Exogenous Ketones: Aiding Keto Adaptation?

Exogenous ketone supplements are synthetic ketones that can be consumed orally. They are usually in the form of a drink and are marketed as a quick way to enter ketosis without having to follow a ketogenic diet. The ketogenic diet is a high-fat, very low-carb diet that encourages a metabolic state called ketosis, in which the body burns fat instead of carbohydrates as its primary source of energy.

Exogenous ketones are available as ketone salts or ketone esters. Ketone salts are ketones bound to a salt, usually sodium, potassium, calcium, or magnesium, and are the most common form of exogenous ketone supplements. Ketone esters are the purest form of ketones and are more effective but are less common and more expensive.

There is some evidence to suggest that exogenous ketones can be beneficial for people already following the keto diet, but research is limited. Exogenous ketones have been shown to increase blood ketone levels, reduce appetite, and improve mental performance and mood. However, they may not aid weight loss and athletic performance. In fact, some studies suggest that they may hinder weight loss and athletic performance.

Overall, while exogenous ketone supplements may offer some benefits, they are not a magic bullet for weight loss or improved athletic performance.

Exogenous ketones may help with athletic performance

Exogenous ketones are synthetic ketone bodies consumed as a supplement. They are available in two forms: ketone salts and ketone esters. Ketone salts are ketones bound to a salt, usually sodium, potassium, calcium, or magnesium, and are the most common form of exogenous ketones. Ketone esters are the purest form of ketones and are less common but more effective.

Exogenous ketones are often marketed as a quick way to achieve ketosis, a metabolic state where the body burns fat instead of carbohydrates for energy. While exogenous ketones can increase blood ketone levels, there is limited research on their effectiveness in improving athletic performance.

The Impact of Exogenous Ketones on Athletic Performance

Some studies suggest that exogenous ketones may improve athletic performance, particularly in elite and endurance athletes. During prolonged physical activity, the body may experience a lack of oxygen supply to the muscles, leading to increased lactic acid production, which can cause muscle soreness and weakness. Exogenous ketones act as an alternative energy source, reducing lactic acid production and potentially enhancing athletic performance.

However, the research on the impact of exogenous ketones on athletic performance is mixed, with some studies finding no effect or even impaired performance. One study found that cyclists who consumed exogenous ketones prior to a time trial experienced gut discomfort and a higher perception of effort.

Factors to Consider When Using Exogenous Ketones

It is important to note that the effects of exogenous ketones on athletic performance may depend on various factors, including the type of exercise, the duration of ketone supplementation, and individual differences. The length and composition of the ketogenic diet, as well as the type of exogenous ketone supplement, may also influence their effectiveness.

Additionally, exogenous ketones are not regulated by the Food and Drug Administration (FDA), and there are concerns about their safety, purity, and effectiveness. They can also be expensive, with a two-week supply costing around $50 or more.

While exogenous ketones may have the potential to improve athletic performance, particularly in endurance athletes, the current research is inconclusive. More studies are needed to fully understand their effectiveness and determine any potential benefits for athletes.

Exogenous ketones may help with cognitive function

Some studies have found that exogenous ketones do not improve cognitive performance. For example, a study on healthy college-aged males found that ketone salts did not improve cognitive performance during a dual-stress challenge. Similarly, another study found that exogenous ketone salts did not improve cognitive responses after a high-intensity exercise protocol in healthy college-aged males.

On the other hand, some studies suggest that exogenous ketones may improve cognitive function. For instance, a study on mice found that exogenous ketone supplementation accelerated recovery following a treadmill endurance test. Another study found that exogenous ketone supplementation may decrease appetite, which could indirectly improve cognitive function by preventing blood sugar spikes and crashes.

Furthermore, exogenous ketones have been found to have neuroprotective effects. For example, a review of the literature found that exogenous ketone supplementation may be an effective treatment for psychiatric diseases. Additionally, exogenous ketones have been found to improve cognitive function in patients with mild cognitive impairment and Alzheimer's disease.

While the research is mixed, exogenous ketones may help with cognitive function by improving cognitive performance, accelerating recovery, decreasing appetite, and providing neuroprotective effects. However, more research is needed to fully understand the effects of exogenous ketones on cognitive function.

Exogenous ketones may help with weight loss

Exogenous ketones are supplements that can help a person achieve ketosis while being slightly less strict about their diet. Ketosis is a metabolic state in which the body burns fat instead of carbohydrates as its primary source of energy. The process of burning fat results in the production of ketones, which the body uses for energy when carbohydrates are in short supply.

Exogenous ketones can be a useful tool for people who want to transition into ketosis without necessarily following a ketogenic diet. However, it is important to note that exogenous ketones are not a substitute for a ketogenic diet and will not induce or maintain ketosis alongside an unsuitable diet.

Appetite Suppression

Exogenous ketone supplements have been shown to decrease appetite, which may aid weight loss by reducing calorie intake. In a study involving 15 people of normal weight, those who drank a beverage containing ketone esters experienced 50% less hunger after an overnight fast than those who drank a sugary beverage. This effect was attributed to lower levels of the hunger hormone ghrelin. However, ketone supplements may not affect appetite as much in people who have eaten a meal beforehand, as studies have shown that ketone levels are higher in those who consume the supplements on an empty stomach.

The Case Against Exogenous Ketones for Weight Loss

Despite the potential appetite-suppressing effects, the weight loss benefits of exogenous ketones are unknown, and some evidence suggests that they may even hinder weight loss efforts.

Ketones Inhibit Fat Breakdown

The purpose of the ketogenic diet for weight loss is to produce ketones from stored fat as an alternative fuel source. However, if ketone blood levels become too high, the blood can become dangerously acidic. To prevent this, the body has a feedback mechanism that slows down ketone production. As a result, taking ketone supplements may prevent body fat from being used as fuel, at least in the short term.

Ketones Contain Calories

Ketone supplements can be a source of calories, with about four calories per gram, the same as carbohydrates or protein. To maintain a state of ketosis, multiple servings of ketone supplements are required throughout the day, which can be costly. Additionally, ketone supplements are bound to salts, and consuming too much can lead to side effects such as stomach discomfort and diarrhea.

Safety

Exogenous ketone supplements are generally considered safe and effective for increasing ketone body concentrations, but the long-term effects are unknown. Reported side effects are more common with ketone salts than ketone esters and include nausea, stomach discomfort, and a poor aftertaste.

While exogenous ketones may help induce ketosis in people who desire weight loss, they are not a substitute for a ketogenic diet. The weight loss benefits of exogenous ketones are currently unknown, and some evidence suggests that they may hinder weight loss efforts. Therefore, ketone supplements cannot be recommended for weight loss at this time.

Exogenous ketones may help with appetite suppression

Exogenous ketones are supplements that can help a person achieve ketosis while being slightly less strict regarding what they eat. Ketone supplements have been shown to decrease appetite, which may help with weight loss by eating less.

In a study conducted on 15 people of normal weight, those drinking a beverage containing ketone esters experienced 50% less hunger after an overnight fast than those drinking a sugary beverage. This appetite-suppressing effect was attributed to lower levels of the hunger hormone ghrelin between two and four hours after drinking the ketone ester drink.

However, ketone supplements may not affect appetite as much in people who have had a meal beforehand. Studies have observed higher blood ketone levels in those who didn't eat a meal before taking a ketone supplement compared to those who did. Since it's the elevated ketones that are associated with reduced appetite and lower ghrelin levels, ketone supplements may only be beneficial during a fast.

In other words, taking a ketone supplement after a meal will still raise blood ketone levels but not as high as if you fasted, suggesting that your body is using fewer ketones as fuel since there is more available glucose from the carbs. One small study found that exogenous ketone supplements reduced appetite for over four hours, which may be promising for weight loss. However, additional studies are needed before ketone supplements can be recommended for appetite control.

Exogenous ketones may help with inflammation

Exogenous ketones, specifically R-βHB, modulate intracellular signalling cascades such as the cellular redox ratios of NAD+/NADH, the activity of NAD-dependent deacetylases SIRT1 and SIRT3, and promote a robust mitochondrial environment. This environment may reduce oxidative stress and inflammation.

The oxidation of R-βHB has been shown to reduce oxidative stress susceptibility through a variety of proposed mechanisms. R-βHB can function as a direct or indirect antioxidant by facilitating reduction reactions, donating electrons to reactive oxygen species, and by acting as a trigger to up-regulate mitochondrial signalling proteins.

The consumption of R-βHB changes cellular ratios of NAD+/NADH, which results in the activation of signalling proteins such as NAD-dependent deacetylases (SIRT1, SIRT3) that are known to increase the activity of antioxidants such as heme oxygenase 1, superoxide dismutases, and catalases.

Additionally, it has been speculated that the mitochondrial consumption of R-βHB activates nuclear factor-erythroid 2-related factor-2 (NRF2), which serves as a mechanism for the up-regulation of endogenous antioxidants.

R-βHB has been shown to directly inhibit histone deacetylase enzymes in a dose-dependent manner and thus promote gene expression and enhanced modulation of the immune system and global reduction in oxidative stress.

However, it is important to note that the majority of the literature examining R-βHB as a signalling metabolite has been performed from endogenous R-βHB production achieved through nutritional ketosis or cell culture and mouse models using exogenous R-βHB.

To the author's knowledge, only one study has attempted to report on the effects of exogenous ketones and the mitigation of oxidative stress/inflammation. McAllister et al. supplemented firefighters for seven days with either a placebo or racemic ketone salt mixture. The findings showed that exercising in personal protective equipment did result in oxidative stress, but exogenous ketone supplementation had no effect on this response. However, a limitation to the investigation was the lack of blood R-βHB analysis throughout the study duration.

In summary, exogenous ketones may help with inflammation by reducing oxidative stress and up-regulating antioxidant defence mechanisms. However, more research is needed to confirm these effects, especially in human trials.

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