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Title:
Enhanced lipid utilization is coupled to the sickness responses triggered by lipopolysaccharide
Authors:
Park, Byong Seo; Kim, Ye Jin; Jeong, Da Yeon; Kim, Yang Tae; Kim, Jae Kwang; Lee, Byung Ju; Kim, Jae Geun
Abstract:
Sickness symptoms exerted via inflammatory responses occur in several infectious and chronic diseases. A growing body of evidence suggests that altered nutrient availability and metabolism are tightly coupled to inflammatory processes. However, the relationship between metabolic shifts and the development of the sickness response has not been explored fully. Therefore, we aimed to evaluate metabolic phenotypes with a mouse model showing sickness symptoms via systemic administration of lipopolysaccharide (LPS) in the present study. LPS injection elevated the lipid utilization and circulating levels of fatty acids. It also increased the levels of β-hydroxybutyric acid, a ketone body produced from fatty acids. We confirmed the functional connectivity between nutrient utilization and inflammatory responses and demonstrated enhanced lipid utilization in the hypothalamus providing insights into hypothalamic control of sickness responses. Collectively, these findings could help develop new therapeutic strategies to treat patients with severe sickness symptoms associated with infectious and chronic human diseases.
Published:
June 18, 2021
Title:
A randomized controlled trial to isolate the effects of fasting and energy restriction on weight loss and metabolic health in lean adults
Authors:
Templeman, Iain; Smith, Harry Alex; Chowdhury, Enhad; Chen, Yung-Chih; Carroll, Harriet; Johnson-Bonson, Drusus; Hengist, Aaron; Smith, Rowan; Creighton, Jade; Clayton, David; Varley, Ian; Karagounis, Leonidas Georgios; Wilhelmsen, Andrew; Tsintzas, Kostas; Reeves, Sue; Walhin, Jean-Philippe; Gonzalez, Javier Thomas; Thompson, Dylan; Betts, James Alexander
Abstract:
Intermittent fasting may impart metabolic benefits independent of energy balance by initiating fasting-mediated mechanisms. This randomized controlled trial examined 24-hour fasting with 150% energy intake on alternate days for 3 weeks in lean, healthy individuals (0:150; n = 12). Control groups involved a matched degree of energy restriction applied continuously without fasting (75% energy intake daily; 75:75; n = 12) or a matched pattern of fasting without net energy restriction (200% energy intake on alternate days; 0:200; n = 12). Primary outcomes were body composition, components of energy balance, and postprandial metabolism. Daily energy restriction (75:75) reduced body mass (−1.91 ± 0.99 kilograms) almost entirely due to fat loss (−1.75 ± 0.79 kilograms). Restricting energy intake via fasting (0:150) also decreased body mass (−1.60 ± 1.06 kilograms; P = 0.46 versus 75:75) but with attenuated reductions in body fat (−0.74 ± 1.32 kilograms; P = 0.01 versus 75:75), whereas fasting without energy restriction (0:200) did not significantly reduce either body mass (−0.52 ± 1.09 kilograms; P ≤ 0.04 versus 75:75 and 0:150) or fat mass (−0.12 ± 0.68 kilograms; P ≤ 0.05 versus 75:75 and 0:150). Postprandial indices of cardiometabolic health and gut hormones, along with the expression of key genes in subcutaneous adipose tissue, were not statistically different between groups (P > 0.05). Alternate-day fasting less effectively reduces body fat mass than a matched degree of daily energy restriction and without evidence of fasting-specific effects on metabolic regulation or cardiovascular health.
Published:
June 16, 2021
Title:
Biomarker Concentrations in White and British Indian Vegetarians and Nonvegetarians in the UK Biobank
Authors:
Tong, Tammy Y N; Perez-Cornago, Aurora; Bradbury, Kathryn E; Key, Timothy J
Abstract:
Prospective studies have shown differences in some disease risks between vegetarians and nonvegetarians, but the potential biological pathways are not well understood.We aimed to assess differences in concentrations of biomarkers related to disease pathways in people with varying degrees of animal foods exclusion.The UK Biobank recruited 500,000 participants aged 40–69 y (54.4% women) throughout the United Kingdom in 2006–2010. Blood and urine were collected at recruitment and assayed for more than 30 biomarkers related to cardiovascular diseases, bone and joint health, cancer, diabetes, renal disease, and liver health. In cross-sectional analyses, we estimated adjusted geometric means of these biomarkers by 6 diet groups (regular meat eaters, low meat eaters, poultry eaters, fish eaters, vegetarians, vegans) in 466,058 white British participants and 2 diet groups (meat eaters, vegetarians) in 5535 British Indian participants.We observed differences in the concentrations of most biomarkers, with many biomarkers showing a gradient effect from meat eaters to vegetarians/vegans. Of the largest differences, compared with white British regular meat eaters, white British vegans had lower C-reactive protein [adjusted geometric mean (95% CI): 1.13 (1.03, 1.25) compared with 1.43 (1.42, 1.43) mg/L], lower low-density lipoprotein cholesterol [3.13 (3.07, 3.20) compared with 3.65 (3.65, 3.65) mmol/L], lower vitamin D [34.4 (33.1, 35.9) compared with 44.5 (44.4, 44.5) nmol/L], lower serum urea [4.21 (4.11, 4.30) compared with 5.36 (5.36, 5.37) mmol/L], lower urinary creatinine [5440 (5120, 5770) compared with 7280 (7260, 7300) μmol/L], and lower γ-glutamyltransferase [23.5 (22.2, 24.8) compared with 29.6 (29.6, 29.7) U/L]. Patterns were mostly similar in British Indians, and results were consistent between women and men.The observed differences in biomarker concentrations, including lower C-reactive protein, lower LDL cholesterol, lower vitamin D, lower creatinine, and lower γ-glutamyltransferase, in vegetarians and vegans may relate to differences in future disease risk.
Published:
June 16, 2021
Title:
The risk of ischemic stroke and hemorrhagic stroke in Chinese adults with low-density lipoprotein cholesterol concentrations < 70 mg/dL
Authors:
Wu, Zhijun; Huang, Zhe; Lichtenstein, Alice H.; Liu, Yesong; Chen, Shuohua; Jin, Yao; Na, Muzi; Bao, Le; Wu, Shouling; Gao, Xiang
Abstract:
BACKGROUND: The risk of stroke in individuals with very low low-density lipoprotein cholesterol (LDL-C) concentrations remains high. We sought to prioritize predictive risk factors for stroke in Chinese participants with LDL-C concentrations < 70 mg/dL using a survival conditional inference tree, a machine learning method. METHODS: The training dataset included 9327 individuals with LDL-C concentrations < 70 mg/dL who were free of cardiovascular diseases and did not use lipid-modifying drugs from the Kailuan I study (N = 101,510). We examined the validity of this algorithm in a second Chinese cohort of 1753 participants with LDL-C concentrations
Published:
June 16, 2021
Title:
Using an erythrocyte fatty acid fingerprint to predict risk of all-cause mortality: the Framingham Offspring Cohort
Authors:
McBurney, Michael I; Tintle, Nathan L; Vasan, Ramachandran S; Sala-Vila, Aleix; Harris, William S
Abstract:
RBC long-chain omega-3 (n–3) fatty acid (FA) percentages (of total fatty acids) are associated with lower risk for total mortality, but it is unknown if a suite of FAs could improve risk prediction.The objective of this study was to compare a combination of RBC FA levels with standard risk factors for cardiovascular disease (CVD) in predicting risk of all-cause mortality.Framingham Offspring Cohort participants without prevalent CVD having RBC FA measurements and relevant baseline clinical covariates (n = 2240) were evaluated during 11 y of follow-up. A forward, stepwise approach was used to systematically evaluate the association of 8 standard risk factors (age, sex, total cholesterol, HDL cholesterol, hypertension treatment, systolic blood pressure, smoking status, and prevalent diabetes) and 28 FA metrics with all-cause mortality. A 10-fold cross-validation process was used to build and validate models adjusted for age and sex.Four of 28 FA metrics [14:0, 16:1n–7, 22:0, and omega-3 index (O3I; 20:5n–3 + 22:6n–3)] appeared in ≥5 of the discovery models as significant predictors of all-cause mortality. In age- and sex-adjusted models, a model with 4 FA metrics was at least as good at predicting all-cause mortality as a model including the remaining 6 standard risk factors (C-statistic: 0.778; 95% CI: 0.759, 0.797; compared with C-statistic: 0.777; 95% CI: 0.753, 0.802). A model with 4 FA metrics plus smoking and diabetes (FA + Sm + D) had a higher C-statistic (0.790; 95% CI: 0.770, 0.811) compared with the FA (P < 0.01) or Sm + D models alone (C-statistic: 0.766; 95% CI: 0.739, 0.794; P < 0.001). A variety of other highly correlated FAs could be substituted for 14:0, 16:1n–7, 22:0, or O3I with similar predicted outcomes.In this community-based population in their mid-60s, RBC FA patterns were as predictive of risk for death during the next 11 y as standard risk factors. Replication is needed in other cohorts to validate this FA fingerprint as a predictor of all-cause mortality.
Published:
June 16, 2021
Title:
Specific Dietary Protein Sources Are Associated with Cardiometabolic Risk Factors in the Boston Puerto Rican Health Study
Authors:
Riseberg, Emily; Lopez-Cepero, Andrea; Mangano, Kelsey M.; Tucker, Katherine L.; Mattei, Josiemer
Abstract:
BACKGROUND: Puerto Rican adults residing in the US mainland experience a high prevalence of metabolic syndrome (MetS). A diet containing healthy protein-rich sources may help control risk factors for MetS. OBJECTIVE: This study aimed to evaluate 2-year longitudinal associations between intake of various protein-rich foods and changes in the six MetS components. DESIGN: This is a secondary analysis of a longitudinal cohort study using data from the baseline (2004-2007) and 2-year follow-up visits (2006-2011) in the Boston Puerto Rican Health Study. PARTICIPANTS/SETTING: Participants were self-identified Puerto Ricans, aged 45 to 75 years, residing in Boston, Massachusetts, or the surrounding area (n = 1,126). MAIN OUTCOME MEASURES: MetS components were fasting glucose, high-density lipoprotein (HDL) cholesterol, triglycerides, systolic and diastolic blood pressures, and waist circumference. STATISTICAL ANALYSIS: Baseline intake of foods reported in a semiquantitative food frequency questionnaire were expressed as servings/day, and protein-rich foods were categorized as unprocessed white meat, unprocessed red meat, processed meat, milk and yogurt, cheese, fish and seafood, beans, nuts, and eggs. Associations between each continuous protein food group and continuous 2-year change in MetS components were assessed using linear mixed models adjusted for socioeconomic and behavioral factors, and other dietary sources. RESULTS: The top contributors to total protein intake were unprocessed red meat (13.3%) and unprocessed poultry (13.0%), and the lowest were eggs (2.92%) and nuts (0.91%). Higher intake of processed meats was associated with an increase in waist circumference over 2 years (β = 1.28; standard error [SE] = 0.63), whereas higher intake of fish and seafood was associated with a decrease in waist circumference (β = -3.47; SE = 1.39). Intake of unprocessed poultry was associated with a decrease in triglycerides (β = -24.5; SE = 9.13). No other significant associations were observed between protein sources and 2-year changes in MetS components. CONCLUSIONS: Consuming less processed meat and more fish and seafood and unprocessed poultry was associated with decreases in waist circumference and triglycerides among US mainland Puerto Ricans. Other dietary protein sources were not related to cardiometabolic health.
Published:
June 15, 2021
Title:
Inflammation but not Glycemic Control is Associated with Neurocognitive Decline After Cardiac Surgery
Authors:
Scrimgeour, Laura; Ikeda, Ian; Sellke, Nicholas; Shi, Guangbin; Feng, Jun; Cizginer, Sevdenur; Ehsan, Afshin; Sodha, Neel; Sellke, Frank
Abstract:
Background: Whether perioperative glycemic control or markers of inflammation is associated with neurocognitive decline (NCD) after cardiac surgery was examined. Methods: Thirty patients undergoing cardiac surgery utilizing cardiopulmonary bypass (CPB) were screened for NCD preoperatively and on post-operative day four (POD4). Serum cytokine levels were measured and human transcriptome analysis was performed on blood samples. Neurocognitive data are presented as a change from baseline to POD4 in a score standardized with respect to age and gender. Results: A decline in neurocognitive function was identified in 73% (22/30) of patients on POD4. Patients with postoperative leukocytosis (WBC [?] 10.5) had more NCD when compared to their baseline function (p=0.03). Patients with elevated IL-8 levels at 6 hours postoperatively had a significant decline in NCD at POD4 (p=0.04). Surprisingly, TNF-α, IL-1β, IL-2, or IL-6 levels were not associated with NCD (p>0.3 for all). There was no difference in neurocognitive function between patients with elevated HbA1c levels preoperatively (p=0.973) or elevated fasting blood glucose levels the morning of surgery (>126mg/dL, p=0.910), or a higher maximum blood glucose levels during CPB (>180mg/dL, p=0.252), or higher average glucose levels during CPB (>160mg/dL, p=0.639). Human transcriptome analysis demonstrated unique and differential patterns of gene expression in patients depending on the presence of DM and NCD. Conclusions: Perioperative glycemic control does not have an effect on NCD soon after cardiac surgery. Postoperative leukocytosis and elevated IL-8 levels are associated with neurocognitive decline. The profile of gene expression was altered in patients with NCD with or without diabetes.
Published:
June 12, 2021
Title:
Peroxidation of n-3 and n-6 polyunsaturated fatty acids in the acidic tumor environment leads to ferroptosis-mediated anticancer effects
Authors:
Dierge, Emeline; Debock, Elena; Guilbaud, Céline; Corbet, Cyril; Mignolet, Eric; Mignard, Louise; Bastien, Estelle; Dessy, Chantal; Larondelle, Yvan; Feron, Olivier
Abstract:
Tumor acidosis promotes disease progression through a stimulation of fatty acid (FA) metabolism in cancer cells. Instead of blocking the use of FAs by acidic cancer cells, we examined whether excess uptake of specific FAs could lead to antitumor effects. We found that n-3 but also remarkably n-6 polyunsaturated FA (PUFA) selectively induced ferroptosis in cancer cells under ambient acidosis. Upon exceeding buffering capacity of triglyceride storage into lipid droplets, n-3 and n-6 PUFA peroxidation led to cytotoxic effects in proportion to the number of double bonds and even more so in the presence of diacylglycerol acyltransferase inhibitors (DGATi). Finally, an n-3 long-chain PUFA-rich diet significantly delayed mouse tumor growth when compared with a monounsaturated FA-rich diet, an effect further accentuated by administration of DGATi or ferroptosis inducers. These data point out dietary PUFA as a selective adjuvant antitumor modality that may efficiently complement pharmacological approaches.
Published:
June 11, 2021
Title:
Glycated Hemoglobin and Subclinical Atherosclerosis in People Without Diabetes
Authors:
Rossello, Xavier; Raposeiras-Roubin, Sergio; Oliva, Belén; Sánchez-Cabo, Fátima; García-Ruíz, José M.; Caimari, Francisca; Mendiguren, José M.; Lara-Pezzi, Enrique; Bueno, Héctor; Fernández-Friera, Leticia; Fernández-Ortiz, Antonio; Sanz, Javier; Ibanez, Borja; Fuster, Valentin
Abstract:
Background The metabolic injury caused by protein glycation, monitored as the level of glycated hemoglobin (HbA1c), is not represented in most risk scores (i.e., Systematic Coronary Risk Estimation or atherosclerotic cardiovascular disease risk scale). Objectives The purpose of this study was to assess the association between HbA1c and the extent of subclinical atherosclerosis (SA) and to better identify individuals at higher risk of extensive SA using HbA1c on top of key cardiovascular risk factors (CVRFs). Methods A cohort of 3,973 middle-aged individuals from the PESA (Progression of Early Subclinical Atherosclerosis) study, with no history of cardiovascular disease and with HbA1c in the nondiabetic range, were assessed for the presence and extent of SA by 2-dimensional vascular ultrasound and noncontrast cardiac computed tomography. Results After adjusting for established CVRFs, HbA1c showed an association with the multiterritorial extent of SA (odds ratio: 1.05, 1.27, 1.27, 1.36, 1.80, 1.87, and 2.47 for HbA1c 4.9% to 5.0%, 5.1% to 5.2%, 5.3% to 5.4%, 5.5% to 5.6%, 5.7% to 5.8%, 5.9% to 6.0%, and 6.1% to 6.4%, respectively; reference HbA1c ≤4.8%; p < 0.001). The association was significant in all pre-diabetes groups and even below the pre-diabetes cut-off (HbA1c 5.5% to 5.6% odds ratio: 1.36 [95% confidence interval: 1.03 to 1.80]; p = 0.033). High HbA1c was associated with an increased risk of SA in low-risk individuals (p
Published:
June 8, 2021
Title:
Dietary Carbohydrate Intake Glycemic Index and Glycemic Load and the Risk of Prostate Cancer among Iranian Men: A Case-Control Study
Authors:
Alboghobeish, Zeinab; Balam, Farinaz Hosseini; Askari, Faezeh; Rashidkhani, Bahram
Abstract:
Previous studies have presented a few evidences on the relationship between dietary carbohydrate intake, glycemic index (GI), glycemic load (GL), with the prostate cancer risk. We performed a case-control study to evaluate these associations in 50 men with histologically confirmed prostate cancer and 100 control men. Odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were derived using logistic regression. The fully adjusted ORs for the top vs. the bottom quartile were 15.02 (P trend = 0.004), 1.04 (P trend = 0.003), and 10.35 (P trend = 0.002) for carbohydrate intake, GI and GL, respectively. Significant associations with prostate cancer remained only among men with reduced fiber intake for carbohydrate intake, GI and GL and among those had increased fiber intake for GI. These findings support the hypothesis that diet with high carbohydrate, GI and GL enhance risk of prostate cancer.
Published:
June 7, 2021
Title:
Chronic Dietary Erythritol Exposure Elevates Plasma Erythritol Concentration in Mice but Does Not Cause Weight Gain or Modify Glucose Homeostasis
Authors:
Ortiz, Semira R; Field, Martha S
Abstract:
Erythritol is both a common nonnutritive sweetener and an endogenous product of glucose metabolism. Recent reports suggest that elevated plasma erythritol is a predictive biomarker of cardiometabolic disease onset and complications.Although short-term erythritol consumption has been evaluated, the effect of chronically elevated circulating erythritol on adiposity and glucose metabolism has not. This study investigated the effect of longer-term erythritol consumption on weight gain and glucose tolerance in young/adolescent mice.Four erythritol supplementation experiments were completed and analyzed separately in male C57BL/6J mice. In experiments 1 and 2, mice aged 8 wk or 20 wk, respectively, were randomly allocated to consume 16% fat diet (LFD) or LFD with 40 g/kg erythritol. In experiments 3 and 4, mice aged 8 wk or 20 wk were fed 45% fat diet (HFD) or HFD with 40 g/kg erythritol (HFD + ERY). In each experiment, we compared the effect of erythritol consumption on plasma erythritol, body weight and composition, glucose tolerance, and brown adipose tissue (BAT) uncoupling protein 1 (UCP1) expression. We also investigated relative endogenous tissue erythritol concentrations in a subset of control (LFD or HFD) mice in experiments 1 and 3.There was no effect of erythritol supplementation on body weight or glucose tolerance in experiments 1–3. In experiment 4, in the 20-wk-old mice fed HFD or HFD + ERY, there was a significant interaction of time and erythritol on body weight (P < 0.0001), but the main effect of diet was not significant. Plasma erythritol was elevated 40-fold in mice consuming erythritol-supplemented diets relative to mice consuming LFD or HFD controls. We found no effect of chronic erythritol consumption on BAT UCP1 protein concentrations. Liver and kidney tissue contained significantly higher endogenous erythritol than quadriceps and visceral adipose (P < 0.001) in young mice fed LFD and HFD.In young/adolescent mice, prolonged erythritol consumption did not significantly affect body weight, composition, or glucose tolerance.
Published:
June 5, 2021
Title:
Ketogenic Diet with Concurrent Chemoradiation in Head and Neck Squamous Cell Carcinoma: Preclinical and Phase 1 Trial Results
Authors:
Ma, Daniel C.; Anderson, Carryn M.; Rodman, Samuel N.; Buranasudja, Visarut; McCormick, Michael L.; Davis, Andrew; Loth, Elizabeth; Bodeker, Kellie L.; Ahmann, Logan; Parkhurst, Jessica R.; Sun, Wenqing; Follmer, Kayla R.; Simons, Andrean L.; Buatt, John M.; Spitz, Douglas R.; Fath, Melissa A.; Allen, Bryan G.
Abstract:
Ketogenic diets (KD) are high in fat and low in carbohydrates, forcing cells to utilize mitochondrial fatty acid oxidation for energy production. Since cancer cells demonstrate increased mitochondrial oxidative stress relative to normal cells, we hypothesized that a KD may selectively enhance metabolic oxidative stress in head and neck cancer cells, sensitizing them to radiation and platinum-based chemotherapy without causing increased toxicity in surrounding normal tissues. This hypothesis was tested in preclinical murine xenografts and in a phase 1 clinical trial (NCT01975766). In this study, mice bearing human head and neck cancer xenografts (FaDu) were fed either standard mouse chow or KetoCal® KD (90% fat, 8% carbohydrate, 2% protein) and exposed to ionizing radiation. Tumors were harvested from mice to test for glutathione, a biomarker of oxidative stress. In parallel, patients with locally advanced head and neck cancer were enrolled in a phase 1 clinical trial where they consumed KD and received radiation with concurrent platinum-based chemotherapy. Subjects consumed KetoCal KD via percutaneous endoscopic gastrostomy (PEG) tube and were also allowed to orally consume water, sugar-free drinks, and foods approved by a dietitian. Oxidative stress markers including protein carbonyls and total glutathione were assessed in patient blood samples both pre-KD and while consuming the KD. Mice bearing FaDu xenografts that received radiation and KD demonstrated a slight improvement in tumor growth rate and survival compared to mice that received radiation alone; however a variation in responses was seen dependent on the fatty acid composition of the diet. In the phase 1 clinical trial, a total of twelve patients were enrolled in the study. Four patients completed five weeks of the KD as per protocol (with variance in compliance). Eight patients did not tolerate the diet with concurrent radiation and platinum-chemotherapy (5 were patient decision and 3 were removed from study due to toxicity). The median number of days consuming a KD in patients who did not complete the study was 5.5 (range: 2-8 days). Reasons for discontinuation included "stress of diet compliance" (1 patient), grade 2 nausea (3 patients), and grade 3 fatigue (1 patient). Three patients were removed from the trial due to dose-limiting toxicities including: grade 4 hyperuricemia (2 patients) and grade 3 acute pancreatitis (1 patient). Median weight loss was 2.95% for the KD-tolerant group and 7.92% for patients who did not tolerate the diet. In conclusion, the ketogenic diet shows promise as a treatment combined with radiation in preclinical mouse head and neck cancer xenografts. A phase 1 clinical trial evaluating the safety and tolerability of KD demonstrated difficulty with diet compliance when combined with standard-of care-radiation therapy and cisplatin chemotherapy.
Published:
June 4, 2021
Title:
Associations between fruit intake and risk of diabetes in the AusDiab cohort
Authors:
Bondonno, Nicola P.; Davey, Raymond J.; Murray, Kevin; Radavelli-Bagatini, Simone; Bondonno, Catherine P.; Blekkenhorst, Lauren C.; Sim, Marc; Magliano, Dianna J.; Daly, Robin M.; Shaw, Jonathan E.; Lewis, Joshua R.; Hodgson, Jonathan M.
Abstract:
BACKGROUND: Fruit, but not fruit juice, intake is inversely associated with type 2 diabetes mellitus (T2DM). However, questions remain about the mechanisms by which fruits may confer protection. Aims were to examine associations between intake of fruit types and 1) measures of glucose tolerance and insulin sensitivity and 2) diabetes at follow-up. METHODS: Among participants of the Australian Diabetes, Obesity and Lifestyle Study, fruit and fruit juice intake was assessed by food frequency questionnaire at baseline. Associations between fruit and fruit juice intake and 1) fasting plasma glucose, 2-h post-load plasma glucose, HOMA2 of β-cell function (HOMA2-%β), HOMA2 of insulin sensitivity (HOMA2-%S), and fasting insulin levels at baseline and 2) the presence of diabetes at follow-up (5 and 12 years) were assessed using restricted cubic splines in logistic and linear regression models. RESULTS: This population of 7,675 Australians (45% males) had a mean±SD age of 54±12 years at baseline. Total fruit intakes were inversely associated with serum insulin and HOMA2-%β, and positively associated with HOMA2-%S at baseline. Compared to participants with the lowest intakes (quartile 1), participants with moderate total fruit intakes (quartile 3) had a 36% lower odds of having diabetes at 5 years [OR (95% CI): 0.64 (0.44, 0.92)], after adjusting for dietary and lifestyle confounders. Associations with 12-year outcomes were not statistically significant. CONCLUSION: A healthy diet including whole fruits, but not fruit juice, may play a role in mitigating T2DM risk.
Published:
June 2, 2021
Title:
Growth, body composition, and cardiovascular and nutritional risk of 5- to 10-y-old children consuming vegetarian, vegan, or omnivore diets
Authors:
Desmond, Małgorzata A; Sobiecki, Jakub G; Jaworski, Maciej; Płudowski, Paweł; Antoniewicz, Jolanta; Shirley, Meghan K; Eaton, Simon; Książyk, Janusz; Cortina-Borja, Mario; De Stavola, Bianca; Fewtrell, Mary; Wells, Jonathan C K
Abstract:
Plant-based diets (PBDs) are increasingly recommended for human and planetary health. However, comprehensive evidence on the health effects of PBDs in children remains incomplete, particularly in vegans.To quantify differences in body composition, cardiovascular risk, and micronutrient status of vegetarian and vegan children relative to omnivores and to estimate prevalence of abnormal micronutrient and cholesterol status in each group.In a cross-sectional study, Polish children aged 5–10 y (63 vegetarian, 52 vegan, 72 matched omnivores) were assessed using anthropometry, deuterium dilution, DXA, and carotid ultrasound. Fasting blood samples, dietary intake, and accelerometry data were collected.All results are reported relative to omnivores. Vegetarians had lower gluteofemoral adiposity but similar total fat and lean mass. Vegans had lower fat indices in all regions but similar lean mass. Both groups had lower bone mineral content (BMC). The difference for vegetarians attenuated after accounting for body size but remained in vegans (total body minus the head: –3.7%; 95% CI: –7.0, –0.4; lumbar spine: –5.6%; 95% CI: –10.6, –0.5). Vegetarians had lower total cholesterol, HDL, and serum B-12 and 25-hydroxyvitamin D [25(OH)D] without supplementation but higher glucose, VLDL, and triglycerides. Vegans were shorter and had lower total LDL (–24 mg/dL; 95% CI: –35.2, –12.9) and HDL (–12.2 mg/dL; 95% CI: –17.3, –7.1), high-sensitivity C-reactive protein, iron status, and serum B-12 (–217.6 pmol/L; 95% CI: –305.7, –129.5) and 25(OH)D without supplementation but higher homocysteine and mean corpuscular volume. Vitamin B-12 deficiency, iron-deficiency anemia, low ferritin, and low HDL were more prevalent in vegans, who also had the lowest prevalence of high LDL. Supplementation resolved low B-12 and 25(OH)D concentrations.Vegan diets were associated with a healthier cardiovascular risk profile but also with increased risk of nutritional deficiencies and lower BMC and height. Vegetarians showed less pronounced nutritional deficiencies but, unexpectedly, a less favorable cardiometabolic risk profile. Further research may help maximize the benefits of PBDs in children.
Published:
June 1, 2021
Title:
Low-fat diets and testosterone in men: Systematic review and meta-analysis of intervention studies
Authors:
Whittaker, Joseph; Wu, Kexin
Abstract:
Background Higher endogenous testosterone levels are associated with reduced chronic disease risk and mortality. Since the mid-20th century, there have been significant changes in dietary patterns, and men’s testosterone levels have declined in western countries. Cross-sectional studies show inconsistent associations between fat intake and testosterone in men. Methods Studies eligible for inclusion were intervention studies, with minimal confounding variables, comparing the effect of low-fat vs high-fat diets on men’s sex hormones. 9 databases were searched from their inception to October 2020, yielding 6 eligible studies, with a total of 206 participants. Random effects meta-analyses were performed using Cochrane’s Review Manager software. Cochrane’s risk of bias tool was used for quality assessment. Results There were significant decreases in sex hormones on low-fat vs high-fat diets. Standardised mean differences with 95 % confidence intervals (CI) for outcomes were: total testosterone [−0.38 (95 % CI −0.75 to −0.01) P = 0.04]; free testosterone [−0.37 (95 % CI −0.63 to −0.11) P = 0.005]; urinary testosterone [−0.38 (CI 95 % −0.66 to −0.09) P = 0.009]; and dihydrotestosterone [−0.3 (CI 95 % −0.56 to −0.03) P = 0.03]. There were no significant differences for luteinising hormone or sex hormone binding globulin. Subgroup analysis for total testosterone, European and North American men, showed a stronger effect [−0.52 (95 % CI −0.75 to −0.3) P
Published:
June 1, 2021
Title:
Red Meat Intake and Glycemic and Insulinemic Risk Factors for Type 2 Diabetes: A Systematic Review and Meta-Analysis
Authors:
Sanders, Lisa; Wilcox, Meredith; Maki, Kevin
Abstract:
Results from observational studies have suggested an association of red meat intake with increased risk of type 2 diabetes (T2D). However, results from randomized controlled trials (RCTs) have not shown clear evidence to support a mechanistic link between red meat intake and T2D risk factors. The objective of this systematic review and meta-analysis was to evaluate the impact of red meat intake on markers of glucose tolerance, including fasting glucose and insulin, postprandial glucose and insulin, insulin sensitivity and glycated hemoglobin (HbA1c).A systematic review and meta-analysis was conducted on RCTs evaluating the effect of red meat intake, compared to lower or no red meat intake, on markers of glucose tolerance in adults. A search of PubMed yielded 17 relevant RCTs. Pooled estimates wereexpressed as standardized mean differences (SMD) between the red meat intervention and the control intervention with less or no red meat.Compared to diets with little or no red meat intake, there was no significant impact of red meat intake on insulin sensitivity (SMD: −0.12; 95% CI: −0.43, 0.19), insulin resistance (SMD: 0.23; 95% CI: −0.22, 0.68), fasting glucose (SMD: 0.12; 95% CI: −0.06, 0.30), fasting insulin (SMD: 0.16; 95% CI: −0.10, 0.42) or HbA1c (SMD: 0.00; 95% CI: −0.42, 0.43). Red meat intake modestly, but significantly, reduced postprandial glucose (SMD: −0.46; 95% CI: −0.77, −0.16; P < 0.003) compared to diets with little or no red meat intake in a small number of studies (n = 3). However, there was no effect on postprandial insulin (SMD: −0.74; 95% CI: −1.64, 0.16).The results of this meta-analysis suggest red meat intake does not impact several glycemic and insulinemic risk factors for T2D. Thus, it is unclear whether there is a causal relationship with red meat intake and T2D risk or if other confounding lifestyle factors may be driving the observed association. Further investigations are needed, particularly on other markers of glucose tolerance, such as pancreatic beta-cell function, to better understand whether a causal relationship exists between red meat intake and risk of T2D. PROSPERO Registration: CRD42020176059This research was funded by Beef Checkoff.
Published:
June 1, 2021
Title:
Successful implementation of classical ketogenic dietary therapy in a patient with Niemann-Pick disease type C
Authors:
Höller, A.; Albrecht, U.; Baumgartner Sigl, S.; Zöggeler, T.; Ramoser, G.; Bernar, B.; Karall, D.; Scholl-Bürgi, S.
Abstract:
Background Niemann-Pick disease type C (NP-C) is a neurodegenerative disease for which only palliative treatment exists, and only miglustat is effective in stabilizing neurological manifestations of NP-C. Ketogenic dietary therapies (KDT) are successfully used in patients with seizure disorders, including those associated with various inherited metabolic diseases (IMD), to reduce seizure frequency and medication requirement as well as to confer neuroprotection. Since patients with NP-C suffer pharmacorefractory seizures associated with ongoing neurodegeneration, KDT might be beneficial. The concomitant use of miglustat and KDT in patients with NP-C has not been reported. Case presentation We describe our experience in a now 17-year-old female with NP-C manifest early in childhood who has been successfully and continuously treated with miglustat and KDT in a palliative care setting for 3y. Although the neurodegeneration of NP-C progressed, she benefited from a reduction in seizure activity, fewer hospital stays related to seizure exacerbation, and increased alertness. Conclusion KDT could be safely deployed in our patient with NP-C, in whom its effects have been beneficial. Generally KDT is demonstratedly efficacious in patients with epilepsy and IMD. It reduces seizure activity and medication requirements and confers neuroprotection. Intracellular cholesterol trafficking and regulation of cholesterol biosynthesis are impaired in NP-C, which may prompt caution with respect to dietary lipid intake.
Published:
June 1, 2021
Title:
The effect of a 6-month ketogenic medium-chain triglyceride supplement on plasma cardiometabolic and inflammatory markers in mild cognitive impairment.
Authors:
Myette-Côté, Étienne; St-Pierre, Valérie; Beaulieu, Sandrine; Castellano, Christian-Alexandre; Fortier, Mélanie; Plourde, Mélanie; Bocti, Christian; Fulop, Tamas; Cunnane, Stephen C.
Abstract:
Abstract
Introduction
Mild cognitive impairment (MCI) is often accompanied by metabolic abnormalities and inflammation that might play a role in the development of cognitive impairment. The use of ketogenic medium-chain triglycerides (kMCT) to improve cognition in this population has shown promising results but remains controversial because of the potentially detrimental effect of elevated intake of saturated fatty acids on cardiovascular (CV) health and perhaps inflammatory processes. The primary aim of this secondary data analysis report is to describe changes in cardiometabolic markers and peripheral inflammation during a 6-month kMCT intervention in MCI.
Methods
Thirty-nine participants with MCI completed the intervention of 30 g/day of either a kMCT drink or calorie-matched placebo (high-oleic acid) for 6 months. Plasma concentrations of cardiometabolic and inflammatory markers were collected before (fasting state) and after the intervention (2 h following the last drink).
Results
A mixed model ANOVA analysis revealed a time by group interaction for ketones (P < 0.001), plasma 8:0 and 10:0 acids (both P < 0.001) and IL-8 (P = 0.002) with follow up comparison revealing a significant increase in the kMCT group (+48%, P = 0.005), (+3,800 and +4,900%, both P < 0.001) and (+147%, P < 0.001) respectively. A main effect of time was observed for insulin (P = 0.004), triglycerides (P = 0.011) and non-esterified fatty acids (P = 0.036).
Conclusion
Under these study conditions, 30 g/d of kMCT taken for six months and up to 2-hour before post-intervention testing had minimal effect on an extensive profile of circulating cardiometabolic and inflammatory markers as compared to a placebo calorie-matched drink. Our results support the safety kMCT supplementation in individuals with MCI. The clinical significance of the observed increase in circulating IL-8 levels is presently unknown and awaits future studies.
Published:
June 1, 2021
Title:
The state of diabetes treatment coverage in 55 low-income and middle-income countries: a cross-sectional study of nationally representative, individual-level data in 680 102 adults
Authors:
Flood, David; Seiglie, Jacqueline A.; Dunn, Matthew; Tschida, Scott; Theilmann, Michaela; Marcus, Maja E.; Brian, Garry; Norov, Bolormaa; Mayige, Mary T.; Gurung, Mongal Singh; Aryal, Krishna K.; Labadarios, Demetre; Dorobantu, Maria; Silver, Bahendeka K.; Bovet, Pascal; Jorgensen, Jutta M. Adelin; Guwatudde, David; Houehanou, Corine; Andall-Brereton, Glennis; Quesnel-Crooks, Sarah; Sturua, Lela; Farzadfar, Farshad; Moghaddam, Sahar Saeedi; Atun, Rifat; Vollmer, Sebastian; Bärnighausen, Till W.; Davies, Justine I.; Wexler, Deborah J.; Geldsetzer, Pascal; Rohloff, Peter; Ramírez-Zea, Manuel; Heisler, Michele; Manne-Goehler, Jennifer
Abstract:
Summary
Background
Approximately 80% of the 463 million adults worldwide with diabetes live in low-income and middle-income countries (LMICs). A major obstacle to designing evidence-based policies to improve diabetes outcomes in LMICs is the scarce availability of nationally representative data on the current patterns of treatment coverage. The objectives of this study were to estimate the proportion of adults with diabetes in LMICs who receive coverage of recommended pharmacological and non-pharmacological diabetes treatment; and to describe country-level and individual-level characteristics that are associated with treatment.
Methods
We did a cross-sectional analysis of pooled, individual data from 55 nationally representative surveys in LMICs. Our primary outcome of self-reported diabetes treatment coverage was based on population-level monitoring indicators recommended in the 2020 WHO Package of Essential Noncommunicable Disease Interventions. Surveys were included if they were done in 2008 or after in an LMIC, as classified by the World Bank in the year the survey was done; were nationally representative; had individual-level data; contained a diabetes biomarker (fasting glucose, random glucose, or glycated haemoglobin); and had data on one or more diabetes treatments. Our sample included non-pregnant individuals with an available diabetes biomarker who were at least 25 years of age. We assessed coverage of three pharmacological and three non-pharmacological treatments among people with diabetes. At the country level, we estimated the proportion of individuals reporting coverage by per-capita gross national income and geographical region. At the individual level, we used logistic regression models to assess coverage along several key individual characteristics including sex, age, body-mass index, wealth quintile, and educational attainment. In the primary analysis, we scaled sample weights such that countries were weighted equally.
Findings
The final pooled sample from the 55 LMICs included 680 102 total individuals and 37 094 individuals with diabetes. Using equal weights for each country, diabetes prevalence was 9·0% (95% CI 8·7–9·4), with 43·9% (41·9–45·9) reporting a previous diabetes diagnosis. Overall, 4·6% (3·9–5·4) of individuals with diabetes self-reported meeting need for all treatments recommended for them. Coverage of glucose-lowering medication was 50·5% (48·6–52·5); antihypertensive medication was 41·3% (39·3–43·3); cholesterol-lowering medication was 6·3% (5·5–7·2); diet counselling was 32·2% (30·7–33·7); exercise counselling was 28·2% (26·6–29·8); and weight-loss counselling was 31·5% (29·3–33·7). Countries at higher-income levels tended to have greater coverage. Female sex and higher age, body-mass index, educational attainment, and household wealth were also associated with greater coverage.
Interpretation
Fewer than one in ten people with diabetes in LMICs receive coverage of guideline-based comprehensive diabetes treatment. Scaling up the capacity of health systems to deliver treatment not only to lower glucose but also to address cardiovascular disease risk factors, such as hypertension and high cholesterol, are urgent global diabetes priorities.
Funding
National Clinician Scholars Program at the University of Michigan Institute for Healthcare Policy & Innovation, National Institute of Diabetes and Digestive and Kidney Diseases, Harvard Catalyst, and National Center for Advancing Translational Sciences of the National Institutes of Health.
Published:
June 1, 2021
Title:
Impact of a ketogenic diet intervention during radiotherapy on body composition: IV. Final results of the KETOCOMP study for rectal cancer patients
Authors:
Klement, Rainer J.; Koebrunner, Petra S.; Meyer, Detlef; Kanzler, Stefan; Sweeney, Reinhart A.
Abstract:
Summary
Background & Aims
Obesity and low muscle mass are associated with worse outcomes of colorectal cancer patients. We conducted a controlled trial to study the impact of a ketogenic diet (KD) based on natural foods versus an unspecified standard diet (SD) on body composition in rectal cancer patients undergoing radiotherapy.
Methods
Patients with non-metastasized rectal cancer were allocated to either the KD (N = 24) or the SD (N = 25) group during radiotherapy. Body composition was measured weekly by bioimpedance analysis and analyzed using linear mixed effects models. Pathologic response in patients undergoing neoadjuvant treatment was evaluated at the time of surgery.
Results
A total of 18 KD and 23 SD patients completed the study and were eligible for analysis. The SD group experienced no noteworthy changes in any body composition parameter. In contrast, patients in the KD group lost significant amounts of body weight and fat mass, averaging 0.5 and 0.65kg/week (p < 0.0001). There was a rapid loss of intracellular water consistent with initial intramuscular glycogen and water depletion, but skeletal muscle tissue was conserved. Pathological tumor responses were somewhat greater in the KD group, with a larger mean Dworak regression grade (p=0.072) and larger percentage of near-complete (yT0N0 or yT1N1) responses (43 versus 15%, p=0.116) that almost reached statistical significance in intention-to-treat analysis (50% versus 14%, p=0.018).
Conclusions
In rectal cancer patients undergoing curative radiotherapy, a KD significantly reduced body weight and fat mass while preserving skeletal muscle mass. We could demonstrate a trend for KDs contributing synergistically to pathological tumor response, a finding in line with preclinical data that warrants future confirmation in larger studies.
Trial registration
ClinicalTrials.gov identifier: NCT02516501, registered on August 06, 2015.
Published:
May 30, 2021
Title:
Compared to serum triglyceride alone, the association between serum triglyceride to high-density lipoprotein cholesterol ratio and 10-year cardiovascular disease risk as determined by Framingham risk scores in a large Korean cohort
Authors:
Lee, Hyang-Rae; Kim, Jong-Koo; Kim, Ji-Hye; Chung, Tae-Ha
Abstract:
BACKGROUND: The incidence of cardiovascular disease (CVD) has gradually increased to the extent that it has become the most common cause of mortality worldwide, and triglyceride/high-density lipoprotein cholesterol (TG/HDL) ratio, a surrogate marker of insulin resistance, has emerged as an independent predictor of CVD. Additionally, several recent studies have reported an independent association between triglyceride-rich lipoproteins and CVD risk. The present study was conducted to investigate the association between the CVD risk determined by the Framingham risk score and the TG alone and TG/HDL ratios in a large Korean cohort. METHODS: This cross-sectional study included 7,050 participants aged 30 to 69 years that participated in a health examination program. TG/HDL ratio quartiles and TG quartiles were categorized as follows: Q1: ≤ 1.25, Q2: 1.26-2.07, Q3: 2.08-3.48, and Q4: ≥3.49; Q1: ≤ 71, Q2: 72-105, Q3: 106-159, and Q4: ≥160, respectively. Odds ratios (ORs) and 95% confidence intervals (CI) for high Framingham 10-year CVD risk (≥ 10%) were calculated across TG/HDL ratio quartiles and TG quartiles using multiple logistic regression analysis after adjusting for confounding variables. RESULTS: The mean values of most cardiometabolic variables including body mass index, blood pressure, fasting plasma glucose levels, leukocyte count, median CRP levels, and Framingham 10-year CVD risk scores increased gradually with TG/HDL ratio quartiles. The OR (95% CI) of the highest TG/HDL ratio quartile and TG quartile as compared with the lowest TG/HDL ratio quartile and TG quartile for high Framingham 10-year CVD risk was 9.27 (6.68-12.86) and 0.97 (0.69-1.36) after adjusting for confounding variables, respectively. CONCLUSION: Compared to TG, the TG/HDL ratio was found to be positively and independently associated with Framingham 10-year CVD risk in a large Korean cohort.
Published:
May 28, 2021
Title:
Does the size of a ketogenic diet admission group influence outcomes?
Authors:
Alem, Danayt; Jager, Leah; Turner, Zahava; Stanfield, Anthony; Kossoff, Eric H.
Abstract:
INTRODUCTION: Most pediatric centers admit children with epilepsy for several days when initiating the ketogenic diet (KD). At some institutions, children are admitted in groups in order to save staff time and allow families to bond together for support. It is unknown if admitting children in larger groups for the KD affects outcomes. METHODS: We performed a retrospective study of all children with intractable epilepsy admitted for KD initiation at Johns Hopkins Hospital from 2010 to 2020. Charts were reviewed for size of admission groups, 3-month seizure reduction, and total KD duration. A linear mixed effects model was used to analyze KD duration between different size admission groups. RESULTS: 245 children were started on the KD, mean age 5.2 years. Thirty-three (13%) children were admitted in one-child admission groups, 52 (21%) in 2-children groups, 78 (32%) in 3-children groups, 72 (29%) in 4-children groups, and 10 (4%) in 5-children groups. At our center, fewer large admission groups and shorter KD durations have occurred over time. After adjusting for time, the 3-children admission group had higher KD duration than 1-child (1.9 times duration, p = 0.035). Additionally, after grouping cohort sizes into small (1-2 patients) versus large (3-5 patients), KD durations in the large groups were 1.6 times those in the small groups, p = 0.036. There was no statistically significant correlation between the size of the admission groups and 3-month seizure reduction. CONCLUSIONS: Admitting children in larger groups, specifically 3 children at a time, was associated with longer KD durations. This may be due to parent support from groups, listening and learning from other parents' questions, or other factors.
Published:
May 28, 2021
Title:
Higher Carbohydrate Amount and Lower Glycemic Index Increase Hunger, Diet Satisfaction, and Heartburn in Overweight and Obese Adults in the OmniCarb Randomized Clinical Trial
Authors:
Wu, Yingfei; Juraschek, Stephen P; Hu, Jiun-Ruey; Mueller, Noel T; Appel, Lawrence J; Anderson, Cheryl A M; Miller, Edgar R, III
Abstract:
The Dietary Approaches to Stop Hypertension (DASH) diet, a high-carbohydrate diet, is highly recommended based on its cardiovascular risk benefits, yet adherence remains persistently low. How subjective impressions of this diet contribute to adherence has not been thoroughly explored. The OmniCarb trial, which compared DASH-style diets varying in glycemic index (GI) and carbohydrate amount, surveyed subjective impressions of such diets.We examined the effects of GI and carbohydrate amount on qualitative aspects of diet acceptability through secondary outcomes in the OmniCarb trial.OmniCarb was a randomized, crossover trial of 4 DASH-style diets varying by GI (≥65 compared with ≤45) and carbohydrate amount (40% compared with 58% kcal) in overweight or obese (BMI ≥25 kg/m2) adults (n = 163). Participants consumed each diet in random order over 5-wk periods, separated by 2-wk washouts. At baseline and the end of each feeding period, participants rated hunger, diet satisfaction, and gastrointestinal symptoms (diarrhea/loose stools, constipation, bloating, nausea, and heartburn).Participant mean age was 52 y, with 52% women, 51% non-Hispanic black, and 56% obese (BMI ≥30). Compared with baseline, all intervention diets decreased heartburn, increased diarrhea/loose stools, and increased bloating, but did not significantly affect constipation or nausea. Compared with lower carbohydrate diets, higher carbohydrate diets increased hunger (RR: 1.16; 95% CI: 1.04, 1.30), increased diet satisfaction (RR: 1.10; 95% CI: 1.01, 1.20), and increased heartburn (RR: 1.49; 95% CI: 1.09, 2.04). Compared with lower GI diets, higher GI diets did not affect hunger (RR: 0.92; 95% CI: 0.83, 1.02), decreased diet satisfaction (RR: 0.83; 95% CI: 0.75, 0.92), and did not affect heartburn (RR: 0.89; 95% CI: 0.70, 1.13). There were no between-diet differences for diarrhea/loose stools, constipation, bloating, and nausea.Although a higher carbohydrate amount in DASH-style diets can increase diet satisfaction, it can also decrease satiety and increase heartburn in adults with overweight or obesity.This trial is registered at clinicaltrials.gov as NCT00608049.
Published:
May 28, 2021
Title:
The Risk of Fasting Triglycerides and its Related Indices for Ischemic Cardiovascular Diseases in Japanese Community Dwellers: the Suita Study
Authors:
Higashiyama, Aya; Wakabayashi, Ichiro; Okamura, Tomonori; Kokubo, Yoshihiro; Watanabe, Makoto; Takegami, Misa; Honda-Kohmo, Kyoko; Okayama, Akira; Miyamoto, Yoshihiro
Abstract:
AIM: A prospective cohort study in a Japanese urban general population was performed to investigate whether triglyceride (TG) and its related indices were associated with the risk for the incidence of ischemic cardiovascular disease (CVD) after the adjustment for low-density lipoprotein cholesterol (LDL-C) in Asian community dwellers. METHODS: A 15.1-year prospective cohort study was performed in 6,684 Japanese community dwellers aged 30-79 years without a history of CVD and whose fasting TG levels were ＜400 mg/dL. After adjusting for covariates, including LDL-C, the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of the deciles (D) of TG and those of 1-standard deviation (SD) increment of log-transformed TG (1-SD of TG) according to LDL-C level (≥ 140 and ＜140 mg/dL) for ischemic CVD incidence were estimated. The multivariable-adjusted HRs and 95%CIs of the quintiles (Q) of TG, TG/HDL-C, and the cardiometabolic index (CMI) for ischemic CVD were also estimated. RESULTS: In 101,230 person-years, 464 ischemic CVD cases occurred. For D10 of TG, the HR (95%CI) was 1.56 (1.05-2.32), and for 1-SD of TG, it was 1.30 (1.00-1.70) in participants with LDL-C ＜140 mg/dL and 1.07 (0.77-1.50) in those with LDL-C ≥ 140 mg/dL. For Q5 of the CMI, the multivariable-adjusted HR was higher than those of TG and TG/HDL-C. CONCLUSIONS: Fasting TG was an independent predictor for ischemic CVD incidence after adjusting for LDL-C in Japanese community dwellers with TG ＜400 mg/dL. Among TG, TG/HDL-C, and the CMI, the CMI could be the most powerful predictor for ischemic CVD.
Published:
May 28, 2021
Title:
A binge high sucrose diet provokes systemic and cerebral inflammation in rats without inducing obesity
Authors:
Patkar, Omkar L.; Mohamed, Abdalla Z.; Narayanan, Ashwin; Mardon, Karine; Cowin, Gary; Bhalla, Rajiv; Stimson, Damion H. R.; Kassiou, Michael; Beecher, Kate; Belmer, Arnauld; Alvarez Cooper, Ignatius; Morgan, Michael; Hume, David A.; Irvine, Katharine M.; Bartlett, Selena E.; Nasrallah, Fatima; Cumming, Paul
Abstract:
While the dire cardiometabolic consequences of the hypercaloric modern ‘Western’ diet are well known, there is not much information on the health impact of a high sucrose diet not inducing weight gain. Here, we tested the hypothesis that rats reared with intermittent binge access to sucrose in addition to normal chow would develop an inflammatory response in brain. To test this hypothesis, we undertook serial PET/MRI scans with the TSPO ligand [18F]DPA714 in a group of (n=9) rats at baseline and again after voluntarily consuming 5% sucrose solution three days a week for three months. Compared to a control group fed with normal chow (n=9), the sucrose rats indeed showed widespread increases in the availability of cerebral binding sites for the microglial marker, despite normal weight gain compared to the control diet group. Subsequent immunofluorescence staining of the brains confirmed the PET findings, showing a widespread 20% increase in the abundance of IBA-1-positive microglia with characteristic ‘semi-activated’ morphology in the binge sucrose rats, which had 23% lower density of microglial endpoints and 25% lower mean process length compared to microglia in the control rats with ordinary feeding. GFAP immunofluorescence showed no difference in astroglial coverage in the sucrose rats, except for a slight reduction in hypothalamus. The binge sucrose diet-induced neuroinflammation was associated with a significant elevation of white blood cell counts. Taking these results together, we find that long-term intake of sucrose in a binge paradigm, similar in sucrose content to the contemporary Western diet, triggered a low-grade systemic and central inflammation in non-obese rats. The molecular mechanism of this phenomenon remains to be established.
Published:
May 27, 2021
Title:
Association of Carbohydrate and Fat Intake with Prevalence of Metabolic Syndrome Can Be Modified by Physical Activity and Physical Environment in Ecuadorian Adults: The ENSANUT-ECU Study
Authors:
Juna, Christian F.; Cho, Yoonhee; Ham, Dongwoo; Joung, Hyojee
Abstract:
The associations of lifestyle and environment with metabolic syndrome (MetS) and cardiovascular disease have recently resulted in increased attention in research. This study aimed to examine interactive associations among carbohydrate and fat intake, physical environment (i.e., elevation and humidity), lifestyle, and MetS among Ecuadorian adults. We used data from the Ecuador National Health and Nutrition Survey 2012 (ENSANUT-ECU), with a total of 6023 participants aged 20 to 60 years included in this study. Logistic regression was used to determine the association of status of carbohydrate and fat intake, low-carbohydrate high-fat diet (LCHF) and medium-carbohydrate and fat (MCF) diet with MetS, where the high-carbohydrate low-fat (HCLF) diet was used as a reference. Women with LCHF and MCF diets showed lower prevalence of increased blood pressure (OR = 0.34, 95% CI: 0.19-0.59; OR = 0.50, 95% CI: 0.32-0.79, respectively). Women with MCF diet also showed lower prevalence of elevated fasting glucose (OR = 0.58, 95% CI: 0.37-0.91). Moreover, there were negative associations between MetS and reduced HDL cholesterol in women with MCF diet residing in low relative humidity (OR = 0.66, 95% CI: 0.45-0.98) and in women with LCHF diet residing at a high elevation (OR = 0.37, 95% CI: 0.16-0.86). Additionally, higher prevalence of increased waist circumference was observed in men with both MFC and LCHF diets who were physically inactive (OR = 1.89, 95% CI: 1.12-3.20; OR = 2.34, 95% CI: 1.19-4.60, respectively) and residing in high relative humidity (OR = 1.90, 95% CI: 1.08-2.89; OR = 2.63, 95% CI: 1.32-5.28, respectively). Our findings suggest that LCHF intake is associated with lower blood pressure, while MCF intake is associated with lower blood pressure and fasting glucose in Ecuadorian women. Furthermore, the associations of carbohydrate and fat intake with prevalence of MetS can be modified by physical activity, relative humidity, and elevation. The obtained outcomes may provide useful information for health programs focusing on dietary intake and lifestyle according to physical environment of the population to promote health and prevent metabolic diseases.
Published:
May 27, 2021
Title:
Beneficial gut microbiome remodeled during intermittent fasting in humans
Authors:
Larrick, Jasmine W.; Mendelsohn, Andrew R.; Larrick, James
Abstract:
Intermittent fasting (IF) is the practice of restricting food intake for 12 to 48 hours per fasting cycle over a prolonged period of time. Previous work shows beneficial health effects such as weight loss and lower risk for cardiometabolic diseases. Although reduced calorie intake may account for some of the observed benefits of intermittent fasting, exact mechanisms are still unclear. Recent evidence indicates that intermittent fasting may lead to remodeling and increased taxonomic diversity in the human gut microbiome. In particular, the Lachnospiraceae family of anaerobic bacteria increased during fasting. This family, in the order Clostridiales, promotes butryogenesis in the gut, a process that is associated with healthful metabolic and prolongevity effects. IF-associated alterations to the microbiome may play a key role in the metabolic and potential healthspan-enhancing benefits of IF and dietary restriction.
Published:
May 27, 2021
Title:
Effect of Dietary Fatty Acids on MicroRNA Expression Related to Metabolic Disorders and Inflammation in Human and Animal Trials
Authors:
MacDonald-Ramos, Karla; Martínez-Ibarra, Alejandra; Monroy, Adriana; Miranda-Ríos, Juan; Cerbón, Marco
Abstract:
Dietary fatty acids (DFAs) play key roles in different metabolic processes in humans and other mammals. DFAs have been considered beneficial for health, particularly polyunsaturated (PUFAs) and monounsaturated fatty acids (MUFAs). Additionally, microRNAs (miRNAs) exert their function on DFA metabolism by modulating gene expression, and have drawn great attention for their potential as biomarkers and therapeutic targets. This review explicitly examined the effects of DFAs on miRNA expression associated with metabolic diseases, such as obesity, non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease (CVD), as well as inflammation, published in the last ten years. DFAs have been shown to induce and repress miRNA expression associated with metabolic disease and inflammation in different cell types and organisms, both in vivo and in vitro, depending on varying combinations of DFAs, doses, and the duration of treatment. However, studies are limited and heterogeneous in methodology. Additionally, recent studies demonstrated that high fat ketogenic diets, many enriched with saturated fats, do not increase serum saturated fat content in humans, and are not associated with increased inflammation. Thus, these findings shed light on the complexity of novel treatment and DFA interventions for metabolic disease and to maintain health. Further studies are needed to advance molecular therapeutic approaches, including miRNA-based strategies in human health and disease.
Published:
May 27, 2021
Title:
Obesity and Circulating Levels of Vitamin D before and after Weight Loss Induced by a Very Low-Calorie Ketogenic Diet
Authors:
Buscemi, Silvio; Buscemi, Carola; Corleo, Davide; De Pergola, Giovanni; Caldarella, Rosalia; Meli, Francesco; Randazzo, Cristiana; Milazzo, Salvatore; Barile, Anna Maria; Rosafio, Giuseppe; Settipani, Valentina; Gurrera, Sabina; Borzì, Antonio Maria; Ciaccio, Marcello
Abstract:
Background: Vitamin D plays a pivotal role in calcium and phosphorus metabolism, also influencing bone tissue. Several studies have reported that vitamin D blood levels were significantly lower in people with obesity, probably due to its uptake by the adipose tissue. Clinical studies that investigated the changes of circulating levels of vitamin D following weight loss reported controversial data. A very low-calorie ketogenic diet is acknowledged as a reliable treatment to achieve a rapid weight loss. Therefore, we investigated the effect of weight loss, consequent to a very low-calorie ketogenic diet, on vitamin D blood concentrations. Methods: A cohort of 31 people with obesity underwent a very low-calorie ketogenic diet for 10-12 weeks. The serum concentrations of vitamin D, parathormone, calcium and phosphorous were measured before and after weight loss; they were compared to a control group of 20 non-obese, non-diabetic, age- and gender-matched persons. Results: Patients with obesity had a higher habitual intake of vitamin D than the control group (p < 0.05). However, the vitamin D blood levels of the obese group were significantly lower than those of the control group (p < 0.005) and they increased after weight loss (p < 0.001). At baseline, vitamin D blood concentrations of the persons with obesity were significantly correlated with both fat mass-kg (r = -0.40; p < 0.05) and body mass index (r = -0.47; p < 0.01). Following very low-calorie ketogenic diet, the change in vitamin D serum concentrations was correlated only with the change in fat mass-kg (r = -0.43; p
Published:
May 27, 2021
Title:
High Consumption of Ultra-Processed Food is Associated with Incident Dyslipidemia: A Prospective Study of Older Adults
Authors:
Donat-Vargas, Carolina; Sandoval-Insausti, Helena; Rey-García, Jimena; Moreno-Franco, Belén; Åkesson, Agneta; Banegas, Jose Ramón; Rodríguez-Artalejo, Fernando; Guallar-Castillón, Pilar
Abstract:
BACKGROUND: Ultra-processed food (UPF) consumption has been associated with higher cardiovascular disease (CVD) and mortality risks. OBJECTIVES: The aim of this study was to assess the relationship between UPF consumption and incident dyslipidemia in older adults, where evidence is limited. METHODS: We studied a prospective cohort of 1082 community-dwelling adults in Spain, older than 60 (mean age, 68 ± 6 years old). Participants (52% were women) were recruited between 2008-10 and followed up to 2015. At baseline, food intake data were collected using a validated computerized face-to-face dietary history. UPFs were identified according to the nature and extent of their industrial processing (NOVA classification). Triglycerides, HDL cholesterol, and LDL cholesterol were measured in fasting plasma samples collected at baseline and at follow-up. Statistical analyses were performed with logistic regression adjusted for the main potential confounders. RESULTS: Among those free of corresponding dyslipidemia at baseline, and after a follow-up of between 5 to 7 years, 60 (out of 895) developed incident hypertriglyceridemia (≥150 mg/dL), 112 (out of 878) had low HDL cholesterol (<40 in men/129 mg/dL). The mean percentage of UPF consumption was 19% ± 11% of total energy intake. Those in the highest versus the lowest tertile of energy intake from UPFs had more than twice the odds of incident hypertriglyceridemia (OR, 2.66; 95% CI: 1.20-5.90; P-trend, 0.011) or low HDL cholesterol (OR, 2.23; 95% CI: 1.22-4.05; P-trend, 0.012). UPF consumption was not associated with high LDL cholesterol plasma concentrations. CONCLUSIONS: Although UPF consumption in Spain was low among older adults, high consumption of UPFs was clearly associated with incident dyslipidemia. The increase in CVD risk recently found to be associated with UPF consumption might be mediated by these atherogenic lipid abnormalities.
Published:
May 26, 2021
Title:
Reduction of Cardio-Metabolic Risk and Body Weight through a Multiphasic Very-Low Calorie Ketogenic Diet Program in Women with Overweight/Obesity: A Study in a Real-World Setting
Authors:
Tragni, Elena; Vigna, Luisella; Ruscica, Massimiliano; Macchi, Chiara; Casula, Manuela; Santelia, Alfonso; Catapano, Alberico L.; Magni, Paolo
Abstract:
BACKGROUND: The prevention and treatment of obesity and its cardio-metabolic complications are relevant issues worldwide. Among lifestyle approaches, very low-calorie ketogenic diets (VLCKD) have been shown to lead to rapid initial weight loss, resulting in better long-term weight loss maintenance. As no information on VLCKD studies carried on in a real-world setting are available, we conducted this multi-centre study in a real-world setting, aiming at assessing the efficacy and the safety of a specific multiphasic VLCKD program in women with overweight or obesity. METHODS: A multi-center, prospective, uncontrolled trial was conducted in 33 outpatient women (age range 27-60 y) with overweight or obesity (BMI: 30.9 ± 2.7 kg/m2; waist circumference: 96.0 ± 9.4 cm) who started a VLCKD dietary program (duration: 24 weeks), divided into four phases. The efficacy of VLCKD was assessed by evaluating anthropometric measures and cardiometabolic markers; liver and kidney function biomarkers were assessed as safety parameters. RESULTS: The VLCKD program resulted in a significant decrease of body weight and BMI (-14.6%) and waist circumference (-12.4%). At the end of the protocol, 33.3% of the participants reached a normal weight and the subjects in the obesity range were reduced from 70% to 16.7%. HOMA-IR was markedly reduced from 3.17 ± 2.67 to 1.73 ± 1.23 already after phase 2 and was unchanged thereafter. Systolic blood pressure decreased after phase 1 (-3.5 mmHg) and remained unchanged until the end of the program. Total and LDL cholesterol and triglycerides were significantly reduced by VLCKD along with a significant HDL cholesterol increase. Liver, kidney and thyroid function markers did not change and remained within the reference range. CONCLUSIONS: The findings of a multi-center VLCKD program conducted in a real-world setting in a cohort of overweight/obese women indicate that it is safe and effective, as it results in a major improvement of cardiometabolic parameters, thus leading to benefits that span well beyond the mere body weight/adiposity reduction.
Published:
May 26, 2021
Title:
Hyperketonemia as the diagnostic basis in for Hypothermia: An experimental study in diabetic and control mice
Authors:
Nogami, Makoto; Nishio, Tadashi; Hoshi, Tomoaki; Toukairin, Yoko; Arai, Tomomi
Abstract:
Hypothermia is an important cause of death in forensic pathology. For the forensic diagnosis of hypothermia, some reports point out the possibility that hypothermia without diabetes may cause ketoacidosis. In this study, we evaluated the diagnostic value of ketoacidosis in a murine model of hypothermia, using the cold stress at 4 °C for 3 or 5 hrs in genetically diabetic (BKS.Cg-+Leprdb/+Leprdb/J) mice, compared with control (BKS.Cg- Dock7m+/Dock7m+/J) mice. The core temperature decrease was larger in diabetic mice than in control mice. We observed a novel finding that ketoacidosis assessed by elevated serum 3-hydroxybutyrate (3HB) occurs in hypothermia both in diabetic and control mice. Diabetic mice showed a prominent elevation of serum 3HB under cold stress. The protein expressions of monocarboxylate cotransporter 1 (MCT1), the channel protein used for the uptake of 3HB in skeletal muscles, showed a statistically significant decrease under cold stress for 3 hrs in control mice, indicating that the serum 3HB increase may be partially due to the decrease in the cellular uptake through the channel protein. Our results suggest the usefulness of hyperketonemia for the diagnosis of hypothermia not only in diabetic but also in non-diabetic cases.
Published:
May 25, 2021
Title:
Intermittent fasting enhances long-term memory consolidation, adult hippocampal neurogenesis, and expression of longevity gene Klotho
Authors:
Dias, Gisele Pereira; Murphy, Tytus; Stangl, Doris; Ahmet, Selda; Morisse, Benjamin; Nix, Alina; Aimone, Lindsey J.; Aimone, James B.; Kuro-O, Makoto; Gage, Fred H.; Thuret, Sandrine
Abstract:
Daily calorie restriction (CR) and intermittent fasting (IF) enhance longevity and cognition but the effects and mechanisms that differentiate these two paradigms are unknown. We examined whether IF in the form of every-other-day feeding enhances cognition and adult hippocampal neurogenesis (AHN) when compared to a matched 10% daily CR intake and ad libitum conditions. After 3 months under IF, female C57BL6 mice exhibited improved long-term memory retention. IF increased the number of BrdU-labeled cells and neuroblasts in the hippocampus, and microarray analysis revealed that the longevity gene Klotho (Kl) was upregulated in the hippocampus by IF only. Furthermore, we found that downregulating Kl in human hippocampal progenitor cells led to decreased neurogenesis, whereas Kl overexpression increased neurogenesis. Finally, histological analysis of Kl knockout mice brains revealed that Kl is required for AHN, particularly in the dorsal hippocampus. These data suggest that IF is superior to 10% CR in enhancing memory and identifies Kl as a novel candidate molecule that regulates the effects of IF on cognition likely via AHN enhancement.
Published:
May 25, 2021
Title:
Intermittent fasting enhances long-term memory consolidation, adult hippocampal neurogenesis, and expression of longevity gene Klotho
Authors:
Dias, Gisele Pereira; Murphy, Tytus; Stangl, Doris; Ahmet, Selda; Morisse, Benjamin; Nix, Alina; Aimone, Lindsey J.; Aimone, James B.; Kuro-O, Makoto; Gage, Fred H.; Thuret, Sandrine
Abstract:
Daily calorie restriction (CR) and intermittent fasting (IF) enhance longevity and cognition but the effects and mechanisms that differentiate these two paradigms are unknown. We examined whether IF in the form of every-other-day feeding enhances cognition and adult hippocampal neurogenesis (AHN) when compared to a matched 10% daily CR intake and ad libitum conditions. After 3 months under IF, female C57BL6 mice exhibited improved long-term memory retention. IF increased the number of BrdU-labeled cells and neuroblasts in the hippocampus, and microarray analysis revealed that the longevity gene Klotho (Kl) was upregulated in the hippocampus by IF only. Furthermore, we found that downregulating Kl in human hippocampal progenitor cells led to decreased neurogenesis, whereas Kl overexpression increased neurogenesis. Finally, histological analysis of Kl knockout mice brains revealed that Kl is required for AHN, particularly in the dorsal hippocampus. These data suggest that IF is superior to 10% CR in enhancing memory and identifies Kl as a novel candidate molecule that regulates the effects of IF on cognition likely via AHN enhancement.
Published:
May 25, 2021
Title:
Is protein the forgotten ingredient: Effects of higher compared to lower protein diets on cardiometabolic risk factors: a systematic review and meta-analysis of randomised controlled trials
Authors:
Vogtschmidt, Yakima D.; Raben, Anne; Faber, Ilona; Wilde, Claudia de; Lovegrove, Julie A.; Givens, D. Ian; Pfeiffer, Andreas F. H.; Soedamah-Muthu, Sabita S.
Abstract:
Abstract
Background and aims
Higher protein (HP) diets may lead to lower cardiometabolic risk than lower protein (LP) diets. This systematic review and meta-analysis aims to investigate the effects of HP vs. LP diets on cardiometabolic risk factors in adults, using most up-to-date evidence from randomised controlled trials (RCTs).
Methods
Systematic searches were conducted in electronic databases, up to November 2020. Random effects meta-analyses were conducted to pool the standardised mean differences (SMD) and 95% confidence intervals (CI). The main outcomes were weight loss, body mass index (BMI), waist circumference, fat mass, systolic and diastolic BP, total cholesterol, HDL-and LDL-cholesterol, triacylglycerol, fasting glucose and insulin, and glycated haemoglobin.
Results
Fifty-seven articles reporting on 54 RCTs were included, involving 4,344 participants (65% female, mean age: 46 (SD 10) years, mean BMI: 33 (SD 3) kg/m2), with a mean study duration of 18 weeks (range: 4 to 156). Compared to LP diets (range protein (E%):10-23%), HP diets (range protein (E%): 20-45%) led to more weight loss (SMD -0.13, 95% CI: -0.23, -0.03), greater reductions in fat mass (SMD -0.14, 95% CI: -0.24, -0.04), systolic BP (SMD -0.12, 95% CI: -0.21, -0.02), total cholesterol (SMD -0.11, 95% CI: -0.19, -0.02), triacylglycerol (SMD -0.22, 95% CI: -0.30, -0.14) and insulin (SMD -0.12, 95% CI: -0.22, -0.03). No significant differences were observed for the other outcomes.
Conclusions
Higher protein diets showed small, but favourable effects on weight loss, fat mass loss, systolic blood pressure, some lipid outcomes and insulin, compared to lower protein diets.
Published:
May 25, 2021
Title:
Erectile Dysfunction Is a Hallmark of Cardiovascular Disease: Unavoidable Matter of Fact or Opportunity to Improve Men's Health?
Authors:
Yannas, Dimitri; Frizza, Francesca; Vignozzi, Linda; Corona, Giovanni; Maggi, Mario; Rastrelli, Giulia
Abstract:
Erectile dysfunction (ED) is an early manifestation of cardiovascular (CV) disease. For this reason, men with ED should be carefully assessed for CV risk factors in order to prevent future major adverse CV events (MACE). Traditional risk factors are not found in all subjects at high CV risk. In fact, a relevant proportion of MACE occurs in men who are apparently risk factor free. In men with ED, it is important to take into account not only traditional risk factors but also unconventional ones. Several parameters that derive from good clinical assessment of subjects with ED have proven to be valuable predictors of MACE. These include family history of cardiometabolic events, alcohol abuse, fatherhood, decreased partner's sexual interest, severe impairment in erection during intercourse or during masturbation, impaired fasting glucose, increased triglycerides, obesity even without metabolic complications, decreased penile blood flows or impaired response to an intra-cavernosal injection test. Recognizing these risk factors may help in identifying, among subjects with ED, those who merit stricter lifestyle or pharmacological interventions to minimize their CV risk. Effective correction of risk factors in ED men considered as high risk, besides reducing CV risk, is also able to improve erectile function.
Published:
May 20, 2021
Title:
Postprandial Lipid Metabolism in Normolipidemic Subjects and Patients with Mild to Moderate Hypertriglyceridemia: Effects of Test Meals Containing Saturated Fatty Acids, Mono-Unsaturated Fatty Acids, or Medium-Chain Fatty Acids
Authors:
Folwaczny, Alexander; Waldmann, Elisa; Altenhofer, Julia; Henze, Kerstin; Parhofer, Klaus G.
Abstract:
Fasting and postprandial hypertriglyceridemia are causal risk factors for atherosclerosis. The prevalence of hypertriglyceridemia is approximately 25-30% and most hypertriglyceridemic patients suffer from mild to moderate hypertriglyceridemia. Data regarding dietary interventions on postprandial triglyceride metabolism of mildly to moderately hypertriglyceridemic patients is, however, sparse. In a randomized controlled trial, eight mildly hypertriglyceridemic patients and five healthy, normolipidemic controls received three separate standardized fat-meals containing either saturated fatty acids (SFA), mono-unsaturated fatty acids (MUFA), or medium-chain fatty acids (MCFA) in a randomized order. Fasting and postprandial lipid parameters were determined over a 10 h period and the (incremental) area under the curve (AUC/iAUC) for plasma triglycerides and other parameters were determined. MCFA do not lead to a significant elevation of postprandial total plasma triglycerides and other triglyceride parameters, while both SFA (patients: p = 0.003, controls: p = 0.03 compared to MCFA) and MUFA (patients: p = 0.001; controls: p = 0.14 compared to MCFA) do lead to such an increase. Patients experienced a significantly more pronounced increase of plasma triglycerides than controls (SFA: patients iAUC = 1006 mg*h/dL, controls iAUC = 247 mg*h/dL, p = 0.02; MUFA: patients iAUC = 962 mg*h/dL, controls iAUC = 248 mg*h/dL, p = 0.05). Replacing SFA with MCFA may be a treatment option for mildly to moderately hypertriglyceridemic patients as it prevents postprandial hypertriglyceridemia.
Published:
May 20, 2021
Title:
The effect of ketogenic diet escalation in adolescents and adults with drug-resistant epilepsy: a prospective study
Authors:
Kishk, Nirmeen Adel; Yousof, Hanaa Zaghloul; Ebraheim, Asmaa Mohamed; Elkholy, Thanaa Abdel Fattah Ali; Soliman, Shaimaa H.; Mohammed, Randa Adel; Shamloul, Reham Mohamed
Abstract:
Background Ketogenic diet (KD) is an accepted and effective treatment modality in patients with drug-resistant epilepsy (DRE). Different versions of ketogenic diets have been studied, however, the effect of ratio escalation in adolescence and adults has not been previously investigated.Methods The current open-labeled interventional study was conducted on 80 patients with drug-resistant epilepsy DRE, 40 patients (intervention group) were exposed to dietary intervention besides their regular antiseizure medication (ASM) and compared to 40 control patients. The intervention group received Ketogenic diet in 2:1 ratio for 1 month then were divided into 2 subgroups, group A1 continued the 2:1 ratio for another 2 months while group A2 escalated to 3:1 dietary regimen. Socio-demographic, anthropometric measurements, epilepsy clinical parameters, and laboratory tests were recorded in addition to safety and tolerability documentation. The response rate was recorded after 1month and 3month.Results Significant decrease in seizure frequency and severity were detected in Group A1 and A2 patients compared to controls after the 3 month period of intervention with significant improvement of quality of life scores in both subgroups. Both subgroups also showed comparable results regarding their response rate to KD. Better acceptance of diet taste were reported by subgroup A1 with a significantly higher lipid profile detected in subgroup A2.Conclusion KD has a beneficial effect as adjunctive treatment in adolescents and adults with DRE. Escalation from 2:1 to 3:1 ratio is associated with less compliance rather than better response in patients with DRE.
Published:
May 20, 2021
Title:
The effect of morning vs evening exercise training on glycaemic control and serum metabolites in overweight/obese men: a randomised trial
Authors:
Moholdt, Trine; Parr, Evelyn B.; Devlin, Brooke L.; Debik, Julia; Giskeødegård, Guro; Hawley, John A.
Abstract:
AIMS/HYPOTHESIS: We determined whether the time of day of exercise training (morning vs evening) would modulate the effects of consumption of a high-fat diet (HFD) on glycaemic control, whole-body health markers and serum metabolomics. METHODS: In this three-armed parallel-group randomised trial undertaken at a university in Melbourne, Australia, overweight/obese men consumed an HFD (65% of energy from fat) for 11 consecutive days. Participants were recruited via social media and community advertisements. Eligibility criteria for participation were male sex, age 30-45 years, BMI 27.0-35.0 kg/m2 and sedentary lifestyle. The main exclusion criteria were known CVD or type 2 diabetes, taking prescription medications, and shift-work. After 5 days, participants were allocated using a computer random generator to either exercise in the morning (06:30 hours), exercise in the evening (18:30 hours) or no exercise for the subsequent 5 days. Participants and researchers were not blinded to group assignment. Changes in serum metabolites, circulating lipids, cardiorespiratory fitness, BP, and glycaemic control (from continuous glucose monitoring) were compared between groups. RESULTS: Twenty-five participants were randomised (morning exercise n = 9; evening exercise n = 8; no exercise n = 8) and 24 participants completed the study and were included in analyses (n = 8 per group). Five days of HFD induced marked perturbations in serum metabolites related to lipid and amino acid metabolism. Exercise training had a smaller impact than the HFD on changes in circulating metabolites, and only exercise undertaken in the evening was able to partly reverse some of the HFD-induced changes in metabolomic profiles. Twenty-four-hour glucose concentrations were lower after 5 days of HFD compared with the participants' habitual diet (5.3 ± 0.4 vs 5.6 ± 0.4 mmol/l, p = 0.001). There were no significant changes in 24 h glucose concentrations for either exercise group but lower nocturnal glucose levels were observed in participants who trained in the evening, compared with when they consumed the HFD alone (4.9 ± 0.4 vs 5.3 ± 0.3 mmol/l, p = 0.04). Compared with the no-exercise group, peak oxygen uptake improved after both morning (estimated effect 1.3 ml min-1 kg-1 [95% CI 0.5, 2.0], p = 0.003) and evening exercise (estimated effect 1.4 ml min-1 kg-1 [95% CI 0.6, 2.2], p = 0.001). Fasting blood glucose, insulin, cholesterol, triacylglycerol and LDL-cholesterol concentrations decreased only in participants allocated to evening exercise training. There were no unintended or adverse effects. CONCLUSIONS/INTERPRETATION: A short-term HFD in overweight/obese men induced substantial alterations in lipid- and amino acid-related serum metabolites. Improvements in cardiorespiratory fitness were similar regardless of the time of day of exercise training. However, improvements in glycaemic control and partial reversal of HFD-induced changes in metabolic profiles were only observed when participants exercise trained in the evening. TRIAL REGISTRATION: anzctr.org.au registration no. ACTRN12617000304336. FUNDING: This study was funded by the Novo Nordisk Foundation (NNF14OC0011493).
Published:
May 19, 2021
Title:
Effects of a low-carbohydrate ketogenic diet on health parameters in resistance-trained women
Authors:
Vargas-Molina, Salvador; Carbone, Leandro; Romance, Ramón; Petro, Jorge L.; Schoenfeld, Brad J.; Kreider, Richard B.; Bonilla, Diego A.; Benítez-Porres, Javier
Abstract:
PURPOSE: The aim of this study was to evaluate the effect of a ketogenic diet on blood pressure, visceral adipose tissue (VAT), bone mineral content (BMC), and bone mineral density (BMD) in trained women. METHODS: Twenty-one resistance-trained women performed an 8-week resistance training program after a 3-week familiarization phase. Participants were randomly assigned to a non-ketogenic diet (n = 11, NKD) or ketogenic diet (n = 10, KD) group. Health parameters were measured before and after the nutritional intervention. Blood pressure was measured using a digital automatic monitor, while VAT, BMC, and BMD changes were measured by dual-energy X-ray absorptiometry. RESULTS: There was a significant reduction in systolic blood pressure in KD (mean ± SD [IC 95%], P value, Hedges' g; - 6.3 ± 6.0 [- 10.5, - 2.0] mmHg, P = 0.009, g = - 0.81) but not in NKD (- 0.4 ± 8.9 [- 6.8, 6.0] mmHg, P = 0.890, g = - 0.04). The results on VAT showed no changes in both groups. The KD showed a small favorable effect on BMD (0.02 ± 0.02 [0.01, 0.03] g·cm-2, P = 0.014, g = 0.19) while NKD did not show significant changes (0.00 ± 0.02 [- 0.02, 0.02] g·cm-2, P = 0.886, g = 0.01). No differences in group or in the time × group interaction were found in any of the variables. CONCLUSIONS: Consuming a low-carbohydrate high-fat KD in conjunction with a resistance training program might help to promote the improvement of health-related markers in resistance-trained women. Long-term studies are required to evaluate the superiority of a KD in comparison to a traditional diet.
Published:
May 18, 2021
Title:
Kokumi taste perception is functional in a model carnivore, the domestic cat (Felis catus)
Authors:
Laffitte, A.; Gibbs, M.; Hernangomez de Alvaro, C.; Addison, J.; Lonsdale, Z. N.; Giribaldi, M. G.; Rossignoli, A.; Vennegeerts, T.; Winnig, M.; Klebansky, B.; Skiles, J.; Logan, D. W.; McGrane, S. J.
Abstract:
Kokumi taste is a well-accepted and characterised taste modality and is described as a sensation of enhancement of sweet, salty, and umami tastes. The Calcium Sensing Receptor (CaSR) has been designated as the putative kokumi taste receptor for humans, and a number of kokumi-active ligands of CaSR have been discovered recently with activity confirmed both in vivo and in vitro. Domestic cats (Felis catus) are obligate carnivores and accordingly, their diet is abundant in proteins, peptides, and amino acids. We hypothesised that CaSR is a key taste receptor for carnivores, due to its role in the detection of different peptides and amino acids in other species. Using in silico, in vitro and in vivo approaches, here we compare human CaSR to that of a model carnivore, the domestic cat. We found broad similarities in ligand specificity, but differences in taste sensitivity between the two species. Indeed our in vivo data shows that cats are sensitive to CaCl2 as a kokumi compound, but don't show this same activity with Glutathione, whereas for humans the reverse is true. Collectively, our data suggest that kokumi is an important taste modality for carnivores that drives the palatability of meat-derived compounds such as amino acids and peptides, and that there are differences in the perception of kokumi taste between carnivores and omnivores.
Published:
May 18, 2021
Title:
SARS-CoV-2 infects human pancreatic β cells and elicits β cell impairment
Authors:
Wu, Chien-Ting; Lidsky, Peter V.; Xiao, Yinghong; Lee, Ivan T.; Cheng, Ran; Nakayama, Tsuguhisa; Jiang, Sizun; Demeter, Janos; Bevacqua, Romina J.; Chang, Charles A.; Whitener, Robert L.; Stalder, Anna K.; Zhu, Bokai; Chen, Han; Goltsev, Yury; Tzankov, Alexandar; Nayak, Jayakar V.; Nolan, Garry P.; Matter, Matthias S.; Andino, Raul; Jackson, Peter K.
Abstract:
Published:
May 18, 2021
Title:
Effects of a Self-Prepared Carbohydrate-Reduced High-Protein Diet on Cardiovascular Disease Risk Markers in Patients with Type 2 Diabetes
Authors:
Alzahrani, Ahmad H.; Skytte, Mads J.; Samkani, Amirsalar; Thomsen, Mads N.; Astrup, Arne; Ritz, Christian; Frystyk, Jan; Holst, Jens J.; Madsbad, Sten; Haugaard, Steen B.; Krarup, Thure; Larsen, Thomas M.; Magkos, Faidon
Abstract:
We previously observed beneficial effects of a carbohydrate-reduced, high-protein (CRHP) diet on cardiovascular risk markers in patients with type 2 diabetes mellitus (T2DM) in a crossover 2 × 6-week trial, when all food was provided to subjects as ready-to-eat meals. Here, we report the results from a 6-month open label extension: 28 patients with T2DM were instructed to self-prepare the CRHP diet with dietetic guidance. At weeks 0, 6, 12, and 36, fasting and postprandial (4-h meal test) blood samples were collected for measurements of total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triacylglycerol (TG), apolipoproteins A1 and B, non-esterified fatty acids (NEFA), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6. Diurnal blood pressure and heart rate were also assessed. At the end of the study (week 36), concentrations of fasting total and LDL-cholesterol, fasting and postprandial NEFA and TG, and fasting apolipoprotein-B, CRP and TNF-α concentrations were significantly lower compared with week 0 (p < 0.05). A significant decrease in diurnal heart rate was also observed. From week 12 to 36, an increase in HDL-cholesterol and apolipoprotein-A1 concentrations and a further reduction in fasting and postprandial NEFA (p
Published:
May 17, 2021
Title:
Hyperglycemia as a risk factor in pancreatic cancer: A nested case-control study using prediagnostic blood glucose levels
Authors:
Jacobson, Sara; Dahlqvist, Per; Johansson, Mattias; Svensson, Johan; Billing, Ola; Sund, Malin; Franklin, Oskar
Abstract:
OBJECTIVE: To determine the risk association between fasting glucose levels and pancreatic cancer using systematically collected prediagnostic blood glucose samples. METHODS: Prospective nested case-control study of participants from the Northern Sweden Health and Disease Study, including 182 cases that developed pancreatic cancer and four matched controls per case. Blood glucose levels collected up to 24 years before pancreatic cancer diagnosis were analyzed. The association between fasting glucose levels and pancreatic cancer risk was determined using unconditional and conditional logistic regression models. The association between fasting glucose and the time to pancreatic cancer diagnosis, tumor stage and survival was determined using likelihood-ratio test, t-test and log rank test. RESULTS: The unadjusted risk of developing pancreatic cancer increased with increasing fasting glucose levels (OR 1.30, 95% CI 1.05-1.60, P = .015). Impaired fasting glucose (≥6.1 mmol/L) was associated with an adjusted risk of 1.77 for developing pancreatic cancer (95% CI 1.05-2.99, P = .032). In subgroup analysis, fasting glucose levels were associated with an increased risk in never-smokers (OR 4.02, 95% CI 1.26-12.77, P = .018) and non-diabetics (OR 3.08, 95% CI 1.08-8.79, P = .035) (non-significant for interaction). The ratio between fasting glucose and BMI was higher among future pancreatic cancer patients and an increased ratio was associated with elevated risk of pancreatic cancer (OR 1.66, 95% CI 1.04-2.66, P = .034). Fasting glucose levels were not associated with TNM stage at diagnosis or survival. CONCLUSIONS: High fasting glucose is associated with an increased risk of being diagnosed with pancreatic cancer.
Published:
May 15, 2021
Title:
Renal gluconeogenesis in insulin resistance: A culprit for hyperglycemia in diabetes
Authors:
Sharma, Rajni; Tiwari, Swasti
Abstract:
Renal gluconeogenesis is one of the major pathways for endogenous glucose production. Impairment in this process may contribute to hyperglycemia in cases with insulin resistance and diabetes. We reviewed pertinent studies to elucidate the role of renal gluconeogenesis regulation in insulin resistance and diabetes. A consensus on the suppressive effect of insulin on kidney gluconeogenesis has started to build up. Insulin-resistant models exhibit reduced insulin receptor (IR) expression and/or post-receptor signaling in their kidney tissue. Reduced IR expression or post-receptor signaling can cause impairment in insulin's action on kidneys, which may increase renal gluconeogenesis in the state of insulin resistance. It is now established that the kidney contributes up to 20% of all glucose production via gluconeogenesis in the post-absorptive phase. However, the rate of renal glucose release excessively increases in diabetes. The rise in renal glucose release in diabetes may contribute to fasting hyperglycemia and increased postprandial glucose levels. Enhanced glucose release by the kidneys and renal expression of the gluconeogenic-enzyme in diabetic rodents and humans further point towards the significance of renal gluconeogenesis. Overall, the available literature suggests that impairment in renal gluconeogenesis in an insulin-resistant state may contribute to hyperglycemia in type 2 diabetes.
Published:
May 15, 2021
Title:
The Chemistry of the Ketogenic Diet: Updates and Opportunities in Organic Synthesis
Authors:
Williams, Michael Scott; Turos, Edward
Abstract:
The high-fat, low-carbohydrate (ketogenic) diet has grown in popularity in the last decade as a weight loss tool. Research into the diet's effects on the body have revealed a variety of other health benefits. The use of exogenous ketone supplements to confer the benefits of the diet without strict adherence to it represents an exciting new area of focus. Synthetic ketogenic compounds are of particular interest that has received very little emphasis and is an untapped area of focus for chemical synthesis. In this review, we summarize the chemical basis for ketogenicity and opportunities for further advancement of the field.
Published:
May 15, 2021
Title:
Cardiac Energy Metabolism in Heart Failure
Authors:
Lopaschuk, Gary D.; Karwi, Qutuba G.; Tian, Rong; Wende, Adam R.; Abel, E. Dale
Abstract:
Alterations in cardiac energy metabolism contribute to the severity of heart failure. However, the energy metabolic changes that occur in heart failure are complex and are dependent not only on the severity and type of heart failure present but also on the co-existence of common comorbidities such as obesity and type 2 diabetes. The failing heart faces an energy deficit, primarily because of a decrease in mitochondrial oxidative capacity. This is partly compensated for by an increase in ATP production from glycolysis. The relative contribution of the different fuels for mitochondrial ATP production also changes, including a decrease in glucose and amino acid oxidation, and an increase in ketone oxidation. The oxidation of fatty acids by the heart increases or decreases, depending on the type of heart failure. For instance, in heart failure associated with diabetes and obesity, myocardial fatty acid oxidation increases, while in heart failure associated with hypertension or ischemia, myocardial fatty acid oxidation decreases. Combined, these energy metabolic changes result in the failing heart becoming less efficient (ie, a decrease in cardiac work/O2 consumed). The alterations in both glycolysis and mitochondrial oxidative metabolism in the failing heart are due to both transcriptional changes in key enzymes involved in these metabolic pathways, as well as alterations in NAD redox state (NAD+ and nicotinamide adenine dinucleotide levels) and metabolite signaling that contribute to posttranslational epigenetic changes in the control of expression of genes encoding energy metabolic enzymes. Alterations in the fate of glucose, beyond flux through glycolysis or glucose oxidation, also contribute to the pathology of heart failure. Of importance, pharmacological targeting of the energy metabolic pathways has emerged as a novel therapeutic approach to improving cardiac efficiency, decreasing the energy deficit and improving cardiac function in the failing heart.
Published:
May 14, 2021
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