Serum metabolite profiles in adults with abdominal obesity in response to consuming one avocado daily for six months: An exploratory analysis

Authors: MATTHAN, NIRUPA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; DUSCOVA, ECATERINA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MATUSZEK, GREGORY - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; ZHANG, WEN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; KRIS-ETHERTON, PENNY - Pennsylvania State University; PETERSEN, KRISTINA - Pennsylvania State University; RAJARAM, SUJATHA - Loma Linda University; LI, ZHAOPING - University Of California (UCLA); REBOUSSIN, DAVID - Wake Forest University; SABATE, JOAN - Loma Linda University; LICHTENSTEIN, ALICE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of the American Heart Association
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/9/2026
Publication Date: 3/10/2026
Citation: Matthan, N., Duscova, E., Matuszek, G., Zhang, W., Kris-Etherton, P.M., Petersen, K., Rajaram, S., Li, Z., Reboussin, D., Sabate, J., Lichtenstein, A.H. 2026. Serum metabolite profiles in adults with abdominal obesity in response to consuming one avocado daily for six months: An exploratory analysis. The American Journal of Clinical Nutrition. 15(6). https://doi.org/10.1161/JAHA.125.044144.
DOI: https://doi.org/10.1161/JAHA.125.044144

Interpretive Summary: Avocados are rich in monounsaturated fatty acids, fiber, essential nutrients, and bioactive compounds. Avocado intake has been associated with healthy dietary patterns and measures of heart health. This study measured small molecules known as metabolites in blood samples collected from individuals with abdominal obesity (waist fat) who ate an avocado every day for six months. The goal was to determine if long-term avocado consumption affected metabolite levels and heart disease risk factors. We found changes in 75 metabolites related to fat (lipid), sugar (carbohydrate), and amino acid (protein) metabolism, as well as metabolites produced by the gut microbiota. The changes in several lipid metabolites were linked to changes in blood cholesterol and triglyceride levels, and visceral adiposity, a measure of body fat in the mid-section. These findings suggest that daily avocado intake alters metabolite levels that may be favorable for some heart disease markers.

Technical Abstract: Background: Habitual avocado consumption has been reported to improve diet quality and cardiometabolic risk factors (CMRFs). Effects on serum metabolite profiles remain underexplored. Objectives: This ancillary study explored serum metabolite changes following 6-months of daily avocado consumption in participants with abdominal obesity from the Habitual Diet and Avocado Trial (HAT). Methods: Secondary analysis was conducted using untargeted metabolomics to assess fasting serum metabolite profiles at baseline (pre-intervention) and 6-months (post-intervention) in a subset of HAT participants randomized to the avocado group (n=120; 70% female; age 49 + or - 13 years; BMI 33.1 + or - 5.7 kg/m2). Pre-post intervention changes in metabolites, CMRFs (blood pressure, lipids, glucose, insulin, high-sensitivity C-reactive protein [hsCRP]), visceral adiposity (VAT), and hepatic fat (HFF) were evaluated using Wilcoxon tests. Partial-least squares discriminant analysis examined metabolite covariance with avocado intake, and multiple regression assessed metabolite-CMRF associations, adjusting for covariates (age, sex, BMI, smoking status, physical activity, energy intake) and multiple testing (FDR <0.1). Results: Plasma LDL-C (-6%), systolic (-3%), and diastolic (-2%) blood pressures decreased, while VAT increased (3%) post-intervention (all p<0.05). We identified 31 primary (sugar acids/alcohols, amino/carboxylic/hydroxy acids, indoles, xenobiotics) and 44 lipid-related metabolites (fatty acids, cholesteryl esters, glycerolipids, glycerophospholipids, sphingolipids) as key drivers of separation between pre-post intervention timepoints (VIP >1). Significant but weak to modest associations (multiple-R range=0.21-0.52) were observed between 96 predominantly lipid-related metabolites and VAT, plasma TG and TC concentrations. Conclusions: Avocado intake caused subtle shifts in serum metabolites associated with lipid, carbohydrate, and amino acid metabolism, with weak effects on VAT, plasma TG and TC concentrations. Keywords: avocado; dietary intervention; metabolomics; cardiometabolic risk factors; visceral adiposity; primary metabolites, complex lipids, gut-derived metabolites