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.

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.

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.

A combination of tomato and soy products for men with recurring prostate cancer and rising prostate specific antigen.

Tomato and soy products are hypothesized to reduce the risk of prostate cancer or enhance efficacy of therapy. A study was completed to determine if men with active prostate cancer will adhere to a dietary intervention rich in tomato products and a soy protein supplement men (n = 41) with recurrent, asymptomatic prostate cancer were randomized among 2 groups: Group A (n = 20) consumed tomato products (no soy) for Weeks 0 through 4, targeting a minimum of 25 mg of lycopene/day. Group B (n = 21) consumed soy (no tomatoes) for Weeks 0 through 4, providing 40 g of soy protein/day. For Weeks 4 through 8, all men consumed a combined tomato-rich diet and soy supplements. No grade II through IV toxicities were observed. During Weeks 0 through 4, mean daily lycopene intake for Group A was 43 mg (+/- 15 mg) and mean soy intake for Group B was 39 g (+/- 1 g), remaining similar during Weeks 4 through 8. Serum lycopene increased from 0.72 +/- 0.09 micromol/l to 1.21 +/- 0.10 micromol/l (P < 0.0001) and urinary isoflavone excretion increased from not detectable to 54.1 +/- 5.7 micromol/l (P < 0.05) with 8 wk of diet intervention. Serum prostate-specific antigen decreased between Weeks 0 and 8 for 14 / 41 men (34%). Mean serum vascular endothelial growth factor for the entire group was reduced from 87 to 51 ng/ml (P < 0.05) over 8 wk. In conclusion, prostate cancer patients will consume diets rich in tomato products and soy with excellent compliance and bioavailability of phytochemicals. Further studies combining tomato and soy foods to determine efficacy for prostate cancer prevention or management are encouraged.

Consumption of dietary supplements and over-the-counter and prescription medications in men participating in the Prostate Cancer Prevention Trial at an academic center.

OBJECTIVE: It is hypothesized that dietary patterns, individual nutrients, and specific prescription and over-the-counter medications may influence prostate carcinogenesis. Little information is available regarding the use of these products among men who are participating in prevention trials targeting prostate cancer. MATERIALS AND METHODS: A total of 92 men (mean age 69 years) participating in the Prostate Cancer Prevention Trial (PCPT) at an academic center were asked to bring all nutritional supplements and medications to regularly scheduled study visits. RESULTS: Data were collected on 86 of 92 men. We found that 85% of men in the PCPT regularly consumed at least 1 nutritional supplement. The mean (+/-standard deviation) number of dietary supplements consumed per man was 3.3 +/- 3.5 (range 0-21). A multivitamin and multimineral (73%) supplement was the most common product consumed. Single-nutrient supplements regularly consumed included: vitamin E (48%), vitamin C (31%), calcium (24%), and selenium (7%). Of men, 36% reported consumption of herbal products. Medications frequently consumed during the study period that may influence prostate carcinogenesis included nonsteroidal antiinflammatory drugs (57%), antihypertensives (49%), lipid lowering agents (27%), and aspirin (64%). CONCLUSIONS: Participants in the PCPT at an academic center have a high propensity for dietary supplement use. Many, such as vitamin E and selenium, are hypothesized to influence the risk of prostate cancer. Several of the medications commonly consumed, including aspirin, nonsteroidal antiinflammatory drugs, and statins, are being investigated as chemopreventive agents. Investigators designing prostate cancer chemoprevention trials should consider including detailed documentation of exposure to these products that may influence study outcomes.