Chapter 1: Understanding Ketosis and Its Mechanisms

The intricate processes of ketogenesis and gluconeogenesis have intrigued me for years, stemming from rigorous research and personal experimentation.

Having adopted a ketogenic lifestyle, I reflect on how our ancestors thrived through ketogenesis and gluconeogenesis over millennia. Yet, in today’s society, many still dismiss ketosis as ineffective or even harmful. With my extensive background in this field, I aim to shed light on the nuanced advantages and disadvantages of self-induced ketosis without overly technical jargon.

During my postgraduate studies in biochemistry, I found subjects like ketogenesis, gluconeogenesis, and nutritional biochemistry particularly transformative. While ketosis benefits certain individuals, such as those suffering from epilepsy, it may not be appropriate for everyone, especially individuals with type I diabetes or specific cases of type II diabetes.

For me, embracing ketosis has significantly transformed my health, helping me tackle abdominal obesity, prediabetes, chronic inflammation, arthritis, mood fluctuations, and cognitive issues. My journey into a keto lifestyle spans several years, and I have shared many of my experiences previously. This lifestyle focuses on low carbohydrate intake, healthy fats, and moderate protein, combined with a structured eating schedule and targeted exercise.

Through decades of investigation, I have gained insights into the interactions between ketosis, gluconeogenesis, and glycogen. I believe sharing this knowledge will be beneficial to my readers who often seek guidance on this topic.

Many friends and readers express a strong desire to achieve ketosis, which is commendable. However, they often follow generic advice from various sources, hoping to see that elusive purple color on their ketone-testing strips. Unfortunately, many beginners end up disheartened. Some friends humorously remark that they will throw a celebration when they finally see that purple color. I empathize with their struggles.

I too faced disappointment when I first embarked on a keto journey and saw no immediate results. However, I later discovered valuable information hidden in older textbooks and recent scientific studies.

What are ketogenesis and gluconeogenesis, and why are they vital for our health and well-being?

Ketosis is a metabolic state that arises when the body senses a shortage of glucose or overall energy. As glycogen reserves diminish, the liver produces ketone bodies, which serve as alternative energy sources for various organs. The primary purpose of ketosis is to provide energy for organs when glucose is scarce, particularly for the brain and heart, which readily utilize ketones like β-hydroxybutyrate.

Despite this, certain organs, such as the liver, cannot use ketones for energy. As a result, during ketosis, the body also engages in gluconeogenesis to generate glucose, ensuring that all tissues receive the energy they need. Even on a low-carb diet, like mine, the body can produce glucose from amino acids and fat.

Research shows that gluconeogenesis is a series of metabolic reactions that maintain stable blood glucose levels during fasting. This process primarily occurs in the liver and, to a lesser extent, in the kidneys.

In simple terms, gluconeogenesis synthesizes glucose from non-carbohydrate sources, supporting energy needs during periods of fasting, low carb intake, or intense exercise.

You might wonder about the relationship between glycogen and ketosis. Glycogen, stored in the liver and muscles, provides rapid energy, especially when refined carbohydrates are consumed. However, our main energy source lies in fat stores, which sustain us over the long term. When glycogen levels fall due to reduced carb intake or intense workouts, the body initiates ketosis.

This metabolic shift is a genetic adaptation that helped our ancestors survive during times of food scarcity. Ketones become the primary energy source, while the liver continues to produce glucose through gluconeogenesis.

The ancient physiology of ketosis has evolved over millions of years, enabling human survival. Criticisms of ketosis often stem from a lack of understanding of the complex biochemistry involved. It’s crucial to appreciate the mechanisms that have allowed humans to thrive throughout history, including in modern times.

A 2017 review highlighted that ketone bodies may mimic the effects of caloric restriction, potentially extending lifespan. For a deeper understanding of ketogenesis, check out this chapter from the NIH book.

The first video, "Ketosis || Biochemistry Rapid Revision By Dr Amit," offers a concise overview of the biochemistry involved in ketosis, shedding light on its mechanisms and implications for health.

How can we achieve ketosis and promote gluconeogenesis?

Several methods exist for inducing ketosis, with intermittent fasting being particularly effective based on my personal experience. However, for those aiming for deeper ketosis, long-term fasting may be necessary. While ketosis offers numerous benefits, it may not be suitable for everyone, especially those with specific medical conditions.

Ketogenic diets and fasting-mimicking diets can also be effective in achieving low or moderate ketosis. Additionally, over-the-counter supplements like MCT oil and ketone salts can aid in the induction of ketosis.

Recent research into ketogenic diets has shown promising results. A clinical trial demonstrated that the ketogenic diet outperformed the Dash diet, yielding excellent outcomes for individuals with insulin resistance, high blood sugar, and hypertension.

While MCT oil can have side effects, caution is warranted. Ketone salts, though generally considered safe, have not been extensively studied for long-term risks. Therefore, supplementation should be approached with care.

Based on my experience, natural ketosis through fasting and nutritional adjustments is invaluable for overall health and cognitive function. Consequently, I maintain a ketogenic diet, consuming around 200 grams of fat daily, along with a time-restricted eating approach, to harness the benefits of ketosis for cellular, metabolic, and mental health.

Ketosis has proven effective in reducing visceral fat, maintaining a healthy weight, and enhancing mental clarity. Many individuals adopt ketosis to lower the risk of neurodegenerative diseases and potentially promote longevity, with some clinics successfully employing this approach.

Several older friends have subscribed to such services and have seen benefits. However, I prefer to enter ketosis at my own convenience and monitor my ketone levels. Earlier this year, as part of my New Year’s health celebration, I completed a ten-day fast, achieving glucose levels of 5.3 and ketone levels of 7.3.

Remarkable Health Benefits of Long-Term Fasting

Here’s why I fast for ten days at the end of each year.

Today, I penned this narrative on the seventh day of my second long-term fast this year. A few hours ago, I tested my glucose and ketone levels after some joyful barefoot walks, experiencing mental clarity without hunger pangs, even with such low blood glucose.

If someone with diabetes or prediabetes were to experience low blood sugar, they would require immediate intervention, such as consuming carbohydrates or sugary drinks. My lower sugar levels during this fast were due to increased physical activity. As I rest and meditate, my levels stabilize.

I must admit, entering ketosis wasn't easy initially. In the early days, I experienced what is commonly referred to as the “keto flu,” leaving me feeling fatigued and sluggish. However, after a few weeks, I alleviated these symptoms by improving my hydration and replenishing electrolytes, particularly sodium and magnesium. By increasing my water and electrolyte intake, I permanently overcame the keto flu.

With decreased insulin levels and depleted glycogen stores, we naturally lose fluids, which helps prevent bloating. However, electrolyte balance is crucial during ketosis. I have documented the side effects of fasting and keto diets, especially regarding sleep, in previous articles.

As I age, I prefer to remain in ketosis longer, as it enhances mitochondrial function, increases energy, reduces inflammation, promotes faster recovery from exercise, and improves mental clarity through the influence of β-hydroxybutyrate, which serves as both an energy source and a signaling molecule for cells.

One of the most significant benefits of ketosis for me has been its ability to combat chronic inflammation, providing relief from arthritis symptoms. Ketosis has demonstrated its potential to enhance metabolic and mental well-being through six key mechanisms.

Being fat-adapted has made me more insulin-sensitive. Some athletes thrive on ketosis, benefiting from unlimited energy sourced from fat compared to the limited energy from glycogen stores. I have witnessed bodybuilders and athletes performing exceptionally well on an empty stomach.

If you’re contemplating the keto lifestyle, approach the transition gradually. It can take time for the body to adapt to a new energy source. For further insights into ketosis, consider reading my previous article: Why and How to Enter Ketosis via Lifestyle Choices.

Regardless of dietary preferences—herbivore, carnivore, or omnivore—anyone can enter ketosis. It is possible to achieve ketosis even while consuming some carbohydrates, as long as refined carbohydrates are avoided. Here are some quick tips for transitioning to a ketogenic lifestyle: