Five Days a Month on 720 Calories: What the Fasting-Mimicking Diet Trials Actually Show
Water-only fasting for several days does things to the body that ordinary dieting does not. Insulin-like growth factor 1 falls, ketone production climbs, and in mice, cells that survive the fast rebuild tissue when food returns. The problem is that almost nobody will go five days on water, and many people should not try. In 2015 Valter Longo's group at the University of Southern California published a mouse study of a low-protein, low-sugar, plant-based diet that delivers roughly a third to half of normal calories and appeared to trigger many of the same fasting signals. That diet became a commercial product, ProLon, sold by a company Longo co-founded called L-Nutra. Since then it has been tested in a 100-person randomized trial, a year-long trial in type 2 diabetes, a breast cancer trial and a 2024 reanalysis that reported people came out 2.5 years biologically younger. This article walks through what each study measured, where the effects were real, where they were small, and what a man over 40 should weigh before spending five days a month on soup.
Key Takeaways: What the Research Shows About the Fasting-Mimicking Diet
The fasting-mimicking diet is a 5-day plan supplying about 1,100 kcal on day 1 and about 720 kcal on days 2 to 5, low in protein and sugar and high in unsaturated fat, repeated once a month. In the randomized phase of the Wei 2017 trial in Science Translational Medicine, three monthly cycles reduced body weight by 2.6 kg, waist by 4.1 cm, systolic blood pressure by 4.5 mmHg and IGF-1 by 21.7 ng/mL compared with a normal diet. Fasting glucose, cholesterol, triglycerides and C-reactive protein did not differ between groups in that randomized phase; improvements in those markers appeared only in a post hoc analysis of participants who started with out-of-range values. A 2024 Nature Communications reanalysis of blood from two trials reported that three cycles lowered median biological age by 2.5 years, independent of weight loss, using a blood-chemistry method from the Levine group. In the 12-month FIT trial in type 2 diabetes, monthly cycles alongside usual care improved glycaemic management in 53 percent of participants against 8 percent on usual care, while lowering weight by 3.6 kg and HbA1c by 3.2 mmol/mol. No human study of the fasting-mimicking diet has measured lifespan or mortality, and every major trial involved the developer or manufacturer through supply, funding or licensing.
Five Days at Roughly 30 to 45 Percent of Normal Intake
Approximate daily calories. In the Wei 2017 trial, day 1 of the fasting-mimicking diet supplied about 4,600 kJ (roughly 1,100 kcal; 11% protein, 46% fat, 43% carbohydrate) and days 2 to 5 about 3,000 kJ each (roughly 720 kcal; 9% protein, 44% fat, 47% carbohydrate). The 2,500 kcal bar is an illustrative maintenance intake for an adult man, not a trial value.
What is a fasting-mimicking diet?
A fasting-mimicking diet is a short, very low calorie eating plan designed to produce the metabolic signals of a water-only fast while still supplying food and micronutrients. The version tested in human trials lasts five days. Day 1 provides about 4,600 kilojoules, roughly 1,100 kcal, split into 11 percent protein, 46 percent fat and 43 percent carbohydrate. Days 2 through 5 provide about 3,000 kilojoules, roughly 720 kcal, at 9 percent protein, 44 percent fat and 47 percent carbohydrate. The food comes as vegetable soups, nut-based bars, olive-based snacks, herbal teas, a glycerol drink and a vitamin supplement. The design logic is specific. Protein, and particular amino acids, drive IGF-1 and the mTOR growth pathway, so protein is kept very low. Sugar drives insulin, so simple carbohydrate is kept low. Fat is allowed because it supports ketone production without strongly activating those growth signals. After five days the person returns to normal eating for about 25 days, and the cycle repeats. The diet is not a way of eating less over the month; the Wei trial authors estimated that participants on the monthly cycle and controls consumed broadly similar total calories across a month.
What did the fasting-mimicking diet do in mice?
In mice, cycles of a fasting-mimicking diet started in middle age extended lifespan and reduced several markers of aging. Brandhorst and colleagues reported in Cell Metabolism in 2015 that C57BL/6 mice fed a 4-day fasting-mimicking diet twice a month from 16 months of age lived longer on average than mice on a standard diet, with a median lifespan gain of about 11 percent. The same mice had less visceral fat, fewer and later tumors, fewer skin lesions, slower loss of bone mineral density and a more youthful immune cell profile. In older mice, the diet cycles increased the birth of new neurons in the hippocampus and improved performance on memory and motor coordination tests. During each fasting phase, organs such as the liver and kidney shrank measurably, and after refeeding the tissue regrew with a rise in progenitor and stem cells. Longo's group interprets that shrink-and-rebuild pattern as the core mechanism. The mouse result is a single laboratory's study in a single inbred strain. The National Institute on Aging Interventions Testing Program, which replicates longevity interventions in genetically mixed mice at three sites, has not tested the fasting-mimicking diet, so the lifespan finding has not been independently reproduced.
What did the 100-person randomized trial find?
The Wei 2017 trial found that three monthly fasting-mimicking cycles modestly lowered body weight, waist size, blood pressure and IGF-1 in generally healthy adults compared with eating normally. Min Wei, Sebastian Brandhorst and colleagues randomized 100 people aged 20 to 70 in the United States, 37 of them men, to either three months of their usual diet or three monthly five-day cycles. Measurements were taken 5 to 7 days after the third cycle, once participants had been back on normal food. In the randomized comparison, the diet group lost 2.6 kg while controls gained 0.1 kg. Waist circumference fell 4.1 cm, systolic blood pressure 4.5 mmHg and diastolic 3.1 mmHg, and IGF-1 dropped 21.7 ng/mL while it rose 8.7 ng/mL in controls. Total body fat and trunk fat fell. Lean mass stayed stable as a share of body weight, but absolute lean mass did decline in the randomized diet arm, which matters for men trying to hold on to muscle. Several markers did not move in the randomized phase. Fasting glucose, triglycerides, total cholesterol, LDL, HDL and C-reactive protein showed no significant difference between the two groups. That point is often lost in coverage of the trial.
The Randomized Result: Three Cycles Against Three Months of Normal Eating
Mean change from baseline in the randomized phase of Wei and colleagues, Science Translational Medicine 2017, measured 5 to 7 days after the third cycle. IGF-1 is shown divided by 10 to fit the scale (actual: minus 21.7 ng/mL on the diet, plus 8.7 ng/mL on control). Fasting glucose, triglycerides, cholesterol and CRP did not differ significantly between groups in this phase.
- Fasting-mimicking diet (n up to 39)
- Normal diet (n up to 43)
Who benefited most from fasting-mimicking cycles?
People who started with worse numbers improved the most, according to a post hoc analysis of the 71 participants who completed three cycles in either arm of the Wei trial. In participants with fasting glucose above 99 mg/dL, glucose fell by 11.8 mg/dL, bringing most of them back into the normal range, while glucose did not change in people who started below that line. IGF-1 fell by 55.1 ng/mL in those starting above 225 ng/mL, nearly four times the 14.1 ng/mL drop in those below it. C-reactive protein fell by 1.6 mg/L in people starting above 1 mg/L and did not change in those below it. In the roughly 50 people who came back for an optional visit about three months after their last cycle, the reductions in weight, waist size, IGF-1 and diastolic blood pressure were still present, as were the glucose and systolic pressure changes in the at-risk subgroups. The at-risk analysis carries two caveats that the authors acknowledged. It was done after the fact rather than planned, and some at-risk subgroups contained only a handful of people. People with high starting values also tend to drift back toward average on retesting regardless of treatment. The finding is a reasonable hypothesis for larger trials, not an established effect.
Bigger Changes in People Who Started Out of Range
Post hoc analysis of the 71 completers in Wei 2017. At-risk cut-offs: IGF-1 above 225 ng/mL, fasting glucose above 99 mg/dL, diastolic pressure above 80 mmHg, CRP above 1 mg/L. IGF-1 is shown divided by 10 (actual: minus 55.1 against minus 14.1 ng/mL). Glucose and CRP did not change in the normal-range groups. Several at-risk subgroups were small and the analysis was not prespecified.
- At-risk at baseline
- Normal range at baseline
Does the fasting-mimicking diet lower biological age?
A 2024 reanalysis reported that three fasting-mimicking cycles lowered median biological age by 2.5 years, but the estimate comes from a blood-chemistry formula rather than a direct measure of aging. Brandhorst and colleagues published the analysis in Nature Communications in February 2024 using stored blood from the Wei trial and a second clinical study. Biological age was estimated with a method from Morgan Levine's group that combines routine blood markers such as glucose, albumin, creatinine, C-reactive protein and white cell counts into a score that predicts illness and death in population data. The same paper reported lower insulin resistance and HbA1c, less liver fat on MRI and a higher ratio of lymphoid to myeloid immune cells, which tends to fall with age. The authors reported that the biological age reduction held after accounting for weight loss, and that the second study produced nearly identical results. A blood-marker age score is a useful summary, but it moves whenever its inputs move. A diet that lowers glucose, CRP and insulin will lower the score by construction, whether or not it changes the pace of aging in any deeper sense. The paper was described by its authors as a secondary and exploratory analysis. No one has yet shown that a reduction in this score from fasting-mimicking cycles translates into fewer diagnoses or longer life.
What happened in the year-long diabetes trial?
In the FIT trial, adding a monthly fasting-mimicking cycle to normal primary care for 12 months let people with type 2 diabetes reduce glucose-lowering medication while their HbA1c still improved. Elske van den Burg and colleagues at Leiden University Medical Center published the results in Diabetologia in 2024. They randomized 100 adults aged 18 to 75 with a BMI of 27 or higher, who used metformin alone or diet alone, to monthly five-day cycles plus usual care from their general practitioner, or usual care alone. After 12 months, the diet group had a lower medication effect score, an HbA1c 3.2 mmol/mol (0.3 percentage points) lower than controls and 3.6 kg more weight loss. When medication and HbA1c were combined into a single measure, glycaemic management improved in 53 percent of the diet group against 8 percent of controls and deteriorated in 23 percent against 59 percent. Eight diet participants and ten controls were lost to follow-up. FIT is the strongest human trial of the diet because it ran for a full year and used intention-to-treat analysis with blinded assessors. It was co-funded by L-Nutra. Medication changes were made by each participant's own doctor, and the trial excluded people on insulin or sulfonylureas, the drugs most likely to cause dangerous low blood sugar during a fast.
The Longest Trial: Twelve Monthly Cycles in Type 2 Diabetes
Share of participants whose glycaemic management improved, stayed stable or deteriorated after 12 months, combining medication use and HbA1c. FIT trial, van den Burg and colleagues, Diabetologia 2024: 100 adults on metformin only or diet alone, randomized to monthly 5-day cycles plus usual GP care (n=51) or usual care (n=49). Medication changes were made by participants' doctors.
- Monthly FMD + usual care
- Usual care
Is the fasting-mimicking diet safe for men over 40?
For generally healthy men, the trials reported mostly mild side effects, with fatigue, weakness and headache the most common and no adverse events of grade 3 or higher in the Wei trial. About a quarter of participants who started the diet dropped out before finishing three cycles, mostly for scheduling or personal reasons, and a smaller number because they disliked the food. Men on glucose-lowering drugs, especially insulin or sulfonylureas, face a real risk of hypoglycaemia on 720 kcal a day and should not attempt a cycle without their prescriber adjusting doses first. Men on blood pressure medication may find their pressure drops further during the fasting days. The diet is not suitable for anyone underweight, with a history of eating disorders, or with significant kidney or liver disease. Two male-specific points deserve attention. Short fasts suppress the reproductive axis: Cameron and colleagues reported in the Journal of Clinical Endocrinology and Metabolism in 1991 that 48 hours of fasting slowed luteinizing hormone pulses in men, and testosterone falls with it before recovering on refeeding. Whether a monthly five-day cycle affects average testosterone over the month has not been studied. Second, absolute lean mass fell in the randomized diet arm of the Wei trial, so men who lift should protect protein intake and training during the 25 non-fasting days.
Why does the diet lower IGF-1, and is that good for men?
The fasting-mimicking diet lowers IGF-1 because very low protein intake reduces the liver's production of the hormone, and the drop is deliberate. Lower IGF-1 signalling extends lifespan in worms, flies and mice, and people with Laron syndrome, a genetic insensitivity to growth hormone, have very low rates of cancer and diabetes. In the Wei trial IGF-1 fell by about 13 percent on average after three cycles, from 168.6 to 146.9 ng/mL. For men, IGF-1 has a U-shaped relationship with health in large observational studies. Very high levels track with some cancers, while low levels track with frailty, muscle loss and higher cardiovascular risk in older men. A temporary monthly dip in a man whose IGF-1 sits in the upper half of the range is a different proposition from pushing down a level that is already low. Men who are using growth hormone secretagogues or peptides aimed at raising IGF-1 should recognise that the fasting-mimicking diet pulls the same lever in the opposite direction.
How strong is the evidence overall?
The human evidence for the fasting-mimicking diet is promising on short-term risk markers and absent on hard outcomes. Across the main published trials, fewer than 400 people have been enrolled. The Wei trial randomized 100, the FIT trial 100, the DIRECT trial of women with breast cancer 131, the original pilot 19, and a 2025 GeroScience pilot of autophagy markers 30. The 2024 biological age paper reanalysed blood from existing trials. The DIRECT trial, published by de Groot and colleagues in Nature Communications in 2020, tested the diet around chemotherapy and found no difference in its primary endpoint of toxicity, though tumor response was more frequent in the diet group. It says little about healthy men but shows the diet is being studied seriously in medical settings. The conflict of interest runs through the whole literature. The University of Southern California licenses the intellectual property to L-Nutra and can receive royalties. Longo holds equity in L-Nutra, which the papers disclose along with his commitment to assign all of it to a nonprofit foundation. L-Nutra supplied the food for the trials and co-funded FIT and the 2025 autophagy pilot. None of that makes the results wrong, but independent replication is what the field lacks.
The Whole Human Evidence Base Fits in a Lecture Hall
Participants enrolled in the main published human trials of the commercial fasting-mimicking diet. The 2024 biological age paper reanalysed blood from the Wei trial and a second trial rather than enrolling a new cohort. None of these studies measured mortality, and every one involved the diet's developer or its manufacturer, L-Nutra, through supply, funding or licensing.
What should a man take from the fasting-mimicking diet research?
A healthy man can reasonably expect three monthly fasting-mimicking cycles to take off 2 to 3 kg, shave a few points off blood pressure and lower IGF-1 temporarily, with larger changes if his glucose, CRP or IGF-1 start high. He should not expect a measurable change in cholesterol if his numbers are already normal, and he should treat the 2.5-year biological age figure as a change in blood markers rather than proof of slower aging. Cost is a practical factor. The FIT trial costed twelve monthly cycles at about 2,043 euros per participant for the year, roughly 170 euros per box. Some people build their own low-protein, plant-based five-day plan to match the published macronutrients, but those homemade versions have not been tested in trials. Men with prediabetes, a thick waist or high CRP are the group the data most favour. Men on diabetes or blood pressure drugs should involve their doctor before the first cycle, and men focused on muscle should keep protein and resistance training high between cycles. The research case is real, still early and still funded largely by the company that sells the product.
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