The BHB research library.

In fasting obese subjects, infused ketones raised total ketone levels by 47 to 92 percent and reduced endogenous ketone production to 67 to 90 percent of control, showing that ketone bodies inhibit their own production.

Sodium DL-hydroxybutyrate infusion increased plasma leucine concentration and turnover and decreased glucose concentration and turnover in fasted patients, and this response was not affected by hip replacement surgery.

In fasting normal subjects, ketone body production and concentration rise markedly early and begin to plateau after about 5 days, and insulin-deprived type I diabetic patients showed no ketone removal defect specific to diabetes.

D-beta-hydroxybutyrate infusion in septic patients decreased lipolysis and glucose production but did not decrease leucine oxidation, so it had no beneficial effect on protein metabolism as measured with leucine.

Oral DL sodium beta-hydroxybutyrate raised beta-OHB in blood, cerebrospinal fluid and brain in two infants, demonstrating effective uptake across the blood-brain barrier.

The review states that ketones can provide as much as 70 percent of the brain's energy needs and that cerebral ketone uptake increases significantly in acute brain injury, supporting exploration of ketone supplementation in traumatic brain injury.

A single dose of up to 714 mg/kg of the ketone monoester raised plasma beta-hydroxybutyrate to 3.30 mM within 1 to 2 hours and was generally well tolerated over 5 days of three-times-daily dosing.

Dietary 1,3-butanediol and ketone ester prolonged survival in mice with systemic metastatic cancer by 51 and 69 percent respectively (p < 0.05).

The article states that ketone ester-induced ketosis improves mitochondrial metabolism and prevents or delays AD-like changes in animal models, and argues that its effect on AD biomarkers in people with early preclinical disease should be tested.

In a single patient with Alzheimer's disease dementia, 20 months of oral ketone monoester was well tolerated and was followed by marked improvement in mood, self-care and cognitive performance that tracked plasma beta-hydroxybutyrate levels.

In 39 high-performance athletes, ketone ester-induced ketosis improved physical endurance by altering fuel competition, decreasing muscle glycolysis and plasma lactate and increasing intramuscular triacylglycerol oxidation.

The review reports that published trials show moderate nutritional ketosis has a modest beneficial effect on cognition in mild-to-moderate Alzheimer's disease and mild cognitive impairment.

With constant high glucose, the ketone ester drink raised postexercise muscle glycogen by 50 percent compared with the control drink (246 versus 164 mmol glycosyl units per kilogram dry weight, P < 0.05).

The authors hypothesize that raising ketone body levels will extend human life span and that caloric restriction extends life span at least partly through ketones, and report that d-beta-hydroxybutyrate extends life span in C. elegans cultures.

The abstract contains no findings and only directs the reader to the highlighted article on the effects of a dietary ketone ester in a 3xTgAD mouse model of Alzheimer's disease.

The review identifies inflammasome modulation, antioxidation and possible mTOR influence as mechanisms by which ketones might help treat inflammatory skin diseases, and it reports no clinical results.

The review explains that ketone esters allow acute beta-hydroxybutyrate ingestion that produces nutritional ketosis without restrictive diets, with initial reports suggesting altered exercise metabolism and improved performance.

The review concludes that, at the time of writing, no data suggest that ingesting ketone bodies during exercise improves athletes' performance where evidence-based nutritional strategies are applied appropriately.

The review finds contrasting evidence on whether exogenous ketones improve endurance performance and concludes further studies are needed.

Co-ingestion of 750 mg/kg ketone ester with carbohydrate did not improve shuttle run time to exhaustion or sprint times in 11 team sport athletes, but the rise in multitasking errors after exhausting exercise seen with placebo did not occur.

The review reports that ketosis has been linked to histone modifications such as acetylation, methylation and hydroxybutyrylation, while it remains to be established whether ketone bodies themselves are responsible.

Ketone monoester taken 30 minutes before a 75 g oral glucose tolerance test reduced the glucose area under the curve by 17 percent in healthy young adults, without an increase in insulin secretion.

The ketone ester drink lowered plasma ghrelin and significantly suppressed reported hunger and desire to eat 1.5 hours after consumption compared with dextrose.

Ketone monoester added to carbohydrate did not improve 10 km running time trial performance (2402 s vs 2422 s, p = 0.483) in 8 endurance-trained runners.

Raising blood beta-hydroxybutyrate from 0.1 to 4.1 mM three times a day for 28 days with a ketone monoester produced no adverse changes in safety measures in 24 healthy adults.

The review states that ketogenic diets or ketone supplementation, as non-toxic approaches, showed a positive therapeutic advantage in a broad range of malignancies based on tumor metabolism.

A ketone monoester drink taken before an oral glucose tolerance test reduced glucose area under the curve by 11 percent in 15 individuals with obesity, with no increase in circulating insulin.

Ketone ester taken after each session during 3 weeks of strenuous endurance training attenuated the development of overreaching, with sustainable training load and late-session power output 15 percent higher than control.

The authors conclude that sodium beta-hydroxybutyrate therapy is lifesaving in severe MADD but can have significant adverse effects, and that the tolerable long-term dose was not high enough to notably raise blood beta-hydroxybutyrate.

The review reports that brain imaging studies in Alzheimer's disease support enhanced brain energy metabolism with ketones, and that a few studies show modest functional improvement in Parkinson's disease and cognitive benefit in Alzheimer's disease.

The paper proposes, without presenting trial data, that a clinical study give COVID-19 patients a permissive diet plus ketone ester to raise blood ketones to 1 to 2 mM.

The review reports that intravenous ketone infusion acutely improves heart function in heart failure patients and concludes that increasing cardiac ketone oxidation may be a therapeutic strategy.

This review discusses the opportunities, risks and research gaps for using exogenous ketone bodies as immunometabolic interventions against influenza A and SARS-CoV-2, and the abstract reports no experimental findings.

Exogenous ketone supplements improved rotarod motor performance to varying degrees in rodent models, with the improvement depending on rodent strain, ketone formulation, age and exposure frequency.

The review states that despite glucose hypometabolism brain cells can utilize ketones efficiently, which provides a rationale for ketogenic interventions in Alzheimer's disease and other neurodegenerative diseases.

The review states that nutritional ketosis from ketogenic diets and from exogenous ketones shares a number of features but is far from identical, with important differences between the two.

The review concludes that current evidence suggests potential benefit of therapeutic ketosis in heart failure, in particular in HF with reduced ejection fraction.

Ketone ester intake during a simulated cycling race did not cause muscle glycogen sparing and did not change final-stage performance (time-trial power 273 versus 272 W) in 12 trained male cyclists.

A pre-workout supplement of BHB salts, caffeine and amino acids increased cycling time to exhaustion by 8.3 percent in keto-naive and 9.8 percent in keto-adapted adults compared with water.

Most of the 11 included human studies showed significant improvement in cognitive outcomes with ketone supplementation or ketogenic diet, and the authors suggest these approaches might be promising for Alzheimer's disease, especially at the prodromal stage.

The review concludes that beta-HB shows potential against age-associated pathology and that this therapeutic area is worthy of attention.

Raising beta-hydroxybutyrate with a ketone monoester had no apparent effect on LPS-stimulated caspase-1 activation in 11 people with obesity, although plasma IL-1beta fell in the ketone condition only.

In humans, acute consumption of a ketone ester drink reduced feelings of hunger and increased satiety compared with a dextrose drink, while the threshold of ketosis and mechanisms for appetite suppression remain unclear.

The review presents the d-beta-hydroxybutyrate monoester as a salt-free precursor of only the active d-isoform that can quickly and accurately raise blood ketone concentration, with proposed rationales across several chronic diseases.

Acetoacetate, but not beta-hydroxybutyrate, reduced glioblastoma cell viability in a dose-dependent manner, and combining it with low-dose 2-deoxy-D-glucose produced a greater-than-additive effect at low concentrations.

Increased myocardial ketone body metabolism is a feature of heart failure, and whether it is adaptive or maladaptive is unknown, though it offers the possibility of using exogenous ketones to treat the failing heart.

The review presents exogenous oral ketone supplements as a novel, non-pharmacological approach with potential application for breaking the vicious cycle of type 2 diabetes pathophysiology.

In 5 patients with VLCAD deficiency, ketone ester plus carbohydrate lowered plasma acylcarnitines, glycolytic intermediates and the Pi/PCr ratio during exercise compared with carbohydrate alone.

The review concludes that nutritional ketosis, whether from exogenous ketones or keto-adaptation, is rarely ergogenic for endurance performance and can impair it.

The review reports that ketosis-inducing strategies have shown different degrees of success in preventing neuronal damage, motor alterations and cognitive decline, and that more investigation is needed to establish safe clinical protocols.

Across 16 performance outcomes from 10 studies, 3 were positive, 10 were null and 3 were negative for ketone supplementation, and high heterogeneity made it difficult to conclude any benefit or detriment.

Ketone ester slightly counteracted the hypoxia-induced drop in blood and muscle oxygenation by about 3 percent during prolonged exercise, without changing time trial or sprint performance.

In mice with established heart failure, 2 weeks of ketone ester prevented the decline in cardiac function seen with vehicle, a mean difference of 4.7 percent ejection fraction (P < 0.01).

Acute ketone monoester raised beta-hydroxybutyrate to 3.50 mmol/L but did not significantly change hepcidin (p = 0.91) or ferritin (p = 0.10) in people with prediabetes.

Fourteen days of thrice-daily beta-OHB supplementation increased common carotid blood flow by 12 percent and improved digit-symbol substitution test performance by 2.7 correct responses in adults with obesity.

A 4-week ketone ester diet improved systolic and diastolic cardiac function in type 2 diabetic db/db mice, alongside enhanced mitochondrial biogenesis, quality control and oxygen consumption.

The ketone formulation appeared safe in 13 children with Angelman syndrome, with one participant exiting because of difficulty consuming it and stool consistency improving during the formulation phase (P = 0.0027).

The review argues that biologically synthesized D-3HB can raise plasma D-3HB faster than the ketogenic diet, ketone salts or ketone esters, while noting that dose-response relationships and safety margins still need research.

Four weeks of thrice-daily ketone monoester was safe and well tolerated and lowered HbA1c from 61 to 55 mmol/mol (p < .01) in patients with type 2 diabetes.

The review finds that three previous studies of a ketogenic diet in Parkinson's disease suggest non-motor symptom benefit but are not conclusive, and it lists the questions to resolve before recommending the diet.

Consumption of up to 25 g/day of BH-BD for 28 days showed no differences from placebo in tolerability scores and no clinically meaningful changes in safety measures in 59 healthy adults.

The review proposes that exogenous ketogenic supplements may mitigate aging processes and delay age-associated diseases through ketosis-evoked neuroprotective mechanisms.

This review summarizes the chemical basis of ketogenicity and identifies synthetic ketogenic compounds as an under-explored area for chemical synthesis, and the abstract reports no experimental results.

Abdominal fat distribution modulated the response to ketone supplementation, and the authors state that people with high intra-pancreatic, skeletal muscle and subcutaneous fat may not achieve favorable blood glucose control following it.

The review reports that ketogenic diets suppress the increase in ghrelin and hunger seen with non-ketogenic weight loss, with greater ketosis linked to smaller increases in ghrelin and hunger.

Ketone ester ingestion lowered acyl ghrelin by about 25 percent compared with placebo (a difference of -52.1 pg/mL) in 10 healthy young men, without changing GLP-1, GIP, gastrin, or cholecystokinin.

A 600 mg/kg ketone monoester dose increased ventilation, heart rate and perceived exertion during submaximal cycling in 19 endurance-trained adults without a significant difference in time-trial performance.

BH-BD was negative in all three genetic toxicity tests, the bacterial reverse mutation test, the in vitro human cell micronucleus test and the in vivo rat micronucleus test.

Oral ketone ester in non-fasted mice raised brain acetyl-CoA and citric cycle intermediates, and the increased acetyl-CoA inhibited glycolysis, competing with glucose.

The growth response of SH-SY5Y cells to beta-hydroxybutyrate was suppressed by glucose and pyruvate and appeared only under low-glucose or glucose- and pyruvate-deprived conditions.

Fourteen days of premeal ketone monoester lowered postprandial glucose by 8.0 percent and raised flow-mediated dilation from 6.2 percent to 8.9 percent in adults with obesity, with no change on placebo.

After ketone ester, beta-hydroxybutyrate fractional extraction was higher in HFrEF patients than in controls (52 versus 39 percent, p = 0.035), and it correlated with the degree of cardiac dysfunction and remodeling.

Oral bis hexanoyl (R)-1,3-butanediol produced a well-tolerated, sustained and dose-dependent increase in plasma beta-hydroxybutyrate in rats and mice.

Ketone ester lowered mean power output by 1.5 percent in the 30-minute time trial in 14 cyclists, and bicarbonate co-ingestion did not counteract this despite neutralizing the acid-base disturbance.

The authors conclude there is currently insufficient evidence to support the overall effectiveness of ketone supplements in sports.

Plasma FGF21 did not correlate with circulating ketone body levels, indicating to the authors that ketosis per se does not control FGF21 production, although insulin deprivation plus LPS injection raised FGF21 at 120 minutes (p = 0.005).

Race walk performance was impaired by about 6 percent (p < 0.0001) after 5 days of an LCHF diet with ketone ester supplementation, while the high-carbohydrate group was unchanged.

Ketone monoester ingestion lowered the glucose AUC during a 75 g oral glucose tolerance test from 483.2 to 406.6 mg/dL·h (P < 0.0001) in nine people with impaired glucose tolerance.

The review proposes that the energy and signaling mechanisms of ketone bodies may be relevant to military service members facing stressors such as traumatic brain injury and the need for muscle rehabilitation and recovery.

Ketone monoester taken 15 minutes before a mixed meal lowered blood glucose area under the curve by 9.4 percent and nonesterified fatty acid area under the curve by 27.3 percent in 19 young healthy volunteers, without changing insulin.

Exogenous beta-hydroxybutyrate oxidation contributed minimally to energy expenditure (peak 4.46 percent) and did not increase when blood concentrations rose above about 2 mM.

Mean power output in the 15-minute time trial was about 255 W in the ketone ester, bicarbonate and control conditions but was 5 percent higher with ketone ester plus bicarbonate (P = 0.02 versus control).

In cardiomyocytes, 3-beta-hydroxybutyrate caused v-ATPase disassembly, insulin resistance and contractile dysfunction, an effect not seen with acetoacetate and prevented by specific amino acids.

The ketone monoester reduced the decline in correct CRT answers during the simulated soccer match to 1.3 percent versus 3.4 percent with placebo (p = 0.02) in nine men.

Median PCL-5 scores fell from 58.5 to 54.0 in the ketone group and did not change in the control group, but the difference between groups was not statistically significant in this 21-participant trial.

The review reports that some studies suggest exogenous ketone supplements benefit endurance performance, recovery and overreaching, while many studies failed to observe such benefits.

The review concludes that its findings, largely from in vitro and animal work, require confirmation in clinical trials, and that additional studies are needed on the systemic and metabolic consequences of ketone bodies.

Acute ketosis significantly lowered the areas under the curve for remnant cholesterol (p = 0.022) and triglycerides (p = 0.022) in adults with prediabetes.

Exogenous ketosis lowered urine output by about 20 percent during 3 hours of cycling (1,172 mL vs 1,431 mL) and lowered NT-pro ANP by about 20 percent, with similar time trial performance.

The review found evidence that the ketogenic diet and exogenous ketone supplementation may provide treatment benefits in AD patients, but it is unclear which method is better and large long-term randomized trials are lacking.

Based on the available randomized trials in humans with Parkinson's disease, ketogenic therapy did not improve the outcomes assessed, while animal studies tended to show promising results.

Exogenous ketone supplementation increased exercise capacity by 6 to 8 percent on three race days, whereas a ketogenic diet decreased it by 48 to 57 percent on all race days.

Across 43 trials with 586 participants, acute exogenous ketone ingestion raised blood beta-hydroxybutyrate and lowered blood glucose by a mean of 0.54 mM, with larger effects from ketone monoesters than salts.

The review proposes that exogenous ketone supplements using D3HB have become a more effective approach to induce and maintain nutritional ketosis than ketogenic diets.

The caffeine-containing ketone salt supplement improved 20 km cycling time to 37.80 minutes versus 39.40 minutes with placebo (p < 0.003), while the caffeine-free version did not significantly differ from placebo or from the caffeine version.

This abstract describes a trial protocol and reports no results, so no outcome is available.

Across eight trials with 80 participants, acute ketone monoester or precursor ingestion produced no significant difference in endurance performance versus control (Hedges g of 0.136, p = .419).

Thirty minutes after ketone ester ingestion in 20 healthy fasting adults, ejection fraction increased by 3.1 percent and global longitudinal strain by 2.0 percent, alongside higher heart rate and systolic blood pressure.

Adding 2 g of L-alanine reduced the ketone ester-induced fall in blood glucose from 28 percent to 16 percent, indicating the glucose-lowering effect is partly due to beta-hydroxybutyrate decreasing L-alanine availability for gluconeogenesis.

The ketone ester drink was inferior to the ketogenic diet for achieving myocardial glucose suppression (44 percent versus 78 percent for the 24-hour diet and 83 percent for the 72-hour diet), while endogenous BHB predicted suppression with an AUROC of 0.88.