Gluconeogenesis during endurance exercise in cyclists habituated to a long-term low carbohydrate high fat diet


Endogenous glucose production (EGP) occurs via hepatic glycogenolysis (GLY) and gluconeogenesis (GNG) and plays an important role in maintaining euglycemia. Rates of GLY and GNG increase during exercise in athletes following a mixed macronutrient diet; however these processes have not been investigated in athletes following a low carbohydrate high fat (LCHF) diet. Therefore, we studied 7 well-trained male cyclists that were habituated to either a LCHF (7% carbohydrate, 72% fat, 21% protein) or mixed diet (51% carbohydrate, 33% fat, 16% protein) for longer than 8 months. After an overnight fast, participants performed a 2-hour laboratory ride at 72% of maximal oxygen consumption. Glucose kinetics were measured at rest and during the final 30 min of exercise by infusion of [6,6-2H2]-glucose and the ingestion of 2H2O tracers. Rates of EGP and GLY both at rest and during exercise were significantly lower in the LCHF group than the mixed diet group (Exercise EGP: LCHF, 6.0 ± 0.9; Mixed, 7.8 ± 1.1 mg kg−1 min−1, P < 0.01. Exercise GLY: LCHF, 3.2 ± 0.7; Mixed, 5.3 ± 0.9 mg kg−1 min−1, P < 0.01). Conversely, no difference was detected in rates of GNG between groups at rest or during exercise (Exercise: LCHF, 2.8 ± 0.4; Mixed, 2.5 ± 0.3 mg kg−1 min−1, P = 0.15). We conclude that athletes on a LCHF diet do not compensate for reduced glucose availability via higher rates of glucose synthesis compared to athletes on a mixed diet. Instead, GNG remains relatively stable while glucose oxidation and GLY are influenced by dietary factors.

Hot off the press is a new study by Webster and Noakes is published in the Journal of physiology.

The Key Points:

  • Blood glucose is an important fuel for endurance exercise. It can be derived from ingested

carbohydrate, from stored liver glycogen and from newly synthesized glucose


  • Athletes habitually following a low carbohydrate high fat (LCHF) diet

would have higher rates of gluconeogenesis during exercise compared to those that follow a

mixed macronutrient diet

  • The study used stable isotope tracers to study glucose production kinetics during a 2-hour ride in

cyclists habituated to either a LCHF or mixed macronutrient diet.

The LCHF cyclists had lower rates of total glucose production and hepatic glycogenolysis but

similar rates of gluconeogenesis to those on the mixed diet.

  • Therefore, the LCHF cyclists did not compensate for reduced dietary carbohydrate

availability by increasing glucose synthesis during exercise but rather adapted by altering

whole body substrate utilization.


I am writing a summary of this new study on low carbohydrate athletes in regards to new glucose production also known as gluconeogenesis. As the popularity of fat adapted athletes increase, it is important to know what is really going on metabolically in the muscle and liver and other organs.

Just a little note before I get into the meat of the study. This is a study where you need to read the whole paper and be able to tell the significance of statistics. Reading the abstract alone doesn’t really do it justice.

This is the first study about the gluconeogenesis and fat adapted athletes compared to a traditional diet athlete. The research group studied seven trained cyclists who were habituated to either a low carbohydrate high fat or mixed diet. This was definitely a laboratory study in that they all performed an overnight fast and then rode the trainer with a power meter at 55% of their peak power output or 72% of their maximal oxygen consumption for two hours. This was a neat study because they used a radioactive carbon tracer. Once the carbon tracer is injected into the intravenous system, it is taken up by the body and through special measurements we are able to see the rate of new glucose production from organs like the muscle liver and kidney.

It should be noted that before the exercise, each participant was given an infusion of radioactive glucose that amounted to about 600 mg. This is certainly not much in the scheme of glucose intake.

Summary of the findings after two hours of exercise at 55% peak power:

Glucose decreased as expected but it was the same in both groups.

Lactate increased as expected but throughout the exercise it was basically the same in both groups. The lower carb group showed a small increase in lactate per the study this was not significant.

Insulin decreased as expected during exercise, but no difference was found between either group throughout the study.

Free fatty acids. FFA’s increased throughout the study and this was the same in both groups.

Glycerol was measured in order to estimate the amount of glucose that was derived from fat oxidation. There were some small differences noted in the middle of the study but it mentions that overall there were no real differences.

Beta Hydroxy Butyrate or BHB increased significantly in the fat adapted group as expected. And did not increase in the mixed diet group.

Gluconeogenesis was essentially the same for both groups at rest and during exercise. This is perhaps the big finding of the study. Everyone thought that the fat adapted athletes would ramp up their production of glucose via the liver. But this simply wasn’t the case. More on this in a bit.

Muscle glycogen. Was predictably increased in the next diet group as they consumed more carbohydrates. However, after two hours of exercise there was no difference in the amount of muscle glycogen in either group. This parallels the FASTER study that just came out by Drs. Phinney & Volek. It was also found that the fat adapted group used much less glycogen.

The fact that gluconeogenesis was the same in both groups suggested that other factors must be in play. I was surprised to see that nobody mentioned anything about kidneys. The kidneys are a significant source of gluconeogenesis.

The study also says suggests that hepatic blood flow is playing a big part of the liver’s ability to increase glucose production. At higher intensities it is well-known that hepatic blood flow decreases in this is thought to affect gluconeogenesis and other metabolic processes.

This study also suggests that the notion that lactate is converted to glucose via gluconeogenesis probably only occurs at lower exercise intensities and that many other substrates must be contributing to glucose formation besides lactate.

It should also be known that using radioactive markers to estimate metabolic processes can be quite finicky. For example, there are two known ways to measure gluconeogenesis using radioactive isotopes. In the results these two methods give can differ as much as 50% from each other. So one must take into the account that the sensitivity of measuring these metabolic reactions using radioactive isotopes is quite tenuous. A good analogy may be a doctor looking at a metabolic study of a brain MRI, at any given time is only just one picture of an entire film that moves very fast.

When fat adaptation is practiced, fat oxidation doubles and even more. And as we know from the Dr. Sieler study, fat oxidation plays a very important role in very high intensities.

It should be noted that the subjects are not elite athletes. A peak power output of 5 W per kilo for a 75 g male is not very much and is probably that of a lower-level amateur cyclist. So it is hard to extrapolate the data from this study and apply it to Tour de France runners for world-class runners.

What did this study show? For sure what happens to gluconeogenesis when two different diet strategies are employed.

What this study did not show. What happens to gluconeogenesis or new glucose production at very high intensities in very well trained athletes.

The authors make some interesting assertions that fat adapted athletes probably increases gluconeogenesis from fat oxidation and glycerol production. And that someone on a mixed diet increases gluconeogenesis from lactate.

Muscle glycogen is used a lot in mixed diet athletes compared to that of fat adapted athletes. Or in other words glycogen is spared in fat adapted athletes and there is less of it to start with.

It may be possible that higher level athletes are utilizing gluconeogenesis more than regular athletes. This same scenario was found by Dr. Seiler in his study showing increased fat utilization in elite athletes versus less trained athletes.

Finally, “it is yet another confirmation that the body burns what you feed it.” –  Barry Murray

Congratulations to the research team for completing such a detailed study. These are not easy studies to complete and the cost can be very expensive. The hoops that a lab must jump through to use radioactive molecules is pretty extensive. And it is likely that no company put in a lot of money to fund this basic research.