes/families were, however, altered in the short-term vegetarians. A number of bacterial species that are associated with the expression level of IgA, a key immunoglobulin class that protects the gastrointestinal mucosal system, were also identified. Furthermore, a lower diversity of T-cell repertoire and expression level of IgE, as well as a reduced abundance of inflammation-related genes in the gut microbiota were potentially associated with a control group with long-term vegetarians. Thus, the composition and duration of the diet may have an impact on the balance of pro-/anti-inflammatory factors in the gut microbiota and immune system.
Published:
2018
Title:
Impact of a vegan diet on the human salivary microbiota
Authors:
Hansen, Tue H.; Kern, Timo; Bak, Emilie G.; Kashani, Alireza; Allin, Kristine H.; Nielsen, Trine; Hansen, Torben; Pedersen, Oluf
Abstract:
Little is known about the effect of long-term diet patterns on the composition and functional potential of the human salivary microbiota. In the present study, we sought to contribute to the ongoing elucidation of dietary effects on the oral microbial community by examining the diversity, composition and functional potential of the salivary microbiota in 160 healthy vegans and omnivores using 16S rRNA gene amplicon sequencing. We further sought to identify bacterial taxa in saliva associated with host inflammatory markers. We show that compositional differences in the salivary microbiota of vegans and omnivores is present at all taxonomic levels below phylum level and includes upper respiratory tract commensals (e.g. Neisseria subflava, Haemophilus parainfluenzae, and Rothia mucilaginosa) and species associated with periodontal disease (e.g. Campylobacter rectus and Porphyromonas endodontalis). Dietary intake of medium chain fatty acids, piscine mono- and polyunsaturated fatty acids, and dietary fibre was associated with bacterial diversity, community structure, as well as relative abundance of several species-level operational taxonomic units. Analysis of imputed genomic potential revealed several metabolic pathways differentially abundant in vegans and omnivores indicating possible effects of macro- and micro-nutrient intake. We also show that certain oral bacteria are associated with the systemic inflammatory state of the host.
Published:
2018
Title:
Impact of red and processed meat and fibre intake on treatment outcomes among patients with chronic inflammatory diseases: Protocol for a prospective cohort study of prognostic factors and personalised medicine
Authors:
Christensen, R.; Heitmann, B.L.; Andersen, K.W.; Nielsen, O.H.; Sørensen, S.B.; Jawhara, M.; Bygum, A.; Hvid, L.; Grauslund, J.; Wied, J.; Glerup, H.; Fredberg, U.; Villadsen, J.A.; Kjær, Sø.G.; Fallingborg, J.; Moghadd, S.A.G.R.; Knudsen, T.; Brodersen, J.; Frøjk, J.; Dahlerup, J.F.; Bojesen, A.B.; Sorensen, G.L.; Thiel, S.; Færgeman, N.J.; Brandslund, I.; Bennike, T.B.; Stensballe, A.; Schmidt, E.B.; Franke, A.; Ellinghaus, D.; Rosenstiel, P.; Raes, J.; Boye, M.; Werner, L.; Nielsen, C.L.; Munk, H.L.; Nexøe, A.B.; Ellingsen, T.; Holmskov, U.; Kjeldsen, J.; Andersen, V.
Abstract:
Chronic inflammatory diseases (CIDs) are frequently treated with biological medications, specifically tumour necrosis factor inhibitors (TNFi)). These medications inhibit the pro-inflammatory molecule TNF alpha, which has been strongly implicated in the aetiology of these diseases. Up to one-third of patients do not, however, respond to biologics, and lifestyle factors are assumed to affect treatment outcomes. Little is known about the effects of dietary lifestyle as a prognostic factor that may enable personalised medicine. The primary outcome of this multidisciplinary collaborative study will be to identify dietary lifestyle factors that support optimal treatment outcomes. Methods and analysis This prospective cohort study will enrol 320 patients with CID who are prescribed a TNFi between June 2017 and March 2019. Included among the patients with CID will be patients with inflammatory bowel disease (Crohn's disease and ulcerative colitis), rheumatic disorders (rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis), inflammatory skin diseases (psoriasis, hidradenitis suppurativa) and non-infectious uveitis. At baseline (pretreatment), patient characteristics will be assessed using patient-reported outcome measures, clinical assessments of disease activity, quality of life and lifestyle, in addition to registry data on comorbidity and concomitant medication(s). In accordance with current Danish standards, follow-up will be conducted 14-16 weeks after treatment initiation. For each disease, evaluation of successful treatment response will be based on established primary and secondary endpoints, including disease-specific core outcome sets. The major outcome of the analyses will be to detect variability in treatment effectiveness between patients with different lifestyle characteristics. Ethics and dissemination The principle goal of this project is to improve the quality of life of patients suffering from CID by providing evidence to support dietary and other lifestyle recommendations that may improve clinical outcomes. The study is approved by the Ethics Committee (S-20160124) and the Danish Data Protecting Agency (2008-58-035). Study findings will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences. Trial registration number NCT03173144; Pre-results. © Article author(s) 2018.
Published:
2018
Title:
Implementing a low-carbohydrate, ketogenic diet to manage type 2 diabetes mellitus
Authors:
Westman, Eric C.; Tondt, Justin; Maguire, Emily; Yancy, William S.
Abstract:
INTRODUCTION: Type 2 diabetes mellitus (T2DM) has reached epidemic proportions in the modern world. For individuals affected by obesity-related T2DM, clinical studies have shown that carbohydrate restriction and weight loss can improve hyperglycemia, obesity, and T2DM. AREAS COVERED: Reducing carbohydrate intake to a certain level, typically below 50 g per day, leads to increased ketogenesis in order to provide fuel for the body. Such low-carbohydrate, ketogenic diets were employed to treat obesity and diabetes in the 19th and early 20th centuries. Recent clinical research has reinvigorated the use of the ketogenic diet for individuals with obesity and diabetes. Although characterized by chronic hyperglycemia, the underlying cause of T2DM is hyperinsulinemia and insulin resistance, typically as a result of increased energy intake leading to obesity. The ketogenic diet substantially reduces the glycemic response that results from dietary carbohydrate as well as improves the underlying insulin resistance. This review combines a literature search of the published science and practical guidance based on clinical experience. EXPERT COMMENTARY: While the current treatment of T2DM emphasizes drug treatment and a higher carbohydrate diet, the ketogenic diet is an effective alternative that relies less on medication, and may even be a preferable option when medications are not available.
Published:
2018
Title:
Incidence and Treatment of Patients Diagnosed With Inflammatory Bowel Diseases at 60 Years or Older in Sweden
Authors:
Everhov, Åsa H.; Halfvarson, Jonas; Myrelid, Pär; Sachs, Michael C.; Nordenvall, Caroline; Söderling, Jonas; Ekbom, Anders; Neovius, Martin; Ludvigsson, Jonas F.; Askling, Johan; Olén, Ola
Abstract:
BACKGROUND & AIMS: Diagnosis of inflammatory bowel diseases (IBD) is increasing among elderly persons (60 years or older). We performed a nationwide population-based study to estimate incidence and treatment of IBD. METHODS: We identified all incident IBD cases in Sweden from 2006 through 2013 using national registers and up to 10 matched population comparator subjects. We collected data on the patients' health care contacts and estimated incidence rates, health service burden, pharmacologic treatments, extra-intestinal manifestations, and surgeries in relation to age of IBD onset (pediatric, <18 years; adults, 18-59 years; elderly, ≥60 years). RESULTS: Of 27,834 persons diagnosed with incident IBD, 6443 (23%) had a first diagnosis of IBD at 60 years or older, corresponding to an incidence rate of 35/100,000 person-years (10/100,000 person-years for Crohn's disease, 19/100,000 person-years for ulcerative colitis, and 5/100,000 person-years for IBD unclassified). During a median follow-up period of 4.2 years (range, 0-9 years), elderly patients had less IBD-specific outpatient health care but more IBD-related hospitalizations and overall health care use than adult patients with IBD. Compared with patients with pediatric or adult-onset IBD, elderly patients used fewer biologics and immunomodulators but more systemic corticosteroids. Occurrence of extra-intestinal manifestations was similar in elderly and adult patients, but bowel surgery was more common in the elderly (13% after 5 years vs 10% in adults) (P
Published:
2018
Title:
Influence of blue mussel (Mytilus edulis) intake on disease activity in female patients with rheumatoid arthritis: The MIRA randomized cross-over dietary intervention
Authors:
Lindqvist, H.M.; Gjertsson, I.; Eneljung, T.; Winkvist, A.
Abstract:
Rheumatoid Arthritis (RA) is a chronic inflammatory disease. This study evaluates the effect of blue mussel intake on disease activity and quality of life in women with RA. Thirty-nine women with established RA and a disease activity score 28 (DAS28) >3.0 were recruited to a randomized 2 × 11-week cross-over dietary intervention. The participants continued with their medication and habitual diet and exchanged one cooked meal a day, five days a week, with a meal including 75 g blue mussels or 75 g meat. Diets were switched after an eight week washout period. Data regarding quality of life (SF-36), blood lipids, erythrocyte sediment rate (ESR), C-reactive protein (CRP) and tender and swollen joints were examined at the start and end of each dietary period. Thirty women completed one period, and twenty-three completed both. Intake of the blue mussel diet led to a significant reduction of DAS28-CRP (p = 0.048), but not DAS28. The number of EULAR (European League Against Rheumatism) criteria moderate and good responders were higher when consuming blue mussel diet (p = 0.036). Blood lipids did not change. To conclude, blue mussel intake reduced disease symptoms in women with RA and improved perceived health. The reported effects need to be confirmed by non-patient reported outcomes, such as inflammation markers. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.
Published:
2018
Title:
Influence of feeding moringa oleifera pods as phytogenic feed additive on performance, blood metabolites, chemical composition and bioactive compounds of breast meat in broiler
Authors:
Ahmad, S.; Khalique, A.; Pasha, T.N.; Mehmood, S.; Hussain, K.; Ahmad, S.; Rasheed, B.; Awais, M.M.; Bhatti, S.A.
Abstract:
This study was conducted to explore the effect of Moringa oleifera pods meal (MPM) on growth performance, blood metabolites, chemical composition, meat quality and immunity of broilers. For the purpose, two hundred (Hubbard classic) broiler birds having weight 40.4±3.02 g, were assigned to four treatments with five replicates and ten birds per replicate in a completely randomized design. Starter and finisher diets were added with four levels (0, 0.5, 1.0 and 1.5% of MPM) over and above. Results of this study showed that growth performance was improved as feed conversion ratio (FCR) and feed intake (FI) were decreased with the increase in supplementation level (P≤0.05). Dressing percentage was lowered, whereas giblet weights were improved with the MPM supplementation levels (P≤0.05). β-carotene, Quercetin and Selenium content of breast meat was linearly increased resulting in higher values of di-phenyl picryl hydrazil (DPPH) radical scavenging and improved shelf life. Serum biochemical compounds like serum glutamic pyruvic transaminase (SGPT), Creatinine, Glucose and meat cholesterol level was significantly decreased and was recorded lowest in 1.5% MPM supplemented diet (P≤0.05). At the end of the trial it was concluded that Moringa pods may positively affect the growth and chemical composition of broiler meat. © 2017, Veteriner Fakultesi Dergisi. All Rights Reserved.
Published:
2018
Title:
Influence of graded levels ofL-theanine dietary supplementation on growth performance, carcass traits, meat quality, organs histomorphometry, blood chemistry and immune response of broiler chickens
Authors:
Saeed, M.; Yatao, X.; Hassan, F.-U.; Arain, M.A.; Abd El-Hack, M.E.; Noreldin, A.E.; Sun, C.
Abstract:
L-theanine is a water-soluble non-proteinous amino acid mainly found in green tea leaves. Despite the availability of abundant literature on green tea, studies on the use ofL-theanine as a feed additive in animals, and especially broilers are limited. The objective of this study was, therefore, to evaluate the effect of different dietary levels ofL-theanine on meat quality, growth performance, immune response, and blood metabolites in broilers. A total of 400 day-old broiler chicks were randomly divided into four treatment groups using a completely randomized design; C-control, basal diet; 100LT-basal diet + 100 mgL-theanine/kg diet; 200LT-basal diet + 200 mgL-theanine/kg diet; and 300LT-basal diet + 300 mgL-theanine/kg diet. Results revealed that the intermediate level ofL-theanine (200 mg/kg diet) showed better results in terms of body weight gain (BWG), feed consumed (FC), and feed conversion ratio (FCR) as compared with the other supplemented groups and the control. The live weight eviscerated weight and gizzard weight were higher in allL-theanine levels as compared to those of the control group. Increased weight (p ≤ 0.05) of spleen and bursa were found in group 200LT (200 mgL-theanine/kg diet). Concerning meat color parameters, values for yellowness (b*), and redness (a*) were greater inL-theanine-supplemented groups than the control. Supplementing broiler diet withL-theanine reduced (p = 0.02) total serum cholesterol contents while increased HDL. Further analysis revealed lower relative serum cytokines (IL-2 and INF-γ) and reduced mRNA expression of TNF-α and IL-6 in thymus, and IFN-γ and IL-2 in spleen in the treated group. Moreover, supplementation with 200 mg/kg ofL-theanine improved antioxidant status in blood by increasing SOD, GSH-Px, and relative CAT levels. It is concluded that the optimum supplementation level ofL-theanine is 200 mg/kg of diet because it resulted in improved performance parameters in broilers. However, higher levels ofL-theanine (300 mg/kg diet) may have deleterious effects on performance and health of broiler chickens. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.
Published:
2018
Title:
Ingestion of an Inulin-Enriched Pork Sausage Product Positively Modulates the Gut Microbiome and Metabolome of Healthy Rats
Authors:
Thøgersen, R.; Castro-Mejía, J.L.; Sundekilde, U.K.; Hansen, L.H.; Hansen, A.K.; Nielsen, D.S.; Bertram, H.C.
Abstract:
Scope: Processed meat intake is associated with a potential increased colorectal cancer (CRC) risk. In contrast, dietary fiber consumption has been found to lower CRC risk, possibly via mechanisms involving the gut microbiota (GM) and its metabolites. This study investigates the effect of inulin enrichment of a common pork sausage product on GM composition and activity in healthy rats. Methods and results: Thirty Sprague-Dawley rats are fed a diet based on either an inulin-enriched sausage (n = 12), a corresponding control sausage without enrichment (n = 12), or a standard chow diet (n = 6) during a 4 week intervention. NMR-based metabolomics analyses are conducted on fecal and plasma samples, and GM composition is determined using 16S rRNA gene amplicon sequencing. Pronounced effects of diets on GM composition and activity are found. Rats fed the inulin-enriched sausages have increased levels of short chain fatty acids (SCFAs) in the fecal and plasma metabolome and increased fecal levels of Bifidobacterium spp. as compared to rats fed sausages without enrichment. Conclusion: Inulin enrichment of a meat product resembles general effects seen upon dietary fiber consumption and corroborates that healthier processed meats can be developed through strategic inclusion of dietary fiber ingredients. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Published:
2018
Title:
Insulin Resistance in HIV-Patients: Causes and Consequences
Authors:
Pedro, Marcelo N.; Rocha, Guilherme Z.; Guadagnini, Dioze; Santos, Andrey; Magro, Daniela O.; Assalin, Heloisa B.; Oliveira, Alexandre G.; Pedro, Rogerio de Jesus; Saad, Mario J. A.
Abstract:
Here we review how immune activation and insulin resistance contribute to the metabolic alterations observed in HIV-infected patients, and how these alterations increase the risk of developing CVD. The introduction and evolution of antiretroviral drugs ...
Published:
2018
Title:
Insulin sensitivity linked skeletal muscle Nr4a1 DNA methylation is programmed by the maternal diet and modulated by voluntary exercise in mice
Authors:
Kasch, Juliane; Kanzleiter, Isabel; Saussenthaler, Sophie; Schürmann, Annette; Keijer, Jaap; van Schothorst, Evert; Klaus, Susanne; Schumann, Sara
Abstract:
Perinatal maternal high-fat consumption is known to increase the obesity and type 2 diabetes susceptibility and to impair exercise performance in the offspring. We hypothesize that epigenetic modifications in the skeletal muscle are partly responsible for this phenotype. To detect skeletal muscle genes affected by maternal nutrition, male offspring of low-fat (LF) and high-fat (HF) diet fed dams (BL6 mice) received LF diet upon weaning and were sacrificed at 6 or 25 weeks of age. Gene expression of Musculus quadriceps was investigated by microarray analysis revealing an up-regulation of the nuclear receptor Nr4a1 by maternal HF feeding. This was accompanied by promoter hypomethylation of CpG-1408 which correlated with increased Nr4a1 gene expression at both ages. Offspring voluntary exercise training (by supplying running wheels from 7 to 25 weeks of age) normalized Nr4a1 methylation and gene expression respectively, and ameliorated the negative effects of maternal HF feeding on insulin sensitivity. Overall, Nr4a1 gene expression in skeletal muscle correlated with higher insulin levels during an oral glucose tolerance test and could, therefore, be involved in programming type 2 diabetes susceptibility in offspring exposed to perinatal high fat diet.
Published:
2018
Title:
Inter- and Intraspecific Variations in the Pectoral Muscles of Common Chimpanzees (Pan troglodytes), Bonobos (Pan paniscus), and Humans (Homo sapiens)
Authors:
Potau, J. M.; Arias-Martorell, J.; Bello-Hellegouarch, G.; Casado, A.; Pastor, J. F.; de Paz, F.; Diogo, R.
Abstract:
We have analyzed anatomic variations in the pectoralis major and pectoralis minor muscles of common chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) and compared them to anatomic variations in these muscles in humans (Homo sapiens). We have macroscopically dissected these muscles in six adult Pan troglodytes, five Pan paniscus of ages ranging from fetus to adult, and five adult Homo sapiens. Although Pan troglodytes are thought to lack a separate pectoralis abdominis muscle, we have identified this muscle in three of the Pan troglodytes; none of the Pan paniscus, however, had this muscle. We have also found deep supernumerary fascicles in the pectoralis major of two Pan troglodytes and all five Pan paniscus. In all six Pan troglodytes, the pectoralis minor was inserted at the supraspinatus tendon, while, in Pan paniscus and Homo sapiens, it was inserted at the coracoid process of the scapula. Some of the anatomic features and variations of these muscles in common chimpanzees and bonobos are similar to those found in humans, therefore enhancing our knowledge of primate comparative anatomy and evolution and also shedding light on several clinical issues.
Published:
2018
Title:
Interaction Between Nutrition and Metabolism
Authors:
Barrouin-Melo, Stella Maria; Morejón Terán, Yadira Alejandra; Anturaniemi, Johanna; Hielm-Björkman, Anna Katrina
Abstract:
Diet plays a fundamental role in the nutritional status, in the homeostasis and in the capacity of an individual to adapt to the environment. A proper or an inadequate nutrition has an impact on the persistence, remission and incidence of various conditions, including the infectious diseases. Consequently, nutrition has a crucial importance on survival rates and health recovery of individuals or even populations around the globe. The synergistic relationship between nutritional needs and infectious processes has been demonstrated conclusively in diverse studies. This chapter will discuss the most important nutrients, their most common natural dietary sources, the different digestive processes for each one as well as the absorption, transport, storage, excretion and function of each of the nutrients within the organism. We also go through some concepts on the interaction between nutrition and the immune system, as well as examples on the influence of nutrition or specific nutrients on some infectious diseases, and their influence on the gene expression.
Published:
2018
Title:
Intermittent metabolic switching, neuroplasticity and brain health
Authors:
Mattson, Mark P.; Moehl, Keelin; Ghena, Nathaniel; Schmaedick, Maggie; Cheng, Aiwu
Abstract:
During evolution, individuals whose brains and bodies functioned well in a fasted state were successful in acquiring food, enabling their survival and reproduction. With fasting and extended exercise, liver glycogen stores are depleted and ketones are produced from adipose-cell-derived fatty acids. This metabolic switch in cellular fuel source is accompanied by cellular and molecular adaptations of neural networks in the brain that enhance their functionality and bolster their resistance to stress, injury and disease. Here, we consider how intermittent metabolic switching, repeating cycles of a metabolic challenge that induces ketosis (fasting and/or exercise) followed by a recovery period (eating, resting and sleeping), may optimize brain function and resilience throughout the lifespan, with a focus on the neuronal circuits involved in cognition and mood. Such metabolic switching impacts multiple signalling pathways that promote neuroplasticity and resistance of the brain to injury and disease.
Published:
2018
Title:
Joint associations of sauna bathing and cardiorespiratory fitness on cardiovascular and all-cause mortality risk: a long-term prospective cohort study
Authors:
Kunutsor, Setor K.; Khan, Hassan; Laukkanen, Tanjaniina; Laukkanen, Jari A.
Abstract:
© 2017 Informa UK Limited, trading as Taylor & Francis Group. Purpose: We aimed to evaluate the joint impact of cardiorespiratory fitness (CRF) and frequency of sauna bathing (FSB) on the risk of cardiovascular and all-cause mortality. Design: CRF measured by respiratory gas analyses and sauna exposure were assessed at baseline in a prospective study of 2277 men. CRF was categorized as low and high (median cut-offs) and FSB as low and high (≤2 and 3–7 sessions/week, respectively). Results: During a median follow-up of 26.1 years, 520 cardiovascular and 1124 all-cause deaths occurred. Comparing high versus low CRF, the multivariate-adjusted hazard ratios (HRs) 95% CIs for cardiovascular and all-cause mortality were 0.51 (0.41–0.63) and 0.65 (0.57–0.75), respectively. Comparing high versus low FSB, the corresponding HRs were 0.74 (0.59–0.94) and 0.84 (0.72–0.97), respectively. Compared to low CRF & low FSB, the HRs of CVD mortality for high CRF & high FSB; high CRF & low FSB; and low CRF & high FSB were 0.42 (0.28–0.62), 0.50 (0.39–0.63) and 0.72 (0.54–0.97), respectively. For all-cause mortality, the corresponding HRs were 0.60 (0.48–0.76), 0.63 (0.54–0.74) and 0.78 (0.64–0.96), respectively. Conclusions: A combination of high CRF and frequent sauna bathing confers stronger long-term protection on mortality outcomes compared with high CRF or high FSB alone.KEY MESSAGES Cardiorespiratory fitness (CRF) and frequency of sauna bathing are independently associated with reduced mortality risk; a combination of good CRF and frequent sauna bathing may confer additional survival benefits. In a population-based prospective cohort study, a combination of high CRF levels and frequent sauna bathing (3–7 sessions per week) was associated with a substantial risk reduction in fatal cardiovascular and all-cause mortality events compared with good CRF or frequent sauna bathing alone. A combination of good fitness levels produced by aerobic exercises and frequent sauna bathing may have added health benefits and confer more protection on the risk of mortality.
Published:
2018
Title:
Keto-adaptation enhances exercise performance and body composition responses to training in endurance athletes
Authors:
McSwiney, Fionn T.; Wardrop, Bruce; Hyde, Parker N.; Lafountain, Richard A.; Volek, Jeff S.; Doyle, Lorna
Abstract:
Background Low-carbohydrate diets have recently grown in popularity among endurance athletes, yet little is known about the long-term (\textgreater 4 wk) performance implications of consuming a low-carbohydrate high fat ketogenic diet (LCKD) in well-trained athletes. Methods Twenty male endurance-trained athletes (age 33 ± 11 y, body mass 80 ± 11 kg; BMI 24.7 ± 3.1 kg/m2) who habitually consumed a carbohydrate-based diet, self-selected into a high-carbohydrate (HC) group (n = 11, %carbohydrate:protein:fat = 65:14:20), or a LCKD group (n = 9, 6:17:77). Both groups performed the same training intervention (endurance, strength and high intensity interval training (HIIT)). Prior to and following successful completion of 12-weeks of diet and training, participants had their body composition assessed, and completed a 100 km time trial (TT), six second (SS) sprint, and a critical power test (CPT). During post-intervention testing the HC group consumed 30–60 g/h carbohydrate, whereas the LCKD group consumed water, and electrolytes. Results The LCKD group experienced a significantly greater decrease in body mass (HC − 0.8 kg, LCKD − 5.9 kg; P = 0.006, effect size (ES): 0.338) and percentage body fat percentage (HC − 0.7%, LCKD − 5.2%; P = 0.008, ES: 0.346). Fasting serum beta-hydroxybutyrate (βHB) significantly increased from 0.1 at baseline to 0.5 mmol/L in the LCKD group (P = 0.011, ES: 0.403) in week 12. There was no significant change in performance of the 100 km TT between groups (HC − 1.13 min·s, LCKD − 4.07 min·s, P = 0.057, ES: 0.196). SS sprint peak power increased by 0.8 watts per kilogram bodyweight (w/kg) in the LCKD group, versus a − 0.1 w/kg reduction in the HC group (P = 0.025, ES: 0.263). CPT peak power decreased by − 0.7 w/kg in the HC group, and increased by 1.4 w/kg in the LCKD group (P = 0.047, ES: 0.212). Fat oxidation in the LCKD group was significantly greater throughout the 100 km TT. Conclusions Compared to a HC comparison group, a 12-week period of keto-adaptation and exercise training, enhanced body composition, fat oxidation during exercise, and specific measures of performance relevant to competitive endurance athletes.
Published:
2018
Title:
Ketogenic Diet Modulates NAD+-Dependent Enzymes and Reduces DNA Damage in Hippocampus
Authors:
Elamin, Marwa; Ruskin, David N.; Masino, Susan A.; Sacchetti, Paola
Abstract:
The ketogenic diet's (KD) anti-seizure effects have long been documented. Recently, its therapeutic potential in multiple neurodegenerative and neurodevelopmental disorders has emerged. Yet experimental evidence for a fundamental mechanism underlying beneficial effects across numerous diseases remains lacking. We previously showed that feeding rats a KD produced an early (within 2 days) and persistent elevation of hippocampal nicotinamide adenine dinucleotide+ (NAD+), an essential metabolic coenzyme and signaling molecule. NAD+ is a marker of cellular health and a substrate for enzymes implicated in longevity and DNA damage repair such as sirtuins and poly-ADP ribose polymerase-1 (PARP-1). As a result, activation of NAD+-dependent enzymes' downstream pathways could be the origin of KD's broad beneficial effects. Here rats were fed ad libitum regular chow or KD for 2 days or 3 weeks and the levels of hippocampal sirtuins, PARP-1, and the oxidative DNA damage marker 8-hydroxy-2'-deoxyguanosine were quantified. We found a significant immediate and persistent increase in the collective activity of nuclear sirtuin enzymes, and a significant augmentation of Sirt1 mRNA at 2 days. Levels of PARP-1 and 8-hydroxy-2'-deoxyguanosine decreased after 2 days of treatment and further declined at 3 weeks. Our data show that a KD can rapidly modulate energy metabolism by acting on NAD+-dependent enzymes and their downstream pathways. Thus, therapy with a KD can potentially enhance brain health and increase overall healthspan via NAD+-related mechanisms that render cells more resilient against DNA damage and a host of metabolic, epileptic, neurodegenerative, or neurodevelopmental insults.
Published:
2018
Title:
Ketogenic Diet Therapy in Infants: Efficacy and Tolerability
Authors:
Wirrell, Elaine; Eckert, Susan; Wong-Kisiel, Lily; Payne, Eric; Nickels, Katherine
Abstract:
PURPOSE: This study evaluated tolerability and efficacy of the ketogenic diet in infants less than 12 months of age. METHODS: Infants less than 12 months of age, commencing the ketogenic diet between September 2007 and July 2016 were identified. Records were reviewed for epilepsy details, diet initiation details, efficacy and tolerability. RESULTS: Twenty-seven infants commenced the ketogenic diet (56% male, median age seven months). Median age at seizure onset was 1.9 months and 92% had daily seizures. An epilepsy syndrome was noted in 19 (West-11, epilepsy in infancy with migrating focal seizures-5, early myoclonic encephalopathy-1, Ohtahara-1, Dravet-1). Infants were on a median of two and had failed a median of one medications for lack of efficacy. All initiated a traditional ketogenic diet at full calories without fasting, and all but one started the diet in hospital. Significant hypoglycemia during initiation was seen in two - both had emesis +/- decreased oral intake. Eighty-eight percent developed urinary ketosis by 48 hours and all were successfully discharged on the diet (median ratio 3:1). Of those continuing dietary therapy, responder rates at one, six and 12 months were 68%, 82% and 91%, with 20%, 29% and 27% achieving seizure freedom. By 12 months, two stopped the diet for serious adverse effects, five discontinued for lack of efficacy, six were lost to follow-up and two died of unrelated causes. CONCLUSIONS: The ketogenic diet is an effective and well-tolerated treatment for infants with intractable epilepsy. In-hospital initiation is strongly recommended due to risk of hypoglycemia with emesis or reduced intake.
Published:
2018
Title:
Leptin as a breast milk component for the prevention of obesity
Authors:
Palou, Mariona; Picó, Catalina; Palou, Andreu
Abstract:
Leptin ingested as a component of breast milk is increasingly recognized to play a role in the postnatal programming of a healthy phenotype in adulthood. Besides its primary function in controlling body weight, leptin may be an essential nutrient required during lactation to ensure that the system controlling fat accumulation and body composition is well organized from the early stages of development. This review delves into the following topics: (1) the imprinted protective function of adequate leptin intake during lactation in future metabolic health; (2) the consequences of a lack of leptin intake or of alterations in leptin levels; and (3) the mechanisms described for the effects of leptin on postnatal programming. Furthermore, it highlights the importance of breastfeeding and the need to establish optimal or reference intake values for leptin during lactation to design patterns of personalized nutrition from early childhood.
Published:
2018
Title:
Lifestyle risk prediction model for prostate cancer in a Korean population
Authors:
Kim, S.H.; Kim, S.; Joung, J.Y.; Kwon, W.-A.; Seo, H.K.; Chung, J.; Nam, B.-H.; Lee, K.H.
Abstract:
Purpose The use of prostate-specific antigen as a biomarker for prostate cancer (PC) has been controversial and is, therefore, not used by many countries in their national health screening programs. The biological characteristics of PC in East Asians including Koreans and Japanese are different from those in the Western populations. Potential lifestyle risk factors for PC were evaluated with the aim of developing a risk prediction model. Materials and Methods A total of 1,179,172 Korean men who were cancer free from 1996 to 1997, had taken a physical examination, and completed a lifestyle questionnaire, were enrolled in our study to predict their risk for PC for the next eight years, using the Cox proportional hazards model. The model's performance was evaluated using the C-statistic and Hosmer-Lemeshow type chi-square statistics. Results The risk prediction model studied age, height, body mass index, glucose levels, family history of cancer, the frequency of meat consumption, alcohol consumption, smoking status, and physical activity, which were all significant risk factors in a univariate analysis. The model performed very well (C statistic, 0.887; 95% confidence interval, 0.879 to 0.895) and estimated an elevated PC risk in patients who did not consume alcohol or smoke, compared to heavy alcohol consumers (hazard ratio [HR], 0.78) and current smokers (HR, 0.73) (p
Published:
2018
Title:
Linking Glycation and Glycosylation With Inflammation and Mitochondrial Dysfunction in Parkinson’s Disease
Authors:
Videira, Paula A. Q.; Castro-Caldas, Margarida
Abstract:
Parkinson’s disease (PD) is the second most common neurodegenerative disorder, affecting about 6.3 million people worldwide. PD is characterized by the progressive degeneration of dopaminergic neurons in the Substantia nigra pars compacta, resulting into severe motor symptoms. The cellular mechanisms underlying dopaminergic cell death in PD are still not fully understood, but mitochondrial dysfunction, oxidative stress and inflammation are strongly implicated in the pathogenesis of both familial and sporadic PD cases. Aberrant post-translational modifications, namely glycation and glycosylation, together with age-dependent insufficient endogenous scavengers and quality control systems, lead to cellular overload of dysfunctional proteins. Such injuries accumulate with time and may lead to mitochondrial dysfunction and exacerbated inflammatory responses, culminating in neuronal cell death. Here, we will discuss how PD-linked protein mutations, aging, impaired quality control mechanisms and sugar metabolism lead to up-regulated abnormal post-translational modifications in proteins. Abnormal glycation and glycosylation seem to be more common than previously thought in PD and may underlie mitochondria-induced oxidative stress and inflammation in a feed-forward mechanism. Moreover, the stress-induced post-translational modifications that directly affect parkin and/or its substrates, deeply impairing its ability to regulate mitochondrial dynamics or to suppress inflammation will also be discussed. Together, these represent still unexplored deleterious mechanisms implicated in neurodegeneration in PD, which may be used for a more in-depth knowledge of the pathogenic mechanisms, or as biomarkers of the disease.
Published:
2018
Title:
Lipoprotein-associated phospholipase A₂ activity is increased in patients with definite familial hypercholesterolemia compared with other forms of hypercholesterolemia
Authors:
Mattina, A.; Rosenbaum, D.; Bittar, R.; Bonnefont-Rousselot, D.; Noto, D.; Averna, M.; Bruckert, E.; Giral, P.
Abstract:
BACKGROUND AND AIM: Lipoprotein-associated phospholipase A2 (Lp-PLA2) plays a key role in atherosclerosis development. It is considered a marker of increased risk of cardiovascular disease (CVD) and plaque vulnerability. Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated plasma levels of low-density lipoprotein cholesterol and a higher prevalence of early CVD. Our aim was to evaluate the differences in Lp-PLA2 activity in a population of hypercholesterolemic patients with and without definite FH. METHODS AND RESULTS: Hypercholesterolemic patients were consecutively recruited. Definite FH was defined according to Dutch Lipid Clinic Network criteria ≥8. All patients underwent routine clinical examination and biological assessments and Lp-PLA2 activity was measured in blood samples. Among 469 patients, 118 had a definite diagnosis of FH. Lp-PLA2 activity was significantly higher in definite FH patients compared to non-definite FH patients (206.5 ± 54.5 vs. 180.8 ± 48.4 nmol/min/mL, p
Published:
2018
Title:
Longitudinal associations of sauna bathing with inflammation and oxidative stress: the KIHD prospective cohort study
Authors:
Kunutsor, Setor K.; Laukkanen, Tanjaniina; Laukkanen, Jari A.
Abstract:
Purpose: We sought to determine cross-sectional and longitudinal associations of frequency of sauna bathing with high sensitivity C-reactive protein (hsCRP), fibrinogen, leucocyte count and gamma-glutamyltransferase (GGT).Design: Baseline sauna bathing habits were assessed in 2269 men aged 42-61 years. Concentrations of hsCRP, fibrinogen, leucocyte count, and GGT were determined at baseline and 11 years later. The associations of sauna bathing frequency with baseline and 11-year hsCRP, fibrinogen, leucocyte count, and GGT levels were examined using robust multivariate regression analyses.Results: In baseline analysis, 4-7 sauna sessions/week (compared with 1 sauna session/week) was associated with -0.84mg/l (95% CI, -1.55, -0.14; p=.019) lower hsCRP; -0.07g/l (95% CI, -0.15, 0.02; p=.112) lower fibrinogen; and -0.28x10(9)/l (95% CI, -0.51, -0.06; p=.015) lower leucocyte count, after multivariable adjustment. In longitudinal analysis, the corresponding estimates were -1.66mg/l (95% CI, -3.13, -0.19; p=.027); -0.16g/l (95% CI, -0.31, -0.02; p=.031); and -0.49x10(9)/l (95% CI, -0.85, -0.14; p=.007) respectively. Sauna bathing frequency was not associated with GGT at baseline and 11 years.Conclusion: Observational evidence supports the hypothesis that reduction in inflammation may be one of the pathways linking frequent sauna bathing with decreased risk of acute and chronic disease conditions.KEY MESSAGESCross-sectional evidence or short-term studies suggest Finnish sauna bathing may exert its beneficial health effects via reduction in inflammation and oxidative stress; however, the long-term effects of sauna bathing on these outcomes are uncertain.In this population-based prospective cohort study, frequent sauna sessions significantly decreased levels of inflammatory markers at baseline and 11-year follow-up; but had no effect on oxidative stress.The health benefits of sauna bathing may in part be mediated via reduced systemic inflammation.
Published:
2018
Title:
Loss of Metabolic Flexibility in the Failing Heart
Authors:
Karwi, Qutuba G.; Uddin, Golam M.; Ho, Kim L.; Lopaschuk, Gary D.
Abstract:
To maintain its high energy demand the heart is equipped with a highly complex and efficient enzymatic machinery that orchestrates ATP production using multiple energy substrates, namely fatty acids, carbohydrates (glucose and lactate), ketones and amino acids. The contribution of these individual substrates to ATP production can dramatically change, depending on such variables as substrate availability, hormonal status and energy demand. This “metabolic flexibility” is a remarkable virtue of the heart, which allows utilization of different energy substrates at different rates to maintain contractile function. In heart failure, cardiac function is reduced, which is accompanied by discernible energy metabolism perturbations and impaired metabolic flexibility. While it is generally agreed that overall mitochondrial ATP production is impaired in the failing heart, there is less consensus as to what actual switches in energy substrate preference occur. The failing heart shift towards a greater reliance on glycolysis and ketone body oxidation as a source of energy, with a decrease in the contribution of glucose oxidation to mitochondrial oxidative metabolism. The heart also becomes insulin resistant. However, there is less consensus as to what happens to fatty acid oxidation in heart failure. While it is generally believed that fatty acid oxidation decreases, a number of clinical and experimental studies suggest that fatty acid oxidation is either not changed or is increased in heart failure. Of importance, is that any metabolic shift that does occur has the potential to aggravate cardiac dysfunction and the progression of the heart failure. An increasing body of evidence shows that increasing cardiac ATP production and/or modulating cardiac energy substrate preference positively correlates with heart function and can lead to better outcomes. This includes increasing glucose and ketone oxidation and decreasing fatty acid oxidation. In this review we present the physiology of the energy metabolism pathways in the heart and the changes that occur in these pathways in heart failure. We also look at the interventions which are aimed at manipulating the myocardial metabolic pathways toward more efficient substrate utilization which will eventually improve cardiac performance.
Published:
2018
Title:
Low-Calorie Vegetarian Versus Mediterranean Diets for Reducing Body Weight and Improving Cardiovascular Risk Profile: CARDIVEG Study (Cardiovascular Prevention With Vegetarian Diet)
Authors:
Sofi, Francesco; Dinu, Monica; Pagliai, Giuditta; Cesari, Francesca; Gori, Anna Maria; Sereni, Alice; Becatti, Matteo; Fiorillo, Claudia; Marcucci, Rossella; Casini, Alessandro
Abstract:
BACKGROUND: Only a few randomized dietary intervention studies that investigated the effects of lacto-ovo vegetarian diet (Vd) in clinically healthy omnivorous subjects are available. METHODS: We randomly assigned to overweight omnivores with a low-to-moderate cardiovascular risk profile a low-calorie Vd compared with a low-calorie Mediterranean diet (MD), each lasting 3 months, with a crossover design. The primary outcome was the difference in body weight, body mass index, and fat mass changes between the 2 groups. Secondary outcomes were differences in circulating cardiovascular disease risk parameters changes between the 2 groups. RESULTS: One hundred eighteen subjects (mean age: 51.1 years, females: 78%) were enrolled. The total participation rate at the end of the study was 84.7%. No differences between the 2 diets in body weight were observed, as reported by similar and significant reductions obtained by both Vd (-1.88 kg) and MD (-1.77 kg). Similar results were observed for body mass index and fat mass. In contrast, significant differences between the 2 interventions were obtained for low-density lipoprotein cholesterol, triglycerides, and vitamin B12 levels. The difference between the Vd and MD groups, in terms of end-of-diet values, was recorded at 9.10 mg/dL for low-density lipoprotein cholesterol (P=0.01), 12.70 mg/dL for triglycerides (P<0.01), and 32.32 pg/mL for vitamin B12 (P
Published:
2018
Title:
Lower C-reactive protein and IL-6 associated with vegetarian diets are mediated by BMI
Authors:
Jaceldo-Siegl, K.; Haddad, E.; Knutsen, S.; Fan, J.; Lloren, J.; Bellinger, D.; Fraser, G. E.
Abstract:
BACKGROUND AND AIMS: The mechanism by which vegetarian diets are associated with less inflammation is not clear. We investigated the role of BMI as a mediator in the relationship between vegetarian diet and concentrations of C-reactive protein (CRP), and the cytokines IL-6, IL-10 and TNF-α. METHODS AND RESULTS: We used data from participants of the Adventist Health Study 2 (AHS-2) Calibration (n = 893) and Biological Manifestations of Religion (n = 478) sub-studies. Vegetarian diet variations were determined based on reported intake of animal products assessed by FFQ. Combining all participants, the proportion of non-vegetarians (NVs), partial vegetarians (PVs), lacto-ovo vegetarians (LOVs), and strict vegetarians (SVs) was 44%, 16%, 31%, and 9%, respectively. NV and PV participants were older than other dietary groups, and non-vegetarians had the highest BMI. Mediation analyses supported the mediating effect of BMI in associations of vegetarian diet with CRP (p < 0.001 each for PV, LOV and SV), and with IL-6 (p
Published:
2018
Title:
Macrophage-Associated PGK1 Phosphorylation Promotes Aerobic Glycolysis and Tumorigenesis
Authors:
Zhang, Yajuan; Yu, Guanzhen; Chu, Huiying; Wang, Xiongjun; Xiong, Lingling; Cai, Guoqing; Liu, Ruilong; Gao, Hong; Tao, Bangbao; Li, Wenfeng; Li, Guohui; Liang, Ji; Yang, Weiwei
Abstract:
Macrophages are a dominant leukocyte population in the tumor microenvironment and actively promote cancer progression. However, the molecular mechanism underlying the role of macrophages remains poorly understood. Here we show that polarized M2 macrophages enhance 3-phosphoinositide-dependent protein kinase 1 (PDPK1)-mediated phosphoglycerate kinase 1 (PGK1) threonine (T) 243 phosphorylation in tumor cells by secreting interleukin-6 (IL-6). This phosphorylation facilitates a PGK1-catalyzed reaction toward glycolysis by altering substrate affinity. Inhibition of PGK1 T243 phosphorylation or PDPK1 in tumor cells or neutralization of macrophage-derived IL-6 abrogates macrophage-promoted glycolysis, proliferation, and tumorigenesis. In addition, PGK1 T243 phosphorylation correlates with PDPK1 activation, IL-6 expression, and macrophage infiltration in human glioblastoma multiforme (GBM). Moreover, PGK1 T243 phosphorylation also correlates with malignance and prognosis of human GBM. Our findings demonstrate a novel mechanism of macrophage-promoted tumor growth by regulating tumor cell metabolism, implicating the therapeutic potential to disrupt the connection between macrophages and tumor cells by inhibiting PGK1 phosphorylation.
Published:
2018
Title:
Madelung's disease – progressive, excessive, and symmetrical deposition of adipose tissue in the subcutaneous layer: Case report and literature review
Authors:
Szewc, Monika; Sitarz, Robert; Moroz, Nina; Maciejewski, Ryszard; Wierzbicki, Ryszard
Abstract:
Madelung's disease is a rare disorder described for the first time in the year 1846 by Brodie. It is characterized by the occurrence of progressive, excessive, and symmetrical deposits of adipose tissue in the subcutaneous layer. Most often, these changes concern the neck, the nape of the neck, arms, and upper back, giving the patients a specific, pseudoathletic appearance. Madelung's disease is also known as multiple symmetrical lipomatosis, benign symmetrical lipomatosis, and Launois-Bensaude syndrome. The most commonly affected ones are men who drink alcohol in excessive amounts. The fat masses emerging in the course of the disease are painless but can lead to adverse repercussions. Patients may experience dysphagia, dysphonia, difficulty in breathing, and limited mobility of the neck. The reasons for the willingness to take up treatment are also often esthetic reasons. The disease is usually accompanied by numerous metabolic disorders. The etiology of the disease has not been sufficiently explained so far, which creates diagnostic and therapeutic difficulties. Currently used treatment is limited to surgical resection of the resulting lesions or liposuction. Unfortunately, the effectiveness of these activities is limited. Most patients experience recurrence after treatment. This paper discusses the essence of Madelung's disease, numerous aspects of etiology, the manner of diagnosis, and treatment based on current literature data.
Published:
2018
Title:
Management of Glioblastoma Multiforme in a Patient Treated With Ketogenic Metabolic Therapy and Modified Standard of Care: A 24-Month Follow-Up
Authors:
Elsakka, Ahmed M. A.; Bary, Mohamed Abdel; Abdelzaher, Eman; Elnaggar, Mostafa; Kalamian, Miriam; Mukherjee, Purna; Seyfried, Thomas N.
Abstract:
Few advances have been made in overall survival for glioblastoma multiforme (GBM) in more than 40 years. Here, we report the case of a 38-year-old man who presented with chronic headache, nausea, and vomiting accompanied by left partial motor seizures and upper left limb weakness. Enhanced brain magnetic resonance imaging revealed a solid cystic lesion in the right partial space suggesting GBM. Serum testing revealed vitamin D deficiency and elevated levels of insulin and triglycerides. Prior to subtotal tumor resection and standard of care (SOC), the patient conducted a 72-h water-only fast. Following the fast, the patient initiated a vitamin/mineral-supplemented ketogenic diet (KD) for 21 days that delivered 900 kcal/day. In addition to radiotherapy, temozolomide chemotherapy, and the KD (increased to 1,500 kcal/day at day 22), the patient received metformin (1,000 mg/day), methylfolate (1,000 mg/day), chloroquine phosphate (150 mg/day), epigallocatechin gallate (400 mg/day), and hyperbaric oxygen therapy (HBOT) (60 min/session, 5 sessions/week at 2.5 ATA). The patient also received levetiracetam (1,500 mg/day). No steroid medication was given at any time. Post-surgical histology confirmed the diagnosis of GBM. Reduced invasion of tumor cells and thick-walled hyalinized blood vessels were also seen suggesting a therapeutic benefit of pre-surgical metabolic therapy. After 9 months treatment with the modified SOC and complimentary ketogenic metabolic therapy (KMT), the patient's body weight was reduced by about 19%. Seizures and left limb weakness resolved. Biomarkers showed reduced blood glucose and elevated levels of urinary ketones with evidence of reduced metabolic activity (choline/N-acetylaspartate ratio) and normalized levels of insulin, triglycerides, and vitamin D. This is the first report of confirmed GBM treated with a modified SOC together with KMT and HBOT, and other targeted metabolic therapies. As rapid regression of GBM is rare following subtotal resection and SOC alone, it is possible that the response observed in this case resulted in part from the modified SOC and other novel treatments. Additional studies are needed to validate the efficacy of KMT administered with alternative approaches that selectively increase oxidative stress in tumor cells while restricting their access to glucose and glutamine. The patient remains in excellent health (Karnofsky Score, 100%) with continued evidence of significant tumor regression.
Published:
2018
Title:
Management of Type 1 Diabetes With a Very Low-Carbohydrate Diet
Authors:
Lennerz, Belinda S.; Barton, Anna; Bernstein, Richard K.; Dikeman, R. David; Diulus, Carrie; Hallberg, Sarah; Rhodes, Erinn T.; Ebbeling, Cara B.; Westman, Eric C.; Yancy, William S.; Ludwig, David S.
Abstract:
OBJECTIVES: To evaluate glycemic control among children and adults with type 1 diabetes mellitus (T1DM) who consume a very low-carbohydrate diet (VLCD). METHODS: We conducted an online survey of an international social media group for people with T1DM who follow a VLCD. Respondents included adults and parents of children with T1DM. We assessed current hemoglobin A1c (HbA1c) (primary measure), change in HbA1c after the self-reported beginning of the VLCD, total daily insulin dose, and adverse events. We obtained confirmatory data from diabetes care providers and medical records. RESULTS: Of 316 respondents, 131 (42%) were parents of children with T1DM, and 57% were of female sex. Suggestive evidence of T1DM (based on a 3-tier scoring system in which researchers took into consideration age and weight at diagnosis, pancreatic autoimmunity, insulin requirement, and clinical presentation) was obtained for 273 (86%) respondents. The mean age at diagnosis was 16 ± 14 years, the duration of diabetes was 11 ± 13 years, and the time following a VLCD was 2.2 ± 3.9 years. Participants had a mean daily carbohydrate intake of 36 ± 15 g. Reported mean HbA1c was 5.67% ± 0.66%. Only 7 (2%) respondents reported diabetes-related hospitalizations in the past year, including 4 (1%) for ketoacidosis and 2 (1%) for hypoglycemia. CONCLUSIONS: Exceptional glycemic control of T1DM with low rates of adverse events was reported by a community of children and adults who consume a VLCD. The generalizability of these findings requires further studies, including high-quality randomized controlled trials.
Published:
2018
Title:
Management of Type 1 Diabetes With a Very Low–Carbohydrate Diet: A Word of Caution
Authors:
Mayer-Davis, Elizabeth J.; Laffel, Lori M.; Buse, John B.
Abstract:
The public often looks to nutrition to improve health, and reporting on nutrition findings from the scientific literature in the popular media often reveals unproven benefits.1 Lennerz et al2 present data collected via an online community and conclude that exceptional glycemic control in type 1 diabetes with a low risk for adverse events is possible with a VLCD, and research is needed to confirm the generalizability of these findings. Although it may be true that a VLCD can be useful, we find the study of Lennerz et al to fall well short of the level of scientific evidence that merits \ldots E-mail: mayerdav{at}email.unc.edu
Published:
2018
Title:
Manuka honey synergistically enhances the chemopreventive effect of 5-fluorouracil on human colon cancer cells by inducing oxidative stress and apoptosis, altering metabolic phenotypes and suppressing metastasis ability
Authors:
Afrin, Sadia; Giampieri, Francesca; Forbes-Hernández, Tamara Y.; Gasparrini, Massimiliano; Amici, Adolfo; Cianciosi, Danila; Quiles, Josè L.; Battino, Maurizio
Abstract:
The development of chemo-sensitizers is urgently needed to overcome 5-fluorouracil (5-FU) therapeutic resistance and adverse toxicity in colorectal cancer. This work aims to evaluate the synergic effects of 5-FU and Manuka honey (MH), a rich source of bioactive compounds, in enhancing the anticancer effects of this drug on human colon cancer HCT-116 and LoVo cells. Compared to 5-FU alone, MH synergistically enhanced the chemotherapeutic effects of 5-FU, by reducing cell proliferation through the suppression of EGFR, HER2, p-Akt and p-mTOR expression, and promoting apoptosis by the modulation pro-apoptotic (p53, Bax, Cyto c, FasL caspase-3, -8, -9 and cleave-PARP) and anti-apoptotic (Bcl-2) markers. The activations of p-p38MAPK and p-Erk1/2 pathways and ROS production were also involved in this process. Downregulation of transcription factor (NF-κB and Nrf2) and antioxidant enzyme activity (SOD, catalase, glutathione peroxidase and glutathione reductase) and expression (SOD, catalase and HO-1) were more evident after the combined treatment, leading to more cell death by oxidative stress. Moreover, additive effects were also observed by increasing lipid and protein oxidation and arresting cell cycle. All the parameters of mitochondrial respiration and glycolysis function decreased and both cells entered the quiescent stage after the combined treatments. MH also influenced the anti-metastasis effects of 5-FU by decreasing migration ability, suppressing the expression of MMP-2, MMP-9 and increasing N-cadherin and E-cadherin. In conclusion, MH could be a useful preventive or adjuvant agent in the treatment of colorectal cancer with 5-FU.
Published:
2018
Title:
Mechanisms of action for the medium-chain triglyceride ketogenic diet in neurological and metabolic disorders
Authors:
Augustin, Katrin; Khabbush, Aziza; Williams, Sophie; Eaton, Simon; Orford, Michael; Cross, J. Helen; Heales, Simon J.R.; Walker, Matthew C.; Williams, Robin S.B.
Abstract:
High-fat, low-carbohydrate diets, known as ketogenic diets, have been used as a non-pharmacological treatment for refractory epilepsy. A key mechanism of this treatment is thought to be the generation of ketones, which provide brain cells (neurons and astrocytes) with an energy source that is more efficient than glucose, resulting in beneficial downstream metabolic changes, such as increasing adenosine levels, which might have effects on seizure control. However, some studies have challenged the central role of ketones because medium-chain fatty acids, which are part of a commonly used variation of the diet (the medium-chain triglyceride ketogenic diet), have been shown to directly inhibit AMPA receptors (glutamate receptors), and to change cell energetics through mitochondrial biogenesis. Through these mechanisms, medium-chain fatty acids rather than ketones are likely to block seizure onset and raise seizure threshold. The mechanisms underlying the ketogenic diet might also have roles in other disorders, such as preventing neurodegeneration in Alzheimer's disease, the proliferation and spread of cancer, and insulin resistance in type 2 diabetes. Analysing medium-chain fatty acids in future ketogenic diet studies will provide further insights into their importance in modified forms of the diet. Moreover, the results of these studies could facilitate the development of new pharmacological and dietary therapies for epilepsy and other disorders.
Published:
2018
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