Clinical trial NCT05216796: Healthy Liver - Healthy Brain
Official title: Diet Intervention to Promote Liver and Brain Health in Adults With Non-alcoholic Fatty Liver Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metabolic Syndrome
Non-Alcoholic Fatty Liver Disease
NAFLD
Pre-diabetes
Keywords: Neuroimaging
Liver
Low-carbohydrate
Diet
Lead sponsor: University of Texas at Austin
Sponsor class: OTHER
First posted: 2022-02-01
Enrollment: 55
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The investigators will employ a block randomization (n=10) between groups feeding trial where 100 participants will be assigned to receive either low-carbohydrate (LoCHO) or low-calorie (LoCAL) control diet for up to 3 weeks.
Primary purpose: BASIC_SCIENCE

Brief summary: People with liver disease report difficulties with attention and problem-solving skills. Diet plays an important role in the development of liver disease and/or pre-diabetes. The purpose of this study is to examine whether participation in a brief diet intervention (up to 3 weeks) can improve brain and liver health and function.

Detailed description: The importance of liver function for brain and cognitive health is undeniable. Specifically, adults with chronic liver diseases such as non-alcoholic fatty liver disease (NAFLD), a factor of metabolic syndrome (MetS), experience a range of symptoms including problems with attention, problem solving skills and executive function. Importantly, diet plays a role in the development of NAFLD. The investigators propose to be the first to demonstrate that Metabolic syndrome-related brain vulnerability, in the form of elevated free cerebral glutamate, is related to hepatic triglyceride level, through experimental manipulation of liver fat and multiorgan imaging. The investigators seek to improve liver health by altering diet content in a block randomized feeding trial. The investigators selected a low-carbohydrate (\<30 g/d) diet (LoCHO) to reduce liver fat and a low-calorie (LoCAL) diet as a control for weight loss. The investigators hypothesize that LoCHO diet will improve cognitive performance by improving liver health and thus, brain health. This work may provide a way to support brain function in MetS and delay cognitive decline.

Eligibility criteria: Inclusion Criteria:

* at least 40 years of age
* English speakers
* show a minimum of 5% hepatic triglyceride level on liver imaging
* have not taken part in a weight loss/dietary intervention within 6 months
* not currently adhering to a low-carbohydrate diet (e.g., Atkins, Paleo)

Exclusion Criteria:

* younger than 40 years of age
* have a history of neurological disease (e.g. stroke, seizure disorder)
* psychiatric illness (e.g. schizophrenia, bipolar disorder)
* harmful alcohol use (AUDIT-C score \>5)
* morbid obesity (BMI\>40)
* MRI contraindications

Primary outcomes:
measure: Decrease in Liver Fat
timeFrame: Liver fat will be measured at baseline (week 0) and after at least 2 weeks (up to 3 weeks) on the designated diet. The liver 1H MRS scans will happen during Visit 3 (baseline) and Visit 4 (at least 2 weeks on the diet).
measure: Decrease in cerebral gluatamate
timeFrame: Cerebral glutamate will be measured at baseline (week 0) and after at least 2 weeks (up to 3 weeks) on the designated diet. The brain 1H MRS scans will happen during Visit 3 (baseline) and Visit 4 (at least 2 weeks on the diet).
Secondary outcomes:
Other outcomes:
Locations:
city: Austin
country: United States
facility: University of Texas at Austin
state: Texas
Study officials:
affiliation: Department of Psychology, University of Texas at Austin
name: Andreana Haley, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Browning JD, Baker JA, Rogers T, Davis J, Satapati S, Burgess SC. Short-term weight loss and hepatic triglyceride reduction: evidence of a metabolic advantage with dietary carbohydrate restriction. Am J Clin Nutr. 2011 May;93(5):1048-52. doi: 10.3945/ajcn.110.007674. Epub 2011 Mar 2.
citation: Ervin RB. Prevalence of metabolic syndrome among adults 20 years of age and over, by sex, age, race and ethnicity, and body mass index: United States, 2003-2006. Natl Health Stat Report. 2009 May 5;(13):1-7.
citation: Haley AP, Gonzales MM, Tarumi T, Tanaka H. Subclinical vascular disease and cerebral glutamate elevation in metabolic syndrome. Metab Brain Dis. 2012 Dec;27(4):513-20. doi: 10.1007/s11011-012-9306-x. Epub 2012 May 3.
citation: Oh R, Gilani B, Uppaluri KR. Low-Carbohydrate Diet. 2023 Aug 17. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK537084/
citation: Crabb DW, Im GY, Szabo G, Mellinger JL, Lucey MR. Diagnosis and Treatment of Alcohol-Associated Liver Diseases: 2019 Practice Guidance From the American Association for the Study of Liver Diseases. Hepatology. 2020 Jan;71(1):306-333. doi: 10.1002/hep.30866. No abstract available.