Low carbohydrate restriction (LCD) was introduced into the medical and healthcare fields by Drs. of Atkins and Bernstein [1]. The author and collaborators were the first to introduce LCD in Japan and gained extensive clinical experience [2]. We founded the Japan LCD Promotion Association (JLCDPA) and continue to be active in workshops, books, and study group [3]. Through these activities, we have treated a variety of obese and diabetic patients with LCD. Specifically, we have promoted three-stage useful method: super-LCD, standard-LCD, and petite-LCD [4]. At the same time, they are also widely involved in raising awareness of the basics of nutrition.

As a matter of fact, LCD has been highly evaluated for the treatment of obesity and type 2 diabetes (T2D) so far. Some typical inquiries have been found so far. They include i) why reduce carbohydrates, ii) what are the fundamental factors behind LCD, and iii) what kind of relationships among carbo, protein and fat [5]. To understand these, it is necessary to know what role each of the three major nutrients plays in the body and how they complement each other. This article summarizes the characteristics of each nutrient and their relationship in energy metabolism.

1. The Role Of Carbohydrates In The Hunter-Gatherer Era

During the 7 million years of hunter-gatherer history, before the advent of agriculture, the primary role of carbohydrates as food is thought to have been to promote triglyceride accumulation. For early humans, storing triglycerides as body fat was thought to have been their only safety net against the constant threat of famine.

For the hunter-gatherer era, carbohydrates were occasionally available in the form of wild fruits, nuts, and roots such as yams and lily bulbs. When these were available and consumed, blood glucose levels rose. It brought leading to additional insulin secretion and the rise of GLUT4 to the cell surface in muscle cells, which were first utilized by the muscles and then stored there as glycogen [6]. At the same time, GLUT4 in fat cells also rose to the cell surface, capturing excess blood glucose and converting it into triglycerides for storage. GLUT4 is only found in muscle cells and fat cells. In this way, during the hunter-gatherer era, the trio of "insulin, carbohydrates, and GLUT4" is thought to have functioned primarily as a "fat storage device."

2. Insulin Is an Obesity Hormone in Recent Years

In relation to carbohydrates, the issue of insulin would be considered. During the long hunter-gatherer era, humans rarely consumed carbohydrates. Therefore, β cells had little need to function beyond basal insulin production, and additional secretion was almost nonexistent. The primary role of carbohydrates was to promote triglyceride accumulation. As the establishment of agriculture around the world approximately 10,000 years ago, carbohydrates became a daily commodity. Furthermore, since the Industrial Revolution, especially over the past 150 years, refined carbohydrates have become a regular part of our meals. This increased insulin secretion has led to the conditions that favor the accumulation of excess triglycerides, potentially leading to the development of obesity.

Due to the above mechanism, insulin has been called as the "obesity hormone" [7]. When pancreatic β cells become exhausted by continued secretion of large amounts of insulin, diabetes would develop. Especially in recent years, we consume large amounts of refined carbohydrates on a daily basis. As a result, β cells are forced to work excessively from all day long, a period of suffering in human terms. Current era worldwide seems to be an "age of excess carbohydrates."

3. Role Differences of Three Major Nutrients

1. Carbohydrates

Carbohydrates would be the "fast-acting energy source” where the body can utilize most rapidly. In particular, the brain and nerve cells can typically use glucose as their primary fuel, and maintaining stable blood sugar levels is directly linked to survival. They are also quickly converted into energy by muscles during exercise. However, excess carbohydrates tend to be stored as fat, and excessive intake can lead to obesity and worsening insulin resistance.

2. Protein (Amino Acids)

Protein is an important nutrient that provides the building tissues for muscle, skin, enzymes, hormones, antibodies, and other bodily components. While it also serves as an energy source, its primary role is to "maintain structure and function." Especially, nine essential amino acids (such as the branched-chain amino acids (BCAAs) including valine, leucine, and isoleucine) cannot be synthesized in the body and must be obtained through diet [8]. Among these three major nutrients, protein has been actually the one most strongly associated with the term "essential."

3. Fat (Fatty Acids, Lipids)

Fat has a high energy density of 9 kcal per gram and serve as a long-term energy store. They are essential for maintaining bodily functions, serving as components of cell membranes and precursors to steroid hormones. Fat also contain essential fatty acids (such as linoleic acid and alpha-linolenic acid), which cannot be synthesized in the body and must be obtained through diet.

4. Essential Carbohydrates Do Not Exist

While there are essential amino acids and essential fatty acids among the three major nutrients, there are no "essential carbohydrates." This is because the human body has a mechanism called gluconeogenesis, which allows it to synthesize the necessary amount of glucose from proteins and lipids.

An example is now raised. Even during starvation or carbohydrate restriction, glucose is produced through the following pathways. They are i) gluconeogenesis from amino acids (alanine, glutamine, etc.), ii) gluconeogenesis from glycerol produced by lipid metabolism, and iii) brain energy replacement by ketone bodies (reduced glucose demand). Since the body can synthesize the enough amount of glucose necessary for survival, it is not considered "essential." However, this does not mean that it is "unnecessary," and it is important to note that consuming carbohydrates contributes to efficient energy supply during exercise and daily life. The International Dietary Energy Consultation Group report clearly states that "the theoretical minimum requirement for carbohydrates (which in this case is roughly synonymous with sugars) is zero" [9].

The only cells in the human body that absolutely require glucose are red blood cell (RBC) [10]. RBC is the only cell in the human body that does not possess mitochondria, an energy production device, and can only utilize glucose. Even during periods of fasting and sleep, most of the glucose supply to RBC is provided by gluconeogenesis in the liver, with only a small amount coming from food [11]. The brain has mitochondria, so it can use ketone bodies, the metabolized breakdown products of fatty acids, as an energy source, and also utilizes glucose. Other cardiac muscle, skeletal muscle, and somatic cells use fatty acids and ketone bodies as their primary energy sources on a daily basis, occasionally utilizing glucose as well.

5. Metabolic Changes by Carbohydrate Restriction

When carbohydrate intake is reduced, the body switches its energy sources in the following ways. They are i) Consumption of blood glucose and muscle glycogen, ii) Promotion of fat breakdown (activation of lipase), iii) Breakdown of fatty acids in the liver to produce ketone bodies, iv) Partial supply of glucose to the brain and muscles is provided by ketone bodies [12,13], and v) Excess sugar is produced through gluconeogenesis. As a result, insulin secretion is suppressed, making it easier to utilize body fat, which may be effective in improving obesity and diabetes. However, because dependence on protein and lipids increases, attention to nutritional balance and kidney function is required.

6. Relationship of Major Nutrients-Balance Is Key

The three major nutrients complement each other. Drastically reducing any one of them can have the following effects. They are i) Carbohydrate deficiency; Increased gluconeogenesis of protein, risk of muscle loss, ii) Protein deficiency; decreased immunity, muscle atrophy, and skin and hair problems, and iii) Fat deficiency; decreased hormone synthesis and cell membrane function. In other words, when restricting carbohydrates, the goal isn't simply "zero carbohydrates"; it's important to optimize the balance of the three major nutrients to suit each individual's metabolism and condition [14]. For 3 main nutrients, the roles, essentiality, and deficiency were summarized in Table 1.

Among them, low-carbohydrate ketogenic diet (LCKD) has been beneficial for several metabolic diseases [15]. They include infant seizure, children obesity, type 1 diabetes (T1D), heart failure, Maturity-Onset Diabetes of the Young (MODY), Polycystic Ovary Syndrome (POS), Mc Ardle's disease, and so on [16,17].

Table 1: Comparison of 3 Main Nutrients.

Each major nutrient has a different role, and proteins and lipids in particular contain "essential" components that the body cannot produce. On the other hand, carbohydrates can be synthesized in the body in the necessary amounts, so there are no "essential carbohydrates." However, this does not mean that carbohydrates are unnecessary; an appropriate amount is desirable for energy supply and quality of life. LCKD has been shown to be effective in treating various metabolic diseases. While carbohydrate restriction can be effective to some extent in improving obesity and diabetes, it is important to understand the interactions between the three major nutrients and design a diet that is properly balanced and not excessively biased.

Conflict of Interest

The authors declare no conflict of interest.

Funding

There was no funding received for this paper.

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