Gluconeogenesis on a Low Carb Diet

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Gluconeogenesis is the process of synthesizing glucose in the body from non-carbohydrate precursors. It is the biosynthesis of new glucose, not derived from the consumption of carbohydrate. Glucose can be produced from lactate, pyruvate, glycerol (fat), and certain amino acids (protein).

Gluconeogenesis occurs in the liver and the kidneys and can be seen as the reverse anabolic process of glycolysis—the breakdown, and extraction of energy from glucose.

The Role of Glucose

Glucose is the major source of energy for the body and the brain. Even at rest, our bodies need energy to function. For example, the brain alone uses as much as 100 grams of glucose a day. When we are active, our bodies (particularly the working muscles) need even more. Glucose is the body's preferred source of fuel because it can be quickly used for energy.

Energy from glucose can be quickly created through a complex 10-step process called glycolysis. During glycolysis, glucose is split into smaller molecules (called pyruvate) for use as energy throughout the body. Gluconeogenesis ensures that in the absence of glucose from glycolysis that critical limits of glucose are maintained when carbohydrate is absent.

Your body's preferred energy source is glucose. Your body may use either the process of glycolysis or the process of gluconeogenesis to provide your body and your brain with the energy it needs to function.

Standard vs. Low Carb Meal Plans

If you are consuming a typical American diet, your body gets plenty of glucose from the food you consume. For example, starches (plentiful in grains including flour, potatoes, bread products, baked goods) are essentially long chains of glucose.

In addition, naturally-occurring sugars (in foods like fruit) and added sugars (found in many processed foods) are plentiful in the diets of most people. These foods boost glucose levels.

However, starchy and sugary foods are limited on a low carb diet. If carbohydrate is not being consumed, the body needs to make glucose from other sources. Gluconeogenesis is a workaround for your body's metabolism to get and maintain the energy it needs to conduct normal bodily functions.

People on a low-carb diet have less glucose available for energy because less carbohydrate is consumed. Gluconeogenesis is the body's way of providing energy to the body when glucose is not supplied through the diet.

How Gluconeogenesis Works

The process of gluconeogenesis takes place primarily in the liver, where glucose is made from amino acids (protein), glycerol (the backbone of triglycerides, the primary fat storage molecule), and glucose metabolism intermediaries like lactate and pyruvate.

While gluconeogenesis may occur when you are on a low-carb diet, it can also happen during periods of fasting (such as when you are sleeping), starvation, or during intense exercise. It may also happen when you consume excess protein. The complex process is a series of chemical conversions.

A very simple explanation might involve three steps.

  1. The conversion of pyruvate to phosphoenolpyruvic acid (PEP). PEP is an ester or a chemical compound derived from acid.
  2. Glycolysis in reverse. The conversion of PEP to another compound called fructose-6-phosphate, a derivative of fructose.
  3. The conversion of fructose-6-phosphate to glucose.

Gluconeogenesis vs. Ketosis

Those on a very low carb diet are often familiar with a metabolic state called ketosis which is another way of providing fuel to the body if not enough glucose is present. However, ketosis is a metabolic state that differs from the process known as gluconeogenesis.

During ketosis, the body essentially learns to use fat, rather than glucose, as fuel. When you are in this state, your energy supply comes from ketone bodies circulating in the blood. Ketone bodies are produced through a process called ketogenesis which happens in the mitochondria of liver cells.

Ketogenesis and gluconeogenesis are similar in that they are both chemical processes that provide energy to the body when not enough carbohydrate is present in the diet. However, ketogenesis differs in that it produces ketones to be used as fuel, rather than glucose.

Ketogenic diets are low-carb, high-fat eating plans designed to put your body into a state of ketosis. These diets (also known as "keto" diets) are sometimes prescribed for people with certain neurological disorders.

For example, there is some scientific evidence to show that ketogenic diets may help people with epilepsy and other conditions including Parkinson's and Alzheimer's disease. Some athletes and people looking to lose weight also follow ketogenic diets. However, the eating program can be very difficult to maintain.

Additionally, if you consume a lot of protein on your keto eating plan, gluconeogenesis may prevent ketogenesis from occurring. That is, your body will use protein to create glucose, instead of converting fat to fuel. In fact, during the first few days of a ketogenic diet, your body is likely to use gluconeogenesis to produce energy.

To know for sure if and when your body has shifted from gluconeogenesis to a state of ketosis, there are various methods to test for the presence of ketone bodies.

4 Sources
Verywell Fit uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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  2. Schugar RC, Crawford PA. Low-carbohydrate ketogenic diets, glucose homeostasis, and nonalcoholic fatty liver disease. Curr Opin Clin Nutr Metab Care. 2012;15(4):374–380. doi:10.1097/MCO.0b013e3283547157

  3. Hartman AL, Rho JM. Beyond epilepsy: Ketogenic diet use in other disease states. In Dietary Treatment of Epilepsy: Practical Implementation of Ketogenic Therapy. New York: John Wiley and Sons 2013, pp. 225-231.

  4. Paoli A, Rubini A, Volek JS, Grimaldi KA. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets [published correction appears in Eur J Clin Nutr. 2014 May;68(5):641]. Eur J Clin Nutr. 2013;67(8):789–796. doi:10.1038/ejcn.2013.116

Additional Reading

By Laura Dolson
Laura Dolson is a health and food writer who develops low-carb and gluten-free recipes for home cooks.