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In childhood and adolescent migraine, amitriptyline and topiramate were no better than placebo and not significantly different from each other in achieving a 50% or greater reduction in days with headache. The trial was stopped early for futility. More than 6 million children and adolescents in the United States have migraines. 1 – 3 The majority continue to have headaches into adulthood, taking a toll on the U.S. economy of approximately $36 billion and resulting in substantial effects on quality of life. 4 – 7 Pediatric clinical practice guidelines for migraine treatment are consensus based rather than evidence based, 8 , 9 with no Food and Drug Administration (FDA)–approved migraine prevention medication for children younger than 12 years of age. The Childhood and Adolescent Migraine Prevention (CHAMP) trial tested the effects of amitriptyline and topiramate in comparison with each other and with placebo in . . .

Valproate is widely accepted as a drug of first choice for patients with generalised onset seizures, and its broad spectrum of efficacy means it is recommended for patients with seizures that are difficult to classify. Lamotrigine and topiramate are also thought to possess broad spectrum activity. The SANAD study aimed to compare the longer-term effects of these drugs in patients with generalised onset seizures or seizures that are difficult to classify. SANAD was an unblinded randomised controlled trial in hospital-based outpatient clinics in the UK. Arm B of the study recruited 716 patients for whom valproate was considered to be standard treatment. Patients were randomly assigned to valproate, lamotrigine, or topiramate between Jan 12, 1999, and Aug 31, 2004, and follow-up data were obtained up to Jan 13, 2006. Primary outcomes were time to treatment failure, and time to 1-year remission, and analysis was by both intention to treat and per protocol. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN38354748. For time to treatment failure, valproate was significantly better than topiramate (hazard ratio 1·57 [95% CI 1·19–2·08]), but there was no significant difference between valproate and lamotrigine (1·25 [0·94–1·68]). For patients with an idiopathic generalised epilepsy, valproate was significantly better than both lamotrigine (1·55 [1·07–2·24] and topiramate (1·89 [1·32–2·70]). For time to 12-month remission valproate was significantly better than lamotrigine overall (0·76 [0·62–0·94]), and for the subgroup with an idiopathic generalised epilepsy 0·68 (0·53–0·89). But there was no significant difference between valproate and topiramate in either the analysis overall or for the subgroup with an idiopathic generalised epilepsy. Valproate is better tolerated than topiramate and more efficacious than lamotrigine, and should remain the drug of first choice for many patients with generalised and unclassified epilepsies. However, because of known potential adverse effects of valproate during pregnancy, the benefits for seizure control in women of childbearing years should be considered.

Age-related macular degeneration (AMD) is a complex multifactorial disease and the primary cause of legal and irreversible blindness among individuals aged ≥65 years in developed countries. Globally, it affects 30–50 million individuals, with an estimated increase of approximately 200 million by 2020 and approximately 300 million by 2040. Currently, the neovascular form may be able to be treated with the use of anti-VEGF drugs, while no effective treatments are available for the dry form. Many studies, such as the randomized controlled trials (RCTs) Age-Related Eye Disease Study (AREDS) and AREDS 2, have shown a potential role of micronutrient supplementation in lowering the risk of progression of the early stages of AMD. Recently, low-grade inflammation, sustained by dysbiosis and a leaky gut, has been shown to contribute to the development of AMD. Given the ascertained influence of the gut microbiota in systemic low-grade inflammation and its potential modulation by macro- and micro-nutrients, a potential role of diet in AMD has been proposed. This review discusses the role of the gut microbiota in the development of AMD. Using PubMed, Web of Science and Scopus, we searched for recent scientific evidence discussing the impact of dietary habits (high-fat and high-glucose or -fructose diets), micronutrients (vitamins C, E, and D, zinc, beta-carotene, lutein and zeaxanthin) and omega-3 fatty acids on the modulation of the gut microbiota and their relationship with AMD risk and progression.

Background: Excessive fructose intake causes metabolic syndrome in animals and can be partially prevented by lowering the uric acid level. We tested the hypothesis that fructose might induce features of metabolic syndrome in adult men and whether this is protected by allopurinol. Methods: A randomized, controlled trial of 74 adult men who were administered 200 g fructose daily for 2 weeks with or without allopurinol. Primary measures included changes in ambulatory blood pressure (BP), fasting lipids, glucose and insulin, homeostatic model assessment (HOMA) index, body mass index and criteria for metabolic syndrome. Results: The ingestion of fructose resulted in an increase in ambulatory BP (7±2 and 5±2 mm Hg for systolic (SBP) and diastolic BP (DBP), P<0.004 and P<0.007, respectively). Mean fasting triglycerides increased by 0.62±0.23 mmol l−1 (55±20 mg per 100 ml), whereas high-density lipoprotein cholesterol decreased by 0.06±0.02 mmol l−1 (2.5±0.7 mg per 100 ml), P<0.002 and P<0.001, respectively. Fasting insulin and HOMA indices increased significantly, whereas plasma glucose level did not change. All liver function tests showed an increase in values. The metabolic syndrome increased by 25–33% depending on the criteria. Allopurinol lowered the serum uric acid level (P<0.0001) and prevented the increase in 24-h ambulatory DBP and daytime SBP and DBP. Allopurinol treatment did not reduce HOMA or fasting plasma triglyceride levels, but lowered low-density lipoprotein cholesterol relative to control (P<0.02) and also prevented the increase in newly diagnosed metabolic syndrome (0–2%, P=0.009). Conclusions: High doses of fructose raise the BP and cause the features of metabolic syndrome. Lowering the uric acid level prevents the increase in mean arterial blood pressure. Excessive intake of fructose may have a role in the current epidemics of obesity and diabetes.

Background To study the efficacy of the oral administration of maltodextrin and fructose before major abdominal surgery (MAS). Methods This prospective, multicenter, parallel-controlled, double-blind study included patients aged 45–70 years who underwent elective gastrectomy, colorectal resection, or duodenopancreatectomy. The intervention group (IG) was given 800 mL and 400 mL of a maltodextrin and fructose beverage at 10 h and 2 h before MAS, respectively, and the control group (CG) received water under the same experimental conditions. The primary endpoint was insulin resistance index (IRI), and the secondary endpoints were fasting blood glucose, fasting insulin, insulin secretion index, insulin sensitivity index, intraoperative blood glucose, subjective comfort score, and clinical outcome indicators. Results A total of 240 cases were screened, of which 231 cases were randomly divided into two groups: 114 in the IG and 117 in the CG. No time-treatment effect was detected for any endpoint. The IRI and fasting insulin were significantly lower in the IG than CG after MAS ( p  = 0.02 & P  = 0.03). The scores for anxiety, appetite, and nausea were significantly lower in the IG than CG at 1 h before MAS. Compared with baseline, the scores for appetite and nausea decreased in the IG but increased in the CG. Conclusion The oral administration of maltodextrin and fructose before MAS can improve preoperative subjective well-being and reduce postoperative insulin resistance without increasing the risk of gastrointestinal discomfort.

d-allulose is a rare sugar with zero energy that can be consumed by obese/overweight individuals. Many studies have suggested that zero-calorie d-allulose has beneficial effects on obesity-related metabolism in mouse models, but only a few studies have been performed on human subjects. Therefore, we performed a preliminary study with 121 Korean subjects (aged 20–40 years, body mass index ≥ 23 kg/m2). A randomized controlled trial involving placebo control (sucralose, 0.012 g × 2 times/day), low d-allulose (d-allulose, 4 g × 2 times/day), and high d-allulose (d-allulose, 7 g × 2 times/day) groups was designed. Parameters for body composition, nutrient intake, computed tomography (CT) scan, and plasma lipid profiles were assessed. Body fat percentage and body fat mass were significantly decreased following d-allulose supplementation. The high d-allulose group revealed a significant decrease in not only body mass index (BMI), but also total abdominal and subcutaneous fat areas measured by CT scans compared to the placebo group. There were no significant differences in nutrient intake, plasma lipid profiles, markers of liver and kidney function, and major inflammation markers among groups. These results provide useful information on the dose-dependent effect of d-allulose for overweight/obese adult humans. Based on these results, the efficacy of d-allulose for body fat reduction needs to be validated using dual energy X-ray absorption.

Background A large number patients struggle with migraine which is classified as a chronic disorder. The relative efficacy, safety and tolerability of prophylactic medications for migraine play a key role in managing this disease. Methods We conducted an extensive literature search for popular prophylactic medications that are used for migraine patients. Pairwise meta-analysis and network meta-analysis (NMA) were carried out sequentially for determining the relative efficacy, safety and tolerability of prophylactic medications. Summary effect for migraine headache days, headache frequency, at least 50% reduction in headache attacks, all-adverse events, nausea, somnolence, dizziness, withdrawal and withdrawal due to adverse events were produced by synthesizing both direct and indirect evidence. Results Patients with three interventions exhibited significantly less average migraine headache days compared with those treated by placebo (topiramate, propranolol, divalproex). Moreover, topiramate and valproate exhibited a significantly increased likelihood of at least 50% reduction in migraine headache attacks compared to placebo. Patients with topiramate and propranolol also exhibited significantly reduced headache frequency compared to those with placebo. On the other hand, patients with divalproex exhibited significantly higher risk of nausea compared to those with placebo, topiramate, propranolol, gabapentin and amitriptyline. Finally, divalproex was associated with an increased risk of withdrawal compared to placebo and propranolol. Conclusions Topiramate, propranolol and divalproex may be more efficacious than other prophylactic medications. Besides, the safety and tolerability of divalproex should be further verified by future studies.

Abstract Context The consumption of high-fructose beverages is associated with a higher risk for obesity and diabetes. Fructose can stimulate glucagon-like peptide 1 (GLP-1) secretion in lean adults, in the absence of any anorexic effect. Objective We hypothesized that the ingestion of glucose and fructose may differentially stimulate GLP-1 and insulin response in lean adolescents and adolescents with obesity. Design We studied 14 lean adolescents [four females; 15.9 ± 1.6 years of age; body mass index (BMI), 21.8 ± 2.2 kg/m2] and 23 adolescents with obesity (five females; 15.1 ± 1.6 years of age; BMI, 34.5 ± 4.6 kg/m2). Participants underwent a baseline oral glucose tolerance test to determine their glucose tolerance and estimate insulin sensitivity and β-cell function [oral disposition index (oDIcpep)]. Eligible subjects received, in a double-blind, crossover design, 75 g of glucose or fructose. Plasma was obtained every 10 minutes for 60 minutes for the measures of glucose, insulin, and GLP-1 (radioimmunoassay) and glucose-dependent insulinotropic polypeptide (GIP; ELISA). Incremental glucose and hormone levels were compared between lean individuals and those with obesity by a linear mixed model. The relationship between GLP-1 increment and oDIcpep was evaluated by regression analysis. Results Following the fructose challenge, plasma glucose excursions were similar in both groups, yet the adolescents with obesity exhibited a greater insulin (P < 0.001) and GLP-1 (P < 0.001) increase than did their lean peers. Changes in GIP were similar in both groups. After glucose ingestion, the GLP-1 response (P < 0.001) was higher in the lean group. The GLP-1 increment during 60 minutes from fructose drink was correlated with a lower oDIcpep (r2 = 0.22, P = 0.009). Conclusion Fructose, but not glucose, ingestion elicits a higher GLP-1 and insulin response in adolescents with obesity than in lean adolescents. Fructose consumption may contribute to the hyperinsulinemic phenotype of adolescent obesity through a GLP-1–mediated mechanism. Fructose, but not glucose, ingestion causes a rapid and sustained rise in circulating GLP-1 levels in adolescents with obesity. The fructose-induced GLP-1 increase is associated with reduced β-cell function.

•A fructose-rich single meal leads to increased triglyceride and leukocyte levels.•A fructose overload in a typical meal does not affect systemic cytokine levels.•Intake of high-fructose meals potentializes inflammatory and metabolic dysfunction. We aimed to evaluate the acute effect of a fructose-rich single meal on metabolic and inflammatory biomarkers This single-center, double-masked, randomized crossover trial recruited females aged 20 to 47 with a normal body mass index and was conducted at Hospital das Clínicas (Belo Horizonte, MG, Brazil). Participants received a standardized meal with either sucrose, glucose, or a fructose overload. Blood samples were collected after overnight fasting (baseline) and at 30, 60, 120, and 240 minutes postprandial. Serum levels of glucose, triglycerides (primary outcome), total cholesterol, alanine aminotransferase, aspartate aminotransferase, adiponectin, leptin, resistin, interleukin (IL)-2, IL-4, IL-5, IL-6, IL-10, IL-17, interferon-gamma, tumor necrosis factor, eotaxin, and total blood leukocytes were measured. This trial was completed with 25 enrolled participants, and three dropped out. The per-protocol analysis included 22 participants. As expected, postprandial glycemia increased 30 minutes after consuming meals rich in sucrose (P = 0.045) or glucose (P < 0.001). Triglyceride and leucocyte concentrations increased only at 240 minutes after consuming a high-fructose meal (P < 0.05). Regardless of the type of carbohydrate overload, leptin concentrations decreased postprandially compared to baseline at all time points (P < 0.05). Four participants reported adverse events after consuming the standardized meal with glucose or fructose, including nausea and malaise. Our findings indicate that a fructose-rich single meal leads to a more significant increase in triglyceride and leukocyte concentrations compared to glucose and sucrose in healthy women. These findings support concerns regarding the potential inflammatory and metabolic dysfunction associated with frequent consumption of high-fructose meals.

OBJECTIVE-To assess the clinical efficacy of nutritional amounts of grape polyphenols (PPs) in counteracting the metabolic alterations of high-fructose diet, including oxidative stress and insulin resistance (IR), in healthy volunteers with high metabolic risk. RESEARCH DESIGN AND METHODS-Thirty-eight healthy overweight/obese first-degree relatives of type 2 diabetic patients (18 men and 20 women) were randomized in a double-blind controlled trial between a grape PP (2 g/day) and a placebo (PCB) group. Subjects were investigated at baseline and after 8 and 9 weeks of supplementation, the last 6 days of which they all received 3 g/kg fat-free mass/day of fructose. The primary end point was the protective effect of grape PPs on fructose-induced IR. RESULTS-In the PCB group, fructose induced 1) a 20% decrease in hepatic insulin sensitivity index (P < 0.05) and an 11% decrease in glucose infusion rate (P < 0.05) as evaluated during a two-step hyperinsulinemic-euglycemic clamp, 2) an increase in systemic (urinary F2-isoprostanes) and muscle (thiobarbituric acid-reactive substances and protein carbonylation) oxidative stress (P < 0.05), and 3) a downregulation of mitochondrial genes and decreased mitochondrial respiration (P < 0.05). All the deleterious effects of fructose were fully blunted by grape PP supplementation. Antioxidative defenses, inflammatory markers, and main adipokines were affected neither by fructose nor by grape PPs. CONCLUSIONS-A natural mixture of grape PPs at nutritional doses efficiently prevents fructose-induced oxidative stress and IR. The current interest in grape PP ingredients and products by the global food and nutrition industries could well make them a stepping-stone of preventive nutrition.