Associations of dietary patterns with kidney cancer risk, kidney cancer-specific mortality and all-cause mortality among postmenopausal women.

BACKGROUND: The empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP) are novel measures of dietary quality associated with insulin hypersecretion or chronic inflammation, respectively, whereas the Healthy Eating Index (HEI-2015) measures adherence to the Dietary Guidelines for Americans (DGA). We evaluated associations of EDIH, EDIP and HEI-2015 on the risk of both kidney cancer development and mortality. METHODS: We calculated the dietary scores from baseline food frequency questionnaires among 115,830 participants aged 50-79 years in the Women's Health Initiative. Multivariable-adjusted Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) for kidney cancer risk, kidney cancer-specific mortality and all-cause mortality, per 1-standard deviation increment in dietary pattern scores. RESULTS: Higher EDIH was associated with greater risk of kidney cancer development [HR, 1.12; 95%CI, (1.01,1.23)], kidney cancer-specific death [1.22(0.99,1.48)], and all-cause mortality, [1.05(1.02,1.08)]. Higher HEI-2015 was associated with lower risk of kidney cancer development, [0.85(0.77, 0.94)], kidney cancer-specific death, [0.84(0.69,1.03)] and all-cause mortality, [0.97(0.95,1.00)]. However, EDIP was not significantly associated with outcomes. Associations did not differ by BMI categories. CONCLUSIONS: Low-insulinemic dietary patterns and higher quality diets, are worthy of testing in dietary pattern intervention trials for kidney cancer prevention and improved survivorship.

Distinctive patterns of sulfide- and butyrate-metabolizing bacteria after bariatric surgery: potential implications for colorectal cancer risk.

Despite improved cardiometabolic outcomes following bariatric surgery, its long-term impact on colorectal cancer (CRC) risk remains uncertain. In parallel, the influence of bariatric surgery on the host microbiome and relationships with disease outcomes is beginning to be appreciated. Therefore, we investigated the impact of Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) on the patterns of sulfide-reducing and butyrate-producing bacteria, which are hypothesized to modulate CRC risk after bariatric surgery. In this single-center, cross-sectional study, we included 15 pre-surgery subjects with severe obesity and patients who are at a median (range) of 25.6 (9.9-46.5) months after RYGB (n = 16) or VSG (n = 10). The DNA abundance of fecal bacteria and enzymes involved in butyrate and sulfide metabolism were identified using metagenomic sequencing. Differences between pre-surgery and post-RYGB or post-VSG cohorts were quantified using the linear discriminant analysis (LDA) effect size (LEfSe) method. Our sample was predominantly female (87%) with a median (range) age of 46 (23-71) years. Post-RYGB and post-VSG patients had a higher DNA abundance of fecal sulfide-reducing bacteria than pre-surgery controls (LDA = 1.3-4.4, p < .05). The most significant enrichments were for fecal E. coli, Acidaminococcus and A. finegoldii after RYGB, and for A. finegoldii, S. vestibularis, V. parvula after VSG. As for butyrate-producing bacteria, R. faecis was more abundant, whereas B. dentium and A. hardus were lower post-RYGB vs. pre-surgery. B. dentium was also lower in post-VSG vs. pre-surgery. Consistent with these findings, our analysis showed a greater enrichment of sulfide-reducing enzymes after bariatric surgery, especially RYGB, vs. pre-surgery. The DNA abundance of butyrate-producing enzymes was lower post-RYGB. In conclusion, the two most used bariatric surgeries, RYGB and VSG, are associated with microbiome patterns that are potentially implicated in CRC risk. Future studies are needed to validate and understand the impact of these microbiome changes on CRC risk after bariatric surgery.

Application of the Updated WCRF/AICR Cancer Prevention Score as an Outcome for Cancer Survivors Participating in a Tailored and Intensive Dietary and Physical Activity Intervention.

The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) has defined evidence-based guidelines for cancer prevention. These recommendations have been operationalized into a quantitative index for individual assessment. Survivors of cancer are increasingly desiring guidance for diet and lifestyle, and in the absence of research in survivors, are often instructed to follow cancer prevention and public health guidelines. In this study, we examine the utility of the quantitative updated WCRF/AICR scoring criteria to assess change among cancer survivors with overweight/obesity (OW/OB) following an intensive behavioral intervention. We applied the WCRF/AICR scoring criteria (range 0−7) to examine changes over the duration of the study by paired t-tests. Two cancer survivor cohorts with OW/OB (n = 91) completed a six-month phase II clinical trial designed to improve dietary and physical activity patterns. At enrollment and post-intervention, participants completed assessments including anthropometrics, food frequency questionnaires, and objective evaluation of physical activity. Participants improved adherence to all scored recommendations, with a significant increase in mean score from enrollment (3.22 ± 1.06) to post-intervention (4.28 ± 1.04) (p < 0.001). Mean BMI and waist circumference improved (both p < 0.001). The greatest improvements were noted for fruit and non-starchy vegetable intakes (+39%, p < 0.001); the greatest decreases were observed for processed meat consumption (−70%, p < 0.001). The updated WCRF/AICR Score can be applied to cancer survivor intervention studies and provides a tool to compare trials in regard to the baseline status of populations enrolled and the success of the intervention. Future interventions incorporating standardized assessments will help guide effective strategies to improve the health and quality of life for cancer survivors.

Assessment of dietary carotenoid intake and biologic measurement of exposure in humans.

Carotenoids are a diverse family of phytochemicals with over 1000 different carotenoids present in nature. A human diet containing a variety of plant foods typically includes approximately 50 different carotenoids, although six (α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, lutein, and zeaxanthin) comprise over 90% of total carotenoid intake. Most carotenoids do not meet the definition of a nutrient, but several can be cleaved to form vitamin A and are important contributors to vitamin A nutriture and prevention of vitamin A deficiency. Large epidemiologic studies suggest that diets rich in total or specific carotenoids are associated with a reduced risk of several diseases including various types of cancer, cardiovascular disease, cognitive disorders, and age-related macular degeneration. However, accurate measurement of dietary intake is challenging and current methods of dietary assessment, including food frequency questionnaires, diet records and 24-h recalls, have strengths and limitations regarding estimating carotenoid intake. Additionally, carotenoid bioavailability from the diet is influenced by many variables including food processing and cooking, meal composition, and individual characteristics of the host including age, digestive efficiency, nutritional status and genetic polymorphisms. Carotenoids are deposited in many human tissues and can be measured using a variety of techniques including high performance liquid chromatography (HPLC) and mass spectrometry (MS). Continued research is necessary to improve dietary intake assessment and establish biologically relevant dose-response relationships in the context of individual variability to advance our understanding of diet, disease risk, and health promotion.

Adjustable Intragastric Balloon Leads to Significant Improvement in Obesity-Related Lipidome and Fecal Microbiome Profiles: A Proof-of-Concept Study.

INTRODUCTION: Intragastric balloons (IGBs) are a safe and effective treatment for obesity. However, limited knowledge exists on the underlying biological changes with IGB placement. METHODS: This single-institution study was part of an adjustable IGB randomized controlled trial. Subjects with obesity were randomized in a 2 is to 1 ratio to 32 weeks of IGB with diet/exercise counseling (n = 8) vs counseling alone (controls, n = 4). Diet/exercise counseling was continued for 24 weeks post-IGB removal to assess weight maintenance. We used mass spectrometry for nontargeted plasma lipidomics analysis and 16S rRNA sequencing to profile the fecal microbiome. RESULTS: Subjects with IGBs lost 15.5% of their body weight at 32 weeks vs 2.59% for controls (P < 0.05). Maintenance of a 10.5% weight loss occurred post-IGB explant. IGB placement, followed by weight maintenance, led to a -378.9 µM/L reduction in serum free fatty acids compared with pre-IGB (95% confidence interval: 612.9, -145.0). This reduction was mainly in saturated, mono, and omega-6 fatty acids when compared with pre-IGB. Polyunsaturated phosphatidylcholines also increased after IGB placement (difference of 27 µM/L; 95% confidence interval: 1.1, 52.8). Compared with controls, saturated and omega-6 free fatty acids (linoleic and arachidonic acids) were reduced after IGB placement. The fecal microbiota changed post-IGB placement and weight maintenance vs pre-IGB (P < 0.05). Further analysis showed a possible trend toward reduced Firmicutes and increased Bacteroidetes post-IGB and counseling, a change that was not conclusively different from counseling alone. DISCUSSION: IGB treatment is associated with an altered fecal microbiome profile and may have a better effect on obesity-related lipidome than counseling alone.

Dose-Dependent Increases in Ellagitannin Metabolites as Biomarkers of Intake in Humans Consuming Standardized Black Raspberry Food Products Designed for Clinical Trials.

SCOPE: Black raspberry (BRB) phytochemicals demonstrate anti-carcinogenic properties in experimental models, including prostate cancer. Two BRB foods, a confection and nectar, providing a consistent and reproducible product for human clinical studies are designed and characterized. METHODS AND RESULTS: Men with clinically localized prostate cancer are sequentially enrolled to a control group or one of four intervention groups (confection or nectar, 10 or 20 g dose; n = 8 per group) for 4 weeks prior to prostatectomy. Primary outcomes include: safety, adherence, and ellagitannin metabolism. Adherence to the intervention is >96%. No significant (≥grade II) toxicities are detected. Urinary urolithins (A, B, C, and D) and dimethyl ellagic acid (DMEA) quantified by Ultra high performance liquid chromatography tandem mass spectroscopy (UPLC/MS/MS) indicate a dose-dependent excretion yet heterogeneous patterns among men. Men in the BRB confection groups have greater urinary excretion of the microbial urinary metabolites urolithin A and DMEA, suggesting that this food matrix provides greater colonic microflora exposure. CONCLUSION: Fully characterized BRB confections and nectar are ideal for food-based large phase III human clinical studies. BRB products provide a bioavailable source of BRB phytochemicals, however large inter individual variation in polyphenol metabolism suggests that host genetics, microflora, and other factors are critical to understanding bioactivity and metabolism.

Impact of a Tailored Nutrition and Lifestyle Intervention for Overweight Cancer Survivors on Dietary Patterns, Physical Activity, Quality of Life, and Cardiometabolic Profiles.

Survivors of cancer often experience treatment-related toxicity in addition to being at risk of cancer recurrence, second primary cancers, and greater all-cause mortality. The objective of this study was to test the safety and efficacy of an intensive evidence-based garden intervention to improve outcomes for cancer survivors after curative therapy. To do so, a clinical trial of adult overweight and obese cancer survivors within 2 years of completing curative therapy was completed. The 6-month intervention, delivered within the context of harvesting at an urban garden, combined group education with cooking demonstrations, remote motivational interviewing, and online digital resources. Data on dietary patterns, program satisfaction, and quality of life were collected via questionnaires; anthropometrics, physical activity, and clinical biomarkers were measured objectively. Of the 29 participants, 86% were white, 83% were female, and the mean age was 58 years. Compared to baseline, participants had significant improvements in Healthy Eating Index (HEI) scores (+5.2 points, p = 0.006), physical activity (+1,208 steps, p = 0.033), and quality of life (+16.07 points, p = 0.004). Significant improvements were also documented in weight (-3.9 kg), waist circumference (-5.5 cm), BMI (-1.5 kg/m2), systolic BP (-9.5 mmHg), plasma carotenoids (+35%), total cholesterol (-6%), triglycerides (-14%), hs-CRP (-28%), and IGFBP-3 (-5%) (all p < 0.010). These findings demonstrate a tailored multifaceted garden-based biobehavioral intervention for overweight and obese cancer survivors after curative therapy is safe and highly effective, warranting larger randomized controlled trials to identify program benefits, optimal maintenance strategies, program value relative to cost, and approaches for integration into a survivor's oncology management program. This trial is registered on ClinicalTrials.gov NCT02268188.

Single Nucleotide Polymorphisms in ß-Carotene Oxygenase 1 are Associated with Plasma Lycopene Responses to a Tomato-Soy Juice Intervention in Men with Prostate Cancer.

BACKGROUND: Human plasma and tissue lycopene concentrations are heterogeneous even when consuming controlled amounts of tomato or lycopene. OBJECTIVES: Our objective is to determine whether single nucleotide polymorphisms (SNPs) in or near known or putative carotenoid metabolism genes [ß-carotene 15,15' monooxygenase 1 (BCO1), scavenger receptor class B type 1 (SCARB1), ATP-binding cassette transporter subfamily A member 1 (ABCA1), microsomal triglyceride transfer protein (MTTP), apolipoprotein B-48, elongation of very long chain fatty acids protein 2 (ELOVL2), and ATP-binding cassette subfamily B member 1 (ABCB1), and an intergenic superoxide dismutase 2, mitochondrial-associated SNP] are predictive of plasma lycopene responses to steady state tomato juice consumption. METHODS: Secondary linear regression analyses of data from a dose-escalation study of prostate cancer patients [n = 47; mean ± SEM age: 60 ± 1 y; BMI (in kg/m2): 32 ± 1] consuming 0, 1, or 2 cans of tomato-soy juice/d (163 mL/can; 20.6 mg lycopene 1.2 mg ß-carotene/can) for 24 ± 0.7 d before prostatectomy were conducted to explore 11 SNP genotype effects on the change in plasma lycopene and plasma and prostate tissue concentrations of lycopene, ß-carotene, phytoene, and phytofluene. RESULTS: Two BCO1 SNP genotypes were significant predictors of the change in plasma lycopene, with SNP effects differing in magnitude and direction, depending on the level of juice intake (rs12934922 × diet group P = 0.02; rs6564851 × diet group P = 0.046). Further analyses suggested that plasma ß-carotene changes were predicted by BCO1 rs12934922 (P < 0.01), prostate lycopene by trending interaction and main effects of BCO1 SNPs (rs12934922 × diet group P = 0.09; rs12934922 P = 0.02; rs6564851 P = 0.053), and prostate ß-carotene by BCO1 SNP interaction and main effects (rs12934922 × diet group P = 0.01; rs12934922 P < 0.01; rs7501331 P = 0.02). CONCLUSIONS: In conclusion, SNPs in BCO1 and other genes may modulate human plasma and prostate tissue responses to dietary lycopene intake and warrant validation in larger, human controlled feeding intervention and cohort studies. Genetic variants related to carotenoid metabolism may partially explain heterogeneous human blood and tissue responses and may be critical covariates for population studies and clinical trials. This trial was registered at clinicaltrials.gov as NCT01009736.

A Novel Tomato-Soy Juice Induces a Dose-Response Increase in Urinary and Plasma Phytochemical Biomarkers in Men with Prostate Cancer.

Background: Tomato and soy intake is associated with reduced prostate cancer risk or severity in epidemiologic and experimental studies. Objective: On the basis of the principle that multiple bioactives in tomato and soy may act on diverse anticancer pathways, we developed and characterized a tomato-soy juice for clinical trials. In this phase 2 dose-escalating study, we examined plasma, prostate, and urine biomarkers of carotenoid and isoflavone exposure. Methods: Men scheduled for prostatectomy were recruited to consume 0, 1, or 2 cans of tomato-soy juice/d before surgery (mean ± SD duration: 24 ± 4.6 d). The juice provided 20.6 mg lycopene and 66 mg isoflavone aglycone equivalents/177-mL can. Plasma carotenoids and urinary isoflavone metabolites were quantified by HPLC-photometric diode array and prostate carotenoids and isoflavones by HPLC-tandem mass spectrometry. Results: We documented significant dose-response increases (P < 0.05) in plasma concentrations of tomato carotenoids. Plasma concentrations were 1.86-, 1.69-, 1.73-, and 1.69-fold higher for lycopene, ß-carotene, phytoene, and phytofluene, respectively, for the 1-can/d group and 2.34-, 3.43-, 2.54-, and 2.29-fold higher, respectively, for the 2-cans/d group compared with 0 cans/d. Urinary isoflavones daidzein, genistein, and glycitein increased in a dose-dependent manner. Prostate carotenoid and isoflavone concentrations were not dose-dependent in this short intervention; yet, correlations between plasma carotenoid and urinary isoflavones with respective prostate concentrations were documented (R2 = 0.78 for lycopene, P < 0.001; R2 = 0.59 for dihydrodaidzein, P < 0.001). Secondary clustering analyses showed urinary isoflavone metabolite phenotypes. To our knowledge, this is the first demonstration of the phytoene and phytofluene in prostate tissue after a dietary intervention. Secondary analysis showed that the 2-cans/d group experienced a nonsignificant decrease in prostate-specific antigen slope compared with 0 cans/d (P = 0.078). Conclusion: These findings provide the foundation for evaluating a well-characterized tomato-soy juice in human clinical trials to define the impact on human prostate carcinogenesis. This trial is registered at clinicaltrials.gov as NCT01009736.

Tele-Motivational Interviewing for Cancer Survivors: Feasibility, Preliminary Efficacy, and Lessons Learned.

OBJECTIVE: Determine the feasibility, acceptability, and efficacy of tele-Motivational Interviewing (MI) for overweight cancer survivors. DESIGN: Six-month nonrandomized phase 2 clinical trial. SETTING: Urban garden and remote platforms. PARTICIPANTS: Overweight and obese cancer survivors post active treatment. INTERVENTION: Remote tele-MI from a trained registered dietitian nutritionist (RDN). MAIN OUTCOME MEASURES: Feasibility, acceptability, and preliminary efficacy. ANALYSIS: Groups were stratified as users and nonusers based on tele-MI use. Qualitative survey data and remote MI interaction logs were analyzed for trends. Two-sample t tests were performed to assess pre-post intervention changes in physical activity and dietary behaviors, quality of life, self-efficacy, and clinical biomarkers. RESULTS: A total of 29 participants completed the intervention. There were 17 tele-MI users (59%) and 12 nonusers (41%). Users were primarily female (88%), breast cancer survivors (59%), college educated (82%), with a mean age of 58 years. Users set 50% more goals, lost more weight (4.8 vs 2.6 kg), significantly improved quality of life (P = .03), and trended more positively in clinical biomarkers (eg, cholesterol, blood pressure) than did nonusers. CONCLUSIONS AND IMPLICATIONS: Findings from this study indicate that tele-MI is a feasible and acceptable intervention for overweight cancer survivors after active therapy. Larger randomized trials are needed to establish efficacy and generalizability to a variety of demographic populations.

Application of a low polyphenol or low ellagitannin dietary intervention and its impact on ellagitannin metabolism in men.

SCOPE: Plant polyphenols are widespread in the American diet, yet estimated intake is uncertain. We examine the application of the Polyphenol Explorer® (PED) database to quantify polyphenol and ellagitannin (ET) intake of men with prostate cancer and tested the implementation of diets restricted in polyphenols or ETs. METHODS AND RESULTS: Twenty-four men enrolled in a 4-week trial were randomized to usual, low-polyphenol or low-ET diet. Estimated polyphenol and ET intakes were calculated from 3-day diet records utilizing the PED. Urine and plasma metabolites were quantified by UPLC-MS. Adherence to the restricted diets was 95% for the low polyphenol and 98% for low-ET diet. In the usual diet, estimated dietary polyphenol intake was 1568 ± 939 mg/day, with coffee/tea beverages (1112 ± 1028 mg/day) being the largest contributors and estimated dietary ET intake was 12 ± 13 mg/day. The low-polyphenol and low-ET groups resulted in a reduction of total polyphenols by 45% and 85%, respectively, and omission of dietary ETs. UPLC analysis of urinary host and microbial metabolites reflect ET intake. CONCLUSION: PED is a useful database for assessing exposure to polyphenols. Diets restricted in total polyphenol or ET intake are feasible and UPLC assessment of ET metabolites is reflective of dietary intake.

Feasibility, Preliminary Efficacy, and Lessons Learned From a Garden-Based Lifestyle Intervention for Cancer Survivors.

BACKGROUND: Cancer survivors remain at increased risk for secondary malignancies, comorbidities, and all-cause mortality. Lifestyle behaviors, such as diet and physical activity, are strongly linked to a decreased risk of chronic disease and improved health outcomes, yet a paucity of research has been conducted in this vulnerable population. METHODS: Adult cancer survivors were recruited to participate in Growing Hope, an experimental single-group study designed to assess the feasibility and efficacy of a theory-driven and evidence-based intervention. For 4 months, 22 participants received group and individual education and had access to harvesting fresh produce at an urban garden. Data on program satisfaction, compliance, diet, and physical activity were collected via surveys; anthropometrics, blood values, and skin carotenoids were objectively measured. RESULTS: The intervention resulted in significant improvements in consumption of fruits and vegetables (P = .003), decreased consumption of red and processed meats (P = .030) and sugar-sweetened beverages (P = .020). Levels of skin carotenoids, fasting blood glucose, and non-high density lipoprotein cholesterol were also significantly improved (P = .011, P = .043, and P = .05, respectively). CONCLUSIONS: The results of this study support the feasibility and efficacy of a multifaceted, garden-based intervention for cancer survivors. In addition, these preliminary results demonstrate a positive impact aligning with the current lifestyle recommendations for cancer survivorship. Larger randomized controlled trials are warranted to define impact on sustained health outcomes.

Absorption and Distribution Kinetics of the 13C-Labeled Tomato Carotenoid Phytoene in Healthy Adults.

BACKGROUND: Phytoene is a tomato carotenoid that may contribute to the apparent health benefits of tomato consumption. Although phytoene is a less prominent tomato carotenoid than lycopene, it is a major carotenoid in various human tissues. Phytoene distribution to plasma lipoproteins and tissues differs from lycopene, suggesting the kinetics of phytoene and lycopene differ. OBJECTIVE: The objective of this study was to characterize the kinetic parameters of phytoene absorption, distribution, and excretion in adults, to better understand why biodistribution of phytoene differs from lycopene. METHODS: Four adults (2 males, 2 females) maintained a controlled phytoene diet (1-5 mg/d) for 42 d. On day 14, each consumed 3.2 mg (13)C-phytoene, produced using tomato cell suspension culture technology. Blood samples were collected at 0, 1-15, 17, 21, and 24 h and 2, 3, 4, 7, 10, 14, 17, 21, and 28 d after (13)C-phytoene consumption. Plasma-unlabeled and plasma-labeled phytoene concentrations were determined using ultra-HPLC-quadrupole time-of-flight-mass spectrometry, and data were fit to a 7-compartment carotenoid kinetic model using WinSAAM 3.0.7 software. RESULTS: Subjects were compliant with a controlled phytoene diet, consuming a mean ± SE of 2.5 ± 0.6 mg/d, resulting in a plasma unlabeled phytoene concentration of 71 ± 14 nmol/L. A maximal plasma (13)C-phytoene concentration of 55.6 ± 5.9 nM was achieved 19.8 ± 9.2 h after consumption, and the plasma half-life was 2.3 ± 0.2 d. Compared with previous results for lycopene, phytoene bioavailability was nearly double at 58% ± 19%, the clearance rate from chylomicrons was slower, and the rates of deposition into and utilization by the slow turnover tissue compartment were nearly 3 times greater. CONCLUSIONS: Although only differing from lycopene by 4 double bonds, phytoene exhibits markedly different kinetic characteristics in human plasma, providing insight into metabolic processes contributing to phytoene enrichment in plasma and tissues compared with lycopene. This trial was registered at clinicaltrials.gov as NCT01692340.

Compartmental and noncompartmental modeling of ¹³C-lycopene absorption, isomerization, and distribution kinetics in healthy adults.

BACKGROUND: Lycopene, which is a red carotenoid in tomatoes, has been hypothesized to mediate disease-preventive effects associated with tomato consumption. Lycopene is consumed primarily as the all-trans geometric isomer in foods, whereas human plasma and tissues show greater proportions of cis isomers. OBJECTIVE: With the use of compartmental modeling and stable isotope technology, we determined whether endogenous all-trans-to-cis-lycopene isomerization or isomeric-bioavailability differences underlie the greater proportion of lycopene cis isomers in human tissues than in tomato foods. DESIGN: Healthy men (n = 4) and women (n = 4) consumed (13)C-lycopene (10.2 mg; 82% all-trans and 18% cis), and plasma was collected over 28 d. Unlabeled and (13)C-labeled total lycopene and lycopene-isomer plasma concentrations, which were measured with the use of high-performance liquid chromatography-mass spectrometry, were fit to a 7-compartment model. RESULTS: Subjects absorbed a mean ± SEM of 23% ± 6% of the lycopene. The proportion of plasma cis-(13)C-lycopene isomers increased over time, and all-trans had a shorter half-life than that of cis isomers (5.3 ± 0.3 and 8.8 ± 0.6 d, respectively; P < 0.001) and an earlier time to reach maximal plasma concentration than that of cis isomers (28 ± 7 and 48 ± 9 h, respectively). A compartmental model that allowed for interindividual differences in cis- and all-trans-lycopene bioavailability and endogenous trans-to-cis-lycopene isomerization was predictive of plasma (13)C and unlabeled cis- and all-trans-lycopene concentrations. Although the bioavailability of cis (24.5% ± 6%) and all-trans (23.2% ± 8%) isomers did not differ, endogenous isomerization (0.97 ± 0.25 µmol/d in the fast-turnover tissue lycopene pool) drove tissue and plasma isomeric profiles. CONCLUSION: (13)C-Lycopene combined with physiologic compartmental modeling provides a strategy for following complex in vivo metabolic processes in humans and reveals that postabsorptive trans-to-cis-lycopene isomerization, and not the differential bioavailability of isomers, drives tissue and plasma enrichment of cis-lycopene. This trial was registered at clinicaltrials.gov as NCT01692340.

Isoflavone pharmacokinetics and metabolism after consumption of a standardized soy and soy-almond bread in men with asymptomatic prostate cancer.

Epidemiologic associations suggest that populations consuming substantial amounts of dietary soy exhibit a lower risk of prostate cancer. A 20-week randomized, phase II, crossover trial was conducted in 32 men with asymptomatic prostate cancer. The crossover involved 8 weeks each of soy bread (SB) and soy-almond bread (SAB). The primary objective was to investigate isoflavone bioavailability and metabolite profile. Secondary objectives include safety, compliance, and assessment of biomarkers linked to prostate carcinogenesis. Two distinct SBs were formulated to deliver approximately 60 mg aglycone equivalents of isoflavones per day. The isoflavones were present as aglycones (∼78% as aglycones) in the SAB whereas in the standard SB predominantly as glucosides (18% total isoflavones as aglycones). Compliance to SB (97% ± 4%) and SAB (92% ± 18%) was excellent; toxicity was rare and limited to grade 1 gastrointestinal complaints. Pharmacokinetic studies between SB and SAB showed modest differences. Peak serum concentration time (Tmax) was significantly faster with SAB meal compared with SB in some isoflavonoids, and AUC0 to 24 h of dihydrodaidzein and O-desmethylangolensin was significantly greater after an SB meal. An exploratory cluster analysis was used to identify four isoflavone-metabolizing phenotypes. Insulin-like growth factor-binding protein increased significantly by 41% (P = 0.024) with soy intervention. Findings from this study provide the necessary framework to study isoflavone-metabolizing phenotypes as a strategy for identification of individuals that might benefit or show resistance to cancer preventive strategies using dietary soy. A standardized SB used for future large-scale randomized clinical trials to affect human prostate carcinogenesis is feasible.

A comparison of plasma and prostate lycopene in response to typical servings of tomato soup, sauce or juice in men before prostatectomy.

Tomato product consumption and estimated lycopene intake are hypothesised to reduce the risk of prostate cancer. To define the impact of typical servings of commercially available tomato products on resultant plasma and prostate lycopene concentrations, men scheduled to undergo prostatectomy (n 33) were randomised either to a lycopene-restricted control group ( < 5 mg lycopene/d) or to a tomato soup (2-2¾ cups prepared/d), tomato sauce (142-198 g/d or 5-7 ounces/d) or vegetable juice (325-488 ml/d or 11-16·5 fluid ounces/d) intervention providing 25-35 mg lycopene/d. Plasma and prostate carotenoid concentrations were measured by HPLC. Tomato soup, sauce and juice consumption significantly increased plasma lycopene concentration from 0·68 (sem 0·1) to 1·13 (sem 0·09) µmol/l (66 %), 0·48 (sem 0·09) to 0·82 (sem 0·12) µmol/l (71 %) and 0·49 (sem 0·12) to 0·78 (sem 0·1) µmol/l (59 %), respectively, while the controls consuming the lycopene-restricted diet showed a decline in plasma lycopene concentration from 0·55 (sem 0·60) to 0·42 (sem 0·07) µmol/l ( - 24 %). The end-of-study prostate lycopene concentration was 0·16 (sem 0·02) nmol/g in the controls, but was 3·5-, 3·6- and 2·2-fold higher in tomato soup (P= 0·001), sauce (P= 0·001) and juice (P= 0·165) consumers, respectively. Prostate lycopene concentration was moderately correlated with post-intervention plasma lycopene concentrations (r 0·60, P =0·001), indicating that additional factors have an impact on tissue concentrations. While the primary geometric lycopene isomer in tomato products was all-trans (80-90 %), plasma and prostate isomers were 47 and 80 % cis, respectively, demonstrating a shift towards cis accumulation. Consumption of typical servings of processed tomato products results in differing plasma and prostate lycopene concentrations. Factors including meal composition and genetics deserve further evaluation to determine their impacts on lycopene absorption and biodistribution.

The use of daily aspirin, nutritional supplements and alternative medications among Amish and non-Amish living in Ohio Appalachia.

The purpose of this study was to assess daily aspirin and supplement use among Amish and non-Amish adults living in Ohio Appalachia to understand their potential contribution to lower cancer incidence rates among the Amish. A cross-sectional study was conducted with random samples of 134 Amish adults and 154 non-Amish adults. Face-to-face interviews about cancer-related behaviors included questions regarding aspirin and supplement use. Amish compared to non-Amish adults reported 1) taking significantly (P < 0.05) more supplements [mean number of daily products by Amish males (3.5 ± 3.7) and females (5.2 ± 4.3) vs. non-Amish males (1.4 ± 1.3) and females (3.0 ± 3.2)]; 2) taking significantly (P < 0.05) more vitamins, minerals, fiber supplements (females only), and enzymes (females only); 3) taking significantly (P < 0.01) more herbal supplements (approximately 55% and 71% of Amish males and females vs. 17% and 23% of non-Amish males and females, respectively); and 4) taking significantly (P < 0.05) less aspirin on a regular basis. Aspirin and supplement use among Amish and non-Amish adults show significant differences characteristic of their social and cultural norms. Future studies that clarify the impact of aspirin and supplement use among the Amish and their impacts upon the risk of certain cancers and other disease processes are warranted.

Dietary intake, food processing, and cooking methods among Amish and non-Amish adults living in Ohio Appalachia: relevance to nutritional risk factors for cancer.

This study's purpose was to examine the source, storage, preparation, and intake of food among Amish and non-Amish adults to understand dietary practices as a potential contributing factor to lower cancer incidence rates. Interviews were conducted with a random sample of 134 Amish and 154 non-Amish adults including questions about dietary practices and a 24-h dietary recall. Amish compared to non-Amish adults reported (1) less refrigeration in homes (85% vs. 100%, P < .01); (2) rarely/never obtaining food from restaurants and grocery stores (P < .01); (3) consuming less alcohol (P < .01); (4) consuming fewer daily servings of vegetables (males: 1.2 vs. 1.9 servings/day, P < .01; females: 1.0 vs. 2.1 servings/day, P < .01); and (5) a greater percentage of energy from saturated fat (males: 16.7% vs. 12.6%, P < .01; females: 16.3% vs. 12.0%, P < .01). Amish males reported greater amount of energy intake (2780 kcal vs. 2298 kcal, P = .03) compared to non-Amish males. Amish and non-Amish dietary patterns show some differences that may impact cancer although neither group achieves current diet and cancer prevention guidelines. Lifestyle factors, screening, and healthcare access may be contributing to the lower cancer incidence rates among the Amish and these results suggest areas of intervention to reduce the cancer burden.

Tomato-based food products for prostate cancer prevention: what have we learned?

Evidence derived from a vast array of laboratory studies and epidemiological investigations have implicated diets rich in fruits and vegetables with a reduced risk of certain cancers. However, these approaches cannot demonstrate causal relationships and there is a paucity of randomized, controlled trials due to the difficulties involved with executing studies of food and behavioral change. Rather than pursuing the definitive intervention trials that are necessary, the thrust of research in recent decades has been driven by a reductionist approach focusing upon the identification of bioactive components in fruits and vegetables with the subsequent development of single agents using a pharmacologic approach. At this point in time, there are no chemopreventive strategies that are standard of care in medical practice that have resulted from this approach. This review describes an alternative approach focusing upon development of tomato-based food products for human clinical trials targeting cancer prevention and as an adjunct to therapy. Tomatoes are a source of bioactive phytochemicals and are widely consumed. The phytochemical pattern of tomato products can be manipulated to optimize anticancer activity through genetics, horticultural techniques, and food processing. The opportunity to develop a highly consistent tomato-based food product rich in anticancer phytochemicals for clinical trials targeting specific cancers, particularly the prostate, necessitates the interactive transdisciplinary research efforts of horticulturalists, food technologists, cancer biologists, and clinical translational investigators.