Associations between metabolomic biomarkers of avocado intake and glycemia in the Multi-Ethnic Study of Atherosclerosis (MESA)

Authors: WOOD, ALEXIS - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC); GOODARZI, MARK - CEDARS-SINAI MEDICAL CENTER; SENN, MACKENZIE - UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER; GADGIL, MEGHANA - UNIVERSITY OF CALIFORNIA SAN FRANCISCO (UCSF); GRAÇA, GONÇALO - IMPERIAL COLLEGE; ALLISON, MATTHEW - UNIVERSITY OF CALIFORNIA, SAN DIEGO; TZOULAKI, IOANNA - IMPERIAL COLLEGE; MI, MICHAEL - BETH ISRAEL DEACONESS MEDICAL CENTER; GREENLAND, PHILIP - NORTHWESTERN UNIVERSITY; EBBELS, TIMOTHY - IMPERIAL COLLEGE; ELLIOTT, PAUL - IMPERIAL COLLEGE; TRACY, RUSSELL - UNIVERSITY OF VERMONT; HERRINGTON, DAVID - WAKE FOREST SCHOOL OF MEDICINE; ROTTER, JEROME - HARBOR-UCLA MEDICAL CENTER

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/31/2023
Publication Date: 8/9/2023
Citation: Wood, A.C., Goodarzi, M.O., Senn, M.K., Gadgil, M.D., Graça, G., Allison, M.A., Tzoulaki, I., Mi, M.Y., Greenland, P., Ebbels, T., Elliott, P., Tracy, R.P., Herrington, D.M., Rotter, J.I. 2023. Associations between metabolomic biomarkers of avocado intake and glycemia in the Multi-Ethnic Study of Atherosclerosis (MESA). Journal of Nutrition. https://doi.org/10.1016/j.tjnut.2023.07.013.
DOI: https://doi.org/10.1016/j.tjnut.2023.07.013

Interpretive Summary: Eating avocado consumption is linked to better blood sugar control, and a lower risk of type 2 diabetes (T2D). However, not everyone seems to get these health advantages from eating avocado. One reason might be because people digest their food (such as avocados) in different ways. Therefore, we used metabolomic data to identify a biomarker of avocado intake in the blood, representing avocado intake after the fruit has been metabolized, and we examined the association of this biomarker with glucose control and with the likelihood of developing T2D. In a large-scale analysis of over 6,000 older adults, we found metabolite was associated with self-reported avocado intake. This metabolite was associated with lower insulin level, and with a lower risk of developing T2D over an 18-year period, and the associations with the biomarker were much stronger than the same associations with avocado intake. We concluded that eating avocado can help improve blood sugar control, and help prevent the onset of T2D, but differences in how we digest and metabolize our avocado intake is an important consideration in these relationships.

Technical Abstract: Avocado consumption is linked to better glucose homeostasis, but associations are small, suggesting potential population heterogeneity. Metabolomic data capture the effects of food intake after digestion, and metabolism, thus accounting for individual differences in these processes. The objective of the study was to identify metabolomic biomarkers of avocado intake, and to examine their associations with glycemia. Baseline data from 6,224 multi-ethnic older adults (62% female) included self-reported avocado intake, fasting glucose and insulin, and untargeted plasma 1H NMR metabolomic features (metabolomic data were available for a randomly selected subset; N=3,438). Subsequently, incident type 2 diabetes (T2D) was assessed over an approximately18 year follow-up period. A metabolome-wide association study of avocado consumption status (consumer vs. non) was conducted, and the relationship of these features with glycemia via cross-sectional associations with fasting insulin and glucose, and longitudinal associations with incident T2D was examined. Three highly correlated spectral features were associated with avocado intake at metabolome-wide levels of significance (P<5.3*10**-7), and combined into a single biomarker. We did not find evidence that these features were additionally associated with overall dietary quality, nor with any of 47 other food groups (all P>.001), supporting their suitability as a biomarker of avocado intake. Avocado intake showed a modest association only with lower fasting insulin (Beta=-0.07+/0.03,P=.03), an association that was attenuated to non-significance when additionally controlling for BMI. However, our biomarker of avocado intake was strongly associated with lower fasting glucose (Beta=-0.22+/0.02, P<2.0*10**-16), lower fasting insulin (Beta=-0.17+/0.02, P<2.0*10**-16), and a lower incidence of T2D (HR: 0.68 [0.63-074], P<2.0*10**-16), even when adjusting for BMI. Highly significant associations between glycemia and avocado-related metabolomic features, which serve as biomarkers of the physiological impact of dietary intake after digestion and absorption, compared to modest relationships between glycemia and avocado consumption, highlights importance of considering individual differences in metabolism when considering diet-health relationships.