How Does Dietary Carbohydrate Influence the Formation of an Atherogenic Lipoprotein Phenotype (ALP)?

Non-alcoholic Fatty Liver Disease (NAFLD) Clinical Trial

— CHOT  

Official title:

How Does Dietary Carbohydrate Influence the Formation of an Atherogenic Lipoprotein Phenotype?

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01790984
• Other study ID #: RN0172 A/B
• Secondary ID: BB/G009899/1
• Status: Completed
• Phase: N/A
• Start date: April 2009
• Est. completion date: September 2012

Study information

• Verified date: May 2021
• Source: University of Surrey
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The hypothesis of this study is that a diet high in sugars will increase abnormalities in blood lipids which are associated with increased cardiovascular disease risk, relative to a diet which is low in sugar. We predict that this potentially adverse effect of dietary sugars on blood lipids will be more pronounced in people with a raised level of stored fat inside their liver, as compared to people with a low level of stored fat.

Description:

This study aims to determine the metabolic mechanism(s) by which dietary extrinsic sugars (sucrose and fructose), promote the formation of a high risk dyslipidaemia, known as an atherogenic lipoprotein phenotype (raised plasma triglyceride, low HDL and predominance of small, dense LDL), in men with raised cardio-metabolic risk and percentage of liver fat, as determined by magnetic resonance spectroscopy (MRS). The study examined the impact of diets high and low in extrinsic sugars, on the metabolism of lipids and lipoproteins in vivo, of two groups of men with a high (>10%)and low (<2%)percentage of liver fat, by the trace-labelling of these lipid moieties with stable isotopes, and detection by gas chromatography mass spectrometry. The study had a two-way cross-over design, with two, 12 week dietary interventions separated by a six week wash-out period. The dietary intervention with high and low sugars was achieved by a dietary exchange with supermarket foods, which were consumed within the homes of the participants.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: September 2012
• Est. primary completion date: August 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Male gender,
• Increased cardio-metabolic risk ('RISCK' criteria Jebb et al (2010) Am J Clin Nutr 92, 748-758).
• Apo E3E3 genotype

Exclusion Criteria:

• Any abnormal result in blood screen (renal and liver function, haematology)
• Diabetes
• Smoker
• Excessive alcohol consumption (>27units/week)
• Medication likely to affect lipid metabolism
• >3kg weight loss in preceding 3 months
• Any medical condition (eg. GI tract, allergies) affecting lipid metabolism or ability to comply with dietary interventions
• Involvement in any other study

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-alcoholic Fatty Liver Disease
• Non-alcoholic Fatty Liver Disease (NAFLD)

Intervention

Other:
• High sugar low starch diet

• Low sugar high starch diet

Locations

Country	Name	City	State
United Kingdom	University of Surrey	Guildford	Surrey

Sponsors (3)

Lead Sponsor	Collaborator
Bruce A. Griffin	Imperial College London, University of Cambridge

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Production Rate of VLDL-1 Triacylglycerol (TAG)	The in vivo production rate of VLDL-1 TAG, trace-labelled with [1,1,2,3,3-H5] glycerol, measured in units of grams/day.	After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)
Primary	Production Rate VLDL-1 Apoprotein B	The in vivo production rate of VLDL-1 apoprotein B, trace-labelled with [I-13C] leucine (leucine with carbon-13), measured in units of milligrams/day.	After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)
Secondary	Kinetics of Systemic Non-esterified Fatty Acids by [C-13]-Trace-labelled Palmitate	Palmitate was labelled in vivo by the infusion of [U-13 carbon]. This provides a measure of the rate of intra-cellular lipolysis and contribution of systemic palmitate to the synthesis of triacylglycerol in the liver in units of micro mols/L (umol/L).	After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)
Secondary	De Novo Lipogenesis (Rate of Triacylglycerol (TAG) Synthesis in the Liver) as Measured by Contribution to VLDL-1 TAG Production Rate	Acetyl CoA (Co-enzyme-A) is labelled in vivo by the consumption of [2H20] (2H20=deuterated 'heavy'-labelled water). Recovery and detection of this label in VLDL-1 by GC-MS (Gas Chromatography-Mass Spectrometry), provides a measure of fatty acid and TAG synthesis in the liver in terms of its contribution to the production rate of VLDL-1 TAG in units of grams/day.	After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)
Secondary	Intra-hepatocellular Lipid (IHCL) or % Liver Fat	Percentage of intra-hepatocellular lipid (IHCL or % liver fat) was measured by magnetic resonance spectroscopy (MRS).	After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)
Secondary	Plasma Concentration of Triacylglycerol	Plasma concentration of triacylglycerol (TAG) was measured in the post-absorptive state (after 12h fast) and expressed in units of mmol/L (shown as log transformed geometric means)	After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)