Fructose Consumption and Metabolic Dysregulation

• Sponsor: Marja-Riitta Taskinen (Other)
• Overall Status: Completed
• CT.gov ID: NCT01445730
• Collaborator: Sahlgrenska University Hospital, Sweden (Other), Lund University (Other), University of Naples (Other), Laval University (Other)
• Enrollment: 82
• Locations: 4
• Arm: 1
• Duration (Months): 46
• Patients Per Site: 20.5
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

High fructose intake is increasingly recognized as causative in development of prediabetes, metabolic syndrome and cardiovascular disease (CVD). The mechanisms underlying fructose-induced metabolic disturbances are unclear but are beginning to be unraveled. In contrast to metabolism of glucose, the breakdown of fructose leads to the generation of metabolites that stimulate hepatic de novo lipogenesis (DNL) and increased levels of both fasting and postprandial triglycerides. The key lipogenic transcription factor seems to be activated by fructose independently of insulin. However, it is still controversial whether fructose consumption increases DNL in man to the extent that it induces metabolic disturbances. Animal studies have shown that also the adipose tissue is responsive to fructose feeding fructose, and that high fructose-feeding induces insulin resistance and inflammation in the adipose tissue. The role of intestinal insulin resistance in fructose-induced dysmetabolism has not been studied in detail. The critical question is whether the metabolic disturbances are induced by calorie excess or by fructose per se.

Condition or Disease	Intervention/Treatment	Phase
Central Obesity; Hypertriglyceridemia	Dietary Supplement: Fructose	N/A

Detailed Description

Detailed description: Study subjects will participate to studies 1-4 before and 3 m after fructose diet:

1. An oral fat load or a kinetic study with stable isotopes combined with an oral fat load.

2. Determination of liver, subcutaneous and intra-abdominal fat. (Proton magnetic resonance spectroscopy )

3. Lipolytic enzymes, advanced lipid analysis, fat biopsies and genetic studies and gut microbiota profiling

4. Oral glucose tolerance test and analysis of incretins and inflammatory biomarkers.

Study Design

• Study Type: Interventional
• Actual Enrollment: 82 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Fructose Consumption Aggravates Dysregulation of Postprandial Lipid Metabolism in Obese Hypertriglyceridemic Men With High Cardiometabolic Risk Profile and Associates With Liver Fat Deposition
• Study Start Date: Aug 1, 2011
• Actual Primary Completion Date: May 1, 2015
• Actual Study Completion Date: Jun 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: After fructose feeding After 3 month fructose diet 75 g/day	Dietary Supplement: Fructose; 3 month fructose diet 75 g/day

Outcome Measures

Primary Outcome Measures

1. TG Plasma AUC [Form the baseline (time point 1) to end of treatment at 3 months (time point 2)]

   Before vs. after fructose challenge: Triglycerides (TG) plasma Area Under Curve (AUC)

2. B48 Plasma AUC [Form the baseline (time point 1) to end of treatment at 3 months (time point 2)]

   Before vs. after fructose challenge: apolipoprotein (apo)B48 plasma Area Under Curve (AUC)

3. TG Plasma iAUC [Form the baseline (time point 1) to end of treatment at 3 months (time point 2)]

   Before vs. after fructose challenge:Triglycerides (TG) plasma incremental Area Under Curve (iAUC)

Secondary Outcome Measures

1. DNL [Form the baseline (time point 1) to end of treatment at 3 months (time point 2)]

   Before vs. after fructose challenge: de novo lipogenesis (DNL)

2. ApoC-III [Form the baseline (time point 1) to end of treatment at 3 months (time point 2)]

   Before vs. after fructose challenge: Apolipoprotein C-III (ApoC-III)

3. β-OH Butyrate [Form the baseline (time point 1) to end of treatment at 3 months (time point 2)]

   Before vs. after fructose challenge: beta-OH butyrate (β-OH butyrate)

4. Liver Fat [Form the baseline (time point 1) to end of treatment at 3 months (time point 2)]

   Before vs. after fructose challenge

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 60 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Body mass index 27-40

• Waist > 96 cm

• Age 20-60 years

• Male

Exclusion Criteria:

• Smoking

• Active health problems

• Contraindications to MRI scanning

• Bleeding tendency

• Abnormal liver or renal function tests

• Type 2 diabetes

• Evidence of metabolic or viral liver disease

• Alcohol intake > 21 units per week

• Chronic medication except ones needed for stable hypertension

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Université Laval	Québec		Canada
2	Helsinki University Central Hospital, Biomedicum	Helsinki		Finland	00290
3	University of Naples, Federico II, and Faculty of Medicine	Naples		Italy
4	Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital	Gothenburg		Sweden

Sponsors and Collaborators

• Marja-Riitta Taskinen
• Sahlgrenska University Hospital, Sweden
• Lund University
• University of Naples
• Laval University

Investigators

• Principal Investigator: Marja-Riitta Taskinen, Professor, Helsinki University Central Hospital, Biomedicum

Study Documents (Full-Text)

• Study Protocol - Aug 26, 2013

More Information

Publications

None provided.

• Responsible Party: Marja-Riitta Taskinen, Professor, Helsinki University Central Hospital
• ClinicalTrials.gov Identifier: NCT01445730
• Other Study ID Numbers: T1010K0029
• First Posted: Oct 4, 2011
• Last Update Posted: Jun 15, 2021
• Last Verified: May 1, 2021

• Keywords provided by Marja-Riitta Taskinen, Professor, Helsinki University Central Hospital: fructose; hypertriglyceridemia; postprandial lipids; de novo lipogenesis; stable isotopes
• Additional relevant MeSH terms: Hypertriglyceridemia; Obesity, Abdominal

Study Results

Participant Flow

Arm/Group Title	After Fructose Feeding
Arm/Group Description	After 3 month fructose diet 75 g/day
Period Title: Overall Study
STARTED	82
COMPLETED	71
NOT COMPLETED	11

Baseline Characteristics

Arm/Group Title	After Fructose Feeding
Arm/Group Description	After 3 month fructose diet 75 g/day
Overall Participants	82
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	82 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	82 100%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
Canada	4 4.9%
Sweden	10 12.2%
Finland	50 61%
Italy	18 22%

Outcome Measures

1. Primary Outcome

Title	TG Plasma AUC
Description	Before vs. after fructose challenge: Triglycerides (TG) plasma Area Under Curve (AUC)
Time Frame	Form the baseline (time point 1) to end of treatment at 3 months (time point 2)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	After Fructose Feeding
Arm/Group Description	After 3 month fructose diet 75 g/day
Measure Participants	71
Time point 1	1130 (590)
Time point 2	1220 (598)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	After Fructose Feeding
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Primary Outcome

Title	B48 Plasma AUC
Description	Before vs. after fructose challenge: apolipoprotein (apo)B48 plasma Area Under Curve (AUC)
Time Frame	Form the baseline (time point 1) to end of treatment at 3 months (time point 2)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	After Fructose Feeding
Arm/Group Description	After 3 month fructose diet 75 g/day
Measure Participants	71
Time point 1	7660 (3210)
Time point 2	8200 (3340)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	After Fructose Feeding
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Primary Outcome

Title	TG Plasma iAUC
Description	Before vs. after fructose challenge:Triglycerides (TG) plasma incremental Area Under Curve (iAUC)
Time Frame	Form the baseline (time point 1) to end of treatment at 3 months (time point 2)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	After Fructose Feeding
Arm/Group Description	After 3 month fructose diet 75 g/day
Measure Participants	71
Time point 1	377 (422)
Time point 2	422 (270)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	After Fructose Feeding
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Secondary Outcome

Title	DNL
Description	Before vs. after fructose challenge: de novo lipogenesis (DNL)
Time Frame	Form the baseline (time point 1) to end of treatment at 3 months (time point 2)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	After Fructose Feeding
Arm/Group Description	After 3 month fructose diet 75 g/day
Measure Participants	71
Time point 1	12.3 (10)
Time point 2	16.5 (11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	After Fructose Feeding
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

5. Secondary Outcome

Title	ApoC-III
Description	Before vs. after fructose challenge: Apolipoprotein C-III (ApoC-III)
Time Frame	Form the baseline (time point 1) to end of treatment at 3 months (time point 2)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	After Fructose Feeding
Arm/Group Description	After 3 month fructose diet 75 g/day
Measure Participants	71
Time point 1	10.4 (5.1)
Time point 2	11.2 (5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	After Fructose Feeding
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

6. Secondary Outcome

Title	β-OH Butyrate
Description	Before vs. after fructose challenge: beta-OH butyrate (β-OH butyrate)
Time Frame	Form the baseline (time point 1) to end of treatment at 3 months (time point 2)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	After Fructose Feeding
Arm/Group Description	After 3 month fructose diet 75 g/day
Measure Participants	71
Time point 1	0.699 (0.55)
Time point 2	0.542 (0.48)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	After Fructose Feeding
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.01
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

7. Secondary Outcome

Title	Liver Fat
Description	Before vs. after fructose challenge
Time Frame	Form the baseline (time point 1) to end of treatment at 3 months (time point 2)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	After Fructose Feeding
Arm/Group Description	After 3 month fructose diet 75 g/day
Measure Participants	71
Time point 1	6.66 (6.1)
Time point 2	7.33 (6.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	After Fructose Feeding
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.008
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	During 3 month fructose diet 75 g/day.
Adverse Event Reporting Description	Of the 82 subjects, two subjects discontinued the intervention study: one developed a skin rash, which was considered as possible allergic reaction to flavouring and the other subject discontinued in response to his dentist's advice. In addition, the data from magnetic resonance examinations at baseline or after the fructose intervention were not sufficient from nine subjects for technical reasons to allow the analyses of different fat depots. Thus, 71 subjects completed the full study protocol.
Arm/Group Title	After Fructose Feeding
Arm/Group Description	After 3 month fructose diet 75 g/day
All Cause Mortality
	After Fructose Feeding
	Affected / at Risk (%)	# Events
Total	0/82 (0%)
Serious Adverse Events
	After Fructose Feeding
	Affected / at Risk (%)	# Events
Total	0/82 (0%)
Other (Not Including Serious) Adverse Events
	After Fructose Feeding
	Affected / at Risk (%)	# Events
Total	1/82 (1.2%)
Skin and subcutaneous tissue disorders
skin rash	1/82 (1.2%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.