# Mechanisms and consequences of erythritol and erythronate excess in cardiometabolic disease

> **NIH NIH K23** · BAYLOR COLLEGE OF MEDICINE · 2024 · $194,544

## Abstract

PROJECT SUMMARY/ABSTRACT
The obesity and type 2 diabetes (T2D) epidemics parallel a rise in atherosclerotic cardiovascular disease
(ASCVD), and heart failure (HF). Elevated serum erythritol concentrations have been linked to increased
ASCVD with erythritol ingestion as an artificial sweetener implicated. Erythritol has been shown to be
endogenously produced through the pentose phosphate pathway (PPP) and further metabolized to
erythronate. Atherosclerosis Risk in Communities (ARIC) Study analysis of samples from prior to FDA approval
of erythritol as an artificial sweetener found erythritol to be associated with coronary heart disease,
independent of diabetes and obesity, suggesting a role for endogenous production. It is unknown whether
increased erythritol and erythronate are markers of pathophysiological changes in metabolic pathways or
causal markers of ASCVD that are impacted by genetic variability. Absolute erythritol and erythronate
concentrations in people with and without T2D and/or obesity also need to be established. We hypothesize that
(1) erythritol, erythronate, and other PPP enzymes and metabolites have strong associations with
macrovascular and microvascular disease and HF; (2) erythritol and erythronate concentrations are
impacted by genetic variability; and (3) persons with T2D and obesity have higher erythritol and
erythronate concentrations in the fasting state, which are further exaggerated in response to
exogenous glucose and erythritol. Aim 1 examines the association of erythritol, erythronate and other PPP
intermediates to incident micro- and macrovascular disease and HF outcomes in multiethnic observational
studies. Aim 2 determines whether T2D and/or obesity status increase production of erythritol and erythronate
when fasting and/or in response to glucose infusion and oral erythritol. Understanding erythritol and
erythronate’s endogenous production, genetic variability, and association to ASCVD is key to understanding
clinical predictive utility. The effect of exogenous glucose and erythritol intake on erythritol and erythronate
concentration in people with and without T2D and/or obesity will shed light on the role of dietary intake in these
groups. Dr. Abushamat is a board-certified adult endocrinologist and tenure-track assistant professor at Baylor
College of Medicine. Her long-term goal is to become an independent NIH-funded physician-scientist in
cardiovascular metabolism, focusing on genetic variability in metabolic pathways to inform personalized
approaches to prevention, diagnosis, and treatment. The research aims support the PI’s career development
by augmenting her past training as an MD/MPH via master’s level training in clinical investigation with the
addition of skills in multi-omic analysis, Mendelian Randomization, stable-isotope tracer studies and
intermediate biostatistics. This training plan will be carried out via a superb mentoring and advisory team,
advanced coursework, and scholarly activities with...

## Key facts

- **NIH application ID:** 10948231
- **Project number:** 1K23DK140641-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Layla A Abushamat
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $194,544
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10948231

## Citation

> US National Institutes of Health, RePORTER application 10948231, Mechanisms and consequences of erythritol and erythronate excess in cardiometabolic disease (1K23DK140641-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10948231. Licensed CC0.

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