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

Not Applicable

Completed

Conditions: Non-alcoholic Fatty Liver Disease (NAFLD)

Interventions: Other: High sugar low starch diet
Other: Low sugar high starch diet

Registration Number: NCT01790984

Lead Sponsor: Bruce A. Griffin

Brief 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 27

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 & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
High sugar low starch diet	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
Low sugar high starch diet	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 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
High sugar low starch diet	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 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
Low sugar high starch diet	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

Primary Outcome Measures

Name	Time	Method
Production Rate of VLDL-1 Triacylglycerol (TAG)	After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)	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.
Production Rate VLDL-1 Apoprotein B	After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)	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.

Secondary Outcome Measures

Name	Time	Method
De Novo Lipogenesis (Rate of Triacylglycerol (TAG) Synthesis in the Liver) as Measured by Contribution to VLDL-1 TAG Production Rate	After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)	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.
Intra-hepatocellular Lipid (IHCL) or % Liver Fat	After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)	Percentage of intra-hepatocellular lipid (IHCL or % liver fat) was measured by magnetic resonance spectroscopy (MRS).
Kinetics of Systemic Non-esterified Fatty Acids by [C-13]-Trace-labelled Palmitate	After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)	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).
Plasma Concentration of Triacylglycerol	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 (TAG) was measured in the post-absorptive state (after 12h fast) and expressed in units of mmol/L (shown as log transformed geometric means)