The Science of Fasting: Autophagy
On October 3rd 2016, the Nobel Assembly at Karolinska Institutet awarded the Nobel Prize in Physiology or Medicine to Yoshinori Ohsumi for his discoveries of mechanisms for Autophagy.
But what is Autophagy? The word derives from the Greek auto (self) and phagein (to eat). So the word literally means to eat oneself. Essentially, this is the body’s mechanism of getting rid of all the broken down, old cell machinery (organelles, proteins and cell membranes) when there’s no longer enough energy to sustain it. It is a regulated, orderly process to degrade and recycle cellular components.
There is a similar, better known process called apoptosis also known as programmed cell death. Cells, after a certain number of division, are programmed to die. While this may sound kind of macabre at first, realize that this process is essential in maintaining good health. For example, suppose you own a car. You love this car. You have great memories in it. You love to ride it.
But after a few years, it starts to look kind of beat up. After a few more, it’s not looking so great. The car is costing you thousands of dollars every year to maintain. It’s breaking down all the time. Is it better to keep it around when it’s nothing but a hunk of junk? Obviously not. So you get rid of it and buy a snazzy new car.
The same thing happens in the body. Cells become old and junky. It is better that they be programmed to die when their useful life is done. It sounds really cruel, but that’s life. That’s the process of apoptosis, where cells are pre-destined to die after a certain amount of time. It’s like leasing a car. After a certain amount of time, you get rid of the car, whether it’s still working or not. Then you get a new car. You don’t have to worry about it breaking down at the worst possible time.
Autophagy — replacing old parts of the cell
The same process also happens at a sub-cellular level. You don’t necessarily need to replace the entire car. Sometimes, you just need to replace the battery, throw out the old one and get a new one. This also happens in the cells. Instead of killing off the entire cell (apoptosis), you only want to replace some cell parts. That is the process of autophagy.
What activates autophagy?
Nutrient deprivation is the key activator of autophagy. Remember that glucagon is kind of the opposite hormone to insulin. It’s like the game we played as kids — ‘opposite day’. If insulin goes up, glucagon goes down. If insulin goes down, glucagon goes up. As we eat, insulin goes up and glucagon goes down. When we don’t eat (fast) insulin goes down and glucagon goes up. This increase in glucagon stimulates the process of autophagy. In fact, fasting (raises glucagon) provides the greatest known boost to autophagy.
This is in essence a form of cellular cleansing. The body identifies old and substandard cellular equipment and marks it for destruction. It is the accumulation of all this junk that may be responsible for many of the effects of aging.
Fasting is actually far more beneficial than just stimulating autophagy. It does two good things. By stimulating autophagy, we are clearing out all our old, junky proteins and cellular parts. At the same time, fasting also stimulates growth hormone, which tells our body to start producing some new snazzy parts for the body. We are really giving our bodies the complete renovation.
You need to get rid of the old stuff before you can put in new stuff. Think about renovating your kitchen. If you have old, crappy 1970s style lime green cabinets sitting around, you need to junk them before putting in some new ones. So the process of destruction (removal) is just as important as the process of creation. If you simply tried to put in new cabinets without taking out the old ones, it would be pretty fugly. So fasting may in some ways reverse the aging process, by getting rid of old cellular junk and replacing it with new parts.
What turns off autophagy? Eating. Glucose, insulin (or decreased glucagon) and proteins all turn off this self-cleaning process. And it doesn’t take much. Even a small amount of amino acid (leucine) could stop autophagy cold. So this process of autophagy is unique to fasting — something not found in simple caloric restriction or dieting.
Autophagy Benefits
Research suggests that some of the most important autophagy benefits include:
- Providing cells with molecular building blocks and energy
- Recycling damaged proteins, organelles and aggregates
- Regulating functions of cells’ mitochondria, which help produce energy but can be damaged by oxidative stress
- Clearing damaged endoplasmic reticulum and peroxisomes
- Protecting the nervous system and encouraging growth of brain and nerve cells. Autophagy seems to improve cognitive function, brain structure and neuroplasticity.
- Supporting growth of heart cells and protecting against heart disease
- Enhancing the immune system by eliminating intracellular pathogens
- Defending against misfolded, toxic proteins that contribute to a number of amyloid diseases
- Protecting stability of DNA
- Preventing damage to healthy tissues and organs (known as necrosis)
- Potentially fighting cancer, neurodegenerative disease and other illnesses
How to Induce Autophagy
When does autophagy occur? Autophagy is active in all cells but is increased in response to stress or nutrient deprivation (fasting or starvation). This means you can utilize “good stressors” like exercise and temporary calorie-restriction (fasting) to boost autophagic processes. Both of these strategies have been linked with benefits like weight control, longevity and inhibition of many age-associated diseases.
1. Practice Fasting
When it comes to diet and lifestyle habits that are in your control, the thing that triggers autophagy most is fasting, including the dietary strategy known as intermittent fasting (or IMF). Fasting is a pretty simple concept: You abstain from eating for a certain period of time (you can still drink water and liquids like coffee or tea).
If you’re not yet familiar with intermittent fasting, this is a type of cyclic fasting that involves time-restricted eating. There are many different forms of IMF that you can practice to promote autophagy, such as Alternate Day Fasting or limiting your daily “eating window” to somewhere between just 4 to 8 days per day.
How long do you have to fast for autophagy? Studies suggest that fasts between 24–48 hours probably have the strongest effects, but this isn’t always doable for many people. (4) Try to at least fast for 12 to 36 hours at a time.
An easy way to accomplish this is to eat just 1 or 2 meals per day, rather than grazing on many small meals and snacks. If you usually finish dinner at 6 or 7 p.m, then try to fast until at least 7 a.m the next morning — or even better, don’t eat until 11 a.m. or 12 p.m.
You might choose to occasionally do a 2–3 day fast, or even longer once you’re more experienced with fasting. If you prefer alternate day fasting, then you will severely restrict the amount of calories you eat during fasting days (eating only 1 or 2 meals of about 500 calories), then eating to your stomach’s content on non-fasting days.
2. Consider the Ketogenic Diet
The ketogenic (“keto”) diet is a very high-fat, very low-carb diet that works in similar ways to fasting. The keto diet (KD) involves getting about 75 percent or more of your daily calories from fat, and no more than 5–10 percent of calories from carbs. This forces your body to go through some major changes, as metabolic pathways are shifted so that you start using fat for fuel instead of glucose from carbs.
What types of foods are most beneficial if you plan to follow the KD? High-fat, whole foods like coconut oil, olive oil, eggs, grass-fed butter, ghee, grass-fed meat, fermented cheeses, avocado, seeds and nuts. Vegetables are also included for fiber, vitamins and antioxidants.
In response to such severe carb restriction, you’ll begin to start producing ketone bodies that have many protective effects. Studies suggest that ketosis can also cause starvation-induced autophagy, which has neuroprotective functions. For example, in animal studies when rats are put on the ketogenic diet, the keto diet has been shown to start autophagic pathways that reduces brain injury during and after seizures. (5)
3. Exercise
Another “good stress” that can induce autophagy is exercising. Recent research has shown that “Exercise induces autophagy in multiple organs involved in metabolic regulation, such as muscle, liver, pancreas and adipose tissue.” (6)
While exercise has many benefits, it’s actually a form of stress because it breaks down tissues, causing them to be repaired and grow back stronger. It’s not exactly clear yet how much exercise is needed to boost autophagy, but research does suggest that intense exercise is probably most beneficial.
In skeletal and cardiac muscle tissue, as little as 30 minutes of exercise can be sufficient to induce autophagy. Can you exercise while fasting? Most people can. You might even find that you feel energetic once you get the hang of fasting, giving you more motivation for exercise.
Precautions Regarding Autophagy & Fasting
There’s still a lot we have to learn about autophagy and how to best induce it. Beginning to induce autophagy by incorporating fasting and regular exercise into your routine is a great place to start.
However, if you are taking certain medications to control any health conditions, it’s best to consult your doctor about introducing fasting.
Final Thoughts on Autophagy Benefits & Mechanisms
- Autophagy translates to “self-eating.” It’s a beneficial process that describes consumption and recycling of the body’s own tissue as a metabolic process.
- Researchers believe that autophagy is a survival mechanism that has anti-aging benefits. It helps cleanse waste from the body, provides energy, and potentially fights cancer, neurodegenerative disease, and other chronic illnesses.
- Autophagy is induced through starvation, fasting and other “stressors.” You can increase autophagic processes by doing some type intermittent or alternate day fasting, exercising, and/or following the ketogenic diet.
