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

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

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.

Study Overview

• Status: Completed
• Conditions: Non-alcoholic Fatty Liver Disease (NAFLD)
• Intervention / Treatment: Other: High sugar low starch diet; Other: Low sugar high starch diet

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Surrey
    • Guildford, Surrey, United Kingdom, GU2 7XH
      • University of Surrey

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High sugar low starch diet; A high sugar, low starch diet was provided by the exchange of two thirds of the participants daily intake of carbohydrate. This was achieved by exchanging foods with low sugar to starch content, with foods containing a high sugar to starch content to reach a target ratio of starch to sugar of 1:1.2	Other: High sugar low starch diet; Other: Low sugar high starch diet
Experimental: Low sugar high starch diet; A high sugar, low starch diet was provided by the exchange of two thirds of the participants daily intake of carbohydrate. This was achieved by exchanging foods with a high sugar to starch content, with foods containing a low sugar to starch content to reach a target ratio of starch to sugar of 5:1	Other: High sugar low starch diet; Other: Low sugar high starch diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)

Collaborators and Investigators

• Sponsor: Bruce A. Griffin
• Collaborators: Imperial College London; University of Cambridge
• Investigators: Principal Investigator: Bruce A Griffin, PhD, University of Surrey

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: February 11, 2013
• First Submitted That Met QC Criteria: February 11, 2013
• First Posted (Estimate): February 13, 2013

Study Record Updates

• Last Update Posted (Actual): May 27, 2021
• Last Update Submitted That Met QC Criteria: May 4, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Sugars, Fatty liver, Lipoprotein kinetics, Triglycerides
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: RN0172 A/B; BB/G009899/1 (Other Grant/Funding Number: BBSRC)