The Profound Benefits of Fasting (and Autophagy)

Graham Ryan

03 May 2017

In the endless debates over what-to-eat and what-not-to-eat, consideration of when to eat too often gets overlooked. This is unfortunate - research shows pretty convincingly that timing our meals intelligently can produce remarkable health benefits.

I’m referring specifically to fasting, defined loosely as the practice of abstaining from food for periods ranging anywhere from 12 hours to several weeks.

Intermittent fasting (IF) - the practice of regularly reducing calorie intake to zero for periods of 12-24 hours - continues to gain popularity with many IF-practitioners experiencing dramatic (and largely effortless) improvements in cognitive function and/or body composition.

For the past 4 years or so I’ve been following the most popular version of IF; restricting (almost) all of my calorie consumption to a 6-hour window each day (thus doing a daily 18-hour “fast”). The benefits of this practice are profound, and it’s probably the single most impactful dietary practice I’ve adopted in the past 5 years.

Recently, however, after diving into newer research elucidating the mechanisms behind the benefits of fasting, I’ve changed the timing and structure of my fasts a bit in an effort to maximize the activity of these mechanisms.

The 2016 Nobel Prize in Physiology Or Medicine went to a Japanese scientist by the name of Yoshinori Ohsumi for his discoveries of the mechanisms behind autophagy, a cellular maintenance process - stimulated by fasting - that is critical in disease resistance, longevity and general body and brain vitality.

To vastly (but not inaccurately) oversimplify: healthy cells are actively autophagic, unhealthy cells are not.

The changes I’ve made to my own fasting protocol were specifically intended to increase stimulation of autophagic activity. Before going into these let’s first look at the ridiculously-long list of beneficial metabolic and hormonal processes stimulated by fasting, which should make it pretty clear why I consider fasting to be an indispensable practice for anyone that values body and brain performance.

Why You Should Be Fasting

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 stimulates essentially all of them.

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. [1] 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. [2]

Slowing/Reversing Markers Of Aging

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

Owing largely to the stimulation of autophagy, fasting can reverse this process, stimulating cells to “clean house”, preventing the dysfunction that can lead to disease (including cancer). [3]

Improved Body Composition

There’s a lot of confusion out there around the factors that determine an individual’s body. Most people - including many nutritionists - incorrectly assume changes in body composition are largely attributable to the calories-in-calories-out model of diet and exercise. In reality, body composition is largely a function of our hormonal state.

Fasting increases insulin sensitivity and increases adiponectin levels, two key hormonal factors that determine if existing fat gets oxidized (used for energy) as well as if incoming caloric energy gets used immediately or stored (as fat) for future use. [3] These positive hormonal changes persist well after a fast is completed. So while you will likely run a calorie deficit on fasting days, the hormonal changes will have a far bigger impact on body composition over weeks and months.

A lot of gym-goer-types assume that fasting will also lead to the body breaking down muscle for energy, and while this could be true under certain conditions, it’s also fairly easy to avoid with a bit of strategy, which I’ll outline later. Done smartly, short-term fasting increases lipolysis (fat burning) while largely maintaining muscle.

Fasting Brings Improved Digestion

Intuitively, fasting acts as a sort of “digestive reset” allowing the gastrointestinal (GI) tract relax for a bit. In practice, this produces both reduced intestinal inflammation and improved motility (the contraction of GI muscles in digestion). Both lead to improved nutrient absorption and better bowel movement quality.

Interestingly, a recent study showed that fasting might stimulate the growth of specific species of bacteria in the gut that promote lipolysis (fat burning). [4]

Cardiovascular Health

Fasting reduces resting heart rate and blood pressure while increasing parasympathetic tone (an important indicator for health of the cardiovascular system). In general, the resilience of the cardiovascular system to stress is improved by fasting. [3]

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 cell treatment toolkit.

Fasting has been shown to comparable in efficacy to chemotherapy in delaying the growth of certain types of tumors. [5][6] 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 this not more used in oncology?

At minimum, a fasting protocol should be used in addition to chemotherapy, as it has been shown to preferentially protect non-cancerous cells from chemo drugs. [7]

Autophagy: The Metabolic Fountain Of Youth?

Autophagy deserves special attention here, as a case can be made it’s the single most important metabolic process to select for if the aim is to slow the aging process and promote a high-performing body and brain. You don’t win a Nobel Prize in medicine unless you’re working on something that legitimately has the potential to change humanity.

Autophagy is still relatively obscure outside the biochemistry/cell biology/endocrinology worlds, but my intuition (and hope) is that it will receive increasing attention in mainstream natural health and nutrition media over the next 5 years or so.

As Yoshinori Ohsumi and others have described, autophagy is the process by which cells degrade and then recycle unneeded or dysfunctional proteins and organelles (via lysosomes).

If allowed to accumulate, dysfunctional proteins and organelles eventually lead to dysfunctional cells that either die, persist as dysfunctional cells (contributing to poor tissue/organ function) or become cancerous. Needless to say, all of these outcomes are in opposition to a youthful, vibrant, high-performing body and brain.

In the brain, upregulation of autophagy is strongly neuroprotective while disruption of autophagy causes neurodegeneration. In the liver, upregulation of autophagy increases lipolysis (fat usage) and insulin sensitivity, while disruption of autophagy leads to prediabetes and metabolic syndrome. The list goes on, but I think you get the point: autophagy is important.

Fasting To Maximize Autophagy

Fasting has been shown to be, far and away, the most effective way to stimulate autophagy in both the body and brain. Despite this, there’s not a clear consensus on exactly how long to fast for to maximize autophagy.

I located a few studies that looked at the level of autophagy occurring in both the liver and brain, and there were some clear patterns when looking at the data of each.

The level of autophagy activity can be measured by simply counting the number of autophagosomes (the cellular organelles that handle dysfunctional protein degradation), as these will increase in number when autophagy is stimulated.

The study looking at liver cells found that the number of autophagosomes increased 300% after 24 hours of fasting, and a further 30% after 48 hours of fasting. Studies looking at autophagosomes in brain cells had a similar findings. [8]

In addition to looking at the number of autophagosomes in a cell, the brain study looked at a handful of metabolic markers that are indicative of autophagy being stimulated. Almost of these markers peaked between 24 and 36 hours, explaining why the increase in autophagosomes between 24 and 48 hours is substantially less than between hours 0 and 24.

My take-away from this is that while there is certainly value in fasting longer, there also seems to be an element of diminishing returns once a fast passes the 36 hour mark. As such, I’ve designed my fasting protocol to get close to the 36 hour mark with as little stress and discomfort as possible. More on this in a bit.

Psychological Benefits (Why I Love Fasting)

A quick word on the utility and value of fasting. It feels incomplete to express the benefits of fasting simply as “stimulation of autophagy” or “increased neurotrophic factors”, etc.

Talk to anyone who fasts on a regular basis and it will be clear that there is more to derive from the experience than simply an abstract understanding that you’re “doing something healthy.” There is an undeniable physical and emotional high that comes with fasting. Almost everyone gets this the day following a fast, and for a lot of people, there is a high in the fasting period that outweighs the slight discomfort of an empty stomach.

I think the reason for this it two-fold - yes, stimulating dozens of vitality-promoting metabolic processes surely contributes to the sense of well being, but I think the psychological component is even more important.

Fasting requires an element of self-mastery. Most of us are conditioned both psychologically and hormonally to be eating multiple times during the day, and any deviation from this causes people to get cranky. This is not healthy.

Fasting also requires us to be present with the initial discomfort of not stuffing our faces every time we feel like it. This is a reversal of the typical power structure in body-brain relations. It puts us in the position of consciously making the decision to eat or not to eat, rather than our stomach (aka hormones) effectively making that decision for us.

Almost all of us would benefit hugely from consciously redefining our relationship to food, and fasting is a powerful opportunity to do this redefinition.

My Fasting Protocol

The Day Before

Hunger is not a function of the presence or absence of food in your stomach, nor is it a function of levels of essential nutrients in your body.

Hunger is largely a function of blood sugar. In general, if your blood sugar is high, your body releases hormones (leptin, etc) that tell your brain “I’m full”. If your blood sugar drops, your body releases hormones (ghrelin, cortisol) that tell your brain “get me food”.

The best way to minimize the hunger and discomfort you feel during a fast is to reduce the magnitude of your blood sugar fluctuations in the day or two prior to a fast.

Doing this is quite simple: cut way back on carbohydrates.

For 1 to 2 days ahead of a fast, cut out rice, bread, pasta, fruit, sugary drinks and desserts. Replace these with leafy greens (spinach, kale, broccoli, etc) and healthy fats (avocado, butter, olive oil, coconut oil, coconut milk, etc). Find my complete list of approved fats and veggies here.

If you include enough healthy fats and greens, you’ll still feel plenty satisfied after your meals.

Fasting Day

If our sole goal was to maximize benefits of fasting, a fasting period of 3-5 days is probably the best way to do this before running into undesirable effects (stress on the endocrine system, etc).

If you feel up for doing a 3-5 day fast, I totally encourage it as there are a lot of benefits that come with prolonged fasting that are not seen in these shorter fasts. That being said, I think it’s possible to get 70+% of the benefits of a 3-5 day fast with a fraction of the challenge that would present. As I mentioned in the section above, I shoot to get as close to that magic 36-hour number as I can, and if all goes to plan, I can get close to that number keeping energy levels and brain function high while experiencing little discomfort.

Here’s how I do this:

The previous day, eat dinner a few hours earlier than you normally would. I generally finishing about 5pm rather than my normal 9pm. Hydrate well, but don’t eat anything else the remainder of the day.
On day one, wake up and drink between 32 and 64 ounces of lightly salted water (to increase absorption, more on this here). Being well hydrated throughout the day makes the process much smoother.
Every 4-5 hours throughout the day, have a serving of C8 MCTs.
(This one is optional. The benefits are the same with or without this step...it just makes life a bit easier.)

What are C8 MCTs? "MCT" refers to medium chain triglyceride, a specific type of fat that is readily converted into ketones (i.e. energy) in the body. "C8" is caprylic acid, the specific MCT most efficiently converted into energy in the body.

Why is this useful when fasting? C8 MCTs are an energy source that won’t disrupt the beneficial processes of fasting. Eating protein or carbs will quickly stop autophagy and other beneficial fasting-stimulated metabolic processes. Even consuming pure fat like coconut oil or olive oil requires the gut and liver to be recruited for processing, which essentially is a a signal to your cells to slow autophagy.

C8 MCTs are different in this capacity because they are generally converted to ketones directly in muscle and (particularly) brain cells, rather than in the liver. This means autophagy is not disrupted when the body uses C8 for energy.

C8 MCTs are a quick energy source for the brain and promote oxidation of stored fat in adipose tissue. These processes together keep the brain adequately fueled, making the fast easier in the process.

We developed Ketobasis, a zero-carb C8 MCT powder ideal for this fasting application.
Eat dinner on the second day a bit later than you normally would. For me, this is a 10pm dinner rather than my usual 9pm. Finishing the day before at 5pm and eating the next day at 10pm means I’ve just fasted for 29 hours.

Not quite the 36 I’d ideally go for, but those additional 7 hours feel like work. The reason this protocol works well is you never have to go to sleep hungry, which can be difficult for some people, myself included. If I were to finish eating at 10am the previous day, getting to sleep that night could be a challenge, and it will feel more like I fasted for two days instead of one (way more challenging psychologically).
I recommend doing a 24-to-29 hour fast once every 2 weeks. I’ve found this to be the perfect interval for maximizing benefits of fasting without the protocol ever feeling like a chore.

Tips For Getting Started With Fasting

If the idea of fasting for 24+ hours is intimidating to you, don’t worry; it will almost certainly be easier than you think.

For your first attempt at fasting, commit to 18 hours or thereabouts (so finishing dinner at 8pm and then waiting until 2pm the following day to eat again. If you arrive at the 18 hour mark and you feel like you must eat, do so. 18 hours is a great start. The following week, try for 20 hours and then 22 the following week.

There’s a good chance, however, that you’ll arrive at the 18 hour mark and realize that 6+ more hours feels way more achievable than you imagined.

Stay Synchro,

Graham Ryan