Thursday, July 8, 2010

Our body’s priority is preventing hypoglycemia, not hyperglycemia

An adult human has about 5 l of blood in circulation. Considering a blood glucose concentration of 100 mg/dl, this translates into a total amount of glucose in the blood of about 5 g (5 l x 0.1 g / 0.1 l). That is approximately a teaspoon of glucose. If a person’s blood glucose goes down to about half of that, the person will enter a state of hypoglycemia. Severe and/or prolonged hypoglycemia can cause seizures, comma, and death.

In other words, the disappearance of about 2.5 g of glucose from the blood will lead to hypoglycemia. Since 2.5 g of glucose yields about 10 calories, it should be easy to see that it does not take much to make someone hypoglycemic in the absence of compensatory mechanisms. An adult will consume on average 6 to 9 times as many calories just sitting quietly, and a proportion of those calories will come from glucose.

While hypoglycemia has severe negative health effects in the short term, including the most severe of all - death, hyperglycemia has primarily long-term negative health effects. Given this, it is no surprise that our body’s priority is to prevent hypoglycemia, not hyperglycemia.

The figure below, from the outstanding book by Brooks and colleagues (2005), shows two graphs. The graph at the top shows the variation of arterial glucose in response to exercise. The graph at the bottom shows the variation of whole-body and muscle glucose uptake, plus hepatic glucose production, in response to exercise. The full reference to the Brooks and colleagues book is at the end of this post.

Note how blood glucose increases dramatically as the intensity of the exercise session increases, which means that muscle tissue consumption of glucose is also increasing. This is particularly noticeable as arm exercise is added to leg exercise, bringing the exercise intensity to 82 percent of maximal capacity. This blood glucose elevation is similar to the elevation one would normally see in response to all-out sprinting and weight training within the anaerobic range (with enough weight to allow only 6 to 12 repetitions, or a time under tension of about 30 to 70 seconds).

The dashed line at the bottom graph represents whole-body glucose uptake, including what would be necessary for the body to function in the absence of exercise. This is why whole-body glucose uptake is higher than muscle glucose uptake induced by exercise; the latter was measured through a glucose tracing method. The top of the error bars above the points on the dashed line represent hepatic glucose production, which is always ahead of whole-body glucose uptake. This is our body doing what it needs to do to prevent hypoglycemia.

One point that is important to make here is that at the beginning of an anaerobic exercise session muscle uses up primarily local glycogen stores (not liver glycogen stores), and can completely deplete them in a very localized fashion. Muscle glycogen stores add up to 500 g, but intense exercise depletes glycogen stores locally, only within the muscles being used. Still, muscle glycogen use generates lactate as a byproduct, which is then used by the liver to produce glucose (gluconeogenesis) to prevent hypoglycemia. The liver also makes some glycogen (glycogenesis) during this time. This means that it is not only pre-exercise liver glycogen that is being used to maintain blood glucose levels above whole-body glucose uptake. This makes sense, since the liver stores only about 100 g of glycogen.

The need to prevent hypoglycemia at all costs is the main reason why there are several hormones that increase blood glucose, while apparently there is only one that decreases blood glucose. Examples of hormones that increase blood glucose are cortisol, adrenaline, noradrenaline, growth hormone, and, notably, glucagon. The only hormone that decreases blood glucose levels in a significant way is insulin. These hormones do not increase or decrease blood glucose directly; they signal to various tissues to either secrete or absorb glucose.

Evolution typically prioritizes processes that have a higher impact on reproductive success, and one must be alive to successfully reproduce. Hypoglycemia causes death. Often those processes that have a significant effect on reproductive success rely on redundant mechanisms. So our evolved mechanisms to deal with hypoglycemia are redundant. Evolution is not an engineer; it is a tinkerer!

What about hyperglycemia – doesn’t it cause death? Well, not in the short term, so related selection pressures were fairly small compared to those associated with hypoglycemia. Besides, there were no foods rich in refined carbohydrates and sugars in the Paleolithic - e.g., white bread, bagels, doughnuts, pasta, cereals, fruit juices, regular sodas, table sugar. Those are the foods that contribute the most to hyperglycemia.


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


Gretchen said...

"one must be alive to successfully reproduce"

Well, not anymore, with frozen sperm and frozen embryos.

Ned Kock said...

Hi Gretchen.

Of course, but I was referring to our ancestors living in the Paleolithic.

Kindke said...

Ned the title of this post is very thought provoking.

Gluconeogenesis is increased during ketogenic diets, theres alot of anecdotal evidence on body building forums that it is much much harder to build muscle following a low-carb diet. I guess becuase the body is more concerned with converting the dietery protein to glycogen than to muscle.

Also, wouldnt the logic here imply that it is beneficial to keep glycogen stores topped off during exercise and/or to immediately post exercise ingest carbs to quickly refil your glycogen, the ultimate aim being to down-regulate then gluconeogenic pathways so that when you finally ingest protein after exercise, it goes to muscle and not your liver glycogen?

At the other end of the spectrum, theres alot of people on low-carb forums with anecdotal evidence that they had more success loosing weight following a 80% fat 20% protein diet, compared to say 35% protein 65% fat.

during protein and carb starvation im wondering if the body will deliberately burn trigs in excess of its needs just to simply get the glycerol for gluconeogenesis. Obviously ketones drastically reduce the bodies need for glucose, and im aware the body can catabolise muscle for gluconeogenesis, but if your exercising this should also be low.

Btw Ned is it still worth getting Physiology of sport and exercise book, despite the always advancing research in the field and the ease of availability of such information on the internet.

Ned Kock said...

Hi Kindke.

I think that book has very long-lived information and knowledge in it. It is certainly worth having, in my opinion.

Yes, losing fat is easier on low-carb, and it is hard to put on muscle on low-carb. Low-carbing combining with resistance exercise seems a very effective way of losing fat and keeping the muscle one has, if one is obese.

But many people reach a plateau of fat loss with pure low carb when they get to 10-15 percent body fat. So one can get lean, but still ends up with stubborn subcutaneous fat, often around the waist. As far as overall health is concerned, this is not a very bad state to be in.

Gluconeogenesis is not such a bad thing, and can be fueled by dietary protein, not necessarily carbs. Also, I don't think it is a big deal to undergo some muscle catabolism, if the anabolic stage after exercise is highly effective. In the end, the net result is positive.

Replenishing glycogen stores after exercise makes sense, and one of the best ways is to consume carb sources with both fructose and glucose. You also need protein post-exercise.

The thing to bear in mind is that liver glycogen gets replenished in hours, whereas muscle glycogen takes days. So eating one fruit and some starch post-exercise should be a good thing, but not much more than that.

Ned Kock said...


In the post above, when I say "carb sources with both fructose and glucose", I mean "natural" carb sources.

Foods rich in refined carbs and sugars eventually have their toll on the body.

russ1abear said...

I went for a run this morning(fasted state and I'm not diabetic)and afterwards checked my blood glucose and it was at 120! I'm low carb (sub 70 grams per day) and was having a panic attack until I read this. It seems so bizarre that there isn't more literature out there on this.