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Modified7 studies in people cited

Fasting-Mimicking Diet

5 days without food · Five consecutive days, once a month for three months in the trials

Written by Reviewed Sep 2026

Also called: FMD, 5-day fasting-mimicking cycle, ProLon-style protocol

Five days of special low-calorie, low-protein food, built to copy a fasting state while you still eat. In the main study it lowered weight, body fat, waist size, the top blood pressure number and IGF-1. It did not change blood sugar, blood fats, cholesterol, LDL, HDL or an inflammation marker (CRP).

Overview

The fasting-mimicking diet is plant-based food that is low in protein and low in sugar, eaten for five days in a row. It is not a fast. Its results do not carry over to or from water fasting.

In the main study, day 1 was about 4,600 kJ (roughly 1,100 calories): 11% protein, 46% fat and 43% carbs. Days 2 to 5 were about 3,000 kJ a day (roughly 717 calories): 9% protein, 44% fat and 47% carbs.

The headline study had 100 people at a US university and ran three monthly rounds. Compared with the group that ate normally, the diet lowered weight, BMI, total and trunk body fat, waist size, the top blood pressure number and IGF-1. It did not change fasting blood sugar, blood fats, total cholesterol, LDL, HDL or CRP. The blood sugar, CRP and cholesterol results people often quote come from after-the-fact looks at smaller groups of people with higher starting levels, among those who finished. The paper labels them that way.

The diet is sold as a product, and the business ties are disclosed in the journals. Those ties are set out below as facts, not as an argument about the science.

How it works

Five days in a row per round, repeated monthly. Day 1 is roughly 1,100 calories and days 2 to 5 roughly 717, with the food mix above.

The cancer version, used in a Dutch breast cancer study, was a 4-day plant-based diet low in protein building blocks. It was roughly 1,200 calories on day 1 and roughly 200 calories on days 2 to 4. Patients ate it for the 3 days before and on the day of each chemotherapy round. The steroid dexamethasone was left out for that group.

Sticking with it is the real story. In the 100-person study, 10% quit the normal-eating group and 25% quit the diet group before the groups swapped. After the swap, 11 of the 43 people who moved from normal eating to the diet quit, another 26%. 71 of 100 finished all three rounds, and 95 finished at least one.

The cancer study numbers were worse. 53 of 65 finished the first round, and more than half finished two. Only 22 of 65 used it for four or more rounds, and 20.0% stuck to it in every round. Disliking the food was the main reason for stopping.

Side effects in the 100-person study were graded on a standard scale. Depending on the side effect, 54% to 100% of people reported none. The most common mild to moderate ones were tiredness, weakness and headaches. There was nothing severe (grade 3 or higher). Blood tests showed no harm to the liver or kidneys.

What 5 days actually reaches

Here is what the main study found, compared with the group that ate normally. Weight fell 2.6 kg on the diet, while the other group gained 0.1 kg. BMI fell 0.9. Total body fat and trunk fat fell clearly more than in the other group. Waist size fell 4.1 cm against 0.8 cm. The top blood pressure number fell 4.5 mmHg against 0.7. IGF-1 fell 21.7 ng/mL, while it rose 8.7 in the other group. What did not differ between groups: the bottom blood pressure number, fasting blood sugar, blood fats, total cholesterol, LDL, HDL and CRP. The IGF-1 result is the one that ties the diet to its stated purpose, and its timing fits what water fasting shows. On a true fast, IGF-1 was unchanged at 56 hours and fell about 41% by day 5. So five days is the shortest length where lowering IGF-1 is a realistic goal. On autophagy (the cell's clean-up process), the only measurement on a fasting-mimicking diet is a small early study of 30 people on an 8-day version. It measured how fast clean-up ran in white blood cells, using a drug (chloroquine) to track it. It found a difference between groups from the start to day 6, and says the differences were not clear across all time points. It was paid for by the company that makes the diet. So this page does not list autophagy as something this diet reaches. It does not claim mitophagy (clean-up of the cell's power plants) at any length, because no study in people has measured it on any fast.

Fig. 1 · what has been measured, hour by hour
  1. 0h to 4h

    Still digesting

    Burning
    Sugar from the meal you just ate. Insulin is high enough to keep fat locked away.
    • Insulin is at its after-meal peak. While it is up there, the enzyme that releases fat from fat cells stays switched off, so fat is being stored, not released.
    • The hour count on most fasting charts starts at the last bite. But the body is still digesting a mixed meal here, so the clock and what the body is doing are not yet the same thing.

    Read the biologyInsulin and insulin sensitivity during a fast

    Measured in people
    The hour-by-hour fasting studies in people start later than this. Klein 1993 took its first sample at 12 hours, in 6 healthy men. Rothman 1991 gives its first figure for new sugar making as an average across the first 22 hours. This row is the fed state those measurements are compared against. No measurement from a long fast falls inside it.

  2. 4h to 12h

    Meal digested, overnight fast

    Burning
    A mix of leftover sugar and fat. The liver keeps the brain supplied with sugar.
    Blood sugar
    5.58 mmol/L (100.5 mg/dL) at the 12 hour mark, in 6 healthy men
    Ketones
    Total ketones around 0.20 mmol/L after an overnight fast. That figure is acetoacetate and BHB added together, not BHB on its own.
    Insulin
    64.6 pmol/L (9.3 microunits/mL) at 12 hours, in the same 6 men
    • At 12 hours, glycerol is released at 2.08 and palmitic acid at 1.63 micromol/kg/min. These are two markers of fat being released. They are the starting numbers everything later in the fast is compared against.
    • Making new sugar from scratch already supplies most of the body's sugar at this point. It is not a backup waiting to be called on. This is the first place the popular "switch" story breaks down.

    Read the biologyInsulin and insulin sensitivity during a fastGlycogen depletion and gluconeogenesis

    Measured in people
    Klein 1993 measured blood sugar, insulin and fat release with tracers at 12 hours, in 6 healthy men. Féry 1983 measured total ketones in people after an overnight fast and put the starting level at 0.20 mmol/L. Rothman 1991 measured liver glycogen again and again with a special MRI scan through a 68 hour fast in healthy adults. It worked out that new sugar making supplied 64% of all the body's sugar across the first 22 hours.

  3. 12h to 18h

    Ketones have not moved yet

    Burning
    Fat use rising. More and more of the body's sugar is being made fresh, not pulled from storage.
    Ketones
    A middle change of 0% between 12 and 18 hours, measured every 6 hours in 34 adults
    • BHB, the main ketone, does not move in this window. In 34 adults sampled every 6 hours through the standard 72 hour fast doctors use for testing, the middle change from 12 to 18 hours was zero.
    • Making new sugar supplies 64% of the body's sugar across the first 22 hours. A second, unrelated method put it at about 47% by 14 hours. The body does not switch from stored sugar to fat at a set hour.
    • In 11 overweight adults, activity of the autophagy gene LC3A in blood cells was 22% higher after an 18 hour fast than after a 12 hour fast. In the same people, activity of the MTOR gene also rose, by 9%.

    Read the biologyGlycogen depletion and gluconeogenesisKetogenesis and beta-hydroxybutyrateAutophagy

    Measured in people
    Service 2005 measured BHB every 6 hours in 34 adults whose 72 hour test fasts came back clear for a rare insulin-making tumour. Rothman 1991 measured the share of new sugar making with a special MRI scan. Jamshed 2019 measured gene activity in blood cells in an 11-person, 4 day study where each person tried two eating windows: 8am to 2pm, and 8am to 8pm. That is one gene's activity in blood cells. It is not the real speed of autophagy, and it is not muscle. No study in any species has tested a 16 hour time point for autophagy.

  4. 18h to 1d

    The biggest hours for fat release

    Burning
    Fat and glycerol, with ketone making starting its climb
    Ketones
    Climbing. The middle rise from 18 to 36 hours was +333%, the steepest stretch of a 72 hour fast.
    Insulin
    70% of the whole drop seen across a 72 hour fast has already happened by 24 hours
    • The single biggest jump in fat release across a whole 72 hour fast comes between 18 and 24 hours. 60% of the total rise in fat release happens between 12 and 24 hours. The authors put that down to falling insulin, not to any change in blood sugar.
    • In a study of 30 healthy adults, growth hormone was clearly higher after a 24 hour water-only fast than after a normal eating day. Each person did both. The size of that rise is not in the published summary, so it is not given here.
    • In the same study, haemoglobin, red blood cell count and haematocrit all rose together at 24 hours. That pattern means the fluid part of the blood shrank. It does not mean new red blood cells were made.
    • In 20 volunteers, energy burned over 24 hours, measured in a sealed room, fell during a 24 hour fast. How much it fell varied from person to person.

    Read the biologyInsulin and insulin sensitivity during a fastThe growth hormone responseKetogenesis and beta-hydroxybutyrateAutophagy

    Measured in people
    Horne 2013 had 30 seemingly healthy adults do both a 24 hour water-only fast and a normal eating day, in random order. It measured growth hormone, blood counts, cholesterol, triglycerides, bicarbonate and weight. Klein 1993 measured fat release with tracers. Hollstein 2020 measured energy burned over 24 hours in a sealed room in 20 volunteers. The exact percentage drop is not in the published summary, so it is not given here. On autophagy, a 24 hour fast raised p62 (also called SQSTM1) in the thigh muscle of 50 women. That points toward less recycling in muscle, not more.

  5. 1d to 36h

    Thyroid drops before metabolic rate does

    Burning
    Fat. The remaining sugar is built from glycerol, lactate and protein building blocks.
    Ketones
    1.308 mmol/L on average after day 1, in 13 men starting a 10 day water fast, up from 0.177 at the start. People varied a lot: the spread around that average (1.053) was nearly as big as the average itself.
    • Making new sugar supplies 82% of the body's sugar between 22 and 36 hours.
    • In 8 healthy men, the thyroid hormone T3 fell from 2.30 to 1.84 nmol/L by 30 hours. TSH, the hormone that tells the thyroid to work, fell below 1 mU/L, and its usual night-time peak disappeared. Blood cortisol did not change.
    • So the thyroid slows down within the first 30 hours, well before anyone can measure a drop in resting metabolic rate.
    • Salt loss has not turned yet. In 9 women with obesity who kept eating their usual amount of salt while fasting, salt in the urine started to rise after about 48 hours and then went above what they took in.

    Read the biologyGlycogen depletion and gluconeogenesisKetogenesis and beta-hydroxybutyrateAutophagy

    Measured in people
    Rothman 1991 measured the share of new sugar making with a special MRI scan in healthy adults. Hugues 1984 fasted 8 healthy men for 30 hours and tested their thyroid hormones again and again. Dai 2022 measured blood BHB daily in 13 men fasting in a supervised facility. Sigler 1975 collected urine in 3 hour blocks from 9 women with obesity on a hospital ward. On autophagy, the only study in people with several time points in one fast took thigh muscle samples at 2, 12, 24 and 36 hours. The markers LC3I, LC3II and p62 all fell, but only in untrained people. The authors sum it up as muscle recycling being only mildly affected by 36 hours of fasting.

  6. 36h to 2d

    Growth hormone jumps, IGF-1 does not follow

    Burning
    Fat, with ketones now carrying a real share of the load. Nearly all the body's sugar is now made fresh.
    Ketones
    A middle rise of +210% between 36 and 54 hours, in 34 adults
    • In 9 healthy men, daily growth hormone output rose from 78 to 371 micrograms per litre on the second day of a fast. That is a five-fold rise. The number of bursts went from 14 to 32 a day, and the amount per burst went from 6.3 to 11 micrograms.
    • How long growth hormone lasted in the blood did not change, at 18 against 20 minutes. So the body was truly making more, not just clearing it more slowly.
    • Blood IGF-1 had not changed at 56 hours. It does not fall until around day 5, when it dropped from 1.31 to 0.77 U/mL in 6 men.
    • From 36 hours on, making new sugar supplies 96% of the body's sugar.
    • At 48 hours, in a clamp test where insulin is dripped in, the body's sugar use fell from 39.8 to 24.1 micromol/kg/min. Sugar burned for energy crashed from 21.8 to 3.9. Sugar stored did not change. That is a change in which fuel the body burns. It is not the kind of sugar problem seen in diabetes.
    • Energy burned over 24 hours, measured in a sealed room, was 10.9% lower on day 2 of a fast than on a day of normal eating (9.8 against 11.0 MJ).

    Read the biologyThe growth hormone responseGlycogen depletion and gluconeogenesisInsulin and insulin sensitivity during a fast

    Measured in people
    Hartman 1992 took blood every 5 minutes for 24 hours in 9 healthy men, on a normal day and on the second day of a fast, and worked out the true output with maths. IGF-1 was measured at 56 hours. Ho 1988 measured IGF-1 (as somatomedin C) through a 5 day fast in 6 men. Mansell 1990 did clamp tests on 6 men without diabetes at 48 hours without food. Andriessen 2023 put 12 healthy lean men in a sealed room for 60 hours straight, once fasting and once eating. No study in people has measured autophagy in any tissue between 36 and 72 hours. That is why autophagy is not linked from this row.

  7. 2d to 3d

    Ketones reach the brain

    Burning
    Fat and ketones. The brain now gets a measurable share of its fuel from BHB.
    Blood sugar
    4.14 mmol/L (74.6 mg/dL) at 72 hours in 6 healthy men, about 25% below the 12 hour value
    Ketones
    74% of people whose test fast came back clear went above 2.7 mmol/L before the 72 hour mark. The middle rise from 54 to 72 hours was +167%.
    Insulin
    30.1 pmol/L (4.3 microunits/mL) at 72 hours, about half the 12 hour value
    • Brain BHB was measured directly with a strong MRI scanner aimed at the back of the brain. It rose from 0.05 mmol/L before fasting to 0.60 after the second day and 0.98 after the third. Brain lactate rose from 0.69 to 1.47 mmol/L.
    • Blood and brain BHB rose closely together. The brain level rose about 0.26 times as much as the blood level did.
    • Over a 48 hour fast, fat built up in the livers of men and in the muscles of women. Sugar handling and fuel burning, in the whole body and the liver, were the same in both sexes.
    • The two ways of measuring energy burned split apart here, and both are real. Resting energy burned, measured with a hood, rose 14.1% by day 3 in 11 lean people. Energy burned over the whole day, measured in a sealed room, was still 5.5% below a normal eating day on day 3 (10.3 against 10.9 MJ). The resting part can rise while the whole day falls.
    • The 72 hour supervised fast is a routine hospital test that doctors have used for decades to check hormone problems. That is the strongest evidence there is that healthy people handle this length of fast when they are being watched.

    Read the biologyKetogenesis and beta-hydroxybutyrateInsulin and insulin sensitivity during a fast

    Measured in people
    Klein 1993 sampled 6 healthy men at 12, 18, 24, 30, 42, 54 and 72 hours, using tracers and breath gas tests. Service 2005 measured BHB every 6 hours in 34 adults. Pan 2000 measured brain BHB and lactate with MRI scans in healthy adults. Browning 2012 measured liver and muscle fat with scans across 48 hours in healthy men and women. Zauner 2000 measured resting energy burned with a hood in 11 lean people. Andriessen 2023 measured energy burned over 24 hours in a sealed room in 12 lean men. The two are measuring different things. They do not contradict each other.

  8. 3d onward

    Adapted, and the risk moves to eating again

    Burning
    Fat and ketones. As the fast gets longer, sugar making is split between the liver and the kidneys.
    Blood sugar
    3.5 mmol/L (63.1 mg/dL) on day 4 in 11 lean adults, and 3.2 mmol/L (57.7 mg/dL) on day 5 in 6 men
    Ketones
    Ketone making starts to level off after about 5 days. Across a 21 day fast in 13 volunteers, blood ketones went from 0.1 to 6.61 mmol/L.
    Insulin
    Levels off by day 3 in people with obesity fasting for weeks. Glucagon, which raises blood sugar, about doubles and peaks on the same day.
    • In 8 healthy men at 72 hours, muscle samples showed mTOR activity down about 50% and the recycling marker LC3B-II up about 30%. p62 rose about 10% in the same samples. The authors say that makes the real speed of recycling impossible to read from these markers alone.
    • 12 healthy adults wore sugar monitors through a 7 day water-only fast. By day 5, their time spent below 70 mg/dL rose from 3% to 66%, and their lowest daily sugar fell from 76 to 50 mg/dL. None of them reported symptoms of low blood sugar. So checking how you feel stops working as a safety check at this point.
    • In 15 patients with obesity, blood uric acid about doubled by day 7, from 5.9 to 12.5 mg/dL. It then fell back to 7.7 by day 28, while ketosis carried on. The kidneys cleared uric acid less well, more so than they cleared other waste. So this is a specific change in how the kidneys handle uric acid.
    • In 13 volunteers, resting energy burned fell 20.3% across a 21 day complete fast. This is where the slowdown in metabolism finally shows up.
    • Nitrogen in the urine, a sign of protein loss, falls steadily for about 4 weeks and then holds at about 3 to 6 g a day. How much protein is lost per kilogram of weight lost depends on body fat. It is roughly 20 g of nitrogen per kg in people without obesity, and roughly 10 g per kg in people carrying 50 kg or more of fat.
    • The body runs hundreds of milligrams a day short on minerals, while blood phosphorus and magnesium stay the same. That gap is why the deaths in the medical case reports cluster in the period of eating again, not during the fast.

    Read the biologyKetogenesis and beta-hydroxybutyrateAutophagyRefeeding, the leucine threshold and refeeding syndrome

    Measured in people
    Vendelbo 2014 took muscle samples from 8 healthy men after 72 hours, with tracer tests in the forearm. Kolnes 2026 monitored 12 healthy adults around the clock through a 7 day water-only fast. Fox 1976 measured blood uric acid and how well the kidneys cleared it through 28 days in 15 patients with obesity. Dai 2024 measured resting energy burned and blood ketones across a 21 day fast in 13 volunteers. Owen 1969 measured nitrogen in the urine in 11 people with obesity through 5 to 6 weeks. Forbes 1979 worked out how nitrogen loss scales with body fat. Licata 1981 measured mineral balance directly over 40 days on a hospital ward. On average, people ran 104 mg of calcium, 48 mg of magnesium and 363 mg of phosphorus a day short, while blood phosphorus and magnesium did not change at all.

What studies in people found

There is one study of 100 people who tried the diet and normal eating, over three monthly rounds. There is one exploratory second look that pooled two studies. There is one multi-centre breast cancer study that missed both of its main goals, one early safety and immune study in 101 patients, and one company-funded autophagy pilot.

  • DIRECT (de Groot 2020), 129 women with HER2-negative stage II or III breast cancer, across 11 Dutch centres. The people judging results did not know who was in which group. The study missed both of its main goals. Severe side effects hit 75.4% on the diet against 65.6% without it, which was not a real difference. The cancer was fully gone at surgery in 10.8% on the diet against 12.7% without it. The planned larger follow-up study was dropped on the advice of the study's safety board.
  • DIRECT's positive results come from its side questions. On scans, the tumour shrank or vanished more often on the diet, counting everyone. Among patients who stuck to the plan, more tumour cells were killed. But the cancer being fully gone at surgery still did not differ: 13.6% against 12.1%. Only 22 of 65 on the diet used it for four or more rounds.
  • Vernieri 2022, 101 patients with different cancers doing 5-day rounds alongside normal treatment. This was an early safety study. The diet was safe and doable. Blood sugar and growth factors fell every time. Immune cells that hold back the immune system shrank, and immune attack on the tumour got stronger. It did not test whether the diet helped treat cancer.
  • Wei 2017, 100 people at a US university between 2013 and 2015, who each did the diet and normal eating at different times, in three monthly 5-day rounds. Compared with normal eating: weight fell 2.6 kg, total and trunk body fat fell clearly more, waist fell 4.1 cm, the top blood pressure number fell 4.5 mmHg, and IGF-1 fell 21.7 ng/mL. Fasting blood sugar, blood fats, total cholesterol, LDL, HDL and CRP did not differ. 71 of 100 finished all three rounds. Nothing worse than moderate side effects.
  • After-the-fact looks at smaller groups in the same paper, among the 71 who finished, labelled that way by the authors. The top blood pressure number fell 6.7 mmHg in people who started above 120, against 2.4 in those at or below it. Fasting blood sugar fell 11.8 mg/dL in people who started above 99 mg/dL, and did not change in others. IGF-1 fell 55.1 ng/mL in people who started above 225, against 14.1 in others. LDL fell 14.9 mg/dL in people with total cholesterol above 199, and did not fall in people in the normal range. CRP fell 1.6 mg/L in people who started above 1 mg/L, and did not fall in people below it.
  • Brandhorst 2024, a second, exploratory look at the same study plus a separate second study. It is not a new study that assigned people to groups. "Biological age", estimated from seven blood test results, fell by a typical 2.5 years after three rounds, in 52 people. In 19 people in the comparison group, it rose 0.78 years, which was not clear. Pooling 86 people, it fell a typical 2.6 years, and that held after allowing for weight loss. 16 of 52 and 8 of 34 people saw their biological age go up, not down.
  • Espinoza 2025, a small early study of 30 people on an 8-day version. It measured how fast clean-up ran in white blood cells, using chloroquine. It found a difference between groups from the start to day 6, and says the differences were not clear across all time points. It was paid for by L-Nutra Inc.

What this does not tell you: The 100-person study was 5 days a month for 3 months. It looked at blood tests and body measures, not health outcomes. Its most quoted results come from after-the-fact looks at smaller groups among those who finished, not from the main comparison. The biological age paper was an exploratory second look, and its most quotable numbers rest on tiny groups: insulin resistance in 11 people, long-term blood sugar in 3, fatty liver in 5, and MRI scans in 15. Its life expectancy and death figures come from computer models using population data, assuming one round a year up to age 70, and the paper says so. DIRECT missed both main goals, and two thirds of its diet group did not finish four rounds. No study has run the diet for more than a few monthly rounds or tracked real health outcomes.

Reading the research record

Three things are regularly misreported about this diet, and all three can be checked.

The first is what the main comparison showed. Saying the study showed the diet lowers blood sugar, CRP and LDL is wrong. In the main comparison, those three did not differ from normal eating. The results people quote come from after-the-fact looks at smaller groups among those who finished, limited to people whose starting levels were already outside the normal range. The paper labels them that way. That does not make them meaningless. It makes them ideas worth testing, not the study's finding.

The second is the cancer evidence. DIRECT is the multi-centre study that assigned patients to groups, and it missed both of its main goals. The cancer was fully gone at surgery in 10.8% on the diet and 12.7% without it. A commentary from another fasting-mimicking research group describes DIRECT as having overall negative results because it missed its main goals. Three of those authors disclose that they invented a rival diet. DIRECT's positive findings are side questions: tumour response on scans counting everyone, and tumour cell kill among patients who stuck to the plan. And only 22 of 65 patients on the diet finished four or more rounds.

The third is a paper that does not exist. There is no New England Journal of Medicine paper by Valter Longo on the fasting-mimicking diet or on long fasting. Searching that journal for him as an author finds nothing. So do searches of the journal for "fasting mimicking" and for "prolonged fasting". The New England Journal of Medicine fasting paper often wrongly credited to him is a 2019 review by de Cabo and Mattson. He is not an author, and it is a review, not a study.

The business ties, stated as documented fact from the journals' own conflict-of-interest sections. The study diet was supplied by L-Nutra Inc. The University of Southern California has licensed ideas under study here to L-Nutra, and may receive royalty payments. Two of the authors, including Valter Longo, own a stake in L-Nutra and did not take part in collecting or analysing the data. All of Longo's stake is assigned to a nonprofit foundation. Longo founded L-Nutra, which sells the commercial version of the diet. The size of the stake is not published in any journal disclosure, regulatory filing or university statement, so no percentage appears here. The same ties are disclosed in the DIRECT study and its quality-of-life companion paper, where one more author holds shares in a company that invested in L-Nutra.

What happens to muscle

This is one of the few plans on this site where body make-up was a main result, not an afterthought. The diet beat normal eating on fat, not just total weight. Total body fat and trunk fat fell clearly more than in the comparison group, and waist size fell 4.1 cm.

A separate lean mass number from that comparison is not in the part of the paper we could read, so none is printed here. That gap matters, because the fat result cannot tell you what happened to lean mass. Lean mass means the non-fat part of you, mostly muscle and water.

The closest answer on lean mass for a five-day low-protein plan comes from other studies, not this one. In 16 men on a 10-day fast at 200 to 250 calories a day, scan lean mass fell 3.53 kg. But 44% of that was water outside the cells, 14% was stored sugar with its water, and only 42% was working lean tissue. In 20 middle-aged people fasting about 9.8 days on average and then eating again, protein tests pointed to muscle and bone being kept. Neither is this diet, and both are longer.

The protein math is worth saying plainly, because protein is the one part of the design that is low on purpose. At 9% to 11% of roughly 720 to 1,100 calories, the diet gives far less protein than the 1.6 to 2.2 g per kg of body weight a day used in every short-window study that kept lean mass. The one short-window study run at 1.0 g per kg a day lost more lean mass than its comparison group, even though daily muscle building was the same in both. Low protein is what the diet is built around. It is also the thing most tied to lean mass loss elsewhere in this research.

Doing it

It is not a fast and its data do not transfer
Roughly 1,100 calories on day 1 and roughly 717 on days 2 to 5, with 43% to 47% of calories from carbs. Nothing measured on this diet can be applied to a water fast, and nothing measured on a water fast can be applied to it. The two give different ketone levels, different blood sugar and different salt handling.
What the main study actually changed
Weight, BMI, total and trunk fat, waist, the top blood pressure number and IGF-1. Fasting blood sugar, blood fats, total cholesterol, LDL, HDL and CRP did not differ from normal eating. If you pick this diet for a cholesterol or inflammation result, you are picking it on an after-the-fact look at a small group, not on what the study found.
Expect the dropout rate to apply to you too
25% quit the diet group before the swap, and another 26% quit after switching to it. In the cancer study, only 22 of 65 used it for four or more rounds, mainly because they disliked the food. This is the plan on this site that people finish least often.
Protein is deliberately low, and that is the trade
9% to 11% of a small calorie intake for five days. The studies that kept lean mass anywhere in this research used 1.6 to 2.2 g of protein per kg of body weight a day, with weight training. If keeping lean mass is your priority, this diet is built against it.
Medication review still applies
700 calories a day with carbs is not a fast, but it is a big cut in food. The same drugs behave differently against it: insulin, sulfonylureas, meglitinides, SGLT2 inhibitors, ACE inhibitors, ARBs and water pills. The published drug guide for intermittent fasting is the place to start that talk with your prescriber.
The business ties are disclosed, and they are a fact, not a verdict
The diet in the studies was supplied by L-Nutra Inc. The university has licensed ideas to the company and may receive royalties. Two authors own a stake and did not take part in collecting or analysing the data. The size of the stake is not published anywhere we could check, so no figure is given here.

Breaking the fast

The five-day plan ends by going back to normal eating. The studies did not set any schedule for easing back in. That is a real gap in the research, not proof that no schedule is needed. The risk rules say this diet sits below every formal refeeding line for a well-fed person. The US nutrition society (ASPEN) counts no food or almost none for 5 to 6 days as one of two signs of medium risk, and more than 7 days as a high-risk sign on its own. 700 calories a day with carbs is not almost no food. The UK NICE lines are little or no food for more than 5 days as one of two warning signs, and more than 10 days as enough on its own. The reason behind those lines still applies on a small scale and is worth knowing. When you cut calories, the body runs low on phosphate, potassium and magnesium while blood tests look normal. When you eat carbs again, insulin rises and pushes all three into the cells at once. In the clearest study in people, during a 40-day fast with added protein, people lost 104 mg of calcium, 48 mg of magnesium and 363 mg of phosphorus a day on average, while blood phosphorus and magnesium did not change at all. The real way this goes wrong after five days at 700 calories is behaviour, not blood chemistry. People overeat on the first normal day. That is the most common way people undo the calorie cut they built.

Sources

  1. Study in people2017
    Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease

    Science Translational Medicine

    100 people at a US university did three monthly 5-day cycles of a low-calorie diet, about 1,100 calories on day 1 and 717 on days 2 to 5, or ate as usual. The diet group lost 2.6 kg against a 0.1 kg gain, and waist, belly fat, blood pressure and IGF-1 fell, while blood sugar, cholesterol and blood fats did not change. 71 of 100 finished all three cycles. L-Nutra supplied the diet, the university may earn royalties from it, and two authors own shares.

    100 randomised at a US university, three monthly 5-day cycles of approximately 1,100 kcal on day 1 and approximately 717 kcal on days 2 to 5. Randomised comparison against control: weight -2.6 ± 2.5 against +0.1 ± 2.1 kg (p < 0.0001), total body fat -1,393 ± 1,786 against -44 ± 1,365 (p = 0.0002), trunk fat -636 ± 1,198 (p = 0.018), waist -4.1 ± 5.2 cm (p = 0.0035), systolic blood pressure -4.5 ± 6.0 mmHg (p = 0.023) and IGF-1 -21.7 ± 46.2 ng/mL (p = 0.0017). Fasting glucose (p = 0.27), triglycerides (p = 0.27), total cholesterol (p = 0.81), LDL (p = 0.50), HDL (p = 0.90) and CRP (p = 0.27) did not differ. Dropout 25% in the diet arm against 10% in control; 71 of 100 completed all three cycles. No adverse event above grade 2. The diet was provided by L-Nutra Inc, the university has licensed intellectual property to the company with royalty potential, and two authors hold equity and did not participate in data collection or analysis.

  2. Study in people2024
    Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk

    Nature Communications

    A second look at the 2017 study plus a separate second study, not a new trial. A biological age estimate from seven blood tests fell about 2.5 years after three diet cycles in 52 people, while the comparison group's did not clearly change. But 16 of 52 and 8 of 34 dieters saw their estimated age go up, and several headline results rest on just 3 to 15 people. The life expectancy figures are computer models, as the paper says.

    A secondary and exploratory analysis of the 2017 trial plus an independent second trial, not a new randomised trial. Biological age, estimated from seven clinical-chemistry biomarkers, fell a median of about 2.5 years after three cycles (n = 52, p = 0.0007) while controls showed a non-significant increase of 0.78 years (n = 19, p = 0.76); pooled median -2.6 years (n = 86), still significant after weight adjustment (p = 0.029). 16 of 52 and 8 of 34 diet participants had an increase in biological age. The most quotable secondary results rest on very small samples: HOMA-IR n = 11, HbA1c n = 3, hepatic steatosis n = 5, imaging n = 15. The life expectancy and mortality figures are model simulations assuming annual cycles to age 70, which the paper states.

  3. Study in people2020
    Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial

    Nature Communications

    129 patients with breast cancer at 11 Dutch centres tried a 4-day plant-based diet before each chemo cycle. It missed both main goals: severe side effects (75.4% against 65.6%) and full tumour clearance (10.8% against 12.7%) did not clearly differ. Tumours did shrink more on scans and under the microscope, but those were side questions. Only 20.0% stuck to the diet through every cycle, mostly because they disliked the food, and a larger final-stage study was dropped on safety board advice.

    129 analysed across 11 Dutch centres, HER2-negative stage II/III breast cancer, a 4-day plant-based low-amino-acid diet before each chemotherapy cycle. Both primary endpoints were missed: grade III/IV toxicity 75.4% against 65.6%, not significantly different, and pathological complete response 10.8% against 12.7%, odds ratio 0.830 (95% CI 0.282 to 2.442, p = 0.735). Secondary endpoints were positive: radiological complete or partial response in the intention-to-treat population, multivariate odds ratio 3.168 (95% CI 1.062 to 9.446, p = 0.039), and Miller and Payne 4/5 per protocol, multivariate odds ratio 4.109 (95% CI 1.297 to 13.02, p = 0.016). Only 22 of 65 (33.8%) used the diet for four or more cycles and 20.0% complied during all cycles, with dislike of the components the main reason for stopping. The phase III component was abandoned on data safety monitoring board advice.

  4. Review of studies2020
    Fasting-mimicking diet plus chemotherapy in breast cancer treatment

    Nature Communications

    A comment on the DIRECT breast cancer study from a different fasting-mimicking research group. It calls the overall results negative because the main goals were missed, and asks for better-designed studies. Three of its authors invented their own fasting-mimicking diet.

    A commentary on DIRECT from a separate fasting-mimicking research group, describing the trial as having overall negative study results because the primary endpoints were not met, and calling for better trial design. Three of its authors disclose that they are themselves inventors of a fasting-mimicking regimen.

  5. Study in people2022
    Fasting-Mimicking Diet Is Safe and Reshapes Metabolism and Antitumor Immunity in Patients with Cancer

    Cancer Discovery

    101 patients with different cancers did 5-day fasting-mimicking cycles alongside their usual treatment. It was safe and doable in this early study. Blood sugar and growth factors fell, immune cells that hold back the attack on tumours shrank, and the immune attack inside tumours got stronger. The study did not test whether it helped treat the cancer.

    101 patients with mixed tumour types on cyclic 5-day fasting-mimicking cycles alongside standard therapy. Phase Ib: safe and feasible, with consistent falls in blood glucose and growth factors, contraction of immunosuppressive myeloid and regulatory T cell compartments, and enhanced intratumour Th1 and cytotoxic responses. There is no efficacy endpoint in this trial.

  6. Study in people2025
    Effect of fasting-mimicking diet on markers of autophagy and metabolic health in human subjects

    GeroScience

    A small trial run in 30 people measured cell clean-up (autophagy) in blood cells across an 8-day fasting-mimicking diet. There was a difference between groups from the start to day 6, but not at every time point. It was paid for by L-Nutra.

    A pilot in 30 subjects measuring autophagic flux in peripheral blood mononuclear cells with chloroquine across an 8-day fasting-mimicking diet. A between-group difference was found for the baseline to day 6 comparison, and the paper states that differences were not significant across all time points. Sponsored by L-Nutra Inc.

  7. Review of studies2019
    Effects of Intermittent Fasting on Health, Aging, and Disease

    New England Journal of Medicine

    This is the real fasting paper in the New England Journal of Medicine, and it is a review, not a trial. It is here because fasting-mimicking diet claims often cite a paper in that journal that does not exist. This one is by de Cabo and Mattson, and Valter Longo is not an author.

    The actual New England Journal of Medicine fasting paper, and a review rather than a trial. It is included here because the fasting-mimicking literature is frequently credited with a paper in this journal that does not exist: searches for Valter Longo as an author in the journal, and of the journal for fasting mimicking and for prolonged fasting, return nothing. This paper is by de Cabo and Mattson, and Longo is not an author.

  8. Study in people1988
    Fasting enhances growth hormone secretion and amplifies the complex rhythms of growth hormone secretion in man

    Journal of Clinical Investigation

    6 healthy men were tested on a normal day and on days 1 and 5 of a 5-day fast. IGF-1, a growth signal, fell roughly 41% by day 5, while a separate 2-day fast study found no change at 56 hours. Blood sugar fell from 4.9 to 3.2 mmol/L and fat in the blood rose. It shows that lowering IGF-1 takes several days of fasting.

    6 normal adult men across a control fed day and days 1 and 5 of a 5 day fast. Somatomedin C, which is IGF-1, fell from 1.31 ± 0.22 to 0.77 ± 0.18 U/mL by day 5, roughly 41%, against no change at 56 hours in a separate 2 day fasting study. Glucose fell from 4.9 ± 0.2 to 3.2 ± 0.2 mmol/L (88.3 to 57.7 mg/dL) and free fatty acids rose from 0.43 ± 0.12 to 1.55 ± 0.35 mmol/L. Included here because it establishes that IGF-1 suppression is a multi-day effect, which is the timescale this protocol targets.

  9. Study in people2021
    Quality of life and illness perceptions in patients with breast cancer using a fasting mimicking diet as an adjunct to neoadjuvant chemotherapy in the phase 2 DIRECT (BOOG 2013-14) trial

    Breast Cancer Research and Treatment

    Quality of life results from the DIRECT breast cancer study, in the same patients. Patients who stuck to the diet said they felt better emotionally, physically and socially, and had less tiredness, nausea and poor sleep. This counted only the patients who stuck to the diet. The same L-Nutra share ties apply, plus one author owns shares in a company that invested in L-Nutra.

    The quality-of-life and illness-perception secondary paper from the DIRECT trial, in the same patients. In the per-protocol analysis, diet-adherent patients reported better emotional, physical, role, cognitive and social functioning and less fatigue, nausea and insomnia. The same L-Nutra equity disclosure applies, with one further author holding shares in a company that invested in L-Nutra.

What people report

These are things people say about their own fasting. Nobody checked them, so they are not evidence. They are here because they tell you what to expect and what to watch for, which the studies do not. They cannot tell you whether anything works.

  • Tiredness, weakness and headaches. These were also the most common graded side effects in the study.
  • Disliking the specific foods. That was the main reason people gave for stopping in the cancer study.
  • Finding a low-calorie plan harder to keep than a full fast, because eating a little keeps your appetite switched on.
  • Hunger through the first two days, then easing. That is the same pattern people describe on water fasts.

Sources: These are self-reports with no comparison group, except where noted. Tiredness, weakness and headaches were graded side effects in the main study, where 54% to 100% of people reported none depending on the side effect, and nothing was worse than moderate. Disliking the food is the reason recorded in the cancer study's own look at who stuck with it, where only 22 of 65 patients used the diet for four or more rounds.

Who this is wrong for

  • Anyone taking an SGLT2 inhibitor, unless a prescriber manages it first. Cutting carbs while the drug keeps pushing sugar out in the urine is the same thing that causes ketoacidosis (a dangerous acid build-up while blood sugar looks normal) on a true fast. The first published case of this during Ramadan-style calorie cutting is on record.
  • Anyone on insulin, a sulfonylurea or a meglitinide, unless a prescriber changes the dose for a 700-calorie day.
  • Anyone with type 1 diabetes outside a set program with glucose monitoring.
  • Pregnancy and breastfeeding. Neither has been studied on this diet, and making milk alone pulls about 30 to 50 g of sugar a day out of the mother.
  • Anyone with a past eating disorder, or who now has episodes of eating they cannot control. A five-day set-food plan repeated every month is a food rule with a score attached.
  • Children and teens. No fasting plan has long-term studies on growth or development.
  • Anyone with a BMI under 18.5, or who already meets the UK NICE risk list for refeeding problems.
  • Anyone with cancer thinking of doing this alongside treatment outside a study. The main study missed both of its goals. Its positive results are side questions, in a study where two thirds of the diet group did not finish four rounds. The planned larger follow-up was dropped on the safety board's advice.
  • Anyone whose priority is keeping lean mass, since the diet gives only 9% to 11% of a small calorie intake as protein for five days in a row.
  • Anyone with chronic kidney disease on an ACE inhibitor, ARB or water pill, or with primary adrenal insufficiency, for the same reasons that apply to a true fast.

Questions

Did the trial show the diet lowers glucose, cholesterol and inflammation?
Not in the main comparison. Fasting blood sugar, blood fats, total cholesterol, LDL, HDL and CRP did not differ from normal eating. The numbers people quote for blood sugar, CRP and LDL come from after-the-fact looks at people who finished and whose starting levels were already outside the normal range. The paper labels them that way. What did beat normal eating was weight, BMI, body fat, trunk fat, waist, the top blood pressure number and IGF-1.
Is there a New England Journal of Medicine paper behind this diet?
No. There is no paper by Valter Longo in that journal on the fasting-mimicking diet or on long fasting. The New England Journal of Medicine fasting paper usually wrongly credited to him is a 2019 review by de Cabo and Mattson. He is not an author.
What is the commercial relationship?
Here it is as the journals state it. The study diet was supplied by L-Nutra Inc. The University of Southern California has licensed ideas under study here to L-Nutra, and may receive royalty payments. Two of the authors, including Valter Longo, own a stake in L-Nutra and did not take part in collecting or analysing the data. All (100%) of Longo's stake is assigned to a nonprofit foundation. Longo founded L-Nutra, which sells the commercial version. The size of the stake is not published in any journal disclosure, regulatory filing or university statement, so no figure appears here.
Did it work alongside chemotherapy?
The multi-centre study that tested it missed both of its main goals. Severe side effects hit 75.4% on the diet against 65.6% without it, which was not a real difference. The cancer was fully gone at surgery in 10.8% against 12.7%. Its positive results are side questions: tumour response on scans counting everyone, and tumour cell kill among patients who stuck to the plan. Only 22 of 65 patients on the diet finished four or more rounds. The planned larger follow-up study was dropped on the safety board's advice.
Does it trigger autophagy?
The only measurement is a small early study of 30 people on an 8-day version. It measured how fast clean-up ran in white blood cells, using chloroquine. It found a difference between groups from the start to day 6, and says the differences were not clear across all time points. It was paid for by the company that makes the diet. That is not enough for this page to list autophagy as something the diet reaches.