Brain dopamine responses to ultra-processed milkshakes are highly variable and not significantly related to adiposity in humans

Valerie L Darcey¹, Juen Guo², Meible Chi², Stephanie T Chung³, Amber B Courville⁴, Isabelle Gallagher², Peter Herscovitch⁵, Paule V Joseph⁶, Rebecca Howard², Melissa La Noire², Lauren Milley², Alex Schick², Michael Stagliano², Sara Turner⁷, Nicholas Urbanski², Shanna Yang⁷, Nan Zhai², Megan S Zhou², Kevin D Hall⁸

Affiliations

¹ Integrative Physiology Section, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA; Center on Compulsive Behaviors, Intramural Research Program, NIH, Bethesda, MD, USA.
² Integrative Physiology Section, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
³ Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
⁴ Human Energy and Body Weight Regulation Core, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
⁵ Positron Emission Tomography Department, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
⁶ Section of Sensory Science and Metabolism, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA; National Institute of Nursing Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA; National Institute on Deafness and Other Communication Disorders, Smell and Taste Center, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
⁷ Nutrition Department, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
⁸ Integrative Physiology Section, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address: kevin.hall@nih.gov.

PMID: 40043691
DOI: 10.1016/j.cmet.2025.02.002

Brain dopamine responses to ultra-processed milkshakes are highly variable and not significantly related to adiposity in humans

Valerie L Darcey et al. Cell Metab. 2025.

. 2025 Mar 4;37(3):616-628.e5.

doi: 10.1016/j.cmet.2025.02.002.

Authors

Affiliations

¹ Integrative Physiology Section, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA; Center on Compulsive Behaviors, Intramural Research Program, NIH, Bethesda, MD, USA.
² Integrative Physiology Section, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
³ Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
⁴ Human Energy and Body Weight Regulation Core, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
⁵ Positron Emission Tomography Department, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
⁶ Section of Sensory Science and Metabolism, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA; National Institute of Nursing Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA; National Institute on Deafness and Other Communication Disorders, Smell and Taste Center, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
⁷ Nutrition Department, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
⁸ Integrative Physiology Section, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address: kevin.hall@nih.gov.

PMID: 40043691
DOI: 10.1016/j.cmet.2025.02.002

Abstract

Ultra-processed foods high in fat and sugar have been theorized to be addictive due to their purported ability to induce an exaggerated post-ingestive brain dopamine response akin to drugs of abuse. Using [¹¹C]raclopride positron emission tomography (PET) displacement methods used to measure brain dopamine responses to addictive drugs, we measured striatal dopamine responses beginning 30 min after ingesting an ultra-processed milkshake high in fat and sugar in 50 young, healthy adults over a wide body mass index (BMI) range (20-45 kg/m²). Surprisingly, milkshake consumption did not result in a significant post-ingestive dopamine response in the striatum (p = 0.62) nor in any striatal subregion (p > 0.33), and the highly variable interindividual responses were not significantly related to adiposity (BMI: r = 0.076, p = 0.51; % body fat: r = 0.16, p = 0.28). Thus, post-ingestive striatal dopamine responses to an ultra-processed milkshake were likely substantially smaller than for many addictive drugs and below the limits of detection using standard PET methods.

Keywords: PET; [(11)C]raclopride; brain; controlled feeding; dopamine; high fat; high sugar; milkshake; obesity; ultra-processed.

Published by Elsevier Inc.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Update of

Brain dopamine responses to ultra-processed milkshakes are highly variable and not significantly related to adiposity in humans.
Darcey VL, Guo J, Chi M, Chung ST, Courville AB, Gallagher I, Herscovitch P, Joseph PV, Howard R, LaNoire M, Milley L, Schick A, Stagliano M, Turner S, Urbanski N, Yang S, Zhai N, Zhou MS, Hall KD. Darcey VL, et al. medRxiv [Preprint]. 2024 Jun 25:2024.06.24.24309440. doi: 10.1101/2024.06.24.24309440. medRxiv. 2024. Update in: Cell Metab. 2025 Mar 04;37(3):616-628.e5. doi: 10.1016/j.cmet.2025.02.002. PMID: 39108535 Free PMC article. Updated. Preprint.

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Brain dopamine responses to ultra-processed milkshakes are highly variable and not significantly related to adiposity in humans

Affiliations

Brain dopamine responses to ultra-processed milkshakes are highly variable and not significantly related to adiposity in humans

Authors

Affiliations

Abstract

Conflict of interest statement

Update of

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