Healthy Liver - Healthy Brain

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.

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.

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.

Participants assigned to the Low-carbohydrate diet will be instructed to limit carbohydrate intake to <30 g/d.

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).

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.

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).

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).

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

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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.

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.

Oh R, Gilani B, Uppaluri KR. Low-Carbohydrate Diet. 2023 Aug 17. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK537084/

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.