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Impact of intermittent fasting on health and disease processes
Open accessAbstract
Humans in modern societies typically consume food at least three times daily, while laboratory animals are fed ad libitum. Overconsumption of food with such eating patterns often leads to metabolic morbidities (insulin resistance, excessive accumulation of visceral fat, etc.), particularly when associated with a sedentary lifestyle. Because animals, including humans, evolved in environments where food was relatively scarce, they developed numerous adaptations that enabled them to function at a high level, both physically and cognitively, when in a food-deprived/fasted state. Intermittent fasting (IF) encompasses eating patterns in which individuals go extended time periods (e.g., 16–48h) with little or no energy intake, with intervening periods of normal food intake, on a recurring basis. We use the term periodic fasting (PF) to refer to IF with periods of fasting or fasting mimicking diets lasting from 2 to as many as 21 or more days. In laboratory rats and mice IF and PF have profound beneficial effects on many different indices of health and, importantly, can counteract disease processes and improve functional outcome in experimental models of a wide range of age-related disorders including diabetes, cardiovascular disease, cancers and neurological disorders such as Alzheimer’s disease Parkinson’s disease and stroke. Studies of IF (e.g., 60% energy restriction on 2 days per week or every other day), PF (e.g., a 5 day diet providing 750–1100 kcal) and time-restricted feeding (TRF; limiting the daily period of food intake to 8 h or less) in normal and overweight human subjects have demonstrated efficacy for weight loss and improvements in multiple health indicators including insulin resistance and reductions in risk factors for cardiovascular disease. The cellular and molecular mechanisms by which IF improves health and counteracts disease processes involve activation of adaptive cellular stress response signaling pathways that enhance mitochondrial health, DNA repair and autophagy. PF also promotes stem cell-based regeneration as well as long-lasting metabolic effects. Randomized controlled clinical trials of IF versus PF and isoenergetic continuous energy restriction in human subjects will be required to establish the efficacy of IF in improving general health, and preventing and managing major diseases of aging.
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“Intermittent fasting can protect neurons in animal models of disease, reduce the number of dopaminergic neurons and improve motor function in Parkinson's disease.250”
From The role of gut dysbiosis in Parkinson’s disease: mechanistic insights and therapeutic options (2021) · cites this paper as [250]
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In the citing paper
“Intermittent fasting (e.g., one day without nutrients, followed by one day of ad libitum feeding) can avoid long-term weight loss induced by caloric restriction, yet increases lifespan in mice 148 and improves biomarkers of health in clinical trials 153,154 .”
From Hallmarks of aging: An expanding universe (2023) · cites this paper as [153]
Experimental — accuracy not yet measuredIn the citing paper
“Besides, inducing starvation via dietary regimens of alternate-day fasting [38] or intermittent fasting [39] has shown to reduce caloric intake and improve health markers related to cardiovascular risk in populations irrespective of obesity status.”
In the citing paper
“Therefore, healthy lifestyles, such as regular physical activity and healthy diet, are associated with weigh loss and reduced the risk of dementia by 0.68 times.375,376”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [375]
In the citing paper
“Intermittent fasting in rodents improved insulin and leptin sensitivity increases ketone body levels and reduced adiposity and inflammation (235).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [235]
In the citing paper
“Interestingly, time-restricted eating, which involves regular periods of fasting, has emerged in the last few years as an intervention with the potential to improve mitochondrial health and increase health span [170,171].”
From Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging (2021) · cites this paper as [171]
In the citing paper
“Various regimens of intermittent fasting have also been found to impact stem and progenitor cells in aged animals213.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [213]
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Citations
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Metadata
- Authors
- Mattson, M. P., Longo, V. D., & Harvie, M.
- Affiliations
- Johns Hopkins University (US)
- University of Southern California (US)
- Wythenshawe Hospital (GB)
- Corresponding author
- Mattson, Mark P.
- Venue
- Ageing Research Reviews
- Publisher
- Elsevier BV
- Published
- 2017-10
- Volume
- 39
- Pages
- 46-58
- ISSN
- 1568-1637 (ISSN-L)
- PMC
- PMC5411330
- OpenAlex
- W2542468576
- Semantic Scholar
- 9368e04d8de55f82fdeabf816d930cd45e879039
- Cited by
- 1,187
- References
- 142
- Citations by year
- 2026: 89 · 2025: 154 · 2024: 152 · 2023: 141 · 2022: 155 · 2021: 175 · 2020: 121 · 2019: 92 · 2018: 69 · 2017: 39
- FWCI
- 7.83
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Ageing Research Reviews (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (ZIAAG000331, ZIAAG000315, ZIAAG000317)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Dietary Effects on Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- intermittent fasting, fasting-mimicking diet, time-restricted feeding, caloric restriction, insulin resistance, metabolic disorders, aging, autophagy, mitochondrial health, DNA repair, stem cell regeneration, weight loss, cardiovascular disease, diabetes mellitus, neurodegenerative diseases, cancer, cellular stress response
- MeSH terms
- Healthy Aging, Animals, Energy Intake, Cardiovascular Diseases, Chronic Disease, Diet, Eating, Fasting, Feeding Behavior, Humans, Insulin Resistance, Obesity, Weight Loss, Caloric Restriction
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