February 16, 2021
As you get older, your body loses some of its cellular power as well as control over its cellular clearing and recycling abilities. This results in an accumulation of old, dysfunctional cells known as senescent cells and poorly functioning mitochondria.
Tiny, but mighty “intracellular powerhouses,” mitochondria reside within each and every one of your cells and make up one-third of your total body weight. By converting glucose and oxygen, they produce ATP to create all of the energy your body needs to run every aspect of each of its cellular functions.
It is because of mitochondria that your brain fires on all cylinders; your hormones stay in check; your heart keeps beating; your lungs constantly bring in, absorb, and expel vital air; your immune system protects you from viruses, bacteria, and molds; your gut is able to absorb nutrients, etc. Basically, any bodily function that relies on energy happens because of mitochondria. It’s no wonder they have been increasingly recognized as essential players in the aging process. Most aging-related diseases, particularly neurodegenerative diseases, have mitochondrial involvement, and mitochondrial dysfunction is one of the hallmarks of metabolic decline resulting from aging. So, needless to say, you would be wise to appreciate and take care of your mitochondria.
There are a number of methods, but improving the clearing and recycling of senescent cells is one of the top ways you can care for your mitochondria. Fasting is one such method for accomplishing this and has been proven to have profound positive effects on overall health, vitality, and longevity. However, there is plenty more you can do to amplify the effects that fasting has on your cells and mitochondria. My friend and former podcast guest, Dr. John Lieurance—whom you may remember from the episode “The Crazy Future Of Medical Biohacking: Skull Resets, Suppositories, Nasal Sprays, Nebulizers, Sound Therapy & More With Dr. John Lieurance.”—just unveiled a brand new 3-phase protocol founded on principles of fasting and solid, current science that will enable you to care for your mitochondria, and thus enhance your health and longevity.
Dr. Lieurance is a naturopathic physician, chiropractic neurologist, and all-around expert in medical biohacking who has been in private practice in Florida for 25 years. He is the chief scientific advisor of MitoZen.com™ and heads up AdvancedRejuvenation.us, a multi-disciplinary clinic with a focus on treating chronic diseases, regenerative medicine, functional neurology, psychedelic therapies, functional medicine, and regenerative stem cell therapy.
In today’s article, a guest post by Dr. Lieruance, you’ll discover everything you need to know about caring for your mitochondria, including how your body recycles old cells and weak mitochondria, how to activate autophagy and accelerate this recycling process with plant extracts, how NAD+ fits into the healthy mitochondria equation, and a brand new protocol invented by Dr. Lieruance—The Mito Fast™ Protocol—that will take your body’s cellular and mitochondrial renewal process to the next level.
How Your Body Recycles Old Cells & Weak Mitochondria
The average cell in your body has anywhere from 1,000-2,000 mitochondria. This population of mitochondria within any given cell is known as the chondriome, and (much like your microbiome) it can be healthy or unhealthy, which dictates how functional (or dysfunctional) your mitochondria are.
Your body is constantly replacing your old, weak, and dysfunctional mitochondria with new, healthy, and fresh mitochondria in a recycling process mediated through a gene expression controlled by mTOR.
The story of mTOR begins in the 1970s on Easter Island, or Rapa Nui if you’re a local. It was there that scientists identified a new antifungal agent and named it after the island (i.e., rapamycin). Isolated from Streptomycin hygroscopic, rapamycin has since been studied intensively for its immunosuppressive qualities. While studying this medication, scientists discovered an entire body signaling system that controlled cell metabolism, growth, cellular proliferation, and survival: a system now known as the “mechanistic target of rapamycin” (mTOR). You can learn more about mTOR in Ben’s article “3 Big Markers Of Aging (& Exactly How To Target Them For Enhanced Longevity),” but essentially, mTOR promotes anabolic cellular processes that lead to cellular growth and repair.
When mTOR is inhibited, your body shifts into a cleaning and recycling phase involving autophagy. This is your body's way of cleaning out damaged cells in order to regenerate newer, healthier cells and is a basic catabolic process that degrades damaged organelles (mitochondria) or dysfunctional proteins to gain energy or free amino acids. During the first step of autophagy, cytoplasmic components that are to be degraded are engulfed in an autophagosome. Autophagosomes then fuse with lysosomes and are exposed to enzymes (hydrolases) that catalyze, or degrade, the contents. Autophagy is a dynamic recycling system that all cells rely on in order to maintain homeostasis and one that produces new building blocks and energy for cellular renovation and homeostasis. Also involved in this cleaning and recycling phase is mitophagy, the selective degradation of old dysfunctional mitochondria through autophagy.
Without autophagy, you would have an accumulation of damaged cells that do not get recycled into new healthy cells, thus making room for senescent, AKA, “zombie” cells.
Cellular senescence is an irreversible cell-cycle arrest mechanism that acts to protect against cancer by limiting the proliferation of old or damaged cells. Basically, cellular senescence is a permanent state of sleep a cell goes into. While this state is good for preventing ailments like cancer, it is also associated with a release of inflammatory products like cytokines and chemokines and higher energy consumption—pulling energy away from your healthy cells. This production of pro-inflammatory cytokines and chemokines happens irrespective of the senescence-inducing stressor or mechanism. Cultured cells usually reach senescence within several weeks after exposure to senescence-inducing stressors, but remain viable for months after that.
This means these “zombies” will float around, spew inflammation, and suck the life out of your body by deferring vital energy that would normally be directed towards healthy cells. They are zombies in the literal sense!
As you can see, there is a delicate balance when it comes to mTOR. Too much mTOR activation can contribute to diseases such as diabetes and a decrease in longevity, and too little mTOR activation can stunt cellular growth and repair, thus preventing you from, say, putting on and maintaining muscle. mTOR regulates different cellular processes in response to environmental clues. It controls the balance between anabolism and catabolism, most notably in this context autophagy and mitophagy. The mTOR pathway regulates transcription factors such as FOXO, FOXA, NRF, NF-κB, SREBPs, and TFEB, and induces ribosome biogenesis, protein synthesis, cellular growth, and secretion of pro-inflammatory and mitogenic factors.
One such cue is nutrition status. When food is plentiful, mTOR inhibits autophagy, but during calorie restriction, one of the strongest inducers of autophagy, mTOR is inhibited. This leads to the inhibition of protein synthesis, thus causing major energy savings which can be directed towards the breakdown and recycling of weak and dying cells and cellular material such as mitochondria. This excess energy can also be used to cleanse your gut and microbiome, liver, gallbladder, and kidneys, as well as reset your endocrine system.
Other Methods For Inducing Autophagy
Fasting is probably the most well-known and most practiced method for cleaning up senescent cells through autophagy. Read Ben’s article “The Powerful Health Benefits Of Fasting (Plus The Top 5 Questions I Get Asked About Fasting).” for a deep dive, but some general advice on fasting for autophagy would be to eat all of your meals within a 6-10 hour window.
An extended fast, such as a 3-5 day water fast, will amplify the autophagy-inducing effects and more efficiently clear senescent cells and activate mitophagy, but this type of fasts should only be done by experienced individuals. So, before starting any fasting protocol, do your homework.
During the induction of autophagy through calorie restriction, certain foods can support autophagy, including black coffee, Ceylon cinnamon, and green, ginger, turmeric (or turmeric supplements), ginseng, Chaga, and reishi teas. Various stressors, such as DNA or protein damage resulting from intense exercise and reactive oxygen species (ROS) from ROS-Ozone, intense exercise, or physical stress, can also induce autophagy.
Figure A, to the right, illustrates how autophagy can be either too high, or too low, and that these levels can be harmful to your mitochondria, cells, body, and brain.
Figure B shows how autophagy changes as you age: Early on in your development, low levels of autophagy support you best. In youth, too much autophagy signaling, such as mTOR inhibition, can lead to disease. As you become older, high autophagy levels become more beneficial, which is where strategies that inhibit mTOR and stimulate autophagy for a healthier more robust body and brain come into play.
Senolytics, which are activators of autophagy, are one example. Senolytics are nutraceuticals that selectively induce the death of senescent cells to improve health and longevity in humans. Rapamycin, which I mentioned above, is a senolytic that has been used by scientists and doctors for years for everything from the prevention of stenosis after angioplasty (the ballooning open of arteries) to treatment for certain cancers and autoimmune diseases.
There are also a few naturally occurring plant compounds worth mentioning that have been reported to inhibit mTOR signaling and promote autophagy:
- Apigenin – A family member of flavonoids, apigenin is abundant in fruits (oranges, apples, cherries, grapes), vegetables (onions, parsley, broccoli, sweet green pepper, celery, barley, tomatoes), and beverages such as tea and wine.
- Cryptotanshinone – Isolated from the root of the Salvia miltiorrhiza Bunge plant.
- Curcumin (diferuloylmethane) – A natural polyphenol product of the plant Curcuma longa.
- Fisetin – Perhaps the most powerful of all polyphenols, fisetin is a family member of flavonoids and occurs in fruits and vegetables such as strawberries, apples, persimmons, and onions.
- Indoles – Natural compounds found in cruciferous vegetables such as broccoli, cauliflower, cabbage, and brussels sprouts.
- Isoflavones – A class of flavonoid phenolic compounds plentiful in soybeans.
- Quercetin – A polyphenolic compound, quercetin can be found in onions, red grapes, and apples.
- Pterostilbene – Mainly found in blueberries.
- Resveratrol – A natural polyphenol found in red grapes and red wine.
- Tocotrienols – Members of vitamin E superfamily.
Taking these compounds during a fasting state will even further support strong mTOR inhibition. However, there is one caveat when it comes to the foods mentioned in this list. Even if you were to eat every fruit or vegetable on this list, you probably wouldn’t come close to the dosage required to move the mTOR-inhibiting dial.
You’re certainly not going to do any harm by consuming foods rich in all of these compounds, but for maximum efficacy, look for a quality supplement that has liposomal delivery of the plant's active compound. Even better, use a suppository. Because suppositories bypass your liver and enzymes in your stomach and intestines, they provide the most superior delivery method, even rivaling IV infusions in terms of absorption.
Why NAD+ Is Important For Healthy Mitochondria
In addition to fasting and certain autophagy-inducing foods and senolytics, maintaining an optimal NAD+/NADH (NAD plus hydrogen) ratio is essential for optimal mitochondrial function. NAD+, or nicotinamide adenine dinucleotide, is a critical coenzyme found in every cell in your body that is involved in hundreds of metabolic processes.
From plants to metazoans, an increase in intracellular levels of NAD+ directs cells to make adjustments to increase energy production and utilization, boost cellular repair, coordinate circadian rhythms, and ensure survival.
Biochemist Hans von Euler-Chelpin, in his 1930 Nobel Prize speech, said “NAD+ is one of the most widespread and biologically most important activators within the plant and animal world.” The problem is, by the time you are middle-aged, your levels of NAD+ will naturally have fallen to half of what they were when you were in your youth. In addition to aging, poor sleep is one of the biggest NAD+ killers of them all. You can read Ben’s comprehensive article on sleep for a deeper dive into methods for improving sleep here. Alcohol use and various stressors can also cause your NAD+ levels to plummet even further. Basically, your NAD+ levels will drop any time you have a higher energy demand, immune system activation due to infection, or are exposed to emotional, physical, chemical, or electromagnetic field (EMF) stressors. Check out Ben’s article “Why Electromagnetic Fields (EMFs) Are Getting More Dangerous (Plus 11 Steps You Should Be Taking To Protect Yourself)” for more on EMFs and limiting your exposure to them.
While addressing these underlying stressors should be your first line of attack against falling NAD+ levels, there are also certain supplements you can take to replenish your levels as they naturally decline with age. You can discover some of these and read more about increasing your NAD+ levels in Ben’s article “How To Keep Your NAD Levels Elevated (Without IVs) For Staving Off Aging, Cellular Health, Full Body Repair & Much More,” but I'll also get to these below. In recent years, several studies have shown that the treatment of old mice with precursors to NAD+ can significantly improve health by increasing insulin sensitivity, reversing mitochondrial dysfunction, reducing stem cell senescence, and extending lifespan.
However, according to one study, boosting levels of NAD+ may also be counterproductive and actually make senescent cells more aggressively inflammatory.
If you remember, these “zombie” cells accumulate with age and are a major cause of the chronic inflammation that comes with aging and that drives the progression of many age-related diseases. For this reason, I don't recommend daily NAD+ supplementation and do recommend taking something like fisetin or quercetin with your NAD+ supplement as well as following up with a senescent cell-clearing and recycling protocol.
Taking NAD+ makes a lot of sense when looking at the research—after all, your cells need to make energy through your mitochondria—but you also need to have a strategy to suppress, and subsequently clear, senescent cells after NAD+ supplementation.
This is where the Mito Fast Protocol comes in.
The Mito Fast Protocol
In order to address this issue of NAD+ supplementation driving inflammation via senescent cells, I developed a 6-day, 3-phase protocol known as Mito Fast that includes 1) a NAD+ loading phase; 2) an autophagy activation phase, and finally 3) a stem cell rejuvenation phase.
Because I developed this protocol during the COVID quarantine (when many of my patients couldn’t safely get in to see me), one unanticipated bonus of this protocol is that it can be done from anywhere.
I'll describe details below, but Mito Fast uses the following four products, combined with fasting:
- NAD+Max™ – For the NAD loading phase, this combination includes both precursors to NAD+ (250 mg of nicotinamide riboside and 250 mg of nicotinamide mononucleotide) as well as 500 mg of NAD+.
- Lucitol™ – A senolytic used for autophagy activation, Lucitol is a potent blend of polyphenols (including many of those mentioned earlier) including fisetin, ECGC, resveratrol, quercetin, apocynin, ginkgo Biloba, lutein, and curcumin.
- StemTOR™ – For healthy stem cell function, a combination of leucine, Rhodiola, and hydroxymethyl butyrate (HMB).
- CytoStemSurge™ – For healthy stem cell function, a combination of deer antler extract, astragalus, and the Chinese herb Fo-Ti.
You can find a full list of all products above that are needed for the full Mito Fast protocol here, and save 5% when you use code BEN. You'll notice that either suppositories or liposomal versions of these products are available. Liposomal delivery wraps up the contents inside a liposome so that it is more easily absorbed orally. Suppositories are a rectal delivery method that can be very powerful because it allows the substance to bypasses your liver and digestive enzymes so the nutrients remain intact and are slowly released over 5-6 hours— which allows for a more prolonged peak plasma in your blood. Both have superior absorption over standard oral routes of administration.
Without further ado, here is an overview of the Mito Fast Protocol I have used in my clinic:
Phase 1: NAD+ Loading Phase (Monday-Tuesday)
As I’ve already covered, NAD+ increases energy production and utilization, boosts cellular repair, coordinates circadian rhythms, and, most importantly, is crucial to mitochondrial health. Therefore, Phase 1 starts with two days of NAD+ loading. Don’t worry, the problem of NAD+ increasing inflammation in senescent cells will be addressed in Phase 2.
- After breakfast: Take (1) NAD+Max suppository or 10 mL of NAD+Max Ultra liposomal.*
- After lunch: Take (1) NAD+Max suppository or 10 mL of NAD+Max Ultra liposomal.*
*You can double up on these doses and take two suppositories at once, which will get even more NAD+ in your loading phase.
Phase 2: Cleaning, Autophagy, Senolytic Phase (Wednesday-Thursday)
It is recommended that after lunch of Phase 1, you begin a water-only fast, enter Phase 2 in a fasted state, and remain fasting throughout this portion of the protocol. If you’re new to water fasting, listen to Ben’s podcast with Dr. Dan Pompa here. Combining fasting with senolytics is the best way to clean, clear, and recycle these “zombie” cells. While not necessary, you can also incorporate ozone therapy (such as rectal insufflation or drinking ozonated water) into this portion of the protocol.
- Twice daily: Take (1) Lucitol suppository, or 10 mL of Lucitol Ultra liposomal.*
*Dosing schedule: Wednesday, Mid-day and Evening – Take (1) Lucitol suppository or 10 mL of Lucitol Ultra liposomal. Thursday, Morning and Mid-day – Take (1) Lucitol suppository or 10 mL of Lucitol Ultra liposomal.
Phase 3, Regeneration, Stem Cell Production, Cellular Growth Phase (Friday – Saturday)
During Phase 3, your dietary protein intake, if it's not already there, should be upped to 1-1.5 g per kilogram of body weight, and you should also supplement with 15-20 g of essential amino acids per day.
For those who are new to this protocol, I generally suggest repeating Mito Fast once a week for three months as well as engaging in a full 3-day water-only fast during Phase 2. After this initial loading program, you can then switch to doing Mito Fast a couple of times a year for maintenance.
Advanced Mito Fast Options
While not necessary, the advanced Phase, to be administered on the 5th day of Phase 3 (Friday, using the example above) includes extra support for stem cell production and avoiding stem cell senescence as well as microbiome and sleep support:
#1: Stem Cell Support
During Phase 3—in which you activate mTOR and thus cellular regeneration, cellular growth, and stem cell production—it is important to note that stem cells are also vulnerable to becoming senescent. Stem cell survival is a real problem in regenerative medicine today, but many doctors are using techniques to provide a better “home” for stem cells by creating an environment that provides the cells more support to proliferate and differentiate to repair and regenerate in your body.
Of the few substances that have been shown to foster stem cell survival, CoQ-10 and fucoidan are two of my favorites. CoQ10 is a powerful antioxidant and fucoidan is a polysaccharide that comes from brown seaweed. CoQ10 has shown to protect stem cell aging and mechanisms of cell senescence and fucoidan rescues mesenchymal stem cells from cellular senescence and increases stem cell proliferation through the regulation of cell cycle-associated proteins.
#2: Microbiome Swarming & Sleep Support
Microbiome swarming (cycles of probiotic growth periods through natural circadian rhythm stimuli that are activated through gut melatonin) is one under-the-radar and very important aspect of achieving quality sleep that simultaneously promotes the growth of good bacteria in your gut. See, your gut produces 400 times more melatonin than your brain, and gut melatonin is the main activator of microbiome swarming, which is the primary signal for the good bacteria in your gut to grow in numbers.
Melatonin is made by your mitochondria to deal with stress and its benefits beyond sleep are well researched in medical research and include antioxidant, anti-inflammatory, and anti-apoptotic activities. Recent studies suggest that your gut flora, which is composed of trillions of healthy bacteria, is regulated primarily by your circadian clock. This circadian rhythm, in turn, is regulated by how much melatonin is secreted by your body, and at what times it is secreted. Melatonin has been shown to specifically increase the magnitude of swarming in the cultures of E. aerogenes, though not in other species like in Klebsiella pneumoniae and Escherichia coli. The swarming appeared to occur on a daily basis by the body's circadian rhythm and was synchronized perfectly with the presence of melatonin.
To promote microbiome swarming, as well as general sleep hygiene and improved mitochondrial function, super high doses of melatonin (100-200 mg) can be helpful. Using melatonin in a suppository makes the most sense for this action as the microbiome primarily exists in your large intestines.
This all brings me to the final (optional) component of Mito Fast, which includes nutrient support for new stem cells to prevent senescence as well as microbiome swarming activation, and microbiome probiotic support.
Advanced Option for Friday of Phase 3
- At bedtime: Take (1) Sandman™ suppository (high-dose 200mg melatonin)
- Morning and evening: Take (1) StemZen™ suppository (CoQ10 & fucoidan)
- Morning and evening: Take (1) Pro ByoMax™ suppository (spore-based probiotic and butyrate)
It is important to use these nutrients post-fast so that once your new stem cells are released, more of them will have a chance to survive. The Sandman suppository can be taken for up to a week or so post-fast for additional microbiome support.
If you want to think more clearly, have more energy, and simply function at a higher level, you can’t ignore the two aspects of health that lead to better and stronger mitochondria: restoring youthful NAD+ levels and promoting cellular cleanup and recycling through autophagy.
The Mito Fast protocol was designed to do just that, is easy-to-do, and well-tolerated by most. The Phases can be repeated weekly, monthly, quarterly, or once a year.
- Phase 1: Support your mitochondrial health, increase cellular energy, and boost cellular repair by naturally boosting your NAD+ through getting plenty of deep, restful sleep, avoiding alcohol, minimizing stress and EMF exposure, and taking supplements that boost NAD+ such as NAD+Max
- Phase 2: Maximize autophagy by fasting; incorporating foods such as black coffee, Ceylon cinnamon, and turmeric into your fasting practice; and combining fasting with naturally occurring senolytic plant compounds and senolytic supplements such as Lucitol.
- Phase 3: Increase stem cell production through mTOR signaling by upping your dietary protein intake and taking supplements such as StemTOR and CytoStemSurge, encourage microbiome swarming with high-dose melatonin, and prevent stem cell senescence post-fast with supplements such as StemZen.
Before you start this protocol or any fasting program mentioned in this article, consult your health care provider and use their guidance. I work with cases virtually via consultation, Instagram, CellularReset Channel on YouTube, and my educational site. You can reach my clinic at (941) 330-8553. This article is not meant to diagnose, treat, or cure any disease, nor is it meant to be construed as medical advice.
I realize this may seem complicated, but both Ben and myself and my patients have been using Mito Fast protocols with very good success, so it's definitely worth weaving in a few times a year to your anti-aging, health, and longevity protocol. Leave your comments, questions, or thoughts on Mito Fast below, and I'll get back to you!