Background: The tripeptide glutathione (GSH) is the most abundant free radical scavenger synthesized endogenously in humans. Increasing mechanistic, clinical, and epidemiological evidence demonstrates that GSH status is significant in acute and chronic diseases. Despite ease of delivery, little controlled clinical research data exist evaluating the effects of oral GSH supplementation. Objectives: The study objectives were to determine the effect of oral GSH supplementation on biomarkers of systemic oxidative stress in human volunteers. Design: This was a randomized, double-blind, placebo-controlled clinical trial. Setting/location: The study was conducted at Bastyr University Research Institute, Kenmore, WA and the Bastyr Center for Natural Health, Seattle, WA. Subjects: Forty (40) adult volunteers without acute or chronic disease participated in this study. Intervention: Oral GSH supplementation (500 mg twice daily) was given to the volunteers for 4 weeks. Outcome measures: Primary outcome measures included change in creatinine-standardized, urinary F2-isoprostanes (F2-isoP) and urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG). Changes in erythrocyte GSH concentrations, including total reduced glutathione (GSH), oxidized glutathione (GSSG), and their ratio (GSH:GSSG) were also measured by tandem liquid chromatography/mass spectrometry. Analysis of variance was used to evaluate differences between groups. Results: There were no differences in oxidative stress biomarkers between treatment groups at baseline. Thirty-nine (39) participants completed the study per protocol. Changes in creatinine standardized F2-isoP (ng/mg creatinine) (0.0±0.1 versus 0.0±0.1, p=0.38) and 8-OHdG (μg/g creatinine) (-0.2±3.3 versus 1.0±3.2, p=0.27) were nonsignificant between groups at week 4. Total reduced, oxidized, and ratio measures of GSH status were also unchanged. Conclusions: No significant changes were observed in biomarkers of oxidative stress, including glutathione status, in this clinical trial of oral glutathione supplementation in healthy adults.

Background: Survey findings report that 48% of people with type 2 diabetes use complementary and alternative medicine (CAM) practice. Publications suggest a high incidence of health promotion counseling in naturopathic practice, yet clinical data on risk factor changes are not available in the literature. Objectives: The primary aim of this study was to describe clinical risk factor changes during the utilization of naturopathic CAM services in patients with type 2 diabetes. Design: A retrospective, observational study design was used to describe naturopathic care. Setting: Abstracted medical charts were from patients of the Bastyr Center for Natural Health in Seattle, WA. Participants: The patients in this study had type 2 diabetes and received naturopathic care between 2001 and 2006. Outcomes: Abstracted data included patient demographics, duration of care, number of visits, laboratory values for hemoglobin A1c (HbA1c), low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol, triglycerides (TAG); and systolic/diastolic blood pressure (SPB, DBP). Results: Thirty-seven (37) patient records met inclusion criteria and were abstracted in detail. Mean and median duration of care were 27 and 20 months, respectively. The mean number of visits was 11. Significant mean changes in clinical laboratory risk factors over the duration of care were: −0.65% for HbA1c (p = 0.046), −45 mg/dL for TAG (p = 0.037), −7 mm Hg in SBP (p = 0.02), and −5 mm Hg in DBP (p = 0.003). Mean changes for cholesterol did not reach statistical significance. The percentage of patients who reached new control, had clinically significant risk factor improvements, or had any improvement was: 26%, 42%, and 68% for HbA1c, 7%, 28%, and 62% for LDL, 0%, 25%, and 39% for HDL, 14%, 38%, and 52% for TAG, 16%, 51%, and 86% for SBP, and 27%, 54%, and 70% for DBP. Comments/conclusions: These preliminary outcomes suggest that risk factor improvements occur during naturopathic care for diabetes, although the contribution of naturopathic care to these changes cannot be determined. Effectiveness and generalizability of naturopathic approaches in treating type 2 diabetes should be evaluated in controlled prospective studies in representative populations or randomized trials.

Background: Marine lipids contain omega-3 fatty acids that can be metabolized into anti-inflammatory and pro-resolving mediators—namely 17-HDHA and 18-HEPE—which can serve as modulators of the pain experience. The purpose of this study was to determine the impact of 4 weeks of oral supplementation with a fractionated marine lipid concentration, standardized to 17-HDHA and 18-HEPE, on health-related quality of life and inflammation in adults with chronic pain. Methods: This study was a prospective, non-randomized, open-label clinical trial. Forty-four adults with ≥ moderate pain intensity for at least 3 months were recruited. The primary outcome was change in health-related quality of life (QOL) using the Patient Reported Outcomes Measurement Information System-43 Profile (PROMIS-43) and the American Chronic Pain Association (ACPA) QOL scale. Exploratory outcomes assessed safety and tolerability, changes in anxiety and depression, levels of pain intensity and interference, patient satisfaction, and impression of change. Changes in blood biomarkers of inflammation (hs-CRP and ESR) were also explored. Results: Outcome measures were collected at Baseline, Week 2, and Week 4 (primary endpoint). At Week 4, PROMIS-43 QOL subdomains changed with significance from baseline (p < 0.05), with borderline changes in the ACPA Quality of Life scale (p < 0.052). Exploratory analyses revealed significant changes (p < 0.05) in all measures of pain intensity, pain interference, depression, and anxiety. There were no statistically significant changes in either hs-CRP or ESR, which stayed within normal limits. Conclusion: We conclude that oral supplementation with a fractionated marine lipid concentration standardized to 17-HDHA and 18-HEPE may improve quality of life, reduce pain intensity and interference, and improve mood within 4 weeks in adults with chronic pain. The consistency and magnitude of these results support the need for placebo-controlled clinical trials of marine lipid concentrations standardized to 17-HDHA and 18-HEPE. Trial registration ClinicalTrials.gov: Influence of an Omega-3 SPM Supplement on Quality of Life, NCT02683850. Registered 17 February 2016—retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02683850.

Xanthohumol (XN), a polyphenol found in the hop plant (Humulus lupulus), has antioxidant, anti-inflammatory, prebiotic, and anti-hyperlipidemic activity. Preclinical evidence suggests the gut microbiome is essential in mediating these bioactivities; however, relatively little is known about XN's impact on human gut microbiota in vivo. We conducted a randomized, triple-blinded, placebo-controlled clinical trial (ClinicalTrials.gov NCT03735420) to determine safety and tolerability of XN in healthy adults. Thirty healthy participants were randomized to 24 mg/day XN or placebo for 8 weeks. As secondary outcomes, quantification of bacterial metabolites and 16S rRNA gene sequencing were utilized to explore the relationships between XN supplementation, gut microbiota, and biomarkers of gut health. Although XN did not significantly change gut microbiota composition, it did re-shape individual taxa in an enterotype-dependent manner. High levels of inter-individual variation in metabolic profiles and bioavailability of XN metabolites were observed. Moreover, reductions in microbiota-derived bile acid metabolism were observed, which were specific to Prevotella and Ruminococcus enterotypes. These results suggest interactions between XN and gut microbiota in healthy adults are highly inter-individualized and potentially indicate that XN elicits effects on gut health in an enterotype-dependent manner.