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The Ketogenic Diet. Is it Paleo?

By Christopher Clark
November 29, 2016
The Ketogenic Diet. Is it Paleo? image

Part One in Our Ketogenic Diet Series.

The Paleo and ketogenic diets are not the same, but does that mean there isn’t a place for the ketogenic diet within the Paleo template? They do have considerable overlap. Additionally, there is strong evidence that ketogenic diets are highly beneficial for a wide range of chronic health conditions.

During the past decade, low-carb diets, such as the Paleo diet, have become increasingly popular, while a cloud of suspicion has formed over government-advocated, low-fat, grain-centric diets.

The reasons for this are simple. Reducing carb intake promotes both improved blood glucose levels and reduced circulating insulin. It also improves metabolic syndrome markers, like obesity, which increase one’s risk for diabetes and cardiovascular disease.1

The nutritional perspective on dietary fat has also changed. Dr. Cordain, Dr. Atkins, and other nutrition pioneers have helped bring two very important nutrition science concepts to the mainstream: 1) fat is an important energy source, and 2) fat doesn’t necessarily make you fat.

While most people are aware that fat as well as carbs are the body’s primary energy sources, researchers and advocates of ketogenic diets have been calling attention to an important third fuel source (albeit a source derived from fat.) This “third fuel” is something called ketones, or ketone bodies (KBs). This third fuel is the basis of the ketogenic diet (as the name implies.)

To understand KBs, we need to recap some biochemistry basics – specifically, the basics regarding a molecule called ATP.

What is ATP?

In 1929, a German chemist named Karl Lohmann discovered adenosine triphosphate (ATP), the molecule that became known as “the molecular unit of currency.”2 ATP is to biochemistry what gold is to the global economy – a universally recognized medium of exchange. Go anywhere in the world with gold and you can make things happen. Likewise, within our bodies, ATP gets things done by transporting chemical energy. All cells require energy to fulfill their jobs and ATP is the molecule that moves this energy from place to place.3

The macronutrients in our diet that give us energy – fat, carbs, and protein – are all used simply to generate ATP, but the body prefers carbs and fat. As Westman et. Al. described in the journal Current Atherosclerosis Reports, one reason humans can survive on opposite diets (high-fat, low-carb versus high-carb, low-fat) is because the body can transition from “glucocentric” metabolism (energy derived primarily from carbohydrates) to “adipocentric” metabolism (energy derived primarily from fatty acids and ketone bodies).4

So how does the body generate ATP from our macronutrients? In 1937, German scientist Hans Krebs made a groundbreaking discovery – a critical cellular pathway by which carbs, fat, and protein are used to produce ATP. For this discovery, known as the Krebs cycle (or the citric acid cycle), Krebs won the Nobel Prize.5

The Krebs cycle, however, is not the only ATP production pathway. There are other ways the body can generate ATP, and one concerns the unique energy needs of the brain and the greater central nervous system (CNS).

Two Kinds of Brain Food

Until the 1960s, scientists thought the CNS could not use fatty acids – that glucose (carbs) was its only fuel source. One of the great fathers of metabolic research, however, Dr. George Cahill, overturned this notion. In a series of landmark experiments during the 1960s, Cahill and his colleagues demonstrated that after 3-4 days without carbs, the CNS secures an alternate source of energy.6,7,8 This alternate “brain food” is ketone bodies (KBs).

What is Ketosis?

Ketosis is essentially a metabolic state that mimics starvation. That may sound scary, but ketosis has amazing health benefits and few risks, as we’ll explore below.

Ketosis occurs when glucose and glycogen (stored glucose) become depleted, forcing the body to use fat (either stored fat or fat consumed as food) as its primary energy source. Broadly speaking, this can occur under four circumstances:

  1. Starvation
  2. Fasting
  3. Prolonged intensive exercise
  4. Carbohydrate-restricted diets

During ketosis, ketone bodies (KBs), which are water-soluble molecules, are produced by the liver from fatty acids. There are three types of KBs:

  1. 3-hydroxybutrayte
  2. Acetoacetate
  3. Acetone

KBs are always present within the body, but usually at very low levels (less than 0.1 mmol/L). During ketosis, however, KBs increase considerably, going as high as 8 mmol/L. Despite the lack of carbohydrates, homeostasis is maintained and blood pH remains stable because the CNS uses KBs efficiently during ketosis.9

It’s important to point out that there is a fifth condition whereby KBs increase. We separate this condition – known as ketoacidosis – from the other four because it’s an extreme condition characterized by dangerously high KBs and potential blood pH dips, which are also dangerous.10 Ketoacidosis is a risk for people with type-1 diabetes, but is not a risk of diet-induced ketosis.

The Ketogenic Diet. Is it Paleo? image

Ketosis versus Low-Carb

It’s important differentiate between ketosis (whereby KBs are produced at concentrations higher than 0.5 mmol/L) and the burning of fatty acids for energy (when glucose/glycogen levels are sufficient).11 In the latter scenario fatty acids are broken down regularly through the Krebs cycle to generate ATP in a process called beta-oxidation.12 Beta-oxidation occurs whenever there are carbs and fat in the diet, particularly when calorie intake matches calorie expenditure.13,14,

In other words, you’ll burn fat as energy on a low-fat diet and on a high-fat diet that includes some carbs. But, when carb intake drops low enough, some of the fatty acids that would have been processed through beta-oxidation will instead be used to make ketone bodies.

There is no absolute agreement as to what constitutes pure ketosis compared to mild ketosis, but an often-cited threshold for pure ketosis is carbohydrate consumption of 50 grams or less per day. This threshold is associated with very-low-carbohydrate ketogenic diets (VLCKD) and low-carbohydrate ketogenic diets (LCKD), whereas 50-100 g/d could be considered a low-carbohydrate diet (LCD).15 The liver may produce some KBs on a LCD, but much less compared to VLCKD/LCKD.

Another way to define ketogenic diets is by the ratio of fat to protein+carbohydrates. Ratios of 2:1 to 4:1 are classified as ketogenic. Higher ratios are thought to be more restrictive, yet more effective.

Many people have success by beginning with higher proportions of fat and then gradually reducing the ratio of fat relative to protein+carbs.16

ATP “Superfuel”

When KBs become sufficiently concentrated within the blood (around 4 mmol/L) the CNS starts using them as energy.17 But what benefits do KBs have over glucose as a fuel source? In a word: efficiency.

In 2003, Dr. Cahill wrote, “Recent studies have shown that 3-hydroxybutyrate, the principal ‘ketone,’ is not just a fuel, but a ‘superfuel’ more efficiently producing ATP energy than glucose or fatty acid.”19 Compared to 100g of glucose, which can yield 8.7 kg of ATP, 100 g of 3-hydroxybutyrate can yield 10.5 kg of ATP, and 100 g of acetoacetate 9.4 kg of ATP.19,20,

Additionally, studies have also shown KBs to be neuroprotective by reducing the production of reactive oxygen species in neurological tissues.21

Benefits of Ketosis

In the early 1920s, Dr. Robert Wilder of the Mayo Clinic was seeking a dietary treatment for epilepsy. Following the work of Pierre Marie, the 19th century French neurologist who proposed fasting as an epilepsy treatment, Wilder surmised that a reduced carbohydrate diet could mimic the effects of fasting. His diet, dubbed the ketogenic diet, reduced seizures by fifty percent, which was far better than then-available anticonvulsant medications.

Nearly a century later, the ketogenic diet has been rigorously studied in numerous randomized controlled trials. As reported by Paoli et al., “There is no doubt that there is strong supportive evidence that the use of ketogenic diets in weight-loss therapy is effective.”23 In a 2013 review, Paoli et al. also reported strong evidence for ketogenc diets with respect to diabetes management and cardiovascular disease prevention, as well as emerging evidence for acne, cancer, polycystic ovary syndrome, and various neurological disorders.24

The Ketogenic Diet. Is it Paleo? image

An Evolutionary Perspective

Environments that are unpredictable and ever-changing have been a constant theme of human evolution. Our migratory ancestors adjusted to varying, often resource-limiting, climates. To survive, they had to endure food scarcity and even starvation while still ensuring steady streams of energy for their large brains.

With this in mind, it makes sense that KBs burn more efficiently than glucose. Hunter-gatherers depended on mental sharpness and visual acuity, so ketosis enabled our ancestors to thrive in challenging situations when food was limited. Even when food was available, they generally ate diets lower in carbs (compared to the sugar-rich and grain-heavy diets of today).25 Had they been eating high-carb diets, shifting into ketosis when food became limited would have been more difficult (compared to shifting from low-carb diets into ketosis).

It’s also instructive to realize that newborn babies are naturally in ketosis.26 Have you ever wondered why babies are so chubby? Relative to body size, their brains are even larger than adult brains. To ensure proper brain development, babies have an ample reserve of body fat, high amounts of dietary fat from breast milk, and the ability to rapidly enter ketosis.27


So the big question – is a ketogenic diet Paleo? Our ancestors were not perpetually in ketosis, but clearly they were keto-adapted, meaning they could efficiently enter ketosis, depending on their circumstances.

There is considerable overlap between the contemporary Paleo diet and the ketogenic diet and because ketosis has both an evolutionary precedent and verifiable health benefits, it seems appropriate to incorporate ketosis into the Paleo template. This could occur in numerous ways, including through occasional fasting, intermittent fasting, and by periodically cutting one’s carb intake to less than 50 g/d, perhaps for several days, weeks, or months at a time.

Furthermore, the ketogenic diet has undeniable benefits for those who are overweight or obese, as well as those at risk for diabetes and heart disease. In these cases, it would be wise to discuss with one’s doctor or health practitioner the possibility of starting a ketogenic diet and then gradually transitioning to a less restrictive Paleo diet.

For more information on how to incorporate periodic ketosis into your Paleo diet, please read Part Two of this series written by Dr Marc Bubbs.


[1] Volek JS and Feinman RD. (Nov 2005). Carbohydrate restriction improves the features of Metabolic Syndrome. Metabolic Syndrome may be defined by the response to carbohydrate restriction. Nutrition and Metabolism, 2(31). Retrieved from

[2] Nobel Media. (2016). ATP first discovered in 1929. Retrieved from

[3] Knowles JR. (July 1980). Enzyme-Catalyzed Phosphoryl Transfer Reactions. Annual Review of Biochemistry, 49. Retrieved from //

[4] Westman EC, et al. (2003). A Review of Low-carbohydrate Ketogenic Diets. Current Atherosclerosis Reports, 5(6). Retrieved from

[5] Nobel Media. (2016). Hans Krebs – facts. Retrieved from

[6] Owen OE, et al. (Oct 1967). Brain metabolism during fasting. The Journal of Clinical Investigation, 46(10). Retrieved from

[7] Owen OE, et al. (Mar 1969). Liver and kidney metabolism during prolonged starvation. The Journal of Clinical Investigation, 48(3). Retrieved from

[8] Felig P, et al. (Mar 1969). Amino acid metabolism during prolonged starvation. The Journal of Clinical Investigation, 48(3). Retrieved from

[9] Paoli A, et al. (2011). [The ketogenic diet: an underappreciated therapeutic option?]. La Clinica Terapeutica, 162(5). Retrieved from

[10] Cahill GF. (2006). Fuel metabolism in starvation. Annual Review of Nutrition, 26. Retrieved from

[11] Laffel L. (Nov-Dec 1999). Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes. Diabetes/Metabolism Research and Reviews, 15(6). Retrieved from

[12] Manninen AH. (2004). Metabolic Effects of the Very-Low-Carbohydrate Diets: Misunderstood "Villains" of Human Metabolism. Journal of the International Society of Sports Nutrition, 1(2). Retrieved from

[13] Minehira K, et al. (Sep 2003). Effect of carbohydrate overfeeding on whole body and adipose tissue metabolism in humans. Obesity Research, 11(9). Retrieved from

[14] Koutsari C, et al. (Aug 2011). Storage of Circulating Free Fatty Acid in Adipose Tissue of Postabsorptive Humans. Diabetes, 60(8). Retrieved from //

[15] Westman EC, et al. (2007). Low-carbohydrate nutrition and metabolism. American Journal of Clinical Nutrition, 86. Retrieved from //

[16] Wirrell EC. (Nov 2008). Ketogenic Ratio, Calories and Fluids: Do They Matter? Epilepsia, 49(Suppl 8). Retrieved from

[17] Veech RL. (Mar 2004). The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism. Prostaglandins Leukot Essent Fatty Acids, 70(3). Retrieved from

[18] Cahill GF and Veech RL. (2003). Ketoacids? Good Medicine? Trans Am Clin Climatol Assoc, 114. Retrieved from

[19] Salway JG. Metabolism at a Glance. Oxford: Blackwell Science; 1999.

[20] Manninen AH. (2004). Metabolic Effects of the Very-Low-Carbohydrate Diets: Misunderstood "Villains" of Human Metabolism. Journal of the International Society of Sports Nutrition, 1(2). Retrieved from

[21] Bough KJ and Rho JM. (Jan 2007). Anticonvulsant Mechanisms of the Ketogenic Diet. Epilepsia, 48(1). Retrieved from //

[22] Freeman JM. (Mar-Apr 2013). Epilepsy’s Big Fat Answer. Cerebrum. Retrieved from

[23] Paoli A, et al. (2013). Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. European Journal of Clinical Nutrition, 67. Retrieved from //

[24] Paoli A, et al. (2013). Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. European Journal of Clinical Nutrition, 67. Retrieved from //

[25] Konner M and Eaton SB. (Dec 2010). Paleolithic nutrition: twenty-five years later. Nutrition in Clinical Practice, 25(6). Retrieved from

[26] Platt MW and Deshpandeb S. (Aug 2005). Metabolic adaptation at birth. Seminars in Fetal and Neonatal Medicine, 10(4). Retrieved from //

[27] Cunnane SC and Crawford MA. (Sep 2003). Survival of the fattest: fat babies were the key to evolution of the large human brain. Comp Biochem Physiol A Mol Integr Physiol, 136(1). Retrieved from

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