by Nils Osmar

The information in this article is not intended as, and should not be taken as, medical advice. Interventions like exercising, dietary changes, and taking medications and supplements can have both benefits and side effects, Please consult with a medical professional about any medical concerns.  See full Medical Disclaimer

I became interested in fasting about six years ago during a time when I was grappling with some major health problems. I had an auto immune condition which had been dealing with for over a decade, which cleared up completely after several rounds of prolonged water fasting, So I am aware on a deep level of its possible benefits.

I’m also aware that it has some dangers. When we fast, we are depriving ourselves of food; we are essentially voluntarily entering a state of starvation, depriving ourselves of the nutrients needed for building and sustaining health. Fasting can have profound health benefits; taking breaks from eating has been a natural part of our evolutionary development, and we’re biologically adapted for it; but it can also be problematic (and dangerous) in some situations, particularly past a certain age.

Fasting Mimicking Diets: A Safety Cushion

There are many types of fasts, and also a number of different diets that are intended to mimic some of the effects of fasting, with the end goal of giving us the benefits while minimizing the dangers. One of the most promising, from an anti-aging point of view, was developed by USC’s Dr. Valter Longo. Longo’s FMD is high in fat, low in calories, low in protein and carbohydrates, and extremely low in leucine and methionine.

Dr. Longo helped formulate a product called ProLon, a medical “diet in a box” designed to support the same healing mechanisms triggered by a water fast — but without actual fasting.

Not a “Diet for Life”

Longo’s fasting mimicking diet is not a “diet for life” or a “way of eating,.” It is intended to be used as a temporary, periodic protocol, followed for a few days at a time,after which we resume eating a diet giving us the full array of nutrients needed to build health.

How it Works

The FMD triggers a process of deep cleaning on a cellular level called autophagy. It keeps us feeling satiated while our bodies are burning fat and moving into deep autophagy and ketosis. In very deep autophagy, our bodies clean out protein fragments, bacteria, and viruses; they also cannibalize senescent cells and senescent mitochondria.

Dr. Longo’s research has shown that what happens after the fast is striking: when we do a re-feed, moving back into eating highly nutritious foods rich in the proteins, fats, vitamins, minerals and other nutrients which were omitted from our diet for a few days, our bodies produce a flood of new stem cells which pour out into our bloodstream, moving to where they are needed to support healing and rejuvenation around the body.

Dr. Longo has described this only somewhat metaphorically (but accurately) as being given a whole new immune system.

We also experience mitochondrial biogenesis, the creation of a flood of new, young mitochondria.

Why It Works — and Why Understanding It Matters

The FMD didn’t begin as a product. It began in the mid-2000s, when Longo’s lab at USC’s Longevity Institute was working out the mechanisms by which short-term starvation protects healthy cells while sensitizing cancer cells to chemotherapy.

That research kept pointing back to a small family of “nutrient-sensing pathways” — IGF-1, mTOR, and PKA chief among them — that act as the body’s switchboard between growth mode and repair mode.

We of course, need highly nutritious foods to build health; but if we are constantly eating them, the body senses the presence of some key nutrients… assumes resources are abundant… and keeps building and growing.

When the nutrients in question drop below certain thresholds, the switchboard flips: growth signals dim, autophagy ramps up, and the body begins recycling its own damaged components.

One way to visualize what is happening is that as we go about our daily lives, eating what we think of as good diets, garbage, and recyclables are piling up in our cells. When we fast or eat a well constructed FMD, mechanisms kick in which take out the garbage and recycle things like protein, fragments and viruses and bacteria that may be cluttering up ourselves into amino acids. If we never fast… if we never take a break from from eating… these natural, beneficial healing processes never have a chance to kick in.

Turning on Autophagy

Taking a break from food for a day… or a week… Is a well-established way of flipping the switches which are dormant in our cellular mechanisms and turning on autophagy.

The interesting question Longo’s team kept asking was: do you actually have to eat nothing to switch it on? Or could a properly designed diet keep us below the activation threshold of those pathways, fooling the body into a fasting state while still providing enough food to keep us functional, compliant, and out of the dizziness-and-hunger territory that drives most fasters off the wagon?

Over roughly two decades, Longo and his associates developed and clinically validated a five-day protocol that does exactly that. It was patented, formalized into the ProLon kit, and tested across what is now more than forty published clinical trials.

The structure. ProLon is a five-day program. Day 1 provides roughly 1,100 calories — a glide path into the fasting state rather than a cold plunge. Days 2 through 5 drop to about 750–800 calories. The macronutrient ratio runs roughly 10–11% protein, 43–47% carbohydrate, and 44–46% fat across the program, with Day 1 slightly higher in protein than the later days. This surprises people who assume fasting protocols must be ketogenic; they aren’t. What matters here isn’t ketosis per se — it’s the absence of the specific nutrient signals that would reactivate mTOR and IGF-1.

What’s in the box. The kit is entirely plant-based and consists of proprietary nut-based bars, vegetable soups (minestrone, tomato, mushroom, quinoa, and similar), kale crackers, olives, herbal teas, an algal-source omega-3 supplement, a multi-micronutrient tablet called NR-1, and a glycerol-based “L-drink” for Days 2–5 that helps stabilize energy without delivering glucose or amino acids in problematic quantities. Every item is portioned, labeled, and sequenced by day.

What’s excluded. There are no animal products of any kind in the ProLon kit. No dairy. There is some sugar, but not much. And — most importantly from a mechanistic standpoint — there are extremely low levels of the amino acids that most powerfully activate the pro-growth pathways mTOR and IGF-1, particularly leucine and methionine.

These amino acids are abundant in meat, eggs, fish, and dairy, which is why the diet is plant-based: it’s not an ideological choice, it’s a biochemical one. If you added even a modest serving of chicken or whey, or a few sardines or a bite of meat, you would literally undo the signaling effect the diet exists to produce.

I normally eat foods such as fish, eggs, meat, yogurt, and kefir, along with some plant-based foods such as wild blueberries. So avoiding these is a major change for me. It’s not that these foods are “bad for people;” it’s that they are highly nutritious and support and growth pathways… the same pathways that we need to turn off occasionally in order to do internal housecleaning on a cellular level.

What the studies have shown.

The landmark human trial was Wei et al., published in Science Translational Medicine in 2017. Generally healthy adults completed three monthly cycles of the FMD and were compared to controls. Results in the FMD group, on average:

• About 6 pounds of weight loss, concentrated in visceral and trunk fat rather than lean mass
• Waist circumference reduced by 1–2 inches
• Systolic blood pressure dropped ~4.5 mmHg, diastolic ~3.1 mmHg
• IGF-1 fell into a range associated with reduced cancer risk (21.7–46.2 ng/mL)
• Reductions in fasting glucose, triglycerides, and C-reactive protein (a key inflammation marker), particularly in participants whose baseline values were elevated
• LDL cholesterol reduced in those with elevated starting values
• No serious adverse effects

A 2024 follow-up published in Nature Communications analyzed blood and imaging data from participants in the 2017 trial along with a second Nashville-based trial, and concluded that three cycles of the FMD reduced biological age by approximately 2.5 years, alongside reductions in liver fat and insulin resistance. Subsequent and ongoing trials have explored applications in type 2 diabetes (with evidence of improved beta-cell function in animal work and improved glucose control in humans), multiple sclerosis, chemotherapy tolerance, and inflammatory bowel disease — though these remain at varying stages of validation.

Why the structure matters for compliance. This is the part that often gets lost. Most people who attempt prolonged water fasting bail somewhere between hours 36 and 60 — when hunger spikes, when dizziness arrives, when social occasions intervene. Longo’s design philosophy was that an intervention that 5% of people can complete is less valuable than a slightly milder intervention that 60% of people can complete.

The small amounts of permitted food don’t just provide micronutrient insurance; they keep people in the protocol long enough to actually capture the autophagic and regenerative benefits. The diet, in other words, was engineered as much around human behavior as around biochemistry.

I Tried the Prolon Diet… and Hated It

I tried the Prolon diet once,

I hated it.

I bought the box… unpacked the ingredients… looked at the food labels… tried eating them… and felt sick.

I was used to eating a low carbohydrate diet, and accustomed to preparing my own meals from fresh natural organically grown ingredients. I was accustomed to avoiding certain foods, including nuts and seeds and grains that I’m allergic or sensitive to.

For people who are accustomed to eating a standard American diet which is high in sugar and starches and unhealthy fats, the Prolon diet would be an improvement. For me, because I had already moved past that kind of diet. it was way too high in carbohydrates and full of foods that left me stuffed up and gave me headaches. I felt hungry, not satiated. It “worked” in the sense that some health markers improved after eating it for a week, but I hated the experience. I felt weak and dizzy and irritable.

So like some others who have tried the Prolon version and deisliked it, I began researching the components of the diet, trying to deepen my understanding of why it worked so that I could create a version of my own.

My Current “Fast” — My Own Version of the Fasting Mimicking Diet

Like many people, I became cautious about prolonged fasting after Peter Attia’s report that one of his patients had lost a lot of muscle after routinely doing a three-day fast once a month. I don’t doubt that this happened to his patient, but I suspect that what may have been going on was that the guy was, like many people in our community, trying to push catabolic pathways almost full-time… eating a low-protein plant-based diet, avoiding animal foods which are rich in the amino acids needed to build muscle (we can get the same aminos from plants, but it takes much more conscious effort and planning to do so).

When we add fasting to that kind of protocol, we are moving into dangerous territory. I don’t know beyond doubt that this is what caused his patient’s problems, but it would fit a pattern that I’ve seen many times in our community.

Worth noting: is that Longo’s FMD was actually designed in part to address exactly this risk — the small amount of plant protein on Days 1 and 2, combined with the specific macronutrient ratios, appears to reduce muscle catabolism compared to water-only fasting of similar length, which is one reason Longo positions it as gentler and more sustainable across multiple cycles per year.

I have almost no health problems, but I do have a form of tendinitis called golfer’s elbow, which can flare up and become painful. It has occurred to me a number of times that if my body had a bigger supply of stem cells, it might be healing faster. So I decided somewhat impulsively to start a fast this past weekend.

My plan at the time was to do a 72-hour fast, so that I could get some deep autophagy, cleaning out some senescent cells and senescent mitochondria. Dr. Longo’s studies have illustrated that when we do a prolonged fast of 3 to 5 days or longer, or a fasting mimicking diet of the same length, we are clearing out debris — and then when we resume eating a high-nutrient diet, our body rapidly creates new stem cells and new mitochondria. He has described it as essentially being given a brand new immune system.

I started fasting on Saturday. I did water fasting (with added coffee and electrolytes) for two days, then I added in certain foods that are approved for Longo’s fasting mimicking diet — foods which provide a few nutrients but do not provide the nutrient signals that stop autophagy.

I had been eating a ketogenic diet — very occasionally going out of ketosis once or twice a week but otherwise sticking to it — for a couple of weeks before I started the FMD. Because I was already in ketosis, there were no hunger signals. I have not been at all hungry.

I am now on day four. I may stop tomorrow afternoon when I reach five days, or I may keep going. I’m feeling wonderful, just as I would in a water fast, but without some of the issues I’ve sometimes experienced when doing water-only fasting, such as dizziness or hunger.

What I’m Eating

When I added the foods on day three, I made sure that they fell within the parameters established by Dr. Longo. I am avoiding foods with certain amino acids, in particular leucine and methionine, and avoiding foods high in oxalates.

The foods which I’m allowed are lettuce (which is basically water in a cellulose wrapper), fresh green olives, raw vinegar with mother, olive oil, mushrooms (mainly shiitake), green onions, and garlic.

Plus water. Coffee is allowed too. I add 1/2 teaspoon of MCT oil to each cup of coffee.

Yesterday, one of my meals was 2.5 cups of mushrooms (shiitake and oyster) sautéed in olive oil with four cherry tomatoes and a chopped green onion. It was delicious and very filling, but it had no leucine or methionine or other nutrients in it which would stop autophagy.

Then last night, my dinner was a large salad — a head of iceberg lettuce, raw vinegar and olive oil, a few olives, a medium-sized avocado, and a small tomato. Again, very filling and satisfying.

I have lost 3.5 pounds so far (some of it fat, some water weight), and according to my tape measure, 1″ of belly fat.

Perhaps because I was doing water fasting for the first two days, I did go through the adventure of needing to stay near the bathroom… of my body dumping all of the food that was in my digestive track, plus a lot of water.

I was feeling a little hungry yesterday morning, but I don’t feel it all hungry today.

Other Types of Fasting Mimicking Diets

Dr. Longo’s diet is unique in some respects: it was developed in a medical context and is being sold as a medical diet, which can be prescribed by a doctor to improve patients’ biomarkers while supporting healthy loss of excess body fat.

There are many other fasting mimicking diets out there, including one which has been developed by Dr. Dom d’Agostino, which I’ll be talking about in another article.

Dr. Longo’s diet, again, was designed to support deep autophagy, fat loss, a reduction in inflammation, the removal of cellular debris (including viruses and bacteria), and other things that occur naturally during a prolonged water fast. There are many fasting mimicking diets which promote healthy weight loss but do not trigger deep autophagy; I’ll write about them in another article.

The information in this article is not intended as, and should not be taken as, medical advice. Interventions like exercising, dietary changes, and taking medications and supplements can have both benefits and side effects, Please consult with a medical professional about any medical concerns.  See full Medical Disclaimer

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More from Nils Osmar

• Anti-Aging Youtube channel Pathways to Longevity
• Anti-Aging Facebook group: Anti-Aging and Life Extension
• Rekindle School classes in Seattle: Rekindl.e School
• My personal website: My articles, art and more: Nilsosmar.com
• Exploring possible consciousness in Claude.AI and other LLMs: AI Consciousness
• Donations make this website possible. To donate using Buymeacoffee, please click here