Carbohydrate Independence: How Your Body Sustains Stable Glucose Levels

Even without any dietary carbohydrate intake, the body continuously maintains blood glucose levels within a strictly regulated range. This ensures a stable supply of glucose to organs and cells that are dependent on glucose for energy, like red blood cells and certain specialized cells in the brain (astrocytes and oligodendrocytes). This metabolic flexibility allows humans to adapt to various dietary patterns and environmental conditions without experiencing drastic fluctuations in blood glucose levels.

The metabolism of glucose encompasses a series of intricate processes. It includes:

• Glycogenesis and glycogenolysis: the processes where excess glucose is converted into glycogen for storage in the liver and muscle cells, and by which glycogen can be broken down into glucose to provide energy for the body.
• Gluconeogenesis: the metabolic pathway that allows the body to synthesize glucose from non-carbohydrate sources such as glycerol, amino acids, and lactate.
• Glucose absorption by tissues and glucose oxidation within cells.

The liver, functioning as the metabolic centerpiece of the body, is pivotal in overseeing glucose equilibrium. It keeps blood glucose stable by

• utilizing glycogenolysis to break down glycogen stores and release glucose for the body and by
• producing new glucose through the pathway of gluconeogenesis.

Let’s have a look at the three substances that can be utilized for gluconeogenesis:

1. Glycerol: The breakdown of triglycerides in fat cells sets glycerol free into the bloodstream. The pathway involving glycerol is relatively straightforward, requiring fewer steps and less energy compared to other substrates.

2. Amino acids: They can come from dietary proteins or the breakdown of proteins in various tissues, including skeletal muscles, and the turnover of cellular proteins within the body.

3. Lactate: A byproduct from the carbohydrate breakdown process.

In individuals who have fasted overnight, around half of the glucose circulating in the bloodstream is derived from the breakdown of glycogen, while the formation of glucose in the process of gluconeogenesis contributes the other half.

While the majority of gluconeogenesis occurs in the liver, the kidneys also play a noteworthy role, accounting for around 10% and, according to some studies, up to 40% of glucose production.

And while liver cells and kidney cortical cells are the largest glucose producers, they are not the only ones! Interestingly, intestinal cells, brain astrocytes, and muscle cells can produce glucose as well.

Though only contributing a small amount to the overall glucose production, intestinal gluconeogenesis still holds importance as it helps modulate the activity of gluconeogenesis occurring in the liver, a regulation facilitated through a complex neurohormonal feedback system involving the portal vein and central nervous system.

Moreover, gluconeogenesis within brain astrocytes is predominantly directed towards nourishing adjacent cells rather than contributing to the systemic glucose pool.

Likewise, the skeletal muscles mainly utilize gluconeogenesis post-exercise to restore their own intracellular glycogen reserves rather than supplying glucose for broader bodily functions.

This last point is quite interesting in the context of the findings from the 2016 ?FASTER? study by Volek et al. https://dx.doi.org/10.1016/j.metabol.2015.10.028

Volek, J. S., Freidenreich, D. J., Saenz, C., Kunces, L. J., Creighton, B. C., Bartley, J. M., Davitt, P. M., Munoz, C. X., Anderson, J. M., Maresh, C. M., Lee, E. C., Schuenke, M. D., Aerni, G., Kraemer, W. J., & Phinney, S. D. (2016). Metabolic characteristics of keto-adapted ultra-endurance runners. Metabolism Clinical and Experimental, 65, 100-110.

In this study, twenty elite ultra-marathon runners and triathletes over the Ironman distance performed a maximal effort program with different power levels. One group ate a traditional high-carbohydrate diet, with 60% of calories from carbohydrates. The other group ate a low-carb diet for an average of 20 months, with 10% of calories coming from carbohydrates.

Compared with highly trained ultra-endurance athletes on high-carbohydrate diets, long-term keto-adaptation resulted not only in exceptionally high-fat oxidation rates. At the same time, glycogen concentrations in skeletal muscle remained normal.

The low-carb athletes showed:

• no differences in muscle glycogen concentration before exercise, glycogen utilization during exercise, and glycogen synthesis rate during the recovery phase;
• twice as high peak rates of fat oxidation during exercise;
• a greater ability to oxidize fat at higher exercise intensities;
• a twofold higher rate of fat oxidation during sustained submaximal running.

Displaying an extraordinary resilience even during high-level athletic performance, glucose metabolism hints at deeper layers of complexity and potential that forthcoming research is bound to explore.

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