Clinical trial NCT01790984: How Does Dietary Carbohydrate Influence the Formation of an Atherogenic Lipoprotein Phenotype (ALP)?
Official title: How Does Dietary Carbohydrate Influence the Formation of an Atherogenic Lipoprotein Phenotype?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Non-alcoholic Fatty Liver Disease (NAFLD)
Keywords: Sugars, Fatty liver, Lipoprotein kinetics, Triglycerides
Lead sponsor: University of Surrey
Sponsor class: OTHER
Collaborators: name: Imperial College London
name: University of Cambridge
First posted: 2013-02-13
Enrollment: 27
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Production Rate of VLDL-1 Triacylglycerol (TAG)
timeFrame: After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)
measure: Production Rate VLDL-1 Apoprotein B
timeFrame: After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)
Secondary outcomes:
measure: Kinetics of Systemic Non-esterified Fatty Acids by [C-13]-Trace-labelled Palmitate
timeFrame: After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)
measure: De Novo Lipogenesis (Rate of Triacylglycerol (TAG) Synthesis in the Liver) as Measured by Contribution to VLDL-1 TAG Production Rate
timeFrame: After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)
measure: Intra-hepatocellular Lipid (IHCL) or % Liver Fat
timeFrame: After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)
measure: Plasma Concentration of Triacylglycerol
timeFrame: After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)
Other outcomes:
Locations:
city: Guildford
country: United Kingdom
facility: University of Surrey
state: Surrey
Study officials:
affiliation: University of Surrey
name: Bruce A Griffin, PhD
role: PRINCIPAL_INVESTIGATOR
References: