Ketone bodies are extremely energy-efficient as fuel. They make more ATP than sugar. As a primary fuel source, studies suggest that ketone bodies can improve weight loss, blood sugar levels, and epilepsy. Limited evidence supports a keto diet for athletic performance and boosting cognitive function. Read on to learn more.
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 .
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 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 .
Finally, the blue cheese gets its sharp smell from a group of methyl ketones .
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 fatty acids. When we say ketone bodies, we refer to [11, 12]:
- Acetoacetic acid (AcAc)
- Beta-hydroxybutyric acid (BHB) – not technically a ketone
Ketone bodies act as an alternate energy source when carbs are not available because of fasting or prolonged exercise .
Beta-hydroxybutyric acid and acetoacetate easily pass through membranes and are a source of energy for the body and the brain .
Mechanism of Action
In the absence of carbohydrates and when glycogen (glucose) stores are depleted, fats move to the liver. Fats are broken down into glycerol and fatty acid molecules. Fatty acids are then converted into ketone bodies by a process called ketogenesis .
Ketogenesis primarily occurs in the mitochondria of liver cells .
Acetoacetate is the precursor to the other 2 ketone bodies, acetone and beta-hydroxybutyric acid .
Ketone bodies move to active tissues (muscle or brain) to be converted to acetyl-CoA by a process called ketolysis. Acetyl-Coa is further used to create ATP (ATP = energy) [11, 17].
Beta-hydroxybutyric acid is the most common ketone body in the blood after ketogenesis .
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 [18, 13].
However, it can also be caused by starvation or diabetes (diabetic ketoacidosis), where it can be detrimental to an individual’s health [13, 19].
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
- Suppressed appetite
- Short-term fatigue
- A short-term decrease in exercise performance
- Short-term decreased focus and energy
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 .
A ketogenic diet brings the body into a state of nutritional ketosis, where the body uses fat instead of carbs, for energy .
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 carbs 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 available as an alternative or addition to the ketogenic diet [21, 22].
Health Benefits of Ketone Bodies
Possibly Effective For
1) Weight Loss
According to a meta-analysis of 13 studies with over 1.5k people, those assigned to a low-carb keto diet lost more weight than those on a low-fat diet over the long term (>12 months) .
In addition, studies have shown that a keto diet improved risk factors for heart disease often found in obesity, including high blood pressure and unhealthy cholesterol levels [24, 25, 26].
2) Diabetes/Blood Sugar Control
A small study of 84 obese patients and those with type 2 diabetes highlighted that a low-carb diet led to improved glycemic control and reduced or eliminated medication use .
In another pilot study with 25 overweight diabetics, those assigned to a keto diet improved their blood sugar control and lost more weight compared to those on a conventional, low-fat diabetes diet online program 
Also, according to a study of 64 healthy obese people, a keto diet improved body weight, BMI, blood sugar, and cholesterol .
Studies suggest that using ketone bodies as fuel may help stabilize blood sugar levels in obese people and reduces cellular dependency on glucose. This prevents health issues resulting from abnormally high or low blood sugar levels [30, 31].
Studies suggest that ketone bodies may have anti-seizure, anticonvulsant, and neuroprotective properties .
It is currently unknown whether these effects are due to elevated ketone bodies, reduced glucose, or a combination of these effects .
The ketogenic diet has been used since the 1920s as a treatment for certain types of epilepsy. It’s an alternative for people not responding well to anticonvulsants .
A review of 11 trials with 778 people (712 children and adolescents and 66 adults) found that those on a keto diet reached seizure freedom in about 55% of cases .
Insufficient Evidence For
4) Reducing Food Cravings And Appetite
Craving specific foods may be why many weight-loss diets fail .
A study of 34 overweight or obese people with prediabetes or diabetes showed that a reduced (medium and low) carbohydrate diet that uses ketone bodies as fuel reduced the urge to eat carbs and sweets. Ketone bodies also increase dietary restraint .
Another study of over 260 obese adults found that compared to a low-fat diet, a low-carb diet decreased urges for carbohydrates and starches, and hunger was less of a bother .
After 3 days of a low-carbohydrate/high-fat diet, GLP-1 hormone levels increased in 9 healthy young men . This hormone signals the brain that enough food has been eaten .
Larger well-designed studies are needed to confirm these findings.
5) Athletic Performance
Ketone drinks (ketone esters) consumed by 39 high-performance athletes in 5 separate studies seemed to improve physical endurance .
Ketone bodies provide a constant supply of energy to the brain. Research ..suggests that 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 .
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 .
One study in cyclists, however, suggests that people on a ketogenic diet may perform worse at activities with high intensity .
6) High Blood Pressure
A study of 146 overweight and obese people found that a low-carb diet was more effective for lowering blood pressure than a low-fat diet .
More studies are needed to confirm this and to check if it applies to all people with high blood pressure irrespective of their body weight.
A study in 96 overweight women with migraines found that keto diet reduced the frequency of attacks and days with headache .
Clinical data obtained from 150 people, suggests that the keto diet may be effective in preventing migraines. Scientists think that the keto diet may contribute to restore brain excitability and metabolism and to counteract neuroinflammation in migraine, although the precise mechanism is still unclear .
Further research is needed to establish whether the absence/restriction of dietary carbs, the presence of ketone bodies, or both, play a role in migraine prevention.
Keto diet seems to be effective in epilepsy. But what about other types of seizures?
In a study of 24 adults with seizures, seizures resolved in 11 out of 14 people who were on a ketogenic diet .
However, this is one small-scale human study. It requires confirmation. In addition, safety and efficacy need to be established with randomized placebo-controlled trials.
Numerous animal studies that administered exogenous ketone bodies showed a protective effect against seizures .
9) Cognitive Function
In a study of 152 patients diagnosed with Alzheimer’s disease, the consumption of an oral ketone supplement improved cognition .
A low-carbohydrate diet improved the memory of individuals in a study of 23 seniors with mild cognitive impairment .
Animals with brain trauma that used ketone bodies as fuel had improved cognitive and motor function post-trauma .
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 .
Larger, well-designed studies are needed to confirm the effect of a keto diet on cognitive function.
Cell studies have found that ketone bodies have an 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 .
Animals fed a ketogenic diet had enhanced the mitochondrial antioxidant status and their mitochondrial DNA was protected from oxidant-induced damage .
Fewer free radicals mean less tissue inflammation [55, 56, 57].
In fact, both animal and human studies have found that the transition from glucose to ketone body metabolism turns on anti-inflammatory mechanisms [58, 59].
Cell studies have found that ketogenesis turns on PPAR-gamma, a known anti-inflammatory molecule. It also inhibits the inflammatory markers (NF-kB, TNF-alpha, COX-2) [60, 61, 62].
Furthermore, ketone bodies may activate the Nrf2 pathway, increasing mitochondrial glutathione [63, 54].
In animal models or multiple sclerosis, a ketogenic diet had a protective effect on brain inflammation .
Side Effects & Precautions
The ketogenic diet is relatively safe (when done right).
The side effects of using ketone bodies as a fuel include [65, 66, 31, 67, 68]:
- Muscle cramps (can be reduced by increasing fluid intake, consumption of allowed vegetables, and a mineral supplement )
- Fatigue (reduced energy due to lack of quick sugars)
- Lower blood glucose levels (caution in diabetic patients)
- Mineral deficiency
- Brain fog
- Flu-like symptoms
- Keto rash (Prurigo pigmentosa)
Many of these negative effects will disappear once your body adjusts to the ketogenic diet.
Studies suggest that a long-term ketogenic diet may increase the risk of kidney stones, but this can usually be counteracted by drinking plenty of water and supplementing with citrate .
Work with your doctor or nutritionists to make sure your keto diet is healthy and well balanced, and contains all important nutrients. It’s best if the keto diet is implemented under careful medical supervision.
Read more about important nutrients on a keto diet here.
Individuals with diabetes should be cautious of diabetic ketoacidosis. Diabetic ketoacidosis increases the pH of blood when attempting to use ketone bodies as fuel .
Individuals who lack PPAR-alpha may not efficiently use ketone bodies as fuel .
There is insufficient evidence that a keto diet is safe in pregnancy and lactation. Avoid using it unless your doctor tells you otherwise.
Ketone Levels in the Body
Ketones in Blood
Ketone bodies greatly increase in the blood of those on a low-carbohydrate, high-fat diet .
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 .
However, increased ketone bodies in the blood can indicate diabetic ketosis. In that case, a blood test measuring the concentration of beta-hydroxybutyrate should be done .
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 .
Large amounts of ketone bodies in the urine may indicate diabetic ketoacidosis which can lead to diabetic coma .
Ketones in Breath
Acetone in the breath is associated with ketone bodies in the blood and can act as a predictor of diabetic ketosis .
The concentration of acetone in the breath is elevated in individuals with type 2 diabetes .
Ingestible ketone supplements and beverages are an alternative or addition to the ketogenic diet [21, 22]. 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 [21, 22].
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 [78, 22].
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 .
Remember, always speak to your doctor before taking any supplements, because they may interfere with your health condition or your treatment/medications!