Fasting Mimicking Diet (FMD): Fasting Effects Without Giving Up Food Completely
You tried fasting and gave in on day two? The fasting mimicking diet could be a middle path. What studies show, where it reaches its limits and who it does not suit.
Fasting is not a competition in going without. It is not whoever goes hungry the longest who benefits the most. It is whoever finds a path their body can follow.
Does this sound familiar? You firmly decide to drink only water and tea for five days. On the first evening your head is pounding. On the second morning your hands are shaking, you are irritable, and in the meeting you cannot think clearly. At some point you find yourself standing at the fridge, feeling like someone who has failed.
I would like to offer you something other than guilt. Maybe your willpower was not the problem. Maybe the method was simply too harsh for your system at that moment. And this is exactly where an idea comes in that researchers have been studying for about ten years: the Fasting Mimicking Diet, FMD for short.
What to expect in this article
- What the fasting mimicking diet is and how it differs from a zero-calorie fast
- Which signals in the body a fasting program might set in motion
- The most important human studies, honestly put into context
- The immune connection from a KPNI perspective
- Why animal data are exciting but not proof
- Who should not do the FMD without medical supervision
What exactly is the fasting mimicking diet?
Imagine your body has a gatekeeper. It does not look at every single calorie. It pays attention to certain signals: Is sugar coming in? Is protein coming in? How much energy is arriving? If these signals are missing for several days, the gatekeeper switches into a different operating mode. Clearing up instead of building up.
The idea of the FMD is to convince this gatekeeper that you are fasting, even though you keep eating small meals. In the best-known randomized study, the researchers describe the FMD as a diet low in calories, low in sugar and low in protein, but with a higher share of unsaturated fats. It was followed for five days in a row, once a month.
Zero-calorie fasting
Several days of only water, tea or broth. In the Buchinger setting about 200 to 250 kcal per day. A strong stimulus that requires preparation and often supervision.
Fasting Mimicking Diet (FMD)
Several days of small, plant-focused meals low in sugar and protein. Aim: fasting-like signals with a bit more everyday practicality.
Intermittent fasting
A daily eating window, for example 16:8. Not a multi-day block, but a recurring rhythm in everyday life.
A fair perspective matters to me. Classic fasting is not inherently dangerous or bad. A large observational study from a fasting clinic showed that supervised fasting can be well tolerated by many people.
The team around Wilhelmi de Toledo accompanied 1,422 people through fasting periods of 4 to 21 days with 200 to 250 kcal per day. Side effects were reported in fewer than 1 percent, and 93.2 percent said they did not feel hungry. What this means for you: in the protected setting of a clinic, classic fasting appears to be manageable for many people, so the FMD is not a must, but an option.
Wilhelmi de Toledo et al., PLoS One 2019. DOI: 10.1371/journal.pone.0209353The question is not: "Am I strong enough for real fasting?" The better question is: "Which form of fasting stimulus fits my everyday life, my stress level and my body right now?"
And now you know why the fasting mimicking diet is not "fasting light for the weak", but a tool of its own with its own logic.
What might happen in the body when the gatekeeper switches modes?
Maybe you are wondering: How is eating a little less supposed to change anything in my cells? The answer lies in messenger molecules that work like growth switches. One of them is called IGF-1. It essentially tells your cells: "There is enough available, grow and divide."
In a review, Longo and Mattson summarized that fasting can activate stress protection programs in cells and animal models. Oxidative damage and inflammation can decrease, and energy metabolism shifts. The broad lines are well described in animals. In humans, many details are still open.
Signal: little sugar, little protein
Growth signals such as IGF-1 and blood sugar can decrease. This was measured in human studies with the FMD.
Protective mode
In animal models, cells switch to stress resistance. Body fat is used as an energy source, ketone bodies rise.
Shrinking and clearing up
In mice, several organs and tissues temporarily became smaller during the FMD.
Refeeding
Only after eating again did the number of progenitor and stem cells rise in mice. Regeneration appears to be tied to the switch.
Brandhorst and colleagues at the University of Southern California originally developed the FMD to reduce the burden of long fasting periods. In mice, FMD cycles twice a month starting in middle age were associated with a longer lifespan, less abdominal fat, fewer cancer cases and a rejuvenated immune profile. What this means for you: a fascinating hint from an animal model that has not been shown in the same way in humans.
Brandhorst et al., Cell Metabolism 2015. DOI: 10.1016/j.cmet.2015.05.012The fasting days may be only half the story. In the animal model, rebuilding happened mainly afterwards. How you eat again could therefore matter just as much as the fasting itself.
And now you know why the rhythm of scarcity and abundance is at the center, and not hunger as such.
What do studies in humans show so far?
Mice are not humans. That cannot be said often enough. So the exciting question is: What remains when real people with jobs, families and appointments follow a fasting mimicking diet for five days?
Wei and colleagues randomly assigned 100 mostly healthy adults to two groups: normal diet or five days of FMD per month for three months. After three cycles, body weight, trunk and total body fat, blood pressure and IGF-1 decreased, and no serious side effects were reported. In a post hoc analysis, people with elevated risk factors benefited more, which means for you: your starting point appears to play a role.
Wei et al., Science Translational Medicine 2017. DOI: 10.1126/scitranslmed.aai8700In 2024, Brandhorst and colleagues re-analyzed blood samples from these trials. Three FMD cycles were associated with less insulin resistance, less liver fat on MRI and a median biological age 2.5 years lower, independent of weight loss. What this means for you: an encouraging signal, although it comes from an exploratory analysis and should still be independently confirmed.
Brandhorst et al., Nature Communications 2024. DOI: 10.1038/s41467-024-45260-9Van den Burg and colleagues from Leiden integrated a monthly five-day FMD program into primary care for people with type 2 diabetes who used only metformin or no medication at all. After twelve months, medication needs decreased, HbA1c fell by 3.2 mmol/mol and weight by 3.6 kg compared with the control group. A follow-up analysis with MRI showed less abdominal and subcutaneous fat with unchanged abdominal muscle mass.
van den Burg et al., Diabetologia 2024. DOI: 10.1007/s00125-024-06137-0 · Schoonakker et al., Nutr Metab Cardiovasc Dis 2025. DOI: 10.1016/j.numecd.2025.104111One detail from this Leiden study touches me in particular. In focus groups, participants said that the FMD days encouraged them to take better care of themselves between cycles as well. The researchers called this a "teachable moment". Physical activity increased measurably in the FMD group.
Perhaps the greatest power of a fasting cycle is not what it changes in five days. But what it sets in motion within you for the remaining 25 days.
A large part of FMD research comes from Longo's research group, and Longo is involved in many of these studies. Longo is connected to the company L-Nutra, which sells FMD products. The Leiden diabetes study lists L-Nutra as one of its co-funders. This does not invalidate the data, since the studies were peer reviewed and published in respected journals. But it belongs to an honest assessment, and independent replications would be desirable. This article does not recommend any specific product.
Supported by randomized trials: favorable changes in metabolic markers such as body fat, blood pressure, IGF-1 and, in type 2 diabetes, also HbA1c. Not yet shown: that the FMD prevents diseases in humans, extends lifespan or is superior to classic fasting.
And now you know why the human studies can give you encouragement without turning into a promise.
How might the fasting mimicking diet communicate with the immune system?
Maybe you live with a body that feels as if it is constantly on alert. Joints, gut, skin, something is always smoldering somewhere. From the perspective of Clinical Psychoneuroimmunology, KPNI for short, the immune system is not an isolated organ. It is closely linked to metabolism, hormones and the nervous system. That is exactly why the question is exciting whether a fasting stimulus could reorganize the immune system.
Choi and colleagues gave mice with a model of multiple sclerosis periodic three-day FMD cycles. Disease severity decreased in all animals, regulatory T cells increased, inflammatory Th1 and Th17 cells declined, and remyelination was seen in nerve tissue. A small pilot study in people with relapsing-remitting MS suggested feasibility and safety, but is far too small to assess an effect.
Choi et al., Cell Reports 2016. DOI: 10.1016/j.celrep.2016.05.009Rangan and colleagues studied a mouse model of inflammatory bowel disease. Four-day FMD cycles were associated with less intestinal inflammation, more stem cells and a more protective gut flora, while water-only fasting improved regeneration markers but did not reverse the tissue damage. In a human study, three FMD cycles lowered markers of systemic inflammation.
Rangan et al., Cell Reports 2019. DOI: 10.1016/j.celrep.2019.02.019Immune system
In animals, the balance shifted from inflammatory to regulatory T cells. In humans, the ratio of lymphoid to myeloid cells increased, a marker associated with a younger immune age.
Metabolism
Falling glucose and IGF-1 take growth pressure out of the system. Liver fat and insulin resistance decreased in human studies. Less visceral fat often also means fewer inflammatory messenger molecules.
Hormonal system
In the MS mouse model, corticosterone, the stress hormone of the mouse, increased. A short, measured cortisol stimulus can dampen inflammation. Chronic stress, on the other hand, is a burden. The dose makes the difference.
Nervous system
In old mice, FMD cycles were associated with more new nerve cell formation in the hippocampus. If you already live under constant stress, you might experience a harsh food restriction as an additional threat. A gentler stimulus may be wiser here.
An irritated nervous system does not distinguish between "healthy fasting" and "famine". It senses scarcity. A mild, predictable fasting program could therefore be the better tolerated entry point for people with a lot of stress or a sensitive gastrointestinal tract. Clinically plausible, but not yet tested in direct comparison studies.
And now you know why in KPNI we never look only at calories when it comes to fasting, but at the whole network of immune system, metabolism, hormones and nerves.
The fasting mimicking diet and cancer: what is research and what is not?
I know this topic raises hope. Maybe you are reading this because someone you love is currently in treatment. That is why I want to be especially clear here: The following data are research. They are not a recommendation to combine cancer treatment with fasting on your own.
De Groot and colleagues from the Netherlands randomized 131 women with stage II or III HER2-negative breast cancer, who received either an FMD or their normal diet around chemotherapy. Side effects did not differ, even though dexamethasone was omitted in the FMD group, and radiological response occurred more often. Women with diabetes or a BMI below 18 were excluded, which shows how strict the selection was.
de Groot et al., Nature Communications 2020. DOI: 10.1038/s41467-020-16138-3Vernieri and colleagues in Milan gave 101 people with various tumor types cyclic five-day FMDs in addition to standard therapy. The FMD was feasible, blood sugar and growth factors decreased, and immunosuppressive cells in the blood declined, while antitumor immune signatures increased in the tumor. The authors themselves emphasize that phase II and phase III trials are needed to test efficacy.
Vernieri et al., Cancer Discovery 2022. DOI: 10.1158/2159-8290.CD-21-0030With cancer, the rule is: Any form of fasting belongs exclusively in the hands of the oncology team. Malnutrition and weight loss can jeopardize treatment.
And now you know why this field of research is exciting and at the same time calls for the most caution.
Who is the fasting mimicking diet not suitable for?
Now comes the part many people would like to skip. Please read it anyway. A milder fasting stimulus is still an intervention in your metabolism. The studies you have just read about had clear exclusion criteria and medical supervision.
Please not without medical supervision, or not at all
- Pregnancy and breastfeeding
- Underweight or unintended weight loss
- Current or past eating disorder
- Diabetes treated with insulin or sulfonylureas: risk of low blood sugar, medication must be adjusted by a physician
- Children and adolescents as well as frail older people
- Severe kidney, liver or heart disease, heart rhythm disorders
- Ongoing cancer treatment outside of studies and without oncological clearance
- Blood pressure lowering, diuretic or anticoagulant medication and other long-term medication: get checked beforehand
Mehanna and colleagues described refeeding syndrome in the BMJ: dangerous shifts in electrolytes such as phosphate, potassium and magnesium when severely malnourished people receive food again too quickly. This mainly affects people with underweight, long periods of food deprivation or eating disorders. What this means for you: the longer and stricter the fasting phase and the smaller the reserves, the more important a slow, medically supervised return to eating becomes.
Mehanna et al., BMJ 2008. DOI: 10.1136/bmj.a301If you recognize yourself in this list, it does not mean that fasting stimuli are off limits forever. It only means that your path needs different support. Sometimes a gentler overnight eating window is the more suitable first step.
And now you know why a good fasting plan begins with the question of who you are, and not with the question of how many days you can manage.
Why this is bigger than a few kilos less
Maybe the scale is not what this is about for you at all. Maybe you wish to feel again that you can trust your body. That it does not just function, but works with you. Fasting stimuli, wisely dosed, could be one way to regain this trust.
In the New England Journal of Medicine, de Cabo and Mattson described the switch between food scarcity and refeeding as a stimulus that could make cells more resilient. They essentially compared it to training: a measured stress can trigger adaptation. Too much of it exhausts.
Health is not the absence of stress. Health is the ability to get back up after stress. And exactly this ability means freedom.
Three levers you can start working on today
Your next steps
- An honest self-check: Go through the list above. If you take medication or one of the points applies to you, discuss any form of fasting with your physician first.
- A gentle start: Before you plan a multi-day block, observe how your body responds to a longer overnight break without snacks. This gives you first clues about how sensitive your system is.
- Plan the days afterwards: Think ahead about how you will eat again after a fasting cycle. Easily digestible, nutrient-rich, no binge buffet. Refeeding could be the part in which your body rebuilds.
If you would like not only to read, but to find out together which fasting stimulus suits you: below this article you will find the option to book an appointment.
Fasting in the system: related topics
Fasting touches almost every area I work with. The gut responds, the immune system responds, the hormones respond. Here you will find more guides on the ViveCura Blog.
Fasting mimicking
Fasting stimulus with small meals
Gut
Microbiome, barrier and inflammation
Hormones
Cortisol, insulin and the stress axis
Nutrition
What you eat between cycles
Frequently asked questions about the fasting mimicking diet (FMD)
What is the fasting mimicking diet (FMD)?
The fasting mimicking diet is a multi-day eating pattern low in calories, low in sugar and low in protein, but with a higher share of unsaturated fats. The idea: your body receives signals similar to those of fasting, even though you keep eating small meals. In studies it was usually followed for five days per month.
Is the fasting mimicking diet as effective as classic fasting?
This has not yet been tested directly in large head-to-head studies in humans. Human studies show that FMD cycles may favorably influence metabolic markers such as body fat, blood pressure and IGF-1. In a mouse model of intestinal inflammation, the FMD performed differently from water-only fasting on some measures. The two are different tools, not competitors.
How long does an FMD cycle last in studies?
In the best-known human studies, one cycle lasted five consecutive days, repeated once a month. In the study by Wei and colleagues it was three cycles over three months, in the Leiden diabetes study monthly for twelve months. The right frequency for you depends on your starting point and belongs in a conversation with your physician.
Can the fasting mimicking diet influence the immune system?
There are indications. In mouse models of multiple sclerosis and intestinal inflammation, FMD cycles were associated with fewer inflammatory immune cells and more regulatory T cells. In humans, one analysis showed a shift in the ratio of lymphoid to myeloid cells, a marker of immune age. Whether this translates into a clinical benefit is still open.
Who is the fasting mimicking diet not suitable for?
The fasting mimicking diet is not suitable without medical supervision during pregnancy and breastfeeding, with underweight, a current or past eating disorder, diabetes treated with insulin or glucose-lowering medication that can cause low blood sugar, severe kidney, liver or heart disease, for children and adolescents, and during ongoing cancer treatment outside of studies. With many long-term medications it also makes sense to get checked beforehand.
Can I do the fasting mimicking diet if I have diabetes?
A Leiden study with 100 people with type 2 diabetes showed favorable effects on HbA1c and medication needs under the supervision of their general practitioner. However, only people taking metformin alone or no medication at all were included. Anyone using insulin or sulfonylureas has a risk of low blood sugar. So the rule is: never on your own, always with your treating physician.
Can the fasting mimicking diet play a role in cancer?
This is research, not a treatment recommendation. In the Dutch DIRECT trial with 131 breast cancer patients, the FMD around chemotherapy was well tolerated and associated with more frequent response. An Italian study with 101 patients showed metabolic and immune changes. Larger studies are still pending. Any form of fasting during cancer treatment belongs exclusively in the hands of the oncology team.
Who is behind the FMD research?
A large part of the basic research comes from the Longevity Institute at the University of Southern California, around Longo's research group. Longo is connected to the company L-Nutra, which sells FMD products, and according to its own disclosure the Leiden diabetes study was co-funded by L-Nutra, among others. This does not make the results wrong, but it matters for an honest assessment. Independent replications would be desirable.
What is the difference between the fasting mimicking diet and intermittent fasting?
Intermittent fasting moves eating into a time window, usually daily, without necessarily reducing the total amount much. The fasting mimicking diet is a block of several days with clearly reduced energy and a specific nutrient distribution, after which you eat normally again. Both approaches work with the switch between scarcity and abundance, but in different rhythms.
What should I pay attention to after an FMD cycle?
The days afterwards may be just as important as the fasting days themselves. In mice, regeneration showed up mainly in the refeeding phase. A gentle transition with easily digestible, nutrient-rich meals makes sense. After very long or very strict fasting periods, especially with underweight, refeeding syndrome can occur, which must be monitored by a physician.
Scientific sources
- Brandhorst S, Choi IY, Wei M et al. A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan. Cell Metab. 2015;22(1):86-99. DOI: 10.1016/j.cmet.2015.05.012 [In vivo, mouse and yeast, plus human pilot study]
- Wei M, Brandhorst S, Shelehchi M et al. Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. Sci Transl Med. 2017;9(377):eaai8700. DOI: 10.1126/scitranslmed.aai8700 [RCT, n=100, crossover]
- Brandhorst S, Levine ME, Wei M et al. Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk. Nat Commun. 2024;15(1):1309. DOI: 10.1038/s41467-024-45260-9 [RCT, secondary analysis of two trials]
- van den Burg EL, Schoonakker MP, van Peet PG et al. 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. Diabetologia. 2024;67(7):1245-1259. DOI: 10.1007/s00125-024-06137-0 [RCT, n=100, type 2 diabetes]
- Schoonakker MP, van den Burg EL, van Peet PG et al. A fasting-mimicking diet programme reduces abdominal adipose tissue while preserving abdominal muscle mass in persons with type 2 diabetes. Nutr Metab Cardiovasc Dis. 2025;35(10):104111. DOI: 10.1016/j.numecd.2025.104111 [RCT, n=100, MRI analysis]
- van den Burg EL, Schoonakker MP, Korpershoek B et al. Self-initiated lifestyle changes during a fasting-mimicking diet programme in patients with type 2 diabetes: a mixed-methods study. BMC Prim Care. 2024;25(1):148. DOI: 10.1186/s12875-024-02405-5 [RCT, mixed-methods analysis, n=100]
- Choi IY, Piccio L, Childress P et al. A Diet Mimicking Fasting Promotes Regeneration and Reduces Autoimmunity and Multiple Sclerosis Symptoms. Cell Rep. 2016;15(10):2136-2146. DOI: 10.1016/j.celrep.2016.05.009 [In vivo, mouse, plus pilot study in MS]
- Rangan P, Choi I, Wei M et al. Fasting-Mimicking Diet Modulates Microbiota and Promotes Intestinal Regeneration to Reduce Inflammatory Bowel Disease Pathology. Cell Rep. 2019;26(10):2704-2719.e6. DOI: 10.1016/j.celrep.2019.02.019 [In vivo, mouse, plus clinical study]
- Cheng CW, Villani V, Buono R et al. Fasting-Mimicking Diet Promotes Ngn3-Driven β-Cell Regeneration to Reverse Diabetes. Cell. 2017;168(5):775-788.e12. DOI: 10.1016/j.cell.2017.01.040 [In vivo, mouse, plus human islet cells in vitro]
- de Groot S, Lugtenberg RT, Cohen D et al. Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial. Nat Commun. 2020;11(1):3083. DOI: 10.1038/s41467-020-16138-3 [RCT, phase 2, n=131]
- Vernieri C, Fucà G, Ligorio F et al. Fasting-Mimicking Diet Is Safe and Reshapes Metabolism and Antitumor Immunity in Patients with Cancer. Cancer Discov. 2022;12(1):90-107. DOI: 10.1158/2159-8290.CD-21-0030 [Cohort, prospective clinical study, n=101]
- Wilhelmi de Toledo F, Grundler F, Bergouignan A, Drinda S, Michalsen A. Safety, health improvement and well-being during a 4 to 21-day fasting period in an observational study including 1422 subjects. PLoS One. 2019;14(1):e0209353. DOI: 10.1371/journal.pone.0209353 [Cohort, prospective observational study, n=1,422]
- Mehanna HM, Moledina J, Travis J. Refeeding syndrome: what it is, and how to prevent and treat it. BMJ. 2008;336(7659):1495-1498. DOI: 10.1136/bmj.a301 [Review, clinical overview]
- de Cabo R, Mattson MP. Effects of Intermittent Fasting on Health, Aging, and Disease. N Engl J Med. 2019;381(26):2541-2551. DOI: 10.1056/NEJMra1905136 [Review]
- Longo VD, Mattson MP. Fasting: molecular mechanisms and clinical applications. Cell Metab. 2014;19(2):181-192. DOI: 10.1016/j.cmet.2013.12.008 [Mechanism Review]
Some of the relationships described here come from animal models and small pilot studies. These findings are biologically plausible, but in humans they are not yet supported with the same certainty as by large, independently replicated randomized trials. This article does not replace medical advice.