Sunday, May 28, 2017

Muscle loss during short-term fasting

This is an issue that often comes up in online health discussions, and was the topic of a conversation I had the other day with a friend about some of the benefits of intermittent fasting. Please note that the term "fast" is used in this post as synonymous with a period of time in which only water is consumed. If one consumes, say, a carrot during a 10 h "fast", then that is not really a fast.

Can the benefits of intermittent fasting be achieved without muscle loss? The answer is “yes”, to the best of my knowledge.

Even if you are not interested in bulking up or becoming a bodybuilder, you probably want to keep the muscle tissue you have. As a norm, it is generally easier to lose muscle than it is to gain it. Fat, on the other hand, can be gained very easily. This is today, in modern urban societies. Among our hominid ancestors, this situation was probably reversed to a certain extent.

Body fat percentage is positively correlated with measures of inflammation markers and the occurrence of various health problems. Since muscle tissue makes up lean body mass, which excludes fat, it is by definition negatively correlated with inflammation markers and health problems.

As muscle mass increases, so does health; as long as the increase in muscle mass is “natural” – i.e., it comes naturally for the individual, ideally without anything other than unprocessed food. Unnatural muscle gain may increase health temporarily, but problems eventually happen. For example, several years ago a colleague of mine gained a great deal of muscle mass by taking steroids. A few months later he had a spinal disc herniation while lifting, and never fully recovered. About a year ago he was obese, diabetic, and considering bariatric surgery.

If you are a natural lightweight, your frame may not adapt fast enough make you a natural heavyweight. And there is nothing wrong with being a natural lightweight.

In short-term fasts (e.g., up to 24 h) one can indeed lose some muscle mass as the body produces glucose using amino acids in muscle tissue through a process known as gluconeogenesis. In this sense, muscle is the body’s main reserve of glucose. Adipocytes are the body’s main reserves of fat.

Muscle loss is not pronounced in short-term fasts though. It occurs after the body’s glycogen reserves, particularly those in the liver, are significantly depleted. This often starts happening 8 to 12 hours into the fast, for people who do not fast regularly, and depending on how depleted their liver  glycogen (liver "sugar") reserves are when they start fasting. Those who fast regularly tend to have greater reserves of liver glycogen, a form of compensatory adaptation, and could go on fasting for as much as 20 h or so before their bodies need to resort to muscle catabolism to meet the brain's hunger for glucose (often about 5 g / h).

The liver is the main store of body sugar used to supply the glucose needs of the brain. This is interesting, since skeletal muscle often stores 5 times more sugar than the liver. That muscle sugar, also stored as glycogen, is pretty much "locked". It can be tapped during intense physical exertion (e.g., sprints, weight training), and pretty much nothing else can release it. The brains of our ancestors living 200 thousand years ago needed as much glucose as ours do, but their fight-or-flight needs took precedence. Our body today is like that; we are largely adapted to life in our ancestral past.

When the body is running short on glycogen, primarily liver glycogen, it becomes increasingly reliant on fat as a source of energy, sparing muscle tissue. That is, it burns fat and certain byproducts of fat metabolism, such as ketone bodies. This benign state is known as ketosis; not to be confused with ketoacidosis, which is a pathological state. There is evidence that ketosis is a more efficient state from a metabolic perspective (see, e.g., Taubes, 2007).

Often people feel an increase in energy, cognitive ability, and stress when they fast.

The brain also runs on fat (through ketone byproducts) while in ketosis, although it still needs some glucose to function properly. That is primarily where muscle tissue comes into the picture, to provide the glucose that the brain needs to function. While glucose can also be made from fat, more specifically a lipid component called glycerol, this usually happens only during very prolonged fasting and starvation.

You do not have to consume carbohydrates at all to make up for the glycogen depletion, after you break the fast. Dietary protein will do the job, as it is used in gluconeogenesis as well. However, it has to be plenty of protein, because of the loss due to conversion to glucose. This picture is complicated a bit by one interesting fact: the body tends to use protein first to meet its caloric needs, then resorting to carbohydrates and fat. Only ethanol takes precedence over protein.

Surprising? Think about this. Many animals, including humans, have a gene (frequently called the "myostatin gene") whose key function is to prevent amino acid storage in muscle beyond a certain point. Those people who have a mutation that impairs the function of this gene tend to put on muscle very easily, have low body fat percentages, and feel a lot of energy all the time. They are also hungry all the time. This genetic mutation is very rare. Children who have it look very muscular, and tend to grow to below-average height as adults.

Dietary protein also leads to an insulin response, which is comparable to that elicited by glucose. The difference is that protein also leads to other hormonal responses that have a counterbalancing effect to insulin (e.g., secretion of glucagon), by allowing for the body's use of fat as a source of energy. Insulin, by itself, promotes fat deposition and prevents fat release at the same time.

When practicing intermittent fasting, one can increase protein synthesis by doing resistance exercise (weight training, HIT), which tips the scale toward muscle growth, and away from muscle catabolism. Having said that, doing resistance exercise while fasting is usually not a good idea.

A combination of intermittent fasting and resistance exercise may actually lead to significant muscle gain in the long term. Fasting itself promotes the secretion of hormones (e.g., growth hormone) that have anabolic effects. The following sites focus on muscle gain through intermittent fasting; the bloggers are living proof that it works.

Muscle catabolism happens all the time, even in the absence of fasting. As with many tissues in the body (e.g., bones), muscle is continuously synthesized and degraded. Muscle tissue grows when that balance is tipped toward synthesis, and is lost otherwise.

Muscle will atrophy (i.e., be degraded) if not used, even if you are not fasting. In fact, you can eat a lot of protein and carbohydrates and still lose muscle. Just note what happens when an arm or a leg is immobilized in a cast for a long period of time.

Short-term fasting is healthy, probably because it happened frequently enough among our hominid ancestors to lead to selective pressures for metabolic and physiological solutions. Consequently, our body is designed to function well while fasting, and triggering those mechanisms correctly may promote overall health.

The relationship between fasting and health likely follows a nonlinear pattern, possibly an inverted U-curve pattern. It brings about benefits up until a point, after which some negative effects ensue.

Long-term fasting may cause severe heart problems, and eventually death, as the heart muscle is used by the body to produce glucose. Here the brain has precedence over the heart, so to speak.

Voluntary, and in some cases forced, short-term fasting was likely very common among our Stone Age ancestors; and consumption of large amounts of high glycemic index carbohydrates very uncommon (Boaz & Almquist, 2001).


Boaz, N.T., & Almquist, A.J. (2001). Biological anthropology: A synthetic approach to human evolution. Upper Saddle River, NJ: Prentice Hall.

Taubes, G. (2007). Good calories, bad calories: Challenging the conventional wisdom on diet, weight control, and disease. New York, NY: Alfred A. Knopf.


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Ned Kock said...

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SEAJ said...

Interesting read. I have been following an intermittent fasting lifestyle for about 9 months now. It has done wonders for my body composition. I am leaner and stronger at age 36 than I ever have been. I would be curious on your take of recent research of protein pulse feeding and using BCAA and or Hydrolyzed proteins to spike blood amino acids and insulin at intervals during the fast to improve anabolism or reduce catabolism. My money is on Pulse feeding and Intermittent fasting for that illusive get stronger while getting leaner goal we all chase.

David Graves said...

Excellent, excellent overview of the subject. I've been investigating many of the forms of fasting/calorie reduction methods and this is as succinct an analysis as you will find. My main worry was losing muscle mass in the fasting process and there is a dearth of information on that subject (unless you're a brainiac who can decipher the medicalese of research papers). If the blogger, Ned, is still active on this thread, I would like your opinion on the 5/2 intermittent fast routine (2 days fast/5 days normal diet): is 48 hours too long to avoid muscle loss and one should stick to the ADF routine instead? You state that weight training during a fast will help prevent atrophy but I don't see doing this on a second fast day.

Anonymous said...

Hi David Graves,

I don't think you are supposed to fast for the 2 days continuous. It is 2 days out of 7 fasting and 5 days out of 7 feeding. I also think it is not advice to fast for 2 days continuous.


Anonymous said...
This comment has been removed by a blog administrator.
Pierre said...

Been low carb since 2011. Lost 50 pounds and have never been stronger in my life. I am 58. For nearly the entire time I have been working out at least 2 times a week and sometimes up to 5 days a week. Mostly body weight exercises but in the last 6 months have been lifting weights. That caused me to go from 195 average weight to 205. 6' tall.

I eat once a day 5 days a week. On the weekends my wife and I love to cook breakfast and what is funny is that eating breakfast makes it difficult to not have a snack before dinner which never happens on weekdays.

My only weakness at this point is the stress from work that is unavoidable right now. Working on curing that problem eventually.

Ned Kock said...

This post is a (significantly) revised version of a previous post. The original comments are preserved here. More comments welcome, but no spam please!

Ugur Gundogmus said...

Hi Ned.

What is your ideal fast? For example:

24 hours in one week?
48 hours in a month?
16 hours?


Also, I think it's time to change your blog platform. It looks outdated and spammers are always here. You have so many excellent articles. Unfortunately, it's almost impossible to have a good user experience when I visit your site/blog.

Why don't you choose a simple, better platform?


Anonymous said...

I would like to know the pathway of protein metabolism which leads to the body fat loss. e.g. by Dukan diet.
As you have mentioned there is a considerable insulin response to proteins similar to the carbs. But this insulin does not increase the body fat storage.
Is this probably related to the secretion of glucagon, which triggers the liver to release glucogen?
And replacing this glucogen later by the liver (by the metabolism of the body fat) leads to decreasing of body fat in long term? Thanks, Franz.

Nigel Kinbrum said...

Hi Ned,

This is spooky! I'm currently embroiled in a twitter argument about fasting. Someone claimed that the large increase in HGH during fasting is anabolic.

I stated that when liver glycogen is exhausted, BG falls to ~3.3mmol/L and the pituitary secretes ACTH which raises cortisol to catabolise muscle to provide AAs for the liver & kidneys to use for the synthesis of glucose.

If/when BG falls to ~2mmol/L, the pituitary secretes HGH to antagonise insulin to prevent any further (possibly fatal) fall in BG. HGH is anti-catabolic, not anabolic. What say you?

Cheers, Nige

Ned Kock said...

Hi Nigel. HGH promotes an anabolic response together with other hormones, such as testosterone, but not by itself. HGH also promotes body fat mobilization, in a marked way. The largest levels of HGH in humans are found in young women. Young men have lower HGH levels, but present markedly higher anabolic responses.

Ned Kock said...

Hi Franz. In my opinion, a diet high in protein (and low in fat) would tend to be low in calories. In such a diet, protein would have to be used as a basis for the production of glucose (initially to replenish liver glycogen, ultimately to feed the needs of the brain), and also to meet the caloric needs of the individual (50 – 100 calories / h). This “jack of all trades” role of protein would reduce its caloric content below the 4 cal / g it is generally believe to have.

Ned Kock said...

Hi Ugur. To me it seems reasonable to fast in a somewhat random fashion, otherwise it becomes stressful. I would definitely fast on days (on the days before) in which I intend to eat a lot of food in one meal; e.g., early dinner the day before, and no food until Thanksgiving dinner the next day.

Ned Kock said...

Btw, folks, keep in mind that you need a caloric “bomb” from time to time – e.g., once every two weeks, or once a month. This is only marginally related to fasting, since you may fast everyday and still be in caloric surplus. Still, those who have the willpower to fast regularly can also withstand prolonged caloric restriction. If you stay in caloric deficit for months on end your body will respond in an undesirable way. One thing that typically will happen is a reduction in thyroid hormones production, to down-regulate your metabolism. You will feel miserable, your lab numbers will cause concern to you and your doctor, and you may become skinny-fat.

Anonymous said...

Hi Ned,
Is there any idea how long the liver needs to regenerate after let's say significantly depletion of glycogen?
Sure there will be differences in individulas. But is it something about 2 hours or 24 hours or even more? Thanks, Franz

Ned Kock said...

Hi Franz. Muscle glycogen replenishment, for fully depleted muscles, often takes days. I have a post here somewhere that provides a graph. I couldn't find it, but I'll link it here if I do.

Anonymous said...

Hi Ned,

Many thanks! I found this post from 2010, but no graph:

"Liver glycogen is replenished in a few hours. Muscle glycogen takes days...

If one’s liver glycogen tank is close to empty, eating a couple of apples will have little to no effect on body fat formation. This will be so even though two apples have close to 30 g of carbohydrates, more than 20 g of which being from sugars. The liver will grab everything for itself, to replenish its 100 g glycogen tank."

My own experience seems to confirm the idea about replenishment of muscle glycogen over days. Sleep problems after about 3 weeks intermittent fasting (about 17 hours a day), low carb diet plus some exercises are clear indication for me that the body needs some glucose!