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Does fasting increase ketone levels?

After a single overnight fast, concentrations of ketones in the body are around 0.1 - 0.5mM, meaning you'll be just below the “threshold” for ketosis. After 48 hours of fasting, ketones can reach 1 - 2mM. 5 days of fasting can increase ketone levels to around 7 - 8mM.

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When it comes to biohacking, there probably aren’t two more popular practices than the ketogenic high-fat diet and fasting. Both regimens have health benefits including improved metabolism, weight loss, and even better cognitive function. Research studies have shown benefits for each, and personal stories on social media serve as some pretty profound anecdotes. It might not be surprising that many often adopt a keto diet with intermittent fasting. Maybe you’re one of those people. This makes sense—keto and intermittent fasting actually have a lot in common. Keto works in many of the same ways that intermittent fasting works. And, in fact, sticking to a low-carbohydrate or ketogenic diet might actually make it much, much easier to practice intermittent fasting. The synergy of keto with intermittent fasting can lead to some pretty remarkable benefits for you body. This article will explore why.

Overview of Ketosis

Ketosis is a metabolic state characterized by the presence of ketones in the blood. This occurs when the body is faced with a “challenge” of low blood sugar and reduced glycogen stores, which initiates a cascade of hormones that signal the body to begin breaking down fat stores and releasing fatty acids into the circulation. Once in the circulation, these fatty acids are transported to the liver and used in the production of ketones—a process termed ketogenesis. In particular, the liver produces a ketone body known as acetoacetate (AcAc), a majority of which is turned into beta-hydroxybutyrate (BHB).

But what’s the purpose of ketosis?

Most of us know that our body can make energy by burning carbohydrates as well as fat. One of the major sources of energy for humans and animals is glucose—which we obtain primarily by consuming dietary carbohydrates: breads, fruits, vegetables, legumes, starches, and sugars. The breakdown of carbohydrates into glucose is one way that we maintain blood sugar. Lots of body tissues use glucose as a fuel—and some can’t use anything else (some eye cells and red blood cells, for instance). In addition to glucose in the blood, we can store glucose in our muscles and liver as glycogen—long chains of glucose. We utilize glycogen during situations where blood glucose starts to run low—like during long-duration exercise. Humans can also burn fat for energy, and several organs like the heart prefer fat as their main energy substrate. Fat is also a great energy source because we have a lot of it! Even the skinniest among us have enough body fat to last a long time. The purpose of ketosis is to provide fuel when the other sources of energy (mainly glucose) are running low. This was (and still is, perhaps) a survival mechanism that allowed organisms to survive under conditions where food supply was low. In order to keep energy levels high and maintain cognitive function, the liver produces ketones to serve as a metabolic fuel for the brain and body. Ketones, unlike fatty acids, can cross the blood brain barrier that separates the brain from our circulation. In this way, the brain can have an energy source when glucose is low. During “starvation”, up to 60% of the brain’s energy might come from ketone body metabolism. While ketosis isn’t necessarily needed for “survival” in our modern times, this “unique” metabolic state likely has some benefits. In this article, we will specifically talk about endogenous ketosis, since it best relates to intermittent fasting.

Benefits of Ketosis

Ketosis achieved through a ketogenic diet has been shown to have benefits for a wide variety of clinical conditions. The keto diet originally started as a treatment for epilepsy, and is still used in this way today. The metabolism of ketones may have some potent brain benefits including a reduction of oxidative stress, lower levels of inflammation, and improved levels of various neurotransmitters involved in health and disease processes. Newman2017 The ketogenic diet has been shown to reduce the frequency of seizures in epileptic patients anywhere from 40 - 90%. These results are probably due to several mechanisms including increased GABA, Yudkoff2008 reduced glutamate, Juge2010 higher activity of potassium ion channels, Bough2007 and reduced brain glucose metabolism. Chen2019 Other brain conditions that benefit from ketosis include Alzheimer’s disease and Parkinson’s disease. Newport2015,Kashiwaya2013,Krikorian2012,Henderson2009,Vanitallie2005 There is even some evidence that ketosis could improve mood, reduce migraines, and enhance mental focus. Strahlman2006,Schnabel1928,Dilorenzo2013,Dilorenzo2015 Along with brain health, ketosis is effective in treating metabolic conditions like type 2 diabetes, which is characterized by insulin resistance. The keto diet reduces blood glucose and lipids, increases weight loss, and improves insulin sensitivity Gannon2006,Hussain2012,Feinman2015,Boden2005 —all of which reduce the risk for diabetes and the metabolic syndrome or attenuate their negative effects. The metabolic benefits of keto might extend to athletes as well, since ketosis is characterized by an increased capacity to burn fat. Several studies have provided evidence that athletes on a keto diet can significantly improve their body composition—build lean muscle mass while reducing body fat. Ketosis can be achieved endogenously (using exercise, fasting, or a ketogenic diet) or exogenously through the use of exogenous ketone supplements. Many benefits of ketosis are similar, regardless of the method achieved to induce it. However, some benefits are specific to endogenous ketosis—in particular those related to weight and fat loss.

This is also a benefit shared by intermittent fasting.

Fasting 101

You’ve likely heard of fasting in one way or another—it seems to be all over the media lately. Whether it’s being talked about as “biohacking” or an eating disorder, fasting is pretty controversial. In a world of overeating, not eating is polarizing. But while controversial, the data don’t lie. Research studies on fasting have shown that this lifestyle practice can have a multitude of health benefits—several of which are similar to those induced by ketosis. This makes sense...since fasting leads to ketone production. Let’s take a look at how this happens.

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What is Intermittent Fasting?

In simple terms, intermittent fasting refers to a reduced meal frequency. While there are many variations of IF, the most common forms include a once-weekly 24 hour fast, alternate day fasting (ADF) or a 5:2 fast—which involves fasting 2 consecutive days out of each week. The “intermittent” part of IF simply means that you aren’t necessarily fasting everyday. That’s what differentiates IF from time-restricted feeding (TRF). TRF is the practice of reducing your eating window to anywhere from 4 - 10 hours during the day, and fasting the rest of the time. In contrast to IF, most people who practice TRF do so every day.

The Science of IF

Every time we eat, a metabolic response is triggered. If the meal contains carbohydrates, this metabolic response will include an increase in blood glucose (of varying degrees) and insulin. The pancreas releases insulin in order to facilitate the uptake of blood glucose into our skeletal muscles. When insulin is released, it signals for the body to store excess energy as glycogen or adipose tissue. The primary storage sites are the liver and skeletal muscle. Along with upregulating processes for the storage of energy, insulin inhibits others—in particular those that release fat from our stored adipose tissue deposits. Basically, insulin is a signal to “grow’ instead of “breakdown”—it’s anabolic rather than catabolic.

During fasting, since no food is coming in, blood glucose and insulin levels begin to drop. After a certain period of time, the body will start to burn fat and produce ketones. How long does it take?

After a single overnight fast, concentrations of ketones in the body are around 0.1 - 0.5mM, meaning you’ll be just below the “threshold” for ketosis. After 48 hours of fasting, ketones can reach 1 - 2mM. 5 days of fasting can increase ketone levels to around 7 - 8mM. Pinckaers2017 Fat burning and ketone production are the primary outcomes of intermittent fasting, and two mechanisms that explain many of IF’s benefits.

Benefits of Intermittent Fasting

There are several advantages to intermittent fasting—both physiological and psychological.

The first benefit may be for those looking to lose weight. While the research isn’t definitive on this, many people report that they find it much easier to stick to than traditional diets where you’re forced to consume much fewer calories than you need. Some might find it easier to simply not eat than to chronically maintain calorie intake well below their means. This could be more of a psychological effect than something physical. In addition, IF may make it easier to meal plan (or not plan...if you catch our drift). If it’s one of your fasting days, you don’t have to worry about preparing a meal, making time to eat, or worrying about WHAT you’re going to eat. When done in the proper context, this could free up some time to be productive in work or hobbies. Intermittent fasting is in its infancy as far as research goes, and most studies have been conducted in mice.

Lean and Mean

IF may benefit body composition. In humans, fasting for 24 hours may reduce weight and maintain that weight loss for up to 48 hours (most is likely just water weight). Multiple cycles of fasting (for example, weekly 24 hours fasts) could lead to long-term weight loss, however. This needs to be explored more in humans. In mice, a diet that mimicked fasting and was repeated twice per month significantly reduced the amount of visceral fat in these rodents; with the added benefits of increased neurogenesis, improved cognitive performance, and bolstered immune system. Brandhorst2015

Live Long and Prosper

It’s hard to study lifespan in humans, so in this area, we don’t have a lot of data on IF promoting a longer life. But, in rodent models, animals were fasted intermittently showed increased lifespan and healthspan compared to mice who ate more frequently. Mitchell2019 Lifespan might be enhanced through several mechanisms involving increased autophagy, reduced oxidative stress, and lower levels of insulin and insulin-like growth factor 1 (IGF-1). Parzych2014,Martinet2006,Mizushima2004,Mojto2018,Lee2012,Fuhrman2002

Metabolic Boost

Several aspects of metabolism and digestive health might improve through IF. Intermittent fasting has been shown to reduce levels of several risk factors for cardiovascular and heart disease including: blood lipids (cholesterol and triglycerides), blood glucose, insulin, blood pressure, and inflammation. Patterson2017,Moro2016 These metabolic benefits might come from the effects that fasting has on regulating our circadian rhythms, sleep, and the gut microbiome. Individuals who report practicing routine, periodic fasting (i.e. IF) have a lower risk of diabetes, reduced levels of blood glucose, and a lower body mass index. Horne2012 This shows that fasting might help prevent the onset of several metabolic diseases. However, fasting may also reverse aspects of diseases like type 2 diabetes. Li2017,Arnason2017 This might include reducing glucose and insulin or improving insulin sensitivity.

Brain Health

We’ve covered the body, what about the brain? This organ may too benefit from what IF has to offer. One benefit may relate directly to ketones—specifically beta-hydroxybutyrate (BHB). BHB is a strong stimulus for the release of a hormone known as brain-derived neurotrophic factor (BDNF) which promotes the growth of new neurons (called neurogenesis). Lutas2014 Unfortunately, other “mental benefits” of fasting haven’t been studied. We don’t have studies on how fasting impacts cognitive function, mental clarity, or focus. However, one study that included 1,422 participants found evidence that physical and emotional well being improve during fasts lasting from 4 to 21 days in duration. This is some fairly strong data that fasting may not only be feasible, but beneficial for the brain in healthy individuals. Wilhelmi2019

Variations of Intermittent Fasting

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Perhaps one of the most attractive aspects of fasting is that it is completely customizable. Whether you’re doing time restricted eating or a once-per week fast, YOU get to choose how to fit fasting into your life. And, since we don’t have data as to what the best fasting protocol is, the only thing that matters is how your fasting regimen uniquely benefits you and fits within your lifestyle. While we mentioned that keto and intermittent fasting are often practiced together, they don’t have to be. For some people, that’s another attractive benefit of IF. Instead of focusing on exactly what to eat, with IF, you’re only worried about when you eat.

The 5:2 Fast

The 5:2 fast has its description in the name. Eat for 5 days each week, fast for 2. It sounds pretty simple, because it is. The 2 days must be consecutive, however; or at least that’s what is recommended by 5:2 advocates. How do you go about eating on the 5 days when you aren’t fasting. Some people might just take up some sort of modified time-restricted feeding regimen and eat what they normally would. Others may just say “no rules.” When 5:2 fasting is described, the “feeding days” are usually said to be “ad libitum”—which essentially means you eat whatever you want. But keep it reasonable.

Alternate day fasting is another self-explanatory regimen.

In this fasting protocol, you eat every other day.

This means you’ll be eating 4 days out of every 7 during any week.

Extended Water Fasting

While similar to 5:2 fasting and ADF, water fasting is a more prolonged IF regimen—typically involving a fast of anywhere from 48 to 72 hours or more where only water is consumed. Given the long time frame of water fasting, it is sometimes advised to consume some minerals and electrolytes like sodium, potassium, and magnesium.

Combining Keto and IF

We have mentioned more than once that fasting is super popular among people who are also following a ketogenic diet. There may be some solid theory behind this. In fact, eating a ketogenic high-fat low-carb diet will make fasting easier and more manageable. This is because a keto diet will help you become more fat adapted, which will enhance your ability to perform an extended fast without feeling lethargic, depressed, or unbearably hungry. Keto diets and intermittent fasting both have the same metabolic goals—train the body to efficiently burn fat for energy and get into a state of ketosis. Both regimens do this by depleting glucose and lowering insulin levels in the body. Another advantage of combining keto with intermittent fasting is that IF may help you get into ketosis even faster and perhaps achieve higher ketone levels. Intermittent fasting promotes ketosis, and ketosis may help with intermittent fasting. A beautiful metabolic marriage.

Keto and IF Diet Plan

Maybe you’re thinking about trying the keto diet or experimenting with fasting. Perhaps you’re already doing both. Either way, we’ve provided a sample daily and weekly layout of what a plan might look like for someone on a keto diet who is also integrating some alternate-day fasting and 16:8 time-restricted feeding into their regimen.

Sunday

6:00am: Water and/or black coffee (no, coffee won’t break the fast)

9:00am: More water or black coffee.

12:00pm: TRF ends. Have a keto-friendly meal: maybe a salad with grilled chicken topped with olive oil and feta cheese, avocado and some hard-boiled eggs or bacon bits. 3:00pm: Snack on some nuts or have some nut butter, and maybe coffee with some MCT oil or coconut oil. 6:00pm: 8 - 12oz of a fatty cut of meat (ribeye steak or fatty fish) plus some vegetables; maybe brussels sprouts cooked in butter. 8:00pm: Small snack of nuts, blueberries, and a piece of strong dark chocolate for “dessert”. This is your last meal of the day.

Monday: Same eating window as yesterday: 12 - 8 pm.

Tuesday: Fasting day. No calories consumed today.

Wednesday: Eating period of 12 - 8pm. You might be hungrier today since you fasted yesterday, especially if you did an early morning workout today.

Thursday: Fasting day

Friday: 12 - 8 eating window. Workout in the morning or, if you want to do a fueled workout, do so in between lunch and dinner.

Saturday: Fast day

Remember, this is only one example out of a nearly unlimited number of iterations! Change this up to fit your lifestyle, use it as a guide to design your own fasting regimen.

Bring on the Benefits

After all of the evidence presented, it’s hard to argue against the keto diet or intermittent fasting. They seem to benefit so many different physical conditions and diseases, along with having benefits for non-disease related functions. It is said that the benefits of keto are basically due to the fact that it activates similar mechanisms to that of fasting—this is true. Fasting and ketosis both seem to call upon ancient biological pathways to promote stress resistance, survival, and longevity. While we advocate both highly, don’t just jump right into fasting and ketosis without a bit of experience first. It takes some time to both metabolically and psychologically adapt to dietary regimens—especially prolonged fasting. Maybe try out TRF first along with a keto diet, and gradually progress your fasting periods. If you’ve had a great experience with keto, IF, or both, tell us in the comments! We’d love to hear.

hvmn.com - Keto and Intermittent Fasting: A Beginner's Guide | H.V.M.N. Blog

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