**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** CORONAVIRUS DISEASE 2019 (COVID-19), THE VIRAL MULTI-SYSTEM ILLNESS CAUSED BY THE NOVEL CORONAVIRUS SARS-COV-2, HAS RESULTED IN SIGNIFICANT MORBIDITY AND MORTALITY ACROSS THE WORLD. APPROXIMATELY 30% OF PATIENTS EXPERIENCE LONG-COVID SYNDROME PRESENTING WITH SYMPTOMS SUCH AS COGNITIVE DIFFICULTIES ('BRAIN FOG'), FATIGUE, DYSPNEA, AUTONOMIC DYSFUNCTION, DEPRESSION AND ANXIETY, LASTING BEYOND 12 WEEKS CAUSING SIGNIFICANT DISABILITY, AND THREATEN HEALTH AND WELLBEING OF MILLIONS AROUND THE WORLD. AT THE CURRENT TIME THERE IS NO EFFECTIVE TREATMENT FOR LONG-COVID.WALNUTS CONTAIN A MIXTURE OF NUTRIENTS AND PHYTOCHEMICALS INCLUDE MONOUNSATURATED FATTY ACIDS (MUFA), POLYUNSATURATED FATTY ACIDS (PUFA), AND ALPHA-LINOLENIC ACID (ALA) THAT ARE IMPORTANT TO HUMAN HEALTH. CROSS-SECTIONAL STUDIES FOUND THAT WALNUT CONSUMPTION WAS DIRECTLY ASSOCIATED WITH COGNITIVE FUNCTION. WALNUTS ARE RICH SOURCE OF ELLAGITANNINS AND ELLAGIC ACID THAT CAN BE FURTHER CONVERTED BY INTESTINAL MICROBIOTA TO UROLITHINS. ALL THOSE COMPOUNDS HAVE BEEN REPORTED TO EXHIBIT NUMEROUS BENEFICIAL EFFECTS ON HUMAN HEALTH OUR RECENT STUDY AT UCLA DEMONSTRATED THAT DAILY CONSUMPTION OF POMEGRANATE JUICE, ANOTHER RICH SOURCE OF ELLAGITANNINS STABILIZED THE ABILITY TO LEARN VISUAL INFORMATION OVER A 12-MO PERIOD IN IN MIDDLE-AGED AND OLDER ADULTS [8]. WE HAVE SHOWN POMEGRANATE AND MIXED NUTS INCLUDING WALNUTS COULD INCREASE BLOOD MICROBIOME METABOLITES OF TRYPTOPHAN METABOLITE INDOLE PROPIONATE (IPA) AND SEROTONIN LEVELS VIA CHANGE OF GUT MICROBIOTA. BOTH IPA AND SEROTONIN PLAY AN ESSENTIAL ROLE IN GUT-BRAIN AXIS INCLUDING COGNITIVE FUNCTION.OUR PROPOSED PILOT STUDY WILL INCLUDE 76 ADULTS (AGES 50-80 YEARS) WITH DOCUMENTED DIAGNOSIS OF SARS-COV2 INFECTION PRESENTING WITH LONG-COVID SYMPTOMS LASTING LONGER THAN 12 WEEKS. THEY WILL BE RANDOMIZED 1:1 TO USUAL CARE VS. AN INTERVENTION GROUP THAT WILL INCLUDE 2 OZ (57G) OF WALNUTS DAILY INTO THEIR HABITUAL DIET FOR 12 WEEKS. WE WILL COMPARE THE IMPROVEMENT IN SYMPTOMS OF COGNITIVE COMPLAINS OF BRAIN FOG, FATIGUE AND DEPRESSION OF THE ACTIVE INTERVENTION GROUP VS. USUAL CARE. IN THIS PILOT STUDY, WE WILL ASSESS ALL ASPECTS OF COGNITION, INCLUDING EPISODIC MEMORY, EXECUTIVE FUNCTION, PROCESSING SPEED, WORKING MEMORY, ATTENTION, AND LANGUAGE, IN ORDER TO DETERMINE THE MOST SENSITIVE OUTCOME MEASURES AS WELL AS TO ESTIMATE THE EFFECT SIZES FOR PLANNING A FUTURE RO1/UO1 OR OTHER FUNDING FOR AN EFFICACY TRIAL. ADDITIONALLY, WE WILL ALSO TEST THE METHODOLOGY PRIOR TO APPLICATION FOR A LARGER CLINICAL TRIAL TO ASSESS RECRUITMENT FEASIBILITY, ADHERENCE, SAFETY, AND ACCEPTABILITY OF THE INTERVENTIONS IN THIS POPULATION. WE WILL EXPLORE THE MECHANISM OF HOW WALNUT CONSUMPTION AFFECTS BRAIN FOG, FATIGUE AND MOOD SYMPTOMS BY MEASURE BACTERIAL TRYPTOPHAN METABOLITES. THE OUTCOME OF THE INVESTIGATION OF THE BENEFIT OF WALNUT CONSUMPTION WILL PROVIDE IMPORTANT NOVEL INFORMATION ON USING DIETARY SOURCES OF POLYUNSATURATED FATTY ACIDS AND PHYTOCHEMICALS TO,MITIGATE THE COMMON SYMPTOMS OF LONG-COVID.
$294,000FY2023National Institute of Food and AgricultureUSDA
University Of California, Los Angeles