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What is Gluconeogenesis…and it’s role with a low carb diet

For the last five years, we have been recommending a low carb diet as a better way to lose excess body fat and maintain good health. You may have heard of some of the versions: Atkins, Paleo, low carb/high fat, low carb/high protein (and I am sure there are others). There are many nuances between them, but they all stem from the basic understanding that high blood glucose and high insulin levels drive fat storage, thus it is wise to keep these as low as possible. All of these versions agree that carbohydrate consumption drives high insulin levels. How they differ is in how much carbohydrate can be taken in without gaining fat, and how much protein plays a role in driving blood glucose and insulin levels. The body can make glucose without carbohydrate consumption, and the process is called gluconeogenesis. And yes, gluconeogenesis can be triggered by the breakdown of protein. So let’s take a closer look at what exactly gluconeogenesis is, how it works, and see if, in fact, eating too much protein can make it harder for you to lose fat on a low carb diet.


Gluconeogenesis is the pathway that creates glucose out of molecules that are not glucose. It does this because there are some tissues that run on glucose only:

  • Red blood cells
  • Kidney Medulla
  • Testicles

The brain also needs some glucose to function as well, but not as much as previously thought. It can run on ketones, just like most of the tissues of the body, but it does need some glucose.

As a matter of fact, too little glucose in the bloodstream can kill you. We are all familiar with the fact that too much glucose can be toxic, leading to metabolic syndrome and full blow diabetes if not treated properly…but we do need some. Blood glucose is tightly regulated because of this.

The main point is this: We need some glucose or we will die, so the body has a pathway that can create glucose indigenously if one is in short supply, such as being on a very low carbohydrate diet, fasting for a period of time, or, heaven forbid, if one is starving.

The substrates that the process of gluconeogenesis uses to create glucose are:

  • Amino acids (Protein). There are two amino acids that the body can use to break down to glucose: alanine and glutamine. The fact that the body uses protein for gluconeogenesis raises an interesting point for all of us who use a low carb/ketogenic diet for fat loss. Some experts believe that too much protein intake, even with a low carb intake, may lead to increased insulin levels causing the body to store fat more readily. Other experts do not think it plays a significant role. More on this later.
  • Lactate. Lactate is the main substrate the body uses to convert to glucose. When you do an intense workout, the cells turn pyruvate into lactate which accumulates in your muscles. It is the lactic acid and other unknown metabolites that build up from intense muscular contractions that causes the burning sensation, making it difficult to continue for more than two or three minutes. Once the hard working muscles get a chance to relax, the lactate that was built up is released back into the bloodstream and delivered to the liver. The liver then, through gluconeogenesis, turns lactate back into glucose to be used for fuel once again. The name of this metabolic pathway is the Cori cycle. I want to take a moment to expand on the importance of the Cori cycle. One of the goals of the Hystrength (sm) training program is to train above the lactate threshold during the exercise session as long as one can stand it. Doing so will increase the enzymes and transporter system of the cori cycle, thus improving overall physical capacity. It is one aspect that differentiates the Hystrength (sm) training program from a more conventional strength training program.
  • Glycerol. Glycerol is the third most preferential substrate to be used for gluconeogenesis. Glycerol comes from the breakdown of triglycerides (fat).

We can go into great detail about the process of gluconeogenesis, but that is not necessary for what we need to know about it. Just know that gluconeogenesis is a pathway in which non-carbohydrate carbon substrates are used to create glucose when the body is running low on glucose. Moreover, this is a critical pathway to have, for humans could not have survived periods of famine without it. It has been called a “demand driven process” for this reason.

The big question in the keto community is: Can gluconeogenesis kick an individual out of ketosis if his protein consumption is too high? For example, the original Atkins diet stressed keeping carbohydrates low, but protein consumption can be whatever the dieter wants to consume. Dr. Atkins believed that excess protein consumption was not a problem. On the other hand, many ketogenic practitioners would say that the reason someone may hit a plateau from going low carb but high protein (say, an Atkins dieter that cannot lose any more fat after a few weeks), was due to the dieter eating too much protein, via the body breaking down the excess protein into amino acids and converted to glucose, thus triggering an insulin response to deal with the extra glucose which would promote fat storage.

This is a sound theory, and I used to believe it until I dug a little deeper. It turns out that the science does not support it. Two articles and one research paper that I came across come to the same conclusions, and that is excess protein intake does not raise blood glucose levels in the same manner as carbohydrates. Specifically, there is barely a noticeable increase at all (see here, here, and here for more on the subject), therefore the body does not produce very much insulin to deal with it. It does lead one to wonder where the excess protein goes. At present, nobody knows for sure but the theory is that the excess protein is used to replenish glycogen stores, and/or it may be released incrementally in an extended period of time.

The bottom line is that excess protein intake does not seem to matter on a ketogenic diet. It will not kick you out of ketosis in and of itself. Mind you, your insulin will always go up anytime you eat anything, but both processed foods and carbohydrate rich foods will drive insulin levels higher than both fat or protein.

Having said that, it does not give one the green light to eat as much protein as he wants. Protein intake activates what is known as the mTor pathway, which many anti-aging experts believe leads to accelerated aging and cancer. This is a fascinating field of study, and I will write a future blog about the mTor pathway…and what I believe to be a good strategy for both slowing down the aging process and maintaining a “buff” body.

In any event, we do not want excessive protein intake, but we do want enough protein intake. So what would that look like?

According to the data from the U.S Department of Agriculture, our protein intake from 1909 to 2004 was very consistent. Americans have been averaging roughly 16% of their caloric intake from protein, and according to this report, that amount of protein is about double of what the body needs for repair and growth. We need approximately 50 grams of protein, give or take, for these functions. The rest (about 50 grams) is broken down into glucose. Of course, if you lift weights or exercise frequently, you may need more, but still not much more. You can safely add about 30 to 40 grams a day to that.

What this means is that we do not have to go out of our way to get enough protein in our diet for good health. So all of those protein shakes that wanna be bodybuilders and power-lifters take after a workout (some lifters would drink protein shakes three times a day!) really are unnecessary. It also means that we should not make protein the main macro nutrient when we attempt to cut our carbohydrate intake. It does mean that we should increase fat intake while lowering carbohydrate intake…and maybe lower overall protein intake a little bit.

In practical terms, it would look like this:

  • Use fattier cuts of beef or pork.
  • Add more butter, ghee, or coconut oil for cooking.
  • If you do use leaner cuts of beef or chicken, do add more good fats to your overall meal. Maybe more olive oil on your salad, some high fat cheese, and eat a smaller portion of the beef or chicken.

And finally, if you do hit a plateau from your fat loss on a ketogenic diet, I would recommend that you add more intermittent fasting to your routine. Remember, any time you eat, you do kick up the insulin response. The best way to keep burning fat is to be in a fasted state (That would keep insulin levels down, for blood glucose would have to be down). Even if you did eat too much protein or carbohydrate at your last meal, staying in a fasted state as long as you can will ensure that you will get back into fat burning mode anyway. Maybe skip breakfast the next day, or even be open to doing a 24 hour fast from time to time. That will keep your body is going the right direction.


Gregg Hoffman

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