Feasibility and Acceptability of a Telephone-Based Smoking Cessation Intervention for Qatari Residents.

The steady increase in smoking rates has led to a call for wide-reaching and scalable interventions for smoking cessation in Qatar. This study examined the feasibility and acceptability of an evidence-based smoking cessation program delivered by telephone for Qatari residents. A total of 248 participants were recruited through primary care centers and received five weekly scheduled proactive behavioral counseling calls from personnel trained in tobacco cessation and navigation to obtain cessation pharmacotherapy from clinics. Outcomes were assessed at end of treatment (EOT), and 1- and-3-month follow up. The Mann-Whitney test was used to compare the average number of participants recruited per month pre- and post-COVID. We recruited 16 participants/month, the majority (85.5%) attended at least one counselling session, and 95.4% used some of pharmacotherapy. Retention rates were 70% at EOT, 64.4% and 71.7% at 1- and 3-month follow up, respectively; 86% reported being 'extremely satisfied' by the program. Our ITT 7-day point prevalence abstinence was 41.6% at EOT, 38.4% and 39.3% at 1-and 3-month, respectively. The average number of participants recruited per month was significantly higher for pre vs. post-COVID (18.9 vs. 10.0, p-value = 0.02). Average number of participants retained at EOT per recruitment month showed a slight decrease from 8.6 pre- to 8.2 post-COVID; average number who quit smoking at EOT per recruitment month also showed a decrease from 6 to 4.6. The study results indicated that our telephone-based intervention is feasible and acceptable in this population and presents a new treatment model which can be easily disseminated to a broad population of Qatari smokers.

Factors associated with baseline smoking self-efficacy among male Qatari residents enrolled in a quit smoking study.

Smoking self-efficacy, described as confidence in one's ability to abstain from smoking in high-risk situations is a key predictor in cessation outcomes; however, there is a dearth of research on factors that influence self-efficacy surrounding smoking behavior. This study examines factors associated with baseline self-efficacy among treatment seeking participants enrolled in a pilot feasibility smoking cessation study. Participants (n = 247) were daily male smokers, residents of Doha in Qatar (18-60 years) who were enrolled in a telephone-based smoking cessation study. Baseline assessments included self-efficacy, home smoking rules, socio-demographic variables, smoking history, and psychosocial characteristics. Factors associated with self-efficacy were assessed using multiple linear regression analysis. Results showed that after controlling for relevant variables, number of cigarettes smoked ([Formula: see text] = -0.22; 95% CI: -0.37, -0.06), having at least one quit attempt in the past year ([Formula: see text] = 2.30; 95% CI: 0.27, 4.35), and reporting a complete home smoking ban ([Formula: see text] = 3.13; 95% CI: 0.56, 5.70) were significantly associated with higher self-efficacy to quit smoking. These results provide data-driven indication of several key variables that can be targeted to increase smoking self-efficacy in this understudied population.

Effect of d-limonene and its derivatives on breast cancer in human trials: a scoping review and narrative synthesis.

BACKGROUND: D-limonene and its derivatives have demonstrated potential chemopreventive and anticancer activity in preclinical and clinical studies. The aim of this scoping review was to assess and critically appraise current literature on the effect of these bioactive citrus peel compounds on breast cancer in human trials and to identify knowledge gaps for exploration in future studies. METHODS: This study followed a scoping review framework. Peer-reviewed journal articles were included if they reported the effect of d-limonene or its derivatives on breast cancer in human subjects. Articles were retrieved from academic databases - PubMed, EMBASE, CINAHL, Web of Science, and Cochrane reviews - and iteratively through review of bibliographies of relevant manuscripts. Titles and abstracts were appraised against the aforementioned inclusion criteria in a first round of screening. Through consensus meetings and full article review by authors, a final set of studies were selected. Results were reported according to the PRISMA extension for scoping reviews. RESULTS: Our search strategy yielded 367 records. Following screening and adjudication, five articles reporting on phase 1(n = 2), phase 2 (n = 2) and both trial phases (n = 1) were included as the final dataset for this review. Trials evaluating the effect of d-limonene (n = 2) showed it was well tolerated in subjects. One study (n = 43 participants) showed d-limonene concentrated in breast tissue (mean 41.3 µg/g tissue) and reduction in tumor cyclin D1 expression, which is associated with tumor proliferation arrest. This study did not show meaningful change in serum biomarkers associated with breast cancer, except for a statistically significant increase in insulin-like growth factor-1 (IGF-I) levels. While elevation of IGF-I is associated with increased cancer risk, the clinical implication of this study remains uncertain given its short duration. Trials with perillyl alcohol (n = 3) showed low tolerance and no effect on breast cancer. CONCLUSION: This review demonstrated a dearth of clinical studies exploring the effect of d-limonene and its derivatives on breast cancer. Limited literature suggests d-limonene is safe and tolerable in human subjects compared to its derivative, perillyl alcohol. Our review demonstrates the need for additional well-powered placebo-controlled trials that assess d-limonene's efficacy on breast cancer compared to other therapies.

A Telephone-Based Tobacco Cessation Program in the State of Qatar: Protocol of a Feasibility Study.

In Qatar, tobacco is the leading preventable cause of death and disease. Telephone-based interventions for smoking are cost-effective and scalable interventions that are effective in promoting smoking behavior change. While many countries have implemented these services within their tobacco control programs, there is a distinct dearth of a telephone-based smoking cessation intervention that is adapted and tailored to meet the needs of people who smoke in Qatar. This study presents the protocol of a primary health care center integrated smoking quitline program in Qatar. Participants will be recruited from seven smoking clinics (recruitment sites). Trained clinic staff will provide brief advice on quitting followed by a referral to the quitline. Eligible participants (male smokers over 18 years of age) will complete baseline questionnaires and receive five weekly proactive counseling calls, an end-of-treatment assessment (approx. 1 week after Session 5), and 1- and 3-month follow-up assessments. The main aim of this study is to assess the feasibility and acceptability, which include the recruitment and retention rate, compliance to pharmacotherapy, and participant satisfaction. This is the first study to integrate an evidence-based smoking cessation intervention delivered via telephone within the healthcare system in Qatar. If effective, results can inform the development of a large-scale telephone-based program that widely reaches users of tobacco in Qatar as well as in the Middle East.

Feasibility and acceptability of a beverage intervention for Hispanic adults: results from a pilot randomized controlled trial.

OBJECTIVE: To assess the feasibility and acceptability of a beverage intervention in Hispanic adults. DESIGN: Eligible individuals identified as Hispanic, were 18-64 years old and had BMI 30·0-50·0 kg/m2. Participants were randomized 2:2:1 to one of three beverages: Mediterranean lemonade (ML), green tea (GT) or flavoured water control (FW). After a 2-week washout period, participants were asked to consume 32 oz (946 ml) of study beverage daily for 6 weeks and avoid other sources of tea, citrus, juice and sweetened beverages; water was permissible. Fasting blood samples were collected at baseline and 8 weeks to assess primary and secondary efficacy outcomes. SETTING: Tucson, AZ, USA.ParticipantsFifty-two participants were recruited over 6 months; fifty were randomized (twenty-one ML, nineteen GT, ten FW). Study population mean (sd) age 44·6 (sd 10·2) years, BMI 35·9 (4·6) kg/m2; 78 % female. RESULTS: Forty-four (88 %) completed the 8-week assessment. Self-reported adherence was high. No significant change (95 % CI) in total cholesterol (mg/dl) from baseline was shown -1·7 (-14·2, 10·9), -3·9 (-17·2, 9·4) and -13·2 (-30·2, 3·8) for ML, GT and FW, respectively. Mean change in HDL-cholesterol (mg/dl) -2·3 (-5·3, 0·7; ML), -1·0 (-4·2, 2·2; GT), -3·9 (-8·0, 0·2; FW) and LDL-cholesterol (mg/dl) 0·2 (-11·3, 11·8; ML), 0·5 (-11·4, 12·4; GT), -9·8 (-25·0, 5·4; FW) were also non-significant. Fasting glucose (mg/dl) increased significantly by 5·2 (2·6, 7·9; ML) and 3·3 (0·58, 6·4; GT). No significant change in HbA1c was demonstrated. Due to the small sample size, potential confounders and effect modifiers were not investigated. CONCLUSIONS: Recruitment and retention figures indicate that a larger-scale trial is feasible; however, favourable changes in cardiometabolic biomarkers were not demonstrated.

Feasibility and acceptability of a beverage intervention for Hispanic adults: a protocol for a pilot randomized controlled trial.

BACKGROUND: In the U.S., Hispanics have among the highest rates of overweight and obesity when compared to other racial/ethnic groups placing them at a greater risk for obesity-related disease. Identifying intervention strategies to reduce caloric intake and/or improve cardiometabolic health in Hispanics is critical to reducing morbidity and mortality among this large and growing population. Evidence exists to support diet-specific behavioral interventions, including beverage modifications, in reducing obesity-related health risks. However, the acceptability and feasibility of a beverage intervention in obese Hispanic adults has not been robustly evaluated. METHODS: The objective of this pilot study is to assess the feasibility and acceptability of a randomized, controlled beverage intervention in 50 obese Hispanic adults ages 18-64 over 8-weeks. Eligible participants were obese (30-50.0 kg/m2), between the ages 18-64, self-identified as Hispanic, and were able to speak, read, and write in either English and/or Spanish. Study recruitment was completed August 2017. Upon the completion of baseline assessments, participants will be randomized to either Mediterranean lemonade, Green Tea, or flavored water control. After completing a 2-week washout period, participants will be asked to consume 32 oz. per day of study beverage for 6-weeks while avoiding all other sources of tea, lemonade, citrus, juice, and other sweetened beverages; water is permissible. Primary outcomes will be recruitment, retention, and acceptability of the intervention strategies. Our study will also evaluate participant-reported tolerance and as an exploratory aim, assess safety/toxicity-related to renal and/or liver function. Fasting blood samples will be collected at baseline and 8-weeks to assess the primary efficacy outcomes: total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Secondary outcomes include fasting glucose, hemoglobin A1c (HbA1c), and high-sensitivity C-reactive protein (hs-CRP). DISCUSSION: This pilot study will provide important feasibility, safety, and early efficacy data necessary to design a larger, adequately-powered randomized controlled trial. TRIAL REGISTRATION: NCT02911753 ( ClinicalTrials.gov ). Registered September 19, 2016. Last updated November 1, 2017.

Smoking Status Effect on Inflammatory Markers in a Randomized Trial of Current and Former Heavy Smokers.

Background. The level of systemic inflammation as measured by circulating levels of C-reactive protein (CRP) and interleukin-6 (IL-6) is linked to an increased risk for cardiovascular diseases (CVD) and cancer. Methods. We recruited 154 current and former smokers between 40 and 80 years of age with 25 or more pack-years of smoking history to study the relationship between inflammatory markers (CRP and IL-6) and smoking status. Results. Our results show that male smokers had significantly higher levels of serum IL-6 compared to male former smokers. We did not find any gender specific differences for smoking and CRP levels but the IL-6 levels were slightly lower in females compared to males. Additionally, our results show that CRP is significantly associated with IL-6 regardless of smoking status. Modelling indicates that the significant predictors of CRP levels were biomarkers of the metabolic syndrome while the significant predictors of IL-6 levels were age and plasma triglycerides among former smokers and the numbers of smoked packs of cigarettes per year among smokers. Conclusions. In conclusion, our study showed that CRP levels were not associated with markers of smoking intensity. However, IL-6 levels were significantly associated with smoking especially among current smokers.

Expression of epidermal growth factor, transforming growth factor-ß1 and adiponectin in nipple aspirate fluid and plasma of pre and post-menopausal women.

BACKGROUND: Nipple aspirate fluid (NAF) contains large amounts of protein thought to reflect the microenvironment of the breast, and is of interest in breast cancer prevention research. The correlation between specific NAF proteins to plasma concentrations have not been well studied in healthy women. We collected matched NAF and plasma from 43 healthy pre and postmenopausal women participating in an early phase clinical study to compare the levels of putative cancer protein biomarkers. We compared baseline NAF and plasma levels of epidermal growth factor (EGF), transforming growth factor-beta 1 (TGF-ß1), and adiponectin and evaluated menopausal status and body mass index (BMI) as potential modifying factors. FINDINGS: NAF and plasma levels of EGF, TGF-ß1 and adiponectin were not correlated. EGF and TGF-ß1 levels in NAF of premenopausal women were significantly higher than postmenopausal women (P's < 0.01). These differences by menopausal status were not observed in plasma. Both NAF and plasma adiponectin levels were non-significantly higher in postmenopausal women. NAF biomarker levels were not associated with BMI whereas plasma EGF, TGF-ß1 and adiponectin levels in postmenopausal women were all inversely correlated with BMI (P's < 0.05). CONCLUSIONS: Protein biomarkers differ significantly between NAF and plasma and are affected differently by both BMI and menopausal status. This study demonstrates important differences in biological information gained by characterizing biomarkers in NAF compared to plasma and suggests each sample source may independently inform on breast cancer risk.

Vitamin D status and breast cancer in Saudi Arabian women: case-control study.

BACKGROUND: The role of vitamin D in breast cancer prevention is equivocal. Saudi Arabian women may be at greater risk of vitamin D deficiency because of a darker skin type and a greater likelihood of reduced ultraviolet B radiation exposure. Data regarding the vitamin D status of Saudi Arabian women and its relation to breast cancer risk are lacking. OBJECTIVE: The purpose of this research was to evaluate the association between circulating concentrations of 25-hydroxyvitamin D [25(OH)D] and breast cancer risk in Saudi Arabian women. DESIGN: A case-control study was conducted among 120 breast cancer cases and 120 controls. The study population was drawn from patients admitted to King Fahd Hospital in Jeddah, Saudi Arabia, from June to August 2009. Participants completed questionnaires on diet and medical history, and serum samples were collected from all women to measure circulating 25(OH)D concentrations. RESULTS: The participants had a mean age of 47.8 y and a mean body mass index (BMI; in kg/m(2)) of 30.0. Breast cancer cases had significantly lower (mean ± SD) serum concentrations of 25(OH)D (9.4 ± 6.4 ng/mL) than did controls (15.4 ± 12.3 ng/mL; P = 0.001). In comparison with those in the highest category of vitamin D status for this population (≥20 ng/mL), the adjusted ORs (95% CIs) for invasive breast cancer were 6.1 (2.4, 15.1) for women with a serum 25(OH)D concentration <10 ng/mL and 4.0 (1.6, 10.4) for women with a serum concentration of ≥10 to <20 ng/mL (P-trend = 0.0001). CONCLUSION: An inverse association exists between serum 25(OH)D concentrations and breast cancer risk in Saudi Arabian women. This trial was registered at clinicaltrials.gov as NCT01817231.

Gender difference in systemic oxidative stress and antioxidant capacity in current and former heavy smokers.

BACKGROUND: Several studies suggested that women may be more susceptible to oxidative damage induced by cigarette smoking, but the role of smoking status and antioxidant capacity in gender difference in susceptibility to oxidative damage has not been well studied. METHODS: We conducted a cross-sectional analysis of the baseline data from 146 current and former heavy smokers enrolled in a chemoprevention trial to determine the gender difference in oxidative damage and antioxidant capacity. Oxidative DNA and lipid damage were assessed by urinary 8-hydroxy-2'-deoxyguanosine (8OHdG) and 8-isoprostaglandin F(2α) (8-iso-PGF(2α)), respectively. The erythrocyte antioxidant enzymes and serum fat-soluble antioxidants were measured to assess antioxidant capacity. RESULTS: Female smokers had significantly greater levels of 8OHdG and 8-iso-PGF(2α) than males but the gender difference was only significant in current smokers. No gender difference was noted in erythrocyte antioxidant enzymes, although female current smokers had significantly lower or a trend for lower antioxidant enzymes. Female smokers had higher serum ß-carotene than males. Biomarkers of oxidative damage did not correlate significantly with the antioxidant enzymes. Urinary 8OHdG did not correlate significantly with fat-soluble antioxidants. Inverse correlations were observed between urinary 8-iso-PGF(2α) and several serum carotenoids. CONCLUSION: Female current smokers have a greater extent of oxidative damage despite having higher serum levels of fat-soluble antioxidants. Lower erythrocyte antioxidant enzymes in female current smokers may contribute to the greater extent of oxidative damage. IMPACT: The study may help identify appropriate high-risk populations for interventions that attenuate oxidative damage and appropriate biomarkers for clinical studies in smokers.

Safety and Feasibility of Topical Application of Limonene as a Massage Oil to the Breast.

BACKGROUND: Limonene, a major component in citrus oil, has demonstrated anti-cancer effects in preclinical mammary cancer models. However, the effective oral dose translates to a human dose that may not be feasible for chronic dosing. We proposed to evaluate topical application of limonene to the breast as an alternative dosing strategy. MATERIALS AND METHODS: We conducted a mouse disposition study to determine whether limonene would be bio available in the mammary tissue after topical application. SKH-1 mice received topical or oral administration of limonene in the form of orange oil every day for 4 weeks. Plasma and mammary pads were collected 4 hrs after the final dosing. We also conducted an exploratory clinical study to evaluate the safety and feasibility of topically applied limonene in the form of orange oil to the breast. Healthy women were recruited to apply orange oil containing massage oil to their breasts daily for four weeks. Safety and feasibility were assessed by reported adverse events, clinical labs, and usage compliance. Pre and post-intervention nipple aspirate fluid (NAF) and plasma were collected for limonene concentration determination. RESULTS: The mouse disposition study showed that topical and oral orange oil administration resulted in similar mammary tissue disposition of limonene with no clinical signs of toxicity. In the clinical study, the topical application of limonene containing massage oil to the breast was found to be safe with high levels of usage compliance for daily application, although NAF and plasma limonene concentrations were not significantly changed after the massage oil application. CONCLUSIONS: Our studies showed that limonene is bio available in mammary tissue after topical orange oil application in mice and this novel route of administration to the breast is safe and feasible in healthy women.

Pharmacokinetic and chemoprevention studies on tea in humans.

Green tea and its major polyphenols constituents, tea catechins, have been shown to have many health benefits including cancer prevention. Tea catechins and tea catechin metabolites/catabolites are bioavailable in the systemic circulation after oral intake of green tea or green tea catechins. The metabolites/catabolites identified in humans include glucuronide/sulfate conjugates, methylated tea catechin conjugates, and microflora-mediated ring fission products and phenolic acid catabolites. Plasma levels of unchanged tea catechins in humans are mostly in the sub-µM or nM concentration range, which is much lower than the effective concentrations determined in most in vitro studies. However, some of the catechin metabolites/catabolites are present in the systemic circulation at levels much higher than those of the parent catechins. The contribution of catechin derived metabolites/catabolites to the biological effects associated with green tea is yet to be defined. A limited number of chemoprevention trials of green tea or green tea catechins have been conducted to date and have observed potential preventive activity for oral, prostate, and colorectal cancer. Emerging data from multiple ongoing intervention trials will further contribute to defining the cancer preventive activity of green tea or green tea catechins.

Adipose tissue accumulation of d-limonene with the consumption of a lemonade preparation rich in d-limonene content.

d-limonene is a bioactive food component found in high concentration in citrus peel oil with anticancer effects in preclinical studies of mammary carcinogenesis. Extrapolation of preclinical data to human cancer is limited, in part, by inadequate information on the oral bioavailability and tissue disposition of d-limonene in humans. As a fat-soluble compound, d-limonene is more likely to deposit in fatty tissues such as the breast. To assess disposition of d-limonene in humans, we conducted a pilot study of oral d-limonene-rich lemonade. Following a 1-wk washout period devoid of citrus, healthy adults consumed 40 oz. of freshly prepared lemonade containing 500 to 600 mg d-limonene daily for 4 wk. On the first and last consumption days, blood and buttock fat biopsy were collected. Matched preintervention and postintervention fat biopsies (n = 7), and matched preintervention and postintervention plasma samples (n = 6), were analyzed for d-limonene levels using gas chromatography and mass spectrometry. There was a significant increase in d-limonene levels in the fat biopsies after 4 wk (P = 0.009); initial levels ranged from nondetectable to 7.79 micromol/kg tissue, and postintervention levels ranged from 53.6 to 294 micromol/kg tissue. Plasma d-limonene levels increased from 0.35 to 0.72 micromol/l initially to postintervention levels of 0.54 to 1.65 micromol/l (P = 0.016). Postintervention adipose d-limonene levels were 51.0 to 195 times higher than plasma levels (P = 0.009). Our results demonstrate accumulation of d-limonene in adipose tissue after oral dosing and support additional studies of d-limonene for chemoprevention in tissues such as the breast that are comprised of a significant fat fraction.

Green tea consumption is associated with decreased DNA damage among GSTM1-positive smokers regardless of their hOGG1 genotype.

The levels of tobacco-related DNA adducts in human tissues reflect a dynamic process that is dependent on the intensity and time of exposure to tobacco smoke, the metabolic balance between activation of detoxification mechanisms, and the removal of adducts by DNA repair and/or cell turnover. Urinary 8-hydroxydeoxyguanosine (8-OHdG) is probably 1 of the most abundant DNA lesions formed during oxidative stress and is proposed as a sensitive biomarker of the overall oxidative DNA damage and repair. We performed this study to determine whether there were differences in increased oxidative stress susceptibility to smoking within the combined GSTM1 and hOGG1 genotypes and the impact of green tea drinking on this. We completed a Phase II randomized, controlled, 3-arm tea intervention trial to study the effect of high consumption of decaffeinated green or black tea or water on urinary 8-OHdG among heavy smokers and to evaluate the roles of GSTM1 and hOGG1 genotypes as effect modifiers. Assessment of urinary 8-OHdG after adjustment for baseline measurements and other potential confounders revealed a significant effect of green tea consumption (P = 0.001). The change from baseline was significant in all GSTM1-positive smokers regardless of their hOGG1 genotype. Our data show that consumption of 4 cups (960 mL) of tea/d is a feasible and safe approach and was associated with a significant decrease in urinary 8-OHdG among green tea consumers. Our finding also suggests that green tea intervention might be effective in decreasing DNA damage in the subgroup of smokers who are GSTM1 positive regardless of their hOGG1 genotype.

Determination of d-limonene in adipose tissue by gas chromatography-mass spectrometry.

We developed a novel method for analyzing d-limonene levels in adipose tissue. Fat samples were subjected to saponification followed by solvent extraction. d-Limonene in the sample extract was analyzed using gas chromatography-mass spectrometry (GC-MS) with selected ion monitoring. Linear calibration curves were established over the mass range of 79.0-2529 ng d-limonene per 0.1g of adipose tissue. Satisfactory within-day precision (R.S.D. 6.7-9.6%) and accuracy (%difference of -2.7 to 3.8%) and between-day precision (R.S.D. 6.0-10.7%) and accuracy (%difference of 1.8-2.6%) were achieved. The assay was successfully applied to human fat biopsy samples from a d-limonene feeding trial.

Modulation of human glutathione s-transferases by polyphenon e intervention.

PURPOSE: Green tea consumption has been associated with decreased risk of certain types of cancers in humans. Induction of detoxification enzymes has been suggested as one of the biochemical mechanisms responsible for the cancer-preventive effect of green tea. We conducted this clinical study to determine the effect of repeated green tea polyphenol administration on a major group of detoxification enzymes, glutathione S-transferases (GST). METHODS: A total of 42 healthy volunteers underwent a 4-week washout period by refraining from tea or tea-related products. At the end of the washout period, a fasting blood sample was collected, and plasma and lymphocytes were isolated for assessment of GST activity and level. Following the baseline evaluation, study participants underwent 4 weeks of green tea polyphenol intervention in the form of a standardized Polyphenon E preparation at a dose that contains 800 mg epigallocatechin gallate (EGCG) once a day. Polyphenon E was taken on an empty stomach to optimize the oral bioavailability of EGCG. Upon completion of the intervention, samples were collected for postintervention GST assessment. RESULTS: Four weeks of Polyphenon E intervention enhanced the GST activity in blood lymphocytes from 30.7 +/- 12.2 to 35.1 +/- 14.3 nmol/min/mg protein, P = 0.058. Analysis based on baseline activity showed that a statistically significant increase (80%, P = 0.004) in GST activity was observed in individuals with baseline activity in the lowest tertile, whereas a statistically significant decrease (20%, P = 0.02) in GST activity was observed in the highest tertile. In addition, Polyphenon E intervention significantly increased the GST-pi level in blood lymphocytes from 2,252.9 +/- 734.2 to 2,634.4 +/- 1,138.3 ng/mg protein, P = 0.035. Analysis based on baseline level showed that this increase was only significant (P = 0.003) in individuals with baseline level in the lowest tertile, with a mean increase of 80%. Repeated Polyphenon E administration had minimal effects on lymphocyte GST-mu and plasma GST-alpha levels. There was a small but statistically significant decrease (8%, P = 0.003) in plasma GST-alpha levels in the highest tertile. CONCLUSIONS: We conclude that 4 weeks of Polyphenon E administration resulted in differential effects on GST activity and level based on baseline enzyme activity/level, with GST activity and GST-pi level increased significantly in individuals with low baseline enzyme activity/level. This suggests that green tea polyphenol intervention may enhance the detoxification of carcinogens in individuals with low baseline detoxification capacity.

Cruciferous vegetable intake questionnaire improves cruciferous vegetable intake estimates.

OBJECTIVE: To develop a validated, focused Cruciferous Vegetable Food Frequency Questionnaire (FFQ) as an assessment tool for specific quantification of dietary cruciferous vegetable exposure. DESIGN/METHODS: Participants (n=107; 18 to 76 years old) completed a standard FFQ and the Cruciferous Vegetable FFQ twice over a 2-week period. Repeat dietary recalls were collected on 3 days over the same 2-week period. Urinary dithiocarbamate was determined as a biomarker of cruciferous vegetable intake. STATISTICAL ANALYSES: Descriptive statistics of intake; paired t tests and sign tests for comparison of intake estimates between instruments; Spearman correlations to assess reliability and associations between diet instruments and urinary dithiocarbamate. RESULTS: Cruciferous vegetable intake was significantly correlated between the two FFQs (r(s)=0.58), although the Cruciferous Vegetable FFQ estimated intake 35 g higher than the standard FFQ. The Cruciferous Vegetable FFQ was reliable, with a repeated measures correlation of 0.69 (P

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.

Effects of dosing condition on the oral bioavailability of green tea catechins after single-dose administration of Polyphenon E in healthy individuals.

PURPOSE: Green tea has been shown to exhibit cancer-preventive activities in preclinical studies. Its consumption has been associated with decreased risk of certain types of cancers in humans. The oral bioavailability of the major green tea constituents, green tea catechins, is low, resulting in systemic catechin levels in humans many fold less than the effective concentrations determined in in vitro systems. We conducted this clinical study to test the hypothesis that the oral bioavailability of green tea catechins can be enhanced when consumed in the absence of food. EXPERIMENTAL DESIGNS: Thirty healthy volunteers were randomly assigned to one of the following doses of Polyphenon E (a decaffeinated and defined green tea catechin mixture): 400, 800, or 1,200 mg, based on the epigallocatechin gallate content (10 subjects per dose group). After an overnight fast, study participants took a single dose of Polyphenon E with or without a light breakfast, which consisted of one or two 4-oz muffins and a glass of water. Following a 1-week wash-out period, subjects were crossed over to take the same dose of Polyphenon E under the opposite fasting/fed condition. Tea catechin concentrations in plasma and urine samples collected after dosing were determined by high-pressure liquid chromatography analysis. RESULTS: Consistent with previous reports, epigallocatechin gallate and epicatechin gallate were present in plasma mostly as the free form, whereas epicatechin and epigallocatechin were mostly present as the glucuronide and sulfate conjugates. There was >3.5-fold increase in the average maximum plasma concentration of free epigallocatechin gallate when Polyphenon E was taken in the fasting condition than when taken with food. The dosing condition led to a similar change in plasma-free epigallocatechin and epicatechin gallate levels. Taking Polyphenon E in the fasting state did not have a significant effect on the plasma levels of total (free and conjugated) epigallocatechin, but resulted in lower plasma levels of total epicatechin. Urinary epigallocatechin gallate and epicatechin gallate levels were very low or undetectable following Polyphenon E administration with either dosing condition. Taking Polyphenon E under the fasting state resulted in a significant decrease in the urinary recovery of total epigallocatechin and epicatechin. Polyphenon E administered as a single dose over the dose range studied was generally well-tolerated by the study participants. Mild and transient nausea was noted in some of the study participants and was seen most often at the highest study agent dose (1,200 mg epigallocatechin gallate) and in the fasting condition. CONCLUSIONS: We conclude that greater oral bioavailability of free catechins can be achieved by taking the Polyphenon E capsules on an empty stomach after an overnight fast. Polyphenon E up to a dose that contains 800 mg epigallocatechin gallate is well-tolerated when taken under the fasting condition. This dosing condition is also expected to optimize the biological effects of tea catechins.

A cross-sectional analysis demonstrated the healthy volunteer effect in smokers.

OBJECTIVE: This cross-sectional descriptive analysis sought to determine if a healthy volunteer effect can be demonstrated among smokers selected to participate in a dietary intervention trial. STUDY DESIGN AND SETTING: Body mass index (BMI), body fat, physical activity, dietary intake, and plasma concentration of antioxidant nutrients and carotenoids were assessed cross-sectionally, at the time of enrollment into a dietary intervention trial, among 136 adult smokers. RESULTS: Mean BMI was below national age- and gender-specific averages as was prevalence of overweight and obesity. Physical activity was reported to average 15.4 h/wk. Compared with other sample populations of smokers, our smokers reported lower total fat and cholesterol intakes, higher vitamin C and beta-carotene intakes, and generally equal vitamin E intakes. Plasma ascorbic acid, alpha-tocopherol, alpha- and beta-carotene, and beta-cryptoxanthin concentrations were higher than those of smokers surveyed by NHANES III. CONCLUSION: These findings suggest that a "healthy volunteer effect" can be described among adult smokers. Future dietary intervention trials among smokers should cautiously estimate sample size because smokers electing to participate may report healthier dietary patterns than other smokers. Screening criteria regarding baseline micronutrient status of smokers should be evaluated given that intervention effects may be dependent on overall health status.