Standard setting in Australian medical schools

Background: Standard setting of assessment is critical in quality assurance of medical programs. The aims of this study were to identify and compare the impact of methods used to establish the passing standard by the 13 medical schools who participated in the 2014 Australian Medical Schools Assessment Collaboration (AMSAC). Methods: A survey was conducted to identify the standard setting procedures used by participating schools. Schools standard setting data was collated for the 49 multiple choice items used for benchmarking by AMSAC in 2014. Analyses were conducted for nine schools by their method of standard setting and key characteristics of 28 panel members from four schools. Results: Substantial differences were identified between AMSAC schools that participated in the study, in both the standard setting methods and how particular techniques were implemented. The correlation between the item standard settings data by school ranged from − 0.116 to 0.632. A trend was identified for panel members to underestimate the difficulty level of hard items and overestimate the difficulty level of easy items for all methods. The median derived cut-score standard across schools was 55% for the 49 benchmarking questions. Although, no significant differences were found according to panel member standard setting experience or clinicians versus scientists, panel members with a high curriculum engagement generally had significantly lower expectations of borderline candidates (p = 0.044). Conclusion: This study used a robust assessment framework to demonstrate that several standard setting techniques are used by Australian medical schools, which in some cases use different techniques for different stages of their program. The implementation of the most common method, the Modified Angoff standard setting approach was found to vary markedly. The method of standard setting used had an impact on the distribution of expected minimally competent student performance by item and overall, with the passing standard varying by up to 10%. This difference can be attributed to the method of standard setting because the ASMSAC items have been shown over time to have consistent performance levels reflecting similar cohort ability. There is a need for more consistency in the method of standard setting used by medical schools in Australia

Post-Prandial Glucose and Insulin Responses of Hummus Alone or Combined with a Carbohydrate Food: A Dose-Response Study

OBJECTIVES: Pulses are low glycemic index (GI) foods and have been associated with reduced risk of heart disease, diabetes and some cancers. However the blood glucose and insulin responses of hummus, a food containing chickpea, have not been thoroughly tested. METHODS: Ten healthy subjects each consumed 11 breakfast study meals in randomized order over a period of 15 weeks. Hummus was consumed alone at three doses (2.7 g, 10.8 g and 25 g available carbohydrate [avCHO] portions) and with 50 g avCHO from white bread at three doses (2.7 g, 5.4 g and 10.8 g avCHO portions). The responses elicited by hummus alone were compared with 25 g avCHO portions of white bread, while those after hummus plus white bread were compared with 50 g avCHO from white bread. Plasma glucose and serum insulin responses were monitored over two hours and the GI and insulin index (II) calculated using standard methodology. RESULTS: The GI and II of hummus were 15 ± 3 and 52 ± 13, respectively, and were significantly lower than white bread (P \u3c 0.05). The glucose and insulin incremental area under the curve (IAUC) for hummus alone were significantly lower than white bread except for insulin IAUC of hummus 25 g avCHO. The peak rise of blood glucose and insulin after hummus were significantly lower than after white bread. Glucose and insulin IAUC after adding hummus to bread did not differ significantly from white bread alone. However the blood glucose 45 min after adding 25 g avCHO from hummus to white bread was significantly lower while at 120 min it was significantly higher than after white bread alone. CONCLUSIONS: This study demonstrated that, similar to chickpeas, hummus has a very low GI and II. Postprandial glucose responses were 4 times less than that of white bread and did not compromise insulin levels

Design, synthesis and preliminary pharmacological evaluation of new imidazolinonesas L-DOPA prodrugs

L-DOPA, the immediate biological precursor of dopamine, is still considered the drug of choice in the treatment of Parkinson's disease. However, therapy with L-DOPA is associated with a number of acute problems. With the aim to increase the bioavailability after oral administration, we designed a multi-protected L-DOPA prodrugs able to release the drug by both spontaneous chemical or enzyme catalyzed hydrolysis. The new compounds have been synthesized and preliminarily evaluated for their water solubility, log P, chemical stability, and enzymatic stability. The results indicate that the incorporation of the amino acidic moiety of L-DOPA into an imidazoline-4-one ring provides prodrugs sufficiently stable to potentially cross unchanged the acidic environment of the stomach, and to be absorbed from the intestine. They also might be able to release L-DOPA in human plasma after enzymatic hydrolysis. The ability of prodrugs 6a-b to increase basal levels of striatal DA, and influence brain neurochemistry associated with dopaminergic activity following oral administration, as well as the radical-scavenging activity against DPPH for compounds 6a-b and 15a are also reported

Water Extract from Inflorescences of Industrial Hemp Futura 75 Variety as a Source of Anti-Inflammatory, Anti-Proliferative and Antimycotic Agents: Results from In Silico, In Vitro and Ex Vivo Studies

Industrial hemp (Cannabis sativa) is traditionally cultivated as a valuable source of fibers and nutrients. Multiple studies also demonstrated antimicrobial, anti-proliferative, phytotoxic and insecticide effects of the essential oil from hemp female inflorescences. On the other side, only a few studies explored the potential pharmacological application of polar extracts from inflorescences. In the present study, we investigated the water extract from inflorescences of industrial hemp Futura 75 variety, from phytochemical and pharmacological point of view. The water extract was assayed for phenolic compound content, radical scavenger/reducing, chelating and anti-tyrosinase effects. Through an ex vivo model of toxicity induced by lipopolysaccharide (LPS) on isolated rat colon and liver, we explored the extract effects on serotonin, dopamine and kynurenine pathways and the production of prostaglandin (PG)E2. Anti-proliferative effects were also evaluated against human colon cancer HCT116 cell line. Additionally, antimycotic effects were investigated against Trichophyton rubrum, Trichophyton interdigitale, Microsporum gypseum. Finally, in silico studies, including bioinformatics, network pharmacology and docking approaches were conducted in order to predict the putative targets underlying the observed pharmacological and microbiological effects. Futura 75 water extract was able to blunt LPS-induced reduction of serotonin and increase of dopamine and kynurenine turnover, in rat colon. Additionally, the reduction of PGE2 levels was observed in both colon and liver specimens, as well. The extract inhibited the HCT116 cell viability, the growth of T. rubrum and T. interdigitale and the activity of tyrosinase, in vitro, whereas in silico studies highlighting the inhibitions of cyclooxygenase-1 (induced by carvacrol), carbonic anhydrase IX (induced by chlorogenic acid and gallic acid) and lanosterol 14-α-demethylase (induced by rutin) further support the observed pharmacological and antimycotic effects. The present findings suggest female inflorescences from industrial hemp as high quality by-products, thus representing promising sources of nutraceuticals and cosmeceuticals against inflammatory and infectious diseases.Fil: Orlando, Giustino. University “G. d’Annunzio”. Department of Pharmacy; ItaliaFil: Recinella, Lucia. University “G. d’Annunzio”. Department of Pharmacy; ItaliaFil: Chiavaroli, Annalisa. University “G. d’Annunzio”. Department of Pharmacy; ItaliaFil: Brunetti, Luigi. University “G. d’Annunzio”. Department of Pharmacy; ItaliaFil: Leone, Sheila. University “G. d’Annunzio”. Department of Pharmacy; ItaliaFil: Carradori, Simone. University “G. d’Annunzio”. Department of Pharmacy; ItaliaFil: Di Simone, Simonetta. University “G. d’Annunzio”. Department of Pharmacy; ItaliaFil: Ciferri, Maria Chiara. University “G. d’Annunzio”. Department of Pharmacy; ItaliaFil: Zengin, Gokhan. Universidad de Selcuk; TurquíaFil: Ak, Gunes. Universidad de Selcuk; TurquíaFil: Abdullah, Hassan H.. Salahaddin University-Erbil; Iraq. Universiti Sains Malaysia; MalasiaFil: Cordisco, Estefanía. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Sortino, Maximiliano Andrés. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Svetaz, Laura Andrea. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Politi, Matteo. University “G. d’Annunzio”. Department of Pharmacy; ItaliaFil: Angelini, Paola. Università di Perugia; ItaliaFil: Covino, Stefano. Università di Perugia; ItaliaFil: Venanzoni, Roberto. Università di Perugia; ItaliaFil: Cesa, Stefania. Università degli Studi di Roma "La Sapienza"; ItaliaFil: Menghini, Luigi. University “G. d’Annunzio”. Department of Pharmacy; ItaliaFil: Ferrante, Claudio. University “G. d’Annunzio”. Department of Pharmacy; Itali

Impact of Foods and Dietary Supplements Containing Hydroxycinnamic Acids on Cardiometabolic Biomarkers: A Systematic Review to Explore Inter-Individual Variability

Plant-based diets rich in bioactive compounds such as polyphenols have been shown to positively modulate the risk of cardiometabolic (CM) diseases. The inter-individual variability in the response to these bioactives may affect the findings. This systematic review aimed to summarize findings from existing randomized clinical trials (RCTs) evaluating the effect of hydroxycinnamic acids (HCAs) on markers of CM health in humans. Literature searches were performed in PubMed and the Web of Science. RCTs on acute and chronic supplementation of HCA-rich foods/extracts on CM biomarkers were included. Forty-four RCTs (21 acute and 23 chronic) met inclusion criteria. Comparisons were made between RCTs, including assessments based on population health status. Of the 44 RCTs, only seven performed analyses on a factor exploring inter-individual response to HCA consumption. Results demonstrated that health status is a potentially important effect modifier as RCTs with higher baseline cholesterol, blood pressure and glycaemia demonstrated greater overall effectiveness, which was also found in studies where specific subgroup analyses were performed. Thus, the effect of HCAs on CM risk factors may be greater in individuals at higher CM risk, although future studies in these populations are needed, including those on other potential determinants of inter-individual variability. PROSPERO, registration number CRD42016050790

Nordic dietary patterns and cardiometabolic outcomes : a systematic review and meta-analysis of prospective cohort studies and randomised controlled trials

Funding Information: AZ is a part-time research associate at INQUIS Clinical Research (formerly Glycemic Index Laboratories), a contract research organisation, and a consultant for the Glycemic Index Foundation. AJG has received consulting fees from Solo GI Nutrition and an honorarium from the Soy Nutrition Institute. LC was a Mitacs Elevate postdoctoral fellow jointly funded by the Government of Canada and the Canadian Sugar Institute. She was previously employed as a casual clinical coordinator at INQUIS Clinical Research. TAK has received research support from the CIHR, the International Life Science Institute (ILSI) and the National Honey Board. He has been an invited speaker at the Calorie Control Council Annual Meeting for which he received an honorarium. EMC reports grants from the Natural Sciences and Engineering Research Council of Canada and the CIHR while this study was being conducted, has received research support from Lallemand Health Solutions and Ocean Spray, and has received consultant fees and speaker and travel support from Danone and Lallemand Health Solutions (all are outside this study). DR is director of Vuk Vrhovac University Clinic for Diabetes, Endocrinology and Metabolic Diseases at Merkur University Hospital, Zagreb, Croatia. He is the president of the Croatian Society for Diabetes and Metabolic Disorders of the Croatian Medical Association. He serves as an Executive Committee member of the Croatian Endocrine Society, Croatian Society of Obesity and Croatian Society for Endocrine Oncology. He was a board member and secretary of IDF Europe and is currently the chair of the IDF Young Leaders in Diabetes (YLD) Programme. He has served as an Executive Committee member of the Diabetes and Nutrition Study Group of the EASD and currently serves as an Executive Committee member of the Diabetes and Cardiovascular Disease Study Group of the EASD. He has served as principal investigator or co-investigator in clinical trials for AstraZeneca, Eli Lilly, MSD, Novo Nordisk, Sanofi Aventis, Solvay and Trophos. He has received travel support, speaker fees and honoraria for advisory board engagements and/or consulting fees from Abbott, Amgen, AstraZeneca, Bayer, Belupo, Boehringer Ingelheim, Eli Lilly, LifeScan – Johnson & Johnson, the International Sweeteners Association, Krka, Medtronic, Mediligo, Mylan, Novartis, Novo Nordisk, MSD, Pfizer, Pliva, Roche, Salvus, Sandoz, Solvay, Sanofi Aventis and Takeda. HK is Director of Clinical Research at the Physicians Committee for Responsible Medicine, a non-profit organisation that provides nutrition education and research. JS-S reports serving on the board of and receiving grant support through his institution from the International Nut and Dried Fruit Council (INC) and the Eroski Foundation. He reports serving on the Executive Committee of the Instituto Danone Spain. He reports receiving research support from the Instituto de Salud Carlos III, Spain; Ministerio de Educación y Ciencia, Spain; the Departament de Salut Pública de la Generalitat de Catalunya, Catalonia, Spain; the European Commission; the California Walnut Commission, USA; Patrimonio Comunal Olivarero, Spain; La Morella Nuts, Spain; and Borges, Spain. He reports receiving consulting fees or travel expenses from Danone, the California Walnut Commission, the Eroski Foundation, the Instituto Danone Spain, Nuts for Life, the Australian Nut Industry Council, Nestlé, Abbot and Font Vella y Lanjarón. He is on the Clinical Practice Guidelines Expert Committee of the EASD and served on the Scientific Committee of the Spanish Agency for Food Safety and Nutrition and the Spanish Federation of the Scientific Societies of Food, Nutrition and Dietetics. He is a member of the International Carbohydrate Quality Consortium (ICQC) and an Executive Board Member of the Diabetes and Nutrition Study Group of the EASD. CWCK has received grants or research support from the Advanced Food and Materials Network, Agriculture and Agri-Food Canada (AAFC), the Almond Board of California, Barilla, the CIHR, the Canola Council of Canada, the International Nut and Dried Fruit Council, the International Tree Nut Council Nutrition Research and Education Foundation, Loblaw Brands, the Peanut Institute, Pulse Canada and Unilever. He has received in-kind research support from the Almond Board of California, Barilla, the California Walnut Commission, Kellogg Canada, Loblaw Brands, Nutrartis, Quaker (PepsiCo), the Peanut Institute, Primo, Unico, Unilever, WhiteWave Foods/Danone. He has received travel support and/or honoraria from Barilla, the California Walnut Commission, the Canola Council of Canada, General Mills, the International Nut and Dried Fruit Council, the International Pasta Organization, Lantmannen, Loblaw Brands, the Nutrition Foundation of Italy, the Oldways Preservation Trust, Paramount Farms, the Peanut Institute, Pulse Canada, Sun-Maid, Tate & Lyle, Unilever and White Wave Foods/Danone. He has served on the scientific advisory board for the International Tree Nut Council, International Pasta Organisation, McCormick Science Institute and Oldways Preservation Trust. He is a founding member of the ICQC and an Executive Board Member of the Diabetes and Nutrition Study Group of the EASD, is on the Clinical Practice Guidelines Expert Committee for Nutrition Therapy of the EASD and is a Director of the Toronto 3D Knowledge Synthesis and Clinical Trials foundation. JLS has received research support from the Canadian Foundation for Innovation, the Ontario Research Fund, the Province of Ontario Ministry of Research, Innovation and Science, the CIHR, Diabetes Canada, the American Society for Nutrition (ASN), the International Nut and Dried Fruit Council Foundation, the National Honey Board (US Department of Agriculture [USDA] honey ‘Checkoff’ programme), the Institute for the Advancement of Food and Nutrition Sciences (IAFNS; formerly ILSI North America), Pulse Canada, the Quaker Oats Center of Excellence, the United Soybean Board (USDA soy ‘Checkoff’ programme), the Tate and Lyle Nutritional Research Fund at the University of Toronto, the Glycemic Control and Cardiovascular Disease in Type 2 Diabetes Fund at the University of Toronto (established by the Alberta Pulse Growers), the Plant Protein Fund at the University of Toronto (which has received contributions from IFF) and the Nutrition Trialists Fund at the University of Toronto (established by an inaugural donation from the Calorie Control Council). He has received food donations to support RCTs from the Almond Board of California, the California Walnut Commission, the Peanut Institute, Barilla, Unilever/Upfield, Unico/Primo, Loblaw Companies, Quaker, Kellogg Canada, WhiteWave Foods/Danone, Nutrartis and Dairy Farmers of Canada. He has received travel support, speaker fees and/or honoraria from the ASN, Danone, Dairy Farmers of Canada, FoodMinds, Nestlé, Abbott, General Mills, the Comité Européen des Fabricants de Sucre (CEFS), Nutrition Communications, the International Food Information Council (IFIC), the Calorie Control Council and the International Glutamate Technical Committee. He has or has had ad hoc consulting arrangements with Perkins Coie, Tate & Lyle, Phynova and INQUIS Clinical Research. He is a member of the European Fruit Juice Association Scientific Expert Panel and former member of the Soy Nutrition Institute Scientific Advisory Committee. He is on the Clinical Practice Guidelines Expert Committees of Diabetes Canada, the EASD, the Canadian Cardiovascular Society and Obesity Canada/Canadian Association of Bariatric Physicians and Surgeons. He serves or has served as an unpaid member of the Board of Trustees and an unpaid scientific advisor for the Food, Nutrition, and Safety Program (FNSP) and the Carbohydrates Committee of the IAFNS. He is a member of the ICQC, an Executive Board Member of the Diabetes and Nutrition Study Group of the EASD, and Director of the Toronto 3D Knowledge Synthesis and Clinical Trials foundation. His spouse is an employee of AB InBev. PM, EV, SBM, VC, US, UR, MU, A-MA, KH and IT declare that there are no relationships or activities that might bias, or be perceived to bias, their work. Funding Information: Open access funding provided by University of Eastern Finland (UEF) including Kuopio University Hospital. The Diabetes and Nutrition Study Group of the EASD commissioned this systematic review and meta-analysis and provided funding and logistical support for meetings as part of the development of the EASD clinical practice guidelines for nutrition therapy. This work was also supported by the Canadian Institutes of Health Research (CIHR; reference no. 129920) through the Canada-wide Human Nutrition Trialists’ Network (NTN). The Diet, Digestive tract, and Disease (3D) Centre, funded through the Canada Foundation for Innovation and the Ministry of Research and Innovation’s Ontario Research Fund, provided the infrastructure for the conduct of this work. PM was funded by a Connaught Fellowship, an Onassis Foundation Fellowship and a Peterborough KM Hunter Charitable Foundation Scholarship. AZ was funded by a Toronto3D Postdoctoral Fellowship Award and a Banting and Best Diabetes Centre (BBDC) Fellowship in Diabetes Care. AJG was funded by a Nora Martin Fellowship in Nutritional Sciences, the Banting & Best Diabetes Centre Tamarack Graduate Award in Diabetes Research, the Peterborough K. M. Hunter Charitable Foundation Graduate Award and an Ontario Graduate Scholarship. LC was funded by a Mitacs Elevate Postdoctoral Fellowship Award. TAK was funded by a Toronto 3D Postdoctoral Fellowship Award. EMC held the Lawson Family Chair in Microbiome Nutrition Research at the Lawson Centre for Child Nutrition, Temerty Faculty of Medicine, University of Toronto. JS-S is partially supported by the Catalan Institution for Research and Advanced Studies (ICREA) under the ICREA Acadèmia programme. JLS was funded by a PSI Graham Farquharson Knowledge Translation Fellowship, Canadian Diabetes Association Clinician Scientist Award, CIHR Institute of Nutrition, Metabolism and Diabetes (INMD)/Canadian Nutrition Society (CNS) New Investigator Partnership Prize and BBDC Sun Life Financial New Investigator Award. Publisher Copyright: © 2022, The Author(s).AIMS/HYPOTHESIS: Nordic dietary patterns that are high in healthy traditional Nordic foods may have a role in the prevention and management of diabetes. To inform the update of the EASD clinical practice guidelines for nutrition therapy, we conducted a systematic review and meta-analysis of Nordic dietary patterns and cardiometabolic outcomes. METHODS: We searched MEDLINE, EMBASE and The Cochrane Library from inception to 9 March 2021. We included prospective cohort studies and RCTs with a follow-up of ≥1 year and ≥3 weeks, respectively. Two independent reviewers extracted relevant data and assessed the risk of bias (Newcastle-Ottawa Scale and Cochrane risk of bias tool). The primary outcome was total CVD incidence in the prospective cohort studies and LDL-cholesterol in the RCTs. Secondary outcomes in the prospective cohort studies were CVD mortality, CHD incidence and mortality, stroke incidence and mortality, and type 2 diabetes incidence; in the RCTs, secondary outcomes were other established lipid targets (non-HDL-cholesterol, apolipoprotein B, HDL-cholesterol, triglycerides), markers of glycaemic control (HbA 1c, fasting glucose, fasting insulin), adiposity (body weight, BMI, waist circumference) and inflammation (C-reactive protein), and blood pressure (systolic and diastolic blood pressure). The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of the evidence. RESULTS: We included 15 unique prospective cohort studies (n=1,057,176, with 41,708 cardiovascular events and 13,121 diabetes cases) of people with diabetes for the assessment of cardiovascular outcomes or people without diabetes for the assessment of diabetes incidence, and six RCTs (n=717) in people with one or more risk factor for diabetes. In the prospective cohort studies, higher adherence to Nordic dietary patterns was associated with 'small important' reductions in the primary outcome, total CVD incidence (RR for highest vs lowest adherence: 0.93 [95% CI 0.88, 0.99], p=0.01; substantial heterogeneity: I 2=88%, p Q<0.001), and similar or greater reductions in the secondary outcomes of CVD mortality and incidence of CHD, stroke and type 2 diabetes (p<0.05). Inverse dose-response gradients were seen for total CVD incidence, CVD mortality and incidence of CHD, stroke and type 2 diabetes (p<0.05). No studies assessed CHD or stroke mortality. In the RCTs, there were small important reductions in LDL-cholesterol (mean difference [MD] -0.26 mmol/l [95% CI -0.52, -0.00], p MD=0.05; substantial heterogeneity: I 2=89%, p Q<0.01), and 'small important' or greater reductions in the secondary outcomes of non-HDL-cholesterol, apolipoprotein B, insulin, body weight, BMI and systolic blood pressure (p<0.05). For the other outcomes there were 'trivial' reductions or no effect. The certainty of the evidence was low for total CVD incidence and LDL-cholesterol; moderate to high for CVD mortality, established lipid targets, adiposity markers, glycaemic control, blood pressure and inflammation; and low for all other outcomes, with evidence being downgraded mainly because of imprecision and inconsistency. CONCLUSIONS/INTERPRETATION: Adherence to Nordic dietary patterns is associated with generally small important reductions in the risk of major CVD outcomes and diabetes, which are supported by similar reductions in LDL-cholesterol and other intermediate cardiometabolic risk factors. The available evidence provides a generally good indication of the likely benefits of Nordic dietary patterns in people with or at risk for diabetes. REGISTRATION: ClinicalTrials.gov NCT04094194. FUNDING: Diabetes and Nutrition Study Group of the EASD Clinical Practice.Peer reviewe

The Effects of Fructose Intake on Serum Uric Acid Vary among Controlled Dietary Trials1234

Hyperuricemia is linked to gout and features of metabolic syndrome. There is concern that dietary fructose may increase uric acid concentrations. To assess the effects of fructose on serum uric acid concentrations in people with and without diabetes, we conducted a systematic review and meta-analysis of controlled feeding trials. We searched MEDLINE, EMBASE, and the Cochrane Library for relevant trials (through August 19, 2011). Analyses included all controlled feeding trials ≥7 d investigating the effect of fructose feeding on uric acid under isocaloric conditions, where fructose was isocalorically exchanged with other carbohydrate, or hypercaloric conditions, and where a control diet was supplemented with excess energy from fructose. Data were aggregated by the generic inverse variance method using random effects models and expressed as mean difference (MD) with 95% CI. Heterogeneity was assessed by the Q statistic and quantified by I2. A total of 21 trials in 425 participants met the eligibility criteria. Isocaloric exchange of fructose for other carbohydrate did not affect serum uric acid in diabetic and nondiabetic participants [MD = 0.56 μmol/L (95% CI: −6.62, 7.74)], with no evidence of inter-study heterogeneity. Hypercaloric supplementation of control diets with fructose (+35% excess energy) at extreme doses (213–219 g/d) significantly increased serum uric acid compared with the control diets alone in nondiabetic participants [MD = 31.0 mmol/L (95% CI: 15.4, 46.5)] with no evidence of heterogeneity. Confounding from excess energy cannot be ruled out in the hypercaloric trials. These analyses do not support a uric acid-increasing effect of isocaloric fructose intake in nondiabetic and diabetic participants. Hypercaloric fructose intake may, however, increase uric acid concentrations. The effect of the interaction of energy and fructose remains unclear. Larger, well-designed trials of fructose feeding at “real world” doses are needed