Insulin Resistance, Non-Alcoholic Fatty Liver Disease
Conditions
Brief summary
It will be evaluated whether carnitine, a dietary supplement, reduces liver fat and improves metabolism in individuals who have a high concentration of fat within their liver. Participants will be given either Carnitine or placebo, together with a meal replacement milkshake twice daily for 6 months.
Detailed description
NAFLD occurs when too much fat accumulates in liver tissue. This can, over time, cause inflammation and scarring of the liver, eventually leading to chronic liver disease and cirrhosis. It is strongly associated with diabetes and obesity, both of which are endemic in Western societies. Carnitine enables cells in the body to use fat as a fuel, and recent studies have suggested that carnitine supplementation may reduce liver triglyceride content. Muscle and liver are the major sites in the body which coordinate glucose and fat metabolism. As well as assessing the effect of carnitine supplementation on liver fat, its effect on metabolic processes within these tissues will also be measured
Interventions
DIETARY_SUPPLEMENTL-Carnitine tartrate
2g L-Carnitine tartrate as a powder consumed twice a day
DIETARY_SUPPLEMENTMeal Replacement Drink
325ml dairy-based meal replacement drink ('Slimfast' trademark of KSF Acquisition UK Ltd) consumed twice a day
DIETARY_SUPPLEMENTMaltodextrin
2g Maltodextrin powder packaged to mimic carnitine powder consumed twice a day
Sponsors
Nottingham University Hospitals NHS Trust
National Institute for Health Research, United Kingdom
University of Nottingham
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Elevated liver fat on screening abdominal ultrasound * Capable of providing informed consent * Non-vegetarian diet * BMI \<40 kg/m2 * Weekly ethanol consumption \<21 units/week * Negative non-invasive liver screen, including Hepatitis B and C serology, liver autoantibodies, transferrin saturation, α1-antitrypsin levels.
Exclusion criteria
* Known history of cardiovascular disease * Known diabetes mellitus * Known psychiatric comorbidity * Chronic kidney disease * Surgery within 6 months prior to start of study * Exposure to drugs known to influence hepatic steatosis (including steroids, statins, omega-3-fatty acids) * Current smokers * Contraindications to magnetic resonance scanning, including implanted ferrous material (implantable pacemakers or defibrillators), metallic ocular foreign bodies, ferromagnetic aneurysm clips or severe claustrophobia.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intrahepatic triglyceride (IHTG) content | 24 weeks | IHTG measured by proton magnetic resonance spectroscopy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Muscle lipid content | 24 weeks | lipid content of the vastus lateralis muscle measured by proton magnetic resonance spectroscopy |
| Skeletal muscle sensitivity to insulin | 24 weeks | Arterialised-venous vs. femoral venous difference in blood glucose concentration during the last hour of a 2 hour 50 mU.m-2.min-1 hyperinsulinaemic euglycaemic clamp |
| Liver energy metabolism | 24 weeks | hepatic ATP flux assessed by 31-phosphorous magnetic resonance spectroscopy |
| liver sensitivity to insulin | 24 weeks | suppression of glucose output from the liver during a 20 mU.m-2.min-1 hyperinsulinaemic euglycaemic clamp |
| whole body insulin sensitivity | 24 weeks | whole body glucose uptake during a 50 mU.m-2.min-1 hyperinsulinaemic euglycaemic clamp |
| whole body composition | 24 weeks | Fat and lean tissue mass assessment by dual energy X-ray absorptiometry |
Countries
United Kingdom
Outcome results
None listed