What is the probability that you are NOT diabetic if your fasting blood glucose is 110-126 mg/dl?

Often I hear from readers who have changed their diets and lifestyles toward a more evolutionarily sound direction () that their fasting blood glucose (FBG) readings have gone up. Frequently numbers in the range 110-126 mg/dl (6.1-7 mmol/l) are mentioned.

If you have a FBG reading of 110-126 mg/dl (6.1-7 mmol/l) very likely your doctor will tell you that you are either diabetic or well on your way be becoming diabetic.

Diabetes is a condition that in humans is most frequently associated with damage to the beta cells in the pancreas, significantly impairing insulin secretion. With limited insulin, glucose levels tend to go up, leading to high FBG levels and high glucose peaks after consumption of carbohydrates. The latter, high glucose peaks, appear to be particularly damaging when happening regularly over time.

What is the probability that you are NOT diabetic with this FBG reading?

I put together the table below, based on data from a widely cited meta-analysis () conducted by the research group called The Emerging Risk Factors Collaboration. It shows the distribution of FBG levels in urban settings among individuals who do not have diabetes.

The numbers in this table are fairly consistent with those from various other surveys of large numbers of individuals in urban settings.

The study mentioned above also tells us that the incidence of diabetes in urban populations is in the neighborhood of 6.8 percent. This may not sound like much, but as disease incidences goes, it is very high – approximately 1 in every randomly selected group of 15 people has diabetes.

The vast majority of those diagnosed will have diabetes mellitus type 2, which tends to develop over time and be associated with the metabolic syndrome ().

We know from Bayes' theorem, which is a fundamental element of the increasingly popular Bayesian statistics, that the probability of an event A given that an event B has occurred [denoted P(A|B)] is given by:

P(A|B)=P(B|A)*P(A)/P(B).

In the equation above, P(B|A) is the probability of event B given A, P(A) is the probability of event A, and P(B) is the probability of event B.

To answer the question posed in the title of this blog post, we need to calculate the probability that a person will have no diabetes given that he or she has a fasting blood glucose of 110-126 mg/dl.

Replacing A and B in the equation above with “NoDiabetes” (short for not having diabetes) and “FBG=110-126 mg/dl” respectively, we arrive at the formula to calculate the probability that answers the question:

P(NoDiabetes|FBG=110-126 mg/dl)=P(FBG=110-126 mg/dl|NoDiabetes)*P(NoDiabetes)/P(FBG=110-126 mg/dl).

From the table above we know that P(FBG=110-126 mg/dl|NoDiabetes)=7 percent. From our previous discussion, we know that P(NoDiabetes)=(100-6.8)/100 =93.2 percent.

Finally, the study tells us that P(FBG=110-126 mg/dl) is 9.1 percent. This includes individuals with diabetes (2.1 percent) and without diabetes (7 percent).

With these numbers, we can calculate the probability that a person will have no diabetes given that he or she has a FBG of 110-126 mg/dl:

P(NoDiabetes|FBG=110-126 mg/dl)=0.07*(1-0.068)/0.091=0.72.

That is, if your fasting blood glucose is in the 110-126 mg/dl range (6.1-7 mmol/l) then the probability that you DO NOT have diabetes is 72 percent. It would be much safer to bet that you do not have diabetes than that you do, even at that relatively high range.

Surprising eh!?

The above discussion not only highlights the lack of reliability of fasting blood glucose levels for diabetes diagnoses in the 110-126 mg/dl range (6.1-7 mmol/l), but also begs the question – what could cause high fasting blood glucose levels in healthy individuals?

Some of the folks I heard from have gone through insulin sensitivity tests (see, e.g., ), and were found to be insulin sensitive (in at least one case, highly sensitive), even though their baseline glucose levels are generally high. This goes against the possible speculation that they are prediabetics well on their way to becoming diabetic.

One possibility has been discussed in a previous post, which also mentions what could happen with HbA1c levels ().

Doing crossfit and looking like a bodybuilder?

Top crossfit athletes like Annie Thorisdottir and Rich Froning Jr. (pictured below; photos from Crossfitthestables.com and List09.com) look like bodybuilders even though their training practices are markedly different from those of most top natural bodybuilders. It is instructive, from a human physiology perspective, to try to understand why.

First of all we should make it clear that what makes Annie Thorisdottir and Rich Froning Jr. look the way they do is not only crossfit training. Genetics plays a key role here. Some people don’t accept this argument at all. Can you imagine someone arguing that top basketball players are generally tall because the stretching and reaching moves inherent in playing basketball make them tall? Top basketball players are not tall because they play basketball; the causality is stronger in the opposite direction: they play basketball because they are tall. The situation is not all that different with top crossfit competitors.

Often people will point at before and after photos as evidence that anyone can achieve the level of muscularity of a champion natural bodybuilder, if they do the right things. The problem with these before and after photos is that one can “go down” in terms of muscularity and definition quite a lot, but there is a clear ceiling in terms of “going up”. For example, if one goes from competitive marathon running to competitive bodybuilding, after a few years the difference will be dramatic if the person has the genetics necessary to gain a lot of muscle.

In other words, those who have the genetics to become very muscular can lose muscle and/or gain body fat to the point that they would look like they don’t have much genetic potential for muscle gain. Someone who doesn’t have the required genetics, on the other hand, will also be very effective at losing muscle and/or gaining body fat, but will be much more limited at the upper end of the scale.

The table below is from a widely cited and classic study by Fryburg and colleagues on the effects of growth hormone, insulin, and amino acid infusion on muscle accretion of protein. The article is available online as a PDF file (). The measurements shown on the table were taken basally (BAS) and at 3 h and 6 h after the start of the infusions, one of which was of a balanced amino acid mixture that raised arterial phenylalanine concentration to about twice what it was before the infusion. Phenylalanine is one of the essential amino acids present in muscle ().

There were four experimental conditions, two with only amino acid infusion, one with insulin and amino acid infusions, and one with insulin-like growth factor 1 (IGF-1) and amino acid infusions. Protein synthesis and breakdown numbers are based on phenylalanine kinetics inferences. The balance number is based on the synthesis and breakdown numbers; the former minus the latter. Note that at BAS the balance is always negative; this implies a net amino acid loss from muscle. At BAS the measurements were taken after a 12 h fast.

All infusions – of insulin, IGF-1, and amino acids – were continuously applied during the 6 h period. There was no exercise involved in this infusion study, and the amino acid mixture was balanced; as opposed to focused on certain amino acids, such as BCAAs.

The numbers in the table suggest that insulin infusion brings the balance to positive territory at the 3-h mark, with the effect wearing down at 6 h. IGF-1 infusion brings the balance to positive territory at 3 h, with the effect increasing and almost doubling at 6 h. Amino acid infusion alone brings the balance to positive territory a bit at 3 h and 6 h, and much less than when it is combined with insulin or IGF-1 infusions.

The effects of these infusions were due to both reductions in breakdown (amino acid loss) and increases in synthesis. We see that insulin exerts its effect on the balance primarily by suppressing breakdown. IGF-1 exerts its effect on the balance primarily by increasing synthesis. The effect of IGF-1 on the balance is significantly stronger than those of insulin and amino acid infusions, even when these latter two are taken together.

While this is an infusion study, one can derive conclusions about what would happen in response to different types of exercise and nutrients. Under real life conditions, insulin will increase in response to ingestion of carbohydrates and/or protein. IGF-1 will increase in response to growth hormone (GH) elevation, of which a major trigger is intense exercise.

The type of exercise that leads to the highest elevation of GH levels is intense exercise that raises heart rate significantly and rapidly. Examples are sprints, large-muscle resistance exercise, and resistance exercise involving multiple muscles at the same time. At the very high end of GH secretion are exercises that use large upper and lower body muscles at the same time, such as the deadlift. At the low end of GH secretion are localized small-muscle exercises, such as calf raises and isolated curls.

Anecdotally it seems that, at least for beginners, those exercises that lead to the highest GH secretion are the least “comfortable” for them. That is, those are the exercises that cause the most “huffing and puffing”. So next time you do an exercise like that, use this as a motivator: these are the exercises with the biggest return on investment; whether you are looking for health improvement, muscle gain, or both.

Competitive crossfit practitioners tend to favor variations of high-intensity interval training (HIIT), with an emphasis on a blend of endurance and strength exercises. Endurance and strength are both needed in crossfit competition. Competitive bodybuilders tend to focus more on strength, often exercising with more resistance or weight than competitive crossfit practitioners.

Extrapolating from the infusion study, one could argue that high GH secretion exercises are critical for amino acid accretion in muscle. Both groups mentioned above – competitive crossfit practitioners and competitive bodybuilders – exercise in ways that lead to high GH secretion. Surprising as this may sound (to some), if you do chin-ups, you’ll probably have better results in terms of biceps hypertrophy than if you do isolated bicep curls. This will happen even though the overall load on the bicep muscles will be lower with the chin-ups. The reason is that the GH secretion will be significantly higher with the chin-ups, because more muscles are involved at the same time, including large ones (e.g. the lats).

It is interesting to see competitive crossfit practitioners talking about needing to lose some weight but not being able to (). The reason is that they do not have much body fat to lose, and the types of exercise that they do create such a powerful stimulus toward positive nitrogen balance () that they end up gaining weight even as they restrict calorie intake.

Carbohydrate ingestion prior to exercise may raise insulin levels, but will blunt GH secretion; protein without carbohydrate, on the other hand, will raise insulin levels without blunting GH secretion (). Whether ingesting protein immediately before exercising is necessarily good in the long run is an open question, however, because GH secretion is likely to be greater for someone who is exercising in the fasted state, as GH secretion is in part a response to glycogen depletion (, ). And, as we have seen from the infusion study, GH secretion is disproportionately important as a positive nitrogen balance factor.

Compensatory adaptation applied to human biology () suggests that the body responds to challenges over time, in a compensatory way. Which scenario poses the bigger challenge: (a) high GH exercise with more amino acid loss during the exercise, or (b) high GH exercise with less amino acid loss during the exercise? I think it is (a), because the message being sent to the body is that “we need more muscle to do all of this and still compensate for the loss during exercise”.

Maybe this is why top crossfit practitioners end up looking like bodybuilders, and cannot lose muscle even when a slightly lighter frame would make them more competitive in crossfit games. Their bodies are just responding to the stimuli they are getting.

My transformation: How I looked 10 years ago next to a thin man called Royce Gracie

The photos below were taken about 10 years ago. The first is at a restaurant near Torrance, California. (As you can see, the restaurant was about to close; we were the last customers.) I am standing next to Royce Grace, who had by then become a sensation (). He became a sensation by easily defeating nearly every champion fighter that was placed in front of him. In case you are wondering, Royce is 6’1” and I am 5’8”. The second photo also has Royce’s manager in it – that is his wife. Their children’s names both start with the letter “K”. I wonder how big they are right now.

I think that at the time these photos were taken I weighed around 200-210 lbs. Even though I am much shorter than Royce, I outweighed him by around 40 lbs. Now I weigh 150 lbs, at about 11 percent body fat, and look like the photo on the top-right area of this blog - essentially like a thin guy who does some manual labor for a living, I guess. A post is available discussing the "how" part of this transformation (). I only put a shirtless photo here after several readers told me that my previous photo looked out of place in this blog.

My day job is not even remotely related to fitness instruction. I am a college professor, and like to think of myself as a scholar. I don’t care much about my personal appearance; never did. At least in my mind, putting up shirtless photos on the web should not be done gratuitously. If you are a fitness instructor, or an athlete, that is fine. In my case, it is acceptable in the context of telling people that a few minutes of mid-day sun exposure, avoiding sunburn, yields 10,000 IU of skin-produced vitamin D, which is about 20 times more than one can get through most "fortified" industrial foods.

Royce is such a nice guy that, after much insistence, he paid for the dinner, and then we drove to his house and talked until about midnight. He had told me of a flight the next morning to Chicago, so I ended the interview and thanked him for the wonderful time we had spent together. I had to talk him out of driving ahead of me to I-405; he wanted to make sure I was not going to get lost at that time of the night. This was someone who was considered a demigod at the time in some circles. A humble, wonderful person.

Royce helped launch what is today the mega-successful Ultimate Fighting Championship franchise (), which was then still a no holders barred mixed martial arts tournament. At the time the photos were taken I was interviewing him for my book Compensatory Adaptation, which came out in print soon after (). The book has a full chapter on the famous Gracie Family, including his father Helio and his brother Rickson.

I talked before about the notion of compensatory adaptation and how it applies to our understanding of how we respond to diet and lifestyle changes (). In this context, I believe that the compensatory adaptation notion is far superior to that of hormesis (), which I think is interesting but overused and overrated.

The notion of compensatory adaptation has been picked up in the field of information systems, my main field of academic research. In this field, which deals with how people respond to technologies, it is part of a broader theory called media naturalness theory (). There are already several people who have received doctorates by testing this theory from novel angles. There are also several people today who call themselves experts in compensatory adaptation and media naturalness theory.

The above creates an odd situation, and something funny that happened with me a few times already. I do some new empirical research on compensatory adaptation, looking at it from a new angle, write an academic paper about it (often with one or more co-authors who helped me collect empirical data), and submit it to a selective refereed journal. Then an "expert" reviewer, who does not know who the authors of the paper are (this is called a "blind" review), recommends rejection of the paper because “the authors of this paper clearly do not understand the notion of compensatory adaptation”. Sometimes something like this is added: “the authors should read the literature on compensatory adaptation more carefully, particularly Kock (2004)” - an article that has a good number of citations to it ().

Oh well, the beauty of the academic refereeing process …

Dietary protein does not become body fat if you are on a low carbohydrate diet

By definition LC is about dietary carbohydrate restriction. If you are reducing carbohydrates, your proportional intake of protein or fat, or both, will go up. While I don’t think there is anything wrong with a high fat diet, it seems to me that the true advantage of LC may be in how protein is allocated, which seems to contribute to a better body composition.

LC with more animal protein and less fat makes particularly good sense to me. Eating a variety of unprocessed animal foods, as opposed to only muscle meat from grain-fed cattle, will get you that. In simple terms, LC with more protein, achieved in a natural way with unprocessed foods, means more of the following in one's diet: lean meats, seafood and vegetables. Possibly with lean meats and seafood making up more than half of one’s protein intake. Generally speaking, large predatory fish species (e.g., various shark species, including dogfish) are better avoided to reduce exposure to toxic metals.

Organ meats such as beef liver are also high in protein and low in fat, but should be consumed in moderation due to the risk of hypervitaminosis; particularly hypervitaminosis A. Our ancestors ate the animal whole, and organ mass makes up about 10-20 percent of total mass in ruminants. Eating organ meats once a week places you approximately within that range.

In LC liver glycogen is regularly depleted, so the amino acids resulting from the digestion of protein will be primarily used to replenish liver glycogen, to replenish the albumin pool, for oxidation, and various other processes (e.g., tissue repair, hormone production). If you do some moderate weight training, some of those amino acids will be used for muscle growth.

In this sense, the true “metabolic advantage” of LC, so to speak, comes from protein and not fat. “Calories in” still counts, but you get better allocation of nutrients. Moreover, in LC, the calorie value of protein goes down a bit, because your body is using it as a “jack of all trades”, and thus in a less efficient way. This renders protein the least calorie-dense macronutrient, yielding fewer calories per gram than carbohydrates; and significantly fewer calories per gram when compared with dietary fat and alcohol.

Dietary fat is easily stored as body fat after digestion. In LC, it is difficult for the body to store amino acids as body fat. The only path would be conversion to glucose and uptake by body fat cells, but in LC the liver will typically be starving and want all the extra glucose for itself, so that it can feed its ultimate master – the brain. The liver glycogen depletion induced by LC creates a hormonal mix that places the body in fat release mode, making it difficult for fat cells to take up glucose via the GLUT4 transporter protein.

Excess amino acids are oxidized for energy. This may be why many people feel a slight surge of energy after a high-protein meal. (A related effect is associated with alcohol consumption, which is often masked by the relaxing effect also associated with alcohol consumption.) Amino acid oxidation is not associated with cancer. Neither is fat oxidation. But glucose oxidation is; this is known as the Warburg effect.

A high-protein LC approach will not work very well for athletes who deplete major amounts of muscle glycogen as part of their daily training regimens. These folks will invariably need more carbohydrates to keep their performance levels up. Ultimately this is a numbers game. The protein-to-glucose conversion rate is about 2-to-1. If an athlete depletes 300 g of muscle glycogen per day, he or she will need about 600 g of protein to replenish that based only on protein. This is too high an intake of protein by any standard.

A recreational exerciser who depletes 60 g of glycogen 3 times per week can easily replenish that muscle glycogen with dietary protein. Someone who exercises with weights for 40 minutes 3 times per week will deplete about that much glycogen each time. Contrary to popular belief, muscle glycogen is only minimally replenished postprandially (i.e., after meals) based on dietary sources. Liver glycogen replenishment is prioritized postprandially. Muscle glycogen is replenished over several days, primarily based on liver glycogen. It is one fast-filling tank replenishing another slow-filling one.

Recreational exercisers who are normoglycemic and who do LC intermittently tend to increase the size of their liver glycogen tank over time, via compensatory adaptation, and also use more fat (and ketones, which are byproducts of fat metabolism) as sources of energy. Somewhat paradoxically, these folks benefit from regular high carbohydrate intake days (e.g., once a week, or on exercise days), since their liver glycogen tanks will typically store more glycogen. If they keep their liver and muscle glycogen tanks half empty all the time, compensatory adaptation suggests that both their liver and muscle glycogen tanks will over time become smaller, and that their muscles will store more fat.

One way or another, with the exception of those with major liver insulin resistance, dietary protein does not become body fat if you are on a LC diet.

Book review: Biology for Bodybuilders

The photos below show Doug Miller and his wife, Stephanie Miller. Doug is one of the most successful natural bodybuilders in the U.S.A. today. He is also a manager at an economics consulting firm and an entrepreneur. As if these were not enough, now he can add book author to his list of accomplishments. His book, Biology for Bodybuilders, has just been published.

(Source: www.dougmillerpro.com)

Doug studied biochemistry, molecular biology, and economics at the undergraduate level. His co-authors are Glenn Ellmers and Kevin Fontaine. Glenn is a regular commenter on this blog, a professional writer, and a certified Strength and Conditioning Specialist. Dr. Fontaine is an Associate Professor at the Johns Hopkins University’s School of Medicine and Bloomberg School of Public Health.

Biology for Bodybuilders is written in the first person by Doug, which is one of the appealing aspects of the book. This also allows Doug to say that his co-authors disagree with him sometimes, even as he outlines what works for him. Both Glenn and Kevin are described as following Paleolithic dieting approaches. Doug follows a more old school bodybuilding approach to dieting – e.g., he eats grains, and has multiple balanced meals everyday.

This relaxed approach to team writing neutralizes criticism from those who do not agree with Doug, at least to a certain extent. Maybe it was done on purpose; a smart idea. For example, I do not agree with everything Doug says in the book, but neither do Doug’s co-authors, by his own admission. Still, one thing we all have to agree with – from a competitive sports perspective, no one can question success.

At less than 120 pages, the book is certainly not encyclopedic, but it is quite packed with details about human physiology and metabolism for a book of this size. The scientific details are delivered in a direct and simple manner, through what I would describe as very good writing.

Doug has interesting ideas on how to push his limits as a bodybuilder. For example, he likes to train for muscle hypertrophy at around 20-30 lbs above his contest weight. Also, he likes to exercise at high repetition ranges, which many believe is not optimal for muscle growth. He does that even for mass building exercises, such as the deadlift. In this video he deadlifts 405 lbs for 27 repetitions.

Here it is important to point out that whether one is working out in the anaerobic range, which is where muscle hypertrophy tends to be maximized, is defined not by the number of repetitions but by the number of seconds a muscle group is placed under stress. The anaerobic range goes from around 20 to 120 seconds. If one does many repetitions, but does them fast, he or she will be in the anaerobic range. Incidentally, this is the range of strength training at which glycogen depletion is maximized.

I am not a bodybuilder, nor do I plan on becoming one, but I do admire athletes that excel in narrow sports. Also, I strongly believe in the health-promoting effects of moderate glycogen-depleting exercise, which includes strength training and sprints. Perhaps what top athletes like Doug do is not exactly optimal for long-term health, but it certainly beats sedentary behavior hands down. Or maybe top athletes will live long and healthy lives because the genetic makeup that allows them to be successful athletes is also conducive to great health.

In this respect, however, Doug is one of the people who have gotten the closest to convincing me that genes do not influence so much what one can achieve as a bodybuilder. In the book he shows a photo of himself at age 18, when he apparently weighed not much more than 135 lbs. Now, in his early 30s, he weighs 210-225 lbs during the offseason, at a height of 5'9". He has achieved this without taking steroids. Maybe he is a good example of compensatory adaptation, where obstacles lead to success.

If you are interested in natural bodybuilding, and/or the biology behind it, this book is highly recommended!

Strength training plus fasting regularly, and becoming diabetic!? No, it is just compensatory adaptation at work

One common outcome of doing glycogen-depleting exercise (e.g., strength training, sprinting) in combination with intermittent fasting is an increase in growth hormone (GH) levels. See this post for a graph showing the acute effect on GH levels of glycogen-depleting exercise. This effect applies to both men and women, and is generally healthy, leading to improvements in mood and many health markers.

It is a bit like GH therapy, with GH being “administered” to you by your own body. Both glycogen-depleting exercise and intermittent fasting increase GH levels; apparently they have an additive effect when done together.

Still, a complaint that one sees a lot from people who have been doing glycogen-depleting exercise and intermittent fasting for a while is that their fasting blood glucose levels go up. This is particularly true for obese folks (after they lose body fat), as obesity tends to be associated with low GH levels, although it is not restricted to the obese. In fact, many people decide to stop what they were doing because they think that they are becoming insulin resistant and on their way to developing type 2 diabetes. And, surely enough, when they stop, their blood glucose levels go down.

Guess what? If your blood glucose levels are going up quite a bit in response to glycogen-depleting exercise and intermittent fasting, maybe you are one of the lucky folks who are very effective at increasing their GH levels. The blood glucose increase effect is temporary, although it can last months, and is indeed caused by insulin resistance. An HbA1c test should also show an increase in hemoglobin glycation.

Over time, however, you will very likely become more insulin sensitive. What is happening is compensatory adaptation, with different short-term and long-term responses. In the short term, your body is trying to become a more efficient fat-burning machine, and GH is involved in this adaptation. But in the short term, GH leads to insulin resistance, probably via actions on muscle and fat cells. This gradually improves in the long term, possibly through a concomitant increase in liver insulin sensitivity and glycogen storage capacity.

This is somewhat similar to the response to GH therapy.

The figure below is from Johannsson et al. (1997). It shows what happened in terms of glucose metabolism when a group of obese men were administered recombinant GH for 9 months. The participants were aged 48–66, and were given in daily doses the equivalent to what would be needed to bring their GH levels to approximately what they were at age 20. For glucose, 5 mmol is about 90 mg, 5.5 is about 99, and 6 is about 108. GDR is glucose disposal rate; a measure of how quickly glucose is cleared from the blood.

As you can see, insulin sensitivity initially goes down for the GH group, and fasting blood glucose goes up quite a lot. But after 9 months the GH group has better insulin sensitivity. Their GDR is the same as in the placebo group, but with lower circulating insulin. The folks in the GH group also have significantly less body fat, and have better health markers, than those who took the placebo.

There is such a thing as sudden-onset type 2-like diabetes, but it is very rare (see Michael’s blog). Usually type 2 diabetes “telegraphs” its arrival through gradually increasing fasting blood glucose and HbA1c. However, those normally come together with other things, notably a decrease in HDL cholesterol and an increase in fasting triglycerides. Folks who do glycogen-depleting exercise and intermittent fasting tend to see the opposite – an increase in HDL cholesterol and a decrease in triglycerides.

So, if you are doing things that have the potential to increase your GH levels, a standard lipid panel can help you try to figure out whether insulin resistance is benign or not, if it happens.

By the way, GH and cortisol levels are correlated, which is often why some associate responses to glycogen-depleting exercise and intermittent fasting with esoteric nonsense that has no basis in scientific research like “adrenal fatigue”. Cortisol levels are meant to go up and down, but they should not go up and stay up while you are sitting down.

Avoid chronic stress, and keep on doing glycogen-depleting exercise and intermittent fasting; there is overwhelming scientific evidence that these things are good for you.

Do you lose muscle if you lift weights after a 24-hour fast? Probably not if you do that regularly

Compensatory adaptation (CA) is an idea that is useful in the understanding of how the body reacts to inputs like dietary intake of macronutrients and exercise. CA is a complex process, because it involves feedback loops, but it leads to adaptations that are fairly general, applying to a large cross-section of the population.

A joke among software developers is that the computer does exactly what you tell it to do, but not necessarily what you want it to do. Similarly, through CA your body responds exactly to the inputs you give it, but not necessarily in the way you would like it to respond. For example, a moderate caloric deficit may lead to slow body fat loss, while a very high caloric deficit may bring body fat loss to a halt.

Strength training seems to lead to various adaptations, which can be understood through the lens provided by CA. One of them is a dramatic increase in the ability of the body to store glycogen, in both liver and muscle. Glycogen is the main fuel used by muscle during anaerobic exercise. Regular strength training causes, over time, glycogen stores to more than double. And about 2.6 the amount of glycogen is also stored as water.

When one looks bigger and becomes stronger as a result of strength training, that is in no small part due to increases in glycogen and water stored. More glycogen stored in muscle leads to more strength, which is essentially a measure of one’s ability to move a certain amount of weight around. More muscle protein is also associated with more strength.

Thinking in terms of CA, the increase in the body’s ability to store glycogen is to be expected, as long as glycogen stores are depleted and replenished on a regular basis. By doing strength training regularly, you are telling your body that you need a lot of glycogen on a regular basis, and the body responds. But if you do not replenish your glycogen stores on a regular basis, you are also sending your body a conflicting message, which is that dietary sources of the substances used to make glycogen are not readily available. Among the substances that are used to make glycogen, the best seems to be the combination of fructose and glucose that one finds in fruits.

Let us assume a 160-lbs untrained person, John, who stored about 100 g of glycogen in his liver, and about 500 g in his muscle cells, before starting a strength training program. Let us assume, conservatively, that after 6 months of training he increased the size of his liver glycogen tank to 150 g. Muscle glycogen storage was also increased, but that is less relevant for the discussion in this post.

Then John fasted for 24 hours before a strength training session, just to see what would happen. While fasting he went about his business, doing light activities, which led to a caloric expenditure of about 100 calories per hour (equivalent to 2400 per day). About 20 percent of that, or 20 calories per hour, came from a combination of blood glucose and ketones. Contrary to popular belief, ketones can always be found in circulation. If only glucose were used, 5 g of glucose per hour would be needed to supply those 20 calories.

During the fast, John’s glucose needs, driven primarily by his brain’s needs, were met by conversion of liver glycogen to blood glucose. His muscle glycogen was pretty much “locked” during the fast; because he was doing only light activities, which rely primarily on fat as fuel. Muscle glycogen is “unlocked” through anaerobic exercise, of which strength training is an instance.

One of the roles of ketones is to spare liver glycogen, delaying the use of muscle protein to make glucose down the road, so the percentage of ketones in circulation in John’s body increased in a way that was inversely proportional to stored liver glycogen. According to this study, after 72 hours fasting about 25 percent of the body’s glucose needs are met by ketones. (This may be an underestimation.)

If we assume a linear increase in ketone concentration, this leads to a 0.69 percent increase in circulating ketones for every 2-hour period. (This is a simplification, as the increase is very likely nonlinear.) So, when we look at John’s liver glycogen tank, it probably went down in a way similar to that depicted on the figure below. The blue bars show liver glycogen at the end of each 2-hour period. The red bars show the approximate amount of glucose consumed during each 2-hour period. Glucose consumed goes down as liver glycogen decreases, because of the increase in blood ketones.

As you can see, after a 24-hour fast, John had about 35 g of glycogen left, which is enough for a few extra hours of fasting. At the 24-hour mark the body had no need to be using muscle protein to generate glucose. Maybe some of that happened, but probably not much if John was relaxed during the fast. (If he was stressed out, stress hormones would have increased blood glucose release significantly.) From the body’s perspective, muscle is “expensive”, whereas body fat is “cheap”. And body fat, converted to free fatty acids, is what is used to produce ketones during a fast.

Blood ketone concentration does not go up dramatically during a 24-hour fast, but it does after a 48-hour fast, when it becomes about 10 times higher. This major increase occurs primarily to spare muscle, including heart muscle. If the increase is much smaller during a 24-hour fast, one can reasonably assume that the body is not going to be using muscle during the fast. It can still rely on liver glycogen, together with a relatively small amount of ketones.

Then John did his strength training, after the 24-hour fast. When he did that, the muscles he used in the exercise session converted locally stored glycogen into lactate. A flood of lactate was secreted into the bloodstream, which was used by his liver to produce glucose and also to replenish liver glycogen a bit. Again, at this stage there was no need for John’s body to use muscle protein to generate glucose.

Counterintuitive as this may sound, the more different muscles John used, the more lactate was made available. If John did 20 sets of isolated bicep curls, for example, his body would not have released enough lactate to meet its glucose needs or replenish liver glycogen. As a result, stress hormones would go up a lot, and his body would send him some alarm signals. One of those signals is a feeling of “pins and needles”, which is sometimes confused with the symptoms of a heart attack.

John worked out various muscle groups for 30 minutes or so, and he did not even feel fatigued. He felt energetic, in part because his blood glucose went up a lot, peaking at 150 mg/dl, to meet muscle needs. This elevated blood glucose was caused by his liver producing blood glucose based on lactate and releasing it into his blood. Muscle glycogen was depleted as a result of that.

Do you lose any muscle if you lift weights after a 24-hour fast?

I don’t think so, if you deplete your glycogen stores by doing strength training on a regular basis, and also replenish them on a regular basis. In fact, your liver glycogen tank will increase in size, and you may find yourself being able to fast for many hours without feeling hungry.

You will feel hungry after the strength training session following the fast though; probably ravenous.

References

Brooks, G.A., Fahey, T.D., & Baldwin, K.M. (2005). Exercise physiology: Human bioenergetics and its applications. Boston, MA: McGraw-Hill.

Wilmore, J.H., Costill, D.L., & Kenney, W.L. (2007). Physiology of sport and exercise. Champaign, IL: Human Kinetics.