Pharmacokinetic and pharmacodynamic drug-drug interactions between evogliptin and empagliflozin or dapagliflozin in healthy male volunteers.

Evogliptin (EV) is a novel dipeptidyl peptidase-4 inhibitor (DPP4i) for glycemic control in patients with type 2 diabetes mellitus (T2DM). This study evaluated the pharmacokinetic (PK) and pharmacodynamic (PD) interactions between EV and sodium glucose cotransporter-2 inhibitors (SGLT2i) in healthy volunteers since combination therapy of DPP4i and SGLT2i has been considered as an effective option for T2DM treatment. A randomized, open-label, multiple-dose, two-arm, three-period, three treatments, two-sequence crossover study was conducted in healthy Korean volunteers. In arm 1, subjects were administered 5 mg of EV once daily for 7 days, 25 mg of empagliflozin (EP) once daily for 5 days, and the combination once daily for 5 days (EV + EP). In arm 2, subjects were administered 5 mg of EV once daily for 7 days, 10 mg of dapagliflozin (DP) once daily for 5 days, and the combination once daily for 5 days (EV + DP). Serial blood samples were collected for PK analysis, and oral glucose tolerance tests were conducted for PD analysis. In each arm, a total of 18 subjects completed the study. All adverse events (AEs) were mild with no serious AEs. The geometric mean ratio and confidence interval of the main PK parameters (maximum concentration of the drug in plasma at steady state and area under the plasma drug concentration-time curve within a dosing interval at a steady state) between EV and either EP or DP alone were not significantly altered by co-administration. Administration of EV + EP or EV + DP did not result in significant PD changes, as determined by the glucose-lowering effect. Administration of EV + EP or EV + DP had no significant effects on the PK profiles of each drug. All treatments were well-tolerated.

Diffeomorphic Surface Modeling for MRI-Based Characterization of Gastric Anatomy and Motility.

OBJECTIVE: Gastrointestinal magnetic resonance imaging (MRI) provides rich spatiotemporal data about the movement of the food inside the stomach, but does not directly report muscular activity on the stomach wall. Here we describe a novel approach to characterize the motility of the stomach wall that drives the volumetric changes of the ingesta. METHODS: A neural ordinary differential equation was optimized to model a diffeomorphic flow that ascribed the deformation of the stomach wall to a continuous biomechanical process. Driven by this diffeomorphic flow, the surface of the stomach progressively changes its shape over time, while preserving its topology and manifoldness. RESULTS: We tested this approach with MRI data collected from 10 rats under a lightly anesthetized condition, and demonstrated accurate characterization of gastric motor events with an error in the order of sub-millimeters. Uniquely, we characterized gastric anatomy and motility with a surface coordinate system common at both individual and group levels. Functional maps were generated to reveal the spatial, temporal, and spectral characteristics of muscle activity and its coordination across different regions. The peristalsis at the distal antrum had a dominant frequency and peak-to-peak amplitude of [Formula: see text] cycles per minute and [Formula: see text] mm, respectively. The relationship between muscle thickness and gastric motility was found to be distinct between two functional regions in the proximal and distal stomach. CONCLUSION: These results demonstrate the efficacy of using MRI to model gastric anatomy and function. SIGNIFICANCE: The proposed approach is expected to enable non-invasive and accurate mapping of gastric motility for preclinical and clinical studies.

Novel LC-MS/MS analysis of the GLP-1 analog semaglutide with its application to pharmacokinetics and brain distribution studies in rats.

Semaglutide, one of the most potent glucagon-like peptide (GLP)-1 analogs, has widely been used to treat type II diabetes mellitus and obesity. Recent studies have shown that semaglutide also works on the brain, suggesting its potential utility for various diseases, including Parkinson's disease and Alzheimer's disease. This study aimed to develop a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of semaglutide in both plasma and brain to characterize the pharmacokinetics and brain distribution in rats. Semaglutide was extracted by simple protein precipitation with methanol from plasma and by solid phase extraction from brain tissue. Liraglutide was used as an internal standard. Gradient elution profiles with mobile phases comprising 0.1 % formic acid in water and acetonitrile were used for chromatographic separation. The lower limit of quantification (LLOQ) of the LC-MS/MS assay was 0.5 ng/mL for both rat plasma and brain. Intra- and inter-day accuracy ranged 89.20-109.50 % in the plasma and 92.00-105.00 % in the brain. Precision was within 8.92 % in the plasma and 7.94 % in the brain. Sprague-Dawley rats were given semaglutide by intravenous (IV, 0.02 mg/kg) and subcutaneous (SC, 0.1 and 0.2 mg/kg) injection. Plasma concentrations of semaglutide showed a multi-exponential decline with an average half-life of 7.22-9.26 hr in rats. The subcutaneous bioavailability of semaglutide was 76.65-82.85 %. The brain tissue to plasma partition coefficient (Kp) value of semaglutide was estimated as <0.01. Among the different regions of the brain, semaglutide concentrations were significantly higher in the hypothalamus. The analytical method and pharmacokinetic information may be helpful toward a better understanding of the effect of semaglutide in the brain and further development of GLP-1 analogs for various brain diseases.

Representation learning of resting state fMRI with variational autoencoder.

Resting state functional magnetic resonance imaging (rsfMRI) data exhibits complex but structured patterns. However, the underlying origins are unclear and entangled in rsfMRI data. Here we establish a variational auto-encoder, as a generative model trainable with unsupervised learning, to disentangle the unknown sources of rsfMRI activity. After being trained with large data from the Human Connectome Project, the model has learned to represent and generate patterns of cortical activity and connectivity using latent variables. The latent representation and its trajectory represent the spatiotemporal characteristics of rsfMRI activity. The latent variables reflect the principal gradients of the latent trajectory and drive activity changes in cortical networks. Representational geometry captured as covariance or correlation between latent variables, rather than cortical connectivity, can be used as a more reliable feature to accurately identify subjects from a large group, even if only a short period of data is available in each subject. Our results demonstrate that VAE is a valuable addition to existing tools, particularly suited for unsupervised representation learning of resting state fMRI activity.

Decreases in Concentrations and Human Dietary Intakes of Polychlorinated Biphenyls (PCBs) and Polybrominated Diphenyl Ethers (PBDEs) in Korean Seafood Between 2005 and 2017.

Concentrations of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) were measured in 23 seafood species widely consumed by the Korean population in the periods of 2005-2007, 2010-2011, and 2015-2017. The Σ82PCB (sum of 82 PCB congeners) and Σ19PBDE (sum of 19 PBDE congeners) concentrations in the seafood samples of 2015-2017 were 0.06-6.69 ng/g wet weight and 0.01-1.60 ng/g wet weight, respectively. The Σ82PCB and Σ19PBDE concentrations in the samples were significantly correlated. Elevated PCB and PBDE concentrations were found in fatty fish, such as herring, mackerel, and tuna. The current human intakes of PCBs and PBDEs were much lower than the tolerable daily intake or lowest observed adverse effect level. The levels and human dietary intakes of PCBs and PBDEs in the 2015-2017 survey showed decreases of 17-73% and 57-86%, respectively, compared with those in 2005-2007 and 2010-2011 surveys. This indicates that global bans on PCBs and PBDEs have been effective, and their levels and human exposure to them have been gradually declining.

Enhanced selective enrichment of partial nitritation and anammox bacteria in a novel two-stage continuous flow system using flat-type poly (vinylalcohol) cryogel films.

To improve stability of nitrogen removal in partial nitritation (PN)-anammox process, flat-type cryogel films using poly (vinylalcohol) named as FT-CPVAF were applied in continuous reactors. Stable PN operation was maintained with short acclimation of 8 days and ammonium oxidation rate of 1.68 ± 0.12 kg N m-3 d-1 comparatively higher than previous studies. The nitrogen removal, initially inhibited by an oxygen shock, was immediately reactivated with short lag-period by immobilization of anammox bacteria in FT-CPVAF. A novel two-stage PN-anammox process was operated in a continuous flow using FT-CPVAF for treatment of ammonium-rich synthetic wastewater (influent 315 mg NH4+-N L-1) showing 89.6 ± 0.76% of nitrogen removal at short hydraulic retention time (7.7 h). The use of FT-CPVAF enhanced selective enrichment of AOB and anammox bacter ia confirmed by high-throughput sequencing of i.e., relative abundances of Nitrosomonas europaea C-31 (37.14% in PN reactor) and 'Candidatus Jettenia caeni' (34.36% in anammox reactor).

Spatial and temporal trends of PCDD/Fs in sediment and bivalves along the Korean coasts during 2001-2012.

Concentrations of polychlorinated dibenzo-para-dioxins and dibenzofurans (PCDD/Fs) were measured in sediment and bivalves at 25 locations along the Korean coasts during 2001-2012. Concentrations of PCDD/Fs in sediment and bivalves ranged from 0.15 to 18.9 pg TEQ/g dry weight and from 0.06 to 7.70 pg TEQ/g wet weight, respectively. Elevated PCDD/F concentrations were found at locations close to largest industrial complexes and commercial harbors. A significant decreasing trend of PCDD/Fs in sediment was associated with strong regulation of PCDD/Fs, whereas levels in bivalves did not show a decreasing trend. Octachlorinated dibenzo-p-dioxin (OCDD) was predominant in sediment, while tetrachlorinated dibenzofuran and OCDD were predominant in bivalves. Almost half (46%) of sediment samples exceeded the threshold effect level suggested by the US National Oceanic and Atmospheric Administration, implying ecotoxicological risks to benthic organisms. Our findings support the effectiveness of legislative action on PCDD/Fs for coastal environments of Korea.

An improved rapid analytical method for the arsenic speciation analysis of marine environmental samples using high-performance liquid chromatography/inductively coupled plasma mass spectrometry.

Arsenic contamination in marine environments is a serious issue because some arsenicals are very toxic, increasing the health risks associated with the consumption of marine products. This study describes the development of an improved rapid method for the quantification of arsenic species, including arsenite (AsIII), arsenate (AsV), arsenocholine (AsC), arsenobetaine (AsB), dimethylarsinic acid (DMA), and monomethyl arsonic acid (MMA), in seaweed, sediment, and seawater samples using high-performance liquid chromatography/inductively coupled plasma-mass spectrometry (HPLC/ICP-MS). ICP-MS based on dynamic reaction cells was used to eliminate spectral interference. Ammonium nitrate- and phosphate-based eluents were used as the mobile phases for HPLC analysis, leading to shorter overall retention time (6 min) and improved peak separation. Arsenicals were extracted with a 1% HNO3 solution that required no clean-up process and exhibited reasonable sensitivity and peak resolution. The optimized method was verified by applying it to hijiki seaweed certified reference material (CRM, NMIJ 7405-a) and to spiked blank samples of sediment and seawater. The proposed method measured the concentration of AsV in the CRM as 9.6 ± 0.6 µg/kg dry weight (dw), which is close to the certified concentration (10.1 ± 0.5 µg/kg dw). The recovery of the six arsenicals was 87-113% for the sediment and 99-101% for the seawater. In the analysis of real samples, AsV was the most abundant arsenical in hijiki and gulfweed, whereas AsB was dominant in other seaweed species. The two inorganic arsenicals (AsIII and AsV) and AsV were the most dominant in the sediment and seawater samples, respectively.

Association between Body Fat and Bone Mineral Density in Normal-Weight Middle-Aged Koreans.

BACKGROUND: Osteoporosis and osteopenia are characterized by reduced bone mineral density (BMD) and increased fracture risk. Although the risk of fractures is higher in underweight people than in overweight people, the accumulation of body fat (especially abdominal fat) can increase the risk of bone loss. This study aimed to evaluate the association between body fat percentage and BMD in normal-weight middle-aged Koreans. METHODS: This study included 1,992 adults (mean age, 48.7 years; 52.9% women). BMD and body fat were measured using dual-energy X-ray absorptiometry. Multiple linear regression analyses and analysis of covariance were used to assess the association between BMD and body fat. Body fat percentage was grouped by cut-off values. The cut-off values were 20.6% and 25.7% for men with a body mass index of 18.5-22.9 kg/m2 , while the cut-off values were 33.4% and 36% for women. RESULTS: Body fat percentage tended to be negatively associated with BMD. Increased body fat percentage was associated with reduced BMD in normal-weight middle-aged adults. The effects of body fat percentage on BMD in normal-weight individuals were more pronounced in men than in women. CONCLUSION: There was a negative correlation between BMD and body fat percentage in middle-aged Korean men and women with normal body weight. This association was stronger in men than in women.

Negligible seeding source effect on the final ANAMMOX community under steady and high nitrogen loading rate after enrichment using poly(vinyl alcohol) gel carriers.

This study investigated the effect of seeding source on the mature anaerobic ammonia oxidation (ANAMMOX) bacterial community niche in continuous poly(vinyl alcohol) (PVA) gel systems operated under high nitrogen loading rate (NLR) condition. Four identical column reactors packed with PVA gels were operated for 182 d using different seeding sources which had distinct community structures. The ANAMMOX reaction was achieved in all the bioreactors with comparable total and ANAMMOX bacterial 16S rRNA gene quantities. The bacterial community structure of the bioreactors became similar during operation; some major bacteria were commonly found. Interestingly, one ANAMMOX species, "Candidatus Brocadia sinica", was conclusively predominant in all the bioreactors, even though different seeding sludges were used as inoculum source, possibly due to the unique physiological characteristics of "Ca. Brocadia sinica" and the operating conditions (i.e., PVA gel-based continuous system and 1.0 kg-N/(m3·d) of NLR). The results clearly suggest that high NLR condition is a more significant factor determining the final ANAMMOX community niche than is the type of seeding source.

Effective seeding strategy using flat type poly (vinyl alcohol) cryogel for anammox enrichment.

In this study, anammox enrichment reactors were operated using flat type poly (vinyl alcohol) cryogel (cryoPVAG) with precultured anammox bacteria (PAB) and activated sludge (AS) from an anoxic tack of the A2O process to evaluate the effect of different seeding sources on anammox enrichment. In addition, cryoPVAGs with different thicknesses (1, 2, and 3 mm) were used to investigate the effects of the thickness on anammox enrichment. The regression analysis with a modified Gompertz model showed that the start-up period of the anammox enrichment using PAB inoculum was approximately 14 days earlier than that of AS inoculum at a nitrogen loading rate of approximately 1 kg-N m-3 day-1. Substrate diffusion was limited in 3-mm cryoPVAG with respect to trend in nitrogen removal rate. Quantitative PCR analysis indicated that in the initial phase, the 16S rRNA gene copy numbers of anammox microorganism in cryoPVAG were significantly different according to the seeding source, but finally converged to a similar level after anammox enrichment. The anammox reaction was initially promoted by cryoPVAG. Next, anammox biomass detached from cryoPVAG and enriched in the bulk phase to maximize NRR. Illumina MiSeq sequencing revealed that Candidatus Brocadia sinica led to the active anammox reaction, and its relative abundance decreased with increasing gel thickness.

Cardiovascular disease risk factor clustering in children and adolescents: a prospective cohort study.

OBJECTIVE: The early identification of predictors related to cardiovascular disease risk factor clustering (CVD-RFC) can help prevent chronic disease. We aimed to identify the risk factors for CVD-RFC in adolescents. METHODS: A prospective longitudinal cohort study design was used to obtain data included in these analyses from school-aged children who participated in the Korean Child-Adolescent Study 2008-2014. A total of 1309 children aged 6-15 years were enrolled. We compared the participants based on the presence or absence of CVD-RFC and examined the cumulative incidence of CVD-RFC. RESULTS: Of the total 1309 children, 410 (31.32%) had CVD-RFC in adolescence. A higher average household income ≥3 million Korean Republic won (KRW)/month (3-5 million KRW/month: HR 0.75 (95% CI 0.58 to 0.97); ≥5 million KRW/month: HR 0.58 (95% CI 0.44 to 0.77)) was associated with a lower CVD-RFC incidence, while the presence of parental CVD history (HR 1.28 (95% CI 1.04 to 1.57)), overweight or obesity (HR 3.83 (95% CI 3.05 to 4.80)) and shorter sleep duration of 8-9 hour/day (HR 1.80 (95% CI 1.05 to 3.07)) and <8 hour/day (HR 1.93 (95% CI 1.11 to 3.34)) had higher CVD-RFC incidences. CONCLUSIONS: Obesity in childhood, short sleep duration and parental factors such as low socioeconomic status and parental history of CVD are significant risk factors for the development of CVD-RFC in adolescents. Efforts to create awareness regarding sufficient sleep duration in children via intervention programmes targeting cardiometabolic health in children and special attention to lifestyle modifications and socioeconomic components of the family should be considered.

Effects of the ammonium loading rate on nitrite-oxidizing activity during nitrification at a high dose of inorganic carbon.

In this study, the effects of the ammonium loading rate (ALR) and inorganic carbon loading rate (ILR) on the nitrification performance and composition of a nitrifying bacterial community were investigated in a moving bed biofilm reactor, using poly(vinyl alcohol) (PVA) sponge cubes as a supporting carrier. Between the two ALRs of 0.36 and 2.16 kg-N m-1 d-1, stable partial nitritation was achieved at the higher ALR. Inorganic carbon was dosed at high levels: 33.1, 22.0, 16.4, 11.0, and 5.4 times the theoretical amount. Nonetheless, nitrification efficiency was not affected by the ILR at the two ALRs. Quantitative PCR analysis of ammonia- and nitrite-oxidizing bacteria revealed that ALR is an important determinant of partial nitritation by accumulating ammonia-oxidizing bacteria in the nitrification system. In comparison, two nitrite-oxidizing bacterial genera (Nitrobacter and Nitrospira) showed almost the same relative abundance at various ALRs and ILRs. Terminal restriction fragment length polymorphism targeting the gene of ammonia monooxygenase subunit A revealed that Nitrosomonas europaea dominated under all conditions.

An optimized method for the analysis of cyclic and linear siloxanes and their distribution in surface and core sediments from industrialized bays in Korea.

Environmental contamination by siloxanes is a matter of concern due to their widespread consumption in personal care as well as industrial products and potential toxicity. Nevertheless, methods for simultaneous determination of cyclic and linear siloxanes in sediment are lacking. In this study, we developed an optimized analytical method to determine cyclic and linear siloxanes based on gas chromatography coupled to tandem mass spectrometry (GC-MS/MS). This method was applied to determine concentrations of 19 siloxane compounds in surface and core sediments from industrialized bays in Korea to assess contamination status, spatial distribution, and historical trends. Total concentrations of siloxanes ranged from 15.0 to 11730 (mean: 712) ng/g dry weight, which were similar to or higher than those reported in other countries. The highest concentrations of siloxanes were found in rivers/streams that discharge into coastal waters and bays close to industrial complexes, indicating that industrial activities are major sources of siloxane contamination. Cyclic siloxanes such as D5 and D6 were predominant in surface and core sediments. A significant correlation existed between the concentrations of cyclic and linear siloxanes, suggesting similar sources in the marine coastal environment. The historical record of cyclic siloxanes in core sediments revealed a clear increasing trend since the 1970s. This finding is consistent with the history of local industrialization and global production of siloxanes. This is the first study of historical trends in siloxanes in the coastal environment.

Predictive Coding for Dynamic Visual Processing: Development of Functional Hierarchy in a Multiple Spatiotemporal Scales RNN Model.

This letter proposes a novel predictive coding type neural network model, the predictive multiple spatiotemporal scales recurrent neural network (P-MSTRNN). The P-MSTRNN learns to predict visually perceived human whole-body cyclic movement patterns by exploiting multiscale spatiotemporal constraints imposed on network dynamics by using differently sized receptive fields as well as different time constant values for each layer. After learning, the network can imitate target movement patterns by inferring or recognizing corresponding intentions by means of the regression of prediction error. Results show that the network can develop a functional hierarchy by developing a different type of dynamic structure at each layer. The letter examines how model performance during pattern generation, as well as predictive imitation, varies depending on the stage of learning. The number of limit cycle attractors corresponding to target movement patterns increases as learning proceeds. Transient dynamics developing early in the learning process successfully perform pattern generation and predictive imitation tasks. The letter concludes that exploitation of transient dynamics facilitates successful task performance during early learning periods.

Comparison of inoculum sources for long-term process performance and fate of ANAMMOX bacteria niche in poly(vinyl alcohol)/sodium alginate gel beads.

The process performance and microbial niche of anaerobic ammonia oxidation (ANAMMOX) bacteria were compared in two identical bioreactors inoculated with different inoculum sources (i.e., pre-cultured ANAMMOX bacteria: PAB and activated sludge: AS) entrapped in poly(vinyl alcohol)/sodium alginate (PVA/SA) gel beads for a long-term period (i.e., 1.5 years). The start-up period with AS was longer than that with PAB; however, both bioreactors were successfully operated over the long-term with stable ANAMMOX activity. After long-term operation, the 16S rRNA gene concentration of ANAMMOX bacteria in both bioreactors was significantly increased, and thereby became comparable. In addition, Candidatus Jettenia sp. became the dominant ANAMMOX species in both bioreactors. Our results suggested that the ANAMMOX performance and microbial niche of ANAMMOX bacteria became nearly identical during long-term operation despite the use of different inoculum sources. Therefore, the use of PVA/SA gel beads entrapping AS appears to be a relevant option for constructing an ANAMMOX process in places where a full-scale ANAMMOX process has never been done previously.

Concentrations of trace metals in tissues of Chionoecetes crabs (Chionoecetes japonicus and Chionoecetes opilio) caught from the East/Japan Sea waters and potential risk assessment.

The concentrations of trace metals (As, Cd, Co, Cu, Fe, Hg, Pb, and Zn) were measured in muscle and hepatopancreas of two Chionoecetes crabs (Chionoecetes japonicus and C. opilio) caught from the East/Japan Sea (EJS) in order to assess the potential health risk by the consumption of deep sea crabs. The highest metal concentrations in muscle and hepatopancreas were As and Fe, respectively, while the lowest metal concentration in two tissues was Pb. The mean concentrations of Cd, Co, Cu, Fe, and Pb in Chionoecetes crabs were one or two orders of magnitude higher in hepatopancreas than in muscles. The mean concentrations of As, Cu, and Hg in muscle and hepatopancreas were relatively higher in C. japonicus than in C. opilio. The estimated daily intakes (EDI) of all metals in muscle were below 0.1% of the provisional tolerable daily intake (PTDI) adopted by the Joint FAO/WHO Expert Committee on Food Additives. Similarly, the target hazard quotient (THQ) of all trace metals in muscle was less than 1.0. These results imply that Chionoecetes crabs caught from EJS do not have an adverse impact on the Korean health. Based on the mean metal concentrations, PTDI, and THQ, the daily maximum permissible intakes of C. japonicus and C. opilio were estimated to be approximately 240 and 410 g/day, respectively.

Association of dietary patterns with the fecal microbiota in Korean adolescents.

BACKGROUND: The gut microbiota has emerged as an important environmental factor associated with obesity, type 2 diabetes, and cardiovascular disease, through its interactions with dietary factors. Therefore, we analyzed the composition of the fecal microbiota and levels of biochemical markers related to metabolic disease according to dietary pattern in Korean adolescents. METHODS: We collected fecal samples from 112 student subjects aged 13-16 years with sufficient information available regarding clinical biomarkers and diet, and performed 16S rRNA targeted gene sequencing. RESULTS: Regarding bacterial composition according to taxonomic rank, we found that traditional dietary patterns enriched in plant-based and fermented foods were associated with higher proportions of Bacteroides (Bacteroidaceae) and Bifidobacterium (Bifidobacteriaceae-Actinobacteria) and a lower proportion of Prevotella (Prevotellaceae) relative to modified Western dietary patterns (a greater proportion of animal-based foods). Specifically, the proportion of Bacteroides (Bacteroidaceae) was associated with intake of plant-based nutrients such as fiber; however, that of Prevotella (Prevotellaceae) was negatively associated with these factors. Additionally, we observed that the increase of prevotella (Prevotellaceae) and decrease of Bacteroides (Bacteroidaceae) and Ruminococcaceae had a higher risk of obesity. We also found that the traditional dietary pattern was negatively associated with general and central adiposity and levels of clinical biomarkers, including AST, ALT, total cholesterol, triglyceride, hs-CRP, insulin, and HOMA-IR, whereas the positive associations were found for a modified Western dietary pattern. CONCLUSIONS: These findings suggest that the gut microbiota composition differs markedly according to dietary intake and suggest a role for diet in promoting a gut microbiome associated with the pathogenesis of metabolic disease.

Efficacy and safety of fermented garlic extract on hepatic function in adults with elevated serum gamma-glutamyl transpeptidase levels: a double-blind, randomized, placebo-controlled trial.

PURPOSE: Alcoholic liver disease or non-alcoholic fatty liver disease/non-alcoholic steatohepatitis are well-known risk factors for liver fibrosis or cirrhosis and hepatocellular carcinoma; it is a major global health concern, but there are few effective and safe management options. Therefore, we aimed to investigate the effects of fermented garlic extracts (FGEs) on hepatic function in adults with mild hepatic dysfunction without underlying hepatic disease. METHODS: In this double-blind, randomized, placebo-controlled study, seventy-five adults with elevated serum gamma-glutamyl transpeptidase (GGT) levels were included in a FGE-administered group (n = 36) or a placebo group (n = 39), and received either two sachets/day containing FGEs or placebo over a 12-week period. Primary endpoint was the change in serum GGT levels. Data were analysed using a generalized linear mixed effects model. RESULTS: Significant group × time interactions for serum levels of GGT (F = 3.98, P = 0.022) and alanine aminotransferase (ALT; F = 3.28, P = 0.043) were observed with an improvement in levels of GGT (P = 0.066) and ALT (P = 0.014) in the FGE group compared to that reported for the placebo group at the 12-week visits. There was no intergroup difference in the prevalence of adverse events. CONCLUSIONS: Intake of FGEs improved serum GGT and ALT levels in adults with mildly elevated serum GGT level without reported adverse side effects. FGEs might be effective and safe management options for mild hepatic dysfunction.