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Investigating Ketone Bodies as Immunometabolic Countermeasures against Respiratory Viral Infections
Open accessAbstract
Respiratory viral infections remain a scourge, with seasonal influenza infecting millions and killing many thousands annually and viral pandemics, such as COVID-19, recurring every decade. Age, cardiovascular disease, and diabetes mellitus are risk factors for severe disease and death from viral infection. Immunometabolic therapies for these populations hold promise to reduce the risks of death and disability. Such interventions have pleiotropic effects that might not only target the virus itself but also enhance supportive care to reduce cardiopulmonary complications, improve cognitive resilience, and facilitate functional recovery. Ketone bodies are endogenous metabolites that maintain cellular energy but also feature drug-like signaling activities that affect immune activity, metabolism, and epigenetics. Here, we provide an overview of ketone body biology relevant to respiratory viral infection, focusing on influenza A and severe acute respiratory syndrome (SARS)-CoV-2, and discuss the opportunities, risks, and research gaps in the study of exogenous ketone bodies as novel immunometabolic interventions in these diseases.
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“Additionally, ketones, which are largely produced during either ketogenic diets or fasting periods, can impact immune function and may have possible therapeutic effects for COVID-19194.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [194]
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Items 201–245 of 245
Protective effects of exogenous β-hydroxybutyrate on paraquat toxicity in rat kidney
Wei, T., Tian, W., Liu, F., & Xie, G. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.04.074 · Cited by 64
Ketone Bodies Attenuate Wasting in Models of Atrophy
Koutnik, A., Poff, A., Ward, N. P., Deblasi, J., Soliven, M. A., Romero, M., Roberson, P. A., Fox, C. D., Roberts, M., & D'Agostino, D. (2020) · Journal of Cachexia, Sarcopenia and Muscle · doi:10.1002/jcsm.12554 · Cited by 64
Self-citationJain, S. K., Rains, J., & Croad, J. L. (2007) · Antioxidants and Redox Signaling · doi:10.1089/ars.2007.1577 · Cited by 63
Ni, F.-F., Li, C.-R., Liao, J., Wang, G., Lin, S., Xia, Y., & Wen, J. (2016) · Seizure · doi:10.1016/j.seizure.2016.03.006 · Cited by 59
Leung, H. J., Duran, E. M., Kurtoğlu, M., Andreansky, S. S., Lampidis, T. J., & Mesri, E. A. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01126-12 · Cited by 57
Radigan, K. A., Nicholson, T. T., Welch, L. C., Chi, M., Amarelle, L., Angulo, M., Shigemura, M., Shigemura, A., Runyan, C. E., Morales‐Nebreda, L., et al. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1701433 · Cited by 57
Izuta, Y., Imada, T., Hisamura, R., Oonishi, E., Nakamura, S., Inagaki, E., Ito, M., Soga, T., & Tsubota, K. (2017) · Aging Cell · doi:10.1111/acel.12699 · Cited by 56
Yan, H., Wang, H., Ma, L., Ma, X., Yin, J., Wu, S., Huang, H., & Li, Y. (2018) · Virology Journal · doi:10.1186/s12985-018-0995-6 · Cited by 56
Bacterial infections in patients with type 1 diabetes: a 14-year follow-up study
Simonsen, J. R., Harjutsalo, V., Järvinen, A., Kirveskari, J., Forsblom, C. M., Groop, P., & Lehto, M. J. (2015) · BMJ Open Diabetes Research & Care · doi:10.1136/bmjdrc-2014-000067 · Cited by 55
Gessi, S., Merighi, S., Stefanelli, A., Fazzi, D., Varani, K., & Borea, P. A. (2013) · Pharmacological Research · doi:10.1016/j.phrs.2013.08.002 · Cited by 54
Shi, S. T., Yu, G., & Lai, M. M. C. (2003) · Journal of Virology · doi:10.1128/jvi.77.19.10584-10593.2003 · Cited by 54
Serum biomarkers of delirium in the elderly: a narrative review
Toft, K., Tontsch, J., Abdelhamid, S., Steiner, L. A., Siegemund, M., & Hollinger, A. (2019) · Annals of Intensive Care · doi:10.1186/s13613-019-0548-1 · Cited by 54
Glycemic Variability in Diabetes Increases the Severity of Influenza
Marshall, R. J., Armart, P., Hulme, K. D., Chew, K. Y., Brown, A. C., Hansbro, P. M., Bloxham, C. J., Flint, M., Ronacher, K., Bielefeldt‐Ohmann, H., et al. (2020) · mBio · doi:10.1128/mbio.02841-19 · Cited by 54
Kovács, Z., D’Agostino, D. P., Dobolyi, Á., & Ari, C. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00235 · Cited by 53
Neudorf, H., Durrer, C. G., Myette‐Côté, É., Makins, C., O’Malley, T., & Little, J. P. (2019) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201801171 · Cited by 53
Integrating Geriatric Principles into Critical Care Medicine: The Time is Now
Brummel, N. E., & Ferrante, L. E. (2018) · Annals of the American Thoracic Society · doi:10.1513/annalsats.201710-793ip · Cited by 52
Nabirotchkin, S., Peluffo, A. E., Bouaziz, J., & Cohen, D. (2020) · Preprints.org · doi:10.20944/preprints202003.0302.v1 · Cited by 49
An update on the NLRP3 inflammasome and influenza: the road to redemption or perdition?
Tate, M. D., & Mansell, A. S. (2018) · Current Opinion in Immunology · doi:10.1016/j.coi.2018.06.005 · Cited by 48
Zhao, M., Huang, X. H., Cheng, X., Lin, X., Zhao, T., Wu, L., Yu, X., Wu, K., Fan, M., & Zhu, L. (2017) · PLoS ONE · doi:10.1371/journal.pone.0174477 · Cited by 47
Effects of Ketone Bodies on Basal and Insulin-Stimulated Glucose Utilization in Man*
Beylot, M., Khalfallah, Y., Riou, J. P., Cohen, R., Normand, S., & Mornex, R. (1986) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-63-1-9 · Cited by 45
Lund, T. M., Ploug, K. B., Iversen, A. K. S., Jensen, A. A., & Jansen‐Olesen, I. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12975 · Cited by 44
Hypoxia induced preferential ketone utilization by rat brain slices.
Kirsch, J. R., & D’Alecy, L. G. (1984) · Stroke · doi:10.1161/01.str.15.2.319 · Cited by 44
Wang, Y., Zhou, J., & Du, Y. (2013) · Virology · doi:10.1016/j.virol.2013.11.009 · Cited by 42
Bartley, J. M., Pan, S. J., Keilich, S. R., Hopkins, J. W., Al‐Naggar, I. M., Kuchel, G. A., & Haynes, L. (2016) · Aging · doi:10.18632/aging.100882 · Cited by 41
Exogenous Ketone Bodies as Promising Neuroprotective Agents for Developmental Brain Injury
Wood, T. R., Stubbs, B. J., & Juul, S. E. (2018) · Developmental Neuroscience · doi:10.1159/000499563 · Cited by 41
Self-citationCellular hnRNP A2/B1 interacts with the NP of influenza A virus and impacts viral replication
Chang, C.-K., Chen, C.-J., Wu, C., Chen, S.-W., Shih, S., & Kuo, R. (2017) · PLoS ONE · doi:10.1371/journal.pone.0188214 · Cited by 39
Capelozzi, V. L., Allen, T. C., Beasley, M. B., Cagle, P. T., Guinee, D., Hariri, L. P., Husain, A. N., Jain, D., Lantuéjoul, S., Larsen, B. T., et al. (2017) · Archives of Pathology & Laboratory Medicine · doi:10.5858/arpa.2017-0115-sa · Cited by 37
Histone Deacetylase 2 Is a Component of Influenza A Virus-Induced Host Antiviral Response
Nagesh, P. T., Hussain, M., Galvin, H. D., & Husain, M. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.01315 · Cited by 37
HIF‑1α promotes NLRP3 inflammasome activation in bleomycin‑induced acute lung injury
Huang, J., Xia, J. L., Huang, L., & Li, Y. (2019) · Molecular Medicine Reports · doi:10.3892/mmr.2019.10575 · Cited by 36
Li, Z., Zeng, W., Ye, S., Lv, J., Nie, A., Zhang, B., Sun, Y., Han, H., & He, Q. (2018) · Viruses · doi:10.3390/v10030127 · Cited by 34
Kovács, Z., D’Agostino, D. P., & Ari, C. (2018) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2018.00029 · Cited by 34
Neudorf, H., Myette‐Côté, É., & Little, J. P. (2020) · Nutrients · doi:10.3390/nu12030854 · Cited by 33
Metabolic Responses in Endothelial Cells Following Exposure to Ketone Bodies
Meroni, E., Papini, N., Criscuoli, F., Casiraghi, M. C., Massaccesi, L., Basilico, N., & Erba, D. (2018) · Nutrients · doi:10.3390/nu10020250 · Cited by 31
Kovács, Z., D’Agostino, D. P., Diamond, D. M., & Ari, C. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00045 · Cited by 24
Effect of glycosylation inhibitors on the release of enveloped vaccinia virus
Payne, L. G., & Kristensson, K. (1982) · Journal of Virology · doi:10.1128/jvi.41.2.367-375.1982 · Cited by 21
Ööpik, V., Timpmann, S., Medijainen, L., & Lemberg, H. (2001) · Nutrition Research · doi:10.1016/s0271-5317(01)00319-0 · Cited by 21
Liu, F., Fu, Y., Wei, C., Chen, Y., Ma, S., & Xu, W. (2014) · PubMed · Cited by 20
McCarty, M. F., Barroso-Aranda, J., & Contreras, F. (2009) · Medical Hypotheses · doi:10.1016/j.mehy.2009.04.052 · Cited by 19
Monoacetoacetin and protein metabolism during parenteral nutrition in burned rats
Alberto Maiz, G., Moldawer, L. L., Bistrian, B. R., Birkhahn, R. H., Long, C. L., & Blackburn, G. L. (1985) · Biochemical Journal · doi:10.1042/bj2260043 · Cited by 19
The Influenza A Virus Genotype Determines the Antiviral Function of NF-κB
Dam, S., Kracht, M., Pleschka, S., & Schmitz, M. L. (2016) · Journal of Virology · doi:10.1128/jvi.00946-16 · Cited by 19
Conway, B. N., Lopes-Virella, M. F., & Blot, W. J. (2018) · Diabetic Medicine · doi:10.1111/dme.13617 · Cited by 14
Cardiac injury in patients with pandemic 2009 influenza A (H1N1) infection
Ni, Z., Guo, Z., Chen, X., Wang, Q., Qiu, Y., Wu, T., Yang, Y., & Zhao, L. (2011) · Acta cardiologica. Supplementum · doi:10.1080/ac.66.4.2126589 · Cited by 8
Malnutrition affects negatively the outcome of intensive care unit (ICU) patients
Shpata, V., Kreka, M., Mjekaj, E., Naço, M., Gjyzari, A., & Soxhuku, A. (2013) · European Journal of Anaesthesiology · doi:10.1097/00003643-201306001-00589 · Cited by 5
Poff, A. M., Koutnik, A. P., DeBlasi, J. M., Rogers, C. Q., Kesl, S., Ward, N. P., & D’Agostino, D. P. (2018) · The FASEB Journal · doi:10.1096/fasebj.2018.32.1_supplement.812.38 · Cited by 4
Self-citationLaffel (1999) · doi:10.1002/(sici)1520-7560(199911/12)15:6
Flagged first, then by citations
6 of the 251 references couldn’t be matched to a known paper.
Research works printed but not linked: 3
- Shimazu, 2013, Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor, Science, 339, 211, 10.1126/science.1227166 · DOI · Paper page
- Mo, 2020, Clinical characteristics of refractory COVID-19 pneumonia in Wuhan, China, Clin. Infect. Dis.
- Han, 2020, Lactate dehydrogenase, a risk factor of severe COVID-19 patients, medRxiv
Cited by
Sorted by citations
SARS-CoV-2, COVID-19 and the aging immune system
Bartleson, J. M., Radenkovic, D., Covarrubias, A. J., Furman, D., Winer, D. A., & Verdin, E. (2021) · Nature Aging · doi:10.1038/s43587-021-00114-7 · Cited by 359
Self-citationMetabolic and Signaling Roles of Ketone Bodies in Health and Disease
Puchalska, P., & Crawford, P. A. (2021) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-111120-111518 · Cited by 304
Ketones and the Heart: Metabolic Principles and Therapeutic Implications
Matsuura, T. R., Puchalska, P., Crawford, P. A., & Kelly, D. P. (2023) · Circulation Research · doi:10.1161/circresaha.123.321872 · Cited by 191
Galmés, S., Serra, F. A., & Palou, A. (2020) · Nutrients · doi:10.3390/nu12092738 · Cited by 179
Very‐low‐carbohydrate diet enhances human T‐cell immunity through immunometabolic reprogramming
Hirschberger, S., Strauß, G., Effinger, D., Marstaller, X., Ferstl, A., Müller, M. B., Wu, T., Hübner, M., Rahmel, T., Mascolo, H., et al. (2021) · EMBO Molecular Medicine · doi:10.15252/emmm.202114323 · Cited by 99
Metadata
- Authors
- Stubbs, B. J., Koutnik, A. P., Goldberg, E. L., Upadhyay, V., Turnbaugh, P. J., Verdin, E., & Newman, J. C.
- Affiliations
- Buck Institute for Research on Aging (US)
- Florida Institute for Human and Machine Cognition (US)
- University of California, San Francisco (US)
- Corresponding author
- Newman, John C.
- ORCID
- Venue
- Med
- Publisher
- Elsevier BV
- Published
- 2020-12
- Volume
- 1
- Issue
- 1
- Pages
- 43-65
- ISSN
- 2666-6340 (ISSN-L)
- PMC
- PMC7362813
- OpenAlex
- W3043137980
- Cited by
- 71
- References
- 251
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 11 · 2023: 11 · 2022: 16 · 2021: 12 · 2020: 6
- FWCI
- 1.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Med (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Buck Institute for Research on Aging (T32 HL007185)
- National Institutes of Health (K08 AG048354)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Diet and metabolism studies
- Health Sciences › Medicine › Physiology (medical) › Dietary Effects on Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- ketone bodies, immunometabolic therapy, respiratory viral infections, influenza A virus, SARS-CoV-2, COVID-19 pandemic, immunomodulation, metabolic signaling, diabetes mellitus, cardiovascular disease, age-related risk factors, cardiopulmonary complications, functional recovery
- MeSH terms
- COVID-19, SARS-CoV-2, Humans, Influenza, Human, Ketone Bodies, Pandemics
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