I was griping to
about my inability to feel inspired to write due to being on day 3 of Prolon combined with the fact that I have to help my son make an assortment of 7 dozen cookies, brownies and protein balls tonight. Which of course means I can’t try the dough, enjoy the delight of warm goodies fresh out of the oven but instead just smell them. Perhaps my words weren’t so eloquent when I as venting. Thankfully he kindly suggested I let myself off the hook and just write about Prolon. Originally, I had planned to write a post-mortem and share both my Prolon experience combined with my Oura results along with other before and after metrics, but looks like that will be a Part II.I’m legit feeling hungry and cranky, but it’s because my body is supposedly deep in the throws of “autophagy” which whining aside, is why I am such a huge fan of Prolon. As Prolon puts it “Today may feel more challenging as you experience symptoms associated with ketosis, but remember that every challenge brings the possibility of great victory, and on Day 3, that victory is autophagy.”
Raise your hand if you’ve “done Prolon”. I’m guessing not too many hands were raised. Congrats and condolences to those that raised their hands. This is my 5th or 6th time. I’m an OG, I think the first time I completed a Prolon program was in 2017.
For those of you that didn’t raise your hands I’m sure most are asking, “What Is Prolon?”
The ProLon “Fast Mimicking Diet”
It’s a 5-day “Fast Mimicking Diet” which means you get kit that includes a tiny box of “food” each day that is nutritionally designed to give your body all the benefits of a fast but without the need to abstain from food completely.
Before you roll your eyes, it’s the real deal. As my kids would say “no cap.” It’s backed by over 25 years of research, 32 clinical trials, and $48 million+ in research grants (including NIH). Dr. Valter Longo who co-founded Prolon is an absolute legend and OG of longevity medicine. He’s one of my super duper unicorns. He is a biogerontologist and cell biologist renowned for his research on aging, calorie restriction, and fasting, pretty much coining the concept of a “fast mimicking diet” (FMD).
Here is what a typical day looks like.
The daily kit is comprised of a small nut based bar, 2 soup packets, and either a packet of 6 hearty crackers or 2 packets of olives (6ish) and a teeny tiny choco crisp square, herbal tea packets and a flavored drink syrup that you add to water and sip to stave off hunger. The exception is Day 1 when you get an extra nut bar and both the crackers, olives AND choco crisp.
The five days also build upon one another to trigger the various stages of fasting that contribute to cellular rejuvenation, so each day has its own unique and important role in that process.
Day 1 - Transition Day - shift to reduced calories, glucose stores start to diminish, you begin to burn fat for fuel and you generally enter a mild state of ketosis (a process that converts fat into energy) about halfway into the day
Day 2 - Ketosis - you begin to rely entirely on internal fat stores to produce ketones, a process known as ketosis and while ketosis eventually boosts post-fast mental clarity, memory, and focus, the initial transition may bring on symptoms such as brain fog, headaches, fatigue, body aches, or even nausea (thankfully I eat clean so I don’t experience these side effects). Ketosis can cause also cause gastro issues for some folks.
Day 3 - Autophagy - although I hate the early part of this process, I LOVE the whole idea of autophagy! It is the biological process that’s typically activated after three days of a prolonged fast. It’s your body's natural process of recycling damaged cells, it’s like a deep, internal spring cleaning to promote cellular rejuvenation. This critical part of the process continues 2 days after the fast ends in fact.
Day 4 - Deep Cellular Rejuvenation - Supposedly this is the day that some lucky participants experience "keto-euphoria,” a phase where positive effects of the fast, such as increased mental clarity, focus, energy, and vitality, may start to emerge. And they also say for many, hunger diminishes, and the fast's benefits become more noticeable. Unfortunately, I have experienced neither in my past programs and am generally just happy that I get the choco crisp this particular day.
Day 5 - Obsesss About What I Am Going To Eat Tomorrow (that’s what I call it, the call it Cellular Rejuvenation) - Last day of FMD and autophagy. Supposedly some people wake up feeling sharper and recharged because the body has undergone a significant transformation. I generally spend the day thinking regularly about what I will eat tomorrow after I’m DONE.
Day 6 - Transition Day - The recommendation is that you gradually introduce traditional foods and start with easy-to-digest foods, starting with liquid foods and then add small portions of rice, pasta and small amounts of protein. I can’t do the liquid thing, I’m just plain hungry. The good thing is that I generally eat 90%+ fruits, veggies and proteins.
Since you are allowed to eat the items whenever you want and in whatever order you want throughout the day they are provided, I have a strategy. I drink a warm beverage - either decaf espresso or herbal tea for as much of the morning as possible. Optimally holding off eating any of the paltry portions until lunchtime. Starting with a soup and trying to save the substantive items until late in the day. Somehow having a bowl of soup and 5 crackers for dinner creates the illusion that I’ve eaten dinner and will sleep normally. Other days I eat a packet of olives hastily, throw the bag away and then panic that perhaps one olive was still in the bag. I won’t tell what happens next. But I digress.
The Science
This program is designed to mimic the effects of fasting without requiring you to abstain from food completely. Each day is designed to activate your body's natural cell-rejuvenating processes for longevity and healthy aging.
But it’s the science that came far before the program was even an idea that is so very important. It’s the part of healthcare/medicine that in my opinion is missing. It gets to the root cause, cellular level. It was Longo’s groundbreaking work on cancer that really got my attention almost a decade ago.
Dr. Longo often uses the term “differential stress resistance” to explain how normal cells, under fasting conditions, ramp up protective genes that help them survive stress (like toxins or chemo), whereas cancer cells—locked into hyper‐proliferation—cannot shift as effectively. Going on to talk about Immune System Modulation which is the idea that fasting can alter immune cell populations, potentially boosting certain anti‐tumor immune responses. With autophagy (cellular “clean‐up” process) likely increasing, removing damaged proteins and organelles, which can prime tumor cells for better recognition and destruction. And finally can lead to metabolic rewiring by reducing glucose and growth signals, where fasting can force cancer cells into metabolic pathways that increase oxidative stress or nutrient depletion, making them more susceptible to therapy.
Early Mouse & Cell Studies
Dr. Longo’s lab explored the impact of calorie restriction and specific nutrient reductions in yeast, mice, and human cells. His lab first noticed that restricting nutrients in yeast cells protected them from toxic agents while making certain cancerous or damaged cells more vulnerable.
These studies showed improved markers related to aging, including enhanced cell regeneration, autophagy (cellular cleaning/recycling), and resistance to stress.
Follow‐up studies in mice demonstrated that short‐term fasting or a fasting‐like diet could sensitize tumor cells to chemotherapy, leading to improved treatment outcomes in animal models of multiple cancer types (including breast, melanoma, and glioma).
It brought to life the starvation response, the idea that healthy cells adapt to nutrient scarcity by shifting into a “protective” state, reducing growth signals, and activating cellular repair pathways.
While malignant cells often struggle to adapt to a low‐nutrient environment because they rely heavily on growth‐promoting signals (e.g., IGF‐1, mTOR pathways). This mismatch can render them more vulnerable to chemotherapy or oxidative stress.
One landmark study from Dr. Longo’s group and collaborators showed that short‐term fasting in mice made multiple types of cancer cells more sensitive to chemotherapy, while protecting normal cells from some of the toxic side effects and this led to the idea of combining fasting or FMD with standard cancer therapies.
Effects on Different Tumor Types
Research has been conducted on breast cancer, melanoma, glioblastoma, and various other solid tumors in animal models. In many cases, fasting cycles appeared to slow tumor growth and/or enhance the efficacy of chemo drugs like doxorubicin and cyclophosphamide.
Reduced IGF‐1 and Growth Factors
Fasting lowers IGF‐1 (Insulin‐Like Growth Factor 1) levels, a critical growth signal. High IGF‐1 is correlated with cancer growth and progression; thus, reducing IGF‐1 can hamper tumor cell proliferation.
Human Clinical Trials
Randomized controlled trial involving healthy adult participants who followed the Fasting Mimicking Diet for five days per month for three months.
Subjects experienced reductions in body weight, trunk fat, blood pressure, IGF-1 (Insulin-like Growth Factor 1), and markers of inflammation. The results suggested improved metabolic health and potential protective effects against age-related diseases.
The diet was reported to be safe, with minimal adverse effects when followed correctly.
Cardiovascular & Metabolic Markers
Subsequent papers and ongoing research have examined markers like cholesterol, triglycerides, blood glucose, C-reactive protein (CRP), and ketone levels. The FMD protocol often leads to:Decreased LDL (“bad”) cholesterol
Modest improvements in fasting glucose and insulin sensitivity
Lower levels of IGF-1, a hormone linked to growth and aging processes
Indications of increased ketone bodies, reflective of a “fat-burning” state
Autophagy and Cellular Regeneration
In both preclinical and clinical settings, fasting protocols (including FMD) are associated with stimulation of autophagy—your cells’ way of clearing out damaged components and recycling them. This has implications for healthy aging and disease prevention, though the human data on this specific mechanism is still emerging.
Like I said, one of my heroes.
The Reality
It’s HARD. Period. Getting your body to do hard things doesn’t usually feel good. Just like vigorous excerise - once the dopamine hits it’s great but it’s not all dopamine. Prolon FMD isn’t for everyone, but nor is any protocol in medicine, including pharmaceuticals or any other intervention. That’s the challenge with healthcare today - we try to come up with one size fits all solutions when every one of us is completely unique at the cellular level.
and I have both done Prolon multiple times and survived, but one of our friends tried it and had to stop on the third day because it activated too many gastro issues.When I shared with someone yesterday that I was doing Prolon he shared he could never do it, doesn’t fit with this lifestyle and that he is using GLP-1s. That spoke volumes to me.
But it got me thinking. Isn’t part of the problem here that we consider this hard. Overconsumption is real. Overabundance of cheap calories is wreaking havoc. Our convenience culture is softening us.
When I emerge from my brain fog, I’ll finish Part II assuming I survive and talk about how this ties into GLP-1s, personalized medicine and more. Time to get back to autophagy…and BAKING COOKIES - urg.
Oh and bonus we interviewed the CEO last fall for the podcast so we will be sharing that in the future!