DyslipidemiaNCT01363791
Meta-analyses of Fructose and Cardiometabolic Risk
An observational study of Dyslipidemia and Diabetes, run by John Sievenpiper at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Dyslipidemia, Diabetes, Prediabetes
- What is being tested?
- Dietary fructose
- Type of treatment
- Pill or oral medicine
- How many people
- 1 participants
- Where
- 1 siteCanada
- Study dates
- May 2009to Mar 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Varied.
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Canada1 site
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
About this study
Official title: Effect of Fructose on Metabolic Control in Humans: A Series of Systematic Reviews and Meta-analyses to Provide Evidence-based Guidance for Nutrition Guidelines Development
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.
Read the detailed description
Background: Fructose has been implicated in chronic disease guidelines. The American Heart Association (AHA) and American (ADA), Canadian (CDA), and European (EASD) Diabetes Associations discourage dietary fructose at high intakes (>15-20% energy), citing its ability to aggravate blood lipids. The American Heart Association (AHA) and the World Health Organization (WHO) recommend reduced consumption (<5-7% and <10% energy, respectively) of added sugars, especially as high fructose corn syrup in sugar sweetened beverages, to decrease the risk of weight gain. These concerns, however, are based on inconsistent intervention data in humans. There is also paradoxical evidence that small, catalytic doses of fructose at a level obtainable from fruit (<10-g/meal) may improve glycemic control in humans.
Objective: To improve evidence-based guidance for fructose recommendations, the investigators propose conducting a series of 7 systematic reviews and meta-analyses of controlled feeding trials to assess the effect of oral fructose on cardiometabolic risk in humans. The first 6 systematic reviews and meta-analyses will each be conducted on a different area of cardiometabolic risk: (1) lipids, (2) glycemic control, (3) body weight, (4) uric acid, (5) blood pressure, and (6) non-alcoholic fatty liver (NAFL). The seventh meta-analysis will investigate the effect of small, "catalytic" doses of fructose at a level obtainable from fruit (<10-g/meal) on all areas of cardiometabolic risk.
Design: The planning and conduct of the proposed meta-analyses will follow the Cochrane handbook for systematic reviews of interventions. The reporting will follow the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines.
Data sources. MEDLINE, EMBASE, CINAHL and The Cochrane Central Register of Controlled Trials (Clinical Trials; CENTRAL) will be searched using appropriate search terms, supplemented by manual, hand searches of bibliographies.
Study selection: We will include controlled feeding trials investigating the effect of fructose in isocaloric exchange for other carbohydrate sources (isocaloric trials) or added to a control diet as a source of excess energy (hypercaloric trials) on cardiometabolic risk factors in humans. Studies that are <7-days diet duration, lack a control, or do not provide viable endpoint data will be excluded. To isolate the effects of fructose, we will also exclude trials in which fructose was administered exclusively as sucrose (bound fructose) or high-fructose corn syrup (42% to 55% of free fructose), except where these sweeteners were the comparator.
Data extraction. Two investigators will independently extract information about study design, sample size, subject characteristics, fructose form, dose, reference-carbohydrate, follow-up, and background diet profile. Mean±SEM values will be extracted for all outcomes. Standard computations and imputations will be used to derive missing variance data. Investigators will assess the quality/validity of each study using the Heyland Methodological Quality Score (MQS).
Outcomes: The first 6 of 7 proposed analyses will each assess a set of outcomes related to a different area of cardiometabolic risk: (1) lipids (fasting lipids [triglycerides, HDL-cholesterol [C], LDL-C, apo-B, total-C:HDL-C ratio, apo-B:apo-A1 ratio, non-HDL-C] and postprandial lipids(non-fasting peak, mean, and area under the curve [AUC] triglycerides), (2) glycemic control (fasting glucose and insulin, glycated blood proteins) and 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]), (3) body weight, (4) uric acid, (5) blood pressure (systolic BP, diastolic BP, mean arterial pressure), and (6) NAFL (imaging and spectroscopy endpoints of liver fat and biomarkers of hepatocellular injury [transaminases]). The last proposed analysis investigating the effect of small, "catalytic" doses of fructose will focus on all 6 outcomes.
Data synthesis. Meta-analyses will be conducted using the Generic Inverse Variance method applying random effects models expressed as standardized mean differences (SMDs) with 95% CIs. Paired analyses will be applied for crossover trials according to Elbourne et al. (Int J Epidemiol. 2002;31:140-149). Heterogeneity will be assessed by the Q statistic and quantified by I2. A priori subgroup analyses will be undertaken to explore sources of heterogeneity including the effect of underlying disease status, reference carbohydrate (comparator), fructose form, dose, follow-up, study design, baseline measurements, and study quality on the effect of fructose. Significant unexplained heterogeneity will be investigated by additional post hoc subgroup analyses (e.g. age, sex, level of feeding control, energy balance and composition of the background diet, etc.) and sensitivity analyses. Meta-regression analyses will assess the significance of subgroups analyses with piece-wise meta-regression techniques used to identify dose or follow-up thresholds. Publication bias will be investigated by inspection of funnel plots.
Knowledge translation plan: The results will be disseminated through interactive presentations at local, national, and international scientific meetings and publication in high impact factor journals. Target audiences will include the public health and scientific communities with interest in nutrition, diabetes, obesity, and cardiovascular disease. Feedback will be incorporated and used to improve the public health message and key areas for future research will be defined. Applicant/Co-applicant Decision Makers will network among opinion leaders to increase awareness and participate directly as committee members in the development of future guidelines.
Preliminary findings: A pilot project which explored the effect of fructose on lipids in diabetes identified 786 articles, of which 14 (16 trials)were included in a meta-analysis. Isocaloric exchange of fructose for carbohydrate had a triglyceride raising effect in type 2 diabetes only where the reference carbohydrate was starch, dose was >60-g/d, or follow-up was ≤4-weeks. These distinctions had not been appreciated previously (Sievenpiper et al. Diabetes Care 2009;32:1930-1937).
Significance: The proposed project will aid in knowledge translation related to the effects of dietary fructose on diabetes, and cardiovascular risk factors, strengthening the evidence-base for recommendations and improving health outcomes through informing consumers and guiding future research.
- Conditions
- Dyslipidemia, Diabetes, Prediabetes, Dysglycemia, Overweight, Obesity
- Being tested
- Dietary fructose
- 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
- Medical subject headings
- Dyslipidemias, Diabetes Mellitus, Prediabetic State, Overweight, Obesity, Gout, Hypertension, Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dietary fructoseOther
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).
What is being measured
The primary outcome is the main question the study is designed to answer.
Lipid Analysis
Analyses:
- Fasting lipids (triglycerides, HDL-cholesterol [C], LDL-C, apo-B, total-C:HDL-C ratio, apo-B:apo-A1 ratio, non-HDL-C)
- Postprandial lipids (peak, mean, and area under the curve [AUC] triglycerides)
Measured: June 2012
Body Weight Analysis
Analyses:
- Body weight
Measured: November 2011
Glycemic Control Analysis
Analyses:
- Glycated blood proteins (HbA1c, fructosamine, glycated albumin), glucose, and insulin in people with diabetes
- Glycated blood proteins (HbA1c, fructosamine, glycated albumin), glucose, and insulin in people without diabetes
- 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])
Measured: June 2012
Blood Pressure (BP) Analysis
Analyses:
- Systolic BP, diastolic BP, and mean arterial pressure (MAP)
Measured: January 2012
Uric Acid Analysis
Analyses:
- uric acid
Measured: February 2012
"Catalytic" Fructose Across Cardiometabolic Endpoints Analysis
Analyses:
- Lipids, glycemic control, body weight, blood pressure, and uric acid
Measured: January 2012
Non-Alcoholic Fatty Liver (NAFL) Analysis
Analyses:
- 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])
Measured: June 2012
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2011 (estimated)
- Study startMay 2009
- Primary completionMar 2014
- Study completionMar 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for DyslipidemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Enrolment
- 1 participants (estimated)
Sponsor and investigators
- Lead sponsor
- John Sievenpiper
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Canada Research Chairs Endowment of the Federal Government of Canada, Calorie Control Council
- Responsible party
- Sponsor-investigator, John Sievenpiper, University of Toronto
- Investigators
- John L Sievenpiper, MD, PhD, Study director, Department of Pathology and Molecular Medicine, McMaster University and Clinical Nutrition and Risk Factor Modification Centre, St. Michael's HospitalDavid JA Jenkins, MD, PhD, DSc, Principal investigator, Department of Nutritional Sciences and Medicine, University of Toronto and Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01363791
- Sponsor's protocol ID
- CIHR-KS-2009-205030
- Status last verified
- May 2015
- First submitted
- 25 May 2011
- Last updated
- 27 May 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 19592634Ha 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.
PubMed 22331380Sievenpiper 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.
PubMed 22351714Wang 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.
PubMed 22457397Sievenpiper 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.
PubMed 22354959Sievenpiper 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.
PubMed 22358823Sievenpiper 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.
PubMed 21272692David 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.
PubMed 24401226Sievenpiper 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.
PubMed 24370846Sievenpiper 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.
PubMed 23204150Chiavaroli 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.
PubMed 25441580Chiavaroli 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.
PubMed 26358358Cozma 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.
PubMed 22723585
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Fructose on Metabolic Control in Humans: A Series of Systematic Reviews and Meta-analyses to Provide Evidence-based Guidance for Nutrition Guidelines Development
- ClinicalTrials.gov ID
- NCT01363791
- Acronym / sponsor ID
- CIHR-KS-2009-205030
- Conditions
- Dyslipidemia, Diabetes, Prediabetes, Dysglycemia, Overweight, Obesity
- 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
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 1 participants (estimated)
- Lead sponsor
- John SievenpiperUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Canada Research Chairs Endowment of the Federal Government of Canada, Calorie Control Council
- Study start
- May 2009
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2016 (estimated)
- First posted
- 2 Jun 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Background: Fructose has been implicated in chronic disease guidelines. The American Heart Association (AHA) and American (ADA), Canadian (CDA), and European (EASD) Diabetes Associations discourage dietary fructose at high intakes (>15-20% energy), citing its ability to aggravate blood lipids. The American Heart Association (AHA) and the World Health Organization (WHO) recommend reduced consumption (<5-7% and <10% energy, respectively) of added sugars, especially as high fructose corn syrup in sugar sweetened beverages, to decrease the risk of weight gain. These concerns, however, are based on inconsistent intervention data in humans. There is also paradoxical evidence that small, catalytic doses of fructose at a level obtainable from fruit (<10-g/meal) may improve glycemic control in humans.
Objective: To improve evidence-based guidance for fructose recommendations, the investigators propose conducting a series of 7 systematic reviews and meta-analyses of controlled feeding trials to assess the effect of oral fructose on cardiometabolic risk in humans. The first 6 systematic reviews and meta-analyses will each be conducted on a different area of cardiometabolic risk: (1) lipids, (2) glycemic control, (3) body weight, (4) uric acid, (5) blood pressure, and (6) non-alcoholic fatty liver (NAFL). The seventh meta-analysis will investigate the effect of small, "catalytic" doses of fructose at a level obtainable from fruit (<10-g/meal) on all areas of cardiometabolic risk.
Design: The planning and conduct of the proposed meta-analyses will follow the Cochrane handbook for systematic reviews of interventions. The reporting will follow the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines.
Data sources. MEDLINE, EMBASE, CINAHL and The Cochrane Central Register of Controlled Trials (Clinical Trials; CENTRAL) will be searched using appropriate search terms, supplemented by manual, hand searches of bibliographies.
Study selection: We will include controlled feeding trials investigating the effect of fructose in isocaloric exchange for other carbohydrate sources (isocaloric trials) or added to a control diet as a source of excess energy (hypercaloric trials) on cardiometabolic risk factors in humans. Studies that are <7-days diet duration, lack a control, or do not provide viable endpoint data will be excluded. To isolate the effects of fructose, we will also exclude trials in which fructose was administered exclusively as sucrose (bound fructose) or high-fructose corn syrup (42% to 55% of free fructose), except where these sweeteners were the comparator.
Data extraction. Two investigators will independently extract information about study design, sample size, subject characteristics, fructose form, dose, reference-carbohydrate, follow-up, and background diet profile. Mean±SEM values will be extracted for all outcomes. Standard computations and imputations will be used to derive missing variance data. Investigators will assess the quality/validity of each study using the Heyland Methodological Quality Score (MQS).
Outcomes: The first 6 of 7 proposed analyses will each assess a set of outcomes related to a different area of cardiometabolic risk: (1) lipids (fasting lipids [triglycerides, HDL-cholesterol [C], LDL-C, apo-B, total-C:HDL-C ratio, apo-B:apo-A1 ratio, non-HDL-C] and postprandial lipids(non-fasting peak, mean, and area under the curve [AUC] triglycerides), (2) glycemic control (fasting glucose and insulin, glycated blood proteins) and 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]), (3) body weight, (4) uric acid, (5) blood pressure (systolic BP, diastolic BP, mean arterial pressure), and (6) NAFL (imaging and spectroscopy endpoints of liver fat and biomarkers of hepatocellular injury [transaminases]). The last proposed analysis investigating the effect of small, "catalytic" doses of fructose will focus on all 6 outcomes.
Data synthesis. Meta-analyses will be conducted using the Generic Inverse Variance method applying random effects models expressed as standardized mean differences (SMDs) with 95% CIs. Paired analyses will be applied for crossover trials according to Elbourne et al. (Int J Epidemiol. 2002;31:140-149). Heterogeneity will be assessed by the Q statistic and quantified by I2. A priori subgroup analyses will be undertaken to explore sources of heterogeneity including the effect of underlying disease status, reference carbohydrate (comparator), fructose form, dose, follow-up, study design, baseline measurements, and study quality on the effect of fructose. Significant unexplained heterogeneity will be investigated by additional post hoc subgroup analyses (e.g. age, sex, level of feeding control, energy balance and composition of the background diet, etc.) and sensitivity analyses. Meta-regression analyses will assess the significance of subgroups analyses with piece-wise meta-regression techniques used to identify dose or follow-up thresholds. Publication bias will be investigated by inspection of funnel plots.
Knowledge translation plan: The results will be disseminated through interactive presentations at local, national, and international scientific meetings and publication in high impact factor journals. Target audiences will include the public health and scientific communities with interest in nutrition, diabetes, obesity, and cardiovascular disease. Feedback will be incorporated and used to improve the public health message and key areas for future research will be defined. Applicant/Co-applicant Decision Makers will network among opinion leaders to increase awareness and participate directly as committee members in the development of future guidelines.
Preliminary findings: A pilot project which explored the effect of fructose on lipids in diabetes identified 786 articles, of which 14 (16 trials)were included in a meta-analysis. Isocaloric exchange of fructose for carbohydrate had a triglyceride raising effect in type 2 diabetes only where the reference carbohydrate was starch, dose was >60-g/d, or follow-up was ≤4-weeks. These distinctions had not been appreciated previously (Sievenpiper et al. Diabetes Care 2009;32:1930-1937).
Significance: The proposed project will aid in knowledge translation related to the effects of dietary fructose on diabetes, and cardiovascular risk factors, strengthening the evidence-base for recommendations and improving health outcomes through informing consumers and guiding future research.
Study design
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Varied.
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dietary fructoseOral 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). | Other | – |
Primary outcome
Lipid Analysis
Time frame: June 2012
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)
Body Weight Analysis
Time frame: November 2011
Analyses: 1. Body weight
Glycemic Control Analysis
Time frame: June 2012
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])
Blood Pressure (BP) Analysis
Time frame: January 2012
Analyses: 1. Systolic BP, diastolic BP, and mean arterial pressure (MAP)
Uric Acid Analysis
Time frame: February 2012
Analyses: 1. uric acid
"Catalytic" Fructose Across Cardiometabolic Endpoints Analysis
Time frame: January 2012
Analyses: 1. Lipids, glycemic control, body weight, blood pressure, and uric acid
Non-Alcoholic Fatty Liver (NAFL) Analysis
Time frame: June 2012
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])
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 May 2015.
- Background: PubMed 19592634Sievenpiper 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.
- Results publication: PubMed 22331380Ha 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.
- Results publication: PubMed 22351714Sievenpiper 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.
- Results publication: PubMed 22457397Wang 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.
- Results publication: PubMed 22354959Sievenpiper 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.
- Results publication: PubMed 22358823Sievenpiper 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.
- Results publication: PubMed 21272692Sievenpiper 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.
- Results publication: PubMed 24401226David 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.
- Results publication: PubMed 24370846Sievenpiper 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.
- Results publication: PubMed 23204150Sievenpiper 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.
- Results publication: PubMed 25441580Chiavaroli 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.
- Derived from this study: PubMed 26358358Chiavaroli 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John L Sievenpiper, MD, PhD study director
Department of Pathology and Molecular Medicine, McMaster University and Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital
David JA Jenkins, MD, PhD, DSc principal investigator
Department of Nutritional Sciences and Medicine, University of Toronto and Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Dyslipidemia and Diabetes, run by John Sievenpiper at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 27 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Lipid Analysis (time frame: June 2012). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01363791, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 May 2015.