# Modulation of alcohol sensitivity and alcohol tolerance by exogenous ketones in humans

> **NIH NIH R21** · UNIVERSITY OF PENNSYLVANIA · 2024 · $209,378

## Abstract

PROJECT SUMMARY/ABSTRACT
Most adults in the United States consume alcohol at some point in their lifetimes. Excessive drinking may elicit
detrimental consequences, such as liver cirrhosis, increased cancer risk, motor vehicle accidents, and legal
problems, and increase the risk for the development of alcohol use disorder (AUD). Progression to problematic
drinking varies depending upon individual differences in responses to alcohol, for which dietary differences may
be a contributing factor. Preliminary data from our laboratory suggest a pharmacokinetic interaction of ketones
with alcohol, such that ketones paired with alcohol decreased the intoxicating and pleasurable effects of alcohol
in human participants. Ketones (-hydroxybutyrate (BHB), acetoacetate, and acetone) are produced
endogenously during periods of glucose restriction or administered exogenously with nutritional ketone
supplements (KS). In comparison to glucose, ketone metabolism for energy production spares nicotinamide
adenine dinucleotide (NAD+) utilization. NAD+ serves as a cofactor for key alcohol metabolism enzymes, namely
alcohol dehydrogenase (ADH), and increased NAD+ availability following ketosis may have implications for
accelerating alcohol breakdown. Here, we propose to examine the effects of KS on alcohol sensitivity and
tolerance in human participants. We propose the following specific aims: Aim 1: to characterize the
pharmacokinetic effects of exogenous ketones on alcohol sensitivity, alcohol tolerance, and cognitive functioning
(R21 Phase), and Aim 2: to characterize the effect of exogenous ketones and alcohol on brain NAD+
concentrations (R33 phase). We propose to utilize a cross-over designs for the R21 and R33 studies, in which
socially drinking participants will undergo alcohol challenge tests on separate study visits following ingestion of
KS or a taste-matched placebo. In the R21 phase, we hypothesize that KS vs. placebo will lead to a faster
breakdown of alcohol and reduced sensitivity to alcohol. We will compare effects of a low (10g) and high (25g)
of KS on a moderate dose of alcohol targeting breath alcohol levels of 0.08% and high dose. We will pilot proton
magnetic resonance spectroscopic imaging (1H-MRS) methodology at high-field strength for the quantification
of brain NAD+ concentrations. The milestones for the transition to R33 are the detection of significant effects of
KS vs placebo on breath and blood alcohol levels, the reliable quantification of the 1H-MRS NAD+ peak at 9.3
ppm, and the tolerability of KS and alcohol in the high-field strength 7T scanner environment. In the R33 phase,
we will perform 1H-MRS and functional imaging, and we hypothesize that NAD+ levels will increase with KS vs
placebo, and brain NAD+ levels will significantly decrease with alcohol intake. The present study will test the
degree to which exogenous ketones affect alcohol sensitivity and tolerance and prevent neurocognitive
impairments after drinking alcohol. The study ...

## Key facts

- **NIH application ID:** 10896789
- **Project number:** 1R21AA031088-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Ravi Prakash Reddy Nanga
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $209,378
- **Award type:** 1
- **Project period:** 2024-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896789

## Citation

> US National Institutes of Health, RePORTER application 10896789, Modulation of alcohol sensitivity and alcohol tolerance by exogenous ketones in humans (1R21AA031088-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10896789. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*