Testing the Efficacy of a Scalable Telephone-Delivered Guided Imagery Tobacco Cessation Treatment: Protocol for a Randomized Clinical Trial.

BACKGROUND: Tobacco use continues to be a leading preventable cause of death and disease in the United States, accounting for >480,000 deaths each year. Although treatments for tobacco use are effective for many, there is substantial variability in outcomes, and these approaches are not effective for all individuals seeking to quit smoking cigarettes. New, effective therapeutic approaches are needed to meet the preferences of people who want to stop smoking. Guided imagery (GI) is a mind-body technique that involves the guided visualization of specific mental images, which is enhanced with other sensory modalities and emotions. Preliminary evidence provides initial support for the use of GI as a treatment for cigarette smoking. Meta-analyses have shown that standard treatment for cigarette smoking delivered over the telephone via quitlines is effective. A telephone-based intervention that uses GI might provide another effective treatment option and increase the reach and effectiveness of quitlines. OBJECTIVE: This study aims to test the efficacy of Be Smoke Free, a telephone-delivered GI treatment for smoking cessation. METHODS: This multisite randomized clinical trial (RCT) will compare a novel telephone-delivered GI tobacco cessation treatment with a standard evidence-based behavioral treatment. The study will be conducted over 5 years. In phase 1, we refined protocols and procedures for the New York State and West Virginia sites for use in the RCT. During phase 2, we will conduct an RCT with 1200 participants: 600 (50%) recruited via quitlines and 600 (50%) recruited via population-based methods. Participants will be randomly assigned to either the GI condition or the behavioral condition; both treatments will be delivered by trained study coaches located at the University of Arizona. Assessments will be conducted at baseline and 3 and 6 months after enrollment by University of Arizona research staff. The primary outcome will be self-reported 30-day point prevalence abstinence 6 months after enrollment. Secondary outcomes include biochemically verified 7-day point prevalence abstinence 6 months after enrollment. RESULTS: Recruitment in West Virginia and New York began in October 2022. As of March 31, 2023, a total of 242 participants had been enrolled. Follow-up assessments began in November 2022. As of March 31, 2023, of the 118 eligible participants, 97 (82.2%) had completed the 3-month assessment, and 93% (26/28) of eligible participants had completed the 6-month assessment. Biochemical verification and qualitative interviews began in April 2023. Recruitment will continue through 2025 and follow-up assessments through 2026. Primary results are expected to be published in 2027. CONCLUSIONS: The Be Smoke Free study is a first-of-its-kind RCT that incorporates GI into telephone-based tobacco cessation treatment. If successful, Be Smoke Free will have substantial benefits for the long-term health of people who use tobacco across the United States. TRIAL REGISTRATION: ClinicalTrials.gov NCT05277831; https://clinicaltrials.gov/ct2/show/NCT05277831. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/48898.

Gastric Cancer Surgery in the US: a Contemporary Trend Analysis of Lymphadenectomy and the Impact of Minimally Invasive Approaches.

BACKGROUND: The National Comprehensive Cancer Network guidelines recommend harvesting 16 or more lymph nodes for the adequate staging of gastric adenocarcinoma. This study examines the rate of adequate lymphadenectomy over recent years, its predictors, and its impact on overall survival(OS). STUDY DESIGN: The National Cancer Database was utilized to identify patients who underwent surgical treatment for gastric adenocarcinoma between 2006-2019. Trend analysis was performed for lymphadenectomy rates during the study period. Logistic regression, Kaplan-Meier survival plots, and Cox proportional hazard regression were utilized. RESULTS: A total of 57,039 patients who underwent surgical treatment for gastric adenocarcinoma were identified. Only 50.5% of the patients underwent a lymphadenectomy of ≥ 16 nodes. Trend analysis showed that this rate significantly improved over the years, from 35.1% in 2006 to 63.3% in 2019 (p < .0001). The main independent predictors of adequate lymphadenectomy included high-volume facility with ≥ 31 gastrectomies/year (OR: 2.71; 95%CI:2.46-2.99), surgery between 2015-2019 (OR: 1.68; 95%CI: 1.60-1.75), and preoperative chemotherapy (OR:1.49; 95%CI:1.41-1.58). Patients with adequate lymphadenectomy had better OS than patients who did not: median survival: 59 versus 43 months (Log-Rank: p < .0001). Adequate lymphadenectomy was independently associated with improved OS (HR:0.79; 95%CI:0.77-0.81). Laparoscopic and robotic gastrectomies were independently associated with adequate lymphadenectomy compared to open, OR: 1.11, 95%CI:1.05-1.18 and OR: 1.24, 95%CI:1.13-1.35, respectively. CONCLUSION: Although the rate of adequate lymphadenectomy improved over the study period, a large number of patients still lacked adequate lymph node dissection, negatively impacting their OS despite multimodality therapy. Laparoscopic and robotic surgeries were associated with a significantly higher rate of lymphadenectomy ≥ 16 nodes.

Genome-Wide Association Study of Metachronous Colorectal Adenoma Risk among Participants in the Selenium Trial.

Genetic variants related to colorectal adenoma may help identify those who are at highest risk of colorectal cancer development or illuminate potential chemopreventive strategies. The purpose of this genome-wide association study was to identify genetic variants that are associated with risk of developing a metachronous colorectal adenoma among 1,215 study participants of European descent from the Selenium Trial. Associations of variants were assessed with logistic regression analyses and validated in an independent case-control study population of 1,491 participants from the Colorectal Cancer Study of Austria (CORSA). No statistically significant genome-wide associations between any variant and metachronous adenoma were identified after correction for multiple comparisons. However, an intron variant of FAT3 gene, rs61901554, showed a suggestive association (P = 1.10 × 10-6) and was associated with advanced adenomas in CORSA (P = 0.04). Two intronic variants, rs12728998 and rs6699944 in NLRP3 were also observed to have suggestive associations with metachronous lesions (P = 2.00 × 10-6) in the Selenium Trial and were associated with advanced adenoma in CORSA (P = 0.03). Our results provide new areas of investigation for the genetic basis of the development of metachronous colorectal adenoma and support a role for FAT3 involvement in the Wnt/ß-catenin pathway leading to colorectal neoplasia.Trial Registration number: NCT00078897 (ClinicalTrials.gov).

Cellular Cytosolic Energy Replenishment Increases Vascularized Composite Tissue Tolerance to Extended Cold Ischemia Time.

BACKGROUND: Vascularized composite allotransplantation (VCA) is a restorative surgical procedure to treat whole or partially disfiguring craniofacial or limb injuries. The routine clinical use of this VCA surgery is limited using compromised allografts from deceased donors and by the failure of the current hypothermic preservation protocols to extend the allograft's cold ischemia time beyond 4 h. We hypothesized that the active replenishment of the cellular cytosolic adenosine-5`-triphosphate (ATP) stores by means of energy delivery vehicles (ATPv) encapsulating high-energy ATP is a better strategy to improve allograft's tolerance to extended cold ischemia times. MATERIALS AND METHODS: We utilized established rat model of isolated bilateral in-situ non-cycled perfusions of both hind limbs. Ipsilateral and contralateral limbs in the anesthetized animal were randomized for simultaneous perfusions with either the University of Wisconsin (UW) solution, with/without O2 supplementation (control), or with the UW solution supplemented with the ATPv, with/without O2 supplementation (experimental). Following perfusion, the hind limbs were surgically removed and stored at 4°C for 12, 16, or 24 hours as extended cold ischemia times. At the end of each respective storage time, samples of skin, and soleus, extensor digitalis longus, and tibialis anterior muscles were recovered for assessment using tissue histology and tissue lysate studies. RESULTS: Control muscle sections showed remarkable microvascular and muscle damage associated with loss of myocyte transverse striation and marked decrease in myocyte nucleus density. A total of 1,496 nuclei were counted in 179 sections of UW-perfused control muscles in contrast to 1,783 counted in 130 sections of paired experimental muscles perfused with the ATPv-enhanced perfusate. This yielded 8 and 13 nuclei/field for the control and experimental muscles, respectively (P < .004). Oxygenation of the perfusion solutions before use did not improve the nucleus density of either the control or experimental muscles (n = 7 animals, P > .05). Total protein isolated from the muscle lysates was similar in magnitude regardless of muscle type, perfusion protocol, or duration of cold ischemia time. Prolonged static cold preservation of the hind limbs completely degraded the composite tissue's Ribonucleic acid (RNA). This supplementary result confirms the notion that that reverse transcription-Polymerase Chain Reaction, enzyme-linked immunosorbent assay, or the respiratory complex II enzyme activity techniques should not be used as indices of graft quality after prolonged static cold storage. CONCLUSIONS: In conclusion, this study demonstrates that active cellular cytosolic ATP replenishment increases hind limb composite tissue tolerance to extended cold ischemia times. Quality indicators and clinically relevant biomarkers that define composite tissue viability and function during static cold storage are warranted.

The Feasibility of Tai Chi Exercise as a Beneficial Mind-Body Intervention in a Group of Community-Dwelling Stroke Survivors with Symptoms of Depression.

Depression is prevalent among one-third to two-thirds of acute and chronic stroke survivors. Despite the availability of pharmacotherapies and/or psychotherapies, depression persists, even for 5-10 years after stroke, reflecting limited treatment responses and/or adherence to this conventional care. Mind-body interventions are commonly used among adults to ameliorate depressive symptoms. Thus, the feasibility of Tai Chi, alongside conventional care, to manage poststroke depression was investigated using a single-group pre-post intervention design. Recruitment and retention, intervention adherence, safety, acceptability, and fidelity were assessed. Symptoms of depression, anxiety, and stress were assessed using standardized questionnaires, objective sleep was assessed via a research-grade triaxial accelerometer, and blood samples were taken to measure oxidative stress, inflammatory markers, and a neurotrophic growth factor using commercially available kits per manufacturer's protocol. Pre-post intervention changes were assessed using paired t-tests. We enrolled stroke survivors (N = 11, mean age = 69.7 ± 9.3) reporting depression symptoms. After the intervention, we observed significant reductions in symptoms of depression (-5.3 ± 5.9, p=0.01), anxiety (-2.2 ± 2.4, p=0.01), and stress (-4.6 ± 4.8, p=0.01), along with better sleep efficiency (+1.8 ± 1.8, p=0.01), less wakefulness after sleep onset (-9.3 ± 11.6, p=0.04), and less time awake (-9.3 ± 11.6, p=0.04). There was a 36% decrease in oxidative stress (p=0.02), though no significant changes in the other biomarkers were found (all p values >0.05). Tai Chi exercise is a feasible intervention that can be used alongside conventional care to manage poststroke depression, aid in reducing symptoms of anxiety and stress, and improve sleep.

Genome-Wide Association Study of Response to Selenium Supplementation and Circulating Selenium Concentrations in Adults of European Descent.

BACKGROUND: Selenium (Se) is a trace element that has been linked to many health conditions. Genome-wide association studies (GWAS) have identified variants for blood and toenail Se levels, but no GWAS has been conducted to date on responses to Se supplementation. OBJECTIVES: A GWAS was performed to identify the single nucleotide polymorphisms (SNPs) associated with changes in Se concentrations after 1 year of supplementation. A GWAS of basal plasma Se concentrations at study entry was conducted to evaluate whether SNPs for Se responses overlap with SNPs for basal Se levels. METHODS: A total of 428 participants aged 40-80 years of European descent from the Selenium and Celecoxib Trial (Sel/Cel Trial) who received daily supplementation with 200 µg of selenized yeast were included for the GWAS of responses to supplementation. Plasma Se concentrations were measured from blood samples collected at the time of recruitment and after 1 year of supplementation. Linear regression analyses were performed to assess the relationship between each SNP and changes in Se concentrations. We further examined whether the identified SNPs overlapped with those related to basal Se concentrations. RESULTS: No SNP was significantly associated with changes in Se concentration at a genome-wide significance level. However, rs56856693, located upstream of the NEK6, was nominally associated with changes in Se concentrations after supplementation (P = 4.41 × 10-7), as were 2 additional SNPs, rs11960388 and rs6887869, located in the dimethylglycine dehydrogenase (DMGDH)/betaine-homocysteine S-methyltransferase (BHMT) region (P = 0.01). Alleles of 2 SNPs in the DMGDH/BHMT region associated with greater increases in Se concentrations after supplementation were also strongly associated with higher basal Se concentrations (P = 8.67 × 10-8). CONCLUSIONS: This first GWAS of responses to Se supplementation in participants of European descent from the Sel/Cel Trial suggests that SNPs in the NEK6 and DMGDH/BHMT regions influence responses to supplementation.

Selenium supplementation and insulin resistance in a randomized, clinical trial.

Objective: While controversial, observational and randomized clinical trial data implicate the micronutrient selenium (Se) in the development of type 2 diabetes (T2D). The aim of this study was to test the hypothesis that Se supplementation adversely affects pancreatic ß-cell function and insulin sensitivity. Research design and methods: In a subset of 400 individuals participating in a randomized, placebo-controlled trial of Se at 200 µg/day for colorectal adenomatous polyps, fasting plasma glucose and insulin were measured before randomization and within 6 months of completing intervention. Change in the homeostasis model assessment-ß cell function (HOMA2-%ß) and insulin sensitivity (HOMA2-%S) were compared between arms. A subgroup of 175 (79 Se and 96 placebo) participants underwent a modified oral glucose tolerance test (mOGTT) at the end of intervention and change in glucose values was assessed. Results: No statistically significant differences were observed for changes in HOMA2-%ß or HOMA2-%S between those who received Se compared with placebo. After a mean of 2.9 years on study, mean HOMA2-%ß values were 3.1±24.0 and 3.1±29.8 for the Se and placebo groups, respectively (p=0.99). For HOMA2-%S, the values were -0.5±223.2 and 80.9±1530.9 for the Se and placebo groups, respectively (p=1.00). Stratification by sex or age did not reveal any statistically significant effects on insulin sensitivity by treatment group. For mOGTT, mean baseline fasting blood glucose concentrations were significantly higher among participants in the placebo group compared with the Se group (96.6±14.6 and 92.3±12.0, respectively; p=0.04), a trend which remained through the 20 min assessment. Conclusions: These findings do not support a significant adverse effect of daily Se supplementation with 200 µg/day of selenized yeast on ß-cell function or insulin sensitivity as an explanation for previously reported associations between Se and T2D. Further clarification of longer term effects of Se is needed. Clinical trial registry: NIH Clinical Trials.gov number NCT00078897.

Selenium Supplementation for Prevention of Colorectal Adenomas and Risk of Associated Type 2 Diabetes.

BACKGROUND: Selenium supplementation may help to prevent colorectal cancer; as precursors of colorectal cancer, colorectal adenomas are a surrogate for colorectal cancer. Selenium supplementation may increase risk of type 2 diabetes (T2D). METHODS: The Selenium and Celecoxib (Sel/Cel) Trial was a randomized, placebo controlled trial of selenium 200 µg daily as selenized yeast and celecoxib 400 mg once daily, alone or together, for colorectal adenoma prevention. Men and women between age 40 and 80 years were eligible following colonoscopic removal of colorectal adenomas. The primary outcome was adenoma development. Celecoxib was suspended because of cardiovascular toxicity in other trials, but accrual continued to selenium and placebo. A total of 1621 participants were randomly assigned to selenium or placebo, of whom 1374 (84.8%) were available for analysis. All statistical tests were two-sided. RESULTS: In the respective placebo and selenium arms of 689 and 685 participants, adenoma detection after medians of 33.6 (range = 0.0-85.1 months) and 33.0 months (range = 0.0-82.6 months) were 42.8% and 44.1% (relative risk [RR] = 1.03, 95% confidence interval [CI] = 0.91 to 1.16, P = .68). In participants with baseline advanced adenomas, adenoma recurrence was reduced by 18% with selenium (RR = 0.82, 95% CI = 0.71 to 0.96, P = .01). In participants receiving selenium, the hazard ratio for new-onset T2D was 1.25 (95% CI = 0.74 to 2.11, P = .41), with a statistically significantly increased risk of selenium-associated T2D among older participants (RR = 2.21; 95% CI = 1.04 to 4.67, P = .03). CONCLUSIONS: Overall, selenium did not prevent colorectal adenomas and showed only modest benefit in patients with baseline advanced adenomas. With limited benefit and similar increases in T2D to other trials, selenium is not recommended for preventing colorectal adenomas in selenium-replete individuals.

Pilot study on the bioactivity of vitamin d in the skin after oral supplementation.

Laboratory studies suggest that vitamin D (VD) supplementation inhibits skin carcinogenesis. However, epidemiologic studies report mixed findings in the association between circulating VD levels and skin cancer risk. We conducted a clinical study to determine whether oral cholecalciferol supplementation would exert direct bioactivity in human skin through modulation of the VD receptor (VDR). We enrolled 25 individuals with serum 25-hydroxyvitamin-D levels <30 ng/mL and with skin photodamage to take 50,000 IU of cholecalciferol biweekly for 8 to 9 weeks. Then, we obtained baseline and end-of-study skin biopsies from photodamaged (PD) and photoprotected (PP) skin, and from benign nevi (BN) and tested for mRNA expression of VDR and cytochrome P450-24 (CYP24), and markers of keratinocytic differentiation. High-dose cholecalciferol supplementation significantly elevated circulating levels of 25-hydroxyvitamin-D (P < 0.0001) and 1,25-dihydroxyvitamin-D (P < 0.0001). VDR expression in PD- and PP-skin showed minimum changes after supplementation. CYP24 expression in PD- and PP-skin was increased after supplementation by 186%, P = 0.08, and 134%, P = 0.07, respectively. In BNs from 11 participants, a trend for higher VDR and CYP24 expression was observed (average of 20%, P = 0.08, and 544%, P = 0.09, respectively). Caspase-14 expression at the basal layer in PD skin samples was the only epidermal differentiation marker that was significantly increased (49%, P < 0.0001). High-dose cholecalciferol supplementation raised serum VD metabolite levels concurrently with CYP24 mRNA and caspase-14 levels in the skin. Our findings of significant variability in the range of VDR and CYP24 expression across study samples represent an important consideration in studies evaluating the role of VD as a skin cancer chemopreventive agent.

Results of a phase II randomized, double-blind, placebo-controlled trial of Polyphenon E in women with persistent high-risk HPV infection and low-grade cervical intraepithelial neoplasia.

OBJECTIVE: In vitro data and pilot data suggest that green tea catechins may possess chemopreventive activity for cervical cancer and precursor lesions. We conducted a randomized, double-blind, placebo-controlled trial of Polyphenon E (decaffeinated and enriched green tea catechin extract) in women with persistent human papillomavirus (HPV) infection and low-grade cervical intraepithelial neoplasia (CIN1) to evaluate the potential of Polyphenon E for cervical cancer prevention. METHODS: Ninety-eight eligible women were randomized to receive either Polyphenon E (containing 800 mg epigallocatechin gallate) or placebo once daily for 4 months. The primary study outcome was oncogenic HPV clearance and clearance of CIN1. RESULTS: Polyphenon E was shown to be acceptable, safe and well tolerated. There was no difference in the response rate by treatment allocation. Complete response, defined as negative for high-risk HPV and normal histopathology, was noted in 7 (17.1%) and 6 (14.6%) women in the Polyphenon E and placebo arms, respectively. Progression, defined as persistent oncogenic HPV with histopathologic evidence of progression, was more common in the Polyphenon E group than in the placebo group [6 (14.6%) vs. 3 (7.7%)]. CONCLUSION: Based on the largest randomized placebo-controlled trial of a green tea extract for HPV related cervical disease, we conclude that 4 months of Polyphenon E intervention did not promote the clearance of persistent high-risk HPV and related CIN1. Further studies may be necessary to better delineate the risk factors for persistent HPV infection and biology of the disease to facilitate the evaluation of chemopreventive strategies.

Design and baseline characteristics of participants in a phase III randomized trial of celecoxib and selenium for colorectal adenoma prevention.

COX inhibitors reduce colorectal adenoma recurrence by up to 45% and selenium supplementation may prevent colorectal cancer. Following colonoscopic adenoma resection, 1,600 men and women, ages 40 to 80 years, were randomized to celecoxib (400 mg daily), a selective COX-2 inhibitor, and/or selenium (200 µg daily as selenized yeast), or double placebo. The trial was initiated in November 2001. The primary trial endpoint is adenoma recurrence in each intervention group compared with placebo, as determined by surveillance colonoscopy conducted three to five years after baseline. Randomization was stratified by use of low-dose aspirin (81 mg) and clinic site. Following reports of cardiovascular toxicity associated with COX-2 inhibitors, the celecoxib arm was discontinued in December 2004 when 824 participants had been randomized. Accrual continued with randomization to selenium alone or placebo. Randomization of the originally planned cohort (n = 1,621) was completed in November 2008. A further 200 patients with one or more advanced adenomas (denoting increased risk for colorectal cancer) were accrued to enhance statistical power for determining intervention efficacy in this higher-risk subgroup. Accrual of the total cohort (n = 1,824) was completed in January 2011. Baseline cohort characteristics include: mean age 62.9 years; 65% male; body mass index (BMI) 29.1 ± 5.1; 47% taking low-dose aspirin while on trial; 20% with three or more adenomas; and 38% with advanced adenomas. Intervention effects on adenoma recurrence will be determined, and their modification by genetic background and baseline selenium level. The effect of selenium supplementation on risk for type II diabetes will also be reported.

A meta-analysis of clinical improvements of general well-being by a standardized Lycium barbarum.

Four randomized, blind, placebo-controlled clinical trials were pooled to study the general effects of oral consumption of Lycium barbarum at 120 mL/day, as a standardized juice, GoChi(®) (FreeLife International, Phoenix, AZ, USA). A questionnaire consisting of symptoms graded 0-5 was given to the participants. For each question, the score changes in the questionnaire between pre- and postintervention were summarized by the standardized mean difference and associated SE to perform the meta-analysis. The change was also characterized into a binary outcome, improved or not, to derive odds ratio (OR) and associated SE derived by a binary outcome using the Mantel-Haenszel method. The meta-analysis and heterogeneity were evaluated with the R program using the rmeta package. Statistical significance was set at 5%. In total, 161 participants (18-72 years old) were included in the meta-analysis. Compared with the placebo group (n=80), the active group (n=81) showed significant improvements in weakness, stress, mental acuity, ease of awakening, shortness of breath, focus on activity, sleep quality, daydreaming, and overall feelings of health and well-being under a random effects model. A fixed effects model showed additional improvements in fatigue, depression, circulation, and calmness. The OR indicated significantly higher chance to improve fatigue, dizziness, and sleep quality. Three studies had statistically significant heterogeneity in procrastination, shoulder stiffness, energy, and calmness. The present meta-analysis confirmed the various health effects of L. barbarum polysaccharides-standardized L. barbarum intake found in the previous randomized, double-blind, placebo-controlled human clinical trials and revealed it resulted in statistically significant improvements in neurological/psychological performance and overall feelings of health and well-being compared with the placebo group under both the fixed and the random effects models of the R program.

Randomized, double-blind, placebo-controlled trial of polyphenon E in prostate cancer patients before prostatectomy: evaluation of potential chemopreventive activities.

Compelling preclinical and pilot clinical data support the role of green tea polyphenols in prostate cancer prevention. We conducted a randomized, double-blind, placebo-controlled trial of polyphenon E (enriched green tea polyphenol extract) in men with prostate cancer scheduled to undergo radical prostatectomy. The study aimed to determine the bioavailability of green tea polyphenols in prostate tissue and to measure its effects on systemic and tissue biomarkers of prostate cancer carcinogenesis. Participants received either polyphenon E (containing 800 mg epigallocatechin gallate) or placebo daily for 3 to 6 weeks before surgery. Following the intervention, green tea polyphenol levels in the prostatectomy tissue were low to undetectable. Polyphenon E intervention resulted in favorable but not statistically significant changes in serum prostate-specific antigen, serum insulin-like growth factor axis, and oxidative DNA damage in blood leukocytes. Tissue biomarkers of cell proliferation, apoptosis, and angiogenesis in the prostatectomy tissue did not differ between the treatment arms. The proportion of subjects who had a decrease in Gleason score between biopsy and surgical specimens was greater in those on polyphenon E but was not statistically significant. The study's findings of low bioavailability and/or bioaccumulation of green tea polyphenols in prostate tissue and statistically insignificant changes in systemic and tissue biomarkers from 3 to 6 weeks of administration suggests that prostate cancer preventive activity of green tea polyphenols, if occurring, may be through indirect means and/or that the activity may need to be evaluated with longer intervention durations, repeated dosing, or in patients at earlier stages of the disease.

No effect of selenium supplementation on serum glucose levels in men with prostate cancer.

BACKGROUND: Literature indicates a relationship between selenium supplementation and risk of diabetes. However, because these data are inconclusive, we investigated the effect of selenium supplementation on serum glucose levels in men with prostate cancer enrolled in a clinical trial testing of the effect of selenium on prostate cancer progression. METHODS: Subjects were randomized to receive placebo (n=46), selenium 200 microg/day (n=47), and selenium 800 microg/day (n=47). Serum glucose levels were obtained every 6 months for up to 5 years. Longitudinal analysis was carried out to assess whether rate of change of serum glucose levels was significantly different in the selenium-supplemented groups as compared with placebo. Sensitivity analyses were performed to assess the robustness of findings. RESULTS: Changes in serum glucose levels during the course of the trial were not statistically significantly different as compared with placebo for the selenium 200 microg/day (P=.56) or selenium 800 microg/day (P=.91) treatment groups. CONCLUSION: These results do not support a relationship between selenium supplementation and changes in serum glucose levels. Recommendations about selenium supplementation and risk of diabetes will require more definitive studies.

Oral selenium supplementation has no effect on prostate-specific antigen velocity in men undergoing active surveillance for localized prostate cancer.

The Nutritional Prevention of Cancer trial showed a 52% lower incidence of prostate cancer in men supplemented with selenium. As a result, our study was designed to assess whether selenium supplementation attenuates the progression of prostate cancer. A phase 2 randomized, double-blind, placebo-controlled clinical trial was conducted in men with localized nonmetastatic prostate cancer who had elected to forgo active treatment and be followed by active surveillance. A total of 140 men were randomized to placebo (n = 46), 200 microg/d (n = 47), or 800 microg/d (n = 47) selenium p.o. (as selenized yeast) and followed every 3 months for up to 5 years. Prostate-specific antigen (PSA) velocity was used as a marker of prostate cancer progression and was estimated using mixed-effects regression. Adjusting for age, body mass index, baseline selenium, smoking, baseline PSA, race, PSA method, and Gleason score, PSA velocities for the 200 microg/d and 800 microg/d treatment groups were not statistically significantly different from placebo (P = 0.32 and P = 0.61, respectively). In the highest quartile of baseline selenium, men supplemented with 800 microg selenium showed statistically significantly higher PSA velocity as compared with placebo (P = 0.018). Selenium supplementation did not show a protective effect on PSA velocity in subjects with localized prostate cancer. On the contrary, supplementation with high-dose selenium was observed to be a risk factor for increased PSA velocity in men with high baseline plasma selenium concentrations.

Effects of repeated green tea catechin administration on human cytochrome P450 activity.

PURPOSE: Preclinical studies suggested that green tea or green tea catechins can modulate the activities of drug-metabolizing enzymes. We conducted this clinical study to determine the effect of repeated green tea catechin administration on human cytochrome P450 (CYP) enzyme activities. METHODS: Forty-two healthy volunteers underwent a 4-week washout period by refraining from tea or tea-related products. At the end of the washout period, study participants received a cocktail of CYP metabolic probe drugs, including caffeine, dextromethorphan, losartan, and buspirone for assessing the activity of CYP1A2, CYP2D6, CYP2C9, and CYP3A4, respectively. Blood and urine samples before and 8 h after probe drug administration were collected to determine parent drug and metabolite concentrations for measurements of baseline CYP enzyme activities. Following the baseline evaluation, study participants underwent 4 weeks of green tea catechin intervention at a dose that contains 800 mg epigallocatechin gallate (EGCG) daily. The green tea catechin product was taken on an empty stomach to optimize the p.o. bioavailability of EGCG. The EGCG dose given in this study exceeded the amounts provided by average green tea consumption. Upon completion of the green tea catechin intervention, the postintervention CYP enzyme activities were evaluated as described above. RESULTS: There are large between-subject variations in CYP enzyme activities in healthy individuals. Four weeks of green tea catechin intervention did not alter the phenotypic indices of CYP1A2, CYP12D6, and CYP12C9, but resulted in a 20% increase (P = 0.01) in the area under the plasma buspirone concentration-time profile, suggesting a small reduction in CYP3A4 activity. CONCLUSIONS: We conclude that repeated green tea catechin administration is not likely to result in clinically significant effects on the disposition of drugs metabolized by CYP enzymes.