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Rebooting the System: The Benefits of a Fasting Mimicking Diet

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While fasting has many health benefits, prolonged calorie restriction can take a toll on patients, both physically and mentally. Diets that mimic the physiological benefits of fasting without the burden of food restriction may be a good alternative. Read on to learn more about fasting mimicking diets, their health benefits, and which patients are likely to benefit most from them.


Prolonged water-only fasting provides many health benefits, including regeneration of the immune system, reduced blood glucose, and autophagy (1). However, prolonged fasting is difficult for most people and can cause adverse effects due to its extreme nature. Researchers have therefore been trying to design diets that might mimic the beneficial effects of prolonged fasting without the stress of complete food restriction.

Previously, I have written about the benefits of intermittent fasting. While intermittent fasting approaches share some characteristics with fasting mimicking diets (FMDs), there are some key distinctions. In this article, I will discuss these differences, the evidence for FMDs in both animal and human studies, and which conditions respond best to FMDs.

Terminology: FMD vs. IF

Before we dive into the evidence, let’s clear up some terminology. My guess is that you’ve probably heard of intermittent fasting (IF) but are less familiar with the concept of a fasting mimicking diet (FMD). Intermittent fasting is a general term used to describe various approaches that use short-term fasting with the overall goal of improving health. Examples of IF approaches include skipping one meal a day, shrinking the eating window (also called time-restricted feeding), or alternate-day fasting.

Under this loose definition, fasting mimicking diets can be considered a type of IF. However, FMDs are much more detailed than most IF approaches and are designed in order to achieve specific biological outcomes. Researchers have developed a very-low-calorie, low-protein diet that causes changes in markers associated with stress resistance and longevity (insulin-growth factor, ketone bodies, and glucose) in a similar manner to prolonged fasting. One FMD cycle on this diet usually lasts for several days (three to five) and cycles are fairly infrequent (one to two times per month). Between cycles, eating resumes as usual without any restrictions (2).

Animal Studies Show FMD Improves Health across the Board

Since FMD is a relatively new concept, most studies to assess the associated health benefits have been performed in animal models. The physiology that allows organisms to respond and adapt to fasting or starvation conditions first appeared billions of years ago and is present in virtually all organisms (3). Even in S. cerevisiae, a type of yeast, periodic fasting extends lifespan and increases resistance to oxidative stress (4).

Five health benefits of the fasting mimicking diet

Animal models allow researchers to analyze a wider range of health outcomes, such as the regeneration of tissues. Mice are among the most commonly used animal models for studying FMD and are typically given two four-day-long FMD cycles per month, with ad libitum (unrestricted) intake between cycles. In the remaining part of this section, we’ll explore the evidence for FMDs in animal studies.

Metabolic Disorders and Diabetes

In one mouse study, FMD cycles had profound effects on visceral fat, glucose, and IGF-1 levels. IGF-1 is an endocrine hormone produced primarily in the liver. IGF-1 signaling has been associated with biological aging in some organisms, but whether high levels are good or bad is somewhat controversial (5). After return to an ad libitum (eat as desired) diet, both glucose and IGF-1 levels returned to baseline, but visceral fat remained lower. Mice also showed evidence of significant liver and muscle regeneration as a result of FMD (4). In another study published in February 2017, FMD cycles were shown to reverse late stage Type 2 and even Type 1 diabetes! The FMD triggered epigenetic changes that resulted in expression of prenatal development genes in the adult pancreas. This led to pancreatic β cell regeneration and the return of insulin secretion (6).

Cognitive Function

An FMD has been shown to promote hippocampal neurogenesis and improve motor learning and memory in old mice (4). In a mouse model of Alzheimer’s, protein restriction cycles have been shown to alleviate the age-dependent impairment in cognitive performance and reduce levels of phosphorylated tau, a protein that forms the tangles characteristic of Alzheimer’s and several other neurological diseases (7).

Autoimmune Disease

In a mouse model of multiple sclerosis, FMD reduced clinical severity in all mice and completely reversed symptoms in 20 percent of animals (8). At the molecular level, FMD increased corticosterone levels and regulatory T cells and promoted remyelination in axons. FMD also reduced levels of pro-inflammatory cytokines and immune cells involved in promoting inflammation.

Cancer

FMD has been shown to rejuvenate the immune system and protect against cancer in mice. One study found a 45 percent reduction in neoplasia incidence in the FMD group relative to the control group. Cycles of FMD beginning at middle age also delayed tumor onset and reduced the number of lesions, which may indicate a switch from malignant to benign tumors. FMD has also been shown to reduce the number of tissues with inflammation and protect against inflammation-associated skin lesions (4).

Aging

Immunosenescence is the age-associated decline in hematopoiesis (the creation of new blood cells), resulting in diminished or altered production of adaptive immune cells. FMD causes a rejuvenation of the blood profile and a reversal of this decline by increasing the number of hematopoietic and mesenchymal stem and progenitor cells. Four months of FMD cycles resulted in a significant increase in RBC count and hemoglobin levels compared to baseline. FMD also increased median lifespan of mice by 11 percent and either attenuated age-dependent bone mineral density loss or induced bone regeneration in mice.

Interestingly, there were some contraindications to fasting in older mice. The authors suggest that in older animals, a less severe low-calorie and low-protein diet may be preferable to continue to provide beneficial effects while minimizing malnourishment (4).

FMD: Human Clinical Trials

While most studies on FMD have been done in animal models, there have been a few clinical trials in humans. In one of the most substantial studies to date, performed by Wei et al. (9), they had 71 subjects complete three FMD cycles. Each FMD cycle lasted for five days, and was repeated once every month. During the five-day period, subjects in the FMD group consumed about 34 to 54 percent of their normal caloric intake. The diet composition was approximately 9 to 11 percent protein, 43 to 47 percent carbohydrate, and 44 to 46 percent fat by energy.

The researchers measured several markers in the blood after three FMD cycles, some of which were maintained after returning to their normal diet:

  • Subjects who completed three full FMD cycles and returned to their normal diet for five to seven days had significantly reduced body weight, total body fat, trunk fat, absolute lean body mass, waist circumference, IGF-1, systolic and diastolic blood pressure, total cholesterol, LDL, and HDL.
  • The effects of FMD on body weight, BMI, waist circumference, IGF-1, and diastolic blood pressure persisted for at least three months after the final FMD cycle.

FMD was found to have especially profound effects in patients at high risk for cardiovascular, metabolic, and age-related disease.

  • Individuals who had high baseline levels (>1 mg/liter) of C-reactive protein, a potent marker of inflammation, had significantly lower CRP levels three months post-FMD.
  • Subjects with low baseline HDL showed significantly increased three-month follow-up HDL levels.

Altogether, these data suggest that FMD causes many beneficial changes in risk factors for chronic, age-related diseases in both animals and humans. Further studies will only contribute to our understanding of the mechanism behind these changes.

When to Prescribe a Fasting Mimicking Diet

FMD clearly has numerous health benefits, as I have outlined in this article. However, it should be noted that fasting does have the potential to make some patients worse, depending on their condition.

Patients who are good candidates for FMD include: those who are fighting chronic infections or trying to lose weight; those who have a weak immune system, neurological issues, type 2 diabetes, or other metabolic problems; and those who are healthy and are simply trying to optimize longevity.

Patients who are typically not good candidates for FMD include: those who are pregnant or have HPA axis dysregulation (“adrenal fatigue”), an eating disorder, or thyroid problems. Fasting is also not usually recommended for children or teens.

Always be sure to monitor patients closely when they start to implement FMD or any type of fasting. If patients start to exhibit symptoms of HPA-D or hypothyroidism, you will need to reconsider their fasting schedule. Remember that each patient will respond to fasting differently.

The FMD, as studied, is currently available from Prolon as a specific package of prepared foods and micronutrients intended to be administered under a doctor’s supervision.

It’s likely that a “homemade” version with similar macronutrient ratios and foods would have the same effects, but this hasn’t yet been studied in a clinical trial. Stay tuned for more discussion about the benefits and practical application of fasting in the future, as this is a topic I’m exploring deeply.

36 Comments

  1. I am doing this for the fourth time. I hate the fasting but it just makes me feel really good. I used recipes but the cooking aspect was a real pain so i went to the repetitive mode of eating the same things every day just to make it easier. Do not make the big mistake of exercising a lot when doing this. I was taking in 600 calories and burning up slightly more than that during the first fast. At the end my wife said i looked wasted. But she said as soon as I started to eat all that changed.I felt quite strong the next day and just felt more vital. Now I. do take lipitor but my cholestrol (including min 10 miles of vigorus biking 5/6 times a week went from 204 to 137. Slowly loosing execess weight. So I think it shows a benefit for me. What was weird is that after not doing it for about 5 weeks I simply wanted to feel that good again and here I am doing it again . Of course I am going to bake a loaf of bread That will be ready exactly when the fast is over.

  2. I do a 72hour fast in conjunction with supplements, exercise and chemotherapy in treating my cancer. I found a significant reduction in how inflamed my body felt after each round of chemo, reduced mouth side effects, and after 7 rounds my bloods are still within the standard reference ranges. I have advanced cancer with multiple mets and I think fasting has contributed to my current success with treatment so far. At the very least, I will continue with it for the reduced inflammation benefits and I would recommend it, where suitable and under guidance, for other cancer patients.

  3. I am on day 4 of my 3rd FMD in 3 months. I have secondary progressive MS and have clearly seen improvement. It’s nothing miraculous but my mobility has gotten better and I always “feel it” late in the refeeding stage. Once I tried Prolon and twice created my own using Dr. Longo’s macros. I believe the only critical thing is to keep protein low and aroun d 10% of calories at most. Other than that I eat roughly 40% carbs and 50% fats. And I don’t think their is any real difference between Prolon and my homeade diets, in fact I prefer my own. Only side effects are weight loss dry mouth and my body purging fluids and a bit of insomnia day 3 and 4. I do think during the refeeding it’s important to reintroduce foods slowly( I start with fruits and vegetables and soups. Hope this helps

  4. I have hashimotos and I am on day 5 of prolon. I am experiencing some pretty difficult stomach upset.
    I probably have adrenal issues as well. What did you mean when you said this was not a good plan for thyroid and adrenal patients?

  5. Great article and fantastic insight. It appears many of the comments do not understand the benefits of fasting. This was just introducing the latest research not selling prepackaged foods!

  6. I tried a “homemade” five-day FMD in May. It was interesting. I lost eight pounds, wasn’t overwhelmingly hungry compared to a water fast, and generally was able to function. The main challenge was a sort of low-level hangry mood, like, when will this be over? My BG right before breaking the fast was 54…never seen it that low. I hope to do another FMD sometime. Give it a try!

  7. Dr. Longo states that too much protein (specifically meat that contains a lot of animal fat) has been shown to increase levels of IGF-1. In one of his Five Pillars of Longevity, Centenarian Studies, he looks at Blue Zones where people have the longest life spans and sees that none of these peoples eat a diet heavy in animal protein.
    The current debate in keto circles about protein mainly centers around protein being gluconeogenic and whether eating too much protein kicks you out of ketosis. Robb Wolf and others have refuted this but none of these people have addressed the effects protein has on longevity. The Protein Sparing Modified Fast states that eating adequate amounts of protein while fasting is key to not losing lean muscle mass but Dr. Longo states that once one goes off a long fast lean muscle mass is replaced and even exceeds the amount lost during the fast. His Longevity Diet is essentially the Mediterranean Diet and even includes quite a bit of grains.
    So low carb/high protein vs The Longevity Diet. I’m confused. Where do you stand on this?