The Fasting Mimicking Diet (FMD) has gained considerable attention as a dietary strategy designed to replicate the physiological effects of fasting while still allowing for food intake. This approach typically involves a significant reduction in calorie intake, with a specific focus on a low-protein, low-carbohydrate, and high-fat composition, rich in nutrients. FMDs are generally followed for short periods, typically ranging from 3 to 7 days, and are often repeated cyclically, such as monthly, to achieve ongoing benefits. The primary goals of an FMD are to trigger beneficial cellular and metabolic responses similar to those obtained through water-only fasting, such as improved metabolic health, reduced inflammation, and potential longevity benefits.
Understanding the Fasting Mimicking Diet
What is the ProLon “fasting mimicking diet?”
ProLon is a specific type of FMD designed to take the headache out of fasting. It is a five-day diet program that contains no animal protein, low amounts of plant protein, very low amounts of saturated fat, high amounts of unsaturated fats, very low amounts of sugars, and high amounts of complex carbohydrates.
Why was ProLon invented?
ProLon was invented by Dr. Valter Longo, an esteemed longevity researcher who is the head of longevity at USC. His work on intermittent fasting and fasting-mimicking diets (FMD) has focused largely on using fasting to enhance cancer treatment and mitigate the negative impact of chemotherapy, with considerable success.
Key Concepts in Fasting and Diet
- Fasting - a complete absence of food intake.
- Intermittent fasting or alternate-day fasting - a long-term practice of fasting every other day, with standard food intake on non-fasting days.
- Fasting mimetics - pharmacological agents that trigger some of the effects of fasting.
- Fasting mimicking diet (FMD) - a dietary regimen composed of macronutrients and micronutrients, with minimal calorie restriction, designed to trigger a response akin to fasting.
- Caloric restriction - A 20-40 percent reduction in standard calorie intake, but a standard intake of micronutrients.
Benefits and Applications of FMD
Potential Anti-Aging Benefits
ProLon may have been designed to support people during cancer treatment, but it is now being used and researched for its potential anti-aging benefits.
Impact on IGF-1 Levels
Valter Longo designed ProLon to support people undergoing chemotherapy or radiotherapy for cancer. This is, in part, because intermittent fasting has been found to reduce levels of insulin-like growth factor-1 (IGF-1). Lowering levels of IGF-1 can enhance the resistance of normal cells to chemotherapy-dependent damage while simultaneously increasing the susceptibility of a large number of tumors to chemo and radiotherapy.
Read also: Comprehensive Guide to Tea Fasting
Reassessing Relationship with Food
One interesting additional benefit of ProLon is that it seems to make a person reassess their relationship to food (and alcohol!). After ‘fasting’ for five days, you’ll probably think harder about everything you put in your mouth. Smaller portion sizes may suddenly seem much more reasonable, and you’re likely to be better at forgoing snacks and foods that were unhealthy habits.
Promoting Metabolic Flexibility and Cellular Clean-Up
reSET promotes metabolic flexibility and supports “cellular clean-up.” It is long enough to generate lasting positive effects, yet short enough to avoid overburdening the body. The findings of a study with reSET indicate that FMDs can promote weight loss - largely due to fat burn, alter bioenergetic substrate utilization, and enhance gut microbiome activity.
Simplicity and Convenience
ProLon makes it super simple to give fasting a try without having to worry about malnutrition. The product packaging is easy on the eye and the food, by most accounts, tastes pretty delicious!
The ProLon Experience
Which ProLon Fast Day is the Hardest?
ProLon is designed as a five day fast. Everyone’s body is different. Based on personal experience with ProLon, days 1 and 5 are the hardest, by far. Although day 1 is one of the highest calorie days, it starts to dawn on you what you have signed up for. Your body isn’t yet in ketosis, and heading to bed without dinner feels abnormal, even a little depressing. However, when you wake up on day 2, things settle, and some of the euphoria people report on ProLon starts to kick in. The elevated mood, and energy boost associated with fasting is a real phenomenon that has been experienced first-hand each time ProLon has been tried. Lasting the full five days on a severely calorie restricted diet becomes harder the longer into the week you go. By day 5, exhaustion with the protocol sets in, and one becomes very tired of the powdered soups in particular. Each time ProLon has been done, there is a temptation to end the fast on the evening of day five, but instead heading to bed again without dinner and wait for the morning of day 6 to break my fast by slowly introducing small portions of gentle on the stomach plant foods, like oats or sweet potato soup.
Which ProLon Meals Taste the Best?
The L-Bars, and olives are also tasty. The food that is toughest to consume during the FMD, are the soups. Everyday of the fast has at least some soup, which is powdered. You can’t just drop a soup in and pour water over it, either. That will result in lumps. After several lumpy soups haphazardly prepared, the soup packet should be poured in a bowl and thoroughly whisking the mixture to make sure all of the powder has dissolved. Letting the soups “steep” with a plate placed over the bowls will soften the dried peas which are added to the minestrone & quinoa soup mix.
Read also: The Hoxsey Diet
Potential Side Effects
Clinical studies have identified potential risks and discomfort associated with low calorie and low protein diets such as reSET, including anxiety, depression, dizziness, drowsiness, fatigue, headache, hunger, irritability, muscle aches, nausea or spinal pain. You may also feel kidney and liver pain as your body works very hard to detoxify.
Managing Uric Acid Levels
Fasting, including fasting mimicking diets, increase uric acid levels. To mitigate some of the increase in uric acid levels during ProLon by taking quercetin, which is a supplement that can help make urin more alkaline, which in turn, helps the body get rid of more uric acid. It is also crucial to drink plenty of water during a ProLon fast.
Symptoms During the reSET Program
Many people experience few, if any, symptoms during the reSET program. However, some symptoms are indicative of toxins leaving your body. In fact, the more toxins there are to be eliminated, the more symptoms you can experience. These feelings typically pass within the first 3 days.
You may feel weak, flu like symptoms, nausea, dry mouth, constipation or diarrhea, bloating and/or gas, feeling cold, feeling hungry, and irritability. Headaches, ranging from mild to strong migraines, are also very common during the first 2 to 3 days especially when you eliminate caffeinated drinks and refined sugars. Headaches can be relieved by drinking additional water or one black coffee.
The hungry feeling comes from the hunger hormone called Ghrelin which spikes around mealtimes.
Read also: Walnut Keto Guide
The Science Behind Fasting and FMD
Longo's Research and Beliefs
Longo has spent decades studying aging in yeast cells and lab mice. He now believes he’s developed a diet that may boost longevity - by mimicking the effect of periodic fasting.
Fasting, he and others argue, gives cells a break to rest, renew, rebuild themselves and, essentially, take out the trash as the body shifts from storing fat to burning it. “The animal data is very striking,” Mattson said.
Animal Studies and Human Trials
Mice and rats on fasting regimes are slimmer, live longer, and stay smarter and physically stronger as they age. They resist tumors, inflammatory diseases, and the neurodegeneration that characterizes diseases like Parkinson’s and Alzheimer’s. They handily fight off infection and can even sprout new neurons.
Small clinical trials in humans have shown patients report less fatigue and fewer gastrointestinal symptoms while fasting during chemotherapy treatments. Longo has found that mice on fasting diets reap a number of health benefits.
Concerns and Criticisms
Some experts say there just isn’t enough clinical data to prove the diet does everything Longo claims. “These are only animal studies. There isn’t a big body of evidence in humans,” said Kristen Gradney, a dietician in Louisiana and a spokeswoman for the Academy of Nutrition and Dietetics.
A study published in the Journal of the American Medical Association this May startled some diet researchers by showing alternative day fasting was no better at decreasing cardiovascular health risk factors than normal dieting - and was harder to maintain.
The Big Question: Calorie Restriction vs. Other Benefits
“In humans, is intermittent fasting only effective for weight loss because we’re restricting calories? In my mind, that’s the big question,” said Grant Tinsley, an assistant professor of kinesiology at Texas Tech University who studies sports nutrition.
Longo's Journey and Motivation
Italian by birth, he spent summers in his family’s ancestral home, a town called Molochio in southern Italy that’s home to an unusually high percentage of centenarians. His father is 91.
Convinced his work was important, Longo kept his head down and kept going. “I didn’t pay attention to what people were saying,” he said.
The Turning Point
The turning point, Longo said, came when an editor at Science recognized that his rejected paper was part of the new paradigm to understand the genetics of aging. The paper was published in 2001, seven years after he’d first submitted it.
Fasting and Cellular Reprogramming
Once he had the aging pathway worked out, Longo went on to look more deeply at what restricting calories did to yeast cells. He found withholding food “completely reprogrammed” the yeast - cells lived longer and were resistant to threat after threat. Fasting “is at the foundation of the body’s ability to protect, repair, and rejuvenate itself,” he said.
Pancreatic Cell Research
San Diego computational biologist Karmel Allison, who blogs at the diabetes lifestyle site ASweetLife, took a deep dive into Longo’s paper on pancreatic cells and found the data unconvincing. Other scientists agree that’s a key question for further study, in both mice and people.
Testing on Cancer Patients
Longo came up with the idea for the fasting mimicking diet about 10 years ago. He was trying to test the effect of a water-only diet for cancer patients. So Longo decided to devise a diet with minimal calories that would provide the nutrition the patients needed, but also confer the benefits of fasting. The cancer fasting diet amounts to just 200 to 500 calories a day for four days.
The Panini Shop Soups
The two worked together after hours in Ditonno’s panini shop concocting extremely low-calorie soups - some just 30 to 45 calories per serving - out of pumpkin, beets, tomatoes, and broth. They’d then freeze individual portions of the soups for delivery to cancer patients.
The Business Side
Longo created a company, L-Nutra, to market the diet, and retains majority ownership. He intends to funnel any personal profits into a nonprofit to fund research. For now, not much money is rolling in, though he says about 5,000 people have used ProLon - some paying customers, some research subjects.
“The general public wants something encapsulated, they want a prescription,” he said. “Valter’s done a very smart thing.
Bibliometric Analysis of FMD Research
Overview of the Study
In recent years, FMD become more and more popular since it may have potential benefits for human health, including cancer and diabetes. However, there lacks a bibliometric analysis that consolidates existing publication patterns and forecasts emerging research focal points in this domain. In light of this, a study aimed to undertake an exhaustive bibliometric analysis to identify the leading edges and areas of concentrated research activity in the FMD field.
Data Sources and Methods
Relevant literature pertaining to the FMD was systematically sourced from the Web of Science Core Collection (WoSCC). Recognized for its comprehensiveness and authority, WoSCC served as the primary database for this study. The search was delimited to documents published between 1 January 2000 and 15 September 2023. The specific search terms employed for this literature hunt were: “Fasting-Mimicking Diet” OR “Fasting-Mimicking Diets” OR “Fasting-Mimicking” OR “Fasting mimicking Diet” OR “Fasting mimicking Diets” OR “fasting mimicking.”
Once the data was compiled, the WoSCC Online Analysis Platform facilitated a detailed bibliometric analysis. This analysis centered around annual publication numbers, the top 10 in terms of productive countries/regions, authors, organizations, and journals, and spotlighted the top 20 high-citation publications. For a more visual representation and understanding of the data, VOSviewer 1.6.16 software was employed. The software enabled the mapping and visualization of several facets, such as co-authorships across institutions, countries/regions, and authors; citation patterns across journals and references; and co-occurrence patterns of keywords.
Publication Trends
Based on the provided data related to the FMD, a total of 169 documents were identified. Analyzing the time frames, the literature can be grouped into two primary phases: in the initial phase, which spans from 2012 to 2016, there was a modest number of publications, never surpassing 10 annually. The subsequent phase from 2017 to 2023 represents a significant uptick in research intensity and focus. During this period, the yearly number of documents consistently increased, peaking at 44 publications in 2022. This increasing trend suggests a growing recognition of the relevance and significance of FMD in the scientific community.
Key Contributors
In total, 945 authors from 342 institutions and 25 countries/regions contributed to the field of FMD in 111 journals. The most productive country was USA with 86 publications, followed by Italy (61 publications) and the People’s Republic of China (33 publications). For institutions, the University of Southern California tops the list with 45 publications, followed by the Ifom Fire Institute of Molecular Oncology with 42 publications, and the Chinese Academy of Sciences with 15 publications. In terms of individual researchers, Valter D. Longo stands out with 47 publications, showcasing him as a leading expert in this area.
Highly Cited Documents
The first high-cited document was published in Ageing Research Reviews and authored by Mattson et al. In the context of the FMD, the article may discuss how intermittent fasting, such as the FMD, can potentially promote various health benefits. These benefits may include improved metabolic health, weight management, and even potential effects on delaying aging processes and reducing the risk of chronic diseases.
The second high-cited document was published in Cell Metabolism by Longo et al. In this review, they explored the relationship between time-restricted feeding and fasting including the FMD and circadian rhythms, and their potential impacts on a healthy lifespan.
The third high-cited document was published in Aging Cell by Longo et al. The article may explore specific dietary intervention involving FMD, can influence aging processes, with the potential benefits of periodic fasting for promoting longevity and improving age-related health markers.
The fourth high-cited document was published in Science Translational Medicine by Wei et al. In this article, they investigate the effects of a FMD on various markers and risk factors associated with aging, diabetes, cancer, and cardiovascular disease, and explores how this diet can impact biomarkers related to these health conditions.
The fifth high-cited document was published in Cell Reports by Choi et al. They explore the effects of FMD on tissue regeneration, autoimmunity, and symptoms of multiple sclerosis (MS).
Keyword Analysis
The central and prominent cluster revolves around “fasting-mimicking diet,” “caloric restriction,” “intermittent fasting,” and “ketogenic diet.” This is indicative of a core research area focused on dietary interventions and their impacts. On the left side, terms like “cancer,” “chemotherapy,” “cancer therapy,” and “breast cancer” are connected, suggesting research on how fasting or dietary interventions might affect cancer and its treatment. Terms like “metabolism,” “glucose metabolism,” “insulin resistance,” and “oxidative stress” suggest a focus on the metabolic impacts of fasting and dietary restriction. “Regeneration,” “inflammation,” “resilience,” and “autophagy” point toward the potential health outcomes or cellular processes influenced by these diets.
Key Research Hotspots
For this field, the FMD for cancer is the most popular topic. Many studies investigate the effects of FMD for cancer.
FMD for Cancer Treatment
Synergistic Effects with Hormone Therapy
Caffa et al. demonstrates the efficacy of combining a FMD (FMD) with hormone therapy to potentiate cancer treatment in hormone-receptor-positive breast cancers, which constitute roughly 75% of all breast cancer cases. In mouse models, the FMD synergistically improved the cancer-fighting impact of endocrine therapies, such as tamoxifen and fulvestrant, by significantly lowering systemic levels of IGF-1, insulin, and leptin, and impeding AKT-mTOR signaling pathways through the increased expression of EGR1 and PTEN. This combination, particularly when a cycle of FMD was added to a regimen of fulvestrant and palbociclib (a CDK4/6 inhibitor), not only induced durable tumor regression but also countered the development of acquired resistance to the medications. Additionally, it prevented tamoxifen-induced endometrial hyperplasia, a common side effect of this drug. Encouragingly, early-phase clinical observations in human patients mirrored the metabolic alterations seen in mice and were associated with prolonged anti-cancer benefits.
DIRECT Trial Results
Subsequently, the phase 2 DIRECT trial, which was the first randomized controlled study evaluating the effects of an FMD on toxicity and efficacy of chemotherapy in patients with cancer. In this study, they evaluated the effects of the FMD as an accompaniment to neoadjuvant chemotherapy in breast cancer patients. 131 HER2-negative stage II/III breast cancer patients participated, with half receiving an FMD and the other half their regular diet. Results showed no notable difference in toxicity levels between the two groups, even though one group did not receive dexamethasone with their treatment. The FMD group exhibited a higher likelihood of a significant or complete radiological response to chemotherapy. Importantly, DNA damage in T-lymphocytes was also reduced in the FMD group, hinting at the diet’s protective qualities.
Benefits for Other Cancers
In addition, FMD may be also benefits for other types of cancer besides breast cancer, including lung cancer, colorectal cancer, and prostate cancer.
Practical Guides and Cookbooks
The Fast Mimicking Diet Cookbook
The Fast Mimicking Diet Cookbook is your complete guide to harnessing the science of Dr. Valter Longo’s revolutionary FMD. Designed to give your body the benefits of fasting-cellular repair, improved metabolism, and sustainable weight loss-without complete food deprivation, this cookbook makes the process both simple and satisfying.
Inside, you’ll find everything you need to Step-by-step guidance: Understand how the Fast Mimicking Diet works and how to structure your 5-day plan for maximum results. Daily meal plans: Calorie breakdowns, portion sizes, and shopping lists that remove all guesswork. Delicious recipes: Nourishing breakfasts, hearty soups, savory dinners, smart snacks, and healing teas-all crafted to keep you energized and full while staying within FMD guidelines. Practical strategies: Tips for overcoming cravings, staying motivated, and transitioning back to regular eating safely. Long-term benefits: Learn how regular FMD cycles can support brain and heart health, reduce inflammation, and promote longevity.
Intermittent Fasting Made Easy
This book presents a practical framework for partial fasting that delivers remarkable results without the struggle of traditional fasting methods. Unlike conventional diets that often lead to frustration and rebound weight gain, the Fasting Mimicking Diet offers a sustainable path to lose belly fat fast while activating your body's natural rejuvenation processes. Based on cutting-edge research, this approach triggers the same beneficial metabolic changes as extended fasting while still allowing you to consume carefully selected foods.