It's going to be a challenge to keep this short.
IN GENERAL:
Ketones and glucose are both fuel sources for the body.
Glucose comes from dietary carbs, or can be produced in the liver from non-carb sources (gluconeogenesis) in times of carb scarcity.
The body strictly regulates glucose levels in the blood, because some tissues require glucose for energy.
Very low-carb (20g-50g of carbs per day for most people) or no-carb (fasting) both force gluconeogenesis.
In these gluconeogenesis scenarios, ketone production in the liver (ketogenesis) ramps up significantly.
The presence of significant ketones in the blood indicates that the body is 'fat-adapted', efficiently utilizing fat for energy (the metabolic state of 'nutritional ketosis').
A supply of ketones in the blood, ready to go where needed, means stable energy with hunger suppressed.
I hope I've explained why there can be no fat-adaptation without extreme carb scarcity. More than just a few carbs, no ketones. Just a few carbs, ketones.
Why this is IN GENERAL: Both gluconeogenesis and ketogenesis can happen in special circumstances outside of the carb restriction that leads to nutritional ketosis. Gluconeogenesis can also take place to a lesser extent in the kidneys.
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Why should I care about fat-adaptation?
Before the extensive development of agriculture about 12,000 years ago, human ancestors lived as hunter-gatherers for millions of years. Food availability and diets would have varied significantly based on geographical location, season, and available resources, but generally lacked any consistent high-carb availability. Ketosis was a recurrent and natural metabolic state.
While no one argues that humans lived in deep ketosis everywhere year-round, the ability to thrive in ketosis would have been a fundamental survival advantage. Our bodies are well-adapted to utilizing ketones and the metabolic pathways involved are not emergency systems, but rather integral to human physiology.
Evolution for complex physiological systems operates on much longer timescales than 12,000 years. While the Agricultural Revolution brought about dramatic shifts in diet (from diverse wild foods to a more narrow, carb-heavy reliance on staple crops like grains and legumes) and lifestyle (from nomadic to sedentary), our underlying genome and metabolic machinery remain optimized for the environment in which we spent the overwhelming majority of our evolutionary history. This mismatch is often cited as a root cause of many modern non-communicable diseases (NCDs).
So human physiology, from a broad evolutionary perspective, has changed little since the Agricultural Revolution. There have been some specific small adaptations, such as a degree of lactose tolerance and increased salivary amylase in some populations with high-starch diets. Not so successful has been an adaptation to gluten; humans are still grappling with the relatively new dietary component of wheat.
Our physiological machinery, including our metabolic pathways for handling fats and carbs, remains the same as our pre-agricultural ancestors.
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Fat-adaptation, a metabolic state achieved through prolonged periods of low-carb eating or fasting, offers several key advantages. Primarily, it means the body becomes highly efficient at utilizing fat (both dietary and stored body fat) as its main fuel source instead of relying heavily on carbs. This metabolic flexibility typically leads to more stable energy levels throughout the day, avoiding the 'crashes' associated with fluctuating blood sugar. Individuals often report significantly reduced hunger and cravings, making appetite management easier.
There is a growing body of evidence and theoretical understanding that nutritional ketosis is protective against various NCDs, that are killing us and getting worse. NCDs include conditions like type 2 diabetes, cardiovascular disease, neurodegenerative diseases, and most cancers.
The protective mechanisms of ketosis involve several pathways:
1. Improved Metabolic Health: Ketosis inherently leads to lower insulin levels and more stable blood glucose. This directly addresses key drivers of NCDs like insulin resistance, hyperinsulinemia, and hyperglycemia, which are central to metabolic syndrome, type 2 diabetes, and contribute to cardiovascular disease. This often results in favorable changes in lipid profiles (e.g., lower triglycerides, higher HDL).
2. Anti-inflammatory Effects: Ketone bodies have been shown to inhibit a major component of the inflammatory response. Chronic low-grade inflammation is a significant contributor to the development and progression of many NCDs, including heart disease, neurodegenerative disorders, and cancer.
3. Antioxidant Effects: Ketone bodies can enhance the body's endogenous antioxidant defense systems and reduce oxidative stress, which is a key factor in cellular damage and disease pathogenesis.
4. Mitochondrial Function Enhancement: Ketones are a highly efficient fuel for mitochondria, leading to improved mitochondrial function and biogenesis (creation of new mitochondria). Healthy mitochondria are crucial for cellular energy production and are often dysfunctional in NCDs.
5. Autophagy and Cellular Cleanup: Nutritional ketosis, especially combined with time-restricted eating, can also induce or enhance autophagy, a cellular recycling process that removes damaged cellular components, contributing to cellular resilience and longevity. Cells with pre-cancerous mutations or malignant potential arise frequently in the body. A healthy and robust immune system continuously patrols the body, identifying and eliminating cells that have become abnormal or potentially cancerous before they can proliferate uncontrollably and form a tumor. Enhancing autophagy supports the body's immune system's protective or anti-cancer effort.
6. Anti-Glycation Effects: Nutritional ketosis significantly reduces the formation of Advanced Glycation End Products (AGEs). Glycation is a harmful process where excess sugar molecules non-enzymatically bind to proteins and lipids in the body, creating these damaging compounds. By consistently lowering and stabilizing blood glucose levels, a core feature of ketosis, the body provides far less circulating sugar to fuel this process. Reduced AGE formation lessens cellular damage, mitigates chronic inflammation, and diminishes oxidative stress, thereby contributing to cellular resilience and slowing the progression of age-related diseases and NCDs.
7. Weight Management: Ketogenic diets are highly effective for weight loss due to appetite suppression and metabolic changes. Reducing obesity and excess visceral fat is a powerful protective factor against a wide range of NCDs.
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