Impact of Exercise on the Presence of Urinary Ketones Based on Korean National Health and Nutrition Examination Survey Data, 2014-2015

한종민,주남석 대한비만학회 2020 The Korean journal of obesity Vol.29 No.2

Background: Ketone bodies are a well-known metabolite from the utilization of fatty acids in the fasting state. Some studies have demonstrated the metabolic benefits of urinary ketones in a specific population in whom ketone bodies were detected. However, other studies described the influence of associated factors on the presence of urinary ketone bodies. In the present study, we analyzed lifestyle factors that are hypothesized to be related to the presence of ketone bodies in urine. Methods: Data from the Korea National Health and Nutrition Examination Survey (KNHANES, 2014–2015) were analyzed. The urinary ketone-positive group was defined as the population in whom urinary ketones were detected. We compared differences in metabolic characteristics as well as lifestyle characteristics such as smoking, alcohol intake, education levels, and exercise between the urine ketone-positive and -negative groups. Results: Of the 9,379 identified eligible subjects, the urine-ketone group showed metabolic benefits with respect to several factors such as body mass index, waist circumference, triglyceride, and high density lipoprotein cholesterol after adjustment for sex and age. A higher proportion of urinary ketones was associated with current smoking (P=0.050), high education level (P=0.008), and aerobic exercise (P=0.021). Conclusion: Aerobic exercise was identified as a factor associated with the presence of urinary ketones. It is also an important lifestyle intervention factor for the recovery of urinary ketones in patients with obesity.

A Focused Review of the Role of Ketone Bodies in Health and Disease

Muhammad Akram 한국식품영양과학회 2013 Journal of medicinal food Vol.16 No.11

Ketone bodies are produced in the liver and are utilized in other tissues in the body as an energy source when hypoglycemia occurs in the body. There are three ketone bodies: acetoacetate, beta hydroxy butyrate, and acetone. Ketone bodies are usually present in the blood, and their level increases during fasting and starvation. They are also found in the blood of neonates and pregnant women. In diabetic ketoacidosis, high levels of ketone bodies are produced in response to low insulin levels and high levels of counter-regulatory hormones.

T-KB-H와 3-HB 키트를 이용한 혈중 총 케톤과 베타-히드록시부틸산 측정법 평가

이경훈,전선희,이광우,한민제,송상훈,박경운,송정한 대한진단검사의학회 2014 Laboratory Medicine Online Vol.4 No.1

Background: Diabetes mellitus and alcohol consumption are the most common causes of ketoacidosis in adults. Recently, β-hydroxybutyric acid (βHBA) was reported to be a potential serum biomarker in the diagnosis and monitoring of ketoacidosis. We evaluated the performance of T-KB-H and 3-HB kits for the measurement of ketone bodies [acetoacetate (AcAc)+βHBA] and βHBA, respectively. Methods: Quantitative enzymatic assays were performed using the T-KB-H and 3-HB kits (Nittobo Medical Co., Japan) and the Architect ci16200 Integrated System (Abbott Laboratories, USA). Simultaneously, the ketone body levels in these serum samples were determined by gas chromato-graphy-mas spectrometry (GC-MS). We evaluated precision and linearity of these kits and correlation with GC-MS, and established reference intervals in children and adults. Results: The coefficients of variation for the T-KB-H and 3-HB kits were less than 4.0% at analyte levels of 50, 100, and 400 μmol/L. Linearity was observed for AcAc and βHBA over a 0-1,000 μmol/L range (R2<0.99). Results from the T-KB-H and 3-HB kits were in good agreement with those from the GC-MS analysis, with correlation coefficients of 0.94 for AcAc and 0.96 for βHBA. Reference intervals determined for the T-KB-H kit were 9.8-270.1 μmol/L and 18.5-531.8 μmol/L in children and adults, respectively. For the 3-HB kit, the reference intervals were 6.4-234.0 μmol/L and 16.0-437.2 μmol/L in children and adults, respectively. Conclusions: The T-KB-H and 3-HB kits displayed good precision, clinically acceptable linearity, and reliable correlation with an established assay. This indicates that the kits can be used clinically for measuring serum ketone bodies. 배경: 성인에서 케톤산증의 가장 많은 원인은 당뇨병과 알코올의 섭취에 의한 것이다. 이러한 케톤산증을 진단 및 치료 효과의 모니터링을 하는데 혈중 베타-히드록시부틸산(βHBA)의 측정을 권장하고 있다. 본 연구는 총케톤체[아세토아세테이트(AcAc)+βHBA]와 βHBA를 각각 측정할 수 있는 T-KB-H와 3-HB 키트의 유용성을 평가하고자 하였다. 방법: 효소법을 이용한 혈중 케톤 정량은 Nittobo 사의 T-KB-H와 3-HB 키트와 Abbott사의 Architect ci16200 기기를 사용하여 측정하였으며, 동시에 가스크로마토그래피-질량분석법(GC-MS)으로 측정하였다. CLSI의 지침에 따라서 정밀도, 직선성, 기존 장비와의 상관성과 소아 및 성인의 참고범위를 설정하였다. 결과: 각 키트마다의 측정한 두가지 농도에 대한 모든 정밀도는 4.00% 미만이었다. 직선성은 0-1,000 mol/L 범위에서 우수하였다(R2<0.99). GC-MS 결과와 비교하였을 때 AcAc의 경우 상관계수가 0.94, βHBA의 경우 0.96으로 양호한 상관관계를 보였다. 그리고 각각의 키트에서 구한 참고범위는 T-KB-H 키트의 경우 소아는 9.8-270.1 mol/L, 성인은 18.5-531.8 mol/L, 3-HB 키트의 경우 소아는 6.4-234.0 mol/L, 성인은 16.0-437.2 mol/L이었다. 결론: T-KB-H와 3-HB 키트는 정밀도 및 직선성이 우수하였고 기존 방법과의 상관성이 양호하므로, 임상적으로 혈중 케톤체의 농도를 측정하는데 유용하게 사용할 수 있을 것으로 생각된다.

Ketone ester supplementation of Atkins type diet prolongs survival in an orthotopic xenograft model of glioblastoma

Hassan Azari,Angela Poff,Dominic D’Agostino,Brent Reynolds 대한해부학회 2024 Anatomy & Cell Biology Vol.57 No.1

Heavy reliance on glucose metabolism and a reduced capacity to use ketone bodies makes glioblastoma (GBM) a promising candidate for ketone-based therapies. Ketogenic diet (KD) is well-known for its promising effects in controlling tumor growth in GBM. Moreover, synthetic ketone ester (KE) has demonstrated to increase blood ketone levels and enhance animal survival in a metastatic VM-M3 murine tumor model. Here, we compared the efficacy of a KE-supplemented Atkins-type diet (ATD-KE) to a classic KD in controlling tumor progression and enhancing survival in a clinically relevant orthotopic patient-derived xenograft GBM model. Our findings demonstrate that ATD-KE preserves body weight (percent change from the baseline; 112±2.99 vs. 116.9±2.52 and 104.8±3.67), decreases blood glucose (80.55±0.86 vs. 118.6±9.51 and 52.35±3.89 mg/dl), and increases ketone bodies in blood (1.15±0.03 mM vs. 0.55±0.04 and 2.66±0.21 mM) and brain tumor tissue (3.35±0.30 mM vs. 2.04±0.3 and 4.25±0.25 mM) comparable to the KD (results presented for ATD-KE vs. standard diet [STD] and KD, respectively). Importantly, the ATD-KE treatment significantly enhanced survival compared to the STD and was indistinguishable from the KD (47 days in STD vs. 56 days in KD and ATD-KE), suggesting that a nutritionally balanced low carbohydrate ATD combined with KE may be as effective as the KD alone in reducing brain tumor progression. Overall, these data support the rationale for clinical testing of KE-supplemented low-carb diet as an adjunct treatment for brain tumor patients.

절식요법으로 인한 체중감소가 체조성과 혈청지질 및 뇨중 무기질 배설에 미치는 영향

신현대,조여원,김복순 WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 1996 東西醫學硏究所 論文集 Vol.1996 No.-

본 연구는 1995년 6월부터 1995년 12월까지 경희의료원 재활의학과 비만 Clinic에 입원한 여성을 대상으로 체중, 체지방, 혈장의 단백질과 glucose, 지질성분, 및 소변중에 배설되는 무기질의 변화를 관찰하여 다음과 같이 요약하였다. 1. 절식시 대상자의 체중은 7.12kg(체중의 8.4%)이 감소되었으며, 절식 6일째까지는 1일 평균 약 1kg씩 감소하다가 그 이후는 1일 평균 0.47kg씩 감소하였다. 또한 절식 초기에 LBM와 체수분이 급격히 감소되었으며, 음식 재섭취 2주후에는 LBM와 TBW는 절식전의 상태로 재증가되었다. 지방은 절식 후반부터 감소되기 시작하여 음식 재섭취시에도 지속적으로 감소되어, 음식 재섭취시 급격한 LBM와 TBW의 증가에도 불구하고 체중의 재증가는 보이지 않았다. 2. 절식전의 영양섭취량을 살펴보면 단백질, niacin, Vitamin C, P를 제외하고 총섭취 열량 및 vitaminB1, vitamin B2, calcium, Fe 섭취량은 일일 권장량에 부족하였으며, 음식 재섭취후에는 vitamin A, vitamin C를 제외하고는 모든 영양소의 섭취가 영양권장량에 미치지 못하는 수준이었다. 절식전 총 섭취열량은 1639.24kcal/day로 영양권장량의 82%를 섭취하고 있었다. 3. 물만이 공급되어지는 절식상태에서 혈장의 glucose과 protein 그리고 albumin 농도의 변화를 관찰한 결과 glucose는 절식시 유의적으로 감소하였다 재섭취시 재증가하였으며, 혈청 total protein, albumin 그리고 BUN의 농도는 절식으로 인해 증가하는 경향을 보였으나 통계적으로 유의성은 없었다. 혈청지질의 조성을 보면 triglyceride, HDL-C, VLDL-C은 절식시 감소하는 경향을 보였고, total cholesterol과 LDL-C은 절식시 증가하는 경향을 보였다. 4. 절식시 소변의 Specific gravity에 변화가 없었으며, 뇨의 PH에도 변화가 없었다. 그러나 ketone body는 절식시 유의적으로 증가하였다가 재섭취후 감소하여 절식이전의 수준으로 되돌아갔다. 소변중의 Na은 절식함에 따라 감소되었으며, K은 절식후반부터 감소되어졌고, calcium과 magnesium에는 유의적인 변화가 없었다. The purpose of this study was to investigate the effects of fasting on body composition, plasma lipids and urinary excretion of minerals in obese women. Nine healthy women were admitted to the Obese Clinic of K Oriental hospital to reduce their body weight. The Obese Clinic program consists of three phases, a period of reducing food intakes, total fasting, and refeeding. The mean of body weight and body mass index of all subjects were 86.1kg and 33.7, respectively. Total loss of body weight after the program was 7.2kg. Lean body mass and total body water decreased dramatically during the fasting period whereas body fat weight decreased slowly and continued to decrease during the entire program. At the admission to the Obese Clinic, the subjects consumed 1,639kcal/day, and during the refeeding period, the subjects consumed under 1,000kcal/day. The levels of plasma total protein and BUN increased during the fasting period, however the level of plasma glucose decreased significantly after fasting. The level of plasma triglyceride decreased after fasting and concentration of plasma total lipid, HDL-C and PL was the same throughout the entire fasting period. Whereas the level of total cholesterol and LDL-C increased during the fasting period. The urinary loss of ketone body dramatically increased during fasting period, showing a markedly enhanced ketosis and refeeding bring them back to the first value immediatly. Urinary loss of sodium was the greastest during the first 3 days of fasting. Urinary excretion of potassium was the same during the early part of fasting period and significantly decreased during the latter part of the fasting period, showing an adaptation to the depletion. The losses of calcium and magnesium were not changed as restriction progressed.

간 절제술후 초기 예후 인자로서의 동맥혈 Ketone Body Ratio의 의의

전용성(Yong Sung Jeon),김홍진(Hong Jin Kim),심민철(Min Chul Shim),권굉보(Koing Bo Kwun) 대한소화기학회 1995 대한소화기학회지 Vol.27 No.5

N/A Background/Aims: Recent surgical techniques have enabled surgeons to undertake radical operations for a much wider range of liver diseases, but the invasive nature of such operations requires that they be followed up by careful and intensive postoperative management. Since the introduction of the oxidation-reduction(redox) theory in the beginning of 1980s, the significance of the arterial ketone body ratio(acetoactate/g-hydroxybutylate), which reflects hepatic mitochondria] oxidation-reduction potential, has been discussed as one of the metabolic parameters of organ failure. The aim of this study was to assess the significance of arterial ketone body ratio as an early prognostic indicator in liver surgery. Methods: In this study, arterial ketone body ratio and total ketone body concentration were serially measured in 83 patients who underwent liver resection in the department of surgery of Youngnam University Hospital between May 1992 and Feburary 1994. Results: At the postoperative 1 day, arterial ketone body ratio was significantly higher in successful recovery group(n=71, 1.22 0.59) than that of the postoperative complication and mortality group(n=12, 0.66 l 0.34). And patients were classified into three groups by the decrease of ketone body ratio in the postoperative 1 day: group A(70 cases) with ketone body ratio above 0.7, group B(12 cases) between 0.7 and 0.4, and group C(1 case) below 0.4. In group A, 63 patients(90%) were recovered, 6 patients complicated and 1 patient dead. In B group, 8 patients(66.6%) was recovered, 2 patients complicated and 2 patients dead. The only patient of group C(100%) was dead. Conclusions: Postoperative AKBR is useful as an early prognostic indicator in liver surgery, and maintenance of AKBR above 0.7 is crucial to obtain a good surgical outcome. (Korean J Gastroenterol 1995;27: 555 - 562)

The Ketone Bridge Between the Heart and the Bladder: How Fast Should We Go?

Gabriel Faria-Costa,João Oliveira,Inês Vilas-Boas,Inês Campelo,Elisa Azeredo Silva,Carmen Brás-Silva,Susana Maria Silva,Tiago Antunes-Lopes,Ana Charrua 대한배뇨장애요실금학회 2024 International Neurourology Journal Vol.28 No.-

Metabolic syndrome (MS) is associated with both cardiovascular and bladder dysfunction. Insulin resistance (IR) and central obesity, in particular, are the main risk factors. In these patients, vicious pathological cycles exacerbate abnormal carbohydrate metabolism and sustain an inflammatory state, with serious implications for both the heart and bladder. Ketone bodies serve as an alternative energy source in this context. They are considered a “super-fuel” because they generate adenosine triphosphate with less oxygen consumption per molecule, thus enhancing metabolic efficiency. Ketone bodies have a positive impact on all components of MS. They aid in weight loss and glycemic control, lower blood pressure, improve lipid profiles, and enhance endothelial function. Additionally, they possess direct anti-inflammatory, antioxidant, and vasodilatory properties. A shared key player in dysfunction of both the heart and bladder dysfunction is the formation of the NLRP3 inflammasome, which ketone bodies inhibit. Interventions that elevate ketone body levels—such as fasting, a ketogenic diet, ketone supplements, and sodium-glucose cotransporter 2 inhibitors—have been shown to directly affect cardiovascular outcomes and improve lower urinary tract symptoms derived from MS. This review explores the pathophysiological basis of the benefits of ketone bodies in cardiac and bladder dysfunction.

Effects of Enzyme Type and Molar Ratio on Enzymatic Synthesis of Hydroxybutyrate Methyl Ester

Jemin SON,Kyeonga KIM,Seungmee LEE,Hah Young YOO,Chulhwan PARK 한국생물공학회 2021 한국생물공학회 학술대회 Vol.2021 No.10

Ketone bodies are energy supplements produced from fatty acids by the liver under energy restriction conditions. In recent studies, several clinical effects, such as the increase of cardiac energetics and potential uses as a treatment for cancer and cardiovascular disease, are observed when the ketone body concentration in the blood is maintained over 0.5 mM. Appropriate ingestion ways of ketone bodies are investigated, and ketone esters were recognized as the most effective ingestion way. Hydroxybutyrate methyl ester, one of ketone esters, can effectively increase ketone body concentration in the blood with fewer doses than other options and are shown several clinical effects as ketone bodies and also as itself. Through ingestion of hydroxybutyrate methyl ester, the learning and memory was improved and further, the possibility for the treatment of Alzheimer’s disease was also observed. But still, only few studies are investigated the production of hydroxybutyrate methyl ester. Therefore, the conditions for the production of hydroxybutyrate methyl ester based on enzymes were designed under the consideration of productivity.

개에서 자가 부분 간 이식술전후 동맥혈의 KBR ( Ketone Body Ratio ) 측정과 이식 간의 초기 기능부전 지표로서의 상관관계에 관한 연구

김상준(Sang Joon Kim),김수태(soo Tae Kim),안세현(Sei Hyun Ahn),김병식(Byung Sik Kim),정중기(Jung Kee Jung),김건표(Kyun Pyo Kim),서경석(Kyung Suk Seo) 대한소화기학회 1993 대한소화기학회지 Vol.25 No.5

N/A Living-related segmental liver transplantation is now accepted as a method of liver transplantatior in pediatric group. But if graft failure occurs, mortality is high. Hence the early prediction of graft failure may contribute to the improvement of the chance of survival. The ketone bodies (acetoacetate, B-hydroxybutyrate) are known to be produced in the hepatic mitochondria. KBR (ketone body ratio) is a ratio of acetoacetate/B-hydroxybutyrate, which ref1ects the NAD+/NADH, i.e. oxidoreduction state of NAD of hepatic mitochondria. Because the viability of grafted liver is ultimately depeadant on the oxidoreduction potential of hepatic mitochondria, KBR might reflect the viability of grafted liver. The purpose of this experiment is to study whether KBR is a useful indicator of initial grat failure after liver transplantation. The experiment consisted of ten autologous left lobe liver transplants in dogs. The arterial blood was taken at preoperative period, anhepatic stage, reperfusion-15 minutes, 1 hour, 3 hour, 6 hour anl daily during their survival, and then KBR was calculated by ketone body concentration. The result of KBR measurement was as follows; it was 1.16+-0.33 at preoperative period, and abruptly decreased to 0.46+- 0.21 at anhepatic stage, and recovered to various levels according to initial graft function after reperfusion. To evaluate the initial graft function, the dogs were divided into two groups. A group (n=3) had KBR below 0.7 at reperfusion 1 hour, and B group (n=7) above 1.0. In group A, all of them showed early graft failure and died within 12 hours postoperatively. KBR changes in group A were as follows; it was 1.16 at preoperative period, and decreased to 0.25 at anhepatic stage, and recorded 0.69, 0.54, 0.61, 0.29 at reperfusion-15 min, 1 hour, 3 hour, 6 hour respectively. It never recovered above 0.7 at any period after reperfusion. In group B. they showed good early-graft function with survival of 16 hours to 8 days and died of other causes, ln group B, preoperative KBR was 1.16, and decreased to 0.54 at anhepatic stage, but promptly recovered to 0.95 at reperfusion-15 minute, 1.32 at 1 hour. It slightly decreased to 0.83 at 1 hour but maintained above 1.0 after 6 hour. In conclusion, the decreased KBR at anhepatic stage should promptly recover after reperfusion for the graft viability, and the value below 0.7 of KBR after reperfusion-1 hour represents the early graft failure, and above 1.0 of KBR represents good functioning graft. The KBR is a useful indicator of early graft function in canine autologous segmental liver transplantation, and it is assumed that KBR is further applicable on canine and human allogenic segmental liver transplantation.

SGLT2 Inhibitors and Ketone Metabolism in Heart Failure

Saucedo-Orozco Huitzilihuitl,Voorrips Suzanne N.,Yurista Salva R.,de Boer Rudolf A.,Westenbrink B. Daan 한국지질동맥경화학회 2022 지질·동맥경화학회지 Vol.11 No.1

Sodium-glucose cotransporter-2 (SGLT2) inhibitors have emerged as powerful drugs that can be used to treat heart failure (HF) patients, both with preserved and reduced ejection fraction and in the presence or absence of type 2 diabetes. While the mechanisms underlying the salutary effects of SGLT2 inhibitors have not been fully elucidated, there is clear evidence for a beneficial metabolic effect of these drugs. In this review, we discuss the effects of SGLT2 inhibitors on cardiac energy provision secondary to ketone bodies, pathological ventricular remodeling, and inflammation in patients with HF. While the specific contribution of ketone bodies to the pleiotropic cardiovascular benefits of SGLT2 inhibitors requires further clarification, ketone bodies themselves may also be used as a therapy for HF.