Exogenous Ketones
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Beta-glucan versus psyllium for lowering LDL, PFAS reduction, creatine and caffeine, urolithin A, exogenous ketones, IVF, Botox, and sauna.
In this clip, Dr. Ben Bikman highlights berberine, apple cider vinegar, and ketones—supplements that lower glucose spikes and support metabolic...
In this clip, Dr. Dominic D'Agostino explains the rationale behind the development and use of exogenous ketones.
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Rhonda Pollution Fiber Sauna Caffeine Supplements Urolithin A Creatine Reproductive Health Exogenous Ketones Cholesterol Ubiquinol PfasBeta-glucan versus psyllium for lowering LDL, PFAS reduction, creatine and caffeine, urolithin A, exogenous ketones, IVF, Botox, and sauna.
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In this clip, Dr. Ben Bikman highlights berberine, apple cider vinegar, and ketones—supplements that lower glucose spikes and support metabolic...
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In this clip, Dr. Dominic D'Agostino explains the rationale behind the development and use of exogenous ketones.
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The classic ketogenic diet is high in fat and low in protein and carbohydrates. The ease of following a ketogenic diet varies from person to person, dependin...
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Weight loss can look successful on the scale while concealing whether the body lost fat or muscle. Researchers tested whether raising ketone levels during treatment with semaglutide, the weight-loss drug sold under brand names such as Ozempic and Wegovy, could protect skeletal muscle without interfering with fat loss.
Male mice with diet-induced obesity and poor blood sugar control entered a three-week rapid-weight-loss experiment as they switched from a high-fat diet to regular food under calorie-deficit conditions. They were randomly assigned to inactive saline control injections, semaglutide, or semaglutide plus a ketone ester that raised blood ketones to levels that can occur naturally during fasting.
- The ketone ester preserved lean tissue during semaglutide-driven weight loss while allowing the same fat loss. As a result, the group receiving the combined treatment lost less weight overall but potentially retained more total muscle mass.
- Skeletal muscle weighed more and muscle fibers were larger with ketone cotreatment than with semaglutide alone.
- The ketone ester also protected grip strength and improved exercise endurance.
- Differences in total calorie intake did not explain muscle preservation. At the times when muscle loss was greatest, semaglutide-only mice consumed more total calories than the combination group.
Muscle requires a steady supply of usable energy to maintain and rebuild its proteins. During rapid weight loss, ketones can serve as an alternative fuel when energy from food is limited. In the semaglutide-only group, levels of several components of the cellular machinery for processing ketones and generating energy fell, while several gene signals tied to muscle protein breakdown rose. The ketone ester preserved these molecular patterns. Keeping ketone fuel available may therefore help muscle meet its energy needs and avoid shifting toward tissue breakdown. However, this remains a mechanistic interpretation rather than proof of the precise pathway.
Taken together, ketone cotreatment allowed semaglutide-treated mice to lose fat while retaining more muscle mass, strength, and endurance. The divergence suggests that the composition of rapid weight loss may depend on whether muscle can preserve the flexibility to switch toward alternative fuels when energy intake falls.
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People with type 2 diabetes often experience sharp rises in blood sugar and blood fats after eating, changes that increase the risk of heart disease over time. Researchers investigated whether drinking a ketone supplement before a meal could improve these metabolic swings.
The research consisted of two carefully controlled crossover studies in adult patients with type 2 diabetes who were treated with lifestyle changes or metformin. In the first study, 14 participants drank one of three beverages 30 minutes before a standardized meal: a ketone monoester, a ketone salt, or a placebo. In the second study, 10 participants consumed a placebo or different doses of the ketone monoester at varying times before an oral glucose tolerance test (OGTT), a standard test in which a glucose drink is consumed to measure how the body processes sugar over time.
- Compared with placebo, a single 30 g dose of ketone monoester reduced post-meal blood glucose exposure by 36%, while ketone salts produced a smaller 22% reduction.
- The ketone monoester lowered the peak blood sugar level, whereas ketone salts mainly delayed the rise without reducing the peak.
- Both ketone supplements strengthened the normal post-meal drop in circulating non-esterified fatty acids (fats released from body fat stores) that is typically blunted in patients with type 2 diabetes because their fat tissue does not respond well to insulin. Ketone monoesters reduced their levels by about 51%, and ketone salts by roughly 37%, compared with placebo.
- Only the ketone monoester clearly reduced post-meal triglycerides, lowering overall triglyceride exposure by about 53%.
- Both supplements lowered ghrelin, a hunger-stimulating hormone, and especially ketone salts increased the LEAP-2/ghrelin ratio, a signal associated with fullness and appetite suppression. Reported hunger and later food intake were unchanged.
- During the OGTT, 20 g and 40 g doses of ketone monoester reduced glucose exposure by 29% and 38%, respectively, while 10 g had no clear effect.
- Timing mattered: taking 20 g 30 or 60 minutes before glucose intake reduced glucose exposure by 29% and 25%, respectively, whereas taking it at the same time produced no clear benefit.
- No serious side effects occurred. Digestive symptoms and mild, transient electrolyte changes were more common with ketone salts, and taste was frequently described as unpleasant.
To explore why blood sugar responses improved, a labeled form of glucose was added as a tracer to the test meal to track how glucose entered the bloodstream during digestion. The ketone monoester slowed the entry, suggesting slower movement of food through the gastrointestinal system or slower absorption. Ketone salts did not slow glucose entry, indicating that additional mechanisms may be involved. Across all interventions, glucose production by the liver and glucose uptake by tissues followed similar patterns, suggesting these processes did not drive the improvements.
Overall, the findings suggest that taking a ketone supplement before meals may offer a practical strategy to improve metabolic health in people with type 2 diabetes. Larger and longer studies will be needed to confirm long-term safety, real-world effectiveness, and whether these improvements translate into fewer diabetes-related complications. In this clip, Dr. Dominic D'Agostino shares tactical tips for ketone supplementation.