Efficacy of Integrated Online Mindfulness and Self-compassion Training for Adults With Atopic Dermatitis: A Randomized Clinical Trial.

Importance: Quality of life (QOL) of patients with atopic dermatitis (AD) is reported to be the lowest among skin diseases. To our knowledge, mindfulness and self-compassion training has not been evaluated for adults with AD. Objective: To evaluate the efficacy of mindfulness and self-compassion training in improving the QOL for adults with AD. Design, Setting, and Participants: This randomized clinical trial conducted from March 2019 through October 2022 included adults with AD whose Dermatology Life Quality Index (DLQI) score, a skin disease-specific QOL measure, was greater than 6 (corresponding to moderate or greater impairment). Participants were recruited from multiple outpatient institutes in Japan and through the study's social media outlets and website. Interventions: Participants were randomized 1:1 to receive eight 90-minute weekly group sessions of online mindfulness and self-compassion training or to a waiting list. Both groups were allowed to receive any dermatologic treatment except dupilumab. Main Outcomes and Measures: The primary outcome was the change in the DLQI score from baseline to week 13. Secondary outcomes included eczema severity, itch- and scratching-related visual analog scales, self-compassion and all of its subscales, mindfulness, psychological symptoms, and participants' adherence to dermatologist-advised treatments. Results: The study randomized 107 adults to the intervention group (n = 56) or the waiting list (n = 51). The overall participant mean (SD) age was 36.3 (10.5) years, 85 (79.4%) were women, and the mean (SD) AD duration was 26.6 (11.7) years. Among participants from the intervention group, 55 (98.2%) attended 6 or more of the 8 sessions, and 105 of all participants (98.1%) completed the assessment at 13 weeks. The intervention group demonstrated greater improvement in the DLQI score at 13 weeks (between-group difference estimate, -6.34; 95% CI, -8.27 to -4.41; P < .001). The standardized effect size (Cohen d) at 13 weeks was -1.06 (95% CI, -1.39 to -0.74). All secondary outcomes showed greater improvements in the intervention group than in the waiting list group. Conclusions and Relevance: In this randomized clinical trial of adults with AD, integrated online mindfulness and self-compassion training in addition to usual care resulted in greater improvement in skin disease-specific QOL and other patient-reported outcomes, including eczema severity. These findings suggest that mindfulness and self-compassion training is an effective treatment option for adults with AD. Trial Registration: https://umin.ac.jp/ctr Identifier: UMIN000036277.

Anti-allergic effects of enzymatically modified isoquercitrin (α-oligoglucosyl quercetin 3-O-glucoside), quercetin 3-O-glucoside, α-oligoglucosyl rutin, and quercetin, when administered orally to mice.

Quercetin, a flavonol distributed widely in edible and medicinal plants, has beneficial biological activities in vitro. However, the low water solubility of quercetin limits its bioavailability to exhibit activity in vivo. We evaluated the anti-allergic effects of quercetin, quercetin 3-O-glucoside (isoquercitrin, IQC), α-oligoglucosyl rutin (αOR), and enzymatically modified isoquercitrin (α-oligoglucosyl isoquercitrin; EMIQ) in the murine ear passive cutaneous anaphylaxis (PCA) reaction using ovalbumin as an antigen. The substances to be tested were dissolved or suspended in water, and administered orally to mice (4 mmol 10 ml⁻¹ kg⁻¹). EMIQ exhibited a significant inhibitory effect on the PCA reaction. We detected 600 µM IQC and 95.1 µM Q3Glcn in the plasma of mice 30 min after EMIQ treatment, suggesting that IQC and Q3Glcn might be the genuine active compounds mediating the anti-allergic effects of EMIQ. Oral treatments of quercetin and αOR at this dosage exhibited no anti-allergic effect, and IQC showed less effect than EMIQ. Since IQC and quercetin cannot completely dissolve in water at this concentration, the water solubilities of these substances might affect their biological activities. αOR dissolved well in water at the concentration used but plasma concentrations of quercetin metabolites in mice orally treated with αOR were low, suggesting that αOR might not be converted to IQC or quercetin by the enzymes in small intestine and thus not exhibit any activity. Glycosyl conjugation of quercetin with specific sugar motifs is an effective strategy to improve the biological activity of quercetin in vivo.

Enzymatically modified isoquercitrin, alpha-oligoglucosyl quercetin 3-O-glucoside, is absorbed more easily than other quercetin glycosides or aglycone after oral administration in rats.

Quercetin, a flavonol contained in various vegetables and herbal medicines, has various biological activities including anti-cancer, anti-allergic and anti-oxidative activities. However, low oral bioavailability of quercetin due to insolubility in water has limited its use as a food additive or dietary supplement. Since the water solubility is enhanced by glycosyl conjugation, in the present study, we evaluated the bioavailability of several quercetin glycosides with different sugar moieties in rats. Quercetin, quercetin-3-O-rutinoside (rutin), and quercetin-3-O-glucoside (isoquercitrin, IQC) in suspension, and quercetin-3-O-maltoside (Q3M), quercetin-3-O-gentiobioside (Q3G), alpha-monoglucosyl rutin (alphaMR), alpha-oligoglucosyl rutin (alphaOR), and enzymatically modified isoquercitrin (alpha-oligoglucosyl isoquercitrin, EMIQ) dissolved in water, were orally administered to rats under anesthesia. Bioavailability (F value) was calculated from the concentrations of total quercetin in plasma from 0 to 12 h after the administration. F value of quercetin was 2.0%, and those of IQC, Q3M and EMIQ were 12%, 30%, and 35%, respectively. Although Q3G, alphaMR and alphaOR have high water solubility, their F values were low (3.0%, 4.1%, 1.8%, respectively). In the in vitro study, the homogenate of rat intestinal epithelium rapidly hydrolyzed IQC, Q3M and EMIQ to quercetin, and alphaMR and alphaOR to rutin. However, it could not hydrolyze Q3G or rutin to quercetin. Elongation of alpha-linkage of glucose moiety in IQC enhances the bioavailability of quercetin, and intestinal epithelial enzymes such as lactase-phrolizin hydrolase or mucosal maltase-glucoamylase would play important roles in the hydrolysis and absorption of these flavonol glycosides.

Preventative effect of a flavonoid, enzymatically modified isoquercitrin on ocular symptoms of Japanese cedar pollinosis.

BACKGROUND: Flavonoids are nutrients that exert anti-allergic effects. We investigated the preventative effect of enzymatically modified isoquercitrin (EMIQ), a flavonoid, to relieve the symptoms of Japanese cedar pollinosis. METHODS: In a parallel-group, double-blind placebo-controlled study design, 24 subjects with Japanese cedar pollinosis took 100mg EMIQ or a placebo for 8 weeks, starting 4 weeks prior to the onset of pollen release. Subjective symptoms, ADL scores and the usage of drugs were recorded daily, and the QOL score was obtained every 4 weeks. Blood sampling was performed before and after the study to measure serum levels of IgE and flavonoids. RESULTS: During the entire study period, ocular symptom + medication score for the EMIQ group was significantly lower (p < 0.05) than that of the placebo group. When limited to the period, ocular symptom scores (p < 0.05, weeks 5-6), and ocular congestion scores (p < 0.05, weeks 5-6) for the EMIQ group was significantly lower than that for the placebo group while other scores for the EMIQ group, such as ocular itching scores (p = 0.09, weeks 4-5), lacrimation scores (p = 0.07, weeks 5-6), and ocular congestion scores (p = 0.06, weeks 4-5), all tended to be lower. However no significant differences were found in nasal symptoms between the two groups. Serum concentrations of IgE were not significantly downregulated but the serum concentrations of quercetin and its derivatives were elevated significantly by the intake of EMIQ. CONCLUSIONS: Intake of the quercetin glycoside EMIQ proved to be effective for the relief of ocular symptoms caused by Japanese cedar pollinosis.

Effect of enzymatically modified isoquercitrin, a flavonoid, on symptoms of Japanese cedar pollinosis: a randomized double-blind placebo-controlled trial.

BACKGROUND: Flavonoids exert antiallergic and antioxidant effects. We investigated the efficacy of enzymatically modified isoquercitrin (EMIQ), a flavonoid, to relieve symptoms of pollinosis. METHODS: In a parallel-group, double-blind placebo-controlled study design, 20 subjects with Japanese cedar pollinosis took two capsules daily of 100 mg EMIQ or a placebo for 8 weeks during the pollen season. Subjective symptoms and activities of daily living (ADL) scores were recorded every day, and the quality of life (QOL) score was obtained every 4 weeks. Blood sampling was performed before and after the study to measure serum cytokines, chemokines, IgE, quercetin and oxidized biomarkers. RESULTS: During the entire study period, total ocular score and ocular itching score for the EMIQ group were significantly lower (p < 0.05) than for the placebo group. When limited to the individual periods, total symptom score for the EMIQ group was significantly lower (p < 0.05, week 4-5) than that for the placebo group while other scores for the EMIQ group, such as total nasal score (p = 0.06, week 4-5), nasal obstruction score (p = 0.08, week 4-5), lacrimation score (p = 0.06, week 5-6), ocular congestion score (p = 0.08, week 4-7) and ADL score (p = 0.08, week 4-7), all tended to be lower. The levels of serum cytokines such as interleukin (IL)-4, IL-5, IL-12, IL-13, interferon-gamma, and eotaxin and IgE were not significantly downregulated by the intake of EMIQ but the serum concentrations of oxidized low-density lipoprotein and thymus and activation-regulated chemokine were reduced. CONCLUSION: Intake of the quercetin glycoside EMIQ was safe and influenced ocular symptoms caused by pollinosis.