Metabolic Autophagy

by Siim Land

  Expose Yourself to Hormetic Stressors – Nutrition and exercise aren’t the only components of longevity. You also want to trigger hormetic adaptation outside of the gym. To live a longer and healthier life you have to become more resilient against stress and adaptable to the ever-changing conditions of the natural environment. Of course, modern life allows us to maintain homeostasis in everything we do whether that be our core temperature, daily routines, food consumption, or physical challenges but they’re elusive. To not be swept away by some unexpected circumstances, you want to follow a lifestyle that involves voluntary hormesis. Take cold showers, swim in icy lakes, turn off the central heating, burn some fat at the sauna, practice stress management, fast for 5 days a few times per year, and do something tough.

  The purpose of these principles is to live a more challenging life that would ultimately make it more fulfilling and enjoyable. It might sound paradoxical that not eating for days upon end can make you a happier person but trust me it can.

  Understanding the mechanisms of the human body and acknowledging to yourself the benefits of fasting, working out, or taking ice baths will make them seem that much more appealing. They require a shift from the hedonic mindset into a more stoic one. It might seem grim at first but you’ll actually become more grateful for everything you have and actually yearn for more minimalism. Like Siddharta said: „I can think. I can wait. I can fast.“

  Once you make Metabolic Autophagy a part of your lifestyle, you’ll never want to go back to a normal way of being. You may adjust it according to the situation and your preference but the core tenets will remain the same.

  Chapter XVIII

  What Breaks a Fast

  "Every fool can fast, but only the wise man knows how to break a fast."

  George Bernard Shaw

  You can find many questions on Google about what breaks a fast while intermittent fasting: “Can I drink coffee while fasting? Will lemon water kick me out of a fasted state? Do 100 calories break a fast? What about eating Snickers’ bars and cursing?” Those are all great questions and you may get many different answers from different people. There are several ways people do intermittent fasting and for many reasons.

  What counts as breaking a fast depends on why you’re fasting for and what you’re expecting to gain from it. In this chapter, I’m going to go through all the scenarios and questions in regards to does this break a fast?

  The biggest beneficial effects of fasting come from 3 things: autophagy, ketosis, and hormesis. IF promotes all of them to a certain degree, depending on how long you’ve been in a fasted state. The key trigger is energy deficit and glycogen depletion.

  Eating just 50 calories or even as little as 2-3 grams of leucine can already raise mTOR and put you into an anabolic state.

  Fat doesn’t raise insulin significantly and it keeps mTOR suppressed in small amounts. Endogenous ketone bodies from your own body fat will stimulate autophagy, which can promote brain macroautophagy as well. However, high amounts of ketones and fatty acids in the blood can still make you raise insulin. If there’s too much energy circulating the body, then that’s a signal to stop autophagy and trigger mTOR. Exogenous ketones can also be insulinogenic[632].

  In a study done on rats, they found that exogenous ketones promote insulin secretion when blood glucose was greater than 5.0 mMol/L or 90 mg/dl[633]. If you’re a healthy person who is very lean and low on body fat, then your blood glucose will probably drop below that. If you already have excess energy stored in your body fat then it’s a signal that there’s plenty of energy already around and any form of calories, whether that be from Bulletproof coffee or exogenous ketones will most likely inhibit autophagy.

  It means that you shouldn’t have small snacks like an almond. Okay, probably a single almond won’t break autophagy but you’d still be better off by skipping it altogether.

  Things That Keep You In a Fasted State

  There are some ways to trigger autophagy that you can consume while fasting.

  Green tea has polyphenols and other ingredients like epigallocatechin-3-Gallate (EGCG) that stimulate autophagy. Black tea, herbal teas, and others like chamomile are also okay.

  Coconut oil or MCT oil can also stimulate autophagy in very small amounts by raising ketones[634][635]. However, as we found out, too much fat and too much energy in the system will raise insulin. Any more than 1 tsp will probably have a counter-balancing effect.

  Medicinal Mushrooms - Reishi mushroom extracts are shown to increase autophagy and inhibit breast cancer growth as do the others like chaga and cordyceps. You can take maybe 1 tsp of reishi or chaga but not any more.

  Coffee stimulates lipid metabolism through the autophagy-lysosomal pathway in mice[636][637]. However, excess caffeine consumption may lead to higher blood glucose and insulin levels because of over-stimulating cortisol. That’s why drinking too much coffee may actually interfere with the fast. You shouldn’t drink any more than 2-4 cups a day.

  Apple Cider Vinegar has trace amounts of micronutrients and bacterial residue but it most likely isn’t enough to kick you out of a fasted state. It may actually boost autophagy by promoting the cleaning process. You can use the distilled ACV during the fasting window and opt for the one with the mother when you start eating.

  To be safe, you could just drink water and salt. However, things like green tea and black coffee are great for enhancing the effectiveness of fasting by promoting autophagy. That’s why it’s okay to be consuming them in moderation.

  Artificial Sweeteners

  There’s a lot of conflicting research around artificial sweeteners. Some are shown to be horrible for your health while others can cause an insulin response. Can you add some artificial sweeteners to your drinks while fasting?

  Aspartame doesn’t have any effect on the insulin response whether alone or combined with food[638][639]. When protein produces a significant insulin response, then aspartame doesn’t seem to have any effect[640]. However, aspartame is thought to be linked with many cancers and tumors. I’d skip the diet coke.

  Neither aspartame or saccharin seem to raise insulin. However, in one study they took people in a fasted state and made them swish 8 different taste solutions in their mouth for 45 seconds and then spit them out. Sucrose and saccharin were the only ones that activated an insulin response[641]. However, in another study, they didn’t get the same results[642]. Maybe the subject’s mind created their own placebo response by raising their blood sugar by will. You should remember that the next time you look at cake or think about sweets because it may raise insulin.

  Direct transfusions of Acesulfame K increased insulin in rats[643]. It’s definitely not the same as drinking diet soda but it still matters.

  Sucralose aka Splenda activates certain taste receptors that in some studies may stimulate insulin. However, one study found that infusing sucralose straight into the gut didn’t stimulate the hormones that raise insulin[644].

  Stevia can lower postprandial insulin levels compared to aspartame and sucrose[645]. It’s the only natural sweetener that’s fine to consume in moderation.

  A recent review on low-calorie sweeteners concluded that they don’t seem to have any effects on insulin in vivo[646]. Zero calorie artificial sweeteners aren’t most likely going to raise insulin but they may. The bottom line is to know how they affect YOU specifically by looking at your blood sugar levels.

  Even if artificial sweeteners may not spike your insulin, it doesn’t mean they can’t inhibit autophagy. They’re also shown to have a negative effect on gut microbiome so it’s better to avoid them entirely. The evolutionarily sustainable strategy would be to not be bothered with these things and avoid the potential costs.

  The cephalic phase response describes the process of gastric secretion by your stomach before eating food. It’s caused by sights, smells, tastes, and even thoughts of consuming something good. The hungrier you are the greater the stimulation and most of it is learned behavior. Thinking about biting into a
lemon makes you salivate not because your brain knows what it feels like but because you’ve done it before. This serves as a pre-emptive mechanism for having enough insulin around when you do eat. In an environment of caloric scarcity it’s useful but not so much in a society where you can see empty calories all around you. That’s why you have to avoid tricking your mind with placebo sensations of eating and attain an indifferent mindset towards sweetness. Don’t use artificial sweeteners during fasting.

  Chewing Gum

  If you’ve ever fasted, then you can probably notice the utility of chewing gum. It helps to stave off hunger, keeps your mind engaged, and tastes good. But I hate to break it to you…

  Sugar-free and calorie-free gum actually have calories. #Gasp! Shocking I know…Basically, because the amount of calories in there is so low, the production company doesn’t have to list it as such. The label says something along the lines of: „Not a significant source of calories“.

  Figure 88 Chewing gum actually has some calories and sugars

  Horray! Does this mean I can eat all the gum my heart desires and still continue fasting? Well, that caloric quality refers to a single portion and one piece of gum probably has 2-5 calories. Mostly coming from sugar alcohols and carbohydrates.

  You would definitely want to avoid gums that have corn syrup, fructose, high fructose corn syrup, and aspartame because we know these are quite bad for your health and gut flora. Of course, if you’re only consuming like 1-2 pieces of gum with these ingredients, then you won’t have a negative side effect on your health, granted you’re eating a healthy diet. However, if you’re taking in like 4-5 and even more gum while fasting, then you’ll not only break a fast but you may also end up with some small microbiome issues down the line.

  What about nicotine gum while fasting? Will that break a fast?

  Nicotine in cigars and other forms of tobacco can have some nootropic effects that increase your alertness and cognitive performance. However, smoking is still bad for you and promotes atherosclerosis.

  I don’t consume nicotine gum because I don’t need it but I’d suggest that nicotine will boost your mental performance in very small doses like 1-2 mg-s. One piece of nicotine gum usually has 2-4 mg-s of nicotine, which is the equivalent of nicotine in 1-2 cigars.

  Fasting itself also has nootropics effect and I’m sure everyone who’s fasted for at least a day can attest to the mental clarity and sharpness. When in a fasted state, you raise cortisol, adrenaline, and ketones, which will increase your energy and acuity.

  The concluding answer is that 1-2 pieces of gum won’t break a fast in most cases. Brushing your teeth once is also okay. You just have to make sure you don’t swallow the saliva, not follow it up with 2 cans of diet soda, and not stimulate insulin by starting to crave for more food.

  Lemon Water

  Putting a few slices of lemon, lime, orange, cucumber, or mint leaves into your water has zero effect on your blood sugar, autophagy, or fasting.

  Lemons and other citrus, however, contain calories, namely fructose, which stimulates the liver in a way to break the fasted state.

  If you were to eat some lemons, then you're going to absorb the fructose, digest it, and thus inhibit the fasting. Whether or not it's enough to break the fast completely depends on how much lemon you swallowed and how does it affect your blood sugar. I dare to say that 1-2 slices of lemon have a negligible effect on the fasted state.

  If the lemon slices are simply sitting in the water, then they're maintaining the fructose inside the cellular matrix without releasing them into the liquid (unless you squeeze them empty, of course). In that case, you're not absorbing the fructose either, which won't affect the fasting.

  The general guideline is that just drinking lemon flavored water while fasting won't break the fast as long as it's not lemon juice or some sort of a sugar-filled lemon sports drink.

  Glauber’s Salts

  If you’re doing fasting for health purposes and to promote cellular cleansing, then you can also consume Glauber's salt. It’s commonly named as sodium sulfate decahydrate.

  In medicine, Glauber’s salt is used as a mild laxative that triggers bowel movements. If you add 5-20 grams of Glauber's salt to water, you can remove constipation, reduce bloating and clean the digestive tract. Any more than that may cause diarrhea and can lead to dehydration so don’t overconsume it.

  Bulletproof Coffee

  Well, the rationale is that because Bulletproof Coffee consists of only fat it’s not going to raise blood sugar or insulin and thus keeps you in a fasted state.

  It’s true that adding butter to your coffee will keep you in ketosis and maintains somewhat of a fasted state but I’m afraid it’s still going to inhibit autophagy. This is not necessarily a bad thing as you’ll get energy and stay in ketosis but you’ll be missing out on some of the detox health benefits. Here you have to think about why you’re doing intermittent fasting for.

  If you’re doing fasting for weight loss purposes and adding butter or MCT oil to your coffee helps you to make it through the fast then go for it. However, do remember that you’ll still need to consume fewer calories and putting an entire stick of butter into your cup will give you at least a few hundred calories.

  If you’re fasting to thoroughly clean your body from toxic proteins and inflammation, then I’d advise you to not consume anything at all and do strict water fasting with mineral water with these salts and teas.

  But does Bulletproof Coffee stop autophagy completely? That would depend on the amount of calories consumed and how your body responds to it. If you add like 500 calories of fat then that’s definitely going to kick you out of a fasted state and stop autophagy. If you consume maybe like 100 calories then you may get away with it. It also matters what’s the overall energetic status of your body.

  If you’re sitting on a couch and drinking bulletproof coffee in the morning after having slept for 8 hours, then your body is in a state where it doesn’t need excess energy. You’ve been sedentary and there are no real energy demands on your muscles that you can’t cover with endogenous production of liver ketones. In that case, drinking that coffee will have a much bigger effect on autophagy because your homeostasis for nutrient signaling is much lower. You will get a bigger nutrient signaling effect from smaller amounts of calories because your body’s energy demands are much lower.

  If you were to take that same bulletproof coffee and drink it maybe at noon time when you’ve already moved around, taken a long walk, maybe had a workout or done some chores, then it’s going to have less of an effect because your body will be under higher energy demands. In that case, your ceiling for nutrient signaling is higher because the calories you’d consume would be allocated into use much more effectively and they’ll be burnt off faster. You may still interfere with autophagy a little bit but not to the extent as you would when you drink that same coffee with the same amount of calories in the morning when your body doesn’t need that much energy.

  It's not that black and white...definitely not black and white coffee. This can be taken even further.

  If you do intermittent fasting for longer and then you have a much bigger meal later in the day like 1500 calories, then you’ll definitely interfere with autophagy much less than if you were to eat 2 meals of 700 calories each.

  By the end of the day, your body will be that much more depleted and the food you do eat won’t have that much energetic load to inhibit autophagy completely. It’s almost like your body is still shocked from the catabolic stressor of fasting and because of that it’s not going to turn off autophagy completely either whereas eating 2 meals is enough to say that „okay we’ve got enough nutrients and we don’t need to keep recycling our own cells through autophagy.“ The same effect can occur with having some protein during your workout when doing targeted intermittent fasting after being in a fasted state for over 18 hours.

  In the case of eating once a day, I would say that you’d still maintain higher levels of autophagy
during the meal and you’ll maintain it after the meal as well because the body will use those calories for the mere essentials of energy homeostasis. Of course, if you eat too many excess calories you’ll stop autophagy but if you do it in a very small time frame like with OMAD you’ll go back into it much faster as well. Now, I don’t have any evidence or studies to prove these claims but this is my hypothesis and it makes sense from the perspective of nutrient signaling.

  BCAAs

  There are some calories in BCAAs although they’re used for muscle protein synthesis. One gram of BCAAs usually has about 4-5 calories and a single serving of a standard amino drink will have about 20 calories. Therefore, BCAAs will kick you out of a fasted state, but whether or not it’s a bad thing depends on many things.

  BCAAs play the biggest role in supplying amino acids and energy with muscles specifically. At any given time, the liver is releasing a constant supply of amino acids to skeletal muscle for maintaining blood sugar levels and supporting cellular protein homeostasis. This mechanism is supposed to keep your cells nourished with enough building blocks needed for survival.

  Figure 89 The transport and utilization of BCAAs

  The most common said benefit of BCAAs is that they help you to preserve muscle while at a caloric deficit or when fasting.