What is Autophagy
So since I brought up the concept of autophagy, let’s talk about what it is and why you should care.
In the most basic terms, autophagy is a protective process by which your body cleans itself by consuming itself. During autophagy, cells remove unnecessary components within and use them for energy. This is a natural recycling process. So when you fast long enough for all the glycogen stores in your liver to run out, certain signaling molecules kick-off this process in order to generate energy for your body.
Benefits of Autophagy
There are many known benefits of activating autophagy. It appears that this natural recycling process naturally selects for sick and damaged cells and cell organelles to make room for new ones. We don’t exactly know how or why that happens, but it has been observed over and over in a large number of studies. {*}
Neurodegenerative Diseases
Due to this particular quality, autophagy is currently the subject of many clinical studies. These studies look at a large range of disorders where cellular dysfunction is thought to be causative. These include Huntington’s Disease, Alzheimer’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis (ALS) to name a few.
Cancer Prevention and Treatment
There is research looking at autophagy in cancer treatment and prevention. This makes sense as cancer cells differ from normal cells due to a defect of some sort. If these cells are allowed to replicate in the body, this may likely lead to cancerous growth. As we age, the efficiency and effectiveness of our body to remove dysfunctional cells declines. That’s why regular stimulation of autophagy may be protective against cancer. {*} Although, certainly there needs to be a lot more research on this topic.
Cancer is different, however. Paradoxically in later stages of cancer growth, autophagy may actually offer protective benefits to cancer cells. {*} So there are a number of pharmaceutical trials actually looking at selective inhibition of autophagy to treat some cancers. Interestingly, drugs under research include chloroquine and hydroxychloroquine (anti-malaria drugs). You might find these familiar because these are the same drugs under investigation for the treatment of COVID-19.
Anti-Aging and Longevity
If you look at aging at a cellular level, it is easy to see why some prominent researchers in the area of aging consider aging itself to be a disease. Dr. David Sinclair focuses on that in his recent book “Lifespan: Why We Age – and How We Can Live Longer”.
As we age, our bodies become less effective at identifying and recycling damaged cells and organelles. Essentially, autophagy does not work as well.
Other Benefits of Autophagy
Other benefits of autophagy and fasting that are topics of interest include:
- Weight loss – this one is obvious. When your body is forced to consume itself for energy, the only major sources available are adipose (or fat) and muscle tissues. Dr. Jason Fung wrote a top-selling book Obesity Code, advocating fasting for weight loss and to reverse many metabolic diseases.
- Metabolic syndrome (a complex condition implicated in disrupting the normal work of organs including the liver, heart, pancreas, and adipose tissue) {*}
- Heart diseases – many cardiovascular disorders can be partially or completely reversed using autophagy as a therapy. {*}
- Inflammation and immunity – through highly regulated autophagy pathways that involve key signaling proteins required to maintain cellular homeostasis under conditions of infection. {*}
When Does Autophagy Start
Now that you know the benefits of autophagy, the common question is how long should you fast for autophagy. There have not yet been studies that look to answer that question directly. What complicates matters is that most if not all of the focused research that has been done on autophagy involve in vitro (test tube) or mice models.
Having said that, in mice studies autophagy was observed after about 12-24 hours of fasting. However, mice models can be deceiving, because mice have a much faster metabolism than we do. The general belief is that in order to stimulate autophagy in people, a long term fast of at least 48 hours is required.
But in reality, it is not that black and white. Certainly, some benefits of fasting can still be gleaned even from shorter-term fasts. Even when you practice Time-Restricted Feeding (TRF) commonly known as Intermittent Fasting, autophagy still occurs on some level.
What Happens During Autophagy – A Bit Technical
Autophagy is regulated by several key signaling regulators. These are glucagon, mTOR, and AMPK. There are others, but for simplicity’s sake let’s focus on these three.
Glucagon is a hormone your body releases when your insulin drops. When you do not eat, for instance during a longer fast, insulin drops and this raises glucagon which in turn stimulates autophagy. {*}
The other regulator is mTOR (mammalian target of rapamycin) which responds to the presence of dietary amino acids in the bloodstream. Consequently, when you decrease mTOR by fasting, you signal your body to activate autophagy. {*}
AMPK (AMP-activated protein kinase) is a sensor of intercellular energy balance that looks at the amount of ATP (cellular energy currency) within a cell. When that is drastically reduced, AMPK increases and shuts down pathways to store fat and triggers autophagy instead. {*}
How to Induce Autophagy (Faster)
Autophagy and Fasting
Fasting is the most powerful natural stimulator of autophagy. The liver is an organ that controls the amount of glucose (sugar) in your bloodstream through a number of extremely sensitive and highly regulated processes. The liver can convert carbohydrates to glucose for energy. But in the absence of carbohydrates, it can also manufacture glucose from amino acids (found in proteins and muscle tissues) and fats.
When you consume a lot of carbohydrates, the liver will take up extra glucose to replenish its glycogen (many glucose molecules bound together) stores. Extra glucose can also be converted to triglycerides stored in the adipose tissue (as your body fat). Your muscle tissues also store a limited amount of glycogen for quick energy.
Normally, the liver supplies glucose (sugar) to your tissues by turning stored glycogen into glucose and releasing it into the bloodstream through a process called glycogenolysis. When you fast, and you run out of glycogen stores, your body turns on the processes discussed above by raising glucagon and turning down mTOR.
Autophagy and a Diet High in Fat (Keto Diet)
In a state of ketosis, such as when a person follows a ketogenic diet or fasts for a prolonged period of time, the stores of glycogen in your liver also get depleted.
At this point, the liver can make glucose from either dietary fat and protein or, if you are fasting, by breaking down your stored fat in the adipose tissues and amino acids in your muscle. {*}
Simultaneously, the liver mitochondria (cellular power plants) also start producing ketone bodies. Ketones are a product of fatty acid metabolism (the break down of fat tissues). They are also a great source of energy for most tissues in our body, including the brain.
So if you follow a ketogenic diet prior to fasting, your body has already depleted glycogen stores and has already done the work to use ketones for energy. This will make fasting considerably easier to bear. And your body will be ready to grab and convert dysfunctional cells and cell organelles for energy.
Side note…But what happens to glucose production in a state of ketosis?
This is a bit technical. What some do not know is that when your body is in a state of ketosis, your liver still produces glucose. It’s doing so through the process of gluconeogenesis. In this state, your liver will break down triglycerides (from adipose / fat tissues) into free fatty acids and glycerol (this is important).
Because there isn’t enough glucose to send fatty acids through the Krebs cycle to create energy (the body’s preferred method), free fatty acids get converted to ketones and ketoacids used for energy with the help of acetyl-CoA molecules.
But remember the glycerol?… The glyceride backbone of a triglyceride is a three-carbon glycerol chain that is then released into your bloodstream and used by various tissues, including your brain. In fact, even under starvation conditions, about 30-40% of the energy consumed by your brain is still in the form of glucose.{*} Shocking, I know!
Exercise to Trigger Autophagy
Another very powerful way to induce autophagy (and ketosis) faster is by using more energy. Naturally, that can be done through prolonged exercise. A lot of people actually practice fasted exercise routines in order to deplete liver glycogen stores and get into the state of ketosis, and thus activate autophagy, faster.{*}
The bottom line is, while ketosis and autophagy are not the same, as you can see, they are closely linked together.
How to Stop Autophagy
In order to stop autophagy, you would only need to consume some dietary amino acids (protein) or carbohydrates which both stimulate insulin production. Glucagon will decrease, and mTOR will increase. These will signal your body to shut down autophagy.
More Fasting Resources <LINK THESE>:
XO, Marina
Disclaimer: I am not a medical doctor or Registered Dietitian. The information presented is not medical advice. It is purely to share my experiences and opinions based on the linked research. As always, check with a doctor before making any fitness or nutrition changes. The author and blog disclaim liability for any damage, mishap, or injury that may occur from engaging in any activities or ideas from this site.
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