What the Research Shows About Fasting
Research on fasting is mixed, not uniformly positive. Pooled trials show fasting produces weight loss roughly comparable to ordinary calorie restriction, with no single schedule proven superior. Evidence quality is mostly low to very low certainty, some trials show lean-mass loss alongside fat loss, and claims about autophagy, gut health, and cognition in humans are newer and thinner than often assumed.
Medical caution
This is general information about fasting, not medical advice. Fasting can affect blood sugar, blood pressure, medication timing, and nutritional status. Talk to a clinician before starting or changing a fasting practice if you are pregnant, under 18, living with diabetes or another chronic condition, taking prescription medication, or have a history of an eating disorder.
Weight Loss and Metabolic Health
Fact 1. Pooled across 99 randomized trials in 6,582 adults, intermittent fasting and continuous calorie restriction both reduce body weight versus an unrestricted diet, with alternate-day fasting showing the largest edge among intermittent-fasting variants (Semnani-Azad et al., 2025) [1]; that alternate-day-fasting advantage over calorie restriction (-1.29 kg, moderate certainty) appeared in trials shorter than 24 weeks, while longer trials showed weight benefit only against an unrestricted diet.
Fact 2. In people with type 2 diabetes specifically, a network meta-analysis of 13 trials found no significant difference between four fasting regimens, including the fasting-mimicking diet, with twice-weekly fasting, not 16:8, ranking best on a composite score (Xiaoyu, Yuxin, and Li, 2024) [2].
Fact 3. A dedicated, year-long head-to-head randomized trial found no advantage for alternate-day fasting over daily calorie restriction on weight loss, maintenance, or adherence, and a worse LDL cholesterol signal by month 12 (Trepanowski et al., 2017) [3].
Fact 4. A 12-week randomized trial in 116 adults found that eating only between noon and 8 pm produced no more weight loss than eating three structured meals a day (between-group difference -0.26 kg, 95% CI -1.30 to 0.78), and, in the 50 participants measured in person, a significant reduction in appendicular lean mass in the time-restricted group (Lowe et al., 2020, the TREAT trial) [4].
Cardiometabolic Markers: Blood Pressure, Cholesterol, Blood Sugar
Fact 5. Across human trials of prolonged water-only fasting lasting 5 to 20 days, blood pressure consistently decreased; glycemic measures improved in people with normal blood sugar but not in people with type 1 or type 2 diabetes; and, in the few trials that examined refeeding, the metabolic improvements were no longer detectable 3 to 4 months after the fast ended, even when weight loss was maintained (Ezpeleta et al., 2024) [5]. See prolonged fasting for the full picture.
Fact 6. A meta-analysis pooling 11 fasting-mimicking-diet studies (761 participants) found reductions in HbA1c, IGF-1, and systolic and diastolic blood pressure, but no significant effect on the other cardiovascular risk factors it checked; in the authors' own sensitivity analyses, the IGF-1 reduction was no longer significant without either a breast-cancer trial or the largest single trial, and the blood-pressure reduction was no longer significant without one other trial (Mohammadzadeh et al., 2025) [6].
Body Composition: The Lean-Mass Caveat
Fact 7. Lean or fat-free mass loss alongside fat loss shows up repeatedly across this literature: in the TREAT trial above (fact 4), in a prolonged water-fasting review finding about two-thirds of weight loss was lean mass (fact 5's source), and in an umbrella review of 130 trials where intermittent fasting was found to be associated with reduced fat-free mass (Lowe et al., 2020 [4]; Ezpeleta et al., 2024 [5]; Patikorn et al., 2021 [7]).
How Certain Is This Evidence
Fact 8. Two reviews that graded the certainty of this evidence rate most of it low to very low: a 2021 Cochrane review (searches to December 2019) found the weight reduction from intermittent fasting, versus ad-libitum eating, was not clinically significant, with no study reporting on mortality, stroke, or heart attack at any follow-up (Allaf et al., 2021) [8]; a separate umbrella review of 11 meta-analyses found only 1% of 104 pooled intermittent-fasting outcome associations were backed by high-quality evidence (Patikorn et al., 2021) [7]. The largest network meta-analysis on this page rated its main alternate-day-fasting comparison moderate certainty (Semnani-Azad et al., 2025) [1]. Read every fact on this page with that certainty level in mind.
Safety Data From Large and Supervised Studies
Fact 9. A one-year observational study of 1,422 people doing a supervised, modified fast (4 to 21 days, a small daily intake of 200 to 250 kcal, not strictly zero-calorie) found significant reductions in weight, waist circumference, and blood pressure, with adverse effects reported in fewer than 1% of participants (Wilhelmi de Toledo et al., 2019) [9]. This study had no control group, and it describes a supervised, modified program; its adverse-event rate should not be generalized to unsupervised water-only fasting.
Brain, Mood, and Cognitive Performance
Fact 10. A systematic review of randomized trials assessing diet's effect on cognition found intermittent fasting "a safe intervention, and no adverse effects were found in the reviewed studies," but based this on only 9 low-quality RCTs (Senderovich, Farahneh, and Waicus, 2023) [10].
Fact 11. Two separate randomized trials examined intermittent fasting's effect on cognitive performance and mood, with different designs: an 8-week trial in women with overweight found no difference between intermittent fasting and calorie restriction on mood, sleep quality, or cognition, and performance was unchanged even during an acute 24-hour fast within the fasting group; in the same trial, intermittent fasting produced more weight and body-fat loss than calorie restriction (Teong et al., 2021) [11]. A 10-day trial found 16-hour daily fasting did not reduce cognitive performance or mood versus a waitlist control, though participants did report feeling less concentrated in the late morning before breaking the fast (Bamberg, Reichenberger, and Blechert, 2026) [12]. See hunger during intermittent fasting for more on that late-morning experience.
Fact 12. An 8-week randomized trial in 40 cognitively intact older adults with insulin resistance found 5:2 intermittent fasting produced greater weight loss than a "healthy living diet," but the two diets had comparable effects on brain-aging markers, a reduced brain-age-gap on MRI, lower brain glucose, and on most blood biomarkers; both diets improved executive function and memory, with fasting benefiting certain cognitive measures more (Kapogiannis et al., 2024) [13]. Read this as "fasting matched a comparator diet on brain markers while producing more weight loss," not as "fasting improves brain health" in a way that implies superiority the trial did not find on most of its own measures.
Autophagy: What's Actually Been Measured in Humans
Fact 13. Autophagy, the cell-recycling process most often cited as fasting's anti-aging mechanism, has been studied in people in only a small number of studies, most using indirect markers in blood cells or muscle, and their results disagree. A 6-month trial in 121 adults with obesity that measured autophagic activity (flux) in blood cells calls its own analysis "exploratory": in a post hoc analysis the intermittent-fasting group differed from a standard-care control group at 6 months but not at 2 months, the authors say this "may be driven partly by a tendency for autophagy to decrease" in the control group, and the fasting group did not change significantly from its own baseline (Bensalem et al., 2025) [14]. An 8-week intermittent-fasting trial in 50 women found muscle autophagy markers went down rather than up, which the authors link to weight loss (Chaudhary et al., 2022) [19]. See autophagy and fasting for the full set of human studies.
Gut Health and the Microbiome
Fact 14. A systematic review of 8 human studies found intermittent fasting associated with gut microbiota richness, diversity, and compositional changes, but with substantial heterogeneity: which bacteria changed varied widely study to study, and the review's own conclusion calls for more research before deciding whether the changes are beneficial (Paukkonen et al., 2024) [15]. See fasting and gut health for the full evidence set.
Fasting in Women: Reproductive Hormones
Fact 15. A systematic review of 6 studies on time-restricted eating and female reproductive hormones found randomized trials in women with general obesity consistently showed no significant change in androgens or other key hormones, while non-randomized studies in women with polycystic ovary syndrome (PCOS) reported beneficial hormone changes that may be confounded by weight loss rather than a direct hormonal effect (Jirapak et al., 2026) [16]. A single small PCOS trial in this space (18 women enrolled, 15 completers; a 1-week baseline then 5 weeks of time-restricted feeding, with no control group) found improved menstrual regularity in 11 of 15 participants alongside weight loss, testosterone, and insulin-resistance improvements, consistent with, not independent evidence against, the systematic review's confounding concern (Li et al., 2021) [17]. Read the systematic review as the more authoritative source on this question; the single small trial should not be read as a separate, stronger finding.
A Novel Schedule Worth Knowing About
Fact 16. A randomized trial of water-only 24-hour fasting performed twice weekly for 4 weeks, then once weekly for 22 weeks (the "WONDERFUL" trial, n=103) found no significant change in LDL cholesterol, its pre-specified primary outcome, but did find significant improvement in insulin resistance (HOMA-IR) and a composite metabolic syndrome score versus ad-libitum controls (Bartholomew et al., 2021) [18]. Of 103 enrolled, 71 completed; weight change, a general cognitive score, and BDNF did not differ significantly from controls. This is a useful fact precisely because it is a negative primary-outcome trial that still found secondary benefit: a clean example of why "fasting lowers cholesterol" is not a safe one-line claim.
What the Evidence Does Not Yet Show
No citation on this page establishes that any fasting schedule reduces mortality, stroke, or heart attack risk; a 2021 Cochrane review (searches to December 2019) found no study reporting on those outcomes at any follow-up (Allaf et al., 2021) [8]. No citation here shows a named schedule beating ordinary calorie restriction in a long-term head-to-head trial: the year-long alternate-day-fasting trial found no advantage (fact 3), and the one trial here that found an advantage ran 8 weeks (Teong et al., 2021) [11]. No citation here ties autophagy measurement to a proven health outcome (fact 13). No citation here resolves whether gut-microbiome changes from fasting are beneficial, harmful, or neutral (fact 14). And no citation here isolates a hormonal benefit for women with PCOS from the confounding effect of weight loss itself (fact 15).
Safety and Cautions
This is general information, not medical advice. Evidence quality across this literature is mostly low to very low certainty, and even well-known claims, such as "fasting lowers cholesterol" or "fasting improves brain health," do not hold up cleanly once a dedicated trial tests them head-to-head. Talk to a clinician before fasting of any kind or length if you are pregnant, under 18, have a history of an eating disorder, or manage diabetes or blood pressure with medication.
What the evidence actually supports
Read across all 16 facts below, fasting of various kinds produces real, measurable effects on weight and several cardiometabolic markers, broadly comparable in size to ordinary calorie restriction rather than clearly superior to it, and no single named schedule has been shown to outperform the others in head-to-head evidence. Two reviews that graded evidence certainty rate most of this literature low to very low (Allaf et al., 2021 [8]; Patikorn et al., 2021 [7]), a recurring loss of lean mass alongside fat loss shows up often enough to be a pattern rather than an outlier, and the areas most hyped in popular coverage, autophagy and gut-microbiome "detox" framing, rest on the thinnest and newest human evidence in this entire set, not the deepest.
Where specific head-to-head trials disagree with pooled analyses
Where a dedicated trial tested a specific claim, the result was often less favorable than popular framing: a year-long trial found alternate-day fasting no better than daily calorie restriction on weight, maintenance, or adherence (Trepanowski et al., 2017) [3], although a large pooled analysis found a modest alternate-day-fasting advantage over calorie restriction (-1.29 kg) in trials shorter than 24 weeks (Semnani-Azad et al., 2025) [1]; a 12-week trial found time-restricted eating no better for weight than three structured meals a day (Lowe et al., 2020) [4]; and a once-weekly fasting trial did not lower LDL cholesterol, its primary outcome (Bartholomew et al., 2021) [18]. Not every head-to-head result points the same way: an 8-week trial in women found intermittent fasting produced more weight and body-fat loss than calorie restriction at the same calorie target (Teong et al., 2021) [11]. The right reader takeaway is "fasting works about as well as calorie restriction for many people, with real but modest effects, under-powered evidence on brain and gut claims specifically, and no settled answer on which schedule is best," not "science proves fasting is superior."
Authors and funding of the cited studies
- Semnani-Azad et al., 2025 [1]: multiple authors disclose food- and pharmaceutical-industry funding, honoraria, or advisory roles in the paper's competing-interests statement, including ties to the Almond Board of California, Novo Nordisk, Eli Lilly, General Mills, the Calorie Control Council, Nestlé, and Tate & Lyle.
- Xiaoyu, Yuxin, and Li, 2024 [2]: no conflicts declared.
- Trepanowski et al., 2017 [3]: "Dr Varady reported receiving an advance for the book The Every-Other-Day Diet... published by Hachette Book Group."
- Lowe et al., 2020 [4]: Lowe reported personal fees from Keyto. Weiss "is a cofounder and equity stake holder of Keyto, Inc; and owns stock and was formerly on the board of Virta, Inc." Heymsfield reported personal fees from the Medifast and Tanita advisory boards.
- Ezpeleta et al., 2024 [5]: Varady is senior author. This paper's own funding and competing-interest statement could not be retrieved for this page.
- Mohammadzadeh et al., 2025 [6]: "The authors declare no competing interests."
- Patikorn et al., 2021 [7]: "Dr Varady reported receiving author fees from Hachette Book Group for the book, The Every Other Day Diet." Pham reported personal fees from the Southwest Obesity Symposium.
- Allaf et al., 2021 [8]: no conflicts declared.
- Wilhelmi de Toledo et al., 2019 [9]: "FWT is member of the Directory Board of the Buchinger Wilhelmi Clinic (BWC), where the study was performed," and is managing director of Amplius GmbH, which runs fasting research for BWC. "FG is currently employed, and SD was formerly employed, at BWC. AM is a consultant at BWC and receives financial compensation for this role from Amplius GmbH."
- Senderovich, Farahneh, and Waicus, 2023 [10]: no conflicts declared.
- Teong et al., 2021 [11]: no conflicts declared.
- Bamberg, Reichenberger, and Blechert, 2026 [12]: no conflicts declared.
- Kapogiannis et al., 2024 [13]: an NIH intramural study; no conflicts declared.
- Bensalem et al., 2025 [14]: funded by the National Health and Medical Research Council (Australia) and Diabetes Australia. This paper's own competing-interest statement could not be retrieved for this page.
- Paukkonen et al., 2024 [15]: no conflicts declared; one author discloses serving on a Frontiers editorial board.
- Jirapak et al., 2026 [16]: this paper's own competing-interest statement could not be retrieved for this page.
- Li et al., 2021 [17]: no conflicts declared.
- Bartholomew et al., 2021 [18]: funded by the Intermountain Research and Medical Foundation (Dell Loy Hansen Heart Foundation philanthropy). "B.D.H. is PI of other intermittent fasting grants from the Intermountain Research and Medical Foundation and a member of the scientific advisory board of Sylfph."
- Chaudhary et al., 2022 [19]: this paper's own competing-interest statement could not be retrieved for this page.
- Disclosures are listed where the full text of the paper was available to us; a study not listed here is not a statement that its authors have no ties.
References
- Semnani-Azad Z, Khan TA, Chiavaroli L, Chen V, Bhatt HA, Chen A, Chiang N, Oguntala J, Kabisch S, Lau DC, Wharton S, Sharma AM, Harris L, Leiter LA, Hill JO, Hu FB, Lean ME, Kahleová H, Rahelic D, Salas-Salvadó J, Kendall CW, Sievenpiper JL (2025). Intermittent fasting strategies and their effects on body weight and other cardiometabolic risk factors, systematic review and network meta-analysis of randomised clinical trials. BMJ. PMID 40533200 doi:10.1136/bmj-2024-082007 Finding: supports
- Xiaoyu W, Yuxin X, Li L (2024). The effects of different intermittent fasting regimens in people with type 2 diabetes, a network meta-analysis. Frontiers in Nutrition. PMID 38332802 doi:10.3389/fnut.2024.1325894 Finding: no effect found
- Trepanowski JF, Kroeger CM, Barnosky A, Klempel MC, Bhutani S, Hoddy KK, Gabel K, Freels S, Rigdon J, Rood J, Ravussin E, Varady KA (2017). Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults. JAMA Internal Medicine. PMID 28459931 doi:10.1001/jamainternmed.2017.0936 Finding: contradicts
- Lowe DA, Wu N, Rohdin-Bibby L, Moore AH, Kelly N, Liu YE, Philip E, Vittinghoff E, Heymsfield SB, Olgin JE, Shepherd JA, Weiss EJ (2020). Effects of Time-Restricted Eating on Weight Loss and Other Metabolic Parameters in Women and Men With Overweight and Obesity, the TREAT Randomized Clinical Trial. JAMA Internal Medicine. PMID 32986097 doi:10.1001/jamainternmed.2020.4153 Finding: contradicts
- Ezpeleta M, Cienfuegos S, Lin S, Pavlou V, Gabel K, Varady KA (2024). Efficacy and safety of prolonged water fasting, a narrative review of human trials. Nutrition Reviews. PMID 37377031 doi:10.1093/nutrit/nuad081 Finding: supports
- Mohammadzadeh M, Amirpour M, Ahmadirad H, Abdi F, Khalesi S, Naghshi N, Bahrami A, Hejazi E (2025). Impact of Fasting Mimicking Diet (FMD) on cardiovascular risk factors: a systematic review and meta-analysis of randomized control trials. Diabetology and Metabolic Syndrome. PMID 40287774 doi:10.1186/s13098-025-01709-5 Finding: limited evidence
- Patikorn C, Roubal K, Veettil SK, Chandran V, Pham T, Lee YY, Giovannucci EL, Varady KA, Chaiyakunapruk N (2021). Intermittent Fasting and Obesity-Related Health Outcomes, an Umbrella Review of Meta-analyses of Randomized Clinical Trials. JAMA Network Open. PMID 34919135 doi:10.1001/jamanetworkopen.2021.39558 Finding: limited evidence
- Allaf M, Elghazaly H, Mohamed OG, Fareen MFK, Zaman S, Salmasi AM, Tsilidis K, Dehghan A (2021). Intermittent fasting for the prevention of cardiovascular disease. Cochrane Database of Systematic Reviews. PMID 33512717 doi:10.1002/14651858.CD013496.pub2 Finding: contradicts
- Wilhelmi de Toledo F, Grundler F, Bergouignan A, Drinda S, Michalsen A (2019). Safety, health improvement and well-being during a 4 to 21-day fasting period in an observational study including 1422 subjects. PLoS One. PMID 30601864 doi:10.1371/journal.pone.0209353 Finding: supports
- Senderovich H, Farahneh O, Waicus S (2023). The Role of Intermittent Fasting and Dieting on Cognition in Adult Population, A Systematic Review of the Randomized Controlled Trials. Medical Principles and Practice. PMID 37263255 doi:10.1159/000530269 Finding: limited evidence
- Teong XT, Hutchison AT, Liu B, Wittert GA, Lange K, Banks S, Heilbronn LK (2021). Eight weeks of intermittent fasting versus calorie restriction does not alter eating behaviors, mood, sleep quality, quality of life and cognitive performance in women with overweight. Nutrition Research. PMID 34274552 doi:10.1016/j.nutres.2021.06.006 Finding: no effect found
- Bamberg C, Reichenberger J, Blechert J (2026). Stable cognitive performance while adapting to intermittent fasting, A randomised controlled trial. Journal of Health Psychology. PMID 40698448 doi:10.1177/13591053251351204 Finding: no effect found
- 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 (2024). Brain responses to intermittent fasting and the healthy living diet in older adults. Cell Metabolism. PMID 38901423 doi:10.1016/j.cmet.2024.05.017 Finding: supports
- Bensalem J, Teong XT, Hattersley KJ, Hein LK, Fourrier C, Dang LVP, Singh S, Liu K, Wittert GA, Hutchison AT, Heilbronn LK, Sargeant TJ (2025). Intermittent time-restricted eating may increase autophagic flux in humans, an exploratory analysis. The Journal of Physiology. PMID 40345145 doi:10.1113/JP287938 Finding: limited evidence
- Paukkonen I, Törrönen EN, Lok J, Schwab U, El-Nezami H (2024). The impact of intermittent fasting on gut microbiota, a systematic review of human studies. Frontiers in Nutrition. PMID 38410639 doi:10.3389/fnut.2024.1342787 Finding: limited evidence
- Jirapak A, Adams E, Black GM, Devlin BL (2026). Impact of time-restricted eating on reproductive hormones and androgen markers in adult females, A systematic review. Nutrition and Health. PMID 42429418 doi:10.1177/02601060261467643 Finding: limited evidence
- Li C, Xing C, Zhang J, Zhao H, Shi W, He B (2021). Eight-hour time-restricted feeding improves endocrine and metabolic profiles in women with anovulatory polycystic ovary syndrome. Journal of Translational Medicine. PMID 33849562 doi:10.1186/s12967-021-02817-2 Finding: supports
- Bartholomew CL, Muhlestein JB, May HT, Le VT, Galenko O, Garrett KD, Brunker C, Hopkins RO, Carlquist JF, Knowlton KU, Anderson JL, Bailey BW, Horne BD (2021). Randomized controlled trial of once-per-week intermittent fasting for health improvement, the WONDERFUL trial. European Heart Journal Open. PMID 35919268 doi:10.1093/ehjopen/oeab026 Finding: limited evidence
- Chaudhary R, Liu B, Bensalem J, Sargeant TJ, Page AJ, Wittert GA, Hutchison AT, Heilbronn LK (2022). Intermittent fasting activates markers of autophagy in mouse liver, but not muscle from mouse or humans. Nutrition. PMID 35660501 doi:10.1016/j.nut.2022.111662 Finding: contradicts