FOOD BASED BIOACTIVE DELIVERY SYSTEM FOR DISEASE PREVENTION

• Sponsoring Institution: National Institute of Food and Agriculture
• Project Status: COMPLETE
• Funding Source: HATCH
• Reporting Frequency: Annual
• Accession No.: 0231566
• Project Start Date: Oct 1, 2012
• Project End Date: Sep 30, 2017
• Program Code: [(N/A)]- (N/A)

Project Director
Vodovotz, Y.

Recipient Organization
OHIO STATE UNIVERSITY
1680 MADISON AVENUE
WOOSTER,OH 44691

Performing Department
Food Science & Technology

Non Technical Summary
In spite of improved medical care and the virtual elimination of disorders due to nutritional deficiencies, aging Americans are experiencing epidemics in chronic diseases ranging from cancer obesity, diabetes, vascular disease, arthritic and autoimmune conditions, and neurodegenerative diseases such as Alzheimer?s. It is generally agreed that the combined effects of numerous compounds in foods rather than any single compound provides the optimal health-promoting benefits against the development of chronic degenerative diseases. A logical extension of such conventional wisdom is to develop functional foods. Functional foods are formulated by developing new food products that combine ingredients containing different classes of health-promoting factors in a manner that is both acceptable and attractive to the consumer. Various factors play key roles in delivering known bioactives in a food system. The stability and concentration of the bioactives during processing and storage need to be assessed. Simultaneously, the quality parameters of the food need to be preserved to assure high compliance when used as a dietary intervention in human clinical trials. These key parameters can be quantified by the use of various analytical techniques such as High Performance Liquid Chromatography and Mass Spectrometry as well as physico-chemical methods such as thermal analysis, texture and rheology and sensory analysis. The ultimate indicator of success is conducting a human clinical trial and verifying the efficacy of delivery of these bioactives and assessment of compliance.

Animal Health Component

(N/A)

Research Effort Categories

Basic

(N/A)

Applied

(N/A)

Developmental

(N/A)

Classification

Knowledge Area (KA)	Subject of Investigation (SOI)	Field of Science (FOS)	Percent
502	5010	1010	33%
701	5010	1010	33%
702	5010	1010	34%

Knowledge Area
702 - Requirements and Function of Nutrients and Other Food Components; 502 - New and Improved Food Products; 701 - Nutrient Composition of Food;

Subject Of Investigation
5010 - Food;

Field Of Science
1010 - Nutrition and metabolism;

Keywords

functional foods

metabolites

phytochemicals

bioactives

bioavailability

bioaccessibility

Goals / Objectives
We have used the approach outlined in Ahn-Jarvis et al (2012) to develop and study various functional foods including a soy-tomato drink, soy bread, strawberry and black raspberry confections (1-36). Briefly, a bioactive is selected to be incorporated into a food product due to epidemiological, cellular or animal studies showing efficacy. The food delivery system is based on the bioactive containing food and the target site of delivery. During food formulation and processing, the compound stability and efficacy of delivery are monitored utilizing a variety of molecular and physico-chemical techniques as well as in-vitro methods. The food is also subjected to human sensory analysis to assure the product meets quality and acceptability standards. The food vehicle is reformulated and redesigned as necessary to meet all specified goals. A human trial is designed and approved and production is upscaled to meet the supply demand. We plan on using a similar approach with future bioactives to be explored. Objectives: 1. Define, formulate and assess the quality and stability of new food delivery systems for desired bioactives 2. Evaluate the stability of the desired bioactives through processing and storage of the food product 3. Ascertain (through collaborative research projects) the bioaccessibility and bioavailability of phytochemicals from the developed functional foods. 4. Investigate metabolic differences and metabolite profiling in nutrients and phytochemicals among individuals enrolled in clinical trials.

Project Methods
During product development, the following instrumentation will be used to probe the state and mobility of water and biopolymers in the system. 1. Differential Scanning Calorimetry (DSC) monitors changes in physical or chemical properties of a material as a function of temperature by detecting the heat changes associated with such processes. 2. Thermal Gravimetric Analysis (TGA) measures the amount and rate of change in the weight of a material as a function of temperature or time. 3. Dynamic Mechanical Analysis (DMA) is a micro-rheological technique in which a dynamic stress is applied and the resulting strain is monitored. Food polymers are mostly viscoelastic with stress and strain being out of phase with respect to each other by the sinusoidal angle delta. 4. Nuclear Magnetic Resonance (NMR) a. 1H CR-NMR A 600 MHz Bruker spectrometer (Bruker Instruments, Billerica, MD) will be used. b. 13C CPMAS NMR A 600 MHz spectrometer (Bruker Instruments, Billerica, MD) equipped with an IBM solids unit will be used to acquire the data. Cross polarization (CP) and magic angle spinning (MAS) will be applied. c. Magnetic Resonance Imaging (MRI) All the MRI scans will be conducted at the 4.7T/40cm animal MRI facility on campus. Results from all these methodologies will be compiled and compared to ascertain the physical changes occurring to the system as well as the origin of these changes. Bioactives will be identified and quantified using high performance liquid chromatography (HPLC) and mass spectrometry (MS). Bioactives will be analyzed in the ingredients and the developed functional foods to assess stability during processing, as well as following storage. Bioactives will also be analyzed following in vitro model digestion to examine bioaccessibility, and in human samples following ingestion of the functional food to examine bioavailability. HPLC-MS/MS has become the gold standard for quantitative analysis of many vitamins and phytochemicals, especially in biological samples. The Schwartz lab has extensive experience with various phytochemical extraction conditions and quantitative HPLC and MS procedures. The major analytical instruments in the laboratory include: -Three Waters 2690 HPLC systems with photodiode array detectors -Two HPLC systems with ESA eight channel CoulArray electrochemical detectors -Hewlett Packard 1100 Series HPLC with photodiode array detector -Hewlett Packard 1050 Series HPLC with single wavelength detector -A preparatory HPLC with photodiode array detector -UV-VIS scanning spectrophotometer -Waters Acquity UPLC system interfaced with a Quattro Ultima MS-MS - provides quantitative LC/MS/MS capabilities -Alliance 2695 HPLC interfaced to a QTof Premier - provides accurate mass measurements -Agilent 1200 SL RRLC (Rapid Resolution HPLC) interfaced with an AB Sciex QTRAP 5500 - provides high sensitivity quantitative analysis

Progress 10/01/12 to 09/30/17

Outputs
Target Audience:Target audience is composed of consumers seeking functional foods for health promotion, researchers (faculty, students, industry personnel) seeking to better understand how to study functional foods, companies interested in developing and marketing functional foods and educators eager to learn about foods for health Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?All the research coducted in this project were multidiciplinary and therefore afforded the students/staff excellent opportunities to interact with a variety of experts. Additionally, since the developed functional foods were targeted first for clinical trial use and second to potential commercialization, consumer understanding and acceptability of these foods was key. Therefore, students working on this project were exposed to a crop to the clinic to the consumer mindset, a critical component in functional food development. How have the results been disseminated to communities of interest?Through publications, presentations and media exposure What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? Various functional foods (black raspberry, strawberry, grapefruit and green tea confections, soy bread and pretzels were formulated, analyzed and effectively utilized in human clinical trials. Highly acceptable functional foods were developed and showed excellent potential as vehicles for bioactive delivery, shelf stability and overall quality. Successful human clinical trials were conducted with these functional foods resulting in excellent compliance, successful bioactive delivry and variable modulation of bioamarkers. Utilizing this systematic approach to study functional foods has proven more scientifically sound and highly relevant compared to traditional means.

Publications

• Type: Journal Articles Status: Published Year Published: 2016 Citation: 65. Ahn-Jarvis, J.H., Clinton, S. K., Grainger, E. M., Riedl, K.M., Schwartz, S.J., Lee, M-L. T., Cruz-Cano, R., Young, G.S., Lesinski, G.B. and Vodovotz, Y. 2015. Isoflavone pharmacokinetics and metabolism after consumption of a standardized soy and soy-almond bread in men with asymptomatic prostate cancer. Cancer Prevention Research, 8(11)1045-1054.
• Type: Journal Articles Status: Accepted Year Published: 2016 Citation: 66. Lesinski, G. B., Reville, P.K., Mace, T. A., Young, G.S., Ahn-Jarvis, J.,Thomas-Ahner, J., Vodovotz, Y., Ameen, Z., Grainger, E. , Riedl, K, Schwartz, S. and Clinton, S.K. 2015. Consumption of Soy Isoflavone Enriched Bread in Men with Prostate Cancer Is Associated with Reduced Proinflammatory Cytokines and Immunosuppressive Cells. Cancer Prevention Research, 8(11) 1036-1044.
• Type: Journal Articles Status: Accepted Year Published: 2016 Citation: 72. Sapper, T.N., Mah, E., Ahn-Jarvis, J, .McDonald, J.D., Chitchumroonchokchai, C., Reverri E.J. Vodovotz, Y. and Bruno, R.S. 2016. A green tea-containing starch confection increases plasma catechins without protecting against postprandial impairments in vascular function in normoglycemic adults. Food and Function. 7:3843-3853.
• Type: Journal Articles Status: Published Year Published: 2017 Citation: 73. Roberts, K.M., Granger, E.M., Tomas-Ahner, J.M., Hinton, A., Gu, J., Riedl, K., Vodovotz, Y., Abaza, R., Schwartz, S.J. and Clinton, S.K. Application of a low polyphenol or low ellagitannin dietary intervention and its impact on ellagitanin metabolism in men. 2017. Molecular Nutrition and Food Research. 00, 1-13.
• Type: Journal Articles Status: Accepted Year Published: 2017 Citation: 74. Diamond, S., Cotten, B.M., Banh, T., Hsiao, Y-H., Cole, R., Li, J., Simons, C., Bruno, R.S., Belury, MA., and Vodovotz, Y. Raspberry ketone fails to reduce adiposity beyond decreasing food intake in mice fed a high-fat diet. 2017.Food and Function. 8:1512-1518.
• Type: Journal Articles Status: Published Year Published: 2017 Citation: 75. Ahn-Jarvis, J.H, Teegarden M.D., Schwartz, S.J., Lee, K. and Vodovotz, Y. Modulating conversion of isoflavone glycosides to aglycones using crude beta-glycosidase extracts from almonds and processed soy. 2017. Food Chemistry. 237: 685-692.
• Type: Conference Papers and Presentations Status: Published Year Published: 2017 Citation: 111. J, H. Ahn-Jarvis, K, M. Riedl, S, Oghumu, T, J. Knobloch, S. K. Clinton, Y, Vodovotz, S,J. Schwartz, C. M. Weghorst. 2017. Oral Cancer Biomarker Changes in Smoker and Non-Smokers Following Strawberry Intervention American Association of Dental Research
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2017 Citation: M. Weghorst, Y,Vodovotz, and S,J. Schwartz, 2017. Strawberry consumption alters the urinary metabolome of smokers and nonsmokers. OSU Inaugural Conference on Food and Nutritional Metabolomics for Health.
• Type: Conference Papers and Presentations Status: Published Year Published: 2017 Citation: 114. J. H. Ahn-Jarvis, K. M. Riedl, S.e Oghumu, T. J. Knobloch, G. Brock, S., K. Clinton, Y. Vodovotz, S. J. Schwartz, C. M. Weghorst. 2017. Validation of a tobacco smoke exposure gene expression signature and discovery of intraoral metabolite profiles following administration of a strawberry functional confection in smokers and non-smokers. American Association of Cancer Research Annual Meeting

Progress 10/01/15 to 09/30/16

Outputs
Target Audience:Black raspberries (BRB; Rubus occidentalis) have shown anti-cancer activity in preclinical studies and many phytochemicals in BRBs may contribute to the anti-cancer effects. Translation of these findings for human investigation may be enhanced by the development of novel food products that are fully characterized and provide excellent bioavailability of phytochemicals. We completed a phase IItrial of BRB confections as well as a low ellagitanin and low polyphenol diet in prostate cancer individuals. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Two PhD student in food science developed and optimized and analyzed the black raspberry confection working closely with a research scientist. These students also trained 2 undergraduate students in research and product development. This project served as an excellent training opportunity for these students on how to work with fucntional foods and conduct human clinical trials. How have the results been disseminated to communities of interest?Results on the development of the functional foods have been published or are pending publication, presented at National and local meetings as well as used as examples in departmental tours to external stakeholders. The results of the human clinical trial are pending final analysis and will be published. They have been presented at conferences. Confections have been commercialized. What do you plan to do during the next reporting period to accomplish the goals?We are continuing to work with various functional foods specifically those containg blueberries. We will optimize for quality and bioactive delivery prior to conducting relevant human clinical trials.

Impacts
What was accomplished under these goals? Scope: Plant polyphenols are widespread in the American diet, yet estimated intake is uncertain. We examine the application of the Polyphenol Explorer® (PED) 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.

Publications

• Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: Shi, N., Schwartz, S.J., Chen, T. 2016. Black raspberries show potent activity in prevention of experimental swuamous cell esophageal cancer compared to a combination of selective COX-2 and iNOS inhibitors. Presented at The Ohio State University Comprehensive Cancer Center -- James 17th Annual Scientific Meeting. April 22, Columbus, OH.
• Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: Roberts, K.M., Grainger, E.M., Gu, J., Riedl, K.M., Vodovotz, Y., Thomas-Ahner, J.M., Schwartz, S.J., Clinton, S.K. 2016. Ellagitannin metabolites in men on usual diet, a low polyphenol diet, a low ellagitannin diet or a black raspberry food product. Presened at The Ohio State University Comprehensive Cancer Center -- James 17th Annual Scientific Meeting. April 22, Columbus, OH.
• Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: Teegarden, M.D., Cichon, M.J., Cooperstone, J.L., Ahn-Jarvis, J.H., Weghorst, C.M., Vodovotz, Y., Schwartz, S.J. 2016. Strawberry consumption alters the urinary metabolome of smokers and nonsmokers. 12th Annual Conference of the Metabolomics Society, June 27-30, Dublin, Ireland.
• Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: Vodovotz, Y., Ahn-Jarvis, J.H., Gu, J., Riedl, K.M., Niezgoda, M., Weghorst, C.M., Clinton, S., Kumar, P., Yee, L. Belury, M. Schwartz, S.J. 2016. Food-based strategies for cancer prevention: tailoring food vehicles for localized and systemic delivery of food compounds in clinical trials. Presented at The Ohio State University Comprehensive Cancer Center -- James 17th Annual Scientific Meeting. April 22, Columbus, OH.
• Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: Vodovotz, Y., Ahn-Jarvis, J.H., Gu, J., Riedl, K.M., Niezgoda, M., Weghorst, C.M., Kumar, P., Yee, L., Clinton, S.K., Belury, M., Francis, D., Schwartz, S.J. 2016. Food-based strategies for cancer prevention: tailoring food vehicles for localized and systemic delivery of food compounds in clinical trials. Presented at 25th American Institute for Cancer Research Annual Research Conference, November 14-16, North Bethesda, MD.
• Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: Gu, J., Thomas-Ahner, J., Schmidt, N.S., Riedl, K.M., Vodovotz, Y., Schwartz, S.J., Bailey, M.T., Clinton, S.K. 2016. The impact of black raspberry feeding on the colonic microbiome and phytochemical metabolites in mice. Presented at 25th American Institute for Cancer Research Annual Research Conference, November 14-16, North Bethesda, MD.
• Type: Journal Articles Status: Published Year Published: 2016 Citation: Knobloch, T.J., Uhrig, L.K., Pearl, D.K., Casto, B.C., Warner, B.M., Clinton, S.K., Sardo-Molmenti, C.L., Ferguson, J.M., Daly, B.T., Riedl, K., Schwartz, S.J., Vodovotz, Y., Buchta, A.J., Schuller, D.E., Ozer, E., Agrawal, A., Weghorst, C.M. 2016. Suppression of pro-inflammatory and pro-survival biomarkers in oral cancer patients consuming a black raspberry phytochemical-rich troche. Cancer Prev. Res. 9(2):159-71.
• Type: Journal Articles Status: Published Year Published: 2016 Citation: Shi, N., Riedl, K. M., Schwartz, S. J., Zhang, X., Clinton, S. K., Chen, T. 2016. Efficacy comparison of lyophilised black raspberries and combination of celecoxib and PBIT in prevention of carcinogen-induced oesophageal cancer in rats. J. Funct. Foods, 27: 8494.
• Type: Journal Articles Status: Published Year Published: 2016 Citation: Roberts, K.M., Grainger, E.M., Thomas-Ahner, J.M., Hinton, A., Gu, J., Riedl, K., Vodovotz, Y., Abaza, R., Schwartz, S.J., Clinton, S.K. 2016. Application of a low polyphenol or low ellagitannin dietary intervention and its impact on ellagitannin metabolism in men. Mol. Nutr. Food Res. Epub ahead of print.
• Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: Teegarden, M.D., Cichon M.J., Cooperstone, J.L., Ahn-Jarvis, J.H., Weghorst, C.M., Vodovotz, Y., Schwartz, S.J. 2016. Untargeted profiling of the urinary metabolomes of smokers and nonsmokers after a strawberry intervention. Presented at FASEB Experimental Biology Conference. April 2-6, San Diego, CA.

Progress 10/01/14 to 09/30/15

Outputs
Target Audience:Black raspberries (BRB; Rubus occidentalis) have shown anti-cancer activity in preclinical studies and many phytochemicals in BRBs may contribute to the anti-cancer effects. Translation of these findings for human investigation may be enhanced by the development of novel food products that are fully characterized and provide excellent bioavailability of phytochemicals. We completed a phase I trial of three BRB confections (starch-based, pectin and hard candy) at 2 doses. We have worked to commercializethese products to have them available to the public. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?A PhD student in food science developed and optimized the black raspberry confection working closely with a post doctoral fellow and a research scientist. These students also trained 5 undergraduate students in research and product development. This project served as an excellent training opportunity for thesestudents on how to work with fucntional foods and conduct human clinical trials. How have the results been disseminated to communities of interest?Results on the development of the fucntional foods have been published or are pending publication, presented at National and local meetings as well as used as examples in departmental tours to external stakeholders. The results of the human clinical trial are pending final analysis and will be published. They have been presented at conferences. Various avenues are being pursued in commercializing th confections. What do you plan to do during the next reporting period to accomplish the goals?We are continuing to work with various functional foods specifically those containg grapefruit. We will optimize for quality and bioactive delivery prior to conducting relevant human clinical trials.

Impacts
What was accomplished under these goals? Oral cancer affects nearly 300,000 Americans each year and is a serious health concern due to its poor prognosis and high recurrence rate. We have developed a food-based strategy for oral cancer prevention which allows excellent long-term adherence and efficacy. Three amorphous solids (glassy, elastic, and viscous) containing black raspberry (BRB) bioactive compounds were evaluated in a confectionary system. As release properties between the amorphous forms vary, the interaction between the oral mucosa and food vehicle/bioactives will translate into unique absorption patterns at the cellular level. Objective: To select an optimal amorphous functional confection for delivery of BRB bioactive compounds as measured by dietary compliance as well as absorption and metabolism of BRB compounds using biological measures (saliva, buccal, and urine). Methods: A four week, phase I, randomized, parallel study design with 60 non-smoking adults (30 men and 30 women). Three amorphous forms having three different release rates (prolonged, intermediate, and rapid) and at two doses (4 and 8 g of BRB/day) were used. Sensory evaluation, dietary compliance, and salivary kinetics were evaluated. HPLC with Tandem MS/MS was used to quantify urolithin profiles. Results: A 9-point Hedonic Scale indicated amorphous confections were acceptable with the viscous amorphous (starch-based) confection form being preferred. Adherence to BRB confection intervention (1 or 2 servings of BRB) was 94 ± 2%. Toxicities to BRB intervention was limited to a grade I toxicity (NIH criteria). Oral residence time was 74% longer and saliva volume was 42% greater with glassy than the other two amorphous forms. Urolithin A (22.29±5.16 nmol/24hr) and C (0.43±0.03 nmol/24hr) increased significantly after BRB intervention compared to ellagitannins-free diet with the greatest quantity of urolithin A excretion after glassy confection intervention. Conclusions: Three amorphous confectionary forms had excellent compliance and were effective delivery vehicles of BRB compounds. Amorphous confectionary forms were designed to modulate oral residence time of BRB compounds which was shown to impact BRB absorption and metabolism

Publications

• Type: Journal Articles Status: Published Year Published: 2015 Citation: Gu, J., Ahn-Jarvis, J.H. and Vodovotz, Y. 2015. Development and characterization of different black raspberry confection matrices designed for delivery of phytochemicals. Journal of Food Science. 80(3): E610-E618.
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2015 Citation: Gu, J., Roberts, K.M., Riedl, K.M., Grainger, E.M., Ahn-Jarvis, J.H., Thomas-Ahner, J.M., Schwartz, S.J., Vodovotz, Y., Clinton, S.K. 2014. Impact of novel black raspberry food products for cancer prevention on ellagitannin metabolites in men. Presented at The American Institute for Cancer Research Annual Research Conference. October 29-31, Washington, D.C.

Progress 10/01/13 to 09/30/14

Outputs
Target Audience: Background: Black raspberries (BRB; Rubus occidentalis) have shown anti-cancer activity in preclinical studies and many phytochemicals in BRBs may contribute to the anti-cancer effects. Translation of these findings for human investigation may be enhanced by the development of novel food products that are fully characterized and provide excellent bioavailability of phytochemicals. We completed a phase II trial of two BRB food products (nectar or gummy-confection), each at two doses, in men undergoing prostatectomy. Methods: Men with prostate cancer, choosing prostatectomy for curative therapy, were randomized to one of 7 groups (n=8 per group) for 4 weeks prior to surgery: (1) usual diet; (2) controlled polyphenol diet, (3) controlled ellagitannin diet, (4) low-dose nectar, (5) high-dose nectar, (6) low-dose confection, or (7) or high-dose confection. Groups 4-7 also consumed a controlled ellagitannin diet. Diet records were analyzed in the Polyphenol Explorer Database®. Urinary ellagitannin metabolites were quantified using HPLC-MS/MS. Results: Confections contain 6.8 mg/g of anthocyanins and 706.7 µg/g ellagitannins after processing. High-dose nectars contain 1.6 mg/g of anthocyanins and 226.6 µg/g. Compliance with food products was >98% of product consumed over 22.9 days. The controlled polyphenol diet resulted in a 50% reduction of estimated polyphenol intake compared to a regular diet. A 100% reduction of dietary ellagitannins was achieved with a controlled ellagitannin diet. Ellagitannin urinary metabolites were significantly reduced by controlled polyphenol and ellagitannin diets. Dose-dependent increases in urinary ellagitannin metabolites for both food products were observed. Conclusion: Fully characterized BRB food products with outstanding compliance have been developed for human studies relevant to cancer prevention. Ellagitannin metabolite signatures, influenced by host genetics and the microbiome, illustrate a clear dose response and variation by BRB food product supporting the use of these food products for future cancer prevention studies. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? A PhD student in food science developed and optimized the functional foods and worked closely with a graduate student in Human Nutrition who conducted the human clinical trial. This project served as an excellent training opportunity for these students on how to work with fucntional foods and conduct human clinical trials. How have the results been disseminated to communities of interest? Results on the development of the fucntional foods have been published or are pending publication, presented at National and local meetings as well as used as examples in departmental tours to external stakeholders. The results of the human clinical trial are pending final analysis and will be published. They have been presented at conferences. What do you plan to do during the next reporting period to accomplish the goals? We are continuing to work with various functional foods containg strawberry, soy -safflower oil and grapefruit. We will optimize for quality and bioactive delivery prior to conducting relevant human clinical trials.

Impacts
What was accomplished under these goals? Functional foods were developed and optimized for delivery of black raspberry bioactives. Stability of the bioactives after porcessing were confirmed in these foods. A human clinical trial utilizing these deveolped foods was conducted in prostate cancer patients to assess the uptake of these bioctives.Ellagitannin metabolite signatures, influenced by host genetics and the microbiome, illustrate a clear dose response and variation by BRB food product supporting the use of these food products for future cancer prevention studies. This data was instrumental in acquisition of a large NIH funded U01 grant for further testing of the black raspberry foods for oral health.

Publications

• Type: Journal Articles Status: Published Year Published: 2014 Citation: Gu, J., Ahn-Jarvis, J.H., Riedl, K.M., Schwartz, S.J., Clinton, S.K. and Vodovotz, Y. 2014. Characterization of black raspberry functional food products for cancer prevention trials. Journal of Agricultural and Food Chemistry. 62(18): 3997-4006.
• Type: Journal Articles Status: Published Year Published: 2014 Citation: Mace, T.A., King, S.A., Ameen, Z., Elnaggar, O., Young, G., Riedl, K.M., Schwartz, S.J., Clinton, S.K., Knobloch, T.J., Weghorst, C.M., Lesinski, G.B. 2014. Bioactive compounds or metabolites from black raspberries modulate T lymphocyte proliferation, myeloid cell differentiation and Jak/STAT signaling. Cancer Immunol. Immunother. 2014 Sep;63(9):889-900.
• Type: Journal Articles Status: Under Review Year Published: 2014 Citation: Gu, J., Ahn-Jarvis, J.H. and Vodovotz, Y. Development and characterization of different black raspberry confection matrices designed for delivery of phytochemicals. Journal of Food Science.

Progress 10/01/12 to 09/30/13

Outputs
Target Audience: Consumers of functional foods and snacks are the target audience for this project. Additionally, educators and scientists that are curious about the role of foods in health. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Training of a PhD student Training of 8 undergraduate students on confection making How have the results been disseminated to communities of interest? Publications There has been several media reports Presentations at national (Annual Research Conference on Food, Nutrition, Physical Activity and Cancer; Institute of Food Technologists Annual Meeting; International Berry Health Benefits Symposium) and local (OSU Comprehensive Cancer Center – James Annual Scientific Meeting; Ohio Agricultural Research and Development Annual Research Conference) meetings. What do you plan to do during the next reporting period to accomplish the goals? Continue working on confections and nectar for other diseases including oral cancer. Formulate confections from other plant ingrdients including green tea and grapefruit for various diseases

Impacts
What was accomplished under these goals? Our team is designing and fully characterizing black raspberries (BRB) food products suitable for long-term cancer prevention studies. The processing, scale up and storage effect on the consistency, quality, bioactive stability and sensory acceptability of two BRB delivery systems of varying matrices is presented. BRB dosage, pH, water activity and texture were consistent in the scale-up production. Confections retained > 90% of anthocyanins and ellagitannin after processing. Nectars had > 69% of anthocyanins and > 66% of ellagitannin retention which varied with BRB dosage due to the processing difference. Texture remained unchanged during storage. BRB products consumed in a prostate cancer clinical trial were well accepted in sensory tests. Thus, this study demonstrates that two different BRB foods can be formulated to meet quality standards with a consistent bioactive pattern and successfully scaled up for a large human clinical trial focusing on cancer risk and other health outcomes.

Publications

• Type: Journal Articles Status: Submitted Year Published: 2014 Citation: Gu, J., Ahn-Jarvis, J.H., Riedl, K.M., Schwartz, S.J., Clinton, S.K. and Yael Vodovotz. Characterization of black raspberry functional food products for cancer prevention trials. Journal of Agricultural and Food Chemistry
• Type: Journal Articles Status: Accepted Year Published: 2014 Citation: Fisher, E.L., Ahn-Jarvis, J., Gu, J., Weghorst, C.M. and Vodovotz, Y. Assessment of physicochemical properties, dissolution kinetics and storage stability of a novel strawberry confection designed for delivery of chemopreventive agents. Food Structure
• Type: Journal Articles Status: Published Year Published: 2013 Citation: Sessler, T., Weiss, J. and Vodovotz, Y. Influence of pH and soy protein isolate addition on the physicochemical properties of functional grape pectin confections. Food Hydrocolloids, 32:294-302.