Whether you practice extended fasting or just intermittent fasting (TRE), you probably care about the potential health benefits.
But let’s be real…
Going long periods without food sucks. The human body is biochemically wired to eat as much as we can. This ensured our ancestors’ survival.
And there’s a secret that most longevity doctors and experts won’t tell you…Certain fasting biohacks make it easier, healthier, & more beneficial Click To Tweet
I call these, the “fasting amplifiers”.
Listen up, because over the next few years, they’ll become common knowledge. In fact, fasting without the below protocol will seem archaic. So today I am going to share with you some powerful tips to supercharge your fasts to get greater benefits and incredible results.
The Fundamental Strategy to Amplify Your Fasting Benefits & Results
If you do nothing else, the time leading up to your fast makes all the difference.
Whether it feels torturous and yields little (perhaps even harms your metabolism). Did you know that losing fat best predicts weight gain in the future?
Or, conversely, it effortlessly passes all the while improving your health and freeing up your attention.
Start the day before your. By choosing the right kinds of foods, you strategically tune your gut and microbiome and set yourself up for success.
Humans might not need fiber, but the gut and microbiome certainly do.
Our goal on the day before the fast is to drive the production of a postbiotic called butyrate sky-high. We also balance the immune system. How do we do those?
By consuming lots of fiber. Mostly by consuming resistant starches and raw veggies. When you consume lots of fiber, your gut bacteria get to feed on it and multiply (this is fermentation).
We also consume certain polyphenol-rich fruits like berries to increase levels of a class of probiotics (bifidobacteria) and a specifically highly-prized bacteria called Akkermansia.
Both Akkermansia and butyrate protect the gut from degradation and damage induced by fasting. Plus, they make the internal environment more conducive to beneficial adaptation.
This combination mimics what humans naturally experience in everyday living. By strategically implementing this, we amplify the body’s fasting biosignals.
For a lot of people, fasting is unbearable. Whether that’s you, or you just want to extend the benefits, you can use a little biohack called a “fasting-mimicking diet”.
Compared to normal eating, there are several key components to it. You consume:
- Fewer calories
- Little protein
- Low to zero carbs
You must keep levels of the hormone insulin low.
Like fasting, this sends a similar biological signal throughout your body that food is still scarce and it should conserve resources.
This lets the body continue the processes of the cellular renewal processes of autophagy, mitophagy, and pexophagy.
Whether you’re intermittent fasting or doing an extended fast, experts often forget to mention the importance of the period immediately following the fast.
Fasting acts as a powerful catabolic (tissue-destructive) force. When done appropriately, with the right frequency, this has definite health benefits.
The longer and/or the more frequently you fast, the more important this period becomes.
You must consume abundant protein and fat. Ideally, from animal sources. They contain the ideal ratios and quantities of fatty acids and amino acids.
I also recommend using one of these top essential amino acid supplements. ESPECIALLY if you’re plant-based.
Getting ample fats and amino acids tells your body it’s safe to repair, regenerate, and grow. It also facilitates fat loss and strength. Optimizing both of those are powerful longevity biosignals.
The Best Fasting Mimetics & Amplifiers
Armed with the basics, you can add certain things during your fasts to get greater results and notice more benefits.
These fasting mimetics and amplifiers tend to work on one or more of the following:
- Sirtuin Activators – Sirtuins are a family of proteins highly involved in aging. Substances that activate sirtuins also mimic the benefits of caloric restriction.
- AMPK Activators – An enzyme involved in cellular energy balance. It’s activated by exercise, fasting, and calorie restriction and has both mimetic and amplification benefits.
- mTOR Inhibitors – A pathway that regulates cellular growth and metabolism. Substances like the famous rapamycin inhibit growth and mimic the effects of fasting.
- PGC-1α Activators – A primary protein that regulates energy metabolism and mitochondrial biogenesis. Compounds that activate PGC-1α have fasting-mimicking & amplifying effects.
- GLP-1 Activators – A class of compounds that mimic the action of GLP-1, a hormone involved in satiety and insulin secretion. Specifically, they mimic the hormonal effects of fasting on insulin secretion and satiety (and make fasting easier).
- Autophagy Activators – A bodily process of cleaning damaged cells. Substances that induce autophagy mimic the cellular cleaning benefits that occur during fasting.
Some substances have multiple of the above effects. Some work in novel ways.
Exogenous ketones are a special supplement designed to mimic the ketones the body naturally produces during periods of fasting or low-carb intake.
These molecules serve as an alternative fuel source for various organs, particularly the brain. This is one of the main mechanisms behind the ketogenic diet causing profound mental clarity after the adaptation phase.
Exogenous ketones came as ketone “salts” and ketone “esters”. They’re mostly used by those following a ketogenic diet, athletes for performance enhancement, or to support general metabolic health.
Exogenous ketones amplify the benefits of fasting by providing the body with a direct source of ketones, deepening your state of ketosis regardless of your diet. They provide all kinds of potent benefits:
- Suppressing appetite
- Boosting and stabilizing energy levels
- Inducing mental clarity
- Alleviating “keto flu” symptoms caused by insufficient carb intake
- Potential weight loss via increased beta-oxidation (body fat burning)
- Metabolic biomarker improvements
What’s awesome is that these top exogenous ketone supplements don’t increase insulin production or blood sugar.
So if anything, they deepen the metabolic benefits, mimic the effects of fasting, and make it a ton easier to sustain.
Supplemental molecular hydrogen (H2) usually comes as hydrogen-rich tablets that dissolve in water to release hydrogen gas. You can also find molecular hydrogen generators and “Brown’s Gas Generators”.
Molecular hydrogen therapy has been proven effective and powerful in over 2,000 studies across 200+ disease models.
Some of the many relevant benefits of H2 include:
- Steady energy levels
- Selectively reducing damaging oxidative stress
- Optimizing inflammation
- Supporting autophagy
- Stabilizing metabolic biomarkers
Indeed, this 2023 Chinese study found that H2 users feel less tired and more energetic [R].
It’s best known for its selective antioxidant properties. H2 reduces levels of just the harmful reactive oxygen species (ROS) within the body while leaving important signaling molecules and pathways intact. Earning it the nickname…H2 is the molecule of bioharmony Click To Tweet
Fasting naturally induces a stress response, increasing the process cells use to remove dysfunctional components (autophagy). Naturally reducing inflammation and oxidative stress. Molecular hydrogen amplifies both of these effects, making autophagy more effective.
H2 also protects cells and DNA from (non-hormetic) damage during fasting. Plus, molecular hydrogen supports the beneficial fasting-induced metabolic changes.
Finally, studies suggest it improves lipid and glucose metabolism. Further improving metabolic biomarkers like blood glucose levels and insulin sensitivity.
This is one of those supplements that I actually feel a difference from using. Especially when I fast. You can get any of these top molecular hydrogen tablet products to add to your water. Or you can do what I do, and use a quality Brown’s Gas generator like the AquaCure.
Grains of Paradise
Grains of Paradise, scientifically called Aframomum melegueta, is a spice related to ginger and native to West Africa. It’s most often used in traditional African medicine.
The seeds contain many compounds. The main bioactive (6-Paradol, 6-Gingerdione, 6-Shogaol, & 6-Gingerol) have thermogenic properties. Meaning they increase metabolic rate.
Grains of Paradise benefits fasting by stimulating brown adipose tissue (BAT) activity. BAT burns calories and generates heat, a process called non-shivering thermogenesis.
Potentially increasing energy expenditure and fat burning. It’s especially great for reducing the most unhealthy (visceral) form of body fat. Since people often fast to improve their body composition, Grains of Paradise can help.
This may also help mimic the effects of caloric restriction without difficult and unsustainable food reduction.
The spice’s impact on BAT should also improve insulin sensitivity and glucose regulation. Further improving metabolic health.
Grains of Paradise is more of a fasting amplifier than a mimetic but, nevertheless, makes a great addition to a regimen. Especially when you’re exposed to cold temperatures.
Medium-chain triglyceride (MCT) oil is a special type of dietary fat derived from coconut oil. It bypasses normal digestion and the liver rapidly converts it into ketones. C8 MCT oil, particularly, is the most potent form of MCT with the fewest side effects.
Since it’s a dietary fat (and contains calories), technically it inhibits some aspects of fasting. However, unless you’re doing it for medical purposes, the benefits of MCT outweigh the potential cons (for most people).
Like exogenous ketones, C8 MCT oil induces a state of ketosis quickly. Leading to similar benefits:
- Mental clarity and performance
- Appetite suppression
- Alleviating “keto flu” symptoms caused by insufficient carb intake
- Potential weight loss via increased beta-oxidation (body fat burning)
- Metabolic biomarker improvements
C8 MCT also yields many metabolic benefits, like improved insulin sensitivity and blood sugar levels.
Interestingly, C8 intake is associated with greater energy expenditure and improved thermogenesis. Meaning it can potentially increase calorie burn during fasting, and thus lead to greater fat loss. Despite it containing calories.
So why would you choose C8 MCT oil over exogenous ketones? Price. These are quite a bit cheaper, although not as potent.
Check out my favorite brand here, and make sure to follow the serving size (or risk GI upset). This is a key ingredient in my Outliyr Genius Coffee recipe and a much better alternative to cream or half and half.
Adaptogens are a class of natural substances known for their potential to help the body resist and adapt to stressors. Adaptogens help you effectively buffer stress (and fasting is a major stressor).
Three specific adaptogens in particular help during fasts:
- Rhodiola Rosea
Rhodiola rosea, also known as golden root, is well-studied to support metabolic health and resilience against stress. It contains bioactives that improve energy metabolism, mood, focus, learning, strength, fatigue, and even reduce irritability.
Rhodiola also helps modulate levels of stress hormone. Improving energy, clarity, and vitality.
Ashwagandha, called Indian ginseng or the “royal herb”, is perhaps the best-studied adaptogen of all. It’s associated with better metabolism and is nicknamed the “king of stress reduction”. It supports adrenal health (which is taxed during fasts).
Ashwagandha improves glucose metabolism, powerfully combats stress, slows biological aging, boosts resilience to stress, increases energy, helps build muscle and strength, and even improves feelings of well-being.
Ginseng, particularly a kind called Panax ginseng, is the final example proven to complement many facets of fasting. Ginseng helps with stress modulation and metabolic function. This adaptogen helps with glucose metabolism, insulin sensitivity, energy, stamina, inflammation, cardiovascular health, cognitive function, and mental clarity.
The best fasting support supplements stack all three of these adaptogens together into one product. Each of them helps mitigate the negative hormonal and neurochemical consequences of fasting. They pass the evolutionary biology test, as ancient hunters would use these same roots/botanicals/etc to heighten their experience.
Berberine is a bioactive alkaloid extracted from several plants. It has a long and rich history of use in traditional Chinese and Ayurvedic medicine. For many ailments. It’s best known for its ability to improve insulin sensitivity and regulate glucose and fat metabolism.
Fasting typically improves metabolic health biomarkers like blood glucose levels, insulin sensitivity, and lipid profiles. Berberine can amplify these effects by sensitizing the body to insulin and regulating blood sugar.
By activating AMP-activated protein kinase (AMPK), an enzyme often referred to as a metabolic master switch, berberine mimics the cellular effects of calorie restriction. Activating this “switch” increases fat burning and reduces the creation of new fat cells.
Berberine is also known to benefit those with high cholesterol and triglycerides.
Fasting naturally modulates the gut microbiota. Berberine can improve gut health by amplifying this effect.
Plus, like H2, it should help reduce inflammation and oxidative stress (albeit, not selectively). Complementing the cellular cleaning process of autophagy that’s already induced by fasting.
Do note that berberine can be a bit rough on the gut and can dramatically reduce blood sugar. Fasting often already results in low blood sugar, especially if you’re not accustomed to it. Keep that in mind before using it while fasting.
Personally, I sometimes use berberine’s superior cousin called Dihydroberberine while fasting to normalize any metabolic biomarkers that are imbalanced (or to support blood sugar when consuming a high-carb meal).
Check out my guide to the best berberine supplements to avoid making common mistakes.
Spermidine is a naturally occurring “polyamine” compound found in foods like aged cheese, mushrooms, soy products, legumes, and whole grains. If you have the right gut microbiome, your bacteria can also produce Spermidine.
It plays a key role in cellular processes like cell growth and proliferation. Spermidine’s also one of the best substances known to induce the cellular renewal process of autophagy.
This is the main mechanism behind its ability to amplify the benefits of a fast and one of the core reasons a company called Mimio chose to use it in their fasting biomimetic supplement.
For context, Autophagy is the process by which cells break down and recycle their components, removing damaged proteins and organelles. The better cells function, the more efficient the body and the longer your potential health span.
Spermidine also has the potential to benefit other common goals of fasting.
It has cardiovascular benefits, including lowering blood pressure and improving heart function.
On the neuroprotective side, spermidine may protect neurons and support cognitive health.
Finally, like fasting, it also helps modulate the immune system. This can really help balance the immune response and manage chronic inflammation. Both improve health outcomes and longevity.
Learn everything you should know in my ultimate guide to the best spermidine supplements.
Senolytics are a class of substances that target and eliminate a type of cell that drains resources, doesn’t perform its roles, and infects other cells. For this reason, senescent cells are sometimes called “zombie cells”. They accumulate with age and cause tissue dysfunction, chronic inflammation, and age-related diseases.
Senolytic complexes refer to a combination of substances that aid the removal of senescent cells from the body.
They complement the effects of fasting on cellular rejuvenation and longevity. As we’ve covered, fasting induces autophagy. Senolytics further enhance this clearance by eliminating senescent cells that persist even during/after fasting.
Removing senescent cells promotes tissue regeneration, enhances organ function, and potentially undoes age-related diseases associated with cellular senescence.
These senolytic supplement complexes also contain natural compounds that reduce oxidative stress and inflammation.
Senolytic therapy is a hot frontier of modern anti-aging medicine. To incorporate this into my fasting, I would only use a strong senolytic for a maximum of about two days per month. Ideally, in a short period (like back-to-back days).
Learn more in my scientific guide to the best senolytic therapy supplements.
Pterostilbene is a natural phenolic substance found in small quantities within foods like blueberries, grapes, and the bark of the Indian Kino Tree. Pterostilbene is related to resveratrol, another compound known for its potential health benefits, but pterostilbene has better bioavailability and stronger effects.
Pterostilbene impacts pathways related to caloric restriction and fasting. Specifically, it activates the SIRT1 protein (as do caloric restriction and fasting). Since it also improves insulin sensitivity and lipid profiles, pterostilbene mimics metabolic changes that occur during fasting.
It’s also a strong antioxidant and potentially cognitive-enhancing and neuroprotective. Pterostilbene may even support neuroplasticity and cognitive performance. Potentially complementing the neurological benefits of fasting.
Finally, pterostilbene’s anti-inflammatory properties amplify the anti-inflammatory effects of fasting.
Pterostilbene is one of the fasting mimetics and amplifiers that many of the world’s top longevity scientists know about and the general public hasn’t really discovered.
Urolithin-A is a postbiotic metabolite produced after the gut ferments ellagitannins (a family of natural compounds found in pomegranates, strawberries, walnuts, and raspberries). Not everyone can produce urolithin-A, as it requires the presence of specific bacteria in the gut.
Once it reaches the bloodstream, urolithin-A has various health benefits, like cellular rejuvenation, mitochondrial biogenesis, and anti-inflammatory effects.
Urolithin-A promotes the cellular process of removing damaged components (autophagy). Yet it is also one of few substances that activate the similar process of mitophagy.
Mitophagy is the selective removal of damaged mitochondria. Improving energy metabolism and reducing oxidative stress within cells. Overall helping us maintain mitochondrial quality and cellular health.
Urolithin-A also increases mitochondrial biogenesis, the formation of new mitochondria within cells.
Plus, it shows promise for reducing inflammation and supporting immune function.
Then there are the potential urolithin-a cognitive health benefits for brain function and neuroprotection.
While less known, this substance also appears to have muscle and endurance benefits too. Possibly due to the improved mitochondrial health & performance.
Urolithin-A is an autophagy and mitophagy-enhancing superstar. I expect this supplement to become well-known and quite popular over the next five years or so.
Nicotinamide adenine dinucleotide (NAD+) is a coenzyme found in all living cells. It’s key to countless cellular processes, including energy metabolism, DNA repair, and gene expression.
Without NAD+, we’d be dead in seconds. Levels of it decline with age, and this decline causes age-related issues.
Fasting has been shown to increase NAD+ levels, and combining fasting with NAD+ supplementation can amplify these effects.
Especially, to enhance mitochondrial function. NAD+ is key for mitochondria, the cellular energy factory. Supplementing with NAD+ boosters can improve energy utilization and fat burning.
NAD+ supplementation helps improve DNA repair and genomic stability. This is especially helpful in promoting the removal of damaged cellular components through autophagy.
Plus, NAD+ regulates many enzymes, including sirtuins. Sirtuins help cellular maintenance and longevity. Pterostilbene (discussed earlier) is a powerful sirtuin activator.
Combining NAD+ boosters with sirtuin activators is a potent strategy to gain maximum cellular repair benefits.
NAD+ also helps regulate circadian rhythm, which gets disrupted by aging and irregular eating patterns (ie fasting). Meaning that this can help optimize the timing of cellular processes, aligning with the potential benefits of time-restricted eating or intermittent fasting regimens.
If you’ve tried to sleep while fasting, you probably noticed that becomes harder. This supplement can help provide a clean source of energy the next day and mitigate some of the side effects of sleep deprivation.
Finally, it impacts immune function and chronic inflammation.
But here’s the catch…
The famous NAD+ precursors, like Nicotinamide Riboside (NR) supplements and Nicotinamide Mononucleotide (NMN) supplements, may help boost levels of NAD+. But they’re not the best way and they can come with serious side effects.
The smart approach to optimizing NAD+ levels is via:
- Improving the body recycling process (salvage pathway)
- Using polyphenols like apigenin and quercetin to slow down the activity of the CD38 enzyme (which degrades NAD+)
- Adding the proven cheap and strategically formulated complexes
I suggest checking out this guide to the free & cheap ways to optimize your NAD+ levels.
AICAR (5-Aminoimidazole-4-carboxamide ribonucleotide) is an analog of adenosine monophosphate (AMP). It’s known to activate AMPK, the key “switch” regulating cellular energy balance.
AICAR shares the properties of classic exercise mimetics, and because it activates AMPK, it’s both a fasting mimetic and an amplifier.
It also influences other cellular processes. Like glucose uptake, insulin sensitivity, and fatty acid oxidation. Research suggests it can help improve metabolic health and may confer some of the many benefits of exercise.
This substance also promotes the creation of new mitochondria within cells (mitochondrial biogenesis). Nicely complimenting the mitochondrial adaptations induced by fasting.
I wouldn’t turn to AICAR as one of my first strategies. It’s not very well studied in humans compared to the others.
But it’s potent, and due to its potential ergogenic benefits is banned by the World Anti-Doping Agency (WADA) for use in sports.
L-β-Aminoisobutyric acid (L-BAIBA) is a naturally occurring amino acid derivative showing promise for metabolic health and as a potential exercise mimetic. It’s a byproduct of the breakdown of thymine, an important component of DNA.
Through an evolutionary lens, fasting and exercise often went together.
Research suggests that L-BAIBA levels increase during exercise, which may explain its role in modulating metabolic processes (especially via PPAR activation). It’s a key signaling molecule resulting from exercise.
L-BAIBA has insulin-sensitizing effects and promotes fatty acid oxidation. Both are key adaptations caused during fasts.
L-BAIBA also supports metabolic health by acting as an anti-inflammatory, insulin sensitizer, and blood sugar regulator.
Lastly, it appears to influence brown adipose tissue activity. Potentially increasing energy expenditure and thermogenesis. Helping you burn body fat for energy.
This wouldn’t be my top pick, but it would stack nicely with fasting and Grains of Paradise (and perhaps some cold exposure) to transform your body fast.
Peptides like SS-31 and MitoQ are specialized substances that specifically target and optimize mitochondrial function. Popular therapeutic peptides have incredible power-to-safety ratios.
These substances “suggest” changes to the body rather than bluntly forcing them.
Fasting is a great tool to promote cellular renewal (autophagy), and a similar process of mitochondrial renewal (mitophagy).
SS-31 and MitoQ support mitochondrial function by reducing oxidative stress, promoting energy production, and enhancing cellular respiration. They also protect mitochondria from damage and support overall cellular health.
These mitochondrial peptides also have anti-inflammatory effects.
They are another form of fasting mimetic and amplifier.
Whenever I use them, I enjoy a nice uptick in steady all-day energy.
See this article to learn more about using therapeutic peptides to enhance the benefits of fasting.
Interesting Substances That Warrant More Research
There are tons of cool and emerging fasting amplifiers and mimetics that may warrant attention.
I’m not comfortable including them in the above list because they lack significant research.
The main two I’ve come across include:
- 2-Deoxy-D-glucose (2-DG) – A glucose analog that inhibits glycolysis and is being studied for its potential to mimic calorie restriction.
- GDF11 (Growth Differentiation Factor 11) – Mouse studies suggest it may rejuvenate aging tissues, potentially complementing autophagy. But the research is quite preliminary.
You can look into more of those on your own.
Amplifying the Benefits of Your Fasting
Throughout history, humans naturally experienced periods of abundance (feasting) and scarcity (famine).
Today, the mere click of a button grants us access to nearly unlimited calories. For much of the world, over-nutrition has become the norm.
Strategies like intentional fasting can help restore this vital balance.
But few people enjoy fasting. It’s not fun, and can even be harmful.
So in this post, I laid out ways to get more out of your time spent fasting. Greater benefits, faster and easier.
The most important strategy centers around optimizing your nutrient intake the day before a fast. Getting lots of fiber and polyphenols to nourish your gut microbiome.
Gut bacteria ferment fiber into a super-protective postbiotic called butyrate.
The polyphenols act like fuel to help shift the composition and function of your gut toward an ideal state to amplify periods without food.
Once you master those, you can experiment with other substances that either mimic or amplify your fast.
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Now, what about you? If you do anything to amplify your fasts, drop a comment below and let us know!