Meta-analyses of Fructose and Cardiometabolic Risk

NCT01363791 | Unknown

• 1 other identifier: CIHR-KS-2009-205030
• Study Type: observational
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Diabetes and heart associations continue to discourage high intakes of dietary fructose, a constituent part of the sucrose molecule that is found in fruits and vegetables as a natural sugar and in some processed foods and beverages as an added sweetener. The concern relates to its ability to increase certain blood fats and cholesterol, which increase the risk of cardiovascular disease. The evidence for an adverse effect of fructose on these risk factors, however, is inconclusive. To improve the evidence on which nutrition recommendations for fructose are based, the investigators therefore propose to study the effect of fructose on blood fats, cholesterol, sugars, blood pressure, and body weight, by undertaking a systematic synthesis of the data taken from all available clinical studies in humans. This technique has the strength of allowing all of the available data to be pooled together and differences to be explored in groups of different study participants (healthy humans of different sex, weight, and age and in those with diseases which predispose to disturbances in metabolism, such as diabetes) with dietary fructose in different forms, doses, and with differing durations of exposure. The findings generated by this proposed knowledge synthesis will help improve the health of consumers through informing recommendations for the general public, as well as those at risk of diabetes and cardiovascular disease.

Conditions

Dyslipidemia; Diabetes; Prediabetes; Dysglycemia; Overweight; Obesity; Gout; Hypertension; Non-alcoholic Fatty Liver Disease; Metabolic Syndrome; Cardiovascular Disease

Keywords

Systematic review and meta-analysis; Evidence-based medicine (EBM); Evidence-based nutrition (EBN); Clinical practice guidelines; Clinical trials; Dietary sugars; Fructose; High fructose corn syrup; Fruit; Isocaloric; Hypercaloric; Cardiometabolic risk factors; Triglycerides; Cholesterol; Glycemic control; Insulin resistance; Body weight; Uric acid; Blood pressure; Fatty liver; Fasting; Postprandial

Outcome Measures

Primary Outcomes (7)

• Lipid Analysis

  Analyses: 1. Fasting lipids (triglycerides, HDL-cholesterol \[C\], LDL-C, apo-B, total-C:HDL-C ratio, apo-B:apo-A1 ratio, non-HDL-C) 2. Postprandial lipids (peak, mean, and area under the curve \[AUC\] triglycerides)

  June 2012

• Body Weight Analysis

  Analyses: 1\. Body weight

  November 2011

• Glycemic Control Analysis

  Analyses: 1. Glycated blood proteins (HbA1c, fructosamine, glycated albumin), glucose, and insulin in people with diabetes 2. Glycated blood proteins (HbA1c, fructosamine, glycated albumin), glucose, and insulin in people without diabetes 3. Insulin sensitivity (Euglycemic-hyperinsulinemic clamp, frequent sampling intravenous glucose tolerance test \[FSIGT\], Homeostasis model assessment of insulin resistance \[HOMA-IR\], oral glucose tolerance test insulin sensitivity index \[OGTT-ISI\])

  June 2012

• Blood Pressure (BP) Analysis

  Analyses: 1\. Systolic BP, diastolic BP, and mean arterial pressure (MAP)

  January 2012

• Uric Acid Analysis

  Analyses: 1\. uric acid

  February 2012

• "Catalytic" Fructose Across Cardiometabolic Endpoints Analysis

  Analyses: 1\. Lipids, glycemic control, body weight, blood pressure, and uric acid

  January 2012

• Non-Alcoholic Fatty Liver (NAFL) Analysis

  Analyses: 1\. Imaging and spectroscopy endpoints of liver fat (Liver ultrasound \[US\], computed tomography \[CT\], magnetic resonance imaging \[MRI\], or magnetic resonance spectroscopy \[MRS\]) and biomarkers of hepatocellular injury (transaminases \[ALT, AST, GGT\])

  June 2012

Interventions

Dietary fructose OTHER

Oral dietary fructose in free (unbound) form in isocaloric exchange for other non-fructose carbohydrate sources (isocaloric trials) or added to a control diet as a source of excess energy (hypercaloric trials).

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Varied.

You may qualify if:

• Trials in humans
• Oral fructose intervention
• Suitable control (i.e. another carbohydrate source in isocaloric exchange for fructose or a control diet which is compared with the same diet supplemented with excess energy from fructose)
• \>= 7-days diet duration
• Viable endpoint data

You may not qualify if:

• Non-human studies
• IV or parenteral fructose
• High fructose corn syrup or sucrose intervention (except where these are the comparators)
• Lack of a suitable control
• \< 7-days diet duration.
• No viable endpoint data

Sponsors & Collaborators

• John Sievenpiper: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• Canada Research Chairs Endowment of the Federal Government of Canada: collaborator
• Calorie Control Council: collaborator

Study Sites (1)

The Toronto 3D (Diet, Digestive tract and Disease) Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Micheal's Hospital

Toronto, Ontario, M5C 2N8, Canada

Location

Related Publications (13)

• Sievenpiper JL, Carleton AJ, Chatha S, Jiang HY, de Souza RJ, Beyene J, Kendall CW, Jenkins DJ. Heterogeneous effects of fructose on blood lipids in individuals with type 2 diabetes: systematic review and meta-analysis of experimental trials in humans. Diabetes Care. 2009 Oct;32(10):1930-7. doi: 10.2337/dc09-0619. Epub 2009 Jul 10.

  PMID: 19592634 BACKGROUND

• Ha V, Sievenpiper JL, de Souza RJ, Chiavaroli L, Wang DD, Cozma AI, Mirrahimi A, Yu ME, Carleton AJ, Dibuono M, Jenkins AL, Leiter LA, Wolever TM, Beyene J, Kendall CW, Jenkins DJ. Effect of fructose on blood pressure: a systematic review and meta-analysis of controlled feeding trials. Hypertension. 2012 Apr;59(4):787-95. doi: 10.1161/HYPERTENSIONAHA.111.182311. Epub 2012 Feb 13.

  PMID: 22331380 RESULT

• Sievenpiper JL, de Souza RJ, Mirrahimi A, Yu ME, Carleton AJ, Beyene J, Chiavaroli L, Di Buono M, Jenkins AL, Leiter LA, Wolever TM, Kendall CW, Jenkins DJ. Effect of fructose on body weight in controlled feeding trials: a systematic review and meta-analysis. Ann Intern Med. 2012 Feb 21;156(4):291-304. doi: 10.7326/0003-4819-156-4-201202210-00007.

  PMID: 22351714 RESULT

• Wang DD, Sievenpiper JL, de Souza RJ, Chiavaroli L, Ha V, Cozma AI, Mirrahimi A, Yu ME, Carleton AJ, Di Buono M, Jenkins AL, Leiter LA, Wolever TM, Beyene J, Kendall CW, Jenkins DJ. The effects of fructose intake on serum uric acid vary among controlled dietary trials. J Nutr. 2012 May;142(5):916-23. doi: 10.3945/jn.111.151951. Epub 2012 Mar 28.

  PMID: 22457397 RESULT

• Sievenpiper JL, Chiavaroli L, de Souza RJ, Mirrahimi A, Cozma AI, Ha V, Wang DD, Yu ME, Carleton AJ, Beyene J, Di Buono M, Jenkins AL, Leiter LA, Wolever TM, Kendall CW, Jenkins DJ. 'Catalytic' doses of fructose may benefit glycaemic control without harming cardiometabolic risk factors: a small meta-analysis of randomised controlled feeding trials. Br J Nutr. 2012 Aug;108(3):418-23. doi: 10.1017/S000711451200013X. Epub 2012 Feb 21.

  PMID: 22354959 RESULT

• Sievenpiper JL, de Souza RJ, Jenkins DJ. Sugar: fruit fructose is still healthy. Nature. 2012 Feb 22;482(7386):470. doi: 10.1038/482470e. No abstract available.

  PMID: 22358823 RESULT

• Sievenpiper JL, de Souza RJ, Kendall CW, Jenkins DJ. Is fructose a story of mice but not men? J Am Diet Assoc. 2011 Feb;111(2):219-20; author reply 220-2. doi: 10.1016/j.jada.2010.12.001. No abstract available.

  PMID: 21272692 RESULT

• David Wang D, Sievenpiper JL, de Souza RJ, Cozma AI, Chiavaroli L, Ha V, Mirrahimi A, Carleton AJ, Di Buono M, Jenkins AL, Leiter LA, Wolever TM, Beyene J, Kendall CW, Jenkins DJ. Effect of fructose on postprandial triglycerides: a systematic review and meta-analysis of controlled feeding trials. Atherosclerosis. 2014 Jan;232(1):125-33. doi: 10.1016/j.atherosclerosis.2013.10.019. Epub 2013 Nov 2.

  PMID: 24401226 RESULT

• Sievenpiper JL, de Souza RJ, Cozma AI, Chiavaroli L, Ha V, Mirrahimi A. Fructose vs. glucose and metabolism: do the metabolic differences matter? Curr Opin Lipidol. 2014 Feb;25(1):8-19. doi: 10.1097/MOL.0000000000000042.

  PMID: 24370846 RESULT

• Sievenpiper JL; Toronto 3D (Diet, Digestive Tract, and Disease) Knowledge Synthesis and Clinical Trials Unit. Fructose: where does the truth lie? J Am Coll Nutr. 2012 Jun;31(3):149-51. doi: 10.1080/07315724.2012.10720021. No abstract available.

  PMID: 23204150 RESULT

• Chiavaroli L, Ha V, de Souza RJ, Kendall CW, Sievenpiper JL. Re. "Association of fructose consumption and components of metabolic syndrome in human studies: a systematic review and meta-analysis". Nutrition. 2015 Feb;31(2):419-20. doi: 10.1016/j.nut.2014.07.018. Epub 2014 Aug 8. No abstract available.

  PMID: 25441580 RESULT

• Chiavaroli L, de Souza RJ, Ha V, Cozma AI, Mirrahimi A, Wang DD, Yu M, Carleton AJ, Di Buono M, Jenkins AL, Leiter LA, Wolever TM, Beyene J, Kendall CW, Jenkins DJ, Sievenpiper JL. Effect of Fructose on Established Lipid Targets: A Systematic Review and Meta-Analysis of Controlled Feeding Trials. J Am Heart Assoc. 2015 Sep 10;4(9):e001700. doi: 10.1161/JAHA.114.001700.

  PMID: 26358358 DERIVED

• Cozma AI, Sievenpiper JL, de Souza RJ, Chiavaroli L, Ha V, Wang DD, Mirrahimi A, Yu ME, Carleton AJ, Di Buono M, Jenkins AL, Leiter LA, Wolever TM, Beyene J, Kendall CW, Jenkins DJ. Effect of fructose on glycemic control in diabetes: a systematic review and meta-analysis of controlled feeding trials. Diabetes Care. 2012 Jul;35(7):1611-20. doi: 10.2337/dc12-0073.

  PMID: 22723585 DERIVED

MeSH Terms

Conditions

Dyslipidemias; Diabetes Mellitus; Prediabetic State; Overweight; Obesity; Gout; Hypertension; Non-alcoholic Fatty Liver Disease; Metabolic Syndrome; Cardiovascular Diseases; Insulin Resistance; Body Weight; Fatty Liver; Fasting

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Glucose Metabolism Disorders; Endocrine System Diseases; Overnutrition; Nutrition Disorders; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Arthritis; Joint Diseases; Musculoskeletal Diseases; Crystal Arthropathies; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Vascular Diseases; Liver Diseases; Digestive System Diseases; Hyperinsulinism; Feeding Behavior; Behavior

Study Officials

• John L Sievenpiper, MD, PhD

  Department of Pathology and Molecular Medicine, McMaster University and Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital

  STUDY DIRECTOR

• David JA Jenkins, MD, PhD, DSc

  Department of Nutritional Sciences and Medicine, University of Toronto and Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Adjunct Research Fellow

Study Record Dates

• First Submitted: May 25, 2011
• First Posted: June 2, 2011
• Study Start: May 1, 2009
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2016
• Last Updated: May 27, 2015

Record last verified: 2015-05

Locations

CA (1)