"How long does it take to enter ketosis?"

"Liver glycogen stores typically deplete within 12-36 hours of carbohydrate restriction, but measurable blood ketones usually take 2-4 days to rise above the 0.5 mmol/L threshold that defines nutritional ketosis. The timeline depends on your starting glycogen stores, activity level, and how strictly carbs are restricted. Exercise accelerates the transition by depleting glycogen faster."

"Does the brain need glucose to function?"

"The brain cannot use fatty acids directly (they don't cross the blood-brain barrier well). But it can use ketones quite effectively. Research by Owen et al. (1967, Journal of Clinical Investigation) measured brain metabolism during extended fasting and found the brain derives 60-70% of its fuel from ketones after several weeks. Glucose remains necessary for a portion of brain energy needs even in deep ketosis, but the body can synthesize this via gluconeogenesis from amino acids and glycerol."

"Is ketosis the same as the Atkins diet?"

"The Atkins diet includes a ketogenic induction phase (under 20g carbs daily) but gradually reintroduces carbohydrates. A strict ketogenic diet maintains carb restriction permanently to stay in ketosis. The Atkins approach is lower-carb, not necessarily ketogenic at higher phases. Both are distinct from a general low-carb diet that allows 100-150g of carbs daily, which typically doesn't produce ketosis."

"Can athletes perform well in ketosis?"

"This depends on what kind of athlete. Endurance athletes who rely primarily on fat oxidation (long, moderate-intensity efforts) can adapt to ketosis reasonably well with several weeks of adaptation. High-intensity athletes who need fast ATP from glycolysis are more compromised, because fat and ketones can't generate ATP fast enough for sprinting or heavy lifting. Research consistently shows reduced performance at VO2max intensities in the ketoadapted state. The deficit is meaningful for power sports and less significant for ultraendurance."

How Ketosis Works: The Biochemistry of a Ketogenic Diet

Quick Answer

Ketosis happens when you restrict carbohydrates enough (typically below 20-50g per day) that liver glycogen depletes and insulin falls low. The liver then ramps up fat oxidation, generating excess acetyl-CoA that gets converted into ketone bodies. These ketones circulate in blood and feed the brain, heart, and muscles. Nutritional ketosis reaches blood ketone levels of 0.5-3 mmol/L. Diabetic ketoacidosis reaches 10-25 mmol/L and is a medical emergency.

The Science

The human body runs on a flexible fuel system. Under normal eating conditions, glucose is the primary fuel. When glucose runs low, the body has a backup: converting fat into ketone bodies and running most tissues on ketones instead. This metabolic switch is ketosis.

It’s not a trick or a hack. It’s a deeply conserved survival mechanism that humans evolved during periods when carbohydrates weren’t reliably available.

Why Ketosis Happens

The trigger for ketosis is low insulin combined with low glucose availability. Under normal conditions, insulin keeps fatty acid mobilization from fat cells under control. When you eat carbohydrates, insulin rises, fatty acid release from adipose tissue is suppressed, and the liver focuses on glucose metabolism.

Cut carbohydrates enough and two things happen. Glycogen stores start depleting (first liver glycogen, which maintains blood glucose, then muscle glycogen). And insulin falls, releasing the brake on adipose lipolysis. Fat cells begin releasing large amounts of fatty acids into circulation.

The liver soaks up these fatty acids. Most cells can use fatty acids directly for energy through beta-oxidation. The liver does too, but it also has a problem: when fatty acid delivery exceeds the liver’s ability to push acetyl-CoA (the end product of fat oxidation) through the citric acid cycle, acetyl-CoA accumulates.

Acetyl-CoA overflow is what generates ketone bodies.

Beta-Oxidation and the Acetyl-CoA Overflow

Beta-oxidation is the metabolic process that breaks down fatty acids, two carbons at a time, into acetyl-CoA. Normally this acetyl-CoA enters the citric acid cycle (combining with oxaloacetate to form citrate) and gets fully oxidized for energy.

The problem during heavy fat oxidation is that oxaloacetate becomes scarce. Why? Because oxaloacetate is also used for gluconeogenesis, the synthesis of new glucose from non-carbohydrate precursors. In a low-carb state, gluconeogenesis is running hard to maintain blood glucose for tissues that need it. This pulls oxaloacetate away from the citric acid cycle, leaving acetyl-CoA without enough of its usual partner.

The liver’s solution: bundle those orphaned acetyl-CoA molecules into ketone bodies.

The Three Ketone Bodies

The liver produces three ketone bodies. Acetoacetate is the first one made. It gets reduced to beta-hydroxybutyrate (BHB) for transport in the blood. BHB is technically not a ketone by strict chemistry (it’s a hydroxy acid), but it’s the most abundant ketone in the blood during nutritional ketosis and the one measured in blood ketone meters.

Acetone is the third, formed spontaneously from acetoacetate by decarboxylation. It’s exhaled, which is why breath smells different in ketosis.

BHB circulates in blood and can cross the blood-brain barrier. The brain picks it up and converts it back to acetoacetate, then to acetyl-CoA, entering the citric acid cycle to generate ATP. This is how the brain runs on fat, indirectly (Cahill, 2006, Annual Review of Nutrition).

Research by Owen et al. (1967, Journal of Clinical Investigation) in fasting humans found that after five to six weeks of starvation, the brain derives roughly 60-70% of its fuel from ketones. This is a substantial adaptation. The brain doesn’t just tolerate ketones. It actively prefers them to glucose under fasting conditions.

Nutritional Ketosis vs. Ketoacidosis

The most important clinical distinction in this area: nutritional ketosis is not diabetic ketoacidosis (DKA).

In nutritional ketosis, blood ketones typically reach 0.5-3 mmol/L. The blood pH stays normal because insulin (even at low levels) suppresses ketone production from going runaway. The system has a ceiling.

In diabetic ketoacidosis, insulin is essentially absent (in type 1 diabetes or severe type 2). Without any insulin brake, fatty acid mobilization and ketone production go unchecked. Blood ketones reach 10-25 mmol/L, overwhelming the blood’s buffering capacity and dropping pH to dangerous levels. DKA is a medical emergency.

The difference is insulin. A functioning pancreas, even one secreting very low amounts in response to a ketogenic diet, prevents ketone levels from rising to dangerous levels.

This is why healthy people and well-controlled type 2 diabetics can safely enter nutritional ketosis, while type 1 diabetics and some type 2 diabetics on certain medications need careful monitoring on very low carb diets.

The Brain Adaptation Period

The transition into ketosis has a rough patch. The first few days involve what’s often called “keto flu”: fatigue, brain fog, headaches, and reduced physical performance. Part of this is from glycogen depletion (glycogen holds water, so depleting it causes rapid water and electrolyte loss). Part of it is the brain running below capacity while it ramps up the enzymes and transport proteins needed to efficiently process ketones.

The brain’s adaptation to ketones is a slow process. Gene expression changes, monocarboxylate transporter density in brain capillaries increases, and enzyme upregulation occurs over 1-4 weeks. Until that adaptation is complete, the brain runs somewhat inefficiently.

After 2-6 weeks in most individuals, the brain runs smoothly on ketones, and most people report stable energy levels and reduced appetite, consistent with what Volek et al. (2009, Lipids) and others have documented in ketogenic diet studies.

Long-Term Outcomes: Where the Evidence Is Murkier

The mechanism of ketosis is well established. What’s less clear is whether maintaining long-term ketosis has unique benefits for most people beyond the initial weight loss (which appears partly driven by reduced appetite and partly from water weight in the first week).

Some populations show strong evidence for benefit: people with drug-resistant epilepsy (ketogenic diet is an established treatment), people with type 2 diabetes (significant blood sugar improvements), and potentially people with certain metabolic conditions. For general weight management, ketogenic diets perform comparably to other calorie-restricted approaches in head-to-head long-term trials.

This is the zone where “strong mechanism” doesn’t automatically translate to “clear clinical superiority.”

This article is for educational purposes only. It’s not medical advice. Talk to your doctor or a registered dietitian before making significant changes to your diet.

What This Means for You

Transitioning into ketosis usually takes 2-4 days of very low carbohydrate intake (under 20-50g/day). The first week often involves fatigue, headaches, and reduced performance as the body and brain adapt to using ketones. These symptoms (sometimes called 'keto flu') are partly from electrolyte loss due to lower insulin and reduced glycogen stores, and supplementing sodium, potassium, and magnesium can help. Once adapted, most people report stable energy and reduced hunger, though athletic performance at high intensities may remain reduced without glucose.