Nutritional Ketosis: Simplified molecular bases of weight and metabolic management

This post aims to evaluate the benefits of nutritional ketosis for weight and metabolic management and associated hormonal events.

Nutritional ketosis occurs when the body shifts from carbohydrates to fat as primary source of energy production.

Weight management describes the avoidance of obesity by the low carbohydrate nutrition AND calorie restriction. 

Obesity is often associated with cardiovascular disease risk, insulin resistance, and pathological lipid profile called hyperlipemia, all part of the umbrella term called metabolic syndrome

Metabolic syndrome, an epidemic in the western world, has five main components: Obesity, high fasting blood sugar levels, high triglycerides, and low high-density lipoproteins (HDL), and hypertension. According to the World Health Organization, obesity increased by 39% in the adult population worldwide. Specifically, in the US, obesity affects tens of millions of adults and causes over $150 Million in related health expenses per year. Over 40% of adults over the age of 60 years have metabolic disease.

The metabolic disease causes chronic systemic inflammation in our bodies and increases morbidity and mortality significantly.

Unfortunately, the industrialization of the food supply focused on providing a surplus of calories in processed food with processed sugar as a cheap source of energy. In parallel, the abundant consumption of food with excessive loads of sugar caused a skyrocketing increase in obesity and metabolic diseases.

Humans have evolved to be omnivores, using both animals and plants as sources of food. Along with this flexibility, humans developed the ability to use non-carbohydrate sources such as fat and proteins as fuel by converting them into ketones or ketone bodies. Albeit it is abundantly and cheaply available, humans do not depend on sugar to generate energy.

In a low carbohydrate diet, our bodies break down dietary fat and proteins and generate ketone bodies through a process called ketogenesis.

Click here for a short video explaining the biochemistry of ketogenesis.

Fat, protein and carbohydrates (not sugar) are the three macronutrients.

Each macronutrient provides the following amount of energy:

  • Carbohydrate provides about 4 calories (4kcal) per gram
  • Protein contains 4 calories (4kcal) per gram
  • Fat contains 9 calories (9kcal) per gram.

From this list, we can see that fat is a better source for calories (or more energy-dense) than either carbohydrates or protein.

Next, let’s discuss the metabolic changes that are induced by the keto diet and how these changes can improve our health. (links are included for more in depth research articles)

Weight loss:

I mentioned above that obesity, and associated metabolic disease is an epidemy in the western world.

The question is, how the keto diet contributes to weight loss?

But let’s first answer this question: What causes obesity?

Energy intake exceeding energy expenditure causes obesity, overeating, in other words. 

The leading cause of obesity is not sugar or carbohydrates but overconsumption of either a diet high in saturated fat, physical inactivity, smoking, and excessive consumption of alcohol. In the US, Body Mass Index (BMI) exceeding 30 (kg/m2) defines obesity.

Furthermore, genetic factors determine an individual’s predisposition to obesity and developing metabolic disease. The genetic base for obesity is estimated to range from 40% to 60%. In these individuals, risk factors exist long before the onset of obesity or metabolic syndrome.

We can’t change our genes, but we can improve our nutritional habits and emphasize risk management by changing our lifestyle. Limiting food intake in general, also called intermittent fasting, and specifically sugar/carbohydrate through the ketogenic diet and increasing our physical activity are crucial for productive weight management.

On the molecular level, multiple factors regulate obesity. Appetite and “hunger” are critical contributors to overeating.

Ghrelin, the “hunger hormone,” is secreted from the stomach into the bloodstream and is known to stimulate the appetite. Ghrelin travels from the stomach to the brain and stimulates appetite-controlling areas in the brain. In experiments, an excessive amount of Ghrelin causes weight gain and suppresses the utilization of fat as an energy source. Individuals with excessive appetite have an excessive amount of Ghrelin, which is only lowered by food intake.

However, Ghrelin is much more than a pure “hunger hormone” that stimulates food intake.

Ghrelin is responsible for glucose balance in our bodies. It works by inhibiting insulin secretion and regulating gluconeogenesis, the production of glucose from fat and proteins. It is a highly complex system. In brief, the suppression of Ghrelin reduces body fat and improves insulin sensitivity.

Unfortunately, it’s not that simple, as Ghrelin plays a significant role in survival after myocardial infarction and improves the function of the heart. Therefore, Ghrelin suppression through pharmacological means is not a very good option to reduce obesity. However, Ghrelin modulation, lowering the Ghrelin levels rather than blocking it, is a new option for obesity prevention and is tested in clinical trials.

Appetite control and reducing overconsumption is a natural way to manage food intake. Also, keto diet low on sugar and high on fat lowers the Ghrelin levels in our body, suppresses hunger and restricts calorie intake, all factors that contribute to productive weight management, and ultimately weight loss.

Appetite control and reducing over consumption is a natural way to manage food intake and body weight.

Leptin is another hormone involved in body weight regulation. Fat cells or adipocytes in fatty tissue produce and release Leptin into the bloodstream. Leptin is involved in metabolic control, insulin sensitivity, and body fat mass regulation. Leptin is secreted into the bloodstream and acts on brain cells called neurons that are involved in food intake. High Leptin levels in the brain reduce food intake, whereas low levels of this hormone have the opposite effect. Leptin deficiency is associated with severe obesity.

There is much talk about the brain-gut connection. Leptin is a critical player in this axis. High levels of Leptin released from the guts and arriving in the brain signal satiety and suppress hunger and promote energy expenditure. Bodyweight is directly associated with Leptin levels: Obese individuals have low Leptin levels, whereas in lean individuals’ high levels of Leptin can be detected.

Similar to insulin resistance, Leptin resistance impairs energy balance and results in high blood sugar levels, obesity, and promotes chronic inflammation in metabolic disease.

In simple calorie restriction or fasting, Leptin and insulin levels change concurrently. In contrast, in the ketogenic diet, Leptin levels double and whereas insulin levels drop significantly, which is unique to the Keto diet. In this diet, the dramatic change in caloric composition, with fats replacing carbohydrates as the primary source of energy, results in this unique metabolic state, promoting weight loss and reduction of body mass index. Furthermore, the ketogenic diet elevates the levels of survival hormones such as Leptin and norepinephrine, promoting brain protection and cancer prevention.

Keto diet is a natural way to regulate the hormones Leptin and Ghrelin.

As described above, these hormones act on the brain and regulate appetite and hunger and are promoted by the keto diet. Therefore, it is not far-fetched to state that the Keto diet not only acts on the digestive system but primarily targets the brain.

In summary, overeating of any macronutrient can cause obesity. The hormones Ghrelin and Leptin regulate appetite, hunger and metabolism. However, pharmacological targeting these hormones is not sufficient and is likely to cause severe side effects.

The healthiest way to reduce Ghrelin and increase Leptin is by proper adaptation of the Ketogenic Diet AND reduced calorie intake.

Improper adaptation of the Keto Diet can cause malnutrition, which we will discuss in an upcoming post.

In another blog post, I will discuss the gut-brain axis and its role in a regular and the keto diet. 

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