Xanthohumol (XN), a dietary flavonoid from hops (Humulus lupulus), possesses anti-inflammatory and microbiome-modulatory properties with potential therapeutic benefits for Crohn's disease (CD). To investigate the effects of XN on the gut environment in CD, we conducted a randomized, placebo-controlled clinical trial-the XN Microbiome and Signature (XMaS) trial (NCT4590508). 19 participants with clinically active CD completed the study. They were randomized to receive 24 mg/day of XN or placebo for 8 weeks, with clinical assessments at baseline and every 2 weeks. We assessed changes to Crohn's disease activity index (CDAI) scores, systemic inflammation, gut barrier function, profiling of microbial metabolism of XN, and gut microbiota composition and metabolism. Integration analysis of gut microbiota abundance, fecal metabolites, and inflammatory markers with CDAI scores revealed a pattern in which reductions in secondary bile acids and increases in IL-10 were associated with improved CDAI score in XN-treated individuals. These findings suggest that XN beneficially modulates the gut environment in CD by influencing microbial bile acid metabolism and host inflammatory response, thereby improving symptoms in individuals with severe innate immune activation.

Background and aims: Despite growing popularity and increasing legal access, psychedelic therapy remains financially inaccessible to many. This study was designed to test the feasibility of conducting group psilocybin therapy in low-income adults with depression in Oregon's regulated psilocybin program. Methods: An open label, uncontrolled design was used. After a medical screening visit, participants were enrolled in cohorts of six. Each cohort participated in two 90-min preparation sessions conducted online followed by two psilocybin administration sessions one week apart where they consumed dehydrated and homogenized whole mushrooms, Psilocybe cubensis (B+ strain) prepared in a tea. Two days after each psilocybin administration they had an online, 90-min integration session. Results: We recruited 26 eligible participants, 20 of whom began treatment and 19 completed. No severe adverse events were reported, and participants rated their satisfaction, on average, as 4.8 out of 5, reporting moderate to high benefit and no harm. Exploratory outcomes include Hamilton Depression scores which demonstrated a significant decrease (t = 8.24, p < 0.001) in a paired t-test and a strong effect size (Cohen's d = 1.89). For the same time periods all eight domains of the PROMIS-29 were significantly improved on paired t-tests at p < .01 with effect sizes ranging from 0.667 to 1.774. Conclusions: The study demonstrates the feasibility of group psilocybin therapy in a low-income population with depression. Further research with rigorous comparator groups is warranted to assess if this intervention can be both effective and cost-effective.

Background: Exercise is important for people with multiple sclerosis (MS) to manage symptoms and improve quality of life. Tai chi and qigong (TCQ) are mind-body exercises shown to benefit physical, emotional, and cognitive health in many conditions, but research has been limited in people with MS. To understand potential benefits from regular TCQ practice and factors influencing feasibility, acceptability, and sustainability, we conducted a mixed-methods study through a survey and focus groups with people with MS who regularly practice TCQ. Methods: We conducted focus groups with people with MS from across the United States who regularly practice TCQ; the data from these groups were analyzed using reflexive thematic analysis. Participants also completed a brief survey that collected data on demographics, MS health history and symptoms, and TCQ practice (including opinions on content, dosage, and delivery). Results: Thirteen people with MS (85% female, 69% White) participated in the study. Reported TCQ benefits included physical (balance, strength), cognitive (memory), psychological (calming), and social (community building), with a dose-response gain over time. Challenges included learning and remembering movements, physical limitations (strength, endurance, fatigue), and transportation barriers. Adaptations specific to MS included tailoring TCQ content to meet individual needs and symptoms, appropriate pace, online delivery, and safety. Keys to sustainable practice included enjoyment, patience and self-compassion, viewing TCQ as medicine, and scheduling time for practice. Conclusions: Results suggest people with MS who maintain a TCQ practice may experience physical, emotional, cognitive, and social benefits, especially when specific practice details and facilitators are met. Future studies might investigate how these factors influence sustainable practice.

ObjectivesMindfulness-Oriented Recovery Enhancement (MORE) aims to foster adaptive attention and pain reappraisal. While research has demonstrated MORE's efficacy, the progression through which participants modify their relationship to pain remains unclear. To understand this process, we conducted a qualitative study with data from a clinical trial of MORE for patients with lumbosacral radicular pain (LRP).MethodThirty session recordings from MORE were coded. Using thematic analysis, we examined therapeutic processing sessions to understand how participants learned and applied mindfulness to pain. Analysis focused on dialogue resulting from MORE's model of processing, Phenomenology, Utilization, Reframing, Education, Reinforcement (PURER).ResultsFour stages and one barrier were identified: (1) Pain Vigilance and Attention Dysregulation, (2) Attention Regulation and its application to Experiential Avoidance, (3) Metacognitive Awareness, and (4) Pain Reappraisal. In addition, some participants engaged in experiential avoidance by using their newfound attention skills to avoid their pain experience. PURER emerged as crucial in facilitating adaptive pain engagement.ConclusionsThe four-stage progression pattern identified here - the Vigilance-Avoidance Metacognition-Reappraisal (VA-MR) framework - may help clinicians anticipate challenges in mindfulness training. This study illuminates how MORE participants develop an adaptive relationship with chronic pain, and while attention regulation skills are necessary, they may initially be used for avoidance. Therapeutic benefit appears to require guidance through these stages by a skilled therapist who can navigate initial avoidance tendencies. These findings offer an actionable model for assessing progress and tailoring MBIs to enhance therapeutic outcomes.

Xanthohumol (XN), a flavonoid from hops (Humulus lupulus), exhibits mucosal anti-inflammatory, antioxidant, and microbiome-modulating effects, making it a candidate therapeutic for inflammatory bowel disease. We assessed the safety and tolerability of XN in adults with Crohn's disease (CD) over 8 weeks. In this randomized, triple-masked, placebo-controlled phase 2 trial, 20 adults with unremitted CD received either 24 mg/day XN or placebo for 8 weeks. Primary outcomes included clinical laboratory toxicology parameters, vital signs and adverse events (AEs). Disease activity was screened and assessed using the Crohn's Disease Activity Index (CDAI). XN was well tolerated, with adherence exceeding 95%. Neither halting nor stopping criteria were met, and all laboratory elevations were minor and transient in both groups. There were no attributable serious AEs in either group, and all moderate AEs were short-term and self-resolving. Between-group comparisons demonstrated differences for changes in BMI and gamma-glutamyltransferase (GGT), favoring XN: BMI: -0.67 (0.0, 1.3), p = 0.04 and GGT: -4.8 U/L, 95% CI 0.8-8.8, p = 0.02, which may reflect beneficial effects on hepatic and metabolic health in CD. XN at 24 mg/day was safe and well tolerated in adults with active CD, supporting further research in inflammatory bowel disease.

There are currently no evidence-based treatment guidelines for antisocial personality disorder (ASPD). Instead, treatment typically focuses on comorbid conditions. There is currently no literature documenting cases or research, theoretical or otherwise of using ketamine-assisted therapy or any other psychedelic therapy in cases of ASPD. In this case report, a 43-year-old man seeking ketamine-assisted psychotherapy (KAP) for alcoholism and depression was diagnosed with comorbid antisocial personality disorder. A series of psycholytic (low dose) ketamine therapy sessions and other integrative approaches over the course of 3 years results in resolution of severe alcoholism, reduction in violent thoughts about people and the world, and a reduction in depression symptoms. With additional precautions, utilizing a ketamine-assisted psychotherapy approach led to clinical improvements in depression, alcohol abuse, and ASPD traits.

Introduction: Complementary and integrative health (CIH) therapies are gaining recognition. However, their utilization within the diverse All of Us (AoU) research program remains unexplored. Methods: A cross-sectional study of AoU electronic health record and survey data compared characteristics of adult CIH users and nonusers. General linear models estimated factors associated with CIH. Results: A total of 3171 participants were CIH users (chiropractic or osteopathic manipulation, acupuncture, dietary modification, massage); they were more likely White and less likely Black with higher education versus nonusers. Education, insurance, sex, and race were associated with individual CIH modalities. Conclusion: Low utilization was observed, and several factors associated with CIH were identified. Further research is needed to address data gaps.

BACKGROUND:Aging is the primary risk factor for developing non-communicable chronic diseases, necessitating interventions targeting the aging process. Outcome measures of biological aging used in these interventions are mathematical algorithms applied to DNA methylation patterns, known as epigenetic clocks. The Methylation Diet and Lifestyle study was a pilot randomized controlled trial of a diet and lifestyle intervention that utilized epigenetic age as its primary outcome, measured using Horvath's clock. Significant reductions in epigenetic age post-intervention were observed but with notable variability. PURPOSE:This research aimed to identify dietary components associated with epigenetic age change across groups. Contributing factors to variability, such as weight changes and baseline differences in chronological and epigenetic age, were explored. RESULTS:In hierarchical linear regression, foods investigated as polyphenolic modulators of DNA methylation (green tea, oolong tea, turmeric, rosemary, garlic, berries) categorized in the original study as methyl adaptogens showed significant linear associations with epigenetic age change (B = -1.24, CI = [-2.80, -0.87]), after controlling for baseline epigenetic age acceleration and weight changes. Although the intervention group lost significantly more weight than the control group, these changes were not associated with epigenetic age changes in the regression model. These findings suggest that consuming foods categorized as methyl adaptogens may reduce markers of epigenetic aging.

BACKGROUND:Observational evidence investigating associations between cannabis use and hypertension is inconsistent. METHODS:The association between cumulative lifetime cannabis use (cannabis-years) and incident hypertension was examined over 35 years in a sample of CARDIA study (Coronary Artery Risk Development in Young Adults) participants free of cardiovascular disease at baseline. Marginal structural models with inverse probability weighting were used to adjust for potential time-dependent confounding and censoring. Hazard ratios and 95% CIs were estimated using Cox proportional hazards regression. Sensitivity analyses included modeling cannabis-years using restricted cubic splines, stratifying the primary analyses by sex, race, alcohol and cigarette smoking, and evaluating an additional exposure measure (days of use in the past month). RESULTS:The analytic sample consisted of 4328 participants at baseline and 2810 (64.9%) at year 35. Median cannabis-years increased minimally and remained low across visits: 0.0 (Q1-Q3, 0.0-0.3) at baseline and 0.2 (Q1-Q3, 0.0-0.7) by year 35. There were 2478 cases of incident hypertension over 88 292 person-years (28.1 cases per 1000 person-years). Cannabis-years were not significantly associated with incident hypertension (adjusted hazard ratio, 0.99 [95% CI, 0.97-1.00]; P=0.18). The association remained unchanged in sensitivity analyses. CONCLUSIONS:In a cohort of Black and White young adults with 35 years of follow-up, no association was found between cumulative lifetime use of cannabis and risk of incident hypertension. This finding was robust to restricted cubic spline analyses, analyses stratified by sex, race, alcohol use and tobacco cigarette smoking, and an additional measure of exposure (days of use in the past month).

Xanthohumol (XN), a polyphenol from hops (Humulus lupulus), exhibits antioxidant, anti-inflammatory, antihyperlipidemic, and chemo-preventive activity. Preclinical evidence suggests gut microbiota are critical to mediating some of these bioactivities. Nevertheless, its precise impact on human gut microbiota, particularly at supplemental doses, remains poorly characterized. We evaluated 200 mg/day XN for 3 weeks on human gut microbiota in a eubiotic and dysbiotic model using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®). Functional assessments of microbiota included quantification of XN metabolites, short-chain fatty acids (SCFAs), and untargeted metabolomics of the digestive metabolome. Bacterial composition was assessed by 16S rRNA gene sequencing. XN reduced alpha-diversity and short-chain fatty acid production in both models, as well as altered taxa abundance variably between models. XN disrupted bile acid metabolism through inhibition of microbial bile salt hydrolase (BSH). The modulation of bile acid metabolism has important implications for host-level bioactivity of XN.

Background: Use of complementary and integrative health care (CIH) varies across racial and ethnic groups in the United States. Lack of racial and ethnic diversity among CIH providers may hinder access to CIH for underrepresented groups. This study aimed to (1) document racial and ethnic representation in licensed CIH professions (chiropractic, acupuncture, traditional East Asian medicine, naturopathic medicine, direct-entry midwifery, and massage therapy), non-licensed CIH professions, and conventional health care; (2) compare diversity in these professions with the U.S. population; and (3) examine changes in CIH diversity in recent years. Methods: We conducted a repeated cross-sectional study design with the 2011-2022 Integrated Postsecondary Education Data System to examine race and ethnicity among graduates in licensed CIH professions, compared with non-licensed CIH professions and conventional health care. Our sample included 53,393 programs representing 3,524,494 individuals. We examined the proportion of graduates from each racial and ethnic group, compared results with the U.S. population, and graphically explored changes between 2011 and 2022. Results: Inclusion or exclusion of massage therapy influenced interpretations across all questions. With massage therapy, licensed CIH professions appeared more diverse, with a higher proportion of Latino and Black graduates. Without massage therapy, diversity in licensed CIH professions was similar or slightly reduced compared with non-licensed CIH professions and conventional health care. Notable differences emerged among licensed CIH professions: acupuncture and East Asian medicine had larger proportions of Asian graduates than other CIH programs and the U.S. population. Racial and ethnic diversity in CIH increased modestly between 2011 and 2022. Discussion: While professions such as massage therapy, acupuncture, and traditional East Asian medicine have greater diversity, a disparity persists between the racial and ethnic composition of licensed CIH professions and the diversity of the overall U.S. population.

BACKGROUND:Studies on cannabis use and adverse cardiovascular outcomes have reported conflicting results. Research on its relationship to calcified arterial plaque remains limited. METHODS:Cross-sectional data from 2152 participants at Exam 6 (2016-2018) in the Multi-Ethnic Study of Atherosclerosis (MESA) were analyzed, including self-reported cannabis smoking patterns and carotid artery calcification (CAC) as measured via computed tomography. Multivariable relative and absolute risk regression models were used to estimate adjusted prevalence ratios (PRs) and prevalence differences, respectively, for the presence of calcified plaque. Multivariable linear regression was then used to compare group differences in the extent of CAC in those with calcified plaque. RESULTS:A minority of participants (n = 159, 7.4%) reported a history of regular cannabis smoking. Among all participants, 36.1% (n = 777) had detectable CAC. In models adjusted for demographics, behavioral, and clinical cardiovascular disease factors, a history of regular cannabis smoking was not associated with the prevalence of CAC in either common carotid artery (PR: 1.14, 95% CI: 0.88 to 1.49). In the subset of participants with calcified plaque, and in separate fully adjusted multivariable linear regression models, a history of regular cannabis smoking was not associated with increased calcium volume (difference = 7.7%, 95% CI: -21.8 to 48.5), calcium density (difference = 0.4%, 95% CI: -6.6 to 7.9), or Agatston score (difference = 32.1%, 95% CI: -31.8 to 155.8) in either carotid artery. Models exploring potential effect modification by age, race/ethnicity, and tobacco smoking status showed no significant association, except for higher CAC prevalence in men with a history of regular cannabis smoking. CONCLUSIONS:In a racially and ethnically diverse cohort of older adults with a moderately high prevalence of CAC, no associations were found between a history of regular cannabis smoking, duration, or recency of cannabis smoking, and the prevalence of carotid calcified plaque. These findings were consistent across age, race/ethnicity, and cigarette smoking, except for an increased prevalence in men with a history of regular cannabis smoking. Similarly, in a subgroup with CAC, no association was found between a history of regular cannabis smoking and extent of calcification as measured by volume, density, and Agatston score.

Introduction: Lumbosacral radiculopathy (LR), also known as sciatica, is a common type of radiating neurologic pain involving burning, tingling, and numbness in the lower extremities. It has an estimated lifetime prevalence as high as 43%. Objectives: The objective of this randomized controlled trial was to evaluate the impact of virtually delivered Mindfulness-Oriented Recovery Enhancement (MORE) on patients with LR during the COVID-19 pandemic. Methods: Potentially eligible patients were identified using electronic health record queries and phone screenings. Participants were then randomized to MORE or treatment-as-usual (TAU) for 8 weeks, with pain intensity assessed daily. At baseline and follow-up visits, participants completed questionnaires assessing the primary outcome, disability, as well as quality of life, depression, mindful reinterpretation of pain, and trait mindfulness. Results: In our study, patients undergoing virtual delivery of MORE had greater improvements in daily pain intensity (P = 0.002) but not in disability (P = 0.09), depression (P = 0.26), or quality of life (P = 0.99 and P = 0.89, SF-12 physical and mental component scores, respectively), relative to TAU patients. In addition, patients in MORE experienced significantly greater increases in mindful reinterpretation of pain (P = 0.029) and trait mindfulness (P = 0.035). Conclusion: Among patients with lumbar radiculopathy, MORE significantly reduced daily pain intensity but did not decrease disability or depression symptoms. Given the long duration of symptoms in our sample, we hypothesize the discrepancy between changes in daily pain intensity and disability is due to fear avoidance behaviors common in patients with chronic pain. As the first trial of a mindfulness intervention in patients with LR, these findings should inform future integrative approaches to LR treatment, particularly when considering the increasing use of virtual interventions throughout the COVID-19 pandemic.

Manipulations to slow biological aging and extend healthspan are of interest given the societal and healthcare costs of our aging population. Herein we report on a randomized controlled clinical trial conducted among 43 healthy adult males between the ages of 50-72. The 8-week treatment program included diet, sleep, exercise and relaxation guidance, and supplemental probiotics and phytonutrients. The control group received no intervention. Genome-wide DNA methylation analysis was conducted on saliva samples using the Illumina Methylation Epic Array and DNAmAge was calculated using the online Horvath DNAmAge clock (2013). The diet and lifestyle treatment was associated with a 3.23 years decrease in DNAmAge compared with controls (p=0.018). DNAmAge of those in the treatment group decreased by an average 1.96 years by the end of the program compared to the same individuals at the beginning with a strong trend towards significance (p=0.066). Changes in blood biomarkers were significant for mean serum 5-methyltetrahydrofolate (+15%, p=0.004) and mean triglycerides (-25%, p=0.009). To our knowledge, this is the first randomized controlled study to suggest that specific diet and lifestyle interventions may reverse Horvath DNAmAge (2013) epigenetic aging in healthy adult males. Larger-scale and longer duration clinical trials are needed to confirm these findings, as well as investigation in other human populations.

Essential minerals are cofactors for synthesis of neurotransmitters supporting cognition and mood. An 8-week fully-blind randomised controlled trial of multinutrients for attention-deficit/hyperactivity disorder (ADHD) demonstrated three times as many children (age 6-12) had significantly improved behaviour ('treatment responders') on multinutrients (54 %) compared with placebo (18 %). The aim of this secondary study was to evaluate changes in fasted plasma and urinary mineral concentrations following the intervention and their role as mediators and moderators of treatment response. Fourteen essential or trace minerals were measured in plasma and/or urine at baseline and week eight from eighty-six participants (forty-nine multinutrients, thirty-seven placebos). Two-sample t tests/Mann-Whitney U tests compared 8-week change between treatment and placebo groups, which were also evaluated as potential mediators. Baseline levels were evaluated as potential moderators, using logistic regression models with clinical treatment response as the outcome. After 8 weeks, plasma boron, Cr (in females only), Li, Mo, Se and vanadium and urinary iodine, Li and Se increased more with multinutrients than placebo, while plasma phosphorus decreased. These changes did not mediate treatment response. However, baseline urinary Li trended towards moderation: participants with lower baseline urinary Li were more likely to respond to multinutrients (P = 0058). Additionally, participants with higher baseline Fe were more likely to be treatment responders regardless of the treatment group (P = 0036.) These results show that multinutrient treatment response among children with ADHD is independent of their baseline plasma mineral levels, while baseline urinary Li levels show potential as a non-invasive biomarker of treatment response requiring further study.

A recent review proposed a role for multi-functional food or supplement products in priming the gut to support both digestive and systemic health. Accordingly, we designed and eva-luated the effect of a multi-functional gastrointestinal (GI) primer supplement on participant-reported measures for digestive health, quality-of-life (e.g., energy/vitality and general health), and reasons for satiation (e.g., attitudes towards food and eating). In this single-arm clinical trial, 68 participants with mild digestive symptoms consumed the GI primer supplement daily for 14 days. Digestive symptoms were evaluated daily from baseline (Day 0) through Day 14. At baseline and Day 14, participants reported their stool consistency, reasons for satiation, and quality-of-life measures using validated questionnaires. At Day 14, participants reported significant improvements in all (13/13) digestive symptom parameters (p-values < 0.05) and an increase in % of stools with normal consistencies. There were significant improvements (p-values < 0.05) in energy/vitality and general health, and in specific attitudes towards food and eating (e.g., physical satisfaction, planned amount, decreased eating priority, decreased food appeal, and self-consciousness). Results suggest the GI primer supplement promotes digestive health, improves quality of life, and impacts attitudes towards food/eating. This study provides preliminary support for the gut priming hypothesis through which multi-functional digestive products may improve GI health.

Background: Acupuncture is a promising treatment for common symptoms after traumatic brain injury (TBI). Our objectives were to explore knowledge, attitudes and beliefs about acupuncture, identify health service needs and assess the perceived feasibility of weekly acupuncture visits among individuals with TBI. Methods: We surveyed adults 18 years of age and older with TBI who received care at the University of Washington. Respondents were asked to complete 143 questions regarding acupuncture knowledge, attitudes and beliefs, injury-related symptoms and comorbidities, and to describe their interest in weekly acupuncture. Results: Respondents (n = 136) reported a high degree of knowledge about acupuncture as a component of Traditional Chinese Medicine, needle use and safety, but were less knowledgeable regarding that the fact that most conditions require multiple acupuncture treatments to achieve optimal therapeutic benefit. Respondents were comfortable talking with healthcare providers about acupuncture (63.4%), open to acupuncture concurrent with conventional treatments (80.6%) and identified lack of insurance coverage as a barrier (50.8%). Beliefs varied, but respondents were generally receptive to using acupuncture as therapy. Unsurprisingly, respondents with a history of acupuncture (n = 60) had more acupuncture knowledge than those without such a history (n = 66) and were more likely to pursue acupuncture without insurance (60%), for serious health conditions (63.3%) or alongside conventional medical therapy (85.0%). Half of all respondents expressed interest in participating in weekly acupuncture for up to 12 months and would expect almost a 50% improvement in symptoms by participating. Conclusion: Adults with TBI were receptive and interested in participating in weekly acupuncture to address health concerns. These results provide support for exploring the integration of acupuncture into the care of individuals with TBI.

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.