Protein Over-consumption in Ketogenic Diets Explained

Protein over-consumption is one of the main issues discussed at the Ketogains Group everyday. People are always reading, hearing and/or misunderstanding that eating protein will cause gluconeogenesis and kick you out of ketosis. Tyler Cartwright splendidly refuted the claim that protein supply activates GNG in this post, I recommend you check it out.



So, if protein consumption doesn’t massively increase gluconeogenesis, then two questions remain:

  • Why doesn’t ketogains recommend you eat tons of protein?
  • Why does protein over-consumption lower ketones?

Ketogains Protein Recommendation


Of these questions, the first is easier to answer. The reason we don’t advocate the consumption of tons of protein is because beyond a certain point -arguably somewhere between .8g and 1.2g per pound of lean mass(lbm)- there’s just no benefit. Protein also carries a couple of minor inconveniences: It tends to be expensive and it can cause indigestion. If there were no other reason not to over-consume protein, this would simply be enough.

There is also a minor debate over whether or not protein over-consumption prolongs the adaptation phase (irrelevant if you are already adapted). Also some people argue that it may be sub-optimal for performance, but these are secondary to the previous points: It’s unnecessary to eat more, so there’s no reason to recommend over-consumption.

Protein and lower ketones


The second gets a bit more complicated, and touches on something that Tyler just hinted at in his article. My soapbox is diabetes, and to a lesser extent, obesity… Diabetes has a lot to tell us about blood sugar control and precisely how and why certain food items impact blood glucose.

pancreatic beta cells and ketosisIn type one diabetes, the population of beta cells in the pancreas mostly dies, leaving the alpha cells of the pancreas free to produce tons of glucagon. You see, the alpha and beta cells directly counteract each other in the pancreas, so that when the beta cells produce insulin, it suppresses the action of the alpha cells, and vice versa. This creates a beautiful symphony of blood glucose and ketone body control in the blood of a normal individual, but in a T1 diabetic tons of terrible things happen, and the alpha cells of the pancreas overproduce glucagon with nothing to suppress their action.

In type one diabetes, this leads to the out-of-control over-stimulation of the liver to produce blood glucose through gluconeogenesis and ketone bodies through beta oxidation of fatty acids. But the plot is thickened by the simple fact that there are glucagon-producing cells that are not in the pancreas as well. In fact, there are glucagon-producing cells in the stomach, and they respond to the presence of protein in the chyme (the goo that your stomach produces from the food you eat… and if you want to get very specific, they respond to various amino acids, as well as, apparently, physically solid items in the stomach). These cells do not react directly to levels of blood glucose (whereas the pancreatic alpha cells tend to be suppressed a bit by high glucose levels. These cells do, however, react somewhat differently to protein meals depending on blood glucose levels. It gets very complicated, and the take-home message is to understand that the digestive system is enormously complex and highly regulated.

In a type one diabetic, these cells produce glucagon after a high protein meal. Because there is no population of beta cells to suppress gluconeogenesis, insulin never rises due to this protein meal, and diabetics must be mindful of the blood glucose raising effect of protein consumption.

But in a normal individual, this rise in glucagon is followed almost immediately by a rise in insulin. This is, at first thought, counter intuitive: glucagon suppresses insulin, and insulin suppresses glucagon, after all. But the critical question to be answered here is why? Insulin and glucagon suppress each other because as they leave the pancreas, they impact the populations of alpha and beta cells. But in the circulation, they don’t have this effect. In other words, as glucagon secreted from the stomach due to a protein meal enters the bloodstream, the rise in blood glucose signals the pancreatic beta cells to secrete insulin, and this in turn signals the pancreatic alpha cells to therefore stop producing glucagon. Once the stomach cells are done producing glucagon, insulin is already elevated and GNG effectively stops until the meal is passed and a non-fed state returns (technically, glucagon tends to stay slightly elevated for slightly longer than insulin).

I just want to highlight once again that “highly regulated and enormously complex” aspect of the digestive system: the concentration of these peptide hormones, as well as the timing of their releases, and their varied sources are all critical aspects of their control over your body’s fuel supply.

What this does for GNG is causes a temporarily elevated rate followed by a temporarily suppressed rate. The net impact, according to the research, is essentially nil. But what it does do that tends to make keto-dieters go nuts is temporarily suppress the production of ketone bodies. It does this because elevated insulin has that effect, in addition to effectively stopping GNG. This is probably not an issue, except possibly during the ketoadaptation phase, when profoundly elevated ketone bodies are probably required for various glucose-dependent tissues to remain as happy as usual.

To recap: this long and drawn-out story of peptide hormones is the reason a high protein meal “suppresses” ketone bodies: a protein meal causes a temporary rise in glucagon and a temporary rise in insulin. One of insulin’s actions is to suppress the beta oxidation of fatty acids. The effect here then is to temporarily slow the production of ketone bodies, which can reduce their presence in your blood somewhat. It’s probably not important for anything related to weight loss, except that maybe during the adaptation phase it could impact feelings of yuckiness. For performance, is possible that huge protein meals are a bad idea, but it’s also possible that they aren’t.

protein over-consumption increases glucagon production. Glugacon Molecule shown
Glucagon Molecule

And now we are entering the realm of speculation:

Extra Amino acids fate


If a high protein meal raises both insulin and glucagon, but doesn’t cause a significant net change in GNG, what happens to the extra amino acids?

This is a very good question, and one that I haven’t seen answered effectively in the literature (not that I’ve looked very hard). But there are logical consequences here that lead us to conclusions about what happens. Unless you eat enormous quantities of protein, you excrete the extra nitrogen. The extra protein doesn’t lead to hugely elevated GNG, so it’s very likely that the excesses are simply oxidized for energy in place of the fatty acids, considering that there isn’t extra glucose around, and that the liver isn’t processing quite as much fat as usual. There are a few biological bases for this that seem compelling (don’t trust that, of course). The brain can use only a limited set of fuels, and some of those fuels are amino acids; if glucose is not elevated, and ketone bodies are suppressed, it is unlikely that the brain does not have access to other fuels, else death would be likely, and the entire process would seem to be very risky for a species that likely had to go for certain periods of time in which neither fat nor carbohydrates were widely available (like winter).

Now, this is also a reason why performance might not be negatively impacted by protein over-consumption. If the brain can use amino acids for fuel, then there’s no reason why the muscles wouldn’t be able to continue to run on their usual fuels while the brain relies on this new source. This idea is supported by the fact that there are plenty of individuals on “ketogenic diets” that eat much more protein than is required to achieve the standard Phinney and Volek definition of nutritional ketosis, and are able to perform at a high level in various athletics.

I’d like to conclude by wrapping up a few of the key ideas here.

Number one is that the digestive system is incredibly complex; diabetes is a good tool for telling us how it works, but there are pitfalls associated with surface-level analyses of hormonal shifts and such.

Number two is, of course, that we need to pay very close attention to what diabetes research has to tell us. Without it, we probably wouldn’t even question whether or not there are glucagon-producing cells in places other than the pancreas.

Number three is that you really don’t need to be afraid of protein over-consumption. Eat a reasonable amount, which is enough to maintain/promote the growth of lean mass but not so much that you get digestive problems; for most of us, that means somewhere between about .8g and 1.2g per pound of lean mass. Eating more may not be much of a negative, but it also does not seem to help much, if at all