Blood Acetoacetate Research Articles

Elevated blood acetoacetate levels reduce major adverse cardiac and cerebrovascular events risk in acute myocardial infarction.

Although elevated blood ketone body levels reduce major adverse cardiac and cerebrovascular events (MACCEs) risk in chronic heart failure, their relationship with acute myocardial infarction remains unknown. We investigated this relationship in patients with acute myocardial infarction. This single-institution retrospective observational study analyzed data from 114 patients with acute myocardial infarction at Nihon University Hospital from May 1, 2018, to November 1, 2022. The cut-off value of acetoacetate for the incidence of in-hospital MACCE was determined by drawing a receiver operating characteristic curve (ROC) and defining patients with acetoacetate above and below the optimal cut-off point value as ROC and low-acetoacetate (LA) groups, respectively. Propensity score matching was performed between the LA and high-acetoacetate (HA) groups. Sex, peak creatine kinase, lactate, and blood glucose were defined as confounding factors between in-hospital MACCEs and acetoacetate, and 1:1 propensity score matching between the LA and HA groups was used, resulting in 40 patients from both groups enrolled in the analysis. There was a significantly lower incidence of in-hospital MACCEs in the HA group (LA group: 9 [22%] vs HA group: 1 [3%], P = 0.014). In conclusion, in acute myocardial infarction, elevated blood acetoacetate levels reduce the risk of MACCE.

Exogenous Beta-Hydroxybutyrate Ketone Salts Elevate Circulating Acetoacetate Levels

Abstract Objectives Ketones are compounds that provide both fuel and protection against various diseases; they are produced naturally by the liver or exogenously to be ingested. Beta-hydroxybutyrate is the most stable ketone and therefore, often used in ketone supplements. Beta-hydroxybutyrate interconverts with acetoacetate, the least stable ketone. Acetoacetate may offer greater neuroprotection than beta-hydroxybutyrate. Therefore, it is important to find methods to increase acetoacetate levels. The purpose of this study was to determine if exogenous beta-hydroxybutyrate salts significantly elevate blood acetoacetate levels 30-minutes after consumption. Methods Sixteen young adults participated in this randomized, triple-blinded, cross-over, placebo-controlled study and met for three laboratory visits: 1) familiarization visit, and 2–3) data collection visits separated by at least one week for washout. During visits two and three, blood samples were collected at baseline and again 30-minutes after consuming either the racemic ketone-salt supplement or placebo. Acetoacetate was stabilized in the blood samples and analyzed via mass spectrophotometry. A two-way repeated-measures ANOVA was conducted to determine the effects of drink and time on blood acetoacetate levels. Results There was a significant (p = .008) interaction between drink and time. Bonferroni-adjusted simple main effects tests demonstrated that between baseline and 30-minutes post drink, blood acetoacetate was not different (p = .50) for the placebo but was significantly increased (p = .001) for the ketone salt supplement. The gain score analysis from a paired samples t-test demonstrated that the increase in acetoacetate after ingestion of ketone salts was significantly (p = .01) and substantially (d = .842) larger than the increase following ingestion of the placebo drink. Conclusions Blood acetoacetate levels can be significantly elevated by exogenous ketone salts, demonstrating a quick interconversion of exogenous beta-hydroxybutyrate to acetoacetate. More studies are needed to determine if this acute increase in acetoacetate is great enough to confer protective benefits demonstrated in previous studies. Funding Sources Augusta University and Keto-Mojo, inc.

Blood Ketone Bodies and Breath Acetone Analysis and Their Correlations in Type 2 Diabetes Mellitus.

Analysis of volatile organic compounds in the breath for disease detection and monitoring has gained momentum and clinical significance due to its rapid test results and non-invasiveness, especially for diabetes mellitus (DM). Studies have suggested that breath gases, including acetone, may be related to simultaneous blood glucose (BG) and blood ketone levels in adults with types 2 and 1 diabetes. Detecting altered concentrations of ketones in the breath, blood and urine may be crucial for the diagnosis and monitoring of diabetes mellitus. This study assesses the efficacy of a simple breath test as a non-invasive means of diabetes monitoring in adults with type 2 diabetes mellitus. Human breath samples were collected in Tedlar™ bags and analyzed by headspace solid-phase microextraction and gas chromatography-mass spectrometry (HS-SPME/GC-MS). The measurements were compared with capillary BG and blood ketone levels (β-hydroxybutyrate and acetoacetate) taken at the same time on a single visit to a routine hospital clinic in 30 subjects with type 2 diabetes and 28 control volunteers. Ketone bodies of diabetic subjects showed a significant increase when compared to the control subjects; however, the ketone levels were was controlled in both diabetic and non-diabetic volunteers. Worthy of note, a statistically significant relationship was found between breath acetone and blood acetoacetate (R = 0.89) and between breath acetone and β-hydroxybutyrate (R = 0.82).

Übersicht zu Zusammenhängen zwischen Änderungen der Bewegungsintensität und Ketose bei Milchkühen

With a prevalence of up to 43 % subclinical ketosis is one of the most common diseases in dairy cows in their transition period. In itself, this may cause subsequent diseases such as clinical ketosis or lameness. Therefore, monitoring of animals in this stage is of importance. In addition to the measurement of β-hydroxybutyrate or acetoacetate in blood, milk, and urine as well as the observation of the animals, computer-assisted systems are suitable means of monitoring. Information such as animal identification and activity data are recorded on a data logger and transmitted to a computer. A change in activity may be an indication of an underlying disease days before the onset of additional clinical signs. In cases of ketosis, a decrease in activity may be observed 5 days before the clinical diagnosis is made. Thus, these data are a valuable contribution in monitoring the cattle herd's health status for both the farmer and the veterinarian. Activity measurement may also be employed for the detection of a beginning lameness. In the presence of lameness, the individual's activity decreases and periods of lying are longer. Activity measurement via transponder as a part of the herd monitoring provides important information on lameness prevalence in the herd. In the presence of a lameness a visual assessment should additionally be made. Lameness scores (Locomotion score, Gait score) have been developed for this purpose and add to determining the lameness status of the herd. This way the animals are divided into different lameness classes. Based on this classification those individuals in need of claw trimming or further treatment may be identified leading to amelioration or prevention of secondary diseases. Due to lameness and subsequent reduction of activity and feed intake, the animals may develop subclinical or clinical ketosis. Therefore, under consideration of both animal welfare and economic factors early disease detection and prophylaxis is desirable and should be a main objective of herd monitoring.

Effects of branched-chain volatile fatty acids and fibrolytic enzyme on rumen development in pre- and post-weaned Holstein dairy calves

The study evaluated the effects of branched-chain volatile fatty acids (BCVFA) and fibrolytic enzyme (FE) on rumen development in calves. Forty Holstein male calves at the same ages (15 ± 2.5 days of age) and weights (45 ± 3.3 kg of body weight [BW]) were assigned randomly to four groups with a 2 × 2 factorial arrangement of treatments. Supplemental BCVFA (0 g/d or 18 g/d) and FE (0 g/d or 1.83 g/d) were fed to calves. Data were analyzed as a 2 × 2 factorial arrangement random design by the mixed procedure of SAS. The BCVFA × FE interaction was observed for ruminal propionate, blood growth hormone (GH) and insulin-like growth factor-1 (IGF-1), and GH receptor (GHR) and IGF-1 receptor (IGF-1R) expression in the rumen mucosa. Dry matter intake was higher for BCVFA addition. The higher average daily gain and ruminal volatile fatty acids were observed for BCVFA or FE addition. Stomach weight and the length and width of rumen papillae were higher for BCVFA addition. The higher expression of GHR, IGF-1R and 3-hydroxy-3-methylglutaryl-CoA synthase 1 in rumen mucosa, and blood GH and IGF-1 were observed with BCVFA or FE addition. Blood β-hydroxybutyrate and acetoacetate were higher for BCVFA addition. The results indicated that rumen development was promoted by BCVFA, but was not affected with FE addition in calves.

Rapid quantification of metabolic intermediates in blood by liquid chromatography-tandem mass spectrometry to investigate congenital lactic acidosis

A novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been established to quantify metabolic intermediates, including lactate (Lac), pyruvate (Pyr), acetoacetate (ACAC) and 3-hydroxybutyrate (3-HB) in blood. Samples were deproteinized with methanol-acetonitrile solution, and analytes were separated on an adamantyl group-bonded reverse phase column and detected in multiple reaction monitoring mode. Total analysis time was 4 min per sample. Method validation results displayed that limits of quantification were 10.0 μmol L−1 for Lac and Pyr, and 5.0 μmol L−1for ACAC and 3-HB. The within- and between-run coefficients of variation were in the range of 1.2–6.4% for all analytes. The recoveries were ranged from 95.6 to 111.5%. The reference values of analytes were determined for the pediatric population. Duo to instability of Lac, Pyr and ACAC in vitro, a comprehensive stability assay was performed to determine optimal conditions for sample collection, pretreatment and storage. Results showed that precipitation of protein in blood at bedside combined with low storage temperature could effectively preserve the integrity of Lac, Pyr and 3-HB, but the precipitated protein accelerated degradation of ACAC. Isolation of supernatant fluid slowed degradation of ACAC. Supernatant samples could store at −20 °C for 10 days. The use of plasma or serum to determine these intermediates was not recommended. In this study, 450 samples from patients were analyzed, and 7 patients were diagnosed as congenital lactic acidosis. With the advantages of rapid, accurate and reliable, this method is very suitable for congenital lactic acidosis screening and researches related to energy metabolism.

Normoglycemic Ketonemia as Biochemical Presentation in Ketotic Glycogen Storage Disease.

According to the textbooks, the ketotic glycogen storage disease (GSD) types 0, III, VI, IX, and XI are associated with fasting ketotic hypoglycemia and considered milder as gluconeogenesis is intact. A retrospective cohort study of biochemical profiles from supervised clinical fasting studies is performed in ketotic GSD patients in our metabolic center. For data analysis, hypoglycemia was defined as plasma glucose concentration <2.6mmol/L. Total KB was defined as the sum of blood acetoacetate and β-hydroxybutyrate concentrations. If the product of glucose and KB concentrations was greater than 10, a ketolysis defect was suspected. Data could be collected from 13 fasting studies in 12 patients with GSD III (n = 4), GSD VI (n = 3), and GSD IX (n = 5). Six patients remained normoglycemic with median glucose concentration of 3.9mmol/L (range, 2.8-4.6mmol/L) and median total KB concentration of 1.9mmol/L (range, 0.6-5.1mmol/L). The normoglycemic patients included type VI (3 out of 3) and type IX (3 out of 5) patients. All type III patients developed ketotic hypoglycemia. Interestingly, in five patients (one GSD III, one GSD VI, and three GSD IX), the biochemical profile suggested a ketolysis defect. Normoglycemic ketonemia is a common biochemical presentation in patients with GSD types VI and IX, and ketonemia can precede hypoglycemia in all studied GSD types. Therefore, GSD VI and GSD IX should be added to the differential diagnosis of ketotic normoglycemia, and KB concentrations should be routinely measured in ketotic GSD patients.

643 Elevated Acetoacetate, Oxidative Stress and Mcp-1 Levels in Cord Blood of Infants of Diabetic Mothers

BackgroundInfants of diabetic mothers (IDM) are at increased risk for metabolic complications. Type 1 and some type 2 diabetic patients have elevated levels of ketone bodies acetoacetate (AA) and β-hydroxybutyrate...

Elevated Acetoacetate and Monocyte Chemotactic Protein-1 Levels in Cord Blood of Infants of Diabetic Mothers

Background: Infants of diabetic mothers (IDMs) are at increased risk for metabolic complications. Type 1 and some type 2 diabetic patients have elevated levels of the ketone bodies acetoacetate (AA) and β-hydroxybutyrate (BHB). Objective: The aim of this study was to examine how hyperketonemia in diabetic mothers affects markers of inflammation and oxidative stress in their offspring. Methods: Blood was obtained from 23 diabetic mothers and 13 healthy mothers and their infants’ umbilical cords at delivery. Interleukin-8, monocyte chemotactic protein-1 (MCP-1) and protein carbonyl (protein oxidation) levels were determined by ELISA. U937 human monocyte cell culture was used to examine the effect of AA and BHB on secretion of MCP-1. Results: There was a significant increase in the levels of AA in cord blood of IDMs compared with cord blood of infants of healthy mothers. A significant increase in the levels of protein oxidation (p < 0.05) and MCP-1 levels (p < 0.05) was observed in the cord blood of IDMs. The level of MCP-1 correlated significantly (r = 0.51, p = 0.01) with the concentration of AA in the IDMs. In further experiments with cultured monocytes treated with exogenous AA (0–4 mM), a significant increase in MCP-1 secretion was observed in AA- but not BHB-treated monocytes. Conclusion: Blood levels of AA and MCP-1 are elevated in IDMs, which may contribute to the development of the metabolic complications seen in IDMs.

Determination of Ketone Bodies in Blood by Headspace Gas Chromatography-Mass Spectrometry

A gas chromatography-mass spectrometry (GC-MS) method for determination of ketone bodies (β-hydroxybutyrate, acetone, and acetoacetate) in blood is presented. The method is based on enzymatic oxidation of D-β-hydroxybutyrate to acetoacetate, followed by decarboxylation to acetone, which was quantified by the use of headspace GC-MS using acetone-(13)C(3) as an internal standard. The developed method was found to have intra- and total interday relative standard deviations < 10% for acetone+acetoacetate levels (∼25 to 8300 μM) and D-β-hydroxybutyrate levels (∼30 to 16500 μM). Recovery values varied from 98 to 107%, demonstrating the suitability of the method for measuring ketone bodies over a wide concentration range. The method has been applied to cases in which ketoacidosis was suspected as the cause of death in diabetics or chronic alcoholics, as well as to cases in which another cause of death was identified.

The postmortem distribution of ketone bodies between blood, vitreous humor, spinal fluid, and urine

The distribution of the ketone bodies: acetone, acetoacetate, and D-beta-hydroxybutyrate, between blood, vitreous humor, spinal fluid, and urine was examined in 105 medico-legal autopsies. The ketone body concentration in the body fluids was determinated by head-space gas chromatography. The correlation between blood and the body fluids could be described with regression lines on the logarithmic-transformed results. The correlation is dependent on the ketone body concentration. The ketone bodies in spinal fluid show the best correlation to blood, followed by vitreous humor, and last urine. The concentration dependence in spinal fluid is mainly due to ketone bodies being metabolized in the brain. The human brain utilizes ketone bodies during normal nutritional state. In vitreous humor, the dependence is mainly due to protein bindings of acetoacetate and beta-hydroxybutyrate in blood and the difference in dry matter between blood and vitreous humor.

Effects of energy balance and metabolizable protein level on tissue mobilization and milk performance of dairy cows in early lactation

The objective of this study was to investigate the effect of dietary energy and metabolizable protein supply on feed intake, milk production, blood metabolites and tissue mobilization in dairy cows during the first 14 weeks of lactation. In the experiment, 36 Norwegian Dairy Cattle were used. Three dietary treatments were evaluated, (1) protein and energy supply according to standard recommendations (SS) for amino acids absorbed in the small intestine (AAT) and net energy lactation (NE L), (2) low protein and low energy (LL; 50% of the concentrate energy fed to SS) and (3) high protein (135% of that fed to LL) and low energy (HL). Energy corrected milk (ECM) was not significantly different between SS and HL but both were higher than LL ( P<0.05), 4.6 and 2.8 kg higher, respectively. Increased AAT supply at low energy intake increased ( P<0.05) ECM, protein yield and stimulated increased mobilization of fat. The latter was verified by higher levels ( P<0.05) of non-esterified fatty acids and acetoacetate in blood and acetone in milk. However, increased fat mobilization showed no effect on incidence of ketosis. It is concluded that the AAT supply in early lactation is an important factor in regulating milk yield and milk protein production.

High β-hydroxybutyrate concentration in liver and skeletal muscle of newly hatched chicks

Characteristic changes in ketone body concentrations in blood, liver, and skeletal muscle were investigated in detail in newly hatched chicks. The concentration of β-hydroxybutyrate in the blood was maximal at hatch (0 day), markedly decreased to 3 days, then maintained at low levels, up to 14 days of age. The concentration of acetoacetate in blood, on the other hand, did not change after hatching but remained lower than that of β-hydroxybutyrate at all ages. In liver and muscles, the concentration of β-hydroxybutyrate changed in a manner similar to that in the blood. The muscle to blood ratio of the β-hydroxybutyrate concentration on days −1 and 0 was significantly higher than those at 1 through 14 days post-hatch. These results show that newly hatched chicks have the same high ketone body concentrations in the skeletal muscle, blood and liver. It is, hence, suggested that uptake of β-hydroxybutyrate by muscles is substantial or that ketogenesis, if any, occurs in muscles immediately before and after hatching of chicks.

Measurement of blood acetoacetate and β -hydroxybutyrate in an automatic analyser

Measurement of blood acetoacetate and β -hydroxybutyrate in an automatic analyser

Ketone Bodies in Milk and Blood of Dairy Cows: Relationship between Concentrations and Utilization for Detection of Subclinical Ketosis

The objective of this study was to investigate the relationship between the concentrations of the different ketone bodies in milk and blood and to evaluate these concentrations for the detection of subclinical ketosis. A total of 60 multiparous cows were used. Concentrations of acetone, acetoacetate, and β-hydroxybutyrate were analyzed quantitatively in blood and milk, and the Ketolac strip test was used for semiquantitative determination of β-hydroxybutyrate in milk. Cows were defined subclinically ketotic when their concentration of blood β-hydroxybutyrate was over 1200 μmol/L. High correlation coefficients were observed between blood acetone and blood acetoacetate, and between blood and milk acetone. On the contrary, concentrations of milk and blood β-hydroxybutyrate were poorly correlated with the other concentrations of ketone bodies. The Ketolac strip test overestimated the concentrations of β-hydroxybutyrate in milk. For the detection of subclinical ketosis, the best sensitivity-specificity combination was obtained with the determination of acetoacetate in blood or milk, with threshold concentrations of 125 and 50 μmol/L, respectively. Determination of β-hydroxybutyrate in the milk via an enzymatic analysis or via the Ketolac strip test provided valuable results, with threshold concentrations of 70 and 100 μmol/L, respectively. The simplicity of use of the Ketolac strip test makes it a valuable way toinvestigate subclinical ketosis.

Measurement of blood acetoacetate and β‐hydroxybutyrate in an automatic analyser

g-hydroxybutyrate and acetoacetate as well as lactate and pyruvate are intermediary metabolites normally present in blood. The g-hydroxybutyrate/acetoacetate ratio is an expression of the mitochondrial oxido-reduction state. This ketone body ratio can provide a clue to diagnosis and metabolic status in congenital errors of the electron transport chain and pyruvate metabolism. The standardization of these analytical procedures improves the interpretation of the results helping in the difficult diagnosis of mitochondrial diseases in children. This study describes an adaptation to a Dimension R 2 L (Dade Behring, Newark, Delaware, USA) automatic analyser for a method to measure blood ketone bodies (g-hydroxybutyrate and acetoacetate). The method allows the metabolites to be measured directly in nondeproteinized plasma (fluoride/ethylenediaminetetraacetic acid). This adaptation simplifies the analytical procedure and limits the turnaround time to 20 minutes. With a sample volume of 200 μ l metabolite concentrations ranging from 12 to 1300 μ molL−1 of g-hydroxybutyrate and from 10 to 450 μ molL−1 of acetoacetate may be measured with a reliable analytical response.

Heart failure ketosis.

To assess whether blood ketone bodies are increased in congestive heart failure (CHF). Thirteen patients with CHF and 11 cardiac patients without CHF took part in the study. Blood acetoacetate and b-hydroxybutyrate levels and the pertinent metabolic and hormonal milieu were measured during 20 h fast and after 2 h glucose infusion. The averaged blood ketone body and free fatty acid levels were significantly higher during the fast and also remained higher after glucose infusion in patients with CHF than in the control group. The areas under ketone body concentration time curve over the last 8 h of the fast were 3522 +/- 662 mumol L-1 h-1 (SE) and 1789 +/- 192 mumol L-1 h-1 in patients with and without CHF, respectively (P = 0.022). Circulating noradrenaline and growth hormone were higher but glucagon lower in patients with CHF than in the controls (P < 0.05 for all differences) whereas the glucose and insulin concentrations were comparable in the study groups. At the time of peak ketonaemia the glucagon-to-insulin ratio was lower in patients with CHF than in patients without CHF (P = 0.04). These data suggest that severe CHF is a ketosis-prone state. Augmented supply of free fatty acids for ketogenesis due to increased stress hormone-related lipolysis is one likely mechanism.

Effect of high fat diet on liver microsomal oxygenations in ferret.

1. Ferret on a high fat diet accumulated large amounts of fat in its liver and had blood acetoacetate and beta-hydroxybutyrate concentrations 250 and 375% of those in control animals. 2. The high fat diet alone increased ferret liver microsomal 7-ethoxyresorufin O-deethylase (EROD) activity by 90%, but had no effect on 7-methoxy-, 7-pentoxy-, or 7-benzyloxy-resorufin, O-dealkylase activities. Administration of 3-methylcholanthrene (MC) increased only liver EROD activity, by 5- to 6-fold, in ferret on both high fat and control diets. Induction of EROD, but not MROD activity, in ferret on the high fat diet indicates that P4501A1, but not P4501A2, is induced. 3. Activation of 3H-paracetamol, measured by covalent tissue binding to ferret liver microsomal fractions, was increased three-fold in ferret on the high fat diet, nine-fold by MC administered to ferret on a control diet, and 13-fold by MC given to ferret on the high fat diet. Similar results were obtained with activation of the cooked-food amine, Glu-P-1, by ferret liver microsomes. 4. Western blots with antibodies to rat liver P450s showed that ferret liver contains proteins orthologous with rat liver P4504A1 and bifunctional protein. However, whereas clofibrate, similar to high fat diets, induced these two proteins in rat liver, no increase of these proteins occurred in liver of ferret fed a high fat diet. Western blots also showed that ferret liver contains no P4501A1 or 1A2, and although these two proteins were induced by MC, no induction occurred when ferret was fed the high fat diet alone. Ferret liver microsomes also contain a protein recognized by rat anti-P4502E1 but of a lower molecular weight. 5. Immunosorbent (ELISA) analyses of ferret liver for P4501A1 and 4A1 showed that the high fat diet increased a protein orthologous to rat P4501A1 but did not increase any protein orthologous to rat P4504A1. 6. These findings indicate that the high fat diet does not induce ferret liver bifunctional protein or P4504A1 enzyme protein, but may enhance liver P4501A1 and 1A2 activities through the hyperketonaemia resulting from the high dietary fat. The conflicting P450 results, namely Glu-P-1 activation but no MROD activity for P4501A2, high EROD activity and ELISA quantification of P4501A1, but no positive Western blot, are probably due to differences in substrate specificity and immunological characteristics between rat and ferret enzymes.

The effects of continuous ruminal dosing with dioctyl sodium sulphosuccinate on ruminal and metabolic characteristics of lactating Holstein cows

Rumen-cannulated Holstein cows were used to study the effect of intraruminal dosing of dioctyl sodium sulphosuccinate (DSS; 0.07 g/kg body weight per d) for 4 weeks. DSS was suspended in nylon bags to allow it to be released slowly into the rumen. Cows were offered a diet containing grass silage and concentrate (45:55, w/w). Intakes of control cows were regulated to those of DSS-dosed cows. Cows dosed with DSS had no rumen ciliate protozoa, lower rumen NH3-N concentrations and acetate and butyrate proportions, higher propionate, isovalerate, and valerate proportions. In vitro fibre digestion by non-ciliate rumen fluid from DSS-dosed cows was apparently impaired. When cows were dosed with DSS, levels of neutral- and acid-detergent fibre in whole rumen contents were increased, rumen solids turnover rate was slower, and whole tract apparent digestibility of cellulose and diethyl ether extract was decreased. Dosing of DSS led to reduced concentrations of blood acetoacetate but elevated plasma glucose levels. Milk protein content was higher, however, lactose content was lower for DSS-dosed than control cows. Milk fat of DSS-dosed cows had a smaller proportion of short-chain fatty acids but a greater proportion of unsaturated fatty acids.

Changes in Blood Glucose, Nonesterified Fatty Acids, and Ketones in Response to Weaning and Feed Intake in Young Calves

Effects of weaning age on blood glucose, ketones, and nonesterifid fatty acids were examined using 16 Holstein heifer calves. Animals entered the study at 6±3.5 d of age and were fed 1.8kg of milk twice daily to 28 (early weaning) or 56 d (late weaning) and a commercial pelleted calf starter from 0 (early) or 28 d (late). Blood was sampled once weekly for 14wk and analyzed for β-hydroxybutyrate and acetoacetate. Plasma was analyzed for glucose and nonesterifid fatty acids. Blood β-hydroxybutyrate increased with increasing grain intake and was greater during wk 0 to 4 and 5 to 8 in calves weaned early than in those weaned late. Blood acetoacetate followed trends similar to β-hydroxybutyrate and averaged 23.8 and 16.1 μM in calves weaned early and late, respectively. Plasma glucose and nonesterifid fatty acids declined with age and were lower during 5 to 8wk in calves weaned early. Data suggest that ketone concentrations resulted from alimentary ketogenesis, which increased rapidly after weaning.