Brain responses to intermittent fasting and the healthy living diet in older adults

doi:10.1016/j.cmet.2024.05.017

Randomized Controlled Trial

. 2024 Aug 6;36(8):1668-1678.e5.

doi: 10.1016/j.cmet.2024.05.017. Epub 2024 Jun 19.

Brain responses to intermittent fasting and the healthy living diet in older adults

Dimitrios Kapogiannis¹, Apostolos Manolopoulos², Roger Mullins³, Konstantinos Avgerinos⁴, Francheska Delgado-Peraza², Maja Mustapic², Carlos Nogueras-Ortiz², Pamela J Yao², Krishna A Pucha², Janet Brooks⁵, Qinghua Chen², Shalaila S Haas⁶, Ruiyang Ge⁷, Lisa M Hartnell⁸, Mark R Cookson⁵, Josephine M Egan², Sophia Frangou⁹, Mark P Mattson¹⁰

Affiliations

¹ Intramural Research Program, Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD, USA; Department of Neurology, Johns Hopkins University, Baltimore, MD, USA. Electronic address: kapogiannisd@mail.nih.gov.
² Intramural Research Program, Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD, USA.
³ Morgan State University, Core Lab, Baltimore, MD, USA.
⁴ Department of Neurology, Wayne State University, Detroit, MI, USA.
⁵ Intramural Research Program, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA.
⁶ Mt. Sinai School of Medicine, Department of Psychiatry, New York, NY, USA.
⁷ Center for Brain Health, University of British Columbia, Vancouver, BC, Canada.
⁸ Intramural Research Program, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
⁹ Mt. Sinai School of Medicine, Department of Psychiatry, New York, NY, USA; Center for Brain Health, University of British Columbia, Vancouver, BC, Canada.
¹⁰ Department of Neuroscience, Johns Hopkins University, Baltimore, MD, USA.

PMID: 38901423
PMCID: PMC11305918 (available on 2025-08-06)
DOI: 10.1016/j.cmet.2024.05.017

Randomized Controlled Trial

Brain responses to intermittent fasting and the healthy living diet in older adults

Dimitrios Kapogiannis et al. Cell Metab. 2024.

. 2024 Aug 6;36(8):1668-1678.e5.

doi: 10.1016/j.cmet.2024.05.017. Epub 2024 Jun 19.

Authors

Affiliations

¹ Intramural Research Program, Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD, USA; Department of Neurology, Johns Hopkins University, Baltimore, MD, USA. Electronic address: kapogiannisd@mail.nih.gov.
² Intramural Research Program, Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD, USA.
³ Morgan State University, Core Lab, Baltimore, MD, USA.
⁴ Department of Neurology, Wayne State University, Detroit, MI, USA.
⁵ Intramural Research Program, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA.
⁶ Mt. Sinai School of Medicine, Department of Psychiatry, New York, NY, USA.
⁷ Center for Brain Health, University of British Columbia, Vancouver, BC, Canada.
⁸ Intramural Research Program, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
⁹ Mt. Sinai School of Medicine, Department of Psychiatry, New York, NY, USA; Center for Brain Health, University of British Columbia, Vancouver, BC, Canada.
¹⁰ Department of Neuroscience, Johns Hopkins University, Baltimore, MD, USA.

PMID: 38901423
PMCID: PMC11305918 (available on 2025-08-06)
DOI: 10.1016/j.cmet.2024.05.017

Erratum in

Brain responses to intermittent fasting and the healthy living diet in older adults.
Kapogiannis D, Manolopoulos A, Mullins R, Avgerinos K, Delgado-Peraza F, Mustapic M, Nogueras-Ortiz C, Yao PJ, Pucha KA, Brooks J, Chen Q, Haas SS, Ge R, Hartnell LM, Cookson MR, Egan JM, Frangou S, Mattson MP. Kapogiannis D, et al. Cell Metab. 2024 Aug 6;36(8):1900-1904. doi: 10.1016/j.cmet.2024.07.012. Epub 2024 Jul 16. Cell Metab. 2024. PMID: 39019039 Free PMC article. No abstract available.

Abstract

Diet may promote brain health in metabolically impaired older individuals. In an 8-week randomized clinical trial involving 40 cognitively intact older adults with insulin resistance, we examined the effects of 5:2 intermittent fasting and the healthy living diet on brain health. Although intermittent fasting induced greater weight loss, the two diets had comparable effects in improving insulin signaling biomarkers in neuron-derived extracellular vesicles, decreasing the brain-age-gap estimate (reflecting the pace of biological aging of the brain) on magnetic resonance imaging, reducing brain glucose on magnetic resonance spectroscopy, and improving blood biomarkers of carbohydrate and lipid metabolism, with minimal changes in cerebrospinal fluid biomarkers for Alzheimer's disease. Intermittent fasting and healthy living improved executive function and memory, with intermittent fasting benefiting more certain cognitive measures. In exploratory analyses, sex, body mass index, and apolipoprotein E and SLC16A7 genotypes modulated diet effects. The study provides a blueprint for assessing brain effects of dietary interventions and motivates further research on intermittent fasting and continuous diets for brain health optimization. For further information, please see ClinicalTrials.gov registration: NCT02460783.

Keywords: Alzheimer’s disease; biomarkers; brain aging; insulin resistance; intermittent fasting; randomized clinical trial.

Published by Elsevier Inc.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Cited by

Role of Peripheral and Central Insulin Resistance in Neuropsychiatric Disorders.
Alagiakrishnan K, Halverson T. Alagiakrishnan K, et al. J Clin Med. 2024 Nov 3;13(21):6607. doi: 10.3390/jcm13216607. J Clin Med. 2024. PMID: 39518747 Free PMC article. Review.

References

1. United Nations, Department of Economic and Social Affairs, Population Division (2022). World Population Prospects 2022: Data Sources. (UN DESA/POP/2022/DC/NO. 9).
1. Harper S (2014). Economic and social implications of aging societies. Science 346, 587–591. 10.1126/science.1254405. - DOI - PubMed
1. Hou Y, Dan X, Babbar M, Wei Y, Hasselbalch SG, Croteau DL, and Bohr VA (2019). Ageing as a risk factor for neurodegenerative disease. Nat Rev Neurol 15, 565–581. 10.1038/s41582-019-0244-7. - DOI - PubMed
1. Goldstein BJ (2002). Insulin resistance as the core defect in type 2 diabetes mellitus. Am J Cardiol 90, 3G–10G. S0002914902025535 [pii]. - PubMed
1. Schrijvers EM, Witteman JC, Sijbrands EJ, Hofman A, Koudstaal PJ, and Breteler MM (2010). Insulin metabolism and the risk of Alzheimer disease: the Rotterdam Study. Neurology 75, 1982–1987. 10.1212/WNL.0b013e3181ffe4f6. - DOI - PMC - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions

Associated data

Actions
- Search in PubMed
- Search in ClinicalTrials.gov

Grants and funding

LinkOut - more resources

Full Text Sources
- Elsevier Science
Miscellaneous
- NCI CPTAC Assay Portal

[1] United Nations, Department of Economic and Social Affairs, Population Division (2022). World Population Prospects 2022: Data Sources. (UN DESA/POP/2022/DC/NO. 9).

[2] United Nations, Department of Economic and Social Affairs, Population Division (2022). World Population Prospects 2022: Data Sources. (UN DESA/POP/2022/DC/NO. 9).

[3] Harper S (2014). Economic and social implications of aging societies. Science 346, 587–591. 10.1126/science.1254405. - DOI - PubMed

[4] Harper S (2014). Economic and social implications of aging societies. Science 346, 587–591. 10.1126/science.1254405. - DOI - PubMed

[5] Hou Y, Dan X, Babbar M, Wei Y, Hasselbalch SG, Croteau DL, and Bohr VA (2019). Ageing as a risk factor for neurodegenerative disease. Nat Rev Neurol 15, 565–581. 10.1038/s41582-019-0244-7. - DOI - PubMed

[6] Hou Y, Dan X, Babbar M, Wei Y, Hasselbalch SG, Croteau DL, and Bohr VA (2019). Ageing as a risk factor for neurodegenerative disease. Nat Rev Neurol 15, 565–581. 10.1038/s41582-019-0244-7. - DOI - PubMed

[7] Goldstein BJ (2002). Insulin resistance as the core defect in type 2 diabetes mellitus. Am J Cardiol 90, 3G–10G. S0002914902025535 [pii]. - PubMed

[8] Goldstein BJ (2002). Insulin resistance as the core defect in type 2 diabetes mellitus. Am J Cardiol 90, 3G–10G. S0002914902025535 [pii]. - PubMed

[9] Schrijvers EM, Witteman JC, Sijbrands EJ, Hofman A, Koudstaal PJ, and Breteler MM (2010). Insulin metabolism and the risk of Alzheimer disease: the Rotterdam Study. Neurology 75, 1982–1987. 10.1212/WNL.0b013e3181ffe4f6. - DOI - PMC - PubMed

[10] Schrijvers EM, Witteman JC, Sijbrands EJ, Hofman A, Koudstaal PJ, and Breteler MM (2010). Insulin metabolism and the risk of Alzheimer disease: the Rotterdam Study. Neurology 75, 1982–1987. 10.1212/WNL.0b013e3181ffe4f6. - DOI - PMC - PubMed

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Brain responses to intermittent fasting and the healthy living diet in older adults

Affiliations

Brain responses to intermittent fasting and the healthy living diet in older adults

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Miscellaneous

Erratum in

Abstract

Conflict of interest statement

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Associated data

Related information

Grants and funding

LinkOut - more resources

Full Text Sources

Miscellaneous