Will you die if you don't consume carbohydrates?

The detective discovered an outrageous post on X today.
"You will die if you don't consume carbohydrates."
What a complete lack of basic knowledge!
Moreover, the person who wrote this is a diabetes specialist.
I was so stunned I was speechless, so I decided not to say anything and wrote an article instead.

Is dietary glucose essential?

First, let's take a look at the statement.

The claims of this diabetes specialist likely boil down to the following two points.

1. You will die if you don't consume carbohydrates.

2. Carbohydrates are not the cause of diabetes.

The claim that "2. Carbohydrates are not the cause of diabetes" is also completely wrong, but I will leave that for the article below.

Here, to understand how nonsensical the claim that "you will die if you don't consume carbohydrates," or in other words,that dietary glucose is essential,is, let's study glucose metabolism once again.

Glucose is "absolutely necessary"—up to this point, it is correct.

First, as a premise, there is no doubt that glucose is a special molecule for living organisms. Red blood cells, which lack mitochondria, cannot perform oxidative phosphorylation, so the glycolytic pathway is their only energy production route. For red blood cells, glucose is an irreplaceable substrate.

The brain is an equally important consumer. However, in the case of the brain, the story is a bit more complex. Regarding brain energy metabolism, there is a framework called the Astrocyte-Neuron Lactate Shuttle (ANLS), a division-of-labor model where astrocytes produce lactate from glucose via glycolysis and supply it to neurons. Neurons themselves retain the ability to directly take up and metabolize glucose, but they can only use it for a short time.

Furthermore, the brain has the pentose phosphate pathway (PPP) as a circuit separate from energy metabolism. This is not for energy production, but a pathway responsible for antioxidant defense and glutathione regeneration through the supply of NADPH. In other words, for the brain, glucose is not just fuel, but also a source of reducing power to protect nerve cells from oxidative stress. This is often overlooked, but it is an important point.
Note that brain glucose metabolism is significantly involved in neuropsychiatric disorders. I would like to discuss this in detail on another occasion.

The renal medulla and testes are also tissues with a high dependence on glucose because they are in low-oxygen environments.

Up to this point, as the specialist says, it is a fact that "there are cells that would be in trouble without glucose." Therefore, if blood glucose levels drop below a certain point, it leads to impaired consciousness, coma, and in the worst case, death. There is no medical disagreement that hypoglycemia is life-threatening.

Because glucose is essential, it is endogenous.

The problem starts here. The proposition that "maintaining blood glucose levels is essential for life" and the proposition that "therefore, you must eat carbohydrates" are completely different things. The specialist's statement unconsciously equates these two.

Why are they not equal? The answer is simple:because glucose is essential for maintaining life, the living body has built-in supply pathways from the start that do not depend on diet.is the reason.

Glycogenolysis—a fast but small-capacity buffer.

Glycogen stored in the liver is rapidly broken down by glycogen phosphorylase, converted to glucose-1-phosphate, and then released into the blood as glucose. The characteristic of this pathway is that the reaction is fast.

Gluconeogenesis: A slow but nearly inexhaustible source

A pathway that synthesizes new glucose from non-carbohydrate precursors such as lactate, glycerol, and amino acids (especially alanine). While this primarily takes place in the liver, it also occurs to some extent in the kidneys and small intestine. The characteristic of this pathway is that the reaction has a slow onset.

What is important is that these two do not have a sequential relationship where one takes over when the other runs out. In fact, studies directly measuring metabolic flux in fasting humans have shown that after an overnight fast (about 10 hours), 30-50% of hepatic glucose production is already derived from gluconeogenesis. Gluconeogenesis begins to operate almost simultaneously with the start of fasting, without waiting for glycogen to be depleted.

The role of liver glycogen

So, why is glycogen necessary? The answer lies in the slow reaction speed of gluconeogenesis. Gluconeogenesis is a synthetic pathway that goes through multiple enzymatic steps and cannot respond immediately to sudden changes in demand. On the other hand, glycogenolysis is highly responsive. In other words, glycogen functions as a short-term buffer that compensates for the slow reaction speed of the 'mainstream' gluconeogenesis pathway. By combining a fast but low-capacity pathway with a slow but high-capacity pathway, the variable of blood glucose is stabilized against demand fluctuations on all time scales.

There is a common misconception about glycogen.

In reality, this does not happen. Studies on athletes who have adapted to a near-zero carbohydrate diet for weeks to long-term have reported that, compared to athletes on a high-carbohydrate diet, the consumption rate of muscle glycogen and the rate of glucose production from the liver are actually kept lower during both rest and exercise, and the available amount of glycogen is preserved. In a state where gluconeogenesis is sufficiently established, a pathway (the indirect pathway via UDP-glucose) also operates where a portion of the glucose derived from gluconeogenesis is reconstructed as glycogen, acting to offset net glycogen breakdown.

In other words, even if you do not consume carbohydrates, the glycogen buffer continues to be maintained by gluconeogenesis. The one-way depletion model of 'glycogen -> depletion -> gluconeogenesis' does not reflect reality; it is more accurately a steady-state system where 'glycogen (fast, low capacity) and gluconeogenesis (slow, high capacity) run in parallel at all times, with the latter continuously supporting the former'.

Because it is essential, it is 'not dependent on carbohydrate intake'

The body's blood glucose maintenance system is designed on the premise that because glucose is essential, it is 'not dependent on carbohydrate intake'. If it were designed to rely on external carbohydrate supply, it would harbor an evolutionarily impossible vulnerability where the brain and red blood cells would cease to function every time one fasted. It is logically impossible for the body to place blood glucose as a fundamental variable for survival while leaving its supply source entirely to the unstable input of external meals.

The meaning of glucose intake

Returning to the specialist's statement, the premise that 'you will die if you don't consume carbohydrates' only holds true if both glycogenolysis and gluconeogenesis are malfunctioning for some reason—for example, in cases of severe liver failure or specific congenital metabolic disorders (such as gluconeogenic enzyme deficiency). For a person with healthy liver and kidney function, blood glucose levels are maintained within the normal range by endogenous gluconeogenesis even if carbohydrate intake is zero. This is also supported by physiological data from practitioners of low-carbohydrate/ketogenic diets and groups that have traditionally lived on animal-based diets.

Nevertheless, even if dietary glucose is not essential, one might have this thought:

In fact, even this does not hold true.

When blood glucose rises after a meal, pancreatic beta cells secrete insulin. What this insulin is doing is not 'maintaining' the ingested glucose as blood glucose, but rather actively 'removing' it from the blood. Specifically, glucose uptake into skeletal muscle and glycogen synthesis account for the largest proportion of postprandial glucose processing, and the liver also stores a significant amount of ingested glucose as glycogen. At the same time, insulin suppresses glucose production (glycogenolysis and gluconeogenesis) in the liver itself.

In other words, after a meal, the function of 'creating blood glucose' stops, and the function of 'diverting blood glucose to storage' becomes dominant; it is merely a state where control opposite to that of fasting is at work. The reality is not that ingested glucose maintains blood glucose, but that insulin processes and stores the rise in blood glucose caused by ingestion, thereby lowering it.

Moreover, if a large amount of glucose is ingested, a large amount of insulin is secreted, which can sometimes even lead to a hypoglycemic state a few hours after the meal.

In other words, exogenous glucose does not replace the mechanism of blood glucose maintenance itself; rather, it disrupts endogenous glucose homeostasis.

Summary

• There are indeed cells that absolutely require glucose, such as red blood cells, the brain (for some metabolism), and the renal medulla.

• However, that necessity is a matter of 'maintaining blood glucose homeostasis,' not a matter of 'dietary carbohydrate intake.'

• The living body is equipped with an endogenous supply system that constantly runs both fast but low-capacity glycogenolysis and slow but high-capacity gluconeogenesis in parallel, so glycogen continues to be maintained through gluconeogenesis even if you do not consume carbohydrates.

• Therefore, the statement 'you will die if you don't consume carbohydrates' is incorrect, and the specialist's remark exposes a complete lack of knowledge regarding glucose metabolism.

Needless to say, since the specialist's premise that 'you will die if you don't consume carbohydrates' is incorrect, the proposition derived from it—that 'people who don't consume carbohydrates won't get diabetes'—is also just an empty joke built upon a false premise.

The medical detective closes in on the true culprit behind neuropsychiatric disorders in 'Your Brain Is Not Broken,' now on sale!

E-book version

Paperback version