Impact of intermittent fasting on health and disease processes

Mattson, Mark P.; Longo, Valter D.; Harvie, Michelle

doi:10.1016/j.arr.2016.10.005

Cited by 1,187Dietary Effects on HealthGenetics, Aging, and Longevity in Model OrganismsSirtuins and Resveratrol in Medicine

Impact of intermittent fasting on health and disease processes

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Mattson, Mark P., Longo, Valter D., Harvie, Michelle·2017·Ageing Research Reviews

DOI 10.1016/j.arr.2016.10.005PMC PMC5411330

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Abstract

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.
“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]
Section 2.1 reports that mice on alternate-day fasting had reduced loss of dopaminergic neurons and improved functional outcomes in a Parkinson’s disease model. This supports the neuroprotection and functional-outcome portions of the claim, but contradicts its statement that fasting reduces the number of dopaminergic neurons. (LLM, conf=0.90)
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Inducing starvation via alternate-day fasting or intermittent fasting reduces caloric intake and improves health markers related to cardiovascular risk in populations irrespective of obesity status.
“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.”
From Impact of a ketogenic diet on metabolic parameters in patients with obesity or overweight and with or without type 2 diabetes: a meta-analysis of randomized controlled trials. (2020) · cites this paper as [39]
Healthy lifestyles, such as regular physical activity and healthy diet, are associated with weight loss and reduced risk of dementia by 0.68 times.
“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]
Intermittent fasting in rodents improved insulin and leptin sensitivity, increased ketone body levels, and reduced adiposity and inflammation.
“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]
Time-restricted eating has the potential to improve mitochondrial health and increase health span.
“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]

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“%) nd triglycerides (−14 to −42) (Tinsley and La Bounty, 2015), as ell as improvements in glucose homeostasis (Seimon et al., 2015). owever the lack of a CER comparator in most of these studies eans again, we cannot determine if these effects are a function of he overall energy restriction/weight…”
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Evaluation of an alternating-calorie diet with and without exercise in the treatment of obesity
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Improvements in Coronary Heart Disease Risk Indicators by Alternate‐Day Fasting Involve Adipose Tissue Modulations
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Long-term intermittent feeding, but not caloric restriction, leads to redox imbalance, insulin receptor nitration, and glucose intolerance
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Genetically engineered mouse models of Parkinson's disease
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Intermittent Fasting Attenuates Increases in Neurogenesis after Ischemia and Reperfusion and Improves Recovery
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Rationale for using intermittent calorie restriction as a dietary treatment for drug resistant epilepsy
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Diet‐induced obesity accelerates the onset of terminal phenotypes in α‐synuclein transgenic mice
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Rapamycin improves motor function, reduces 4-hydroxynonenal adducted protein in brain, and attenuates synaptic injury in a mouse model of synucleinopathy
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Middle age onset short-term intermittent fasting dietary restriction prevents brain function impairments in male Wistar rats
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Dietary Restriction Selectively Decreases Glucocorticoid Receptor Expression in the Hippocampus and Cerebral Cortex of Rats
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Food restriction by intermittent fasting induces diabetes and obesity and aggravates spontaneous atherosclerosis development in hypercholesterolaemic mice
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Calorie Restriction Enhances Insulin-Stimulated Glucose Uptake and Akt Phosphorylation in Both Fast-Twitch and Slow-Twitch Skeletal Muscle of 24-Month-Old Rats
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SIRT1 Gain of Function Does Not Mimic or Enhance the Adaptations to Intermittent Fasting
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Alternate-day fasting reverses the age-associated hypertrophy phenotype in rat heart by influencing the ERK and PI3K signaling pathways
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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.
ORCID: Mattson, Mark P.
Longo, Valter D.
Harvie, Michelle
Venue: Ageing Research Reviews
Publisher: Elsevier BV
Published: 2017-10
Volume: 39
Pages: 46-58
ISSN: 1568-1637 (ISSN-L)
DOI: 10.1016/j.arr.2016.10.005
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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 › 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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