--- topic: "Intermittent Fasting" title: "The Fasting-Mimicking Diet" order: 4 description: "A 5-day monthly eating protocol that triggers fasting's cellular benefits — autophagy, stem cell renewal, IGF-1 reduction — without complete food abstinence." question: "Does the fasting-mimicking diet improve metabolic health and slow aging?" answer: "The fasting-mimicking diet likely improves weight, blood pressure, IGF-1 and diabetes control, but slowing aging is unproven beyond blood-marker estimates." actions: - "Protocol: 5 days a month, about 1,100 calories on day 1 then about 725 a day, with DIY protein under 25–30 g [1][2]." - "Trials used three monthly cycles; skip hard exercise during the five days and refeed gently for a day afterward [2]." - "Keep a healthy baseline diet, such as Mediterranean-style eating, the other 25 days; this is a monthly reset, not an everyday diet." cautions: - "With type 2 diabetes or diabetes medicine, only do it under medical supervision; the trial cut medication needs within a primary-care program [5]." - "Mild fatigue and headache occurred during the five days, and people with normal baseline markers saw little change [2]." - "Safety beyond 12 months, the best frequency, and whether DIY versions match the tested protocol are unknown." confidence: 3 confidenceNote: "Two RCTs (100 healthy adults; 12-month diabetes trial) plus small pilots; most work is from one research group, and aging claims use blood-marker estimates." evidenceSummary: rctCount: 2 observationalCount: 1 metaAnalysisCount: 0 totalParticipants: "100+" replicated: true newestStudyYear: 2024 references: - id: "1" pmid: "26094889" title: "A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan" authors: "Brandhorst S, Choi IY, Wei M, Cheng CW, Sedrakyan S, Navarrete G, Longo VD" year: 2015 journal: "Cell Metabolism" - id: "2" pmid: "28202779" title: "Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease" authors: "Wei M, Brandhorst S, Shelehchi M, Mirzaei H, Cheng CW, Budniak J, Groshen S, Mack WJ, Guen E, Di Biase S, Cohen P, Morgan TE, Dorff T, Hong K, Michalsen A, Laviano A, Longo VD" year: 2017 journal: "Science Translational Medicine" - id: "3" pmid: "27239035" title: "A Diet Mimicking Fasting Promotes Regeneration and Reduces Autoimmunity and Multiple Sclerosis Symptoms" authors: "Choi IY, Piccio L, Childress P, Bollman B, Ghosh A, Brandhorst S, Suarez J, Michalsen A, Cross AH, Morgan TE, Wei M, Paul F, Bock M, Longo VD" year: 2016 journal: "Cell Reports" - id: "4" pmid: "38378685" title: "Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk" authors: "Brandhorst S, Levine ME, Wei M, Shelehchi M, Morgan TE, Nayak KS, Dorff T, Hong K, Crimmins EM, Cohen P, Longo VD" year: 2024 journal: "Nature Communications" - id: "5" pmid: "38546821" title: "Integration of a fasting-mimicking diet programme in primary care for type 2 diabetes reduces the need for medication and improves glycaemic control: a 12-month randomised controlled trial" authors: "van den Burg EL, Schoonakker MP, van Peet PG, van den Akker-van Marle EM, Lamb HJ, Longo VD, Numans ME, Pijl H" year: 2024 journal: "Diabetologia" --- The fasting-mimicking diet (FMD) is a structured 5-day eating protocol, repeated once a month, that delivers roughly 800–1,100 calories on the first day and 700–800 on days two through five. The specific ratio of low protein, moderate carbohydrate, and higher healthy fat keeps the body in a fasting-like metabolic state without requiring complete food abstinence. Developed by longevity researcher Valter Longo at USC, it has been tested in multiple randomised human trials and shown to reduce IGF-1, visceral fat, blood pressure, fasting glucose, and inflammatory markers — with effects persisting well beyond the five days themselves [1][2]. It is one of the most clinically validated dietary protocols for longevity and metabolic health. ## How the FMD Differs from Intermittent Fasting Standard intermittent fasting involves shortening your daily eating window — typically 16 hours fasting, 8 hours eating. The fasting-mimicking diet works differently: you eat normally for roughly 25 days a month, then compress a fasting response into a 5-day block once per month. The protocol is built around a very specific macronutrient composition that fools your body into activating fasting pathways even though you are still eating: - **Day 1:** approximately 1,100 calories — 10% protein, 56% fat, 34% carbohydrate - **Days 2–5:** approximately 725 calories per day — 9% protein, 44% fat, 47% carbohydrate The low protein intake is especially important. Protein — particularly animal protein — stimulates the IGF-1 and mTOR signalling pathways, which suppress autophagy and cellular repair. By keeping protein very low for five days, the FMD shuts down those pathways and allows the cellular maintenance machinery to run [1]. ## What Happens Inside Your Cells **IGF-1 suppression.** Insulin-like growth factor 1 (IGF-1) is a growth hormone that accelerates cell proliferation. High IGF-1 is associated with faster aging and increased cancer risk. Three monthly FMD cycles reduced IGF-1 by 15% on average in a controlled human trial [2]. The protein restriction is the key driver — this is why calorie-matched diets with normal protein don't replicate the effect. **mTOR inhibition and autophagy.** The mechanistic target of rapamycin (mTOR) acts like a cell growth switch. When mTOR is off, autophagy turns on — cells start recycling their damaged proteins, clearing out dysfunctional mitochondria, and performing quality control on all their internal machinery [1]. See our [autophagy page](/autophagy/cellular-recycling) for a deeper explanation of why this matters. **Stem cell regeneration.** In mouse studies, repeated FMD cycles triggered regeneration of white blood cells, gut epithelial cells, and even pancreatic beta cells. The mechanism appears to involve a die-and-regenerate cycle: damaged or senescent cells are cleared during the fast, and stem cell activity increases during refeeding [3]. This regenerative effect is one of the most striking findings in Longo's work. **Reduced systemic inflammation.** The same 2017 human trial found that FMD cycles reduced C-reactive protein (CRP), a key marker of chronic inflammation, particularly in participants who were elevated at baseline [2]. ## Practical Protocol The commercial version of the FMD is a boxed kit called ProLon, which supplies pre-portioned soups, crackers, teas, and supplements calibrated to Longo's macronutrient specifications. A DIY version is possible but requires careful attention to the protein ceiling (typically under 25–30 g/day during the 5-day period). Most people do the five days consecutively, once per month for three months as a reset, then can continue monthly or reduce to every two to three months for maintenance. The five days are often described as manageable — challenging but not as difficult as extended water fasting, because the small amount of food (especially fat) dampens hunger. Common timing: start on a Monday, return to normal eating on Saturday. Avoid high-intensity exercise during the five days and allow a full day of easy refeeding before resuming normal training. The FMD is not intended as an everyday diet or a replacement for good year-round eating. It works best as a monthly reset layered on top of a generally healthy diet — see our [Mediterranean diet page](/mediterranean-diet/cardiovascular-and-longevity) for a strong baseline approach. ## Evidence Review ### The Foundational Animal and Human Pilot Study (Brandhorst et al., 2015) Brandhorst and colleagues at USC published the defining paper on the FMD in *Cell Metabolism* in 2015 [1]. In mice, repeated FMD cycles (equivalent to 5-day monthly cycles scaled to mouse lifespan) produced significant benefits: reduced abdominal fat, improved cognitive performance on maze tests, improved immune function, and extension of median lifespan by 11%. Visceral fat reduction was particularly notable. The paper also included a small human pilot (n=19) that documented reductions in IGF-1, glucose, blood pressure, and cholesterol, with no serious adverse events. This pilot formed the basis for the larger trial that followed. ### The First Human Randomised Controlled Trial (Wei et al., 2017) Wei and colleagues randomised 100 generally healthy adults to either three monthly FMD cycles or an unrestricted diet control group, then allowed the control group to cross over to FMD for three more months [2]. Published in *Science Translational Medicine*, this remains the most cited FMD clinical trial. Key findings after three FMD cycles: - IGF-1 reduced by 15% (from ~170 to ~145 ng/mL) - Body weight reduced by 2.6 kg, with trunk fat showing larger reductions than lean mass - Systolic blood pressure reduced by approximately 4 mmHg - Fasting glucose, total cholesterol, triglycerides, and CRP all showed improvement — particularly in participants who were at higher risk at baseline Effects were largely maintained at a follow-up assessment conducted after participants resumed normal eating. The specificity of the response to baseline risk status is important: participants with normal values at the start showed little change, while those with elevated markers saw meaningful improvements. This suggests the FMD is correcting dysfunction rather than optimising from an already-healthy baseline. No serious adverse effects were reported, though some participants experienced mild fatigue and headache during the five days — consistent with what is seen in other calorie-restricted protocols. ### Autoimmunity and Neurological Applications (Choi et al., 2016) A separate clinical study tested the FMD in patients with relapsing-remitting multiple sclerosis (MS), comparing it to a Mediterranean diet and a ketogenic diet [3]. Published in *Cell Reports*, the FMD group showed improvements in quality of life measures, reduced fatigue, and shifts in immune cell populations consistent with reduced autoimmune activity. Mouse MS models (experimental autoimmune encephalomyelitis) showed even more dramatic effects: FMD cycles reduced disease severity and promoted remyelination — the repair of the myelin sheath around nerve fibres. The mechanism proposed involves regulatory T cell expansion and oligodendrocyte precursor cell regeneration during refeeding. While the human data from this study is preliminary, it opens a meaningful research direction for dietary management of autoimmune conditions. ### Biological Age Reduction (Brandhorst et al., 2024) A 2024 paper in *Nature Communications* applied epigenetic aging clocks to blood and liver marker data from FMD participants and reported that three FMD cycles were associated with markers consistent with a 2.5-year reduction in biological age [4]. The analysis used both hepatic markers and established DNA methylation-based aging algorithms. The authors were careful to note that this is an indirect measurement — blood marker proxies for biological age rather than direct epigenetic clock assessment — and that larger long-term trials are needed. Still, the consistency of the direction of effect across multiple aging-related biomarkers is notable. ### Type 2 Diabetes: Primary Care RCT (van den Burg et al., 2024) Published in *Diabetologia*, this 12-month randomised trial integrated a monthly FMD programme into routine primary care for patients with type 2 diabetes managed by metformin and/or diet alone [5]. Participants in the FMD group achieved: - Lower use of glucose-lowering medication (adjusted treatment effect on the medication effect score −0.3; 95% CI −0.4 to −0.2; p<0.001) - Improved glycaemic management (a combined measure of medication use and HbA1c) in 53% of FMD participants vs. 8% of controls (p<0.001) - HbA1c improvement despite reduction in medication (−3.2 mmol/mol, or −0.3%; p=0.04) - Body weight reduction of 3.6 kg versus controls The finding that glycaemic control improved even as medication was reduced is clinically significant. It suggests the FMD was producing real metabolic change rather than simply compensating for medication effects. Glycaemic management deteriorated in 59% of control participants over 12 months versus 23% in the FMD group — highlighting the progressive nature of type 2 diabetes when left to standard care alone. ### Strength of Evidence The FMD has an unusually strong evidence base for a dietary intervention: multiple mechanism-confirmed animal studies, at least two randomised human trials with hundreds of participants, and replication across different disease states. The largest uncertainties are long-term (beyond 12 months) adherence and safety data, optimal cycling frequency for maintenance versus therapeutic phases, and whether DIY versions can match the macronutrient precision of the validated protocol. The autoimmune and cancer-adjacent applications are promising but need larger dedicated trials before clinical recommendations can be made.