Healthy Liver - Healthy Brain

Study Overview
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Brief Summary
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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
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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.

Official Title
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Diet Intervention to Promote Liver and Brain Health in Adults With Non-alcoholic Fatty Liver Disease

Conditions
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NAFLD, Metabolic Syndrome, Non-Alcoholic Fatty Liver Disease, Pre-diabetes

Intervention / Treatment
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* Behavioral: Diet Intervention


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-carbohydrate diet<br>Participants assigned to the Low-carbohydrate diet will be instructed to limit carbohydrate intake to <30 g/d. | Behavioral: Diet Intervention<br>* Meal will be prepared and delivered by SNAP Kitchen, which has 7 locations in Austin and offers 20+ options for low-carbohydrate and low-calorie meals, each meal available in different sizes varying in energy intake. Meals will be entered into the Nutrition Data System for Research (NDS-R) software to confirm low-calorie profile. Meals will be delivered to participants' homes twice a week.<br>|
| Active Comparator: Low-calorie diet<br>Participants assigned to the Low-calorie diet will be instructed to reduce their energy intake to match the LoCHO block (we are predicting  1200 kcal/d for women and  1500 kcal/d for men, following current recommendations for treatment of NAFLD). | Behavioral: Diet Intervention<br>* Meal will be prepared and delivered by SNAP Kitchen, which has 7 locations in Austin and offers 20+ options for low-carbohydrate and low-calorie meals, each meal available in different sizes varying in energy intake. Meals will be entered into the Nutrition Data System for Research (NDS-R) software to confirm low-calorie profile. Meals will be delivered to participants' homes twice a week.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decrease in Liver Fat | Hepatic triglyceride level will be assessed using liver 1H MRS. | 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). | 
| Decrease in cerebral gluatamate | Cerebral glutamate levels will be measured using 1H MRS. | 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). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diet, Low-carbohydrate, Neuroimaging, Liver