Serum 25-hydroxyvitamin D3 Levels and Diabetes in a Japanese Population: The DOSANCO Health Study.

BACKGROUND: Both decreased insulin sensitivity and impaired insulin secretion are common in Asian populations with diabetes, in contrast to Western populations. There is limited evidence regarding the association between insulin response in diabetes in Asian populations and serum 25-hydroxyvitamin D3 (25[OH]D3) insufficiency. METHODS: The present cross-sectional study compared the prevalence of diabetes, defined as a fasting plasma glucose level ≥126 mg/dL and/or a HbA1c level ≥6.5%, among 480 participants aged 35-79 years not taking anti-diabetes medications, based on serum 25(OH)D3 levels. A logistic regression model was used to calculate the odds ratios for diabetes in each serum 25(OH)D3 group. Furthermore, this study examined the association between serum 25(OH)D3 levels and the index of homeostasis model assessment of insulin resistance (HOMA-IR) using a linear regression model. RESULTS: The prevalence of diabetes was 7.29% in the study population, and was higher in lower serum 25(OH)D3 quartile groups. The odds ratios for diabetes in the first, second, and third serum 25(OH)D3 quartile groups (25[OH]D3: ≤18.10, 18.11-22.90, and 22.91-28.17 ng/mL) were 4.02 (95% confidence interval [CI], 1.25-12.92), 2.50 (95% CI, 0.77-8.10), and 1.91 (95% CI, 0.60-6.09), respectively, with the fourth quartile group (⩾28.18 ng/mL) serving as the reference group, after adjusting for sociodemographic, lifestyle, physical and environmental factors. Serum 25(OH)D3 levels showed an inverse association with log-transformed HOMA-IR after adjusting for similar factors (standardized ß = -0.08; 95% CI, -0.14 to -0.02). CONCLUSION: Serum 25(OH)D3 levels were inversely associated with diabetes prevalence in a general Japanese population, with a slight inverse association between serum 25(OH)D3 levels and HOMA-IR.

Association of accelerometer-measured physical activity with kidney function in a Japanese population: the DOSANCO Health Study.

BACKGROUND: Sedentary behavior and decreased physical activity are associated with reduced kidney function, yet most evidence is based on self-reported physical activity. This study investigated the association between accelerometer-based physical activity level and kidney function in a general Japanese population. METHODS: A cross-sectional study was conducted in 440 community-dwelling Japanese participants, aged 35-79 years. Time (min/d) was assessed for the following types of physical activity: sedentary behavior, light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA). Kidney function was assessed using estimated glomerular filtration rate (eGFR). A linear regression model was employed to calculate the ß coefficient of eGFR for a 60-min/d increase in sedentary behavior and LPA and a 10-min/d increase in MVPA. A logistic regression model was used to calculate the odds ratio for low eGFR (< 60 versus ≥60 mL/min/1.73m2) for a 60-min/d or 10-min/d increase in each physical activity type. RESULTS: MVPA time and eGFR were positively associated in both men and women, after adjusting for age, body mass index, and other clinical characteristics (Men: ß, 0.91; P = 0.021; Women: ß, 0.70; P = 0.034). In women, sedentary behavior and eGFR were inversely associated after adjusting for the same factors (ß, - 1.06; P = 0.048). The odds ratio (95% confidence interval) for low eGFR associated with a 60-min increase in sedentary behavior was 1.65 (1.07-2.55) after adjusting for the same factors in women. CONCLUSION: Longer sedentary behavior and shorter MVPA time were associated with lower kidney function in the Japanese population.

Are Japanese Women Less Physically Active Than Men? Findings From the DOSANCO Health Study.

BACKGROUND: Previous research has established that women accumulate less moderate-to-vigorous physical activity (MVPA) than men. To date, however, little is known about the gender differences in device-based activity patterns of sedentary behavior (SB) and light-intensity physical activity (LPA). We aimed to compare time spent in SB and different intensities of physical activity taking into account of co-dependence of time use domains. METHODS: This cross-sectional study was conducted in Suttu town, Hokkaido, Japan. Data were analyzed from 634 Japanese adults (278 men, aged 19-92 years) who provided valid accelerometer (HJA-750C) data. Gender differences in activity behavior patterns were tested using multivariate analysis of covariance (MANCOVA) based on isometric log-ratio transformations of time use, adjusting for age. We also developed bootstrap percentile confidence intervals (CI) to support the interpretation of which behavior differed between genders. RESULTS: Overall, participants had percent time spent in SB, LPA, MVPA during wearing time (mean, 14.8 hours) corresponding to 53.9%, 41.7%, and 4.4% of wearing time, respectively. Activity behavior patterns differed significantly between genders after controlling for time spent in all activities. Women spent relatively 13.3% (95% CI, 9.9-15.9%) less time in SB and 19.8% (95% CI, 14.9-24.6%) more time in LPA compared to men. The difference of time spent in MVPA was not statistically significant. CONCLUSIONS: In contrast with previous studies, our findings suggest that Japanese women are more physically active than men when all intensities of activities are considered. Given the health benefits of LPA, evaluating only MVPA may disproportionately underestimate the level of physical activity of women.

Reduced Knoevenagel Reaction of Acetetracenylene-1,2-dione with Acceptor Units for Luminescent Tetracene Derivatives.

Acetetracenylene-1,2-dione reacted with 3-ethylrhodanine in the presence of piperidine and Hantzsch ester via a Knoevenagel condensation-reduction sequence to give a tetracene-rhodanine adduct. This reduced Knoevenagel product exhibited magenta luminescence with a fluorescence quantum yield of φ = 0.34 and fluorescence lifetime of τ = 13.2 ns in toluene. Electrochemical studies and charge carrier transport measurements revealed ambipolar properties with hole and electron mobilities of 5.1 × 10-7 and 1.6 × 10-4 cm2/(V s), respectively.

Mechanochromism, Twisted/Folded Structure Determination, and Derivatization of (N-Phenylfluorenylidene)acridane.

(N-Phenylfluorenylidene)acridane (Ph-FA) compounds with electron-withdrawing and -donating substituents (H, MeO, Ph, NO2 , Br, F) at the para position of the phenyl group were successfully synthesized by Barton-Kellogg reactions of N-aryl thioacridones and diazofluorene. By using the substituent on the nitrogen atom to alter the electronic properties, both the folded and twisted conformers of p-NO2 -C6 H4 -FA could be crystallographically characterized, which enabled the charge transfer from the electron-donating acridane moiety to the electron-accepting fluorenylidene moiety to be understood. Ground-state mechanochromism, thermochromism, vapochromism, and proton-induced chromism were demonstrated between the folded and twisted conformations of the conformers. Protonation and chemical oxidation of Ph-FA gave two stable acridinium compounds, namely, the fluorenylacridinium and acridinium radical cations. The present study will contribute to the development of functional dyes and organic semiconductors.

Regiocontrolled Electrosynthesis of [60]Fullerene Bisadducts: Photovoltaic Performance and Crystal Structures of C60 o-Quinodimethane Bisadducts.

C60 o-quinodimethane bisadducts [C60(QM)2] are promising electron acceptors for bulk heterojuction (BHJ) organic solar cells (OSCs). However, previous production of C60(QM)2 often resulted in excessive regioisomers, which were difficult to purify and might consequently obscure the structure-performance study of the organofullerene acceptors. Herein, the electrosynthesis of C60(QM)2 is reported. The reaction exhibits a strong regiocontrol with generation of fewer regioisomers. Pure regioisomers of cis-2, trans-3, and e C60(QM)2 are obtained, and the structures are solved with single-crystal X-ray diffraction. Interestingly, the cis-2 and trans-3 regioisomers exhibit better photovoltaic performance than the e regioisomer in the OSCs based on poly(3-hexylthiophene) (P3HT), which can be correlated with their structural difference.

A V-shaped polyaromatic amphiphile: solubilization of various nanocarbons in water and enhanced photostability.

Nanocarbons are synthetic carbon-rich compounds with polyaromatic frameworks that have lately attracted attention as emerging functional materials. However, their extreme hydrophobicity and aggregation peculiarity, besides their shape and size diversities, precluded their study in solution, especially in "green" water. More convenient and general solubilizing methods of nanocarbon frameworks are required by using non-covalent supramolecular interactions. Here we report a protocol for solubilizing a wide range of nanocarbons, that is, fullerenes (C60 , C70 , C84 , and C120 ), polyarenes (tetracene, pentacene, perylene, coronene, and hexabenzocoronene), and carbon nanotubes (single-walled and multi-walled CNTs), in water through manual grinding with V-shaped polyaromatic amphiphiles. The obtained aqueous nanocomposites are composed of nanocarbons encircled by the polyaromatic frameworks of the amphiphiles through multiple aromatic-aromatic interactions. Notably, the encapsulated photosensitive nanocarbons, such as tetracene, pentacene, and fullerene dimer, exhibit unusual stability toward UV/Vis light.

Approach to high open-circuit voltage in organic solar cells utilizing a structural change of the oxazolino-C70 derivative.

Reactions of 2,5-Bn2 C70 (Bn=CH2 Ph) with hydroxide and ArCN (Ar=Ph, m-ClPh) followed by quenching with I2 and BnBr afforded dibenzylated and tetrabenzylated oxazolino[70]fullerenes, respectively. The latter has a novel structural configuration, in which the addends are positioned from the polar to the transequatorial region. A key structural feature of this compound is that the oxygen atom of the oxazoline ring is bound to the equatorial belt region of C70 , giving structural change in its reduced state. This enables stabilization of the reduced state, suppressing charge recombination dynamics in organic solar cells to give a high open-circuit voltage (0.85, 0.93, and 1.11 V in devices using P3HT, PTB7, and DPP(TBFu)2 , respectively).

Relationships of the Surface Charge of Low-Density Lipoprotein (LDL) with the Serum LDL-Cholesterol and Atherosclerosis Levels in a Japanese Population: The DOSANCO Health Study.

AIM: This study investigated the associations of the surface charge of low-density lipoprotein (LDL) with the serum LDL-cholesterol and atherosclerosis levels in a community-based Japanese population. METHODS: The study had a cross-sectional design and included 409 community residents aged 35-79 years who did not take medications for dyslipidemia. The potential electric charge of LDL and the zeta potential, which indicate the surface charge of LDL, were measured by laser Doppler microelectrophoresis. The correlations of the zeta potential of LDL (-mV) with the serum LDL-cholesterol levels (mg/dL), cardio-ankle vascular index (CAVI), and serum high-sensitivity C-reactive protein (hsCRP) levels (log-transformed values, mg/L) were examined using Pearson's correlation coefficient (r). Linear regression models were constructed to examine these associations after adjusting for potential confounding factors. RESULTS: A total of 201 subjects with correctly stored samples were included in the primary analysis for zeta potential measurement. An inverse correlation was observed between the LDL zeta potential and the serum LDL-cholesterol levels (r=-0.20; p=0.004). This inverse association was observed after adjusting for sex, age, dietary cholesterol intake, smoking status, alcohol intake, body mass index, and the serum levels of the major classes of free fatty acids (standardized ß=-6.94; p=0.005). However, the zeta potential of LDL showed almost no association with CAVI or the serum hsCRP levels. Similar patterns were observed in the 208 subjects with compromised samples as well as all the original 409 subjects. CONCLUSION: A higher electronegative surface charge of LDL was associated with lower serum LDL-cholesterol levels in the general Japanese population.

Shorter sleep time relates to lower human defensin 5 secretion and compositional disturbance of the intestinal microbiota accompanied by decreased short-chain fatty acid production.

Sleep is essential for our health. Short sleep is known to increase disease risks via imbalance of intestinal microbiota, dysbiosis. However, mechanisms by which short sleep induces dysbiosis remain unknown. Small intestinal Paneth cell regulates the intestinal microbiota by secreting antimicrobial peptides including α-defensin, human defensin 5 (HD5). Disruption of circadian rhythm mediating sleep-wake cycle induces Paneth cell failure. We aim to clarify effects of short sleep on HD5 secretion and the intestinal microbiota. Fecal samples and self-reported sleep time were obtained from 35 healthy middle-aged Japanese (41 to 60-year-old). Shorter sleep time was associated with lower fecal HD5 concentration (r = 0.354, p = 0.037), lower centered log ratio (CLR)-transformed abundance of short-chain fatty acid (SCFA) producers in the intestinal microbiota such as [Ruminococcus] gnavus group (r = 0.504, p = 0.002) and Butyricicoccus (r = 0.484, p = 0.003), and lower fecal SCFA concentration. Furthermore, fecal HD5 positively correlated with the abundance of these genera and SCFA concentration. These findings suggest that short sleep relates to disturbance of the intestinal microbiota via decreased HD5 secretion.

Modeling Low Muscle Mass Screening in Hemodialysis Patients.

INTRODUCTION: Computed tomography (CT) can accurately measure muscle mass, which is necessary for diagnosing sarcopenia, even in dialysis patients. However, CT-based screening for such patients is challenging, especially considering the availability of equipment within dialysis facilities. We therefore aimed to develop a bedside prediction model for low muscle mass, defined by the psoas muscle mass index (PMI) from CT measurement. METHODS: Hemodialysis patients (n = 619) who had undergone abdominal CT screening were divided into the development (n = 441) and validation (n = 178) groups. PMI was manually measured using abdominal CT images to diagnose low muscle mass by two independent investigators. The development group's data were used to create a logistic regression model using 42 items extracted from clinical information as predictive variables; variables were selected using the stepwise method. External validity was examined using the validation group's data, and the area under the curve (AUC), sensitivity, and specificity were calculated. RESULTS: Of all subjects, 226 (37%) were diagnosed with low muscle mass using PMI. A predictive model for low muscle mass was calculated using ten variables: each grip strength, sex, height, dry weight, primary cause of end-stage renal disease, diastolic blood pressure at start of session, pre-dialysis potassium and albumin level, and dialysis water removal in a session. The development group's adjusted AUC, sensitivity, and specificity were 0.81, 60%, and 87%, respectively. The validation group's adjusted AUC, sensitivity, and specificity were 0.73, 64%, and 82%, respectively. DISCUSSION/CONCLUSION: Our results facilitate skeletal muscle screening in hemodialysis patients, assisting in sarcopenia prophylaxis and intervention decisions.

In vivo optical coherence tomography of very late drug-eluting stent thrombosis compared with late in-stent restenosis.

BACKGROUND: Autopsy findings have suggested delayed arterial healing as a primary cause of very late stent thrombosis (VLST) after drug-eluting stent (DES) implantation. METHODS AND RESULTS: Optical coherence tomography of DES-treated lesions that developed VLST (n = 6) was compared with that of DES-treated lesions that developed late in-stent restenosis (L-ISR: n = 32) among patients with recurrent ischemia >1 year after DES implantation (mean, 37 ± 17 months), and with the stented segment without any evidence of VLST or L-ISR (no-event: n = 20; mean, 38 ± 19 months). The proportion of uncovered and malapposed struts in each stented segment was evaluated. A total of 961 frames, 9,763 struts were analyzed. The proportion of uncovered struts was higher in the VLST group than in the L-ISR group and the no-event group (29.2 ± 22.8%, 7.9 ± 9.7%, and 7.6 ± 8.0%, respectively; P = 0.0002). The proportion of malapposed struts was higher in the VLST group than in the no-event group (7.3 ± 8.7% vs 1.1 ± 2.4%, P = 0.01). Two patients in the VLST group had lower rates of uncovered and malapposed struts, but this involved lipid-laden-like neointima with disruptions. CONCLUSIONS: Delayed neointimal coverage and incomplete stent apposition were frequently observed in the DES-treated lesions that developed very late thrombosis. Lipid-laden-like neointima with disruption within the DES may be another possible mechanism for very late thrombosis.

Lower human defensin 5 in elderly people compared to middle-aged is associated with differences in the intestinal microbiota composition: the DOSANCO Health Study.

Recently, aging is considered a risk factor for various diseases. Although changes in the intestinal microbiota along with aging are thought to associate with the increased disease risk, mechanisms that cause age-related transition of the intestinal microbiota remain unknown. This study aims to clarify relationships between the amount of human defensin 5 (HD5), a Paneth cell α-defensin, which is known to regulate the intestinal microbiota, and age-related differences of the intestinal microbiota composition. Fecal samples from 196 healthy Japanese (35 to 81 years old) were collected and measured HD5 concentration. HD5 concentration in the elderly group (age > 70 years old) was significantly lower than the middle-aged group (age ≤ 70 years old). Furthermore, individual age was negatively correlated with HD5 concentration (r = - 0.307, p < 0.001). In ß-diversity, the intestinal microbiota of the elderly showed a significantly different composition compared to the middle-aged. At the genus level, relative abundance of Collinsella, Alistipes, Peptococcaceae; unassigned, Lactobacillus, Lactococcus, Weissella, Christensenellaceae R-7 group, Megasphaera, and [Eubacterium] eligens group was significantly higher, and Lachnospiraceae; unassigned, Blautia, Anaerostipes, Fusicatenibacter, Dorea, and Faecalibacterium was significantly lower in the elderly compared to the middle-aged. In addition, HD5 concentration was negatively correlated with Alistipes, Peptococcaceae; unassigned, and Christensenellaceae R-7 group and positively correlated with Lachnospiraceae; unassigned and Dorea. These results provide novel insights into the immunosenescence of enteric innate immunity, indicating low HD5 is suggested to contribute to the age-related differences in the intestinal microbiota and may relate to increased risk of diseases in elderly people.

Different effects of isoflavones on vascular function in premenopausal and postmenopausal smokers and nonsmokers: NYMPH study.

Isoflavone intake has been associated with a reduction in the risk of cardiovascular disease in postmenopausal women. The aim of the present study was to determine if the effects of isoflavones on vascular function differ between premenopausal and postmenopausal women and between women who smoke and those who do not. Women smokers and nonsmokers who consumed 50 mg of isoflavone/day as black soybean tea for a period of 2 months (n = 55, mean age 39) were enrolled in the present study. We examined endothelial function, which was assessed by the percent change in flow-mediated dilation (%FMD) and arterial wall stiffness using the cardio-ankle vascular index (CAVI), as well as by biochemical parameters of the blood. Neither premenopausal (p = 0.697) nor postmenopausal (p = 0.389) smokers experienced an increase in %FMD after daily consumption of isoflavones. However, both premenopausal (p = 0.004) and postmenopausal (p = 0.019) nonsmokers exhibited a marked elevation in %FMD. By contrast, isoflavone intake effectively reduced CAVI among both premenopausal smokers (p = 0.027) and nonsmokers (p = 0.013), but had no effect on CAVI among postmenopausal smokers (p = 0.169) or nonsmokers (p = 0.128). The women smokers and nonsmokers did not differ in age or %FMD at the time of enrollment in the study. Thus, isoflavones have different effects on vascular endothelial function and arterial wall stiffness in premenopausal and postmenopausal smokers and nonsmokers.

Association between Protein Intake and Skeletal Muscle Mass among Community-Dwelling Older Japanese: Results from the DOSANCO Health Study: A Cross-Sectional Study.

Whether the source of dietary protein intake is related to appendicular skeletal muscle mass (AMM) and muscle mass (MM) remains unclear. We conducted this cross-sectional study of 277 residents (115 men, 162 women) aged ≥65 years in Japan to examine the association of the amount of dietary protein intake with AMM and MM. We measured dietary protein intake using a brief self-administered diet history questionnaire. AMM and MM were assessed based on bioelectrical impedance. Multivariable linear regression analyses were used to estimate ß coefficients that were adjusted for potential confounders. Among Japanese women aged ≥75 years, but not among women aged 65-74 years, dietary animal protein intake was significantly associated with AMM (ß (95% confidence interval (CI)): 0.25 (0.10, 0.40)) and MM (ß (95% CI): 0.40 (0.16, 0.64)). However, dietary vegetable protein intake was not associated with AMM (ß (95% CI): -0.17 (-0.74, 0.41)) and MM (ß (95% CI): -0.30 (-1.23, 0.63)). Furthermore, in men aged ≥65 years, dietary protein intake was not associated with AMM or MM. In conclusion, dietary animal protein intake, but not vegetable protein intake, were positively associated with AMM and MM among this population of Japanese women aged ≥75 years.

Inverse correlation between serum high-molecular-weight adiponectin and proinsulin level in a Japanese population: The Dynamics of Lifestyle and Neighborhood Community on Health Study.

Serum high-molecular-weight adiponectin (HMWA) has a positive correlation with insulin secretion in the Japanese population. To validate this correlation, we investigated the correlation between serum HMWA and proinsulin, a marker of ß-cell dysfunction, in this population. A total of 488 participants (53.9% women) aged 35-79 years not taking oral hypoglycemic agents and/or insulin were enrolled. HMWA was significantly and inversely correlated with proinsulin adjusted for age and sex (partial regression coefficient ß = -0.37; 95% confidence interval -0.46 to -0.28). When the participants were divided into two groups by median values of body mass index (23.2 kg/m2 ), serum insulin (4.3 µU/mL) or homeostasis model assessment of insulin resistance (1.0), similar inverse correlations were observed adjusted for age and sex in both groups. Our results showed that the HMWA level was inversely correlated with the proinsulin level in a general Japanese population.

Fecal short-chain fatty acids and obesity in a community-based Japanese population: The DOSANCO Health Study.

In Western populations, fecal concentrations of short-chain fatty acids (SCFAs) are positively correlated with the prevalence of obesity. However, gut microbiota involved in the production of SCFA varies between races. Our purpose was to investigate the associations between fecal SCFAs and the prevalence of obesity in a community-based Japanese population. We classified a total of 568 participants aged ≥18 into four quartiles of fecal concentrations of SCFA subtypes (acetate, butyrate, and propionate) and total SCFAs to compare the prevalence of obesity, defined as a body mass index ≥ 25.0 kg/m2. Using the first quartile SCFA group as a reference, the prevalence ratios of obesity were calculated for each SCFA group through a log-binomial regression model adjusted for major potentially confounding factors including age, sex, exercise habits, total energy intake, and total dietary fiber intake. In the study population, the prevalence of obesity was 35.8%. The prevalence ratios (95% confidence intervals) of obesity in the second, third, and fourth quartile groups of fecal total SCFAs were 1.30 (0.89-1.89), 1.74 (1.23-2.47) and 1.70 (1.19-2.41), respectively, after adjusting for the confounders. Similar positive associations were observed for every subtype. The prevalence ratios (95% confidence intervals) in the fourth quartile groups of fecal acetate, butyrate, and propionate were 1.41 (1.02-1.97), 2.16 (1.49-3.14), and 1.97 (1.35-2.89), respectively, after adjusting for the confounders. In conclusion, our results demonstrated that fecal SCFA concentrations of every subtype were positively associated with the prevalence of obesity in a community-based Japanese population.

Comparison of dimension reduction methods on fatty acids food source study.

Serum fatty acids (FAs) exist in the four lipid fractions of triglycerides (TGs), phospholipids (PLs), cholesteryl esters (CEs) and free fatty acids (FFAs). Total fatty acids (TFAs) indicate the sum of FAs in them. In this study, four statistical analysis methods, which are independent component analysis (ICA), factor analysis, common principal component analysis (CPCA) and principal component analysis (PCA), were conducted to uncover food sources of FAs among the four lipid fractions (CE, FFA, and TG + PL). Among the methods, ICA provided the most suggestive results. To distinguish the animal fat intake from endogenous fatty acids, FFA variables in ICA and factor analysis were studied. ICA provided more distinct suggestions of FA food sources (endogenous, plant oil intake, animal fat intake, and fish oil intake) than factor analysis. Moreover, ICA was discovered as a new approach to distinguish animal FAs from endogenous FAs, which will have an impact on epidemiological studies. In addition, the correlation coefficients between a published dataset of food FA compositions and the loading values obtained in the present ICA study suggested specific foods as serum FA sources. In conclusion, we found that ICA is a useful tool to uncover food sources of serum FAs.

HPLC with spectrophotometric or mass spectrometric detection for quantifying very-long chain fatty acids in human plasma and its association with cardiac risk factors.

BACKGROUND: We developed and compared two liquid chromatography methods, one with UV/Visible spectrophotometric detection (HPLC) and the other with mass spectrometric detection (LC-MS), for quantifying very-long chain fatty acids (VLCFA) in human plasma. Association of VLCFA with various cardiovascular risk factors were evaluated. METHOD: Fasting blood samples were collected from 541 human volunteers (242 men and 299 women; mean age ±SD, 58.9 ± 12.4 years), including 429 and 112 individuals with and without hypertriglyceridemia, respectively. Esterified VLCFA were saponified and derivatized with 2-nitrophenylhydrazine. Separation of VLCFA species was achieved with C4 Mightysil column (HPLC) and Ascentis Express Phenyl-Hexyl column (LC-MS) followed by spectrophotometric and selected-reaction monitoring mode of mass spectrometric detection, respectively. RESULTS: The HPLC assay of VLCFA was precise with intra-assay imprecision of 2.5% to 6.9% and inter-assay imprecision of 3.2% to 9.5%. Moreover, there was an excellent correlation (r > 0.96) between HPLC and LC-MS methods. The 95 percentile reference intervals (RI; upper limit) of VLCFA were determined to be 41.3 µmol/L in healthy volunteers. Plasma VLCFA were significantly correlated with triglycerides (Spearman's ρ = 0.306, P < 0.001) and total cholesterol (Spearman's ρ = 0.251, P < 0.001). All species of VLCFA were significantly elevated in hypertriglyceridaemic individuals compared with control. CONCLUSION: We established LC-based assays of VLCFA with either spectrophotometry or mass spectrometry as a detection system. Hypertriglyceridaemia is significantly associated with elevated concentration of each species of VLCFA.