Fructose Consumption and Metabolic Dysregulation

Fructose Consumption Aggravates Dysregulation of Postprandial Lipid Metabolism in Obese Hypertriglyceridemic Men With High Cardiometabolic Risk Profile and Associates With Liver Fat Deposition

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01445730

Enrollment

Registered

2011-10-04

Start date

2011-08-31

Completion date

2015-06-30

Last updated

2021-06-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Central Obesity, Hypertriglyceridemia

Keywords

fructose, hypertriglyceridemia, postprandial lipids, de novo lipogenesis, stable isotopes

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.

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.

Interventions

DIETARY_SUPPLEMENTFructose

3 month fructose diet 75 g/day

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

BASIC_SCIENCE

Masking

NONE

Eligibility

Sex/Gender

MALE

Age

20 Years to 60 Years

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

Design outcomes

Primary

Measure	Time frame	Description
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)
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)
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

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

Countries

Canada, Finland, Italy, Sweden

Participant flow

Participants by arm

Arm	Count
After Fructose Feeding After 3 month fructose diet 75 g/day	82
Total	82

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	1
Overall Study	For the advice of a dentist	1
Overall Study	The data from magnetic resonance examinations were not sufficient	9

Baseline characteristics

Characteristic	After Fructose Feeding	—
Age, Categorical <=18 years	0 Participants	—
Age, Categorical >=65 years	0 Participants	—
Age, Categorical Between 18 and 65 years	82 Participants	—
Race and Ethnicity Not Collected	—	— Participants
Region of Enrollment Canada	4 participants	—
Region of Enrollment Finland	50 participants	—
Region of Enrollment Italy	18 participants	—
Region of Enrollment Sweden	10 participants	—
Sex: Female, Male Female	0 Participants	—
Sex: Female, Male Male	82 Participants	—

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 82
other Total, other adverse events	1 / 82
serious Total, serious adverse events	0 / 82