Blood Ketone Concentrations Research Articles

Feline acute patient physiologic and laboratory evaluation scores and other prognostic factors in cats with first-time diabetic ketoacidosis.

Acute Patient Physiologic and Laboratory Evaluation (APPLE) scores have not been reported in cats with diabetic ketoacidosis (DKA). In cats with DKA, APPLE scores will be significantly higher in non-survivors compared with survivors and these scores will predict mortality. Sixty-eight cats with DKA. Retrospective study. The APPLE scores, blood glucose concentration (BG), venous pH, and ketone concentrations were compared between survivors and non-survivors. Simple logistic regression was used to determine if these variables predict the binary variable of survival or non-survival, and if they did, an empirical optimal cut point for mortality prediction was calculated. The APPLEfast and APPLEfull scores were significantly higher in non-survivors (30 cats; and , respectively) compared with survivors (38 cats; and ; P = .01 and P = .02, respectively). The APPLEfast (P = .03) but not the APPLEfull scores (P = .06) predicted mortality. For every 1 unit increase in the APPLEfast score, the odds of death increased by 1.08 (95% confidence interval [CI], 1.006-1.17; P = .03). Median BG was significantly higher in non-survivors (431 mg/dL; range, 260-832 mg/dL) compared with survivors (343 mg/dL; range, 256-738 mg/dL; P = .01) and BG predicted mortality (P = .02). For every 1 mg/dL increase in BG, the odds of death increased by 1.004 (95% CI, 1.0006-1.008). Empirical optimal cut points for APPLEfast and BG mortality prediction were 24.5 and 358 mg/dL, respectively. The APPLEfast score and BG predict mortality in cats with DKA and can be used to stratify populations by risk of mortality in clinical trials of DKA in cats.

Ketoacidosis and SGLT2 Inhibitors: A Narrative Review.

An acute metabolic complication of diabetes mellitus, especially type 1, is diabetic ketoacidosis (DKA), which is due to an increase in blood ketone concentrations. Sodium/glucose co-transporter-2 inhibitor (SGLT2-i) drugs have been associated with the occurrence of a particular type of DKA defined as euglycemic (euDKA), characterized by glycemic levels below 300 mg/dL. A fair number of euDKA cases in SGLT2-i-treated patients have been described, especially in the last few years when there has been a significant increased use of these drugs. This form of euDKA is particularly insidious because of its latent onset, associated with unspecific symptomatology, until it evolves (progressing) to severe systemic forms. In addition, its atypical presentation can delay diagnosis and treatment. However, the risk of euDKA associated with SGLT2-i drugs remains relatively low, but it is essential to promptly diagnose and manage it to prevent its serious life-threatening complications. In this narrative review, we intended to gather current research evidence on SGLT2i-associated euDKA from randomized controlled trials and real-world evidence studies, its diagnostic criteria and precipitating factors.

The Effect of Acute Ketone Supplementation on Time to Fatigue in NCAA Division I Cross-Country Athletes

This study investigated the effect of a commercially available ketone supplement on heart rate (HR), perceived exertion (RPE), blood lactate, glucose, and ketone concentrations, along with time to fatigue (TTF) during a running task to voluntary fatigue. Twelve NCAA Division I cross-country athletes took part in this randomized, double-blind, placebo-controlled cross-over study. Bayesian methodologies were employed for all statistical analyses, and point estimates were determined to be statistically significant if the 95% highest-density intervals (HDI) excluded zero. TTF was not significantly different between conditions with a Meandiff = 48.7 ± 6.3 s (95% HDI: −335, 424) and a 0.39 probability derived from the posterior distribution, indicating the likelihood that the supplement would increase TTF compared to the placebo control. Lactate concentrations immediately post-exercise were significantly lower in the supplement trial relative to placebo with an estimated Meandiff = −4.6 ± 1.9 mmol; 95% HDI: −8.3, −0.9. There were no significant interaction effects observed for either blood glucose or ketone concentrations nor HR or RPE. These findings imply that the acute ingestion of ketones before running at lactate threshold pace has a low probability of increasing TTF in highly trained Division I runners.

Prolonged remission followed by low insulin requirements in a patient with type 1 diabetes on a very low-carbohydrate diet.

The use of a low-carbohydrate diet (LCD) reduces insulin requirements in insulinopenic states such as type 1 diabetes mellitus (T1DM). However, the use of potentially ketogenic diets in this clinical setting is contentious and the mechanisms underlying their impact on glycaemic control are poorly understood. We report a case of a patient with a late-onset classic presentation of T1DM who adopted a very low-carbohydrate diet and completely avoided insulin therapy for 18 months, followed by tight glycaemic control on minimal insulin doses. The observations suggest that adherence to an LCD in T1DM, implemented soon after diagnosis, can facilitate an improved and less variable glycaemic profile in conjunction with temporary remission in some individuals. Importantly, these changes occurred in a manner that did not lead to a significant increase in blood ketone (beta-hydroxybutyrate) concentrations. This case highlights the need for further research in the form of randomised controlled trials to assess the long-term safety and sustainability of carbohydrate-reduced diets in T1DM. This case highlights the potential of low-carbohydrate diets (LCDs) in type 1 diabetes mellitus (T1DM) to mediate improved diabetes control and possible remission soon after diagnosis. Could carbohydrate-reduced diets implemented early in the course of T1DM delay the decline in endogenous insulin production? Adherence to an LCD in T1DM can facilitate an improved and less variable glycaemic profile. This case suggests that LCDs in T1DM may not be associated with a concerning supraphysiological ketonaemia.

Mixed Potential Type Acetone Sensor with Ultralow Detection Limit for Diabetic Ketosis Breath Analysis.

Breath analysis using gas sensors is an emerging method for disease screening and diagnosis. Since it is closely related to the lipid metabolism and blood ketone concentration of the body, the detection of acetone content in exhaled breath is helpful for the screening and monitoring of diabetes and ketosis. The development of an acetone sensor with high selectivity, stability, and low detection limit has been the research focus for this purpose. Here, we developed a mixed potential type acetone sensor based on Gd2Zr2O7 solid electrolyte and CoSb2O6 sensing electrode. The developed sensor exhibits an extremely low detection limit of 10 ppb, enabling linear detection for acetone in an extremely wide range of 10 ppb-100 ppm. The good results of systematic evaluation on selectivity, repeatability, and stability prove the superior reliability of the sensor, which is a prerequisite for the application in actual breath detection. The ability of the sensor to distinguish healthy people from diabetic ketosis patients was confirmed by using the sensor to detect the breath of healthy people and diabetic patients, proving the feasibility of the sensor in the diagnosis and monitoring of diabetic ketosis.

A Cross Sectional Study of Capillary Blood Ketone Concentrations in Heart Failure Based on SGLT2i Use, Presence of Decompensation, and Heart Failure Type

A Cross Sectional Study of Capillary Blood Ketone Concentrations in Heart Failure Based on SGLT2i Use, Presence of Decompensation, and Heart Failure Type

The effects of caloric restriction on adipose tissue and metabolic health are sex- and age-dependent.

Caloric restriction (CR) reduces the risk of age-related diseases in numerous species, including humans. CR's metabolic effects, including decreased adiposity and improved insulin sensitivity, are important for its broader health benefits; however, the extent and basis of sex differences in CR's health benefits are unknown. We found that 30% CR in young (3-month-old) male mice decreased fat mass and improved glucose tolerance and insulin sensitivity, whereas these effects were blunted or absent in young females. Females' resistance to fat loss was associated with decreased lipolysis, energy expenditure and fatty acid oxidation, and increased postprandial lipogenesis, compared to males. The sex differences in glucose homeostasis were not associated with differential glucose uptake but with altered hepatic ceramide content and substrate metabolism: compared to CR males, CR females had lower TCA cycle activity and higher blood ketone concentrations, a marker of hepatic acetyl-CoA content. This suggests that males use hepatic acetyl-CoA for the TCA cycle whereas in females it accumulates, stimulating gluconeogenesis and limiting hypoglycaemia during CR. In aged mice (18-months old), when females are anoestrus, CR decreased fat mass and improved glucose homeostasis similarly in both sexes. Finally, in a cohort of overweight and obese humans, CR-induced fat loss was also sex- and age-dependent: younger females (<45 years) resisted fat loss compared to younger males while in older subjects (>45 years) this sex difference was absent. Collectively, these studies identify age-dependent sex differences in the metabolic effects of CR and highlight adipose tissue, the liver and oestrogen as key determinants of CR's metabolic benefits. These findings have important implications for understanding the interplay between diet and health, and for maximising the benefits of CR in humans.

The Effects of A Short Period of A Ketogenic Diet on Blood Biochemistry and Immunological Status in Overweight Thai Subjects

Being overweight and obese is a fundamental health problem worldwide and is associated with many diseases. The ketogenic diet (KD) includes high fat and moderate protein, with the daily consumption of carbohydrates amounting to less than 10 % daily intake. KD is a popular choice for weight loss but has benefited many diseases, such as metabolic diseases and neurodegenerative disorders. Nonetheless, the effect of KD on overweight but healthy individuals is limited. Therefore, the objectives of the present study were to evaluate the effects of the KD program on the physical, blood biochemistry, hematological and immunological status of overweight, healthy individuals. The 9 overweight Thai women with body mass index (BMI) values over 25 kg/m2 participated in a self-conduct KD program for 28 days. The mean age of the group was 28.44 years. With 28-days of KD, a significant (p &lt; 0.01) increase in blood ketone confirmed the ketosis status of participants. The mean blood ketone concentration increased from 0.41 ± 0.061 to 1.22 ± 0.267 mmol/L. Most of the participants’ physical parameters, such as body mass index (BMI), body weight, chest circumferences, hip circumferences, and arm circumferences, significantly decreased after 28-days of KD. Furthermore, the biochemistry indices (total cholesterol, triglyceride, LDL-C, and HDL-C) did not significantly differ from the baseline. However, fasting blood sugar decreased (p &lt; 0.01) from 88.00 ± 1.014 to 83.78 ± 1.289 mg/dL. KD did not influence all hematological and immunological indices such as nitric oxide (NO) production (unstimulated and in 2.5 µg/mL PHA stimulation) and T cell subpopulations. Nonetheless, it increased NO production in 5 µg/mL PHA stimulation and mononuclear cell proliferation capacity (proliferation index). The data revealed that short-term KD in this study decreased participants’ physical body compositions and blood glucose levels. Moreover, the immune status after KD proved the immunomodulation effect of KD. HIGHLIGHTS Thai overweight subjects whose self-conducted 28-days ketogenic diet demonstrated Significantly decreased the bodyweight Significantly decreased the body compositions Significantly decreased blood sugar level. Significantly affected immune systems by increasing immune cell proliferation capacity and responding to the non-specific stimulator GRAPHICAL ABSTRACT

Acute Ingestion of Ketone Monoesters and Precursors Do Not Enhance Endurance Exercise Performance: A Systematic Review and Meta-Analysis.

There has been much consideration over whether exogenous ketone bodies have the capacity to enhance exercise performance through mechanisms such as altered substrate metabolism, accelerated recovery, or neurocognitive improvements. This systematic review aimed to determine the effects of both ketone precursors and monoesters on endurance exercise performance. A systematic search was conducted in PubMed, SPORTDiscus, and CINAHL for randomized controlled trials investigating endurance performance outcomes in response to ingestion of a ketone supplement compared to a nutritive or nonnutritive control in humans. A meta-analysis was performed to determine the standardized mean difference between interventions using a random-effects model. Hedge's g and 95% confidence intervals (CI) were reported. The search yielded 569 articles, of which eight were included in this review (80 participants; 77 men and three women). When comparing endurance performance among all studies, no significant differences were found between ketone and control trials (Hedges g = 0.136; 95% CI [-0.195, 0.467]; p = .419). Subanalyses based on type of endurance tests showed no significant differences in time to exhaustion (Hedge's g = -0.002; 95% CI [-0.312, 0.308]; p = .989) or time trial (Hedge's g = 0.057; 95% CI [-0.282, 0.395]; p = .744) values. Based on these findings, exogenous ketone precursors and monoesters do not exert significant improvements on endurance exercise performance. While all studies reported an increase in blood ketone concentrations after ingestion, ketone monoesters appear to be more effective at raising concentrations than precursors.

Can diet composition estimates using stable isotope analysis of feathers predict growth and condition in nestling mountain bluebirds (Sialia currucoides)?

Insectivorous birds breeding in seasonal environments provision their dependent young during periods when prey diversity and abundance vary. Consequently, the composition and nutritional value of diets parents feed to their offspring may differ within and among broods, potentially affecting the condition of nestlings. In a population of mountain bluebirds (Sialia currucoides), we used two methods to estimate diet composition for individual nestlings: direct observation of provisioning using video recordings at 5 and 9 days post‐hatch, and stable isotopes of the δ13C and δ15N in nestling feathers and prey followed by analysis with mixing models. We determined the macronutrient content (% fat and lean mass) and estimated the metabolized energy from each type of prey. We evaluated whether different methods of estimating diet composition would produce similar results, and whether the types of prey nestlings ate at one or both ages affected their morphology, growth rates, or blood ketone concentration. We found that bluebirds fed their young 5 main types of prey: beetles, cicadas, grasshoppers, insect larvae, and spiders. Both observational and mixing model estimates of diet composition indicated that larvae are traded off with grasshoppers and that fewer larvae are provided to nestlings as the season progresses. In evaluating how diet influences individual growth and condition, estimates from direct observations had greater explanatory power than those from mixing models, indicating that diets rich in the most energy‐dense prey (greatest fat content; cicadas and larvae) were associated with larger size and higher body condition, and faster rate of mass gain and growth of tarsus. Lower value prey had more limited, specific effects on nestlings, but may still be important dietary components. While isotopic methods produced estimates of diet composition that were generally informative, when applied to explain the growth and condition of nestlings they proved less useful.

YSZ-based acetone sensor using a Cd2SnO4 sensing electrode for exhaled breath detection in medical diagnosis

Breath analysis using simple gas sensors is becoming one of the important methods for non-invasive, painless and early diagnosis of certain diseases. Among them, the acetone sensor plays a crucial role in screening and diagnosis of diabetes by detecting acetone concentration in exhaled breath. Here, a stabilized zirconia (YSZ)-based mixed potential type acetone sensor combining with Cd2SnO4 sensing electrode (SE) is introduced, which is expected to be used for pre-diagnosis of diabetes. The developed sensor can effectively detect acetone in the concentration range of 0.05−200 ppm at an optimal operating temperature of 600 °C, with sentivities of −17.3 mV/ppm to 0.05−2 ppm acetone and −88.6 mV/decade to 5−200 ppm acetone. Both the sensing behavior and electrochemical test confirm that the sensing principle of the sensor follows to the mixed potential mechanism. The excellent repeatability, selectivity and long-term stability of the sensor make it reliable in the actual application. In addition, clinical tests for the sensor toward exhaled breath of healthy people and diabetic patients are proposed and strong correlations have been established among the response values, acetone concentrations and blood ketone concentrations, which fully demonstrates the great potential of the sensor for pre-diagnosis of diabetes.

Tolerability and Safety of a Novel Ketogenic Ester, Bis-Hexanoyl (R)-1,3-Butanediol: A Randomized Controlled Trial in Healthy Adults.

Nutritional ketosis is a state of mildly elevated blood ketone concentrations resulting from dietary changes (e.g., fasting or reduced carbohydrate intake) or exogenous ketone consumption. In this study, we determined the tolerability and safety of a novel exogenous ketone diester, bis-hexanoyl-(R)-1,3-butanediol (BH-BD), in a 28-day, randomized, double-blind, placebo-controlled, parallel trial (NCT04707989). Healthy adults (n = 59, mean (SD), age: 42.8 (13.4) y, body mass index: 27.8 (3.9) kg/m2) were randomized to consume a beverage containing 12.5 g (Days 0–7) and 25 g (Days 7–28) of BH-BD or a taste-matched placebo daily with breakfast. Tolerability, stimulation, and sedation were assessed daily by standardized questionnaires, and blood and urine samples were collected at Days 0, 7, 14, and 28 for safety assessment. There were no differences in at-home composite systemic and gastrointestinal tolerability scores between BH-BD and placebo at any time in the study, or in acute tolerability measured 1-h post-consumption in-clinic. Weekly at-home composite tolerability scores did not change when BH-BD servings were doubled. At-home scores for stimulation and sedation did not differ between groups. BH-BD significantly increased blood ketone concentrations 1-h post-consumption. No clinically meaningful changes in safety measures including vital signs and clinical laboratory measurements were detected within or between groups. These results support the overall tolerability and safety of consumption of up to 25 g/day BH-BD.

"Point of Care Blood Ketone and Glucose Concentrations in Full Term Healthy Neonates with in First 48 Hours of Life: The POCK Study"

Metabolic adjustment is the process whereby the newborn adapts from a continuous supply of glucose through the placenta to a fast feed cycle and a diet mostly of maternal milk...

To Keto or Not to Keto? A Systematic Review of Randomized Controlled Trials Assessing the Effects of Ketogenic Therapy on Alzheimer Disease

Alzheimer disease (AD) is a global health concern with the majority of pharmacotherapy choices consisting of symptomatic treatment. Recently, ketogenic therapies have been tested in randomized controlled trials (RCTs), focusing on delaying disease progression and ameliorating cognitive function. The present systematic review aimed to aggregate the results of trials examining the effects of ketogenic therapy on patients with AD/mild cognitive impairment (MCI). A systematic search was conducted on PubMed, CENTRAL, clinicaltrials.gov, and gray literature for RCTs performed on adults, published in English until 1 April, 2019, assessing the effects of ketogenic therapy on MCI and/or AD compared against placebo, usual diet, or meals lacking ketogenic agents. Two researchers independently extracted data and assessed risk of bias with the Cochrane tool. A total of 10 RCTs were identified, fulfilling the inclusion criteria. Interventions were heterogeneous, acute or long term (45-180 d), including adherence to a ketogenic diet, intake of ready-to-consume drinks, medium-chain triglyceride (MCT) powder for drinks preparation, yoghurt enriched with MCTs, MCT capsules, and ketogenic formulas/meals. The use of ketoneurotherapeutics proved effective in improving general cognition using the Alzheimer's Disease Assessment Scale-Cognitive, in interventions of either duration. In addition, long-term ketogenic therapy improved episodic and secondary memory. Psychological health, executive ability, and attention were not improved. Increases in blood ketone concentrations were unanimous and correlated to the neurocognitive battery based on various tests. Cerebral ketone uptake and utilization were improved, as indicated by the global brain cerebral metabolic rate for ketones and [11C] acetoacetate. Ketone concentrations and cognitive performance differed between APOE ε4(+) and APOE ε4(-) participants, indicating a delayed response among the former and an improved response among the latter. Although research on the subject is still in the early stages and highly heterogeneous in terms of study design, interventions, and outcome measures, ketogenic therapy appears promising in improving both acute and long-term cognition among patients with AD/MCI. This systematic review was registered at www.crd.york.ac.uk/prospero as CRD42019128311.

Sodium butyrate and monensin supplementation to postweaning heifer diets: Effects on growth performance, nutrient digestibility, and health

The objective of this study was to evaluate growth and performance of postweaning heifers supplemented with monensin (MON), sodium butyrate (SB), or the combination of MON and SB (MSB) compared with heifers not receiving these feed additives. Forty Holstein heifers [mean age 84.2 ± 1.2 d; body weight (BW) 99.8 ± 10.8 kg (mean ± SD)] were housed in a freestall barn, blocked by birth date, and randomly assigned to 1 of 4 treatments in a randomized complete block design. Treatments were (1) 100 g of soybean meal carrier (control; CON); (2) 0.75 g of SB/kg of BW + carrier (SB); (3) 1 mg of MON/kg of BW + carrier (MON); (4) 1 mg of MON/kg of BW + 0.75 g of SB/kg of BW (MSB). Data were analyzed using single degree of freedom contrasts evaluating CON versus additives (ADD), SB versus MON, and SB and MON versus MSB. Treatments were hand-mixed daily. Feed and orts were measured daily and frozen at -20°C. Orts samples were subsampled for dry matter (DM) determination, and total mixed ration samples were taken weekly and composited monthly for DM and nutrient analysis. Initial BW, heart and paunch girths, body length, blood samples, and fecal coccidia counts were measured before the start and weekly during the 12-wk trial. Blood samples were analyzed for glucose, plasma urea nitrogen (PUN), and ketone concentrations. Apparent total-tract nutrient digestibility was determined from d 21 to 27 and from d 63 to 69 using acid detergent insoluble ash as a marker. Daily dry matter intake (DMI) and metabolizable energy intake were increased in ADD compared with CON, and average BW, final BW, and heart girth tended to increase. Whereas MSB tended to be greater than SB and MON for heart girth, feed efficiency was greater with MON compared with SB. Compared with CON, ADD decreased coccidia counts. No effect of treatment on PUN was detected. Monensin and SB tended to have greater plasma glucose than MSB did. Average blood ketone concentrations were greater with ADD versus CON, in SB versus MON, and in MSB versus SB and MON. During the wk-3 digestibility phase, DMI tended to be greater in heifers fed SB versus MON, as well as in heifers fed MSB versus SB and MON. Digestibility of nutrients were similar, except that starch digestibility was increased in heifers fed MSB versus SB and MON. During the wk-9 digestibility phase, DMI and digestibility of nutrients were similar, except NDF, which tended to be greater in CON than in ADD. Overall, ADD resulted in positive growth and reduced coccidia compared with CON.

The Effect of Blood Ketone Concentration and Exercise Intensity on Exogenous Ketone Oxidation Rates in Athletes.

Exogenous ketones potentially provide an alternative, energetically advantageous fuel to power exercising skeletal muscle. However, there is limited evidence regarding their relative contribution to energy expenditure during exercise. Furthermore, the effect of blood ketone concentration and exercise intensity on exogenous ketone oxidation rates is unknown. Six athletes completed cycling ergometer exercise on three occasions within a single-blind, random-order controlled, crossover design study. Exercise duration was 60 min, consisting of 20-min intervals at 25%, 50%, and 75% maximal power output (WMax). Participants consumed (i) bitter flavored water (control), (ii) a low-dose β-hydroxybutyrate (βHB) ketone monoester (KME; 252 mg·kg BW-1, "low ketosis"), or (iii) a high-dose βHB KME (752 mg·kg BW-1, "high ketosis"). The KME contained a 13C isotope label, allowing for the determination of whole-body exogenous βHB oxidation rates through sampled respiratory gases. Despite an approximate doubling of blood βHB concentrations between low- and high-ketosis conditions (~2 mM vs ~4.4 mM), exogenous βHB oxidation rates were similar at rest and throughout exercise. The contribution of exogenous βHB oxidation to energy expenditure peaked during the 25% WMax exercise intensity but was relatively low (4.46% ± 2.71%). Delta efficiency during cycling exercise was significantly greater in the low-ketosis (25.9% ± 2.1%) versus control condition (24.1% ± 1.9%; P = 0.027). Regardless of exercise intensity, exogenous βHB oxidation contributes minimally to energy expenditure and is not increased by elevating circulating concentrations greater than ~2 mM. Despite low exogenous βHB oxidation rates, exercise efficiency was significantly improved when blood βHB concentration was raised to ~2 mM.

Effects of a modestly lower carbohydrate diet in gestational diabetes: a randomized controlled trial

Lower carbohydrate diets have the potential to improve glycemia but may increase ketonemia in women with gestational diabetes (GDM). We hypothesized that modestly lower carbohydrate intake would not increase ketonemia. To compare blood ketone concentration, risk of ketonemia, and pregnancy outcomes in women with GDM randomly assigned to a lower carbohydrate diet or routine care. Forty-six women aged (mean±SEM) 33.3±0.6 y and prepregnancy BMI 26.8±0.9 kg/m2 were randomly assigned at 28.5±0.4 wk to a modestly lower carbohydrate diet (MLC, ∼135 g/d carbohydrate) or routine care (RC, ∼200 g/d) for 6 wk. Blood ketones were ascertained by finger prick test strips and 3-d food diaries were collected at baseline and end of the intervention. There were no detectable differences in blood ketones between completers in the MLC group compared with the RC group (0.1±0.0 compared with 0.1±0.0 mmol/L, n=33, P=0.31, respectively), even though carbohydrate and total energy intake were significantly lower in the intervention group (carbohydrate 165±7 compared with 190±9 g, P=0.04; energy 7040±240 compared with 8230±320 kJ, P<0.01, respectively). Only 20% of participants in the MLC group met the target intake compared with 65% in the RC group (P<0.01). There were no differences in birth weight, rate of large-for-gestational-age infants, percent fat mass, or fat-free mass between groups. An intervention to reduce carbohydrate intake in GDM did not raise ketones to clinical significance, possibly because the target of 135 g/d was difficult to achieve in pregnancy. Feeding studies with food provision may be needed to assess the benefits and risks of low-carbohydrate diets. This trial was registered at www.anzctr.org.au as ACTRN12616000018415.

Efficacy of propylene glycol on prevention and treatment of ketosis for dairy cows in lactation stage

The objective of this study was to evaluate the efficacy of propylene glycol (PG) on prevention and treatment of ketosis in dairy cows from 09/2018 to 03/2019. The study consisted of 2 experiments using a total of 126 multiparous dairy cows in a HF crossbred herd. Cows in both experiments were randomly assigned to treatments in a randomized complete block design. In Exp. 1, 96 cows without ketosis disease (BHBA &lt; 1.4 mmol/L) were assigned to 2 groups (48 cows/group), including (1) untreated control group (no PG) and (2) treatment group (oral PG for 3 consecutive days after parturition). In Exp. 2, 30 ketotic cows (BHBA ≥ 1.4 mmol/L) were divided into 3 groups (10 cows/group), including (1) cows provided with glucose + vitamin B12 + dexamethasone (TT1), (2) cows treated with PG for 3 days (TT2), and (3) combination of TT1 and TT2 (TT3). The results of the Exp. 1 showed that the proportion of ketotic cows was lower (P &lt; 0.01) in the PG-treated group (18.75%) than in the control group (47.92%). The PG treatment also reduced (P &lt; 0.01) the blood ketone concentration of cows as compared with the control without PG use (0.89 vs. 1.22 mmol/L). In the Exp. 2, after treatment the reduction of blood ketone concentration was much greater (P &lt; 0.01) in TT3 cows (1.97 mmol/L) than in TT2 cows (1.30 mmol/L) and TT1 cows (1.23 mmol/L). The percentage of cows recovered from ketosis was greatest in TT3 (90%), followed by TT2 (60%), and then TT1 (50%) (P &gt; 0.05).

Four‐week Ketogenic Diet Improves Aerobic Metabolic Capacity in Extensor Digitrum Longus Muscle of Sedentary Male Rats

Ketogenic diet is an extremely high‐fat diet with low or absence of carbohydrate in the total nutrient. Thus, this diet causes ketone body production from the liver and shifts energy sources from carbohydrate to fat. Whereas previous studies have suggested that ketogenic diet ameliorates brain disorder such as drug‐resistant epilepsy, its influence on peripheral tissue is unclear. Skeletal muscle is an important organ for locomotion and metabolism. Recent studies have suggested that the ketogenic diet changes the energy metabolic properties in the skeletal muscle as well; however, the results are contradictory. Moreover, it remains unknown whether the ketogenic diet affects the muscle contractile function. Therefore, this study aimed to clarify the effect of ketogenic diet on muscle performance and biochemical adaptation in rat skeletal muscle. This study was approved by Institute for Animal Experimentation at St. Marianna University School of Medicine. Male Wistar rats (8 weeks of age) were assigned to either control group (CON) or ketogenic diet group (KD). CON and KD were fed for 4 weeks either control diet (10% fat, 10% protein, 80% carbohydrate) or ketogenic diet (90% fat, 10% protein, 0% carbohydrate), respectively. Body mass was recorded once a week. After the 4‐week feeding period, the animals were anesthetized, and the blood sample was collected to analyze blood ketone concentration. The right extensor digitrum longus (EDL) muscle was used to evaluate the twitch force, tetanic force, and fatigue ex vivo. The left EDL was homogenized and used to analyze the myosin heavy chain composition, the protein expression of metabolic enzymes, and the citrate synthase activity. Body mass was lower in KD than CON at third and fourth week of the feeding period. Blood ketone concentration in KD was significantly higher than CON. There was no statistical difference in the twitch and tetanic forces as well as muscle fatigue between CON and KD. However, the citrate synthase activity in KD was significantly higher than CON. The protein expression of citrate synthase, succinate dehydrogenase, cytochrome c oxidase subunit 4, and 3‐hydroxyacyl‐CoA dehydrogenase in KD was significantly higher than CON. Moreover, there was a shift of myosin heavy chain from type IIb to IIx in KD. Therefore, we conclude that 4‐week ketogenic diet improves skeletal muscle aerobic capacity without obstructing muscle contractile function in the sedentary male rats.Support or Funding InformationThis work was supported by MEXT/JSPS KAKENHI Grant Numbers JP24650334, JP18K17767.

The Effects of Diet‐Induced Obesity in Male Sprague Dawley Rats on Blood Glucose, Ketones and Markers of Mental and Physical fatigue

ObjectivePrevious studies on the pathology of obesity and obesity‐induced metabolic disorders utilized genetically modified obese rat models. To better mimic the onset and the physiology of obesity in humans, the use of diet‐induced obese rat models is lacking. Therefore, the purpose of this study is to induce obesity in Sprague Dawley rats by administering a high fat (HF) diet and to further investigate the effects of obesity on blood glucose and ketone concentrations as well as locomotor and mental activities as indicators of fatigue.MethodsFifty‐four 7‐week‐old male Sprague Dawley rats were randomized into either a high‐fat diet (HFD) group (n=28) or a standard diet (SD) group (n=26). All rats were housed in individual cages under controlled laboratory conditions and had access to food and water ad libitum. The HFD group received a HF diet (60% fat, 20% CHO, and 20% Pr) for six weeks, while the SD group received a standard diet (17% fat, 56% CHO, 27% Pr). Body weight (BW) was measured weekly and blood glucose and ketones were measured twice a week for 6 weeks. The open field test (OF) was conducted daily for 8 days in week 5, followed by Novel object recognition (NOR) testing at 4 separate days during week 6.ResultsBoth groups gained weight from week 1 to week 6 (HFD: 223.0±16.2g vs. 387.7±23.6g, p&lt;0.001; at week 1 vs. week 6, respectively, SD: 215.0±15.9g vs. 361.5±23.6g, p&lt;0.001; at week 1 vs. week 6, respectively). However, the average within‐subject BW gain was greater in the HFD compared to the SD (168.1±21.6g vs 130.1±16.9g, p&lt;0.001; HFD vs. SD, respectively). Although the average glucose levels were not different between the two groups throughout the study, the HFD showed higher fluctuations of blood glucose levels and at week 4 they had higher glucose levels than the SD (104.1±11.2mg/dL vs. 96.6±6.9mg/dL, p=0.005; for HFD vs. SD, respectively). Ketone levels were not different between the two groups. Although there were no overall differences in OF and NOR test results in HFD vs. SD, the difference between the recognition time of the familiar vs. the novel object in the HFD tended to be smaller than that of the SD at all 4 days of NOR testing (p=ns).ConclusionsThe HF diet results in significant weight gain consistent with obesity in the majority of rats within a 6‐week period of receiving the diet. Overall, diet‐induced obesity was not found to have adverse effects on glucose and ketone levels. However, it might negatively affect memory and lead to mental fatigue in rats.