Fasting-mimicking diet

What it is

A five-day, plant-based, low-calorie, low-protein, higher-unsaturated-fat meal plan eaten once a month, with normal eating in between. It is designed to mimic some effects of fasting while still supplying food; the version studied is a commercial kit made by L-Nutra (sold as ProLon).

What the research says

Evidence is limited and closely tied to the product's maker. In a 100-person randomised trial, three monthly cycles reduced weight (2.6 kg), body fat, blood pressure and IGF-1 compared with an unrestricted diet, but markers already in the normal range did not change significantly, absolute lean mass also fell, and the at-risk benefits came from a non-randomised post hoc analysis. In type 2 diabetes managed with metformin or diet, a 12-month trial found lower HbA1c, less medication and 3.6 kg more weight loss than usual care. In breast cancer chemotherapy, it did not reduce severe toxicity and adherence fell sharply over cycles. Fatigue, weakness, headache and nausea are common during the five days.

Evidence grade: Limited evidence.

The schedule

• Pattern: periodic
• Fasting hours: 120
• Calorie limit on fast days: about 1,100 kcal (4,600 kJ) on day 1 and about 720 kcal (3,000 kJ) on days 2 to 5, plant-based, low protein and sugar

Why people choose it

People choose it because it involves eating some food on only five days a month rather than fasting every week. In trials it reduced weight, body fat, blood pressure and IGF-1 compared with an unrestricted diet, with larger effects in people at higher risk, and in people with type 2 diabetes it reduced medication use and HbA1c. The trials compared it with usual eating, not with ordinary daily calorie restriction. Most trials were run by the diet's inventor or co-funded, supplied or sponsored by the company that sells it.

Cautions

• People taking insulin or sulfonylureas: The 12-month diabetes trial excluded people on these medicines because cutting calories raises their hypoglycaemia risk. (Source 1)
• Pregnant or breastfeeding women, older adults of advanced age, and frail older adults: An expert review says these groups have unique risks and should be dissuaded from fasting regimens. (Source 2)
• People with an eating disorder: The same review says people with eating disorders should not follow intermittent fasting regimens. (Source 2)
• Older adults concerned about muscle: Absolute lean body mass fell in the FMD arm of the main randomised trial. (Source 3)
• Anyone weighing the evidence: The main trial's authors and university have financial ties to the company that sells the diet. (Source 3)

What goes wrong

Absolute lean body mass fell in the fasting-mimicking diet arm, even though the percentage of lean mass did not change significantly. (Source 3)

• Randomized trial, Certainty not rated.
• Size: 100 randomised.
• Who: Generally healthy US adults.
• How long: 3 months.
• Result: Absolute lean body mass reduced (P = 0.004); % lean mass P = 0.07.
• Funding: Industry ties (L-Nutra supply, licence and author equity)

Limit of this finding: Relevant to older adults, for whom muscle loss matters more; the trial did not focus on older adults.

although absolute lean body mass was reduced in arm 2 (P = 0.004)

Fatigue, weakness and headaches were the most common side effects, all mild or moderate, and 29% of participants did not complete three cycles. (Source 3)

• Randomized trial, Certainty not rated.
• Size: 100 randomised; 71 completed three cycles.
• Who: Generally healthy US adults.
• How long: 3 months.
• Result: No grade 3 or higher adverse effects; 95% completed one cycle, 71% three cycles.
• Funding: Industry ties (L-Nutra supply, licence and author equity)

The most common self-reported grade 1 (mild) or grade 2 (moderate) symptoms experienced by the participants were fatigue, weakness, and headaches.

In the diabetes trial, the FMD caused fatigue, headache, dizziness and nausea in a substantial number of participants during each 5-day cycle, and 13 more participants stopped using it partway through. (Source 1)

• Randomized trial, Certainty not rated.
• Size: 51 in FMD arm.
• Who: Adults with type 2 diabetes.
• How long: 12 months.
• Result: Energy-deficit symptoms common; 8 serious adverse events in 5 FMD participants, judged unrelated; 13 stopped FMD, 6 non-compliant lost to follow-up.
• Funding: Co-funded by L-Nutra.

The FMD programme caused typical signs of energy deficit (fatigue, headache, dizziness) and nausea in a substantial number of participants during the 5-day intervention

Only 20% of women in the chemotherapy trial kept to the FMD for every cycle; dislike of parts of the diet was the main reason for stopping. (Source 4)

• Randomized trial, Certainty not rated.
• Size: 65 in FMD arm.
• Who: Women with early breast cancer receiving chemotherapy.
• How long: all chemotherapy cycles.
• Result: 81.5% completed first cycle; 33.8% at least 4 cycles; 20.0% all cycles.
• Funding: Pink Ribbon and Amgen grants.

The main reason for non-adherence to the FMD was dislike of distinct components of the diet, perhaps induced by chemotherapy.

What the evidence supports

In a randomised trial of 100 generally healthy US adults, three monthly 5-day cycles of the fasting-mimicking diet reduced body weight, trunk and total body fat, blood pressure and IGF-1 compared with an unrestricted diet. (Source 3)

• Randomized trial, Certainty not rated.
• Size: 100 randomised (48 control, 52 FMD); 71 completed three FMD cycles including crossover.
• Who: Generally healthy adults in the United States.
• How long: 3 months (3 cycles)
• Result: Weight -2.6 ± 2.5 kg (P < 0.0001) in FMD arm.
• Funding: Industry ties: FMD supplied by L-Nutra; USC licensed the intellectual property to L-Nutra and may receive royalties; authors V.D.L. and T.E.M. hold L-Nutra equity; funding from the USC Edna Jones chair fund and NIH UL1TR001855.

Limit of this finding: Small; participants and staff not blinded; compared with an unrestricted diet, not calorie restriction.

Three FMD cycles reduced body weight, trunk, and total body fat; lowered blood pressure; and decreased insulin-like growth factor 1 (IGF-1).

In people with type 2 diabetes treated with metformin or diet, adding monthly 5-day FMD cycles to usual GP care for 12 months reduced glucose-lowering medication, HbA1c and body weight compared with usual care alone. (Source 1)

• Randomized trial, Certainty not rated.
• Size: 100 randomised (51 FMD, 49 control); 8 and 10 lost to follow-up.
• Who: Adults 18-75 with type 2 diabetes, BMI 27 or more, on metformin only or diet.
• How long: 12 months.
• Result: Medication effect score -0.3 (95% CI -0.4 to -0.2); HbA1c -3.2 mmol/mol (-0.3%), p=0.04; weight -3.6 kg (95% CI -5.2 to -2.1)
• Funding: Co-funded by Health~Holland, the Dutch Diabetes Foundation and L-Nutra.

Limit of this finding: Assessor-blinded but open-label; people on insulin or sulfonylureas were excluded.

body weight (−3.6 kg; 95% CI −5.2, −2.1; p<0.001) at 12 months

A secondary, exploratory analysis of FMD trial blood samples reported that three cycles were associated with lower insulin resistance, less liver fat and a 2.5-year lower median estimated biological age. (Source 5)

• Randomized trial, Very low certainty.
• Size: participants of two clinical trials (NCT02158897, NCT04150159)
• Who: Adult trial participants.
• How long: 3 FMD cycles.
• Result: Median biological age -2.5 years, independent of weight loss.
• Funding: not captured from the fetched page; the research group's earlier trial disclosed L-Nutra equity.

Limit of this finding: Secondary exploratory analysis of blood samples from a randomised clinical trial (NCT02158897), with a second clinical study (NCT04150159); these outcomes were not the trial's endpoints. Biological age is an estimate from blood markers, not a measured outcome.

3 FMD cycles were associated with a decrease of 2.5 years in median biological age, independent of weight loss

What the evidence does not support

Fasting glucose, triglycerides, CRP and cholesterol that were in the normal range at baseline were not significantly changed by three cycles in the randomised comparison; the larger benefits in at-risk people came from a non-randomised post hoc analysis. (Source 3)

• Randomized trial, Certainty not rated.
• Size: 100 randomised.
• Who: Generally healthy US adults.
• How long: 3 months.
• Result: No significant change in normal-range metabolic markers.
• Funding: Industry ties (L-Nutra supply, licence and author equity)

Metabolic markers such as fasting glucose, triglycerides, and CRP, as well as total, HDL, and LDL cholesterol, which were within the normal range at baseline, were not significantly affected in the randomized comparison after three FMD cycles.

In women receiving chemotherapy for breast cancer, a 4-day FMD around each cycle did not reduce severe (grade III/IV) toxicity compared with a regular diet. (Source 4)

• Randomized trial, Certainty not rated.
• Size: 131 randomised.
• Who: Women with HER2-negative stage II/III breast cancer, without diabetes.
• How long: 3 days before and the day of each chemotherapy cycle.
• Result: Grade III/IV toxicity 75.4% FMD vs 65.6% regular diet, not significant; overall pathological complete response 11.7%, no difference between groups.
• Funding: Pink Ribbon and Amgen grants.

Limit of this finding: Radiological response was better with FMD (OR 3.168, P = 0.039), and per-protocol pathological response favoured FMD; the trial was not continued to phase III.

Grade III/IV toxicity, scored during all cycles of chemotherapy, was not significantly different between the FMD group (75.4%) and the regular diet group (65.6%).

Where the evidence is mixed

A small pilot trial sponsored by L-Nutra found some between-group differences in weight, glucose, ketones, insulin resistance and an autophagy marker at the end of the diet, but these differences were not significant at all time points. (Source 6)

• Randomized trial, Certainty not rated.
• Size: 30 healthy participants.
• Who: Healthy adults, mean age 49.
• How long: 8 days.
• Result: Significant changes from baseline to day 6 (p < 0.05) not sustained at all time points.
• Funding: Industry-funded: sponsored by L-Nutra Inc.

however, differences were not significant across all time points

Where the research disagrees

How strong the evidence is that the FMD slows ageing or reduces disease

• Longo, Brandhorst and colleagues (USC; Longo holds L-Nutra equity), rct: FMD cycles are safe, feasible and effective in reducing risk factors and lower estimated biological age (Source 3)
• DIRECT trial investigators (Leiden), rct: In breast cancer chemotherapy, FMD did not reduce severe toxicity and adherence was low (Source 4)

A common belief, and what the research shows

The belief: The fasting-mimicking diet is proven to reverse ageing.

What the research shows: The 2.5-year drop in biological age came from a secondary, exploratory analysis of blood markers by the diet's developers; the NIA says more research is needed on long-term effects, and markers that were already normal did not change significantly in the randomised trial.

References

1. Diabetologia. 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. 2024. PMID 38546821, DOI 10.1007/s00125-024-06137-0. Read the source
2. Nutrients. Clinical Management of Intermittent Fasting in Patients with Diabetes Mellitus. 2019. PMID 31003482, DOI 10.3390/nu11040873. Read the source
3. Science Translational Medicine. Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. 2017. PMID 28202779, DOI 10.1126/scitranslmed.aai8700. Read the source
4. Nature Communications. Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial. 2020. PMID 32576828, DOI 10.1038/s41467-020-16138-3. Read the source
5. Nature Communications. Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk. 2024. DOI 10.1038/s41467-024-45260-9. Read the source
6. GeroScience. Effect of fasting-mimicking diet on markers of autophagy and metabolic health in human subjects. 2025. DOI 10.1007/s11357-025-02035-4. Read the source