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Intermittent Fasting: Health Impacts and Therapeutic Potential

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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Nutrition and Public Health".

Deadline for manuscript submissions: closed (5 February 2026) | Viewed by 30658

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Dr. Cristina Manuela Dragoi

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Department of Biochemistry, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 020956 Bucharest, Romania
Interests: fasting; biochemistry; chronobiology; drug interactions; mechanisms of action; pharmaceutical research; molecular pharmacology
Special Issues, Collections and Topics in MDPI journals

Dr. Alina Crenguta Nicolae

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Faculty of Pharmacy, University of Medicine and Pharmacy “Carol Davila”, 020956 Bucharest, Romania
Interests: fastng; biochemistry; carbapenem derivative; Klebsiella; gentamicins; pharmacotherapy; prolongation; COVID-19; antihypertensive agents; thiazides; blood pressure
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Intermittent fasting, a dietary regimen characterized by alternating periods of fasting and eating, has gained significant attention in recent years due to its potential health benefits, including weight reduction, enhanced insulin sensitivity, and a decreased risk of chronic illnesses (mainly cardiovascular diseases and type 2 diabetes).

Research indicates that intermittent fasting modulates metabolic pathways by activating adaptive cellular stress responses. These responses are critical in reducing oxidative stress and inflammation, promoting DNA repair and autophagy, and enhancing mitochondrial functionality. Such processes are intimately linked with the onset and progression of various types of cancer, Alzheimer's disease, and atherosclerosis, suggesting that intermittent fasting may reduce the prevalence of these conditions across large populations. Moreover, intermittent fasting has been shown to elevate the production of neuroprotective and anti-inflammatory factors, thereby improving cognitive function and offering protection against age-related neurodegenerative diseases. In conclusion, intermittent fasting presents a promising nutritional strategy for the prevention and management of chronic diseases and the modulation of biological aging.

The aim of this Special Issue on “Intermittent Fasting: Health Impacts and Therapeutic Potential” is to compile studies that explore the mechanisms through which intermittent fasting may promote health and longevity. It seeks to provide an overview of the clinical significance of this dietary pattern in preventing and treating cancer, metabolic disorders, cardiovascular diseases, and neurodegenerative diseases.

This Special Issue welcomes contributions from diverse fields and encourages researchers and nutrition experts to submit original research studies, review articles, and communications related to this critical health domain.

Dr. Cristina Manuela Dragoi
Dr. Alina Crenguța Nicolae
Guest Editors

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Keywords

intermittent fasting
nutrition in medicine
cancer
cardio-metabolic diseases
oxidative stress
diabetes
insulin resistance
age-related diseases
metabolism
autophagy
inflammation
neurologic protection

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Published Papers (7 papers)

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Research

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17 pages, 615 KB

Open AccessArticle

Effects of 4:3 Intermittent Fasting on Eating Behaviors and Appetite Hormones: A Secondary Analysis of a 12-Month Behavioral Weight Loss Intervention

by Matthew J. Breit, Ann E. Caldwell, Danielle M. Ostendorf, Zhaoxing Pan, Seth A. Creasy, Bryan Swanson, Kevin Clark, Emily B. Hill, Paul S. MacLean, Daniel H. Bessesen, Edward L. Melanson and Victoria A. Catenacci

Nutrients 2025, 17(14), 2385; https://doi.org/10.3390/nu17142385 - 21 Jul 2025

Cited by 4 | Viewed by 10485

Abstract

Background/Objectives: Daily caloric restriction (DCR) is a common dietary weight loss strategy, but leads to metabolic and behavioral adaptations, including maladaptive eating behaviors and dysregulated appetite. Intermittent fasting (IMF) may mitigate these effects by offering diet flexibility during energy restriction. This secondary analysis compared changes in eating behaviors and appetite-related hormones between 4:3 intermittent fasting (4:3 IMF) and DCR and examined their association with weight loss over 12 months. Methods: Adults with overweight or obesity were randomized to 4:3 IMF or DCR for 12 months. Both randomized groups received a matched targeted weekly dietary energy deficit (34%), comprehensive group-based behavioral support, and a prescription to increase moderate-intensity aerobic activity to 300 min/week. Eating behaviors were assessed using validated questionnaires at baseline and months 3, 6, and 12. Fasting levels of leptin, ghrelin, peptide YY, brain-derived neurotrophic factor, and adiponectin were measured at baseline and months 6 and 12. Linear mixed models and Pearson correlations were used to evaluate outcomes. Results: Included in this analysis were 165 adults (mean ± SD; age 42 ± 9 years, BMI 34.2 ± 4.3 kg/m², 74% female) randomized to 4:3 IMF (n = 84) or DCR (n = 81). At 12 months, binge eating and uncontrolled eating scores decreased in 4:3 IMF but increased in DCR (p < 0.01 for between-group differences). Among 4:3 IMF, greater weight loss was associated with decreased uncontrolled eating (r = −0.27, p = 0.03), emotional eating (r = −0.37, p < 0.01), and increased cognitive restraint (r = 0.35, p < 0.01) at 12 months. There were no between-group differences in changes in fasting appetite-related hormones at any time point. Conclusions: Compared to DCR, 4:3 IMF exhibited improved binge eating and uncontrolled eating behaviors at 12 months. This may, in part, explain the greater weight loss achieved by 4:3 IMF versus DCR. Future studies should examine mechanisms underlying eating behavior changes with 4:3 IMF and their long-term sustainability. Full article

(This article belongs to the Special Issue Intermittent Fasting: Health Impacts and Therapeutic Potential)

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11 pages, 632 KB

Open AccessArticle

Interrelations of Leptin and Interleukin-6 in Vitamin D Deficient and Overweight Orthodox Nuns from Northern Greece: A Pilot Study

by Spyridon N. Karras, Konstantinos Michalakis, Niki Katsiki, Maria Kypraiou, Antonios Vlastos, Marios Anemoulis, Georgios Koukoulis, Zadalla Mouslech, Filotas Talidis, Georgios Tzimagiorgis, Costas Haitoglou, Μichos Georgios, Evangelos G. Papanikolaou, Skoutas Dimitrios and Neoklis Georgopoulos

Nutrients 2025, 17(7), 1144; https://doi.org/10.3390/nu17071144 - 26 Mar 2025

Cited by 5 | Viewed by 1222

Abstract

Background/Objectives: Athonian fasting, a rigorous form of intermittent fasting practiced by Christian Orthodox nuns and a subset of the Mediterranean diet, has known health benefits, but its impact on the interplay of adipokines, inflammatory cytokines, and vitamin D status remains under-investigated. This study aimed to elucidate these relationships within this controlled dietary context. Methods: This cross-sectional study examined the interplay of leptin, interleukin-6 (IL-6), and vitamin D in 41 overweight, vitamin D-sufficient Christian Orthodox nuns practicing Athonian fasting. Anthropometric, biochemical, and inflammatory markers were assessed in the nuns (mean age 53.4 ± 17.1 years, median monastery stay 17 years, median BMI 26.8 kg/m²). Results: Analysis revealed significant positive correlations between age and monastery stay (r = 0.615, p < 0.001), age and visceral fat (ρ = 0.791, p < 0.001), age and IL-6 (ρ = 0.647, p < 0.001), and BMI and IL-6 (ρ = 0.622, p < 0.001). Strong associations existed between adiposity (BMI, body fat, visceral fat), leptin, and IL-6. Specifically, body fat showed substantial positive correlations with visceral fat (ρ = 0.858, p < 0.001), leptin (ρ = 0.538, p < 0.001), and IL-6 (ρ = 0.675, p < 0.001). Visceral fat demonstrated strong positive correlations with leptin (ρ = 0.613, p < 0.001) and IL-6 (ρ = 0.741, p < 0.001). A significant positive correlation was also observed between leptin and IL-6 (ρ = 0.507, p = 0.003). Conversely, a significant negative correlation was found between 25(OH)D and PTH (ρ = −0.380, p = 0.016). Multivariate regression analysis did not reveal independent effects of leptin or IL-6 after adjusting for other factors. Conclusions: This study reveals a complex interplay of adiposity, inflammation, and vitamin D status in this unique population of Orthodox monastery fasters. The strong correlations suggest potential targets for interventions aimed at improving metabolic health. Future research should investigate the effects of vitamin D within the context of Athonian fasting. Full article

(This article belongs to the Special Issue Intermittent Fasting: Health Impacts and Therapeutic Potential)

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19 pages, 4436 KB

Open AccessArticle

Interaction of Cooking-Generated Aerosols on the Human Nervous System and the Impact of Caloric Restriction Post-Exposure

by Motahareh Naseri, Sahar Sadeghi, Milad Malekipirbazari, Sholpan Nurzhan, Raikhangul Gabdrashova, Zhibek Bekezhankyzy, Reza Khanbabaie, Byron Crape, Dhawal Shah and Mehdi Amouei Torkmahalleh

Nutrients 2024, 16(20), 3525; https://doi.org/10.3390/nu16203525 - 17 Oct 2024

Viewed by 1579

Abstract

Background: The inhalation of cooking-generated aerosols could lead to translocation to the brain and impact its function; therefore, the effects of cooking-generated aerosols on healthy adults were investigated using an electroencephalograph (EEG) during the 2 h period post-exposure. Methods: To explore any changes from the impact of exposure to cooking-generated aerosols on the human brain due to the absence of food intake during exposure, we divided the study participants into three groups: (A) no food intake for 2 h (2 h-zero calorie intake), (B) non-zero calorie intake, and (C) control group (simulated cooking). Results: The ultrafine particle concentrations increased from 9.0 × 10³ particles/cm³ at the background level to approximately 8.74 × 10⁴ particles/cm³ during cooking. EEGs were recorded before cooking (step 1), 60 min after cooking (step 2), 90 min after cooking (step 3), and 120 min after cooking (step 4). Comparing the non-zero calorie group with the control group, it was concluded that exposure to cooking-generated aerosols resulted in a 12.82% increase in the alpha band two hours post-exposure, compared to pre-exposure. The results revealed that zero calorie intake after exposure mitigated the impacts of cooking-generated aerosols for the alpha, beta3, theta, and delta bands, while it exacerbated effects on the whole brain for the beta1 and beta2 bands. Conclusions: While these are short-term studies, long-term exposure to cooking-generated ultrafine particles can be established through successive short-term exposures. These results underscore the need for further research into the health impacts of cooking-generated aerosols and the importance of implementing strategies to mitigate exposure. Full article

(This article belongs to the Special Issue Intermittent Fasting: Health Impacts and Therapeutic Potential)

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Review

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24 pages, 614 KB

Open AccessReview

Fasting-Based Dietary Interventions in Cancer Patients and Survivors: A Scoping Review

by Kuang-Yi Wen, Julianne Freedman, Abenezer Tafese, William Kelly and Nicole Simone

Nutrients 2026, 18(7), 1035; https://doi.org/10.3390/nu18071035 - 25 Mar 2026

Viewed by 698

Abstract

Background: Fasting-based interventions are increasingly investigated as adjuncts to cancer treatment for the potential to reduce therapy-related toxicities, improve metabolic health, and enhance quality of life. However, clinical evidence regarding their efficacy, tolerability, and acceptability remains limited and fragmented. This scoping review aimed to systematically map the current evidence on fasting-based interventions in cancer patients and survivors. Methods: A literature search was conducted in PubMed, Scopus, Web of Science, and CINAHL up to 10 June 2025. Eligible interventional studies included cancer patients or survivors and evaluated fasting-based interventions, such as time-restricted eating, intermittent fasting, short-term fasting, or fasting-mimicking diets. Studies were categorized by fasting types and outcomes like fatigue, treatment toxicity, metabolic and hematologic parameters, weight, quality of life, adherence, acceptability, illness perception, and adverse events were assessed. Result: Twenty interventional studies of FMD, TRE, STF, IF, or fasting combined with altered dietary approaches conducted across 10 countries were included, comprising a total of 871 participants. Participant ages ranged from 28 to 75 years. Overall, 9 of 20 studies exclusively enrolled breast cancer patients or survivors, and chemotherapy was the most common treatment context in 11 studies. Five of six studies reported reductions in fatigue. Among the five studies assessing quality of life, one demonstrated improvement, three reported no change, and one yielded mixed results. Six of eight studies reported reductions in chemotherapy-related toxicity, and weight loss was observed in 10 of 12 studies. Reductions in IGF-1 and insulin levels were reported in six of seven and four of five studies, respectively. Hematologic changes were noted in six studies, and only one study assessed illness perceptions, reporting positive findings. Fasting-related adverse events, reported in nine studies, were generally mild and transient. High adherence and acceptability were observed across studies; however, findings were heterogeneous across intervention types and were largely derived from small or moderate-strength studies. A descriptive quality metric assessment indicated that most studies were of moderate methodological strength. More intensive fasting protocols, such as FMD and STF, appeared to demonstrate more consistent metabolic effects, whereas TRE showed higher adherence but more variable clinical outcomes. Conclusions: Fasting-based interventions have the potential to be feasible and well tolerated among cancer patients and survivors, with early evidence suggesting benefits in reducing fatigue, minimizing treatment-related toxicities, and favorable metabolic effects. Large, well-designed trials including diverse cancer populations are needed to confirm long-term outcomes and guide clinical integration. Full article

(This article belongs to the Special Issue Intermittent Fasting: Health Impacts and Therapeutic Potential)

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15 pages, 487 KB

Open AccessReview

Does Energy Restriction and Loss of Body Fat Account for the Effect of Intermittent Fasting on Cognitive Function?

by Fulvia Draicchio and Kathleen V. Axen

Nutrients 2025, 17(15), 2407; https://doi.org/10.3390/nu17152407 - 23 Jul 2025

Cited by 1 | Viewed by 4902

Abstract

Intermittent fasting (IF) and caloric restriction (CR) have garnered attention for their potential to enhance cognitive function, particularly in aging and metabolically compromised populations. This narrative review critically examines whether the cognitive benefits of IF are attributable to its specific fasting patterns or are instead mediated by the production of weight loss, fat loss, and improvements in insulin sensitivity. Evidence from human trials suggests that reductions in body weight, especially visceral adiposity, and improvements in insulin resistance are key factors linked to enhanced cognitive performance. Comparisons between the results of IF and CR trials show comparable cognitive outcomes, supporting the idea that negative energy balance, rather than fasting or altered eating patterns, drive these effects. However, further investigation of specific types of IF patterns, as well as possible cognitive domains to be affected, may identify mechanisms through which IF can yield benefits on neurocognitive health beyond those of loss of body fat and its accompanying inflammatory state. Full article

(This article belongs to the Special Issue Intermittent Fasting: Health Impacts and Therapeutic Potential)

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24 pages, 1226 KB

Open AccessReview

From Soil to Brain: Olive Oil Attributes, Consumer Choices, Intermittent Fasting, and Their Impact on Health

by Ion-Bogdan Dumitrescu, Cristina Manuela Drăgoi and Alina Crenguța Nicolae

Nutrients 2025, 17(11), 1905; https://doi.org/10.3390/nu17111905 - 1 Jun 2025

Cited by 5 | Viewed by 8374

Abstract

Olive oil (OO) has longstanding significance in human history, particularly in the Mediterranean region, where it has been a cornerstone of diet, economy, and culture. This history adds to modern evidence-based knowledge. Background: The Mediterranean diet (MD), rich in plant-based foods and OO, has been extensively associated with improved cardiometabolic and cognitive health. Recent interest has emerged in understanding how intermittent fasting protocols may enhance these effects. Still, the quality of OO does not only lie in the extraction process; it is also dependent on the tree variety, the soil, and the agricultural practices, ending with the way in which the finished product is stored and consumed. Objectives: This review explores the synergistic potential between OO consumption and intermittent fasting, focusing on their combined impact on metabolic health, oxidative stress, and inflammatory pathways. Methods: A literature search was conducted using multiple databases to identify studies addressing the health effects of OO, fasting, and the MD. Both human and relevant preclinical studies were considered, with emphasis on those evaluating inflammatory markers, lipid metabolism, insulin sensitivity, and neuroprotective mechanisms. Results: Evidence suggests that the bioactive compounds in EVOO may potentiate the benefits of fasting by enhancing antioxidant capacity, reducing postprandial inflammation, and modulating gene expression related to cellular metabolism. Combined, these factors may support improved insulin sensitivity, reduced oxidative damage, and delayed onset of age-related diseases. Conclusions: Understanding the integrative role of OO and fasting within the MD framework could offer valuable insights for nutritional strategies aimed at preventing metabolic syndrome, type 2 diabetes, and neurodegeneration. These findings also support the need for future clinical trials exploring the timing, dosage, and dietary context in which these interventions are most effective. Full article

(This article belongs to the Special Issue Intermittent Fasting: Health Impacts and Therapeutic Potential)

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Other

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15 pages, 1080 KB

Open AccessOpinion

Intermittent Fasting and Probiotics for Gut Microbiota Modulation in Type 2 Diabetes Mellitus: A Narrative Review

by Zhiwen Zhang, Shaokang Wang, Guiju Sun and Da Pan

Nutrients 2026, 18(1), 119; https://doi.org/10.3390/nu18010119 - 30 Dec 2025

Cited by 1 | Viewed by 1872

Abstract

Background: Type 2 diabetes mellitus (T2DM) is a global epidemic in which gut microbiota dysbiosis contributes to impaired glucose homeostasis and chronic inflammation. Intermittent fasting (IF) and probiotic supplementation have independently demonstrated glycemic benefits in T2DM, largely through microbiota remodeling. This narrative review synthesizes evidence up to October 2025 to clarify the microbiota-dependent mechanisms of IF and probiotics, and to evaluate the biological plausibility and preliminary clinical data for their combined application in T2DM management. Methods: We conducted a comprehensive literature review of preclinical and clinical studies (PubMed, Embase, Web of Science, and Cochrane Library) examining IF regimens (primarily time-restricted feeding and 5:2 protocols) and multi-strain probiotics containing Lactobacillus and Bifidobacterium species in T2DM or relevant models. Mechanistic pathways, microbial compositional shifts, and metabolic outcomes were qualitatively synthesized, with emphasis on overlapping signaling (short-chain fatty acids, bile acids, GLP-1, and barrier function). Results: IF consistently increases Akkermansia muciniphila and, variably, Faecalibacterium prausnitzii abundance, restores microbial circadian rhythmicity, and enhances SCFA and secondary bile acid production. Multi-strain probiotics modestly reduce HbA1c (–0.3% to –0.6%) and fasting glucose, outperforming single-strain preparations. Both interventions converge on reduced endotoxaemia and improved intestinal integrity. Preclinical models indicate potential synergy, whereas the only direct human trial to date showed neutral results. Conclusions: IF and probiotics engage overlapping microbiota-mediated pathways, supporting their combined use as an adjunctive strategy in T2DM. Adequately powered randomized trials incorporating deep metagenomics, metabolomics, and hard clinical endpoints are now required to confirm additive or synergistic efficacy. Full article

(This article belongs to the Special Issue Intermittent Fasting: Health Impacts and Therapeutic Potential)

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