A recent study aimed to systematically review the available evidence and conduct a meta-analysis of studies reporting on exogenous ketones and blood glucose. Randomized and nonrandomized trials of any length that reported on the use of exogenous ketones were used for the meta-analysis. 

Effects of Exogenous Ketones

The study calculated raw mean differences in blood beta-hydroxybutyrate (BHB) and glucose in two different ways:

• Before acute ingestion of exogenous ketones
• After acute ingestion of exogenous ketones

Participants who ingested exogenous ketones showed increased blood BHB and decreased mean blood glucose. Compared to placebo groups, blood BHB increased and blood glucose decreased. Across both analyses, significantly greater effects were seen in groups with ketone monoesters.

Why are Exogenous Ketones Important?

Exogenous ketones are important because they may be able to help the body achieve natural ketosis without difficult dietary changes. Natural ketosis is being studied for potentially life-changing effects on conditions including epilepsy and gastrointestinal disorders.

Administration of exogenous ketones may also have a positive effect on performance, both athletically and academically. Current research suggests ketosis may help produce more Adenosine triphosphate (ATP) molecules from oxygen. ATP molecules provide energy that drives processes in living cells, like muscle contraction and nerve impulse propagation.

Increased Blood BHB & Ketone Supplementation

Evidence from the meta-analysis study suggests that acute ingestion of exogenous ketones leads to increased blood BHB and decreased blood glucose. Limited evidence on prolonged ketone supplementation was found.

The results of this recent study and other similar meta-analyses suggest that ketone supplementation is worthy of further consideration.

Research at Biofortis

Biofortis is dedicated to protecting consumer health worldwide by delivering a wide range of testing and consultancy services to the food, supplement, and nutrition industries. Biofortis supports this mission in two ways—through clinical trials and sensory and consumer insights testing. We specialize in clinical research targeting foods, ingredients, and dietary supplements that affect body structures, function, and overall health. Contact us with any clinical trial or scientific consulting needs.

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Since then, Ketogenic diets have spread to most places around the world. Ketogenic diets are high-fat, adequate-protein, low-carbohydrate diets that are used mainly to treat hard-to-control epilepsy in children. The idea behind the diet is forcing the body to burn fats rather than carbohydrates. A lack of carbohydrates forces the liver to convert fats into ketone bodies and fatty acids, which replace glucose as an energy source.

While the body can be forced to create ketones, they can also be introduced externally.

What are Exogenous Ketones?

The term exogenous means coming from outside the body. For Ketones, this means direct ketone supplementation or indirect via supplements that have ketone precursors.

Exogenous ketones can be found as oral supplements. Ketogenic diets and exogenous ketones have many similarities but key differences when it comes to application.

Nutritional Ketosis

Clinicians and other medical practitioners are increasingly interested in the proposed performance and therapeutic benefits of nutritional ketosis. Nutritional ketosis is defined as a nutritionally induced metabolic state resulting in higher blood β-hydroxybutyrate (BHB) concentrations. 

Body tissues readily metabolize ketone bodies. In turn, the ketone bodies regulate metabolism and signals in both a systemic and tissue-specific manner. During fasting, starvation, or undergoing a strict ketogenic dietary regimen, endogenous synthesis of ketone bodies is amplified resulting in a state of natural ketosis. 

Natural ketosis results in a number of potential benefits across health, disease, and performance.  Therefore, interest in how to produce the same effect with supplements, which don’t require the intense dietary regimen or fasting, is of interest. 

Consuming an exogenous ketone supplement will lead to a rapid increase in circulating ketone bodies, which produces a similar apparent metabolic state.  However, understanding if the ketosis produced by exogenous supplementation leads to the same health benefits as natural ketosis is under investigation. 

Ketogenic Diets & Natural Ketosis

Natural ketosis has long been used to manage convulsions. Texts from hundreds of years ago reference the anticonvulsant effects of fasting. Medical records from the 19th and 20th centuries describe ketogenic-type diets that benefit patients with metabolic disorders.  However, these diets are strict in their requirements and not considered pleasant by many people, as they can limit protein and many food choices.

A ketogenic diet can be defined as any diet that amplifies ketogenesis, not just the strict therapeutic ketogenic diets (KDs) found in the early 20th-century medical literature. There are now a number of defined ‘alternative’ keto diets like

• The medium-chain triglyceride ketogenic diet
• The Modified Atkins Diet
• The Low Glycemic Index Treatment Diet.

The approach of each diet induces a state of natural ketosis but is formulated with more liberal allowances of protein to appeal to more people. 

Interest in the performance of natural ketosis has rapidly expanded. Researchers continue to look at both natural ketosis and exogenous ketosis, as well as comparing the effects of each, for better understanding of how ketogenesis can be used in the clinic to promote health and performance. 

Research at Biofortis

Biofortis is dedicated to protecting consumer health worldwide by delivering a wide range of testing and consultancy services to the food, supplement, and nutrition industries. Biofortis supports this mission in two ways—through clinical trials and sensory and consumer insights testing. We specialize in clinical research targeting foods, ingredients, and dietary supplements that affect body structures, function, and overall health. Contact us with any clinical trial or scientific consulting needs.

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There has been a long-standing interest in developing ingestible forms of ketone bodies that have recently led to the commercial availability of exogenous ketone supplements (EKS). EKS like ketone salts and esters facilitate nutritional ketosis. 

Studies have suggested the beneficial effects of EKS on endurance performance, and recovery. The potential benefits for athletic performance have been a key area of modern research.

Exogenous Ketone Supplements

Exogenous ketones refer to direct ketone supplementation or supplements that have ketone precursors. Exogenous ketones are sold as supplements. Ketogenic diets and exogenous ketones have many similarities but research is needed to ensure they have the same health and therapeutic outcome effects.

Achieving ketosis without supplements, i.e., through dietary changes, is called natural ketosis.  Natural ketosis takes prolonged periods of dieting or fasting, and the dietary changes are generally extreme.  This is why engaging in a dietary regimen to achieve natural ketosis should be done only under supervision by a medical and/or nutritional professional. 

Using supplements, or exogenous ketones, the achieve ketosis seeks to eliminate dietary restrictions, thereby helping the body achieve a state of ketosis without all the work.

Natural ketosis has shown potential for aiding such functions as athletic performance. Supplementation with ketones, if it provides the same benefits, would allow a quick way of achieving ketosis without major alterations in a person’s lifestyle.

Important Exogenous Ketone Information

Ketone bodies such as acetoacetate and β-hydroxybutyrate (BHB) have wide-ranging metabolic and molecular effects on organs including the brain, heart, and skeletal muscle. In particular, research data has suggested potential benefits to athletes in terms of performance and recovery.

Anecdotal reports and increased commercial availability of ingestible forms of exogenous ketone supplements have amplified interest in increased interest in human exercise studies to better understand and confirm the effects of ketone supplements on athletic performance.

However, most studies on exogenous supplements in various athletic contexts to date have failed to observe benefits to performance or recovery. Some evidence for an effect on biochemical mechanisms underlying performance function has been reported. Whether the changes lead to an actual observable clinical effect under the right conditions or with certain amounts of consumption remains to be seen. Future research on whether there are contexts in which exogenous ketone supplements are effective is greatly needed.

Research at Biofortis

Biofortis is dedicated to protecting consumer health worldwide by delivering a wide range of testing and consultancy services to the food, supplement, and nutrition industries. Biofortis supports this mission in two ways—through clinical trials and sensory and consumer insights testing. We specialize in clinical research targeting foods, ingredients, and dietary supplements that affect body structures, function, and overall health. Contact us with any clinical trial or scientific consulting needs.

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Since that time, numerous studies have explored the metabolic influence of diet on aerobic and anaerobic performance to determine if major shifts in substrate metabolism translate to altered performance outcomes. 

Many modern-day dietary research studies have primarily focused on ketogenic diets and the effects they may have on aerobic athletic performance. The major issue with these lifestyle modifications, however, is the difficulty of maintenance or compliance with the dietary regimen.

What is Ketosis?

Ketosis is defined as elevated circulating levels of ketone bodies. Traditionally ketosis has been achieved through fasting or a ketogenic diet.

Bodily tissues readily metabolize ketone bodies. In turn, the ketone bodies regulate metabolism and generate local, tissue-specific, and systemic signals that can have other effects. In instances of fasting, starvation, or ketogenic diets, endogenous synthesis of ketone bodies is amplified resulting in a state of natural ketosis. 

Exogenous oral ketone supplements rapidly elevate circulating ketone bodies, with the intention to mimic a metabolic state similar to natural ketosis obtained via dietary changes. Ketosis has potential effects across health, disease, and performance, which are being actively studied.

Ketogenic Supplementation & Running

One of the most popular methods of exercise is running. Ketogenic diets have been used with running and other aerobic exercise regimens to assess if there is an effect on performance. Some evidence suggests an effect, although more research is needed.  Still, recent interest has arisen to develop ketone bodies that can be exogenously administered without dietary carbohydrate restriction.  

The emergence of commercially-available exogenous ketone supplements has led to many studies focused on the effect of these supplements on running performance. One recent study reported the effects of strict adherence to a ketone supplement program on people undergoing a 5 km run. Data showed no significant effect of the supplement when administered before or close to the run.

Achieving and maintaining a state of natural ketosis is extremely difficult without professional medical oversight and assistance. While ketone supplements may not be a ‘miracle drug’ when it comes to performance, longer-term studies need to be conducted, particularly on people who strictly adhere to ketone diets or supplement administration.

Research at Biofortis

Biofortis is dedicated to protecting consumer health worldwide by delivering a wide range of testing and consultancy services to the food, supplement, and nutrition industries. Biofortis supports this mission in two ways—through clinical trials and sensory and consumer insights testing. We specialize in clinical research targeting foods, ingredients, and dietary supplements that affect body structures, function, and overall health. Contact us with any clinical trial or scientific consulting needs.

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One area of recent investigation for psychiatric disorder treatment is inducing ketogenesis, either vis dietary changes (i.e., natural ketosis) or the use of supplements (i.e., endogenous ketone supplementation). Ketone diets and exogenous ketone supplementation look to achieve a state of natural ketosis (NK). During a state of NK, certain ketone bodies replace carbohydrates as fuel to the brain and other organs. 

Ketones & Psychiatric Help

Ketogenic diets feature high-fat, adequate-protein, and very low carbohydrate foods and beverages, and from historical accounts may have an alleviating effect on some psychiatric conditions. Research has suggested bioenergetics and ketosis may have effects on neuronal activity, neurotransmitter balance, and inflammatory processes.  

Unfortunately, strict patient compliance with ketogenic diets is necessary to achieve therapeutic ketosis. Adherence to these diets can be difficult or impossible for most people. Ketogenic diets typically need to be overseen by a medical professional, which can be unaffordable or even unavailable for some people.

Potential Psychiatric Benefits of Ketones

A ketogenic diet could potentially lead to numerous benefits for patients suffering from certain psychiatric disorders. The fact that an unmonitored keto diet would likely have low compliance makes it difficult to implement as a successful intervention, or to study in a larger-scale research setting. Strict adherence and oversight are required for a keto diet to succeed, something that can be very hard to achieve in clinical practice or the general population.

The potential for positive effects of a ketogenic diet on psychiatric disorders, however, has led to many smaller-scale studies. Different psychiatric conditions may react differently to ketogenic diets, which is why many modern studies focus on specific conditions.  Psychiatric disorders that are under investigation with ketogenic diets include:

• Anxiety disorders

• Major depressive disorder
• ADHD
• Bipolar disorder
• Schizophrenia

Research at Biofortis

Biofortis is dedicated to protecting consumer health worldwide by delivering a wide range of testing and consultancy services to the food, supplement, and nutrition industries. Biofortis supports this mission in two ways—through clinical trials and sensory and consumer insights testing. We specialize in clinical research targeting foods, ingredients, and dietary supplements that affect body structures, function, and overall health. Contact us with any clinical trial or scientific consulting needs.

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The effects of nutritional ketosis through diet or supplementation are currently being researched.  for potential effects on GAD and other specific anxiety disorders. Ketone diets and exogenous ketone supplementation look to achieve a state of natural ketosis (NK). During a state of NK, certain ketone bodies replace carbohydrates as fuel for the brain and other organs. 

Potential Benefits of Ketogenic Diets

Ketogenic diets feature high-fat, adequate-protein, and very low-carbohydrate foods and beverages that may have an alleviating effect on psychiatric disorders. Research has suggested bioenergetics and ketone metabolism are involved with neuronal activity, neurotransmitter balance, and inflammatory processes.  Whether manipulation of ketone metabolism via diet or supplementation can lead to changes in these functions is of interest to researchers. 

Achieving natural ketosis normally takes a prolonged period of dieting, and implementation of a ketogenic diet should be overseen by a medical and/or nutritional professionals. Exogenous ketones seek to eliminate dietary restrictions and help the body achieve natural ketosis without all the extensive dietary changes.

Natural ketosis has shown potential for improving athletic performance. Supplementation of ketones is under investigation as a quick way of achieving a state similar to natural ketosis without requiring dramatic alteration of a person’s lifestyle.

Ketones & Anxiety

Recent research has shown limited benefit of ketone supplementation in people with some psychiatric disorders. This has increased interest in further researching exogenous ketone supplements as a potential therapy for selected psychiatric disorders. 

A state of natural ketosis can be hard to achieve and regulate, however, making medical oversight a necessity in any therapeutic program. Research exploring the effects of exogenous ketones on the metabolic processes that underlie psychiatric disorders is ongoing. 

The current state of ketone research for both physiological and psychological use looks promising but is in its early stages.

Research at Biofortis

Biofortis is dedicated to protecting consumer health worldwide by delivering a wide range of testing and consultancy services to the food, supplement, and nutrition industries. Biofortis supports this mission in two ways—through clinical trials and sensory and consumer insights testing. We specialize in clinical research targeting foods, ingredients, and dietary supplements that affect body structures, function, and overall health. Contact us with any clinical trial or scientific consulting needs.

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