Search Results (28)

Hyperketonemia (HYK) is a common disorder in high-producing dairy cows, resulting in significant economic losses. Defined by elevated beta-hydroxybutyrate (BHB; ≥1.2 mmol/L) without clinical signs, HYK is often considered a gateway disease, predisposing cows to other metabolic and infectious problems. Our objective was to investigate the association between previous lactation risk factors and both BHB concentration and HYK status during the first week postpartum in the subsequent lactation. A retrospective study was conducted using previously collected blood samples from 2336 Holstein multiparous dairy cows from 7 dairy herds, where BHB concentration was measured during the first week postpartum. Data from the previous lactation were extracted from electronic farm records. Log-transformed BHB concentrations and HYK status were each modeled using separate linear mixed models. Both models included the same set of risk factors—lactation, previous lactation total times bred, dry length period, previous lactation days in milk, previous lactation days open, previous lactation days carried calf, previous lactation peak milk production, previous lactation total milk production, previous lactation total milk fat, and previous lactation total milk protein—to investigate their association with these outcomes. Potential confounding variables were offered to the models, and stepwise backward elimination was used to determine which covariates to retain. Significant associations were detected between BHB concentration and dry period length (DDRY), lactation number (LACT), previous lactation total milk protein (TOTP), and previous lactation days open (PDOPN). Inclusive, significant associations were detected between HYK status and previous lactation total milk production (PTOTM), DDRY, LACT, TOTP, and PDOPN. Our results suggest that a dry period longer than 60 days, days open exceeding 130 days, being in their third or greater lactation, and each additional 1000 kg of milk produced in the previous lactation are associated with an increased risk of having high BHB and HYK in the first week postpartum in the subsequent lactation. Full article

Serum beta-hydroxybutyrate (BHB) and non-esterified fatty acids (NEFAs) are biomarkers of situations of negative energetic balance in bovine. However, knowledge about their possible measurement and use in saliva is limited. In this report, two commercially available methods for the measurement of BHB and NEFAs were validated for use in bovine saliva. Both methods showed good precision and accuracy. The BHB concentrations were correlated between the saliva and the serum, but not the NEFA concentrations. The cows with hyperketonemia (n = 17) had increased salivary BHB compared to the cows with no clinical signs and no hyperketonemia (n = 34) and those with clinical signs of metritis (n = 17). The salivary NEFA concentration increased in newborn calves (n = 10) on days 1 and 2 of life compared to the day of birth before colostrum intake. The calves with symptomatic bovine respiratory disease complex (BRD, n = 7) showed higher salivary NEFA concentrations than those without clinical symptoms (n = 6). Thus, BHB and NEFAs can be reliably measured in bovine saliva using easily automatable colorimetric methods. Salivary BHB increased in hyperketonemia and could be a potential biomarker of this condition. Further studies should be undertaken to clarify the mechanism and possible use of salivary NEFAs as biomarkers. Full article

Ultrasound back-fat thickness (BFT) can indirectly assess the risk of metabolic disease as hyperketonemia. In this study, 129 multiparous and clinically healthy dairy cows were enrolled and examined weekly for the first 8 weeks of lactation for body-condition score (BCS), BFT, β-hydroxybutyrate (BHB), weekly changes (ΔBCS, ΔBFT, ΔBHB), and total changes over the study (TotalΔ_8to1BCS, TotalΔ_8to1BFT, TotalΔ_8to1BHB). Cows with BHB ≥ 1.0 mmol/L were considered to be affected by hyperketonemia (HK; n = 56), while the remaining animals were considered as controls (CTR; n = 73). Statistical analysis included mixed models, spearman correlation matrix, logistic regression, and linear regression analysis. BCS and BFT showed a strong correlation and were greater in the first weeks after calving in HK. The same group had greater BCS and BFT losses over the trial. However, weekly changes were identified only for BFT. Linear and logistic regression analysis for the disease event identified that BFT loss of 1 mm was associated with an increase in BHB (+0.36 mmol/L) and an increased risk of developing hyperketonemia over the week when the loss was between the second and first weeks (+2.5 times), third and second (+51%), and fourth and third (+58%) weeks. In conclusion, BFT can be used to identify the risk of developing hyperketonemia during early lactation. Full article

Metabolic diseases are significant diseases that affect the welfare, health, and production of small ruminant flocks raised for dairy and meat purposes. In breeding females, they mainly occur from six to eight weeks before and after parturition, respectively. Pregnancy toxemia and lactational ketosis are manifestations of hyperketonemia, primarily due to energetic deficit. Hypocalcemia and hypomagnesemia are related to the metabolic unavailability of calcium and magnesium, respectively. This review aimed to identify and discuss the current and most relevant aspects related to individual and herd health management of these interrelated metabolic diseases with impact on the sheep and goats’ farm sustainability. These diseases are primarily due to nutritional deficits, but homeostatic and homeorhetic disruptions are responsible for clinical signs and forms. Currently, their clinical diagnosis and monitoring are mainly assessed by biochemistry of body fluids and feed bromatological evaluation. Epidemiological studies and measuring risk factors also contribute to their prevention. Nevertheless, research on specific biomarkers and composite indices related to these diseases, in the context of herd health management and precision medicine, are new pathways driven to suitable and efficient animal production. Full article

Background/Objectives: Elevating ketone levels with therapeutic nutritional ketosis can help to metabolically manage disease processes associated with epilepsy, diabetes, obesity, cancer, and neurodegenerative disease. Nutritional ketosis can be achieved with various dieting strategies such as the classical ketogenic diet, the modified Atkins diet, caloric restriction, periodic fasting, or the consumption of exogenous ketogenic supplements such as medium-chain triglycerides (MCTs). However, these various strategies can be unpleasant and difficult to follow, so that achieving and sustaining nutritional ketosis can be a major challenge. Thus, investigators continue to explore the science and applications of exogenous ketone supplementation as a means to further augment the therapeutic efficacy of this metabolic therapy. Methods: Here, we describe a structurally new synthetic triglyceride, glycerol tri-acetoacetate (Gly-3AcAc), that we prepared from glycerol and an acetoacetate precursor that produces hyperketonemia in the therapeutic range (2–3 mM) when administered to mice under both fasting and non-fasting conditions. Animal studies were undertaken to evaluate the potential effects of eliciting a ketogenic response systemically. Acute effects (24 h or less) were determined in male VM/Dk mice in both fasted and unfasted dietary states. Results: Concentration levels of β-hydroxybutyrate in blood were elevated (βHB; 2–3 mM) under both conditions. Levels of glucose were reduced only in the fasted state. No detrimental side effects were observed. Conclusions: Pending further study, this novel compound could potentially add to the repertoire of methods for inducing therapeutic nutritional ketosis. Full article

Choline is required for the synthesis of phosphatidylcholine, an important constituent of lipoproteins. Early lactation cows presumably synthesize insufficient phosphatidylcholine, and choline supplementation in a rumen-protected form might benefit metabolism and lactation. The objectives of this study were to determine the effects of feeding rumen-protected choline (RPC) on lactation and metabolism in dairy cows. In experiment 1, 369 nulliparous and parous Holstein cows housed in four pens per treatment were fed 12.9 g/day of choline as RPC from 25 days prepartum until 80 days postpartum. In experiment 2, 578 nulliparous cows housed in five pens/treatment were fed 12.9 g/day of choline as RPC in the last 22 days of gestation only. In both experiments, blood was sampled and analyzed for concentrations of nonesterified fatty acids (NEFAs) and glucose at 1, 14, and 21 days postpartum and of choline at 1 and 14 days postpartum. Blood from all cows was sampled and analyzed for concentrations of β-OH butyrate (BHB) at 1 and 14 days postpartum. Cows with BHB > 1.2 mmol/L were classified as having hyperketonemia. Hepatic tissue was collected from 46 cows from the eight pens in experiment 1 at 9 days postpartum and analyzed for concentrations of glycogen and triacylglycerol. Milk yield and components were measured for 80 days postpartum in experiment 1, whereas only milk yield was measured in experiment 2. The pen was the experimental unit of analysis. Supplementing RPC tended to increase dry matter intake (DMI) prepartum in experiments 1 and 2 and postpartum in experiment 1. Feeding cows with RPC increased yields of 3.5% fat-corrected milk (42.8 vs. 44.8 kg/day), energy-corrected milk (38.5 vs. 40.3 kg/day), milk fat (1.52 vs. 1.61 kg/day), and true protein (1.16 vs. 1.21 kg/day) in experiment 1. Milk yield tended to be greater with RPC (26.4 vs. 27.4 kg/day) in experiment 2. Supplementing RPC increased plasma choline concentrations on day 14 postpartum in experiment 1 (3.32 ± 0.27 vs. 4.34 ± 0.28 µM) and on day 1 in experiment 2 (3.35 ± 0.16 and 13.73 ± 0.15 µM). Treatment did not affect the concentrations of glucose, NEFAs, or BHB in plasma, but the incidence of hyperketonemia was less in multiparous cows fed RPC than those fed the control in experiment 1. Feeding cows with RPC reduced hepatic triacylglycerol content and tended to reduce the ratio of triacylglycerol to glycogen and the risk of hepatic lipidosis in cows in experiment 1. The concentrations of hepatic triacylglycerol on day 9 postpartum were inversely related to those of choline in plasma on day 1 postpartum. Feeding cows with RPC improved lactation and metabolism, but more benefits were noted when it was fed before and after calving. Full article

Hyperketonemia is common in cows postpartum and is associated with a decrease in milk production, reproductive efficiency, and increased risk of periparturient diseases and early culling from the herd. The objective of this research was to determine if feeding an exogenous source of propionate increased milk and milk component yield and reduced the incidence of hyperketonemia and other health events in Holstein dairy cows. Cows were systematically enrolled in the control group (C) or sodium propionate treatment group (SP) in a randomized block design. A subset of cows was sampled for blood glucose and betahydroxybutyrate (BHB) concentrations in milk at 3, 7, and 14 days using a NovaMax^® Plus™ meter (Nova Diabetes Care, Inc., Billerica, MA, USA). Data were analyzed using a mixed model. Average blood BHB and glucose concentrations during the postpartum period did not differ between treatments for multiparous or primiparous cows (C = 0.53 ± 0.02, SP: 0.55 ± 0.02 mmol BHB/L, p = 0.5; C = 44.0 ± 0.77, SP = 43.0 ± 0.78 glucose mg/dL, p = 0.6). However, the prevalence of hyperketonemia and metritis was high in primiparous cows (C = 35.6% and 19.8%, respectively; SP = 35.8% and 18.9%, respectively). Blood glucose was inversely related to BHB concentration for cows below 40 mg/dL blood glucose. Feeding sodium propionate during the postpartum period increased milk fat yield (C = 1.71; SP = 1.86 kg/day, p = 0.01), tended to increase milk yield in multiparous cows (C = 39.3; SP = 40.5 kg/day, p = 0.06) and increased milk fat yield in primiparous cows (C = 1.18; SP = 1.27 kg/day, p = 0.02). Including sodium propionate in the total mixed ration is beneficial to reduce health events and increase milk fat production in multiparous cows but may only increase milk fat production in primiparous cows. Full article

Cell function and energy redistribution are influenced by lipid classes (phospholipids (PLs), free fatty acids (FFAs), triglycerides (TGs), and cholesterol esters (CEs)). The aim of this study was to investigate metabolic alterations that are related to changes in lipid classes according to different levels of energy deficits in early lactating Mediterranean buffaloes (MBs). Sixty-three MBs were enrolled at the beginning of lactation using an observational study with a cross-sectional experimental design. Serum β-hydroxybutyrate (BHB) levels were used to group the animals into a healthy group (Group H; n = 38; BHB < 0.70 mmol/L) and hyperketonemia risk group (Group K; n = 25; BHB ≥ 0.70 mmol/L). Statistical analysis was performed using a linear model that included the effect of the group and body condition score to assess differences in fatty acid (FA) concentrations. A total of 40 plasma FAs were assessed in each lipid class. Among the FAs, eight PLs, seven FFAs, four TGs, and four CEs increased according to BHB levels, while three FFAs, three TGs, and one CE decreased. The changes among lipid class profiles suggested the influence of inflammatory response, liver metabolism, and the state of body lipid reserves. In addition, the possible similarities of buffaloes at risk of hyperketonemia with ketotic cows suggest the necessity of further investigations in these ruminants. Full article

Taurine is a sulfated amino acid derivative that plays an important role in maintaining the cell function of the living body. Although taurine has been shown to ameliorate diabetes, its mechanism of action has not yet been fully elucidated. The present study investigated the effects of taurine on diabetes focusing on glucose metabolism and oxidative stress. Type 1 diabetes was induced by the administration of streptozotocin (STZ) to male C57BL/6J mice. Taurine was dissolved in drinking water at 3% (w/v) and allowed to be freely ingested by diabetic mice. The weight and blood glucose levels were measured weekly. After nine weeks, mice were sacrificed and their serum, liver, and kidney were removed and used for biochemical and histological analyses. A microarray analysis was also performed in normal mice. Taurine alleviated STZ-induced hyperglycemia and hyperketonemia, accompanied by the suppression of the decrease in hepatic glycogen and upregulation of the mRNA expression of hepatic glucose transporter GLUT-2. Furthermore, STZ-induced elevation of oxidative stress in the liver and kidney was suppressed by taurine treatment. These results showed that taurine ameliorated diabetes and diabetic complications by improving hepatic glucose metabolism and reducing oxidative stress. Full article

Although nutritional-risk scoring systems allow the determination of the patient’s malnutrition at admission, additional tools might be useful in some clinical scenarios. Previous medical history could be unavailable in unconscious or demented patients. This study aimed to assess the ketone bodies serum levels in patients undergoing elective surgeries and to determine the possible correlation between ketone bodies serum levels and preoperative body weight loss. The study included 21 patients who underwent elective surgery. Hyperketonemia, defined as ketone bodies over 1 mmol/L, was observed in seven (33.3%) patients. Patients with hyperketonemia had significantly higher preoperative percentage body weight loss (p = 0.04) and higher nutritional risk scores prior to surgery (p = 0.04). Serum glucose and the percentage of body weight loss were associated with increased ketone bodies serum levels (Odds Ratios: 0.978 (0.961–0.996, p = 0.019) and 1.222 (1.0–1.492, p = 0.05), respectively). A significant linear correlation was found between the percentage of body weight loss and both ketones bodies (r² = 0.25, p = 0.02) and albumin serum levels (r² = 0.19, p = 0.04). Our study’s results might suggest a positive association between preoperative body weight loss and ketone bodies serum levels. The observation between increased ketone bodies serum levels in patients and preoperative body mass loss merits further research. Full article

The ketogenic diet (KD) entails a high intake of fat, moderate intake of protein, and a very limited intake of carbohydrates. Ketogenic dieting has been proposed as an effective intervention for type 2 diabetes and obesity since glycemic control is improved and sustained weight loss can be achieved. Interestingly, hyperketonemia is also associated with beneficial cardiovascular effects, possibly caused by improved cardiac energetics and reduced oxygen use. Therefore, the KD has the potential to both treat and prevent cardiovascular disease. However, the KD has some adverse effects that could counteract the beneficial cardiovascular properties. Of these, hyperlipidemia with elevation of triglycerides and LDL cholesterol levels are the most important. In addition, poor diet adherence and lack of knowledge regarding long-term effects may also reduce the broader applicability of the KD. The objective of this narrative review is to provide insights into the KD and its effects on myocardial ketone body utilization and, consequently, cardiovascular health. Full article

Hyperketonemia is a very common metabolic state in dairy cows, which result in lower milk production, impaired fertility, and increased frequency of other diseases. In this study, we aimed to determine the influence of season, parity, and milk yield of cows on beta-hydroxybutyrate (BHB) concentration in the second week of lactation (WK 2) and establish the relationship between BHB concentration in WK 2 and reproduction performance traits such as insemination rate and first insemination day of Lithuanian Black and White dairy cows. The study included clinically healthy Lithuanian Black and White cows (n = 692). Blood BHB concentration was measured using capillary blood samples collected after morning milking when cows were 7–10 DIM. The impact of WK 2 blood BHB concentration on the insemination rate and first insemination day were investigated. The effect of BHB was evaluated according to the season, parity, and milk yield per lactation (305 DIM). Significant differences were observed in BHB concentration in WK 2 due to season and parity, but no statistically significant differences were observed for milk yields (305 d). Increased blood BHB concentration in WK 2 negatively affected insemination rate (p < 0.001) and first insemination day (p < 0.001). The study findings indicate that BHB concentration in WK 2 depends on season and parity, while the milk yield is not associated with BHB concentration. High BHB concentration in WK 2 increases insemination rate and delays the first insemination day for high milk-yielding Lithuanian Black and White dairy cows. Full article

This study gives an overview of the performance and accuracy of devices used for the fast measurement of β-hydroxybutyrate (BHBA) in blood for the on-farm indication of subclinical ketosis. Data were collected on ten dairy farms. In each farm, blood samples were taken from ten cows on four test days (2, 4, 9 and 11), resulting in 400 samples. The reference method was the BHBA concentration in blood serum (BHBA_LAB). Four different devices that measure BHBA in whole blood were tested. The thresholds applied for identifying subclinical ketosis were ≥1.0, ≥1.2 and ≥1.4 mmol/L in blood serum. The BHBA_LAB was assigned in three classes: low—≤0.9 mmol/L; high—>0.9 mmol/L; and total—all values unclassified. Due to initial negative effects on the health and performance of cows with BHBA levels ≥0.9 mmol/L, this cut-off was chosen. The Passing–Bablok regression revealed different constant as well as absolute biases for each device in the aforementioned classes. The area under the receiver operating characteristics curve indicated highly accurate results, with 94–97% accuracy levels. As an overall conclusion, the performance of the devices was good and supports their use by farmers for the detection of subclinical ketotic cows in their herds. Full article

The diagnosis of subclinical ketosis in dairy cows based on blood ketone bodies is a challenging and costly procedure. Scientists are searching for tools based on results of milk performance assessment that would allow monitoring the risk of subclinical ketosis. The objective of the study was (1) to design a scoring system that would allow choosing the best machine learning models for the identification of cows-at-risk of subclinical ketosis, (2) to select the best performing models, and (3) to validate them using a testing dataset containing unseen data. The scoring system was developed using two machine learning modeling pipelines, one for regression and one for classification. As part of the system, different feature selections, outlier detection, data scaling and oversampling methods were used. Various linear and non-linear models were fit using training datasets and evaluated on holdout, testing the datasets. For the assessment of suitability of individual models for predicting subclinical ketosis, three β-hydroxybutyrate concentration in blood (bBHB) thresholds were defined: 1.0, 1.2 and 1.4 mmol/L. Considering the thresholds of 1.2 and 1.4, the logistic regression model was found to be the best fitted model, which included independent variables such as fat-to-protein ratio, acetone and β-hydroxybutyrate concentrations in milk, lactose percentage, lactation number and days in milk. In the cross-validation, this model showed an average sensitivity of 0.74 or 0.75 and specificity of 0.76 or 0.78, at the pre-defined bBHB threshold 1.2 or 1.4 mmol/L, respectively. The values of these metrics were also similar in the external validation on the testing dataset (0.72 or 0.74 for sensitivity and 0.80 or 0.81 for specificity). For the bBHB threshold at 1.0 mmol/L, the best classification model was the model based on the SVC (Support Vector Classification) machine learning method, for which the sensitivity in the cross-validation was 0.74 and the specificity was 0.73. These metrics had lower values for the testing dataset (0.57 and 0.72 respectively). Regression models were characterized by poor fitness to data (R² < 0.4). The study results suggest that the prediction of subclinical ketosis based on data from test-day records using classification methods and machine learning algorithms can be a useful tool for monitoring the incidence of this metabolic disorder in dairy cattle herds. Full article

The benefits of a ketogenic diet in childhood epilepsy steered up hope for neuroprotective effects of hyperketonemia in Parkinson’s disease (PD). There are multiple theoretical reasons but very little actual experimental proof or clinical trials. We examined the long-term effects of the ketogenic diet in an animal model of early PD. A progressive, selective dopaminergic medium size lesion was induced by 6-OHDA injection into the medial forebrain bundle. Animals were kept on the stringent ketogenic diet (1% carbohydrates, 8% protein, 70% fat) for 3 weeks prior and 4 weeks after the brain operation. Locomotor activity, neuron count, dopaminergic terminal density, dopamine level, and turnover were analyzed at three time-points post-lesion, up to 4 weeks after the operation. Energy metabolism parameters (glycogen, mitochondrial complex I and IV, lactate, beta-hydroxybutyrate, glucose) were analyzed in the brain and liver or plasma. Protein expression of enzymes essential for gluconeogenesis (PEPCK, G6PC) and glucose utilization (GCK) was analyzed in the liver. Despite long-term hyperketonemia pre- and post-lesion, the ketogenic diet did not protect against 6-OHDA-induced dopaminergic neuron lesions. The ketogenic diet only tended to improve locomotor activity and normalize DA turnover in the striatum. Rats fed 7 weeks in total with a restrictive ketogenic diet maintained normoglycemia, and neither gluconeogenesis nor glycogenolysis in the liver was responsible for this effect. Therefore, potentially, the ketogenic diet could be therapeutically helpful to support the late compensatory mechanisms active via glial cells but does not necessarily act against the oxidative stress-induced parkinsonian neurodegeneration itself. A word of caution is required as the stringent ketogenic diet itself also carries the risk of unwanted side effects, so it is important to study the long-term effects of such treatments. More detailed metabolic long-term studies using unified diet parameters are required, and human vs. animal differences should be taken under consideration. Full article