Safety and efficacy of long-term nicotinamide mononucleotide supplementation on metabolism, sleep, and nicotinamide adenine dinucleotide biosynthesis in healthy, middle-aged Japanese men.

Obesity and aging are major risk factors for several life-threatening diseases. Accumulating evidence from both rodents and humans suggests that the levels of nicotinamide adenine dinucleotide (NAD+), a regulator of many biological processes, declines in multiple organs and tissues with aging and obesity. Administration of an NAD+ intermediate, nicotinamide mononucleotide (NMN), replenishes intracellular NAD+ levels and mitigates aging- and obesity-associated derangements in animal models. In this human clinical study, we aimed to investigate the safety and effects of 8-week oral administration of NMN on biochemical, metabolic, ophthalmologic, and sleep quality parameters as well as on chronological alterations in NAD+ content in peripheral tissues. An 8-week, single-center, single-arm, open-label clinical trial was conducted. Eleven healthy, middle-aged Japanese men received two 125-mg NMN capsules once daily before breakfast. The 8-week NMN supplementation regimen was well-tolerated; NAD+ levels in peripheral blood mononuclear cells increased over the course of NMN administration. In participants with insulin oversecretion after oral glucose loading, NMN modestly attenuated postprandial hyperinsulinemia, a risk factor for coronary artery disease (n = 3). In conclusion, NMN overall safely and effectively boosted NAD+ biosynthesis in healthy, middle-aged Japanese men, showing its potential for alleviating postprandial hyperinsulinemia.

Morphological alterations in corneal nerves of patients with dry eye and associated biomarkers.

The purposes of the present study were to (1) identify the relationship between dry eye symptoms and morphological changes in corneal subbasal nerves/ocular surfaces, and (2) discover tear film biomarkers indicating morphological changes in the subbasal nerves. This was a prospective cross-sectional study conducted between October and November 2017. Adults with dry eye disease (DED, n = 43) and healthy eyes (n = 16) were evaluated based on their subjective symptoms and ophthalmological findings. Corneal subbasal nerves were observed using confocal laser scanning microscopy. Nerve lengths, densities, branch numbers, and nerve fiber tortuosity were analyzed using ACCMetrics and CCMetrics image analysis systems; tear proteins were quantified by mass spectroscopy. Compared with the control group, the DED group had significantly lower tear breakup times (TBUT) and pain tolerance capacity, and significantly higher corneal nerve branch density (CNBD) and corneal nerve total branch density (CTBD). CNBD and CTBD showed significant negative correlations with TBUT. Six biomarkers (cystatin-S, immunoglobulin kappa constant, neutrophil gelatinase-associated lipocalin, profilin-1, protein S100-A8, and protein S100-A9) showed significant positive correlations with CNBD and CTBD. The significantly higher CNBD and CTBD in the DED group suggests that DED is associated with morphological alterations in corneal nerves. The correlation of TBUT with CNBD and CTBD further supports this inference. Six candidate biomarkers that correlate with morphological changes were identified. Thus, morphological changes in corneal nerves are a hallmark of DED, and confocal microscopy may help in the diagnosis and treatment of dry eyes.

The effects of a steam warming eye mask on the ocular surface and mental health.

PURPOSE: The continuous use of warming eye masks improves tear function. In this double-blind randomized controlled trial, we aimed to analyze the effects of warming eye mask use on the ocular surface and mental health. METHODS: We enrolled 86 participants (age range: 23-89 years) from affiliated institutions who were divided into two groups: the warm group that used warming eye masks that generate moist heat at 40 °C for 10 min and the control group that used non-warming eye masks. The participants used the masks for 10 min once daily for 2 weeks. Before and after the intervention, in 79 participants (warm group 39, control group 40), we analyzed the tear break up time (TBUT) and corneal and conjunctival fluorescein staining results in the right eye and Hospital Anxiety and Depression Score (Anxiety: HADS-A, Depression: HADS-D), and Subjective Happiness Scale (SHS) questionnaires. The parameters before and after the intervention were compared via paired-t tests. RESULTS: The following variables changed after the intervention: TBUT (warm group: 1.4 ± 2.1 s vs. control group: -0.01 ± 2.38 s), fluorescein staining score (-0.7 ± 1.1 vs.-0.2 ± 1.1), HADS-A (-0.8 ± 3.1 vs. -0.2 ± 2.2), and HADS-D (-1.0 ± 2.4 vs. -0.4 ± 1.9). Significant changes were observed in the TBUT (warm group), fluorescein staining score (warm group), and HADS-D (warm group). CONCLUSIONS: Using a warming eye mask improves not only the ocular surface conditions but also the subjective depression scores.

Two case reports of continued progression of chronic ocular graft-versus-host disease without concurrent systemic comorbidities treated by amniotic membrane transplantation.

BACKGROUND: Chronic ocular graft-versus-host disease (oGVHD) is an ocular comorbidity of graft-versus-host disease (GVHD) that usually occurs concurrently with systemic manifestations. Failure to detect and treat oGVHD in its early stages may lead to progression of ocular signs and symptoms leading to oGVHD that is refractory to conventional treatment. CASE PRESENTATION: We report the clinical course of a 19-year-old male and a 59-year-old female with severe and progressive chronic oGVHD without concurrent systemic signs of chronic graft-versus-host disease (cGVHD). Although their systemic conditions had been stable, both suffered from severe oGVHD and were referred to our clinic. Both cases exhibited marked improvement in conjunctival inflammation and fibrotic changes after amniotic membrane transplantation (AMT). Both cases underwent keratoplasty eventually to stabilize ocular surface conditions and to improve visual function. CONCLUSIONS: We reported the clinical outcomes of 2 cases of chronic oGVHD without concurrent systemic comorbidities that were treated with AMT. The clinician should be aware that cGVHD may persist in target organs even in the absence of concurrent systemic comorbidities following seemingly successful systemic treatment. A multidisciplinary team approach is essential in the early detection and therapeutic intervention for chronic oGVHD.

Myopia, corneal endothelial cell density and morphology in a Japanese population-based cross-sectional study: the JPHC-NEXT Eye Study.

This population-based cross-sectional study was performed to determine the mean corneal endothelial cell density (ECD), coefficient of variation (CV), and hexagonality (HEX), and their associations with myopia in Japanese adults living in Chikusei city. Of 7109 participants with available data, 5713 (2331 male and 3382 female) participants were eligible for analysis. After assessing the relationship between participant characteristics and spherical equivalent refraction (SER), the association of SER with the abnormal value of ECD (< 2000 cells/mm), CV (≥ 0.40), and HEX (≤ 50%) were determined using the logistic regression models adjusting for potential confounders (age, intraocular pressure, keratometric power, height, and antihypertensive drug use). In male participants, there was no statistically significant relationships between SER and endothelial parameters. In female participants, compared to emmetropia, SER ≤ - 6 D had significantly higher odds ratio (OR) of having the abnormal value of CV (OR = 2.07, 95% confidence interval [CI] 1.39-3.10) and HEX (OR = 2.04, 95% CI 1.29-3.23), adjusted for potential confounders, indicating that the high myopia was associated with the abnormal values of CV and HEX. Further adjustment for contact lenses wear partly attenuated these associations. Association between the SER and ECD was not detected.

Analysis of the Association between Galectin-3 Concentration in Tears and the Severity of Dry Eye Disease: A Case-Control Study.

This study aimed to investigate the relationship between the severity of dry eye disease (DED) and galectin-3 concentration (gal-3) and its cleavage (gal-3C) in tear fluid. Twenty-eight DED patients and 14 controls were recruited at Keio University Hospital. The lissamine green conjunctival staining (LG) score, fluorescein corneal staining (FL) score, tear film break-up time (TBUT), Schirmer's test, and ocular symptoms questionnaire score (dry eye questionnaire score, DEQS) were evaluated. Furthermore, the correlation between these parameters and the concentrations of gal-3 in tears (ng/µg) and the detection rate of gal-3C (%) were analyzed. Gal-3 concentration in tears was positively correlated with the LG score (R = 0.60, p < 0.01), FL score (R = 0.49, p < 0.01), and DEQS (R = 0.45, p < 0.01), and negatively correlated with the TBUT score (R = -0.40, p < 0.01) and Schirmer's I value (R = -0.36, p < 0.01). The detection rate of gal-3C in tears was significantly associated with the severity of DED, especially with the LG (p < 0.01) and FL (p < 0.01) scores. Therefore, the concentration of gal-3 and the detection rate of gal-3C in tears had a significant relationship with the severity of ocular surface barrier disruption.

Eosinophils promote corneal wound healing via the 12/15-lipoxygenase pathway.

Lipid mediators play important roles in regulating inflammatory responses and tissue homeostasis. Since 12/15-lipoxygenase (12/15-LOX)-derived lipid mediators such as lipoxin A4 (LXA4 ) and protectin D1 (PD1) protect against corneal epithelial cell damage, the major cell types that express 12/15-LOX and contribute to the corneal wound healing process are of particular interest. Here, we found that eosinophils were the major cell type expressing 12/15-LOX during the corneal wound healing process. Eosinophils were recruited into the conjunctiva after corneal epithelium wounding, and eosinophil-deficient and/or eosinophil-specific 12/15-LOX knockout mice showed delayed corneal wound healing compared with wild-type mice. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based mediator lipidomics revealed that a series of 12/15-LOX-derived mediators were significantly decreased in eosinophil-deficient mice and topical application of 17-hydroxydocosahexaenoic acid (17-HDoHE), a major 12/15-LOX-derived product, restored the phenotype. These results indicate that 12/15-LOX-expressing eosinophils, by locally producing pro-resolving mediators, significantly contribute to the corneal wound healing process in the eye.

Conjunctival Epithelial Ingrowth After Penetrating Keratoplasty.

PURPOSE: To report a case of conjunctival epithelial ingrowth after penetrating keratoplasty. METHODS: A 57-year-old woman with herpetic corneal keratitis, endotheliitis, and bullous keratopathy underwent penetrating keratoplasty (PKP) and secondary cataract surgery. One month after cataract surgery, an epithelial ingrowth was observed at the 5 o'clock donor host junction. Ingrowth extended into the anterior chamber and along the iris surface by 9 months. Another PKP was performed, and the excised graft was submitted for histopathology. RESULTS: The graft showed CK13-positive and CK3-negative cells lining the endothelial surface, indicating the conjunctival origin of ingrown epithelium. Ten months postoperatively, no recurrence of ingrowth was observed. CONCLUSIONS: We experienced a rare case of conjunctival epithelial ingrowth after penetrating keratoplasty. There was no recurrence of the ingrowth after surgical removal, and the conjunctival origin may explain the relatively benign course of the complication.

Demodex-Mite Infestation in Cilia and its Association With Ocular Surface Parameters in Japanese Volunteers.

OBJECTIVES: To investigate the presence of Demodex mites on the eyelashes of a Japanese population and to explore its associations with subjective ocular symptoms and clinical ocular surface signs, including lid margin findings and fluorescein breakup time (FBUT). METHODS: Sixty-three Japanese Tokyo-based volunteers were examined (24 men and 39 women; mean±SD of age, 50.6±15.8 years). Eyelash sampling was performed by epilating three lashes from the center of the right upper eyelid. Eyelashes were tested for Demodex mites with a light microscope. The subjects completed questionnaires to assess subjective symptoms and risk factors for dry eye disease (DED) and underwent general examinations for DED, including FBUT and cornea-conjunctival staining with fluorescein. Meibomian gland function was also investigated in lid margin findings, vascularity and mucocutaneous junction movement, lid irregularity, plugging, pouting, and meibum secretion grade scores. RESULTS: Demodex mites were found in 20.6% (13/63) of the volunteers. Lid margin vascularity and meibum grades in the upper eyelid margins were significantly associated with the presence of Demodex mites. However, there were no significant differences in the diagnosis of meibomian gland dysfunction, FBUT, or ocular surface discomfort between the subjects with or without Demodex mites. CONCLUSIONS: Demodex mites are not rare in the cilia of a Japanese population. Lid margin vascularity and lower meibum quality may be associated with the presence of Demodex mites.

Changes in Distribution of Dry Eye Diagnostic Status Among Visual Display Terminal Workers According to the Revised Criteria of the Asia Dry Eye Society.

PURPOSE: The present study aimed to compare the prevalence of dry eye disease (DED) among visual display terminal users using the revised and previous DED criteria. METHODS: This cross-sectional study included 561 participants (187 women). RESULTS: The distribution of diagnostic status according to the previous DED criteria was as follows: definite DED (n = 65, 11.6%), probable DED (n = 303, 54.0%), and non-DED (n = 193, 34.4%). According to the revised criteria, 329 participants (58.6%) were classified as DED and 232 participants (41.4%) were classified as non-DED. CONCLUSIONS: The prevalence of DED among visual display terminal users has increased to 58.6% from 11.6%, according to the revised DED diagnostic criteria of the Asia Dry Eye Society.

Treatment Trends in Dry Eye Disease and Factors Associated with Ophthalmic Follow-up Discontinuation in Japan.

Despite the importance of dry eye disease (DED) treatment, the rate of DED treatment discontinuation, especially discontinuation of ophthalmic follow-up, remains unknown. This study aimed to assess the prevalence and risk factors of ophthalmic follow-up discontinuation for DED. A cross-sectional survey of 1030 participants was conducted using a self-administered web-survey instrument. We collected lifestyle information, history of DED diagnosis, types of treatment, frequency of eye-drop usage, symptoms, and the reasons for discontinuing treatment. Statistical analyses including logistic regression were used to evaluate the risk factors of discontinuing ophthalmic follow-up for DED. A past history of clinical DED diagnosis was reported by 155 (15.0%) subjects. Of those, 130 had persistent DED, and 88 (67.7%) of the subjects reported discontinuation of ophthalmic follow-up for DED. The most prevalent reasons for ophthalmic follow-up discontinuation were time restrictions, followed by dissatisfaction with the DED treatment. Duration after DED diagnosis was the only significant risk factor for discontinuing ophthalmic follow-up after adjusting for age and sex (odds ratio = 1.09, 95% confidence interval = 1.02-1.17, p = 0.009). In conclusion, longer DED duration after diagnosis was a significant risk factor for discontinuing ophthalmic follow-up for DED. This study showed that DED ophthalmic follow-up discontinuation involves both medical and non-medical reasons. Clinicians need to be aware of them, and preventative effort is needed to avoid discontinuation.

Characteristics of Individuals with Dry Eye Symptoms Without Clinical Diagnosis: Analysis of a Web-Based Survey.

Currently, the available treatment for dry eye disease (DED) varies. The present study aimed to investigate the characteristics of undiagnosed DED and patient-based self-care management for DED based on a web-based survey performed for Tear's Day in Japan; 1030 participants (301 women) responded; 155 participants (72 women) had a clinical diagnosis of DED. We defined undiagnosed DED (n = 116; 54 women) as those with DED symptoms, as evaluated by a frequently used questionnaire despite not having a clinical diagnosis. A multivariate adjusted model indicated that younger age (odds ratio (OR), 0.97 for each one-year decrease; 95% confidence interval (CI), 0.95-0.99), female sex (OR, 2.12; 95% CI, 1.28-3.50), and prolonged visual display terminal usage (OR, 1.12; 95% CI, 1.04-1.21) were risk factors for undiagnosed DED. To investigate the efficacy of self-care management for DED, a sub-analysis was conducted. The number of self-care methods used was significantly higher among women than men. For undiagnosed DED, those with less than three self-care methods had a significantly worse Dry Eye-related Quality-of-Life Score compared with those with diagnosed DED. This study revealed risk factors for undiagnosed DED; individuals with those risk factors need to be clinically assessed and should not rely solely on self-care.

A novel and innovative paper-based analytical device for assessing tear lactoferrin of dry eye patients.

PURPOSE: To elucidate the correlation between lactoferrin concentration in the tear film and signs and symptoms of severe dry eye disease (DED) using a novel microfluidic paper-based analytical device (µPAD) and enzyme-linked immunosorbent assay (ELISA). METHODS: Twenty-four patients were recruited at the Keio University Hospital. Using a novel µPAD, lactoferrin concentrations were measured in 4 patients with GVHD-related DED, 3 patients with other types of DED and 2 controls (Group A). For validation by ELISA, 22 patients (7 patients from Group A) comprising 9 patients with GVHD-related DED, 6 patients with other types of DED and 7 controls were examined (Group B). The link between lactoferrin concentration and clinical data about the severity of aqueous tear deficient DED was also investigated by both µPAD and ELISA. RESULTS: The lactoferrin concentration in tear fluid of the DED patients was positively correlated between µPAD and ELISA (p = 0.006, r = 0.886). The tear fluid of the GVHD patients showed low or undetectable lactoferrin concentration. Analysis by ELISA demonstrated that lactoferrin concentrations in the tear film from the GVHD patients were significantly lower than those from the non-GVHD patients (p = 0.010576). ELISA revealed lactoferrin concentration correlated with the value of Schirmer test and tear film breakup time, whereas it was inversely correlated with OSDI, fluorescein and rose bengal scores. CONCLUSIONS: The novel µPAD may pave the way for measuring lactoferrin concentration in tear fluid from DED patients. Our results suggested that lactoferrin concentration in tear fluid reflect the severity of DED.

Prognosis after lamellar keratoplasty for limbal dermoids using preserved corneas.

PURPOSE: To evaluate the safety and efficacy of lamellar keratoplasty using preserved donor corneas to treat limbal dermoids. STUDY DESIGN: Retrospective study. METHODS: The clinical records of 19 patients with limbal dermoids, who underwent lamellar keratoplasty using preserved corneas that were observed for more than 6 months at the Keio University School of Medicine between January, 2000 and December, 2017, were retrospectively reviewed. We retrospectively analyzed demographics, surgical outcomes, the occurrence of any surgically induced changes in refraction, and intra and postoperative complications. RESULTS: Patient age at surgery showed 2 peaks, the first ranged from 0 to 6 years, and the second from 13 to 20 years. All patients except one had good cosmetic results. Preoperative astigmatism was more than 2 diopters in 12 of 16 eyes for which refractive data were recorded. The refractive cylinder in 8 of the 16 eyes differed after surgery by less than 2 diopters. Treatment of amblyopia by occlusion of the fellow eye and spectacle prescription was done either prior to or following surgery, and resulted in improved visual acuity in 7 patients. Intraoperative complications did not occur in any of the patients. Postoperatively, all patients except one showed corneal re-epithelialization within a week. CONCLUSION: Lamellar keratoplasty using preserved corneas for limbal dermoid yields good cosmetic results. However, improvements in astigmatism and visual acuity are not guaranteed. Preoperative treatment of amblyopia gives a better prognosis for improved visual acuity postoperatively. Long-term observation including amblyopia treatment is required before and after surgery.

The Ocular Surface Glycocalyx and its Alteration in Dry Eye Disease: A Review.

Many studies have revealed that transmembrane mucins, large glycoproteins with heavily glycosylated glycans, are essential for maintaining ocular surface epithelium lubrication and wettability. Recent reports indicate that transmembrane mucins and galectin-3, a chimera type of galectin that binds ß-galactoside in the glycan, play a crucial role in maintaining the epithelial glycocalyx barrier. This review summarizes current evidence regarding the role of galectin-3, the role of the three major transmembrane mucins (i.e., MUC1, MUC4, and MUC16), in the maintenance of ocular surface wettability and transcellular barrier. Pathological mechanisms of glycocalyx barrier disruption and epithelial surface wettability decreases in dry eye disease are also summarized. Lastly, new ophthalmic drugs that target transmembrane mucin are described.

Association between tear film break up time and blink interval in visual display terminal users.

AIM: To investigate the association between tear film break up time (TBUT) and blinking interval in visual display terminal (VDT) users. METHODS: Nine hundred and thirty VDT users underwent dry eye testing, and functional visual acuity (FVA) test. The blinking interval during FVA was compared with TBUT. Subjects with longer blinking interval than TBUT were considered as unstable tear film. Logistic regression analysis revealed the risk factors for unstable tear group. RESULTS: Among 930 workers, 858 subjects (92.3%) participated in this study. Almost 80% of the subjects were categorized into the unstable tear group. Unstable tear group has significantly lower Schirmer values and TBUT (17.5±11.6 vs 21.1±11.5 mm, 3.7±2.6 vs 5.7±2.7s, both P<0.001). There were no significant differences in epithelial staining or severity of symptoms. Logistic regression showed that over 40y was a risk for being unstable tear group [odds ratio (OR)=1.53; 95% confidence interval (CI)=1.06-2.20]. Contact lens use was protective factor for being in the unstable tear group (OR=0.37; 95%CI= 0.26-0.53). CONCLUSION: Subjects with shorter TBUT than blinking interval are prevalent among VDT users. Subjects over the age of 40 shows an increased risk for unstable tear film.

What Have We Learned From the Osaka Study?

PURPOSE: To summarize the results of a cross-sectional epidemiologic study of Japanese office workers who use visual display terminals (VDTs). METHODS: Workers in a pharmaceutical company head office were recruited. Participants were requested to complete a questionnaire on symptoms of dry eye disease (DED) and evaluations using the Work Limitations Questionnaire, International Physical Activity Questionnaire, Subjective Happiness Scale, and Pittsburgh Sleep Quality Index. Evaluations of ocular status, including conjunctival and corneal vital staining with lissamine green and fluorescein, measurement of tear film breakup time, and the Schirmer test, were performed. The Japanese 2007 diagnostic criteria for DED were implemented. RESULTS: The prevalence of DED among VDT workers was high. Definite DED was present in 11.6% (18.7% women and 8.0% men) of participants, and probable DED was present in 54.0% (57.8% women and 52.1% men). Total loss of workplace productivity was significantly greater in the definite DED group (4.82%) than in the probable DED group (4.06%) and the non-DED group (3.56%, P < 0.014, trend test). Participants with definite DED had significantly lower physical activity scores than those without DED (P = 0.025). Subjective happiness correlated with the dry eye symptom score (r = -0.188; P < 0.001). Participants with DED reported poor sleep quality at a higher rate compared with those without DED (45% vs. 34%), with a significant difference in the global score (P = 0.002). CONCLUSIONS: Dry eye is prevalent among VDT workers. Its impacts on work productivity, physical activity, and sleep quality warrant further study.

The evaluation of dry eye mobile apps for screening of dry eye disease and educational tear event in Japan.

PURPOSE: To evaluate the usefulness of a dry eye mobile application (app) for screening dry eye disease (DED) at educational tear events in Japan. METHODS: In this cross-sectional study, Japanese subjects visiting a "Tears Day" event were selected randomly. They completed questionnaires and underwent ophthalmic evaluations for DED (using Japanese revised diagnostic criteria) including a functional visual acuity (FVA) test. The app calculated FVA using the average of the continuous VA over 30 s. RESULTS: Sixty-three general-population subjects were included: 25 men and 38 women (average age, 50.8 ±â€¯15.9 years). The prevalence of DED was 66.7% (42 subjects); age was significantly higher among subjects with DED (55.2 ±â€¯3.4 vs. 48.1 ±â€¯2.7 years, p = 0.04; men, 54.0 ±â€¯7.3 vs. 47.0 ±â€¯3.0 years, p = 0.36; women, 55.5 ±â€¯3.9 vs. 50.6 ±â€¯3.8 years, p = 0.4). The prevalence of DED was significantly higher in women (p = 0.04). Tear film breakup time was significantly shorter (3.8 ±â€¯2.4 vs. 8.7 ±â€¯2.0, p = 0.04) and the meibum score was significantly higher (p = 0.02) among subjects with DED. Regarding the tear film breakup pattern, line and random breaks were most prevalent among DED. FVA showed a significant negative correlation with DED (r = -0.25, p = 0.047). CONCLUSIONS: The app might motivate people to perform quick tests with the expectation of getting easy DED screening. The number of subjects diagnosed with DED was relatively high.

Effect of Oral Branched-Chain Amino Acids on Serum Albumin Concentration in Heart Failure Patients with Hypoalbuminemia: Results of a Preliminary Study.

BACKGROUND: We conducted a randomized, controlled trial to determine whether supplementation with oral branched-chain amino acids (BCAAs) improves serum albumin and clinical outcomes in heart failure (HF) patients with hypoalbuminemia. METHODS AND RESULTS: We randomly assigned 18 in-hospital HF patients with serum albumin < 3.5 g/dL to receive oral BCAA granules (LIVACT®) for 28 days during their hospital stay or until discharge (BCAA group; N = 9) or to receive no supplementation (controls; N = 9), in addition to recommended HF therapy. The primary endpoints were changes from baseline in serum albumin and cardiothoracic ratio (CTR). Sixteen patients completed the study. The mean (± standard deviation) period of BCAA supplementation was 18.4 ± 8.4 days. Serum albumin significantly increased in the BCAA group [mean difference vs baseline, 0.44 g/dL; 95% confidence interval (CI) 0.13-0.76; P = 0.014] and did not change in controls (0.18 g/dL; 95% CI - 0.05 to 0.40; P = 0.108). CTR significantly decreased in the BCAA group (- 2.3%; 95% CI - 3.8 to - 0.8; P = 0.014) and did not change in controls (- 1.0%; 95% CI - 2.3 to 0.3; P = 0.111). CONCLUSION: In-hospital HF patients with hypoalbuminemia supplemented with BCAAs showed increased serum albumin and decreased CTR. Clinical trial registration number UMIN000004488 [ http://www.umin.ac.jp/ctr/index.htm ].