Prolonged Fasting and the Fasting-Mimicking Diet: The Science of 5-Day Resets
Time-restricted eating limits the daily eating window. Prolonged fasting goes much further, and the fasting-mimicking diet (FMD) was developed as a lower-burden way to get some of its effects.4 This article covers what has been shown in people, what has only been shown in animals, and who should not try it.
- In prolonged starvation, the brain's use of the ketone beta-hydroxybutyrate is what allows people to survive.1
- The FMD is a diet low in calories, sugars and protein but high in unsaturated fats.5
- In a randomized trial of 100 generally healthy adults, three 5-day FMD cycles reduced body weight, trunk and total body fat, blood pressure and IGF-1.5
- Autophagy is the cell's main system for breaking down and recycling its own components.3 Fasting's protection against disease has been shown mainly in rodents; in people, fasting has helped reduce obesity and high blood pressure.2
- Prolonged fasting is contraindicated in underweight individuals, pregnant women, diabetics on insulin or sulfonylureas, and people with a history of disordered eating.
Most popular fasting advice concerns time-restricted eating. Longer fasts are different: they force the body to rely on stored fuel, and the ketone beta-hydroxybutyrate becomes the brain's alternative fuel.1
What Changes During a Long Fast
Prolonged starvation shifts how the body fuels itself, and the brain's use of beta-hydroxybutyrate is what allows people to survive it.1 In rodents, intermittent or periodic fasting protects against diabetes, cancers, heart disease and neurodegeneration; in people, fasting has helped reduce obesity, hypertension, asthma and rheumatoid arthritis.2
Autophagy
Autophagy is the major system cells use to deliver their own components to lysosomes for breakdown, and it works as a recycling system that supplies new building blocks and energy.3 Yoshinori Ohsumi received the 2016 Nobel Prize in Physiology or Medicine for discovering its mechanisms.
The Fasting-Mimicking Diet
The FMD was developed to reduce the burden of prolonged fasting. In mice, cycles of the diet started at middle age extended lifespan, and a small pilot trial in people found three cycles lowered risk factors for aging, diabetes, cardiovascular disease and cancer without major adverse effects.4
The diet tested in people was low in calories, sugars and protein and high in unsaturated fats.5
Human Evidence
In a randomized trial of 100 generally healthy US adults, three 5-day FMD cycles reduced body weight, trunk and total body fat, lowered blood pressure and decreased IGF-1; after three months the control group crossed over, so 71 people completed three cycles.5 An exploratory analysis of blood samples from the same trial found a 2.5-year decrease in median biological age on a validated blood-based measure, independent of weight loss.6
How Shorter Fasting Windows Compare
Time-restricted eating, the most popular form of fasting, has been tested against regular meals. In a 12-week randomized trial of 116 adults aged 18 to 64 with a body mass index of 27 to 43, run largely through a study app, eating only between noon and 8 pm (a 16:8 time-restricted schedule) led to a small weight loss of 0.94 kg, which did not differ significantly from the 0.68 kg change in people eating three structured meals a day.7 In the in-person subgroup of 50 participants, the time-restricted group lost more appendicular lean mass (the muscle in the arms and legs) than the comparison group, and estimated energy intake did not differ between the groups.7
Fasting-Mimicking Diets During Chemotherapy
The diet has also been tested in cancer care. In the phase 2 DIRECT trial, 131 patients with HER2-negative stage II or III breast cancer were recruited and 129 were randomly assigned to a fasting-mimicking diet or their regular diet for the three days before and the day of each chemotherapy session; the diet improved the clinical response to chemotherapy compared with a regular diet.8 In a secondary analysis, patients on the diet were less worried about treatment side effects, and those who stuck to it had better functioning and fewer symptoms than those who did not.8 That last comparison was not randomized, so it may partly reflect who was able to adhere. This is research in a supervised cancer setting, not a do-it-yourself protocol.
What Supervised Fasting Looks Like
A review of 768 medically supervised, water-only fasting visits found that most adverse events (75%) were mild and known reactions to fasting.9 The most severe event was grade 2 or lower in 555 visits, grade 3 in 212 and grade 4 in one, with no grade 5 events, and 2 visits involved a serious adverse event.9 These fasts took place under medical supervision, which is the setting this evidence describes.
Do not try prolonged fasting or an FMD without medical advice if you are underweight, pregnant or breastfeeding, have type 1 diabetes or take insulin or sulfonylureas, or have had an eating disorder.
Build a Foundation of Time-Restricted Eating First
Use the Published Macros or Commercial FMD Kit
Target 2 to 4 Cycles Per Year
Refeed Gradually on Days 6 and 7
The human evidence comes from three cycles under study conditions. Talk with your clinician before trying it, especially if you take any medicines.
References
- 1Cahill GF Jr. "Fuel metabolism in starvation." Annu Rev Nutr. 2006;26:1-22. PubMed · DOI
- 2Longo VD, Mattson MP. "Fasting: molecular mechanisms and clinical applications." Cell Metab. 2014;19(2):181-92. PubMed · DOI
- 3Mizushima N, Komatsu M. "Autophagy: renovation of cells and tissues." Cell. 2011;147(4):728-41. PubMed · DOI
- 4Brandhorst S, et al. "A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan." Cell Metab. 2015;22(1):86-99. PubMed · DOI
- 5Wei M, et al. "Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease." Sci Transl Med. 2017;9(377). PubMed · DOI
- 6Brandhorst S, et al. "Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk." Nat Commun. 2024;15(1):1309. PubMed · DOI
- 7Lowe DA, et al. "Effects of Time-Restricted Eating on Weight Loss and Other Metabolic Parameters in Women and Men With Overweight and Obesity: The TREAT Randomized Clinical Trial." JAMA Intern Med. 2020;180(11):1491-1499. PubMed · DOI
- 8Lugtenberg RT, et al. "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 Res Treat. 2021;185(3):741-758. PubMed · DOI
- 9Finnell JS, et al. "Is fasting safe? A chart review of adverse events during medically supervised, water-only fasting." BMC Complement Altern Med. 2018;18(1):67. PubMed · DOI