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11 Health Benefits of Ketone Bodies + Side Effects

Written by Andrea McRae, MSc (Molecular Biology) | Reviewed by Biljana Novkovic, PhD | Last updated:
Jonathan Ritter
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology) | Written by Andrea McRae, MSc (Molecular Biology) | Reviewed by Biljana Novkovic, PhD | Last updated:

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Ketone bodies are extremely energy-efficient fuel. They make more ATP than sugar. As a primary fuel source, ketone bodies can improve weight loss, focus, and energy while decreasing inflammation and risks of chronic diseases. Read on to learn more about this “fourth macronutrient” that’s allegedly better than carbohydrates, fats, and proteins.

Ketones vs. Ketone Bodies

What Are Ketones?

Ketones are organic compounds that contain a carbon-oxygen double bond (carbonyl group) that is single bonded to 2 hydrocarbon groups [1].

They are found nearly everywhere in both industry and nature.

In industry, ketones are used as chemical building blocks to make explosives, paints, and textiles [2, 3].

Ketones are used in natural and synthetic pharmaceutical products. These include antibiotics and steroid hormones (cortisone) [4, 5].

In nature, ketones are found in many sugars (ketoses) including fructose, and the hormones (progesterone and testosterone) [6, 7, 8].

Plant-based ketones are known for their sweet smell. They are present in vanilla, cinnamon, almond, and mint extracts [9].

In contrast, the blue cheese gets its sharp smell from a group of methyl ketones [10].

Ketone Bodies

Although “ketones” and “ketone bodies” are often used interchangeably, not all ketones are ketone bodies. Neither are all ketone bodies technically ketones.

Ketone bodies are produced naturally in the liver by the breakdown of fats. When we say ketone bodies, we refer to [11, 12]:

  • Acetone
  • Acetoacetic acid (AcAc)
  • Beta-hydroxybutyric acid (BHB) – not technically a ketone

Ketone bodies act as an alternate energy source of carbohydrates when the body is fasting or enduring prolonged exercise [13].

Beta-hydroxybutyric acid and acetoacetate easily pass through membranes and are a source of energy for the body and the brain [11].

Mechanism of Action

In the absence of carbohydrates and when glycogen stores are depleted, fats move to the liver. Fat cells are broken down into glycerol and fatty acid molecules. Fatty acids are then converted into ketone bodies by a process called ketogenesis [14].

Ketogenesis primarily occurs in the mitochondria of liver cells [15].

Acetoacetate is the precursor to the other 2 ketone bodies, acetone and beta-hydroxybutyric acid [16].

It can spontaneously, or via decarboxylation, convert into acetone [17].

Acetone can be further broken down into pyruvate, lactate, and acetate, which is used for energy [18].

Beta-hydroxybutyric acid is the most common ketone body in the blood after ketogenesis [11].

Ketone bodies move to active tissues (muscle or brain) to be converted to acetyl-CoA by a process called ketolysis [11].

Ketolysis is the process where ketone bodies are used for energy in the mitochondria of tissues [11].

Acetoacetate and beta-hydroxybutyric acid are absorbed from the blood by the tissues, and in cells, they are used to create ATP (ATP = energy) [11, 19].

Ketosis and Its Symptoms

Ketosis is a buildup of ketone bodies in the bloodstream. In healthy individuals, ketosis can be attained by the consumption of a low-carbohydrate/high-fat diet and fasting [20, 13]. However, it can also be caused by starvation or diabetes (diabetic ketoacidosis), where it can be detrimental to an individual’s health [13, 21].

You have reached ketosis if you present some of the following symptoms soon after starting the diet:

  • Bad breath (fruit- or nail polish-like)
  • Weight loss
  • Increased ketone bodies in blood, urine, and breath
  • Appetite suppression
  • Short-term fatigue
  • A short-term decrease in exercise performance
  • Short-term decreased focus and energy

Ketogenic Diet

Ketogenic diets involve low-carbohydrate (under 50 g/day) and high-fat consumption. This diet increases levels of free fatty acids and ketone bodies in the blood [22].

A ketogenic diet brings the body into a state of nutritional ketosis, where the body uses fat, instead of carbohydrates, for energy [22].

Keto-snacks include seeds, nuts, full-fat cheese, dark chocolate, dried meats, cherry tomatoes, avocados, and pickles, among many more.

Keto recipes often replace traditional carbohydrates like pasta and bread with zucchini noodles and ground cauliflower. A variety of keto-adapted recipes is easily accessible.

Ingestible ketone supplements and beverages are an alternative or addition to the ketogenic diet [23, 24].

Supplements include ketone salts, ketone oils, and ketone esters.

Ketone salts contain ketone bodies (beta-hydroxybutyrate) bonded to salt (sodium or calcium) for quick energy and have a decent taste when eaten [23, 24].

Ketone esters contain the raw beta-hydroxybutyrate ketone body without the salt. Ketone esters are rapidly absorbed and used for energy, however, they have an undesirable taste [25, 24].

Eating ketone oil is not as direct as consuming ketone salts or esters because the oil must be digested to extract the energy. Ketone oils include coconut oils or medium-chain triglyceride (MCT) oil powder [26].

Health Benefits of Ketone Bodies

1) Can Reduce Inflammation

Using ketone bodies for energy lessens the production of damaging free radicals. Fewer free radicals reduce tissue inflammation [27, 28, 29].

Transition to ketone bodies as fuel reduces lactate levels and the production of hydroxyl radicals. These are both known to enhance tumor inflammation and inflammatory molecule (cytokine) production [30, 31].

In fact, both animal and human studies highlight that the transition from glucose to ketone body metabolism turns on anti-inflammatory mechanisms [32, 33].

In multiple sclerosis animal models, a ketogenic diet had a protective effect on brain inflammation [34].

Ketogenesis turns on PPAR-gamma, a known anti-inflammatory molecule. It also inhibits the inflammatory markers (NF-kB, TNF-alpha, COX-2) [35, 36, 37].

2) Act as Antioxidants

Ketone bodies have the antioxidant capacity within mitochondria by reducing cell death and reactive oxygen species production. They scavenge the body for free radicals and inhibit oxidative stress that can result in severe damage and disease [38].

Animals fed a ketogenic diet had enhanced the mitochondrial antioxidant status and their mitochondrial DNA was protected from oxidant-induced damage [39].

3) Improve Fat Burning

A randomized, controlled trial of 120 overweight, hyperlipidemic subjects compared the effects of a low-carbohydrate ketogenic diet with a low-fat, low-cholesterol, reduced-calorie diet. Over 24 weeks, subjects consuming the low-carbohydrate diet showed greater weight loss [40].

Four other clinical trials compared the effects of a low-carbohydrate diet with a low-fat diet. These studies found that the low-carbohydrate group lost more weight over 3 to 6 months [41, 42, 43, 44].

4) Can Enhance Brain Function

In a study of 152 patients diagnosed with Alzheimer’s disease, consumption of an oral ketone supplement improved cognition [45].

A low-carbohydrate diet improved the memory of individuals with mild cognitive impairment [46].

Animals with brain trauma that used ketone bodies as fuel had improved cognitive and motor function post-trauma [47].

In a mouse model of amyotrophic lateral sclerosis, a ketogenic diet increased the number of motor neurons in the spinal cord and preserved motor function [48].

5) May Improve Skin Condition

Fatty acids, such as those found in salmon, seeds, and olive oil, help rebuild membranes reducing dry and irritated skin. Fatty acid metabolism by ketogenesis also makes antioxidants and anti-inflammatory molecules (cytokines) to improve skin health [49, 50].

Dark green vegetables eaten during the ketogenic diet are high in vitamin A. Vitamin A improves how skin sheds (skin cell differentiation), leading to improved skin condition [51].

Collagen-rich ingredients such as eggs, beans, and seeds can make the skin smooth [52].

6) Improve Blood Sugar Levels

A small study of 84 obese patients and those with type 2 diabetes highlighted that a low-carbohydrate diet led to improved glycemic control and reduced or eliminated medication use [53].

Using ketone bodies as fuel stabilized blood sugar levels in obese patients and reduced cellular dependency on glucose. This prevents health issues resulting from too high or low blood sugar [54, 55].

7) May Improve Mitochondrial Health

Ketogenesis promotes the production of mitochondrial energy. It does this by increasing mitochondrial respiration and ATP production as shown in a mouse model of Parkinson’s disease [56].

In another mouse study, beta-hydroxybutyric acid protected against mitochondrial damage [57].

Animals fed a ketogenic diet had more mitochondria [58].

Mitochondria are the powerhouses of the cell, thus an increase in number results in an increase in energy production.

Ketone bodies activate the Nrf2 pathway, increasing mitochondrial glutathione. Ketone bodies also reduce the imbalance between the production of free radicals and the body’s ability to get rid of their harmful effects (oxidative stress) in animal models [59, 39].

8) May Reduce Food Cravings

Wanting specific foods can result in failed weight-loss diets [60].

A reduced (medium and low) carbohydrate diet that uses ketone bodies as fuel reduces the urge to eat carbohydrates and sweets. Ketone bodies also increase dietary restraint [61].

Compared to a low-fat diet, a low-carbohydrate diet causes a decrease in urges for carbohydrates and starches, and hunger is less of a bother [62].

After 3 days of a low-carbohydrate/high-fat diet, GLP-1 hormone levels increased in 9 healthy young men [63].

This hormone signals the brain that enough food has been eaten [64].

9) May Reduce the Risk of Chronic Metabolic Diseases

A low-carbohydrate diet is associated with improved risk factors for obesity, including high blood pressure and unhealthy cholesterol levels [43, 65, 42].

Furthermore, a reduced risk of obesity decreases the risk for diabetes, heart disease, and cancer, among other conditions [43, 66].

10) May Improve Athletic Performance

Ketone drinks (ketone esters) consumed by 39 high-performance athletes in 5 separate studies showed improved physical endurance [67].

Ketone bodies provide a constant supply of energy to the brain. Keto-adapted endurance athletes can maintain mental clarity better than non-keto-adapted athletes. This is because non-keto-adapted athletes have to switch from using sugar to ketone bodies as energy [68].

Reduced, delayed onset muscle soreness (less lactic acid byproduct from using sugar as fuel), and accelerated post-exercise recovery may also be beneficial for keto-adapted athletes [68].

11) May Prevent Seizures

Ketone bodies have anti-seizure, anticonvulsant, and neuroprotective properties [69].

It is currently unknown whether these effects are due to elevated ketone bodies, reduced glucose, or a combination of these effects [70].

Ketone bodies affect both inhibitory and excitatory neurotransmitters in addition to mitochondrial targets [71].

Thus, they may affect the levels of neurotransmitters and their receptors in the brain [72].

Numerous animal studies that administered exogenous ketone bodies showed a protective effect against seizures [72].

However, clinical validation in human subjects is required, as ketone levels in the blood and control of seizures have not yet been clearly correlated [71].

Side Effects & Precautions

Negative effects of using ketone bodies as a fuel include [73, 40, 55, 74, 75]:

  • Weakness
  • Headaches
  • Constipation
  • Muscle cramps (can be reduced by increasing fluid intake, consumption of allowed vegetables, and a mineral supplement )
  • Nausea
  • Vomiting
  • Fatigue (reduced energy due to lack of quick sugars)
  • Lower blood glucose levels (caution in diabetic patients)
  • Mineral deficiency
  • Brain fog
  • Irritability
  • Flu-like symptoms
  • Keto rash (Prurigo pigmentosa)

Many of these negative effects may disappear once your body adjusts to the ketogenic diet.

Contraindications

Individuals with diabetes should be cautious of diabetic ketoacidosis. Diabetic ketoacidosis increases the pH of blood when attempting to use ketone bodies as fuel [76].

Individuals who lack PPAR-alpha may not efficiently use ketone bodies as fuel [77].

Ketone Levels in the Body

Ketones in Blood

Ketone bodies greatly increase in the blood of those on a low-carbohydrate, high-fat diet. In non-diabetic individuals, plasma ketone bodies can increase to 6 to 8 mM during a fast without causing hazardous acidosis [78].

Some experts on the ketogenic diet define nutritional ketosis as a blood ketone range from 0.5 to 3.0 mmol/L. Ketones in the blood can be measured by a small pin-prick blood test available over the counter [79].

However, increased ketone bodies in the blood can indicate diabetic ketosis. A blood test measuring the concentration of beta-hydroxybutyrate should be done [80].

Ketones in Urine

Ketonuria indicates an excess production of ketone bodies. It can be detected using at-home test kits that are most sensitive to acetoacetic acid [81].

Large amounts of ketone bodies in the urine may indicate diabetic ketoacidosis and can lead to diabetic coma [82].

Ketones in Breath

Acetone in the breath is associated with ketone bodies in the blood and can act as a predictor of diabetic ketosis [81].

The concentration of acetone in the breath is elevated in individuals with type 2 diabetes [83].

Supplementation

User Experiences

Ketone ester users reported initial symptoms of nausea and jitters. This was followed by an increased ability to focus on work and reduced hunger.

Success stories of the ketogenic diet describe it as a lifestyle, not a diet. These users also reported increased and prolonged energy levels, mental clarity, reduced cravings, and hunger.

Some users experienced the “keto flu” with bouts of nausea, cramping, and fatigue. However, if they persevered with the diet, these symptoms often subsided. Users recommend maintaining the diet for at least 2 weeks before your body adapts and enters nutritional ketosis.

Buy

Exogenous ketone bodies can be consumed in supplement form (salts, oils, or esters) to rapidly increase ketone availability in addition to, or as an alternative to the ketogenic diet. High-performance athletes such as professional cyclists use ketone supplements to support training and recovery to maximize performance [84].

You can also find ketones here:

Want More Targeted Ways to Enhance Brain Function?

If you’re interested in improving your cognitive function, we recommend checking out SelfDecode’s Limitless Mind DNA Protocol. It gives genetic-based diet, lifestyle and supplement tips that can help improve your cognitive function. The recommendations are personalized based on your genes.

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About the Author

Andrea McRae

MSc (Molecular Biology)

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