NUTRIENT BIOAVAILABILITY--PHYTONUTRIENTS AND BEYOND

• Sponsoring Institution: National Institute of Food and Agriculture
• Project Status: COMPLETE
• Funding Source: HATCH
• Reporting Frequency: Annual
• Accession No.: 0220098
• Multistate No.: W-2002
• Project Start Date: Jun 5, 2009
• Project End Date: Sep 30, 2013
• Program Code: [(N/A)]- (N/A)

Recipient Organization
PURDUE UNIVERSITY
(N/A)
WEST LAFAYETTE,IN 47907

Performing Department
Nutrition Science

Non Technical Summary
Diet, including specific nutrients and bioactive food components, plays a vital role in improving health and reducing risk for developmental and chronic disease. This collaborative research project brings together scientists with broad nutrition science expertise and experience to test hypotheses that ultimately will enhance the well-being of the population through reduced risk and incidence of several chronic diseases including cancer, obesity and osteoporosis. We plan to advance the understanding of the requirements for nutrients and bioactive food components in maintaining optimal health and to translate our findings to public health practice. There are numerous chronic diseases and developmental disorders for which risk may be modified in relation to exposure to bioactive dietary constituents. However, for the purpose of this collaborative research project the investigators are targeting cancer, bone health, obesity, birth defects and cognitive function and neurological disease. These diseases, and the associated interactions with nutrients and bioactive food components, are complex and require diverse approaches to advance knowledge that will lead to effective preventive and therapeutic strategies. Outputs: Additional collaborative projects Research data Peer-reviewed publications Presentations and posters at scientific meetings E-files and web-based applications Outreach presentations or publications for non-scientific organizations Outcomes or projected Impacts: Increased knowledge of the bioactivity of nutrients and other food components and their underlying protective mechanisms Increased knowledge of environmental and genetic determinants of the bioavailability of nutrients and other food components Development and publication of models for determining bioactivity and bioavailability of nutrients and other bioactive food components

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
702	5010	1010	100%

Knowledge Area
702 - Requirements and Function of Nutrients and Other Food Components;

Subject Of Investigation
5010 - Food;

Field Of Science
1010 - Nutrition and metabolism;

Keywords

nutrient

bioavailability

phytonutrients

calcium

bone

Goals / Objectives
Determine the bioavailability (absorption, distribution, metabolism, elimination) of nutrients and other food components and their environmental and genetic determinants Evaluate the bioactivity of nutrients and other food components in order to elucidate their underlying protective mechanisms.

Project Methods
Absorption and Metabolism. W-2002 scientists have developed state of the art techniques for assessing all components of bioavailability for several nutrients and for bone turnover. Novel methodologies include use of rare and stable isotopes for calcium and 14C labeled bioactives. Modeling and model development. Kinetic modeling and compartmental analysis will be used to assess vitamin, mineral and bioactive compound turnover rates, pool sizes, and metabolism. Facile methods for assessing nutrient status and bioavailability are being developed. Equations for simple methods to predict true absorption of nutrients such as Ca against full kinetic models are being developed. Evaluate bioactivity in bone health. The expected endpoints resulting from the multidisciplinary, collaborative interactions among the W2002 investigators include establishment of models of bioavailability for key nutrients involved in optimal health, including calcium, vitamin D, and phytochemicals such as isoflavones and peer reveiwed publications.

Progress 06/05/09 to 09/30/13

Outputs
Target Audience: The main audience for this project are the research divisions of the food industry. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? A post-doctoral research associate has had the opportunity to develop research skills by coordinating the potassium study. Graduate students have used these projects to develop their thesis and thus receive their degrees which will enable them to further their professional careers. How have the results been disseminated to communities of interest? Peer reviewed publications are being prepared . Presentations and posters have been presented at scientific meetings. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? Through the collaboration of a group of scientists that have a broad expertise in nutrition science and chronic disease, this project will test hypotheses that have the potential to reduce the risk of several chronic diseases. Calcium is a major nutrient that is critical for skeletal development . Several prebiotics have the potential to increase calcium absorption if incorporated in the diet. Wehave shown that under controlled dietary conditions soluble corn fiber increases calcium absorption and retention.Our recent study testedthe same hypothesis with adolescent girls under free living conditions and a self selected diet using three different doses (0, 10, and 20 g/d) in a cross over design.The highest level of fiber resulted in a similar increase in calcium absorption to the controlled condition.Soluble corn fiber can be used as a food ingredient to increase calcium absorption leading to improvements in skeletal health. Objective 1: Determine the bioavailability (absorption, distribution, metabolism, elimination of nutrients and other food components and their environmental and genetic determinants. The free living study in teen girls to test the effect of soluble corn fiber on calcium absorption has been completed. Preparation of a publication is in progress. The same product is being tested in post menopausal women using 41Ca technology.. Objective 2: Evaluate the bioactivity of nutrients and other food components in order to elucidate their underlying protective mechanisms. A study is underway to evaluate the bioavailability of potassium from food sources (potatoes) and from supplements in adults consuming a controlled diet over a 6 day period . Blood pressure is being monitored. A study evaluating the effect of hesperidin with or without a calcium supplement in post menopausal women has been completed. Data analysis and publication preparation is in progress.

Publications

• Type: Journal Articles Status: Published Year Published: 2013 Citation: Weaver, CM. Potassium and health, Supplement: White vegetables: A forgotten source of nutrients. Adv Nutr. 4: 318S-326S, 2013
• Type: Book Chapters Status: Published Year Published: 2013 Citation: Weaver CM, Hohman EE. Comparison of Natural Products for Effect on Bone Balance. Ch. 14 In: Nutritional Influences of Bone Health. International Congress Series Proceedings of the 8th International Symposium on Nutritional Aspects of Osteoporosis, Lausanne, Switzerland. Burckhardt P, Dawson-Hughes, Weaver CM, eds, Springer, 147-156, 2013
• Type: Book Chapters Status: Published Year Published: 2013 Citation: Alekel LD, Weaver CM, Ronis MJJ Ch. 26 Nutritional Influences on Bone Health and Overview of Methods, In: Bioactive Food as Dietary Interventions for the Aging Populations. Elsevier Inc. London, UK. pp 357-370, 2013.
• Type: Journal Articles Status: Published Year Published: 2013 Citation: Simon RR, Borzellaeca JF, DeLuca HF, Weaver CM. Safety assessment of the post-harvest treatment of button mushrooms (Agaricus bisporus) using ultraviolet light. Food Chem Toxicol 56:278-289, 2013.
• Type: Journal Articles Status: Published Year Published: 2013 Citation: Shaltiel G, Bar-David E, Meiron OE, Waltman E, Schechter A, Afialo ED, Stepensky D, Berman A, Martin BR, Weaver CM, Sagi A. Bone loss prevention in ovariectomized rats using stable amorphous calcium carbonate. Health, Special Issue: New and Emerging Therapies for Osteoporosis. Health 5(7A2): 18-29, 2013.
• Type: Book Chapters Status: Published Year Published: 2013 Citation: Whisner CM, Weaver CM. Galacto-oligosaccharides: Prebiotic Effects on Calcium Absorption and Bone Health. Ch. 30 In: Nutritional Influences of Bone Health. International Congress Series Proceedings of the 8th International Symposium on Nutritional Aspects of Osteoporosis, Lausanne, Switzerland. Burckhardt P, Dawson-Hughes B, Weaver CM, eds, Springer pp. 315-324, 2013.
• Type: Journal Articles Status: Published Year Published: 2013 Citation: miller JJ, Hue SK, Jackson GS, Clark SP, Einstein J, Weaver CM, Bhattacharyya MH. Calcium isolation from large-volume human urine samples for 41Ca analysis by accelerator mass spectrometry. Appl Radiat Isot 78: 57-61, 2013.

Progress 10/01/11 to 09/30/12

Outputs
OUTPUTS: We are conducting two clinical studies on the effect of a prebiotic soluble corn fiber, on calcium absorption and microbiota profiles one in pubertal girls and one in postmenopausal women. This builds on our efficacy study in boys and girls that showed 12% improvement in calcium absorption. This completed study used a controlled diet, whereas the ongoing studies are in free-living subjects on self-selected diets. We are also studying the ability of hesperidin, a bioactive compound in oranges, to reduce bone loss in postmenopausal women. PARTICIPANTS: Studies were funded and products provided by Tate and Lyle and Nestle. TARGET AUDIENCES: Food industry researchers. PROJECT MODIFICATIONS: Not relevant to this project.

Impacts
Calcium absorption was improved by two prebiotics, soluble corn fiber and GOS, in early pubertal to pubertal children. As calcium intakes are below recommendation levels, improving calcium utilization through feeding prebiotics could be impactful for building peak bone mass. Determining whether this effect is true in a free-living population is important to establish effectiveness of a public health recommendation.

Publications

• Legette LL, Lee WH, Martin BR, Story JA, Campbell JK, Weaver CM. Enhanced magnesium absorption and inulin-based fibers exert chronic effects on calcium utilization in a postmenopausal rodent model. J Food Sci 77:89-94, 2012.
• Adamec J, Kannasch A, Huang J, Hohman E, Fleet JC, Peacock M, Ferruzzi MG, Martin B, Weaver CM. Development and optimization of an LC-MS/MS based method for simultaneous quantification of vitamin D2, vitamin D3, 24-hydroxyvitamin D2 and 25-hydroxyvitamin D3. J Sep Sci. 34(1): 11-20, 2011.
• Weaver CM, Martin BR, Nakatsu CH, Armstrong AP, Clavijo A, McCabe LD, McCabe GP, Duignan S, Schoterman MG, van den Heuvel EG. Galactooligosaccharides improve mineral absorption and bone properties in growing rats through gut fermentation. J Agric Food Chem. 59(12): 6501-10, 2011.
• Legette LL, Lee WH, Martin BR, Story JA, Arabshahi A, Barnes S, Weaver CM. Genistein, a phytoestrogen, improves total cholesterol, and Synergy, a prebiotic, improves calcium utilization, but there were no synergistic effects. Menopause 18(8):923-31, 2011.
• Zhang Q, Wastney ME, Rosen CJ, Beamer WG, Weaver, CM. Insulin-like growth factor I increases bone calcium accumulation only during rapid growth in female rats. J Nutr. 141: 2010-6, 2011. Doi: 10.395/jn111.142679
• Elble AE, Hill KM, Park CY, Martin BR, Peacock M, Weaver CM. Effect of calcium carbonate particle size on absorption and retention in adolescent girls. J Am Col Nutr 30:171-177, 2011.
• Hill KM, Braun MM, Egan KA, Martin BR, McCabe LD, Peacock M, McCabe GP, Weaver CM. Obesity augments calcium-induced increases in skeletal calcium retention in adolescents. J Clin Endocrinol Metab 96:2171-7, 2011.
• Cheong J, Gunaratna N, McCabe G, Jackson G, Kempa-Steczko A, Weaver C. Bone seeking labels as markers for bone turnover: Validation of urinary excretion in rats. Osteoporosis Intl. 22:153-157, 2011.
• Hohman EE, Martin BR, Lachcik PJ, Gordon DT, Fleet JC, Weaver CM. Bioavailability and Efficacy of Vitamin D2 from UV -irradiated yeast in growing, Vitamin D-deficient rats. Agri Food Chem 56:2341-2346, 2011.
• Lee W-H, Wastney M E, Jackson GS, Martin BR, Weaver CM. Interpretation of 41Ca data using compartmental modeling in post-menopausal women. Anal Bioanal Chem. 399:1613-1622, 2011.
• Alekel LD, Weaver CM, Ronis MJJ. Bioactive Food as Dietary Interventions for Arthritis and Related Inflammatory Diseases. In: Nutritional Influences on Bone Health and Overview of Methods, Watson RR, ed. Elsevier Limited. Oxford, United Kingdom. Pp., 2013.
• Weaver CM, Alekel DL, Ward WE, Ronis MJ. Flavonoid intake and bone health. J Nutr Gerontol Geriatr 31-239-253, 2012.
• Barnes S, Prasain J, D'Alessandro T, Arabshahi A, Botting N, Lila MA, Jackson G, Janle EM, Weaver CM. The metabolism and analysis of isoflavones and other dietary polyphenols in food and biological systems. Food Funct. 2(5):235-44, 2011.
• Park, CY, Weaver, CM. Calcium and Bone Health: Influence of Prebiotics. Functional Food Reviews 3:62-72, 2011.
• NAMS 2011 Isoflavone Report. The role of soy isoflavones in menopausal health: report of The North American Menopausa Society/Wulf H. Utian Translational Science Symposium in Chicago, IL Menopause 18(7):1-22 2011.

Progress 10/01/10 to 09/30/11

Outputs
OUTPUTS: We completed two clinical studies on the effect of prebiotics on calcium absorption and microbiota profiles. We used our rat model of urinary appearance of calcium tracers incorporated into bone as an indicator of calcium balance/bone turnover to screen various dietary supplements. PARTICIPANTS: Studies were funded and products provided by Tate and Lyle and Friesland. TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
Calcium absorption was improved by soluble corn fiber and GOS in early pubertal to pubertal children. As calcium intakes are below recommendation levels, improving calcium utilization through feeding prebiotics could be impactful for building peak bone mass.

Publications

• Martin BR, Braun MM, Wigertz K, Bryant R, Zhao Y, Lee WH, Kempa-Steczko A, Weaver CM. (2010) Fructo-oligosaccharides and calcium absorption and retention in adolescent girls. J Am Coll Nutr 29:382-386.
• Weaver CM, Martin BR, Story JA, Hutchinson I, Sanders L. (2010)Novel fibers increase bone calcium content and strength beyond efficiency of large intestine fermentation. J Ag Food Chem 58:8952-8957.
• Park, Clara Y, Weaver, Connie M. (2011) Calcium and bone health: Influence of prebiotics. Functional Food Reviews 3:62-72.
• Reinwald S, Akabas SR, Weaver CM. (2010) Whole versus the piecemeal approach to evaluating soy. J. Nutr 140:2335S-2343S.
• Reinwald S, Weaver CM. (2010) Soy components vs. whole soy: Are we betting our bones on a long shot J Nutr 140:2312S-17S.
• Weaver CM, Legette LL. (2010) Equol, via dietary sources or intestinal production, may ameliorate estrogen deficiency induced bone loss. J Nutr 140:1377S-79S.
• Elble AE, Hill KM, Park CY, Martin BR, Peacock M, Weaver CM.(2011) Effect of calcium carbonate particle size on absorption and retention in adolescent girls. J Am Col Nutr 30:171-177
• Hohman EE, Martin BR, Lachcik PJ, Gordon DT, Fleet JC, Weaver CM. (2011) Bioavailability and efficacy of vitamin D2 from UV-irradiated yeast in growing, vitamin D-deficient rats. Agri Food Chem 56:2341-2346.

Progress 10/01/09 to 09/30/10

Outputs
OUTPUTS: We conducted several studies in animal models and humans to investigate the effect of dietary constituents thought to be beneficial for bone health by either enhancing calcium absorption or suppressing bone resorption. In both growing rats and humans we tested the effect of fibers including GOS and FOS on calcium absorption. We continued our studies of the effects of phytoestrogens on preventing bone loss in an OVX rat model and the effect of equol producing status on bone resorption in response to soy in postmenopausal women. PARTICIPANTS: Nothing significant to report during this reporting period. TARGET AUDIENCES: Bone health and nutrition scientists PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
Prebiotics are being marketed for their ability to enhance calcium absorption and phytoestrogens for their ability to prevent bone loss in postmenopausal women. We screened several prebiotic fibers and found the most effective ones for calcium absorption in rats decreased cecal pH and increased cecal content and wall weight, consistent with lower gut fermentation. GOS feeding increased calcium absorption and proportion of secal bifido bacteria in rats, but at the levels fed to early adolescent girls did not increase calcium absorption. Equol status did not affect bone resorption in response to soy feeding in postmenopausal women.

Publications

• Hill, Katherine. Predictors of skeletal calcium accretion in adolescents from pooled metabolic balance studies. PhD. Thesis, 2010.
• Legette, LeeCole. Effect of soy isoflavones and Prebiotics on bone metabolism in a postmenopausal rodent model. PhD. Thesis, 2010.
• Reinwald, S., Mayer, L.P., Hoyer, P.B., Turner, C.H., Barnes, S., Weaver, C.M. A longitudinal study of the effect of genistein on bone in two different murine models of diminished estrogen-poducing capacity. J. Osteoporosis. 2010 DOI: 10.4061/2010/145170.
• Cheong J, Gunaratna N, McCabe G, Jackson G, Kempa-Steczko A, Weaver C. Bone seeking labels as markers for bone turnover: Validation of urinary excretion in rats. Osteoporosis Intl. 2010 DOI: 10.1007/s00198-010-1281-7.
• Janle E, Lila MA, Grannon, MD, Wood L, Higgins A, Yousef GG, Rogers RB, Kim H, Jackson GS, and Weaver C. Method for evaluating the potential of 14C labeled plant polyphenols to cross the blood-brain barrier using accelerator mass spectrometry. Nuclear Instruments and Methods in Physics Research B, 268:1313-1316, 2010.
• Mun JG, Grannan MD, Lachcik PJ, Rogers RB, Yousef GG, Grace MH, Janle EM, Wu QL, Simon JE, Weaver CM, Lila MA. Tracking deposition of a 14C-radiolabeled kudzu hairy root-derived isoflavone-rich fraction into bone. Exp. Biol. Med 235:1224-1235, 2010.
• Janle EM, Lila MA, Grannan M, Wood L, Higgins A, Yousef GG, Rogers RB, Kim H, Jackson GS, Ho L, Weaver CM. Pharmacokinetics and tissues distribution of 14C labeled grape polyphenols in the periphery and the central nervous system following oral administration. J Med Food 13(4)926-33, 2010.
• Klein MA, Nahin RL, Messina MJ, Rader JI, Thompson LU, Badger TM, Dwyer JT, Kim YS, Pontzer CH, Starke-Reed PE, and Weaver C. Guidance from an NIH Workshop on Designing, Implementing, and Reporting Clinical Studies of Soy Interventions. J Nutr 140:1192S-1204S, 2010. doi:10.3945/jn.110.121830
• Mun JG, Grannan M, Lachcik P, Reppert A, Yousef GG, Rogers RB, Janle EM, Weaver CM, Lila MA. Metabolic tracking of 14C-labeled isoflavones. Br J Nutr 9:1-8, 2009.
• Ferruzzi MG, Lobo JK, Janle E, Cooper B, Simon JE, Wu Q-L, Welch C, Ho L, Weaver C, Pasinetti GM. Bioavailability of gallic acid and catechins from grape seed polyphenol extract is improved by repeated dosing in rats: implications for treatment of Alzheimer's Disease. J Alzheimers Dis 18:113-24, 2009.