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Background Aims: With the aim of strengthening the scientific evidence of immune-cell therapy for cancer and further examining its safety, in October 2015, our hospital jointly established the Cancer Immune-Cell Therapy Evaluation Group (CITEG) with 39 medical facilities nationwide., Methods: Medical information, such as patients' background characteristics, clinical efficacy and therapeutic cell types obtained from each facility, has been accumulated, analyzed and evaluated by CITEG. In this prospective study, we analyzed the adverse events associated with immune-cell therapy until the end of September 2022, and we presented our interim safety evaluation., Results: A total of 3839 patients with malignant tumor were treated with immune-cell therapy, with a median age of 64 years (range, 13-97 years) and a male-to-female ratio of 1:1.08 (1846:1993). Most patients' performance status was 0 or 1 (86.8%) at the first visit, and 3234 cases (84.2%) were advanced or recurrent cases, which accounted for the majority. The total number of administrations reported in CITEG was 31890, of which 960 (3.0%) showed adverse events. The numbers of adverse events caused by treatment were 363 (1.8%) of 19661 administrations of αβT cell therapy, 9 of 845 administrations of γδT-cell therapy (1.1%) and 10 of 626 administrations of natural killer cell therapy (1.6%). The number of adverse events caused by dendritic cell (DC) vaccine therapy was 578 of 10748 administrations (5.4%), which was significantly larger than those for other treatments. Multivariate analysis revealed that αβT cell therapy had a significantly greater risk of adverse events at performance status 1 or higher, and patients younger than 64 years, women or adjuvant immune-cell therapy had a greater risk of adverse events in DC vaccine therapy. Injection-site reactions were the most frequently reported adverse events, with 449 events, the majority of which were associated with DC vaccine therapy. Among all other adverse events, fever (228 events), fatigue (141 events) and itching (131 events) were frequently reported. In contrast, three patients had adverse events (fever, abdominal pain and interstitial pneumonia) that required hospitalization, although they were weakly related to this therapy; rather, it was considered to be the effect of treatment for the primary disease., Conclusions: Immune-cell therapy for cancer was considered to be a safe treatment without serious adverse events., (Copyright © 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Phosphoglycerate kinase (PGK) deficiency is an X-linked disorder characterized by a combination of hemolytic anemia, myopathy, and brain involvement. We herein report a Japanese man who had several episodes of rhabdomyolysis but was training strenuously to be a professional boxer. Mild hemolytic anemia was noted. The enzymatic activity of PGK was significantly reduced, and a novel missense mutation, p.S62N, was identified in the PGK1 gene. A literature review revealed only one case with a mixed hemolytic and myopathic phenotype like ours. This mild phenotype indicates the complex pathophysiology of PGK deficiency and suggests the benefits of dietary control and exercise.

Background and Objectives: Pompe disease is reportedly less prevalent in Japan than in neighbouring countries, raising a possibility that some patients may be overlooked. Therefore, all muscle biopsy samples received at our institute were screened for Pompe disease to determine the accuracy of the disease prevalence., Methods: The acid α-glucosidase (GAA) activity was assayed using 10 µm frozen muscle sections from 2408 muscle biopsies received between July 2015 and January 2018. Genetic analysis was performed for samples with decreased activity. The number of myopathologically diagnosed patients was retrospectively assessed., Results: The GAA activity was distributed similarly to previous results from dried blood spot screening. GAA activity measured using muscle sections corresponded to that measured using muscle blocks. Of 163 patients with GAA activity <3 nmol/hour/mg protein, 43 (26%) patients had homozygous pseudodeficiency alleles in GAA (p.G576S and p.E689K). In the retrospective analysis, the number of patients diagnosed with Pompe disease via muscle biopsies decreased to zero over time., Discussion: Muscle pathology is an accurate method to diagnose Pompe disease. It is unlikely that a significant number of patients with Pompe disease are overlooked. Pathological variants were rare, and the majority carried a pseudodeficiency allele, which further supports our conclusion., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Muscle phosphorylase b kinase (PHK) deficiency is a rare mild metabolic disorder caused by mutations of the PHKA1 gene encoding the αM subunit of PHK. A 16-year-old boy experienced myalgia during the maximal multistage 20-m shuttle run test targeting the maximal oxygen consumption. Although an ischemic forearm exercise test was normal, a muscle biopsy revealed subsarcolemmal glycogen accumulation. He harbored a novel insertion mutation in the PHKA1 gene that resulted in premature termination of the αM subunit close to the C-terminus. Compared with previously reported cases, his reduction in PHK activity was relatively mild.

Increasing adaptive thermogenesis through the activation of brown adipose tissue (BAT) is a promising practical strategy for preventing obesity and related disorders. Ingestion of a single dose of 40 mg of an extract of Grains of Paradise (GP), a ginger family species, reportedly triggers BAT thermogenesis in individuals with high but not in those with low BAT activity. We hypothesized that prolonged treatment with GP might revive BAT in individuals who have lost active BAT. In the present study, we recruited 9 healthy young male volunteers with reduced BAT that was assessed by fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) following 2-h cold exposure at 19ºC. The subjects ingested GP extract (40 mg/d) or placebo every day for 5 wk. Before and after the treatment with either GP or placebo, their body composition and BAT-dependent cold-induced thermogenesis (CIT)-a non-invasive index of BAT-were measured in a single-blinded, randomized, placebo-controlled cross-over design. Their whole-body resting energy expenditure at a thermoneutral condition remained unchanged following GP treatment. However, CIT after treatment was significantly higher in GP-treated individuals than in placebo-treated individuals. Body weight and fat-free mass did not change significantly following GP or placebo treatment. Notably, body fat percentage slightly but significantly decreased after GP treatment but not after placebo treatment. These results suggest that repeated ingestion of GP elevates adaptive thermogenesis through the re-activation of BAT, thereby reducing body fat in individuals with low BAT activity.

Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a genetic disorder of fatty acid beta oxidation that is caused by a defect in ACADVL, which encodes VLCAD. The clinical presentation of VLCAD deficiency is heterogeneous, and either a delayed diagnosis or a misdiagnosis may sometimes occur. We herein describe a difficult-to-diagnose case of the muscle form of adult-onset VLCAD deficiency with compound heterozygous ACADVL mutations including c.790A>G (p.K264E) and c.1246G>A (p.A416T).

A 27 year-old Canadian man suffered from fluctuating muscle weakness in the past several years. The patient had a past history of intestinal bleeding, bifid uvula and hypothyroidism in his childhood. Repetitive nerve stimulation tests showed a decrement pattern in the left deltoid muscle. The single fiber electromyography of the left extensor digitorum muscle showed an increment of jitter. Both findings were improved by the edrophonium test. He was diagnosed as having phosphoglucomutase 1 (PGM1) deficiency, as the compound heterozygote mutation of the PGM1 gene was recognized in the whole-exome sequencing and the enzyme activity of PGM1 was defective in the biopsied muscle. Treatment with the galactose lead to improvement of the fluctuating muscle weakness and decremental pattern in the repetitive stimulation test. PGM1 deficiency should be listed in the differential diagnosis of the neuromuscular junction disorder, when the patient is seronegative for antibodies related with myasthenia gravis and shows symptoms or signs consistent with PGM1 deficiency.

Objective: To investigate the effect of guidelines for management of febrile seizures on the clinical practice, we conducted a nationwide survey in Japan., Methods: The Japanese guidelines for management of febrile seizures 2015 (GL2015) was released in 2015. In 2016, a questionnaire was sent to all 512 certified hospitals (3 pediatricians each) of the Japan Pediatric Society and all 47 prefecture Pediatric Associations (10 private pediatricians each) in Japan asking about management policies for febrile seizures (FSs) during 2013-2014 and 2016. The questionnaires were about the following procedures: (1) lumbar punctures, blood examinations, and diazepam suppositories for children after a first simple FS at emergency departments; and (2) prophylactic diazepam during febrile illnesses in children with two or three past simple FSs, with no known predictors of recurrence., Results: A total of 1327 pediatricians (66.2%) answered the questionnaire. Numbers of pediatricians performing lumbar punctures and blood examinations, and giving diazepam suppositories after a first simple FS were less in 2016 than in 2013-2014 (1.2% and 2.0%, 53.1% and 61.3%, and 36.7% and 51.9%, respectively). Pediatricians recommending prophylactic diazepam for children with two and three FSs decreased from 45.7% and 82.4% in 2013-2014 to 31.0% and 65.0% in 2016, respectively., Conclusion: GL2015 had an effect on the clinical practices of pediatricians. On the other hand, 65% recommended prophylactic diazepam to children with three simple FSs even though GL2015 did not recommend use of diazepam based on number of previous FS. Anxiety about frequent seizures may affect pediatricians' clinical practice., (Copyright © 2019 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Phosphoglucomutase 1 (PGM1) deficiency is a recently defined disease characterized by glycogenosis and a congenital glycosylation disorder caused by recessive mutations in the PGM1 gene. We report a case of a 12-year-old boy with first-cousin parents who was diagnosed with a PGM1 deficiency due to significantly decreased PGM1 activity in his muscle. However, Sanger sequencing revealed no pathogenic mutation in the PGM1 gene in this patient. As this case presented with a cleft palate in addition to hypoglycemia and elevated transaminases and creatine kinase, karyotyping was performed and identified homozygous inv(1)(p31.1p32.3). Based on the chromosomal location of the PGM1 gene at 1p31, we analyzed the breakpoint of the inversion. Fluorescence in situ hybridization (FISH) combined with long PCR analysis revealed that the inversion disrupts the PGM1 gene within intron 1. Since the initiation codon in the PGM1 gene is located within exon 1, we speculated that this inversion inactivates the PGM1 gene and was therefore responsible for the patient's phenotype. When standard molecular testing fails to reveal a mutation despite a positive clinical and biochemical diagnosis, the presence of a gross structural variant that requires karyotypic examination must be considered.

Background: The thermogenic effects of green tea catechin have been repeatedly reported, but their mechanisms are poorly understood. Objective: The aim of this study was to investigate the acute and chronic effects of catechin on brown adipose tissue (BAT), a site specialized for nonshivering thermogenesis, in humans. Design: Fifteen healthy male volunteers underwent fluorodeoxyglucose-positron emission tomography to assess BAT activity. To examine the acute catechin effect, whole-body energy expenditure (EE) after a single oral ingestion of a beverage containing 615 mg catechin and 77 mg caffeine (catechin beverage) was measured. Next, to investigate the chronic catechin effects, 10 men with low BAT activity were enrolled. Before and after ingestion of the catechin beverage 2 times/d for 5 wk, cold-induced thermogenesis (CIT) after 2 h of cold exposure at 19°C, which is proportional to BAT activity, was examined. Both the acute and chronic trials were single-blinded, randomized, placebo-controlled, season-matched crossover studies. Results: A single ingestion of the catechin beverage increased EE in 9 subjects who had metabolically active BAT (mean ± SEM: +15.24 ± 1.48 kcal, P < 0.01) but not in 6 subjects who had negligible activities (mean ± SEM: +3.42 ± 2.68 kcal). The ingestion of a placebo beverage containing 82 mg caffeine produced a smaller and comparative EE response in the 2 subject groups. Multivariate regression analysis revealed a significant interaction between BAT and catechin on EE (β = 0.496, P = 0.003). Daily ingestion of the catechin beverage elevated mean ± SEM CIT (from 92.0 ± 26.5 to 197.9 ± 27.7 kcal/d; P = 0.009), whereas the placebo beverage did not change it. Conclusion: Orally ingested tea catechin with caffeine acutely increases EE associated with increased BAT activity and chronically elevates nonshivering CIT, probably because of the recruitment of BAT, in humans. These trials were registered at www.umin.ac.jp/ctr/ as UMIN000016361., (© 2017 American Society for Nutrition.)

Neonatal diabetes mellitus (NDM) is an insulin-requiring monogenic form of diabetes that generally presents before six months of age. The following two types of NDM are known: transient NDM (TNDM) and permanent NDM (PNDM). Here we report on an infant with TNDM caused by a mutation (p.Gly832Cys) of the gene for the ATP binding cassette subfamily C member 8 (ABCC8). The patient exhibited hyperglycemia (600 mg/dL) at five weeks of age and insulin treatment was initiated. As genetic analysis identified a missense mutation within ABCC8 , the insulin was replaced by glibenclamide at five months of age. Thereafter, the insulin was successfully withdrawn and his glycemic condition was well controlled at a dose of 0.0375 mg/kg/d. Since the patient's blood glucose was under control and serum C-peptide levels were measurable, glibenclamide was stopped at 1 yr, 10 mo of age. The lack of DM relapsed to date confirms the TNDM diagnosis. In conclusion, when insulin is replaced with a sulfonylurea-class medication (SU) in NDM patients, serum C-peptide levels should be closely monitored and fine adjustment of SU dose is recommended.

In 2015, the Japanese Society of Child Neurology released new guidelines for the management of febrile seizures, the first update of such guidelines since 1996. In 1988, the Conference on Febrile Convulsions in Japan published "Guidelines for the Treatment of Febrile Seizures." The Task Committee of the Conference proposed a revised version of the guidelines in 1996; that version released in 1996 was used for the next 19years in Japan for the clinical management of children with febrile seizures. Although the guidelines were very helpful for many clinicians, new guidelines were needed to reflect changes in public health and the dissemination of new medical evidence. The Japanese Society of Child Neurology formed a working group in 2012, and published the new guidelines in March 2015. The guidelines include emergency care, application of electroencephalography, neuroimaging, prophylactic diazepam, antipyretics, drugs needing special attention, and vaccines. While the new guidelines contain updated clinical recommendations, many unsolved questions remain. These questions should be clarified by future clinical research., (Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Pompe disease is an autosomal recessive, lysosomal glycogen storage disease caused by acid α-glucosidase deficiency. Infantile-onset Pompe disease (IOPD) is the most severe form and is characterized by cardiomyopathy, respiratory distress, hepatomegaly, and skeletal muscle weakness. Untreated, IOPD generally results in death within the first year of life. Enzyme replacement therapy (ERT) with recombinant human acid alpha glucosidase (rhGAA) has been shown to markedly improve the life expectancy of patients with IOPD. However, the efficacy of ERT in patients with IOPD is affected by the presence of symptoms and cross-reactive immunologic material (CRIM) status. We have treated two siblings with IOPD with ERT at different ages: the first was symptomatic and the second was asymptomatic. The female proband (Patient 1) was diagnosed with IOPD and initiated ERT at 4 months of age. Her younger sister (Patient 2) was diagnosed with IOPD at 10 days of age and initiated ERT at Day 12. Patient 1, now 6 years old, is alive but bedridden, and requires 24-hour invasive ventilation due to gradually progressive muscle weakness. In Patient 2, typical symptoms of IOPD, including cardiac failure, respiratory distress, progressive muscle weakness, hepatomegaly and myopathic facial features were largely absent during the first 12 months of ERT. Her cardiac function and mobility were well-maintained for the first 3 years, and she had normal motor development. However, she developed progressive hearing impairment and muscle weakness after 3 years of ERT. Both siblings have had low anti-rhGAA immunoglobulin G (IgG) antibody titers during ERT and have tolerated the treatment well. These results suggest that initiation of ERT during the pre-symptomatic period can prevent and/or attenuate the progression of IOPD, including cardiomyopathy, respiratory distress, and muscle weakness for first several years of ERT. However, to improve the long-term efficacy of ERT for IOPD, new strategies for ERT for IOPD, e.g. modifying the enzyme to enhance uptake into skeletal muscle and/or to cross the blood brain barrier (BBB), will be required.

18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDGPET/CT) is widely used as a standard method for evaluating human brown adipose tissue (BAT), a recognized therapeutic target of obesity. However, a longitudinal BAT study using FDG-PET/CT is lacking owing to limitations of the method. Near-infrared time-resolved spectroscopy (NIR(TRS)) is a technique for evaluating human BAT density noninvasively. This study aimed to test whether NIRTRS could detect changes in BAT density during or after long-term intervention. First, using FDG-PET/CT, we confirmed a significant increase (+48.8%, P < 0.05) in BAT activity in the supraclavicular region after 6-week treatment with thermogenic capsaicin analogs, capsinoids. Next, 20 volunteers were administered either capsinoids or placebo daily for 8 weeks in a double-blind design, and BAT density was measured using NIR(TRS) every 2 weeks during the 8-week treatment period and an 8-week period after stopping treatment. Consistent with FDG-PET/CT results, NIR(TRS) successfully detected an increase in BAT density during the 8-week treatment (+46.4%, P < 0.05), and a decrease in the 8-week follow-up period (-12.5%, P = 0.07), only in the capsinoid-treated, but not the placebo, group. Thus, NIR(TRS) can be applied for quantitative assessment of BAT in longitudinal intervention studies in humans.

Brown adipose tissue (BAT) contributes to whole-body energy expenditure (EE), especially cold-induced thermogenesis (CIT), in humans. Although it is known that EE and CIT vary seasonally, their relationship with BAT has not been investigated. In the present study, we examined the impact of BAT on seasonal variations of EE/CIT and thermal responses to cold exposure in a randomized crossover design. Forty-five healthy male volunteers participated, and their BAT was assessed by positron emission tomography and computed tomography. CIT, the difference of EE at 27ºC and after 2-h cold exposure at 19ºC, significantly increased in winter compared to summer, being greater in subjects with metabolically active BAT (High BAT, 185.6 kcal/d, 18.3 kcal/d, P<0.001) than those without (Low BAT, 90.6 kcal/d, -46.5 kcal/d, P<0.05). Multivariate regression analysis revealed a significant interaction effect between season and BAT on CIT (P<0.001). The cold-induced drop of tympanic temperature (T ty ) and skin temperature (T skin ) in the forehead region and in the supraclavicular region close to BAT deposits were smaller in the High BAT group than in the Low BAT group in winter but not in summer. In contrast, the drop of T skin in the subclavicular and peripheral regions distant from BAT was similar in the two groups in both seasons. In conclusion, CIT increased from summer to winter in a BAT-dependent manner, paralleling cold-induced changes in T ty /T skin , indicating a role of BAT in seasonal changes in the thermogenic and thermal responses to cold exposure in humans., (Copyright © 2015, American Journal of Physiology - Regulatory, Integrative and Comparative Physiology.)

Introduction: An increasing number of adult patients have been diagnosed with fatty acid β-oxidation disorders with the rising use of diagnostic technologies. In this study, clinical, biochemical, and molecular characteristics of 2 Japanese patients with adult-onset glutaric acidemia type II (GA2) were investigated and compared with those of pediatric cases., Methods: The patients were a 58-year-old male and a 31-year-old male. In both cases, episodes of myopathic symptoms, including myalgia, muscle weakness, and liver dysfunction of unknown cause, had been noted for the past several years. Muscle biopsy, urinary organic acid analysis (OA), acylcarnitine (AC) analysis in dried blood spots (DBS) and serum, immunoblotting, genetic analysis, and an in vitro probe acylcarnitine (IVP) assay were used for diagnosis and investigation., Results: In both cases, there was no obvious abnormality of AC in DBS or urinary OA, although there was a increase in medium- and long-chain ACs in serum; also, fat deposits were observed in the muscle biopsy. Immunoblotting and gene analysis revealed that both patients had GA2 due to a defect in electron transfer flavoprotein dehydrogenase (ETFDH). The IVP assay indicated no special abnormalities in either case., Conclusion: Late-onset GA2 is separated into the intermediate and myopathic forms. In the myopathic form, episodic muscular symptoms or liver dysfunction are primarily exhibited after later childhood. Muscle biopsy and serum (or plasma) AC analysis allow accurate diagnosis in contrast with other biochemical tests, such as analysis of AC in DBS, urinary OA, or the IVP assay, which show fewer abnormalities in the myopathic form compared to intermediate form., (Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Human brown adipose tissue (BAT) activity (SUVmax) has been typically evaluated by 18F-fluorodeoxy glucose (FDG)-positron emission tomography (PET) combined with computed tomography (CT). In this study, the objective was to detect human BAT by near-infrared time-resolved spectroscopy (NIRTRS), a noninvasive and simple method for measuring total hemoglobin concentration [total-Hb] and reduced scattering coefficient (μs') in the tissue. The [total-Hb] in the supraclavicular region of the BAT (+) (SUVmax≥2.0) group was 95.0±28.2 μM (mean+/-SD), which was significantly higher than that of the BAT (-) (SUVmax<2.0) group (52.0±14.8 μM), but not in other regions apart from the BAT deposits. The μs' in the supraclavicular region of the BAT (+) group was 8.4±1.7 cm(-1), which was significantly higher than that of BAT (-) group (4.3±1.0 cm(-1)), but not in other regions. The area under the receiver operating characteristic curve closest to (0, 1) for [total-Hb] and μs' to discriminate BAT (+) from BAT (-) was 72.5 μM and 6.3 cm(-1), respectively. The sensitivity, specificity, and accuracy for both parameters were 87.5, 100, and 93.3%, respectively. Our novel NIRTRS method is noninvasive, simple, and inexpensive compared with FDG-PET/CT, and is reliable for detecting human BAT.

We evaluated the significance of dietary instruction (DI) for patients who are going on a low iodine diet (LID) as a preparation for remnant tissue ablation for thyroid cancer. DI was done by a dietarian using a dedicated handbook we have developed. To assess the effect of LID on depleting body iodine, urinary iodine concentration (UIC) in patients with post-surgical papillary thyroid cancer was measured twice, before and after LID. UIC on the day of radioiodine administration was compared with radioiodine uptake (RU) in the remnant tissue. Additionally, the association between clinical and lifestyle-related features of patients and the outcome of LID were investigated. A questionnaire survey was conducted to determine whether the DI helped patients go on LID. The mean value of UIC after the one-week LID was decreased to about 15% of the baseline value. There was a significant inverse correlation between UIC and RU (r= -0.694). Age and UIC before the start of LID were linked to successful outcome of LID. In the questionnaire survey, 84% of the participants answered that the handbook helped them go on a LID. Likewise, 80% answered that they could manage their LID without using the boil-in-the-bag low iodine food. LID successfully decreased UIC in patients undergoing remnant tissue ablation. DI by a dietitian may make a practice of LID easier.

The long-term efficacy of enzyme replacement therapy (ERT) in patients with Pompe disease has been unraveled. Cardiac muscle responds well to ERT, whereas motor and respiratory functions do not. The screening of newborns, which enables the early initiation of ERT, has improved outcomes of infantile Pompe patients. Myopathies still exist even in patients in whom ERT is initiated early, and have become recognized as an emerging new phenotype of IP on ERT. In addition, this shows the limitation of currently available ERT. It is expected that the development of therapy will improve the outcome of Pompe disease.

Objective: Human brown adipose tissue (BAT) activity has been typically evaluated by (18) F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) combined with computed tomography (CT). However, FDG-PET/CT has serious limitations (e.g., radiation and cold exposure). This study evaluated BAT density using near-infrared time-resolved spectroscopy (NIRTRS ), a simple and noninvasive method of measuring the indices of tissue hemoglobin concentration [total-Hb] and mitochondrial density (µs ')., Methods: The NIRTRS parameters at 760, 800, and 830 nm in the supraclavicular region potentially containing BAT were evaluated. First, the NIRTRS parameters were compared at 27 °C and during a 2-h cold exposure (19 °C) in 18 men. Then, NIRTRS parameters at 27 °C were compared with mean standardized uptake values (SUVmean ) assessed by FDG-PET/CT after the 2-h cold exposure (19 °C) in 29 men., Results: There was no significant difference between the NIRTRS parameters at 27 °C and 19°C. The [total-Hb] and µs ' were significantly correlated to SUVmean (r = 0.73 and r = 0.64, respectively). A receiver operating characteristic analysis revealed that the sensitivity (75.0-82.4%), specificity (91.7-100%), and accuracy (82.8-86.2%) of the NIRTRS parameters were all good to determine the NIRTRS reliability., Conclusions: Our novel NIRTRS method is noninvasive and simple and can reliably assess human BAT density in the supraclavicular region., (© 2014 The Obesity Society.)

Kaempferia parviflora extract (KP) has been reported to have a preventive effect on obesity in mice, probably by increasing energy expenditure (EE). The aims of the current study were to examine the acute effects of KP ingestion on whole-body EE in humans and to analyze its relation to the activity of brown adipose tissue (BAT), a site of non-shivering thermogenesis. After an oral ingestion of an ethanol extract of KP, EE increased significantly, showing a maximal increase of 229±69 kJ/d at 60 min, while it did not change after placebo ingestion. To evaluate BAT activity, the subjects underwent fluorodeoxyglucose-positron emission tomography, and divided into two groups with high- and low-BAT activities. A similar and greater response of EE to KP ingestion was observed in the high-BAT group (351±50 kJ/d at 60 min), but not in the low activity group. Placebo ingestion did not cause any significant EE change in either group. These results indicate that a single oral ingestion of the KP extract can potentially increase whole-body EE probably through the activation of BAT in healthy men, and may be useful as an anti-obesity regimen.