In previous installments of THE SEVEN, we spent a few thousand words discussing what to eat and what not to eat, but there’s another variable to consider here. Perhaps just as important is the consideration of when to (and when not to) eat.

I’m referring, of course, to time-restricted eating (aka fasting) - the practice of abstaining from eating for periods ranging anywhere from 14 hours to several weeks.

The list below of beneficial processes stimulated by time-restricted eating speaks for itself - this is unquestionably one of the most powerful tools we have for promoting health in the body and brain, and slowing the march of biological aging.

Interestingly, when you look at the underlying metabolic mechanisms behind these benefits, many of these are stimulated exclusively (or almost exclusively) by fasting.

In light of this, I think there’s a case to be made that fasting is something we’re “designed” (by millions of years of evolutionary forces) to be doing - and true health simply can’t be fully realized without it.

Time-Restricted Eating: The Benefits

Enhanced Cellular Cleansing (aka Autophagy)

Here’s a general outline of how our cells age:

When cells are young, they generally carry out their functions efficiently, owing in part to an absence of waste matter in the cell.

As time goes on, proteins in the cell are inevitably damaged (or not produced correctly to start with). New proteins are produced in their place and life goes on, but these damaged proteins are effectively waste matter, left floating uselessly around the cell, waiting to get in the way of something important.

As more and more waste matter accumulates in the cell, it becomes less and less efficient and “ages”. When you get a bunch of these waste-filled, inefficient cells in a given tissue or organ, that tissue/organ becomes inefficient and “ages” as well.

Thankfully, this need not be a one-way process, as our cells do have a tool for clearing out this waste and slowing/reversing aging.

That process is autophagy, in which organelles in the cell called lysosomes degrade and then recycle unneeded or dysfunctional proteins.

So what’s the strongest signal we can send our cells to upregulate autophagy and reverse aging? Time-restricted eating of course. [1]

Improved Brain Health + Cognition

There are a set of metabolic processes neurologists will tell you are essential for maintaining a healthy, high-performing brain, and fasting - remarkably - stimulates essentially all of these.

Fasting increases circulating levels of several neurotrophic factors, biomolecules that support the growth, survival, and differentiation of neurons. The result is enhanced network plasticity (critical for learning), increased stress resilience and increased mitochondria (i.e. increased cognitive energy).

Fasting also reduces oxidative stress (and thus, inflammation) in the brain both by stimulating the removal of damaged molecules and stimulating the production of endogenous antioxidants. [2] All of these translate to meaningful improvements in brain performance.

Fasting has also been shown to reduce the neuronal dysfunction that results from Alzheimer’s, Parkinson’s, and other neurodegenerative diseases. [3]

Slowing/Reversing Markers of Aging

A common way biochemists define aging is as “the slow accumulation of dysfunctional proteins and organelles in our cells” - a process that leads eventually to cell dysfunction and/or death.

Because it powerfully stimulates autophagy, fasting can dramatically slow or reverse this process, stimulating cells to “clean house” and preventing the dysfunction that can lead to disease (including cancer). [4]

Improved Body Composition

Fasting increases insulin sensitivity and adiponectin levels, two key hormonal factors that determine if stored body fat gets oxidized (used for energy) as well as if incoming caloric energy gets used immediately or stored (as fat) for future use. [5][6]

These hormonal changes persist well after a fast is completed. So while the calorie deficit you run on fasting days will improve body composition a bit, these hormonal changes will be the force that more substantially improves body composition over days and weeks.

Cancer Prevention/Treatment

Talk to most anyone involved in research around calorie restriction or fasting and they’ll tell you these are tragically underused tools in the cancer-treatment toolkit.

Fasting has been shown to be comparable in efficacy to chemotherapy in delaying the growth of certain types of tumors. [7][8] Think about that: fasting is comparable in efficacy to the unbelievably toxic chemical soup that works by (hopefully) killing cancerous cells ever-so-slightly faster than it kills the recipient. Why is fasting not more used in oncology?

At a minimum, a fasting protocol should be used in addition to chemotherapy, as it has also been shown to preferentially protect non-cancerous cells from chemo drugs. [9]

Digestive Reset

Allowing the GI tract to rest during fasting periods allows for a sort of digestive reset, which reduces intestinal inflammation, improves motility (the contraction of GI muscles during digestion), optimizes nutrient absorption, and ensures bowel movement quality and regularity. [10] This is likely to be the benefit you experience most noticeably when doing daily intermittent fasting.

Studies have also shown that fasting can improve the resilience of gut microbiota,[11] reduce populations of harmful bacteria, [12] and even increase bacterial species that promote lipolysis (fat burning). [13]

Time-Restricted Eating: Implementation

1. [Every Day] 14-18 Hour (Modified) Intermittent Fast

Daily intermittent fasts are simple and, likely, way easier to do than you might be thinking (particularly when using the modification practices described below).

Here’s how intermittent fasting works:

When we’re sleeping we’re (hopefully) not eating. So there’s a 7-8 hour fast without even trying. Turning this into a proper intermittent fast is simply finding the easiest way to tack a few hours onto each end of your sleep.

Research shows that sleep quality is a world better when we finish eating a minimum of 3 hours before bedtime (yes, that includes snacking), so if we adhere to that, we’re already at 11 hours. Now you just have 3 hours after waking up before eating your first meal, and - voila - you’re at 14 hours.

Most of the resistance you’ll encounter tends to be psychological habituation - your brain is likely accustomed to getting mouth pleasure (aka breakfast) within a couple of hours of waking, and this addiction might take a week or so to re-pattern.

Making sure you fully rehydrate in the first hour after waking will do a lot to get you past this resistance point (you can find hydration best practices here). So too will caffeine, which suppresses hunger and - thankfully - doesn’t disrupt the beneficial metabolic processes we’re aiming to set in motion (sans milk or sugar, of course).

14 hours is the minimum for most people to see any level of beneficial metabolic effects, but ideally, we should be aiming for a daily fasting period in the 16-18 hour range, where autophagy tends to be more meaningfully upregulated.

This is where the “modified” part of this protocol comes in to make things a lot more manageable:

Consuming a few hundred calories of easily digested fats like ghee, coconut oil, and (ideally) MCTs doesn’t significantly disrupt the metabolic signal-sending we’re after, but it does make the fasting period more pleasurable.

I usually do this via my late-morning matcha lattes.

4oz Almond Milk
6oz Boiling Water
2tsp (3g) Matcha Powder
2 Scoops (10g) Ketobasis MCTs
1Tbsp (13g) Grass Fed Ghee

Directions: Add contents to a jar or blender, shake/blend. Enjoy.

That’s 23g/207cal of clean, easily utilized fats that keep my energy levels up and my brain sharp for the duration of the modified fasting period (and it’s considerably yummier than any cafe-bought matcha latte I’ve ever had).

2. [Every 1-3 Weeks] 24-30 Hour (Modified) Fast 

Autophagy is not an on/off proposition - the level of cellular cleansing (and all the health benefits that come with it) can vary greatly depending on the strength and duration of the signal we send our cells.

There is good evidence that sending a stronger signal delivers benefits that more frequent, weaker signals do not, even in the cumulative. This is where 24 hour fasts come in.

Researchers measure the level of autophagy by counting the number of autophagosomes (the cellular organelles that handle protein degradation), and have found that this number increases by 300% after 24 hours of fasting, and an additional 30% after 48 hours of fasting. [14] 

Based on this and related research, the 24-36 hour range seems to be the sweet spot where we get the greatest benefit per hour invested. 

Getting to the 24 hour mark is easier than you might think, particularly if you've been doing modified intermittent fasting for a few weeks and are comfortable fasting for 16-18 hours.

A modified 24 hour fast follows the same formula as the modified 14-18 hour fast described above. Hydration is key, caffeine helps a ton, and consuming a bit of MCTs or other easily-digested fats makes things a lot more comfortable.

(I'd avoid eating more than 400 calories of fat throughout your fasting period, as more than this risks engaging the digestive tract and disrupting some of the beneficial processes you've set in motion)

A note: I set the recommended interval for 24-hour fasting at once every 1-3 weeks, but I'll admit this is mostly to make it seem less intimidating. I personally do a 24-30 hour fast once each week, and I believe this to be the ideal interval. That being said, doing a 24 hour fast once every 3 weeks delivers infinitely more benefit than not doing it at all - so start with the interval you're confident you'll actually do.

3. [2-4 Times/Year] 72 Hour Fast

I'm definitely aware that multi-day fasts are intimidating and probably not for everyone. 

Still, multi-day fasts have been shown to deliver a qualitatively unique set of benefits, so they clearly deserved a section of their own.

I do two multi-day fasts each year, on average, and they're among the most significant and transformative days of my year. You learn a LOT about your relationship to food when you go without for a few days. 

I won't say multi-day fasts are "fun", but I always value the experience highly.  My stress resilience tends to drop during these longer fasts, and I definitely recommend doing these at a time when you can rest, relax and largely avoid the typical stresses of your life.

As far as the implementation, I modify the first fasting day (same as described in the sections above) to make the transition a bit smoother, but days two and three are truly zero calorie - nothing goes in my body other than water and tea.

I've done a couple multi-day fasts without caffeine, and these, not coincidentally, were the least fun fasts I've done.  Caffeine is an appetite suppressant, which obviously helps. But really, this is more about not adding the stress and discomfort of caffeine withdrawal on top of the challenges that are inherent to multi-day fasting. Caffeine doesn't significantly disrupt the beneficial metabolic processes we're setting in motion, and studies have shown it may even accelerate autophagy. 

Low-Carbohydrate, Metabolic-Flexibility (LCMF) Diet Makes Everything Easier

You might have noticed some overlap in the recommendations in this article with those in the second installment of this series, [THE SEVEN] 2. Low-Carbohydrate, Metabolic-Flexibility Diet.

That's because these two principles work in synergy - the LCMF diet makes fasting a world easier because the body is metabolically ready to use whatever energy source is available, including our body's stores of glycogen and fat in adipose tissue (which the body will be using for energy almost exclusively during a fast).

References:

[1] http://www.tandfonline.com/doi/full/10.4161/auto.6.6.12376

[2] https://www.ncbi.nlm.nih.gov/pubmed/23168220

[3] https://www.ncbi.nlm.nih.gov/pubmed/17306982

[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946160/

[5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358975/

[6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946160/

[7] https://www.ncbi.nlm.nih.gov/pubmed/12016155

[8] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608686/

[9] https://www.ncbi.nlm.nih.gov/pubmed/18378900

[10] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128599/

[11] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924599/

[12] https://www.sciencedirect.com/science/article/pii/S2590097819300035

[13] https://pubmed.ncbi.nlm.nih.gov/22972297/

[14] https://www.tandfonline.com/doi/full/10.4161/auto.6.6.12376