Annual/Termination Reports:

[05/01/2003] [11/30/2004] [01/31/2007] [04/28/2007] [12/20/2007]

Report Information

Participants

Winzerling, Joy (jwinzerl@ag.arizona.edu) - University of Arizona; Shane, Barry (bandie@socrates.berkeley.edu) - University of California, Berkeley; Clifford, Andrew (ajclifford@ucdavis.edu) - University of California, Davis; Weaver, Connie (weavercm@cfs.purdue.edu) - Purdue University; Medeiros, Denis (medeiros@ksu.edu) - Kansas State University; Bennink, Maurice (mbennink@msu.edu) - Michigan State University; Bock, Ann (abock@soil-physics.nmsu.edu) - New Mexico State University; Manore, Melinda (melinda.manore@oregonstate.edu) - Oregon State University; Koo, Sung (sung.koo@uconn.edu) - University of Connecticut; Bray, Tammy (Tammy.Bray@oregonstate.edu) - Oregon State University; Mathias, Melvin (mmathias@reeusda.gov) - CSREES; Susan Welsh - CSREES; Etta Saltos - CSREES

Brief Summary of Minutes

http://soil-physics.nmsu.edu/marbock/W1002/index.html

Accomplishments

Keys to prevention of osteoporosis which is one of the leading disabling diseases in the United States are maximizing peak bone mass during growth and minimizing bone loss after menopause. Intake of adequate calcium that can be absorbed and utilized is critical to bone health across the lifespan. Estrogen, which diminishes following menopause is also important Because of both of these issues there is increasing interest in the bioavailability of various fortificants and alternatives to estrogen therapy. Evaluating calcium salts used to fortify foods for bioavailability is important for meeting calcium requirements of persons who do not consume adequate amounts of dairy products which are one of the most bioavailable sources of calcium in the human diet. Results indicate that salts currently being used to fortify cereal and beverage products are absorbed as well as traditional calcium sources. Other research has indicated that rat bone morphology, strength and density are compromised by iron deficiency and exacerbated by calcium restriction. Both iron deficiency and below recommended levels of calcium intake are significant health issues in some segments of the American population. Both are problems in the adolescent population which is of concern since this is the time when most of the bone mass is attained.<br /> <br><br /> <br>There is much interest in antioxidants because of the potential that they decrease the risk of developing some of the leading causes of death in the United States. One antioxidant of interest is B carotene and its ability to yield bioactive retinoids. Results indicate bioavailability of B carotene was 55%. It was also noted that the vitamin A activity of B carotene, even under controlled conditions, was low and variable. Such information is important for researchers who are investigating the effects of B carotene in lowering the risk of developing various conditions like cancer and cardiovascular disease.<br /> <br> <br /> <br>Foods with antioxidant properties are also of interest. One is tea, especially green tea. Results from one study indicated that a decoction from green tea was effective in significantly reducing DNA damage in a Caco-2 cell line caused by the oxidizing agent used.<br /> <br><br /> <br>One of the other objectives of this project is the development, refinement and testing of methodologies to assess bioavailability of nutrients and other compounds being tested. An acid extraction protocol coupled to an internally standardized gas chromatography with mass-selective detection was developed to assay total folate in whole blood using common chemicals. In another case, a new sensitive method for measuring bone resorption employing a long-lived isotopic tracer of calcium and accelerator mass spectrometry is being used in post menopausal women to ascertain the efficacy of phytoestrogens in inhibiting bone resorption.<br /> <br><br /> <br>To provide outreach, especially to the scientific community that has limited background and/or resources related to bioavailability research, a website for the W 1002 project is being developed. The initial components of the website can be accessed at http://soil-physics.nmsu.edu/marbock/index.html

Publications

Dueker, SR, Lin Y, Jones AD, Mercer R, Fabbro E, Miller JW Green R and Cliford AJ. Determination of blood folate using acid extraction and internaly standardized gas chromatography-mass spectrometry detection. Anal Biochem 2002, 283:266-275.<br /> <br><br /> <br>Hickenbottom SJ, Follett JR, Lin Y, Dueker SR, Burri BJ, Neidlinger TR and Clifford AJ. Variability in conversion of B carotene to vitamin A in mean measured using double-tracer study design. AJCN 2002, 75:900-907.<br /> <br><br /> <br>Lin Y, Dueker SR, Jones AD and Clifford AJ. A parallel processing SPE protocol for the determination of whole blood folate. Anal Biochem 2002, 301:14-20.<br /> <br><br /> <br>Lunetta JM, Zulim RA, Dueker SR, Lin Y, Flaig V, Schneider PD, Wolfe BM and Clifford AJ. Methods for the simultaneous determination of retinol and B carotene concentration in human tissue and plasma. Anal Biochem 2002, 304:100-109.<br /> <br><br /> <br>Hickenbottom SJ, Lemke SE, Dueker SR, Lin Y, Follett JR, Carkeet C, Buchholz BA, Vogel JS and Clifford AJ. Dual isotope test or assessing B carotene cleavage to vitamin A in humans. EJCN 2002, 41:141-147.<br /> <br><br /> <br>Ebeler SE, Brenneman CA, Kim GS, Jewell WT, Webb MR, Chacon-Rodriguez L, MacDonald E, Cramer AC, Levi A, Islas A, Kraus A, Hinrichs SH and Clifford AJ. Dietary catechin and tumor onset in a transgenic mouse model AJCN 2002, 76:865-872.<br /> <br><br /> <br>Mueller HG, Su CL, Dueker SR, Follett JR, Lin Y, Clifford AJ, Buchholz BA and Vogel JS. Semiparmetric modeling of labeled cell kinetics with application to isotope labeling of erythrocytes. Biomet 2002, 58:232-239.<br /> <br><br /> <br>Kway H, Hansen CM, Leklem JE Hardin K and Shultz TD. Improved vitamin B6 status is positively related to lymphocyte proliferation in young women consuming a controlled diet. J Nutr 2002 132:3308-3313.<br /> <br><br /> <br>Medeiros DM, Plattner A, Jennings D and Stoecker B. Bone morphology, strength and density are compromised in iron deficient rats and exacerbated by calcium restriction. J Nutr 2002 132:3135-3141.<br /> <br><br /> <br>Martin BR, Weaver CM, Heaney RP, Packard PT and Smith DL. Calcium absorption rom three salts and CaSO4-fortified bread in premenopausal women. J Ag Food Chem 2002, 50(13):3874-3876.<br /> <br><br /> <br>Weaver CM, Martin BR, Costa, NMB, Saleeb FZ and Huth PJ. Absorption of calcium fumarate salts is equivalent to other calcium salts when measured in the rat model. J Ag Food Chem 2002, 50:4974-4975.<br /> <br><br /> <br>Weaver CM and Liebman M. Biomarkers of bone health appropriate for evaluating functional foods designed to reduce risk of osteoporosis. Br J Nutr 2002, 88(2):S225-S2232.

Impact Statements

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Report Information

Participants

Tammy Bray (Admin. Advisor), Joy Winzerling (AZ), Barry Shane (CA-B), Richard Clark (CT), Connie Weaver (IN), Denis Medeiros (KS), Judy Driskell (NE), Emily Ho (OR, application pending for joining group), and Barbara Stoecker (OK, interested in joining group).

Brief Summary of Minutes

Accomplishments

W-1002 Annual Report 2004<br /> <br /> <br /> University of California-Davis and University of California-Berkeley: Cellular, metabolic and kinetic effects of genetic polymorphisms on folate metabolism. The Shane laboratory (Berkeley) has continued with studies on folate metabolism of common human genetic polymorphisms that have been shown to influence disease risk. They have developed additional genetic models in mice to mimic the effects of how these polymorphisms influence folate metabolism and development. These new animal models have gene interruptions that disturb mitochondrial folate metabolism and histone methylation, a process involved in regulation of gene expression. They also continue the development of mass spectrometry methods for studying one carbon metabolic fluxes and DNA methylation to allow the study of how nutritional status influences these processes. They have measured one carbon metabolic fluxes, homocysteine remethylation, and DNA methylation in some of the mouse genetic models. Available data indicate that one carbon fluxes are highly influenced by folate and methionine status, and that the influence of genetic variants in folate enzymes on one carbon metabolism is also dependent on nutritional status. They continue to evaluate genetic risk factors for neural tube defects. The genetic and cellular work with the animal models is complemented by the work at the Clifford laboratory (Davis) on kinetic modeling of folate in humans. They have constructed the first kinetic model of the behavior of folate metabolism as it might occur in vivo in humans. They discovered that folate absorption, bile folate flux, and body folate stores are larger than prior estimates. Marrow folate uptake and pteroylpolyglutamate synthesis, recycling, and catabolism are saturable processes. Visceral pteroylpolyglutamate is an immediate precursor of plasma p-aminobenzoylglutamate. The model is a working hypothesis with derived features that are explicitly model-dependent. This model successfully quantified folate metabolism as it might occur in vivo in humans. Further testing is underway. Outcome: In order for information on genetic polymorphisms to be useful in determining disease risk, the changes in folate metabolism at the both the cellular and whole body levels for a given polymorphism must be evaluated. These projects, taken together, provide information on this full spectrum. Impact: The results of these studies, taken together, will provide information on how specific polymorphisms of genes involved in folate metabolism alter nutrient metabolism and will provide the means to apply this information to studies in humans that could suggest appropriate individual dietary changes. <br /> <br /> <br /> Kansas State University and the Western Human Nutrition Research Center at the University of California-Davis: Copper metabolism influences factors involved in oxidative stress. In keeping with studies involving the genetic, cellular and metabolic aspects of nutrient metabolism, these groups are evaluating copper. The Medeiros laboratory (Kansas) continues to research the impact of copper-deficiency upon cardiac hypertrophy. A critical part of this research centers on mitochondrial biogenesis as altered by copper deficiency. They have demonstrated that certain transcription factors, such as mitochondrial transcription factor A, that coordinate gene activation of nuclear and mitochondrial genomes of mitochondrial proteins, are up regulated in copper deficiency. Furthermore, this group has demonstrated that mitochondrial potential is markedly reduced in copper deficient rats. Since this latter observation is an early indication of apoptosis, a cell culture model, murine derived C2C1, was used to determine if copper deficiency can decrease mitochondrial membrane potential and subsequently lead to apoptosis. The cells were made copper-deficient by treatment with the copper chelator tetraethylenepentamine (TEPA). In TEPA treated cells, the activity of Cu, Zn- superoxide dismutase and cytochrome c oxidase decreased dramatically. The protein levels of nuclear encoded subunits of the cytochrome c oxidase decreased, but the mitochondrial encoded subunits remained unchanged. Decreased mitochondrial membrane potential was indicated in TEPA-treated cells, but further investigation of the potential induction of apoptosis by measuring caspase-3 activity, protein concentrations of Bcl-2 and Bax, and DNA fragmentation suggested that apoptosis is not induced in TEPA-treated C2C12 cells. Cells with decreased mitochondrial membrane potential were not destined to apoptosis as a result of copper-deficiency. The results of others showing that markers of apoptosis are increased in hearts from copper-deficient rats could be related more to the heart disease state itself, rather than copper-deficiency per se. If chelation of copper can reduce SOD and cytochrome c oxidase, can high copper intake alter antioxidant status as well? The Turnland laboratory (Davis) has discovered that when long-term copper intake is high (7.8 mg/d), a substantial amount of copper is retained. Some indices of antioxidant status and immune function also change suggesting a possible adverse effect. Outcome: Clearly, factors that influence copper levels can influence oxidative stress at both the cellular and whole body levels. This appears to be the case for both copper deficiency and high copper levels. Future studies of this nutrient should examine this parameter. Impact: The amount of copper used in the intake studies is less than the current UL for copper, suggesting that the current UL is too high.<br /> <br /> <br /> Washington State University, University of Arizona, Oregon State University: Relationship of Smoking to Nutrient Metabolism. The Winzerling laboratory (Arizona) is conducting studies on the impact of smoking at the cellular level using lung cells. Since the lung cell layer represents a single cell surface interface between lung and blood, events in lung tissues can influence whole body antioxidant and nutrient metabolism. Smoke from multiple sources contains iron in the acidic phase as well as numerous compounds that act as oxidants. By the Fenton reaction, if the iron is available, substantive oxidative stress can occur. Normally cells protect against oxidative stress by storing iron in ferritin. However, this group found that exposure of lung cells to low levels of cigarette smoke resulted in a down regulation of ferritin synthesis that was primarily the result of an up regulation in iron regulatory protein 2 (IRP2). IRP2 is one of two proteins primarily responsible for translational control of ferritin synthesis. These results indicate that ferritin levels are reduced at a time when iron storage is desirable and implies that iron-mediated oxidative stress could be, in part, responsible for the oxidative stress observed in smokers. To complement these studies on the impact of smoking on nutrient metabolism and oxidative stress, evaluation of the impact of smoking on whole body human nutrient status by intervention studies are underway. Smokers exhibit reduced B-6 nutritional status and previous research indicates serine hydroxymethyltransferase (SHMT) declines during vitamin B-6 (B-6) deficiency. The Shultz group (Washington) is studying the effects of smoking on SHMT with the consumption of B-6 supplements. They studied smokers during successive 28-d periods. Healthy smokers (S; n=6) and nonsmokers (NS; n=6) consumed controlled diets providing 0.7 (depletion), 1.4 (repletion 1) and 2.2 (repletion 2) mg B-6/d, and a supplemented (10.3 mg B-6/d) self-selected diet. Lymphocyte (LYM) SHMT activity was assayed with (stimulated) and without (basal) added pyridoxal phosphate (PLP). Basal SHMT activity in S was significantly higher (each 35%) than NS after depletion and repletion period 2, respectively. For NS, SHMT activity was significantly higher after supplementation compared to controlled diet periods, and was positively correlated with B-6 intake, plasma (PLA) PLP and 4-pyridoxic (4-PA), LYM PLP, pyridoxamine phosphate and negatively with DNA strand breaks. For S and NS, activity coefficients were inversely correlated with B-6 intake, PLA PLP and 4-PA. These findings indicate that vitamin B-6 intake and smoking exert distinct effects on LYM SHMT activity. In keeping with the effects of smoking on the methyl transfer pathways, the Oregon State group has submitted an NIH grant to determine the effectiveness of an intensive, multi-faceted smoking cessation intervention on abstinence rates in postmenopausal women. Current research shows that older individuals with high blood homocysteine concentrations have more hip fractures than those with lower levels. High homocysteine levels are associated with low intakes of B-vitamins (B-6, folate and B-12) and older individuals are at increase risk of poor intakes of B-vitamins. Thus, there may be protective effects of B-vitamins on fracture risk among current smokers. One objective of this project is to evaluate the consequences of smoking on blood levels of homocysteine and the B-vitamins including Vitamin B-6. Outcome: Smoking can influence metabolism of iron by lung tissues and of vitamin B-6 at the whole body level. These changes could is could have a direct effect on methyl transfer inside cells and ultimately on homcysteine metabolism. Compounds in smoke could prevent synthesis of the primary protein that stores iron in lung cells and thereby increase oxidative stress. Compounds in smoke also influence the use of the vitamin B-6. Impact: Supplements of the B vitamins and consumption of foods high in antioxidants could be required to improve stress response and adverse effects of smoking.<br /> The Oregon State group also is recruiting subjects for a study that will examine whether physical activity at the levels recommended by the IOM increases blood homocysteine levels in active individuals compared to inactive controls, while monitoring dietary intakes of B-vitamins and blood status measures. The results of this study could suggest whether exercise should be considered as a variable in future studies of B-vitamin status in smokers.<br /> <br /> Purdue University, Oregon State University, Kansas State University: Physical Activity, Calcium, Iron and Vitamin Intake Impact on Bone Formation and Bone Health. A central hypothesis of the study described above at Oregon State is that an intensive, multi-faceted intervention will decrease smoking behavior and improve bone health in post-menopausal women. The Oregon group will evaluate the effects of the cessation of smoking on longitudinal changes in bone health and intakes of bone building nutrients in the diet. They also will monitor changes in physical activity for impact on bone health in this population. This study will contribute to the collaborative efforts of work by the W-1002 group on bone formation and bone health. In this area this year, two major studies were by the Medeiros laboratory (Kansas) in animals. One study was conducted on outright iron-deficiency and calcium deficiency with a pair-fed group to correct for the decreased food consumed by rats in the iron-deficient groups. The hypothesis of whether iron-deficiency had direct adverse impacts on vertebral trabecular bone and long bones was answered by this study. Four groups of female weanling rats were fed for five weeks diets that were 1) control; 2) calcium restricted, 1.0 g Ca/kg diet; 3) iron deficient, less than 8 mg Fe/kg diet; or 4) control pair-fed to the iron-deficient group. Whole body and femur DEXA analysis revealed that calcium-restricted and iron-deficient rats had lower bone mineral density (BMD) and content (BMC) than pair-fed and controls. However, pair-fed rats also had decreased BMD and BMC compared to controls. The third lumbar trabecular bone microarchitecture in both diet restricted groups had decreased bone volume fraction (BV/TV) and trabecular number and thickness, a less favorable structural model index, and increased trabecular separation compared with the controls and the pair-fed groups as determined by microcomputer tomography. The control or pair-fed groups did not differ from one another, suggesting that iron-deficiency and calcium-restriction had impacts on vertebrae independent of food intake and body weight. Finite element analysis revealed decreased force to compress the vertebrae, decreased stiffness but greater von Mises stress in calcium-restricted and iron-deficient groups compared to controls and pair-fed groups. Urinary deoxypyridinium crosslinks, serum osteocalcin and cholcalciferol were increased in calcium-restricted rats compared to the other 3 groups. Using Micro-CT imaging technology, this study demonstrated micro-architectural pathology due to iron deficiency upon vertebral trabecular bone, compared to controls and pair-fed rats, though not to the same extent as severe-calcium restriction.<br /> <br /> Since the above study demonstrated compromise in bone in outright deficiency, the Medeiros laboratory then asked whether marginal intakes of iron and/or calcium, likely to be consumed in Western diets, would have any negative impact. Thirty-two female, weanling rats were randomly divided into four groups for 10 weeks: 1) control, 2) calcium restricted (Ca-), 3) iron restricted (Fe-), and 4) calcium and iron restricted (Ca-Fe-). DEXA analysis revealed that marginal Ca- affected bone mineral density (BMD), but marginal Fe- affected whole body bone mineral content (BMC). All treatment groups had decreased BMC and BMD in femurs and the 4th lumbar (L-4) vertebrae. The microarchitecture of the L-4 vertebrae was compromised in Ca-, Fe-, and Ca-Fe- restricted groups: the amount of tissue present in L-4 vertebrae (BV/TV) was reduced in Ca- and Fe- groups; all three treatment groups had decreased trabecular number compared to the control; and both Fe- and Ca-Fe- groups had greater trabecular separation compared to the iron adequate groups. Finite element analysis revealed that L-4 vertebrae from the Fe- group would require less total force to break than Fe adequate groups and the combined Ca-Fe- group. All three treatment groups experienced greater internal stress (Von Mises stress) when force was applied than the control group. Marginal iron restriction, such as that which occurs among some human populations, does reduce bone strength and microarchitecture. <br /> <br /> The findings of the Medeiros group in animals were extended by the work of the Weaver laboratory (Purdue) on the effects of phytonutrients on calcium metabolism and bone. They conducted a study on the effect of kudzu isoflavones on bone health in 6 month OVX Sprague Dawley rats. Kudzu root powder providing 0.9% isoflavones in the diet increased bone mineral density at several bone sites using pQCT, but had estrogenic effects on the uterus.<br /> <br /> This Weaver group extended the isoflavone work in a dose response study of the effect of soy isoflavones in a soy protein powder on bone loss in postmenopausal women using a novel 41Ca technology. Thirteen postmenopausal women (> 6 years since menopause) were pre-dosed with 41Ca intravenously. After a 100-day baseline period, subjects were given 40 grams of soy protein per day that contained 0, 97.5, or 135.5 mg of total isoflavones in randomized order. The soy protein isolate powder was incorporated into baked products and beverages. Each 50-day treatment phase was followed by a 50-day recovery phase. Serum isoflavone levels and biochemical markers were measured at the end of each phase. Twenty-four hour urine collections were performed every ~10 days during each phase for 41Ca/Ca analysis by Accelerator Mass Spectrometry. Serum isoflavone levels reflected the amount of isoflavones consumed in a dose-dependent manner. None of the isoflavone levels had a significant effect on biochemical markers of bone turnover, urinary cross-linked N-teleopeptides of type I collagen (NTx) and serum osteocalcin (OC), or bone turnover as assessed by urinary 41Ca/Ca. In conclusion, soy isoflavones up to 135.5 mg per day did not suppress bone resorption in postmenopausal women.<br /> <br /> The Weaver laboratory also evaluated potential racial differences in calcium retention as a function of intake in adolescent girls. They pooled data from five metabolic studies (Camp Calcium) on adolescent black and white girls aged 12-14. Girls were studied during controlled feeding periods of three weeks on diets ranging in calcium intake from 800 to 2300 mg/day. Calcium retention at all intakes was higher in black than white girls. Black women have higher bone mass than white women. This group previously reported that black girls used calcium more efficiently than white girls on one calcium intake. They determined racial differences in the relationship between calcium intake and calcium retention in 82 black and 160 white girls. Black girls utilize calcium more efficiently at all calcium intakes than white girls.<br /> <br /> University of Maine, University of Nebraska, Purdue University and University of Connecticut: Availability and absorption of nutrients and phytonutrients from food sources. Several studies are designed to determine nutrient availability from food sources or to evaluate nutrient status in a specific population group were completed this year. These studies complement the areas of common research. <br /> <br /> Accompanying the work in bone health and formation described above, the Weaver laboratory (Purdue) evaluated calcium availability from soy milk. Calcium (Ca) fortified soymilk has gained popularity in the United States. Tricalcium phosphate (TCP) fortified soymilk was shown to have a lower Ca bioavailability than that of cows milk in men. However, the most popular soymilk in the U.S. is fortified with calcium carbonate. The objective of this study was to compare Ca bioavailability of Ca carbonate fortified soymilk and TCP fortified soymilk with cows milk in young healthy women using the dual stable isotope technique. In a 3-way crossover design, 19 volunteers (23+1.9 years old) consumed either cows milk, Ca carbonate fortified soymilk, or TCP fortified soymilk labeled with stable isotopes. Fractional Ca absorption was determined from stable isotope ratios in urine samples. Fractional Ca absorption in Ca carbonate fortified soymilk (0.211+0.057) was not significantly different from that of cows milk (0.198+0.037), but was significantly higher than that of TCP fortified soymilk (0.181+0.039). Soymilk fortified with calcium carbonate is comparable to cows milk, but soymilk fortified with TCP is significantly less well absorbed. <br /> <br /> Complementing the work in oxidative stress, the Camaire laboratory (Maine) developed and evaluated four beverage formulations. Although the beverages had high anthocyanin levels and antioxidant activity, consumers only found one formulation to be acceptable. This project also has a practical component in collaboration with the Maine Business School conducting an on-line survey to learn more about consumer attitudes towards healthy beverages. The Camaire group will extend this research component next year with a new project to evaluate the literature and recommend a strategy for a qualified health claim for wild blueberries. As part of the project a database of relevant research articles has been compiled. Data from the blueberry supplement and cognition study are being analyzed. Projects starting this fall include testing the efficacy of cranberry supplements against Helicobacter pylori, and evaluation of the hypoglycemic effects of blueberry flavonoids. Impact: Food consumption is preferred to supplements to provide nutrients and phytonutrients. The study of bioavailability of such from fortified foods as well as the effect of cooking on these constituents is required to utilize the information obtained from cellular, metabolic, kinetic and whole body metabolism studies. <br /> <br /> Extending the work in phytonutrients, the Connecticut group studied a potential relationship between the plasma cholesterol (CH) and carotenoid (CAR) following egg consumption and whether gender influences plasma carotenoids. Using a cross over design, 40 men and 51 pre-menopausal women were randomly assigned to an egg (640 mg/d additional CH and 600 mcg of lutein/zeaxanthin) or a placebo diet (no additional CH or lutein). Based on response to CH, we analyzed plasma CAR concentrations in a subset of 40 subjects (20 hypo- and 20 hyper-responders). Compared to men, women had an average of 30 and 60% higher concentrations of lutein and zeaxanthin respectively (P < 0.01) during the egg period. In addition, with egg intake, plasma lutein concentration of female hyper-responders was greater (1.16 µmol/L) than hypo-responders (0.89 µmol/L) (P < 0.01). A similar, response was observed in men after egg intake with plasma levels of 0.89 µmol/L and 0.63 µmol/L for hyper-responders and hypo-responders respectively (P<0.01). These results suggest that responses to dietary CH and CAR are related and that gender influences plasma CAR concentrations. Impact: This study has addressed some important factors influencing absorption of carotenoids. This is potentially important for human health because of the role of xanthophylls (specifically lutein and zeaxanthin) in preventing age-related macular degeneration.<br /> In addition to the work in carotenoids in adults, the Driskell (Nebraska) laboratory studied intakes of carotenoids in children. They evaluated intake and status of carotenoids, as well as vitamin B-6 and vitamin E for 35 children (19 boys, 16 girls), aged 4-8 years, of Latino immigrants were determined. Data were similar by gender. All subjects had adequate vitamin B-6 status. Plasma alpha-tocopherol concentrations <12 micromoles/Liter were observed in 66% of subjects and <7 micromoles/Liter, in 29%; thus, many subjects were inadequate in vitamin E. The carotenoid intakes and plasma concentrations varied greatly between subjects. <br /> <br /> In a similar practical research area, the Driskell laboratory evaluated microwave steaming as a cooking method on the yields and beta-carotene retentions for broccoli, carrots, green beans, and sweet potatoes. The yields and nutrient retentions were generally higher when cooked by induction-boiling than microwave-steaming. Trained panelists generally scored the flavor and texture of these vegetables as being significantly different by cooking method, but not the color and overall acceptability. Impact: Most children need to consume more alpha-tocopherol, the active form of vitamin E. Cooking vegetables by induction-boiling appears to be a desirable method in terms of cooking yield, carotenoid retention, and sensory characteristics.<br /> <br /> <br /> <br /> <br /> <br />

Publications

Impact Statements

1. University of California-Davis and University of California-Berkeley: Cellular, metabolic and kinetic effects of genetic polymorphisms on folate metabolism. Impact: The results of these studies, taken together, will provide information on how specific polymorphisms of genes involved in folate metabolism alter nutrient metabolism and will provide the means to apply this information to studies in humans that could suggest appropriate individual dietary changes.
2. Kansas State University and the Western Human Nutrition Research Center at the University of California-Davis: Copper metabolism influences factors involved in oxidative stress.Impact: The amount of copper used in the intake studies is less than the current UL for copper, suggesting that the current UL is too high.
3. Washington State University, University of Arizona, Oregon State University: Relationship of Smoking to Nutrient Metabolism:Impact: Supplements of the B vitamins and consumption of foods high in antioxidants could be required to improve stress response and adverse effects of smoking.
4. University of Maine, University of Nebraska, Purdue University and University of Connecticut: Availability and absorption of nutrients and phytonutrients from food sources:Impact: Most children need to consume more alpha-tocopherol, the active form of vitamin E. Cooking vegetables by induction-boiling appears to be a desirable method in terms of cooking yield, carotenoid retention, and sensory characteristics.

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Report Information

Participants

Bray, Tammy (tammy.bray@oregonstate.edu) - Oregon State University;
Camire, Mary Ellen (mary.camire@umit.maine.edu) - University of Maine; Driskell, Judy (jdriskell@unl.edu) - University of Nebraska;
Glahn, Ray (rpg3@cornell.edu) - Cornell University;
Ho, Emily (Emily.ho@oregonstte.edu) - Oregon State University;
Koo, Sung (skoo@uconn.edu) - Storrs, California;
Medeiros, Denis (Medeiros@ksu.edu) - Kansas State University;
Saltos, Etta (CSREES);
Shane, Barry (bandie@socrates.berkeley.edu) - University of California, Berkeley;
Shultz, Terry (Shultz@wsu.edu) - Washington State University;
Stoecker, Barbara (chrom@okstate.edu) - Oklahoma State University;
Thompson, Cyndi (cthomson@u.arizona.edu) - University of Arizona;
Weaver, Connie (weavercm@purdue.edu) - Purdue University;
Winzerling, Joy (jwinzerl@ag.arizona.edu) - University of Arizona

Brief Summary of Minutes

Brief Summary of Minutes of Annual Meeting:

Members Attending: Tammy Bray (Administrative Advisor), Terry Shultz (WA), Sung Koo (CT), Connie Weaver (IN), Etta Saltos (CSREES), Barbara Stoecker (OK), Raymond Glahn (NY, invited participant), Emily Ho (OR), Denis Medeiros (KS), Joy Winzerling (AZ), Cynthia Thomson (AZ, interested in joining), Mary Camire (ME), Judy Driskell (NE), Barry Shane (CA-B).

Barry Shane, Chair, called the meeting to order. All attendees introduced themselves. Barry asked for a volunteer to take minutes and Terry Shultz volunteered.

Etta Saltos, CSREES, presented an overview and update of the CSREES and Nutrition Programs. Etta started her presentation by outlining the NRI Competitive Grants Program which includes:

* Bioactive Food Components for Optimal Health
* Human Nutrition and Obesity
* Improving Food Quality and Value

Other nutrition related multistate research and pending nutrition-related research projects were mentioned. She reminded participants that CSREES will require electronic submission for all proposals submitted to the NRI and SBIR programs in 2007.

Tammy Bray gave the Administrative Report. Tammy stressed the importance of establishing greater collaboration within the technical committee, particularly in relationship to competitive multistate grants. Tammy indicated that the annual report was due within 60 days after our meeting.

The group talked about the website that had been developed. The group understood that Ann Bock had set-up a website for this project. However, the New Mexico website was not current and an updated website was needed. Members then unanimously approved a motion that the website needed updating. Because of the difficulty for any individual member to maintain a website the group then approved a motion to shift responsibility for the website from New Mexico to the USDA maintained website. Tammy Bray indicated that her office would help set up an updated website and that a staff member at Oregon State University would assist as the web master to keep the link updated with appropriate materials. The W1002 group should e-mail materials to Tammy at Tammy.Bray@oregonstate.edu. We thank Ann Bock for her contribution in maintaining the list serve and New Mexico website during past years.

Mary Camire, Joy Winzerling, Ray Glahn, and Denis Medeiros will design outlines for web dissemination of information to be evaluated by committee members. A discussion of roster correction ensued since several members have not attended meetings for sometime. Tammy Bray will check with the appropriate Agricultural Experiment Station Directors for these individuals status in the group.

Tammy Bray indicated that the W1002 project would be terminated next year. One suggested approach for writing the new project proposal was for each person to write a portion of the proposal and submit it to a group who would compile the work. It was thought that the proposal needs to be unique and outcome driven. Joy Winzerling and Connie Weaver said they would help. The meeting will be held in Washington DC next year (2007) in conjunction with Experimental Biology. Connie Weaver will organize next years meeting with Etta Saltos. Judy Driskell announced that she will be leaving the group at the termination of the project (September 30, 2007). We will miss Judy and wish her the very best.

Station reports were given by attending members. Afterwards, the meeting was adjourned.


Terry Shultz
Secretary

Accomplishments

W1002 SAES-422: Accomplishments<br /> <p><br /> Short term outcomes: The individual and collaborative research efforts of the W1002 group listed below have provided new information on the requirements and metabolism of trace metals, vitamins and phytochemicals which have suggested and will suggest dietary modifications to ensure optimal health and which may reduced risk of diseases such as cancer, heart disease and birth defects.<br /> <br /> <p><br /> Outputs: The major outputs have been peer reviewed publications and reports.<br /> <p><br /> Activities: <br /> <p><br /> University of Maine (Mary Ellen Camire): A USDA NRICGP equipment grant provided the Camire laboratory with a Hologic Discovery W bone densitometer that was installed in the fall of 2005. The equipment will be used in osteoporosis and obesity research. Specifically, Dr. Camire is seeking funds to examine the role of appetite-suppressing foods on weight loss in overweight women.<br /> <p><br /> The study of the role of anthocyanin-rich fruits in reducing risks for Type 2 diabetes just ended. Twenty-five overweight persons with elevated fasting glucose levels completed the study; 9 people were assigned to the anthocyanin group and asked to consume two servings of anthocyanin-rich foods per day for three months. Subjects were provided with a list of fruits and servings sizes that should provide about 180 mg of anthocyanins. The control group was matched to the anthocyanin group for size, age and gender, and asked to follow their typical diet, but consume no more than three servings of foods containing anthocyanins per week. The final 3-month laboratory values have not yet been analyzed. Fasting serum glucose levels were not lower in the anthocyanin group at 2 months into the study, but insulin values were significantly higher in the control group. Future work will focus on the effect of anthocyanins and related compounds on digestion and postprandial glucose and insulin responses.<br /> <p><br /> Subject screening has begun for a project on the treatment of Helicobacter pylori infections with cranberry supplements. Adults who test positive for the infection using a breath test will be randomized to a commercially-available cranberry supplement or to a placebo. Three capsules will be consumed daily, with repeat breath tests three and six weeks after the start of supplementation.<br /> <p><br /> University of California-Berkeley (Barry Shane): Cellular, metabolic and kinetic effects of genetic polymorphisms on folate metabolism. The Shane group have continued studies on the metabolic and nutritional effects of common polymorphisms in human folate-related genes that have been shown to influence disease risk. They identified a gene-gene interaction that influences the risk of heart disease and are developing cell culture models to mimic this interaction. They have continued to evaluate two new genetic mouse models to mimic the effects of these polymorphisms and to evaluate their effects on metabolism and how this is modified by nutritional status. These new animal models have gene interruptions that disturb mitochondrial folate metabolism and histone methylation, a process involved in regulation of gene expression. They have continued to study one carbon metabolic fluxes and DNA methylation in these animals and in embryonic fibroblasts. Their data indicate that disturbances in mitochondrial folate metabolism result in early embryonic lethality. <br /> <p><br /> In collaborative human studies with Jess Gregory at Florida, they have shown that a common polymorphism in the MTHFR gene causes elevated homocysteine prior to defective remethylation in folate-restricted young women. They have continued to evaluate genetic risk factors for neural tube defects.<br /> <p><br /> Impact: Neural tube defects are the most common birth defects in humans and identification of genetic risk factors for this condition will allow screening to identify at risk individuals. Polymorphisms in genes encoding folate-dependent enzymes have been implicated as risk factors for cancer and vascular disease. The studies may indicate whether this risk can be modified by dietary changes.<br /> <p><br /> Kansas State University (Denis M. Medeiros): Iron and bone work - Dr. Medeiros previously reported that severe iron deficiency negatively impacts bone microarchitecture. He has now determined whether marginal iron restriction that reflects some human consumption patterns could have similar consequences. Thirty-two weanling female, rats were randomly divided into four groups and fed the following diets for 10 weeks: 1) iron adequate, calcium adequate (FeA:CaA), 2) calcium restricted (FeA:CaR), 3) iron restricted (FeR:CaA), and 4) both calcium and iron restricted (FeD:CaR). DEXA analysis revealed that CaR decreased bone mineral density (BMD), and FeR decreased whole body bone mineral content (BMC). Iron restricted and calcium restricted groups had lower BMD than their adequate counterparts. All treatment restricted groups had lower BMD in the 4th lumbar (L-4) vertebrae than the FeA:CaA group. Vertebrae BMD was lower in all treatment groups compared to the control group and for BMC, the CaR groups were lower than the CaA groups and the FeR groups were lower that the FeA groups.and BMC were lower in iron and calcium restricted groups. The microarchitecture of the L-4 vertebrae was compromised in FeA:CaR, FeR:CaA, and FeR:CaR: 1) the connectivity density was reduced by FeR and by CaR; and 2) trabecular number was decreased and trabecular separation was increased by FeR ; Cortical thickness of the femur was reduced by both FeR and CaR. Finite element analysis revealed that L-4 vertebrae from the FeR:CaA group had greater internal stress with an applied force than the FeA:CaA group, thus would be more likely to break. Chelation of iron in cultured osteoblast cells impaired mineralization, but had no impact upon Type I collagen deposition. Iron depletion, similar to that occurring among some human populations reduced bone strength and microarchitecture based on in vivo and in vitro results reported here. Impaired mineralization with iron depletion appears to be a possible mechanism for the observed bone abnormalities.<br /> <p><br /> Copper and cardiac mitochondrial biogenesis. The Medeiros laboratory continues to research the impact of copper-deficiency upon mitochondrial biogenesis as affected by copper deficiency. Using super-array technology, they conducted a study to determine whether certain metabolic and mitochondrial biogenic pathways were affected as a result of copper-deficiency in the heart. Rats were fed either control diets or diets deficient in copper from weaning until 5 weeks thereafter. RNA was obtained and subsequent hybridization to customized super-arrays were carried out. The genes spotted on the super-arrays included sequences that encode for connective tissue proteins, substrate utilization enzymes for fatty acid and glucose utilization, apoptosis proteins, and cell cycle genes. Early analysis suggests that NFkB-1, a key enzyme involved in cell proliferation and apoptosis was up-regulated in copper deficient rat hearts. Another study using rats suggested that marginal copper intakes at levels likely to be consumed by westerners, can lead to abnormal electrocardiograms in the absence of ultra-structural pathologies, but with enhanced lipid deposition in the heart.<br /> <p><br /> Impact: Marginal iron intake has a negative consequence upon bone health. The levels used in the study are cause for concern in that many humans consume marginal iron diets worldwide. Iron may be an overlooked factor in bone health. The role of copper in maintaining the integrity of the heart may be related to NFkB, a critical gene in cell proliferation. Marginal copper intakes can lead to abnormal electrical activity of the heart.<br /> <p><br /> University of Nebraska (Judy Driskell): Anthropometric measurements and selected nutrient intakes of Latino immigrant children, 4-8 y, in rural Nebraska were determined. 19.4% were at risk of being overweight and 11.1% were overweight. 72% had higher fat intakes; 94.4%, higher saturated fat intakes; and 33.3%, higher cholesterol intakes than recommended. These Latino immigrant children had higher median energy, protein, fat, folate, vitamin C, iron, and calcium intakes than reported for school children, 4-11 y, in a 1998 national Mexican Survey. Anthropometric measurements, selected nutrient intakes, and hemoglobin, hematocrit, and serum cholesterol values of 65 male and 66 female Koreans, 2-6 y, were determined. 8.4% were underweight; 10.7%, at risk of being overweight; and 4.6%, overweight. Hemoglobin concentrations of 3.8% were <110 g/L, 4.6% had hematocrits <.33, and 3.8% had serum cholesterol >5.17 mmol/L. The majority of subjects met the Korean Estimated Average Requirements and U.S./Canadian Estimated Average Requirements for protein, phosphorus, iron, zinc, and vitamin C. Blood concentrations of vitamin A, carotenoids, and vitamin E are currently being quantitated. Anthropometric measurements, selected nutrient intakes, and food beliefs have been collected from over 70 urban American Indians in the Lincoln, NE area. Selected vegetables were prepared by induction stir-frying and carotenoid concentrations and sensory attributes determined using a 78-member consumer panel of college students, 19-30 y. The cooked vegetables retained more than 85% of all their carotenoids (beta-carotene, alpha-carotene, beta-cryptoxanthin, lutein, lycopene). Over three-quarters of the panelists reported liking extremely/liking very much or liking moderately/liking slightly the appearance, color, flavor, texture, and overall acceptability of carrot, green onion, red pepper, snow pea, and yellow pepper; whereas, half to three-quarters reported similarly for white onion. Few differences in attribute responses were observed by gender. Induction stir-frying is a convenient method for cooking vegetables in which most of the carotenoids are retained, while still maintaining their acceptability/desirability to consumers.<br /> <p><br /> Impact: Young children of Latino immigrants living in rural Nebraska have greater nutrient intakes than reported in a national Mexican survey, which is suggestive of acculturation-related dietary changes, some of which are undesirable. Young children in Korea appear to be in the acceptable weight category, have adequate dietary intakes, and have normal hemoglobin, hematocrit, and serum cholesterol values. Cooking vegetables by induction-stir-frying appears to be a desirable method in terms of cooking yield, carotenoid retention, and sensory characteristics.<br /> <p><br /> Oregon State University (Emily Ho): The classic view of cancer etiology is that genetic alterations damage DNA structure and induce mutations resulting in non-functional proteins that lead to disease progression. More recently, the role of EPIGENETIC alterations during cancer has gained increasing attention. These epigenetic alterations affect gene expression without directly changing DNA sequences, but rather turn on or off gene expression by post-translational modifications. Interestingly, many of these epigenetic modifications can also be modified by dietary factors. For example, pharmacological histone deacetylase (HDAC) inhibitors are currently being tested in human clinical trials and are proposed to have potent anti-cancer activity. The Ho laboratory have found that sulforaphane, a chemical found in cruciferous vegetables is also an HDAC inhibitor, increases acetylated histone levels and has anti-cancer properties in the prostate. Addition of 15 mM SFN inhibited HDAC activity and induced accumulation of acetylated histones in both normal and prostate cancer cells. However, SFN induced expression of p21 and a G2/M arrest only in PC3 cells, with no effect in PrEC. Thus, similar to other HDAC inhibitors, SFN exhibited selective anti-proliferative effects to cancer cells. Secondly, they examined the effects of SFN on HDAC inhibition and prostate chemoprevention in vivo using a xenograft model. Dietary SFN (~7.5 mmol per day) caused a significant decrease in HDAC activity and increase in histone acetylation in the xenografts, prostates and peripheral blood mononuclear cells (PBMC) and suppressed the growth of PC3 xenografts. Thus, consumption of SFN in the diet was able to inhibit HDAC activity in circulating blood cells and prostate, and retard prostate tumor growth in vivo. These findings provide evidence that one potential mechanism by which SFN acts as a cancer chemopreventive agent is by the inhibition of HDAC activity.<br /> <p><br /> Impact: Prostate cancer remains a very significant contributor to the morbidity and mortality of U.S. men. Increased vegetable intake has long been associated with decreases in prostate cancer risk. However, mechanisms for chemoprevention are unclear. This research is significant because nutritional strategies that target aberrant epigenetic alterations, such as acetylation, in prostate cancer have the potential to dramatically reduce the incidence of prostate cancer, reduce health care costs associated with prostate cancer, and improve the quality of life of thousands of American men. This work will form the basis for future work and larger trials to identify effective dietary intervention strategies that are broadly applicable nutrition recommendations and will significantly reduce the burden of prostate cancer. <br /> University of Connecticut (Sung Koo): Dr. Koo and associates have been studying whether there is a relationship between plasma cholesterol response and plasma lutein and vitamin E responses after egg consumption. Using a crossover design, postmenopausal women (50-68y) were assigned to a pasteurized whole egg treatment containing 640 mg cholesterol, 600 mcg lutein/zeaxanthin/d (EGG) or an egg substitute treatment containing 0 mg cholesterol, 0 mcg lutein/zeaxanthin and 540 mcg beta-carotene/d (SUB) for 30 d, followed by a 3 wk washout period and 30 d alternate treatment period. Nine women were classified as hyper-responders to cholesterol and 17 women were classified as hypo-responders to cholesterol. After the EGG period cholesterol hyper-responders had a significantly greater increase in plasma lutein (42%) and alpha-tocopherol (33%) compared to the cholesterol hypo-responders who has a 23% increase in lutein and no increase in alpha-tocopherol. Increase in plasma lutein from eggs did not affect other carotenoids in the blood. After the SUB period, the 63% increase in plasma beta-carotene observed in the cholesterol hyper-responders was significantly greater (p<0.05) than the 39% increase observed in the cholesterol hypo-responders. These results suggest plasma responses to dietary cholesterol, carotenoids and alpha-tocopherol are related. <br /> The Koo laboratory have also examined whether the inhibition of intestinal lipid absorption by green tea is associated with the inhibitory effect of its catechins on pancreatic phospholipase A2 (PLA2). PLA2 activity was assayed by using 1,2-dioleoylphosphatidylcholine (DOPC), porcine pancreatic PLA2, and catechins at varying concentrations (0.075-1.80 micromol/L). The amount of 1-oleoyl-2-hydroxyphosphatidylcholine liberated was determined by HPLC. The percentages of inhibition of PLA2 by (-)-epicatechin (EC), (+)-catechin (CAT), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), and (-)-epigallocatechin gallate (EGCG) at 0.6 micromol were 23.3, 24.8, 25.7, 39.7, and 64.9%, respectively. In an in vivo study, ovariectomized rats with lymph cannula were infused intraduodenally for 8 h with a triolein emulsion containing [dioleoyl-1-14C] PC, DOPC, alpha-tocopherol (TP), and retinol (ROH) without (CAT0) or with CAT or EGCG. The lymphatic total 14C-radioactivity (14C) was significantly lowered by EGCG (45.5% dose) compared with CAT (56.2% dose) and CAT0 (64.7% dose). The 14C radioactivity remaining in the small intestinal lumen and cecum was higher in EGCG (24.1% dose) than in CAT (9.5% dose) and CAT0 rats (9.0% dose). Significantly less 14C radioactivity was incorporated into lymph triacylglycerol and cholesteryl ester in EGCG rats. The absorption of TP, used as a marker of extremely hydrophobic lipids, was significantly lower in EGCG (7.8 micromol) than CAT (14.4 micromol) and CAT0 rats (16.8 micromol). The absorption of ROH was unaffected, whereas oleic acid output was lower in EGCG rats. The results show that EGCG inhibits the intestinal absorption of lipids, which is in part associated with its inhibition of PC hydrolysis. <br /> Impact: Study results show: 1) Egg may be used as a vehicle for delivering bioavailable carotenoids in humans and 2) Green tea or catechins lower the intestinal absorption of fat and fat-soluble compounds by inhibiting pancreatic phospholipase A2. The findings indicate that the absorption and bioavailability of fat-soluble compounds are significantly influenced by egg intake in humans and green tea in rats. Data may be used as a basis for specific dietary recommendations regarding the inclusion of eggs and green tea in diets for the prevention and treatment of certain diet-related diseases and disorders. <br /> <p><br /> Oklahoma State University (Barbara J. Stoecker): The Stoecker laboratory have collaborated with several investigators to examine effects of nutrients and phytonutrients on bone strength and structure. Highlights of three projects completed are included below:<br /> <p><br /> Effects of marginal iron status on microarchitecture and strength of bone This study was a collaboration with Dr. Dennis Medeiros and is reported in detail in the Kansas State University W-1002 report. In summary, iron restriction produced a number of changes in microarchitecture in addition to those seen with calcium restriction alone. Connectivity density was decreased both by iron and by calcium restriction. Trabecular number was decreased and trabecular separation was increased by iron restriction. When a force was simulated on the 4th lumbar vertebra, bones from animals fed calcium adequate but iron restricted diets showed greater stress than bones from animals fed calcium adequate, iron adequate diets.<br /> <p><br /> Effects of enhanced antioxidant status on bone quality in a rat model of male osteoporosis One-year-old retired breeder rats were randomly assigned to orchidectomy (ORX) or sham-surgery (SHAM) treatments. Three days post-surgery, ORX rats were assigned to the following treatments: ORX, ORX + 2.5% powdered orange pulp, ORX + 5.0% orange pulp and ORX + 10% orange pulp. This isonitrogenous, isocaloric modified AIN-93M diet was fed for four months with all ORX rats pair fed to the mean intake of the sham group. At the termination of the study, blood and bone samples were collected. Plasma antioxidant capacity was determined spectrophotometrically and bone microarchitecture was assessed using microcomputed tomography (MicroCT-40, Scanco Medical). Data were analyzed using the General Linear Model procedure in SAS (version 9.1) to determine the effects of orange pulp on plasma total antioxidant capacity and on bone microarchitecture. Lack of testosterone decreased (p<0.05) antioxidant status and even the 2.5% level of orange pulp increased antioxidant capacity of ORX rats to that of the SHAM animals. In trabecular cores from the 4th lumbar vertebrae, ORX rats had significantly reduced bone volume fraction, connectivity density, and trabecular number and increased trabecular separation. In ORX rats fed 10% powdered orange pulp, bone volume fraction, and trabecular number were significantly increased and trabecular separation significantly decreased compared to ORX animals. This study was a collaboration with Dr. Farzad Deyhim at Texas A&M University-Kingsville and Dr. B.S. Patil at Texas A&M UniversityCollege Station.<br /> <p><br /> Effects of high does of vitamin E on bone quality in a rat model of male osteoporosis Vitamin E is commonly known to function as an antioxidant. However, little research has been done to discover the effects that Vitamin E might have on bone quality. In this experiment, thirty-two rats were randomly assigned to four treatment groups. Eight rats were sham operated and 24 were orchidectomized. The groups were: Control (SHAM), orchidectomy (ORX), low dose supplemental vitamin E of 65.6 mg/kg diet (ORX+LD), or high dose vitamin E of 656 mg/kg diet (ORX+HD). After four months of feeding, microarchitecture of the 4th lumbar vertebra (L4) were analyzed using a µCT 40 scanner. Orchidectomy significantly reduced bone volume fraction, trabecular number and connectivity density, and increased trabecular separation. Microarchitecture of the ORX+LD group did not differ significantly from the ORX group. Bone volume fraction of the ORX+HD group tended to be lower than the ORX group (15.4 ± 0.6 vs 18.5 ± 1.3, p=0.11) and trabecular thickness was significantly reduced in the ORX+HD group. Bone strength was estimated using finite element analyses. Compared to SHAM, the ORX group required significantly less force for compression and demonstrated decreased stiffness and size independent stiffness and increased von Mises stresses. Strength predictions for the ORX+LD dose did not differ from the ORX group. The ORX+HD showed significantly increased von Mises stresses compared to the ORX group. The changes in bone with ORX demonstrate the importance of testosterone or its metabolites in maintenance of bone quality. The high dose Vitamin E (ORX+HD) had detrimental effects on the microarchitecture and predicted stress with load of the L4 vertebra, suggesting reduced bone quality. This study was a collaboration with Dr. Farzad Deyim at Texas A&M University-Kingsville.<br /> <p><br /> Impact: Various dietary components have the potential to change bone strength and microarchitecture and recent improvements in instrumentation have increased our capacity to measure these effects. Dietary components that affect antioxidant status may be beneficial or detrimental to bone quality depending on dose. Many people take vitamin E supplements greater than 10-fold the Recommended Dietary Allowance and assume these levels of supplements are safe. However, our results raise the concern that high dose vitamin E supplements may have detrimental effects on bone; further studies addressing mechanisms for these effects on microarchitecture and studies in humans are needed. The effects of adding orange pulp to animal diet were positive at the dose levels tested; studies are underway to determine if specific components of orange pulp were responsible for the beneficial effects on bone microarchitecture. Finally, the work with marginal iron intake is important because many women and children around the world are deficient in iron. To date, little attention has been given to possible effects of iron status on development of optimal bone mass.<br /> <p><br /> University of Arizona (Joy Winzerling): Dr. Winzerling was unable to continue with the original objectives proposed for her regional research project because her collaborator was in a severe accident. There are several researchers in her group working on smoking in relationship to disease. Her laboratory is now contributing in the area of human lung cell iron metabolism and comparative iron metabolism in disease insect vectors. Inhalation of airborne pollution particles that contain iron can result in a variety of detrimental changes to lung cells and tissues. A primary concern is the potential for iron-mediated oxidative stress. The lung iron burden can be substantially increased by exposure to cigarette smoke and smoke contains environmental toxins that could influence intracellular iron status. Previously, she reported that although cigarette smoke contains iron particles that enter lung cells, the exposure of lung cells to smoke down regulates ferritin synthesis. Ferritin is important because it is the primary protein for storing iron and decreased levels increase the potential for iron-mediated oxidative stress. Her findings suggest that this mechanism could be compromised in lung cells at a time when the oxidative stress potential is increased. She now reports that iron also alters levels of protein called early growth response 1. This protein controls the synthesis of proteins involved in cell division. Message levels of EGR1 determine how much protein is made. However, in lung cells iron uncouples EGR1 protein levels from EGR1 message levels. Message levels are sustained with iron exposure time, while protein levels decline. She does not yet know the implications of this finding. However, if Egr1 is needed as part of the process for the replacement of cells damaged by smoke, then iron in smoke particulate matter could possibly effect cell replacement. Dr. Winzerlings work in mosquitoes is directed toward evaluating the role of ferritin in these animals. Female mosquitos blood feed to complete their lifecycle. The blood meal is high in iron and females have developed mechanisms that allow use of the iron load in egg development while avoiding oxidative stress. She has found that the majority of iron from a blood meal is moved to the ovaries for egg development indicating a crucial role for iron in this process. She also has found that mosquitoes secrete ferritin in response to the iron load by a non-classical pathway. These findings contrast with those for mammals where ferritin for iron storage is found in the cell cytoplasm.<br /> <p><br /> Impact: Others in the group are working in the area of smoking and nutrition. Our data complements their work. The findings of the lung iron project are important in the short term because they provide insight into the mechanisms that could promote lung cancer, a primary form of cancer in the US. Future work in this area could lead to dietary recommendations for iron intake for smokers or for individuals exposed routinely to smoke that differ from the general population. The mosquito project is important in the short term because iron is required for egg development. Mosquitoes transmit hundreds of millions of cases of disease each year because of the large numbers of these disease vectors. If the iron pathway differs from that of mammals, we can identify potential targets for mosquito control that could reduced the numbers of disease vectors. <br /> Purdue University (Connie Weaver): The Weaver laboratory has been studying the effect of isoflavones on calcium metabolism and bone. They completed their dose response study of the effect of soy isoflavones in a soy protein powder on 44Ca absorption and postmenopausal women using novel 41Ca technology. Thirteen postmenopausal women (>6 years since menopause) were pre-dosed with 41Ca intravenously. After a 100-day baseline period, subjects were given 40 grams of soy protein per day that contained either 0, 97.5, or 135.5 mg of total isoflavones in randomized order. The soy protein isolate powder was incorporated into baked products and beverages. Each 50-day treatment phase was followed by a 50-day recovery phase. Serum isoflavone levels, biochemical markers, and Ca absorption were measured at the end of each phase. Twenty-four hour urine collections were performed every ~ 10 days during each phase for 41Ca/Ca analysis by Accelerator Mass Spectrometry. Serum isoflavone levels reflected the mount of isoflavones consumed in a dose¬-dependent manner. None of the isoflavone levels had a significant effect on biochemical markers of bone turnover, urinary cross-linked N-teleopeptides of type I collagen (NTx) and serum osteocalcin (OC), 44Ca absorption or bone turnover as assessed by urinary 41Ca/Ca. In conclusion, soy isoflavones up to 135.5 mg per day did not suppress bone resorption in postmenopausal women. She now has data showing that bone resorption was significantly reduced by estrogen and a bisphosphonate.<br /> The Weaver group have also carried out calcium bioavailability studies. They conducted acute and chronic feeding studies on the effect of purported calcium absorption enhancing components on calcium absorption and retention and bone measures in growing rats. Whey protein and honey and its constituents enhanced calcium absorption in a dose response manner in single meal experiments, but the effect largely disappeared on chronic feeding attributable to adaptation through the calcium homeostatic mechanism.<br /> <p><br /> Washington State University (Terry D. Shultz): Hypertension is a major controllable risk factor associated with cardiovascular disease events, such as myocardial infarction, stroke, and heart failure. Cleavage of angiotensinogen by rennin produces angiotensin I, which is subsequently hydrolyzed by angiotensin-I-converting enzyme (ACE) to angiotensin II (a potent vasoconstrictor). It has been reported that in vitro incubation of milk proteins with proteinase preparations can result in the release of ACE inhibitory peptides. The Shultz group examined three commercial proteases, Validase BNP L, Validase FP II, and Multifect Neutral for digestion of 20% solutions of whey protein concentrate 80 (WPC80) for production of ACE inhibitory activity. Enzymes were used at 1% (w/w) and incubated at pH 7 for up to 200 min at 50 C. Degree of hydrolysis (DH) was monitored by TNBS assay and ACE inhibition measured using hippuryl-L-histidyl-L-leucine as substrate. Incubation for 5-15 min produced DH of 0.5-3% and maximal ACE inhibitory activity. Validase FP II produced 61% inhibition with an IC50 value of 4.1 mg/mL, Validase BNP L 46% inhibition with an IC50 value of 5.7 mg/mL, and Multifect Neutral 32% with an IC50 value of 8.1 mg/mL. The Validase BNP L hydrolysate was selected for nutraceutical beverage development because the enzyme is readily inactivated by lowering pH.<br /> <p> <br /> Impact: This research brings novel application to the dairy industry: utilization of whey proteins in a beverage with potential use as a dietary treatment for hypertension.<br /> <p> <br /> Milestones: Peer review articles have been published and a number of new extramural research grants have been obtained. New methods for assessing bone function and for measuring trace metal and vitamin turnover have been developed which have allowed a number of new collaborative projects within the W1002 group. <br />

Publications

Journal Articles - Peer Reviewed<br /> <p><br /> Braun, M. and Weaver, C.M. A call to evaluate the impact of calcium-fortified foods and beverages. Nutr. Today 41 :40-47,2006.<br /> <p><br /> Britten, P., Lyon, J., Weaver, C.M., Kris-Etherton, P., Nicklas, T., Weber, J., Davis, C. MyPyramid food intake pattern modeling for the Dietary Guidelines Advisory Committee. JNEB In press, 2006. <br /> <p><br /> Cai, D.J., Zhao, Y., Glasier, J., Cullen, D., Barnes, S., Turner, C.H., Wastney, M., Weaver, C. Comparative effect of soy protein, soy isoflavones and 1713-estradiol on bone metabolism in adult ovariectomized rats. J Bone Miner Res, 20:828-39, 2005.<br /> <p><br /> Camire, M.E., Dougherty, M.P. 2005. Internet survey of nutrition claim knowledge. J Food Sci. Education 4(2):18-21.<br /> <p><br /> Camire ME, Dougherty MP and Briggs JL. 2005. Antioxidant-rich foods retard lipid oxidation in extruded corn. Cereal Chemistry. 82(6):666-670.<br /> <p><br /> Clark, R.M., Herron, K.L., Waters, D., and Fermandez M.L. (2006) Low and High Plasma Response to Egg Cholesterol Predicts Response to Lutein and Beta-Carotene in Men and Women. J. Nutr. (accepted Dec. 23, 2005). <br /> <p><br /> Dashwood, RH, Myzak, MC and Ho, E. (2005) Dietary HDAC inhibitors: time to rethink weak ligands in cancer chemoprevention? Carcinogenesis. 2006 Feb;27(2):344-9<br /> <p><br /> Davis, S. R., Quinlivan, E. P., Shelnutt, K. P., Ghandour, H., Capdevila, A., Coats, B. S., Wagner, C., Shane, B., Selhub, J., Bailey, L. B., Shuster, J. J., Stacpoole, P. W. and Gregory III, J. F. (2005). Homocysteine is elevated but total remethylation is unchanged by the methylenetetrahydrofolate reductase 677C®T polymorphism and by dietary folate restriction in young women. J. Nutr. 135:1045-1050.<br /> <p><br /> Dayal, S., Devlin, A. M., McCaw, R. B., Liu, M.-L., Arning, E., Bottiglieri, T., Shane, B., Faraci, F. M. and Lentz, S. R. (2005). Cerebral vascular dysfunction in methionine synthase-deficient mice. Circulation 112:737-744.<br /> <p><br /> Deyhim F, Stoecker BJ, Brusewitz GH, Devareddy L, Arjmandi BJ. (2006) Dried plum reverses bone loss in an osteopenic rat model of osteoporosis. Menopause (In Press)<br /> <p><br /> Driskell JA, Kim Y-N, Goebel KJ. Few differences found in the typical eating and physical activity habits of lower-level and upper-level university students. J Am Diet Assoc 2005; 105:798-801. <br /> <p><br /> Driskell JA, Marchello MJ, Giraud DW, Sulaeman A. Vitamin and selenium content of ribeye cuts from grass- and grain-finished bison of the same herd. J Food Qual 2004; 27:388-398.<br /> <p><br /> DSouza, N., Skonberg, D.I., Camire, M.E., Guthrie, K.E., Malison, J., Lim,a L. 2005. Influence of dietary genistein levels on tissue genistein deposition and on the physical, chemical, and sensory quality of rainbow trout, Oncorhynchus mykiss. J. Agric. Food Chem. 53(9): 3631-3636. <br /> <p><br /> Gailer J, George GM, Pickering IE, Prince RC, Younis HS, Winzerling JJ. (2002) Biliary excretion of [(GS)(2)AsSe](-) after intravenous injection of rabbits with arsenite and selenate. Chemical Research in Toxicology. 15:1466-71.<br /> <p><br /> Geiser DL, Chavez CA, Flores-Munguia R, Winzerling JJ, Pham DQ. Aedes aegypti ferritin. Eur J Biochem. 2003 Sep;270(18):3667-74. <br /> <p><br /> Geiser DL, Zhang D, Winzerling JJ. Secreted ferritin: Mosquito defense against iron overload? Insect Biochem Mol Biol. 2006 Mar;36(3):177-87. <br /> <p><br /> Gunther, C.W., Legowski, PA, McCabe, L.D., McCabe, G.P., Peacock, M., Lyle, R.M., Weaver, C.M., Teegarden, D. Parathyroid hormone is associated with decreased fat mass in young health women. Int. J. Obesity. 30:94-99, 2006.<br /> <p><br /> Hansen, C.M., Shultz, T.D., Hunt, K.C., Hardin, K., Leklem, J.E., Huang, A. & Ames, B.N. (2006) Vitamin B-6 intake and smoking status influence lymphocyte serine hydroxymethyltransferase activity in healthy adults. Submitted.<br /> <p><br /> Hansen, C.M., Shultz, T.D., James, S.J., Melnyk, S., Leklem, J.E., Hardin, K. & Ames, B.N. (2006) Effects of smoking and vitamin B-6 intake on plasma thiol concentrations. Preparation.<br /> <p><br /> Hansen, C.M., Shultz, T.D., James, S.J., Melnyk, S., Leklem, J.E., Hardin, K. & Ames, B.N. (2006) Effects of smoking and vitamin B-6 intake on plasma thiol concentrations. Preparation.<br /> <p><br /> Hansen, C.M., Shultz, T.D., Hunt, K.C., Hardin, K., Leklem, J.E., Huang, A. & Ames, B.N. (2006) Vitamin B-6 intake and smoking status influence lymphocyte serine hydroxymethyltransferase activity in healthy adults. Submitted.<br /> <p><br /> Heaney, RP. and Weaver, C.M. Newer perspectives on calcium and bone quality. J. Am. Coil. Nutr 24(6):574S-581S, 2005.<br /> <p><br /> Kling, P.J. and Joy J. Winzerling (2002) Iron status and the treatment of the anemia of prematurity. Clinics in Perinatology 29(2):283-94. <br /> <p> <br /> Lim, U., Peng, K., Shane, B., Stover, P. J., Litonjua, A. A., Weiss, S. T., Gaziano, J. M., Strawderman, R. L., Raiszadeh, F., Selhub, J., Tucker, K. L. Cassano, P. A. (2005). Polymorphisms in cytoplasmic serine hydroxymethyltransferase and methylene-tetrahydrofolate reductase affect the risk of cardiovascular disease in Men. J. Nutr. 135:1989-1994.<br /> <p><br /> Mashiyama, S.T., Hansen, C.M., Roitman, E., Sarmiento, S., Leklem, J.E., Shultz, T.D. & <br /> Ames, B.N. (2006) DNA-uracil in healthy humans measured with an improved assay (uracil assay V3.0) is not affected by marginal vitamin B-6 deficiency. Submitted. <br /> <p><br /> Mayo JJ, Kohlhepp P, Zhang D, Winzerling JJ. Effects of sham air and cigarette smoke on A549 lung cells: implications foriron-mediated oxidative damage. Am J Physiol Lung Cell Mol Physiol. 2004 Apr;286(4):L866-76<br /> <p><br /> Medeiros DM, Shiry LJ, McCune SA. 2005. Marginal copper intakes over a protracted time period in genetically and non-genetically susceptible heart disease rats disturbs electrocardiograms and enhances lipid deposition. Nutr. Res. 25: 663-672.<br /> <p><br /> Myzak, MC, Hardin, K. Dashwood, RH and Ho, E. (2004) Sulforaphane Inhibits Histone Deacetylase Activity in BPH-1, LnCaP, and PC-3 Prostate Epithelial Cells. Cancer Epidemiology biomarkers and prevention, 13:1847S.<br /> <p><br /> Myzak, MC, Hardin, K, Rong W, Dashwood, RH and Ho, E. (2005) Sulforaphane inhibits histone deacetylase activity in BPH-1, LnCaP, and PC-3 prostate epithelial cells. Carcinogenesis. 2005 Nov 15; [Epub ahead of print]<br /> <p><br /> Nichol, Helen, John H. Law and Joy J. Winzerling. (2002) Iron Metabolism in Insects. Annual Review of Entomology, 47:535-559.<br /> <p><br /> Nichol H, Winzerling, JJ (2002) Structured RNA upstream of insect cap distal iron responsive elements enhances iron regulatory protein-mediated control of translation. Insect Biochemistry and Molecular Biology, 2002 32(12):1699-710.<br /> <p><br /> Nicklas, T.A., Weaver, C.M., Stitzel, K.F. The 2005 Dietary Guidelines Advisory Committee: Developing a Key Message. JADA 105(9):1418-24,2005.<br /> <p><br /> OLeary, V. B., Mills, J. L., Pangilinan, F., Kirke, P. N., Cox, C., Conley, M., Weiler, A., Peng, K., Shane, B., Scott, J. M., Parle-McDermott, A., Molloy, A. M., Brody, L. C., Members of the Birth Defects Research Group. (2005). Analysis of methionine synthase reductase polymorphisms for neural tube defects risk association. Molec. Genet. Metab. 85:220-227.<br /> <p><br /> Parelman M, Stoecker B, Baker A, Medeiros DM. 2006. Iron restriction negatively affects bone in female rats and mineralization of hFOB osteoblast cells. Exp. Biol. Med. (Maywood) In Press.<br /> <p><br /> Parelman M, Stoecker B, Baker A, Medeiros DM. (2006) Iron restriction negatively affects bone in female rats and mineralization of hFOB osteoblast cells. Exp Biol Med (In Press).<br /> <p><br /> Pham DQ, Kos PJ, Mayo JJ, Winzerling JJ. Regulation of the ribonucleotide reductase small subunit (R2) in the yellow fever mosquito, Aedes aegypti. Gene. 2006 Mar 9; <br /> <p><br /> Pham Q.D. D, Bluchuta B,Nichol H,Winzerling JJ. (2002) Cloning, sequencing and expression of RNR R1 and R2 in mosquito. Insect Biochemistry and Molecular Biology, 32(9):1037-44.<br /> <p><br /> Quinlivan, E. P., Davis, S. R., Shelnutt, K. P., Henderson, G. N., Ghandour, H., Shane, B., Selhub, J., Bailey, L. B., Stacpoole, P. W. and Gregory III, J. F. (2005). Methylenetetrahydrofolate reductase 677C->T polymorphism and folate status affect one-carbon incorporation into human DNA deoxynucleosides. J. Nutr. 135:389-396.<br /> <p><br /> Reinwald, S. and Weaver, C.M. Soy isoflavones and bone health: are they a double¬ edged sword? J. Natural Products In press, 2006.<br /> <p><br /> Ritzenthaler, K.L., McGuire, M.K., Shultz, T.D., McGuire, M.A., Koepp, A.E., Luedecke, L.O., Hanson, T.W., Dasgupta, N. & Chew, B.P. (2005) Consumption of conjugated linoleic acid (CLA) from CLA-enriched cheese does not alter milk fat or immunity in lactating women. J.Nutr. 135:422-430.<br /> <p><br /> Ritzenthaler, K.L., Shultz, T.D., McGuire, M.A., Shahin, M.A., Dasgupta, N. & McGuire, M.K. (2006) Concentrations of conjugated linoleic acid (CLA) in human plasma and lipid fractions and their relationship with dietary CLA intake. Preparation.<br /> <p><br /> Ritzenthaler, K.L., Shultz, T.D., McGuire, M.A., Shahin, M.A., Dasgupta, N. & McGuire, M.K. (2006) Concentrations of conjugated linoleic acid (CLA) in human plasma and lipid fractions and their relationship with dietary CLA intake. Preparation.<br /> <p><br /> Shultz, T.D., Hansen, C.M., Hardin, K., Leklem, J.E. & Ames, B.N. (2006) Assessment of vitamin B-6 status in young men and women cigarette smokers and nonsmokers consuming a controlled diet. Submitted.<br /> <p><br /> Smith BJ, Lucas EA, Turner RT, Evans GL, Lerner MR, Brackett DJ, Stoecker BJ, Arjmandi BH. Vitamin E provides protection for bone in mature hindlimb unloaded male rats. (2005) Calcified Tissue Int 76:272-279. <br /> <p><br /> Spence, L.A, Lipscomb, E.R, Cadogan, J., Martin, B., Wastney, ME, Peacock, M., Weaver, C.M. The effect of soy protein and soy isoflavones on calcium metabolism and renal handling in postmenopausal women: A randomized cross over study. Am. J. Clin. Nutr. 81 :916-922, 2005.<br /> <p><br /> Stempak, J. M., Sohn, K.-J., Chiang, E.-P., Shane, B. and Kim, Y.-I. (2005). Cell and stage of transformation-specific effects of folate deficiency on methionine cycle intermediates and DNA methylation in an in vitro model. Carcinogenesis 26:981-990.<br /> <p><br /> Teh, Y.-H., Dougherty, M.P., and Camire, M.E. 2005. Frozen blueberry-soy dessert quality. J. Food Sci. 70(2):S119-22. <br /> <p><br /> Weaver, C.M. Inulin, oligofructose and bone health: experimental approaches and mechanisms. Br. J. Nutr. 93(1 ):S99-S1 03, 2005.<br /> <p><br /> Weaver, C.M. and Cheong, J.MK Soy isoflavones and bone health: The relationship is still unclear. J. Nutr. 135:1243-1247,2005<br /> <p><br /> Welch, J.M. and Weaver, C.M. Calcium and exercise affect the growing skeleton. Nutr. Reviews 63(11):361-373, 2005.<br /> <p><br /> Weaver, C., Nicklas, T., Britten, P. The 2005 Dietary Guidelines Advisory Committee Report. Nutr. Today 40:102-107,2005.<br /> <p><br /> Wigertz, K., Palacios, C., Jackman, L.A, Martin, B.R, McCabe, L.D., McCabe, G.P., Peacock, M., Pratt, J.H., Weaver, C.M. Racial differences in calcium retention in response to dietary salt in adolescent girls. Am. J. Clin. Nutr. 81 :845-850,2005.<br /> <p><br /> Winzerling JJ, Pham DQ. Iron metabolism in insect disease vectors: Mining the Anopheles gambiae translated protein database. Insect Biochem Mol Biol. 2006 Apr;36(4):310-21. <br /> <p><br /> Zhang D, Dimopoulos G, Wolf A, Minana B, Kafatos FC, Winzerling JJ. (2002) Molecular characterization of two mosquito iron regulatory proteins. Insect Biochemistry and Molecular Biology, 32(5):579-89.<br /> <p><br /> Zhao, Y., Martin, B.R., Weaver, C.M. Calcium bioavailability of calcium carbonate fortified soymilk is equivalent to cow's milk in young women. J Nutr. 135:2379-2392, 2005.<br /> <p><br /> Zhao, Y., Martin, B.R, Wastney, M.E., Schollum, L., Weaver, C.M. Acute Versus Chronic Effects of Whey Proteins on Calcium Absorption in Growing Rats. Exp. BioI. Med. 230:536-542, 2005.<br /> <p><br /> Extension Publication<br /> <p><br /> Driskell JA. Nutrient Recommendations of Adults. NebGuide G-05-1555-A. 2005. Available at http://www.ianrpubs.unl.edu/epublic/pages/publicationD.jsp?publicationId=294. <br /> <p><br /> Books/Book Chapters<br /> <p><br /> Bagley, P. and Shane, B. (2005). Folate. In Encyclopedia of Dietary Supplements, Coates, P., Blackman, M. R., Cragg, G., Levine, M., Moss, J. and White, J., eds., pp. 219-228, Marcel Dekker, New York.<br /> <p><br /> Heaney, RP. and Weaver, C.M. Ch. 7 Requirements for What Endpoint. In: Calcium in Human Health. Weaver, C.M. and Heaney, RP., eds. Humana Press. 97-104,2006.<br /> <p><br /> Wastney, ME, Y. Zhao, Weaver, C.M. Ch. 6 Kinetic Studies. In: Calcium in Human Health. Weaver, C.M. and Heaney, RP., eds. Humana Press. 83-93, 2006.<br /> <p><br /> Weaver, C.M. Ch. 17 Pre-Puberty and Adolescence. In: Calcium in Human Health. Weaver, C.M. and Heaney, RP., eds. Humana Press. 281-296,2006.<br /> <p><br /> Weaver, C.M. Ch. 5 Clinical Approaches for Studying Calcium Metabolism and Its Relationship to Disease. In: Calcium in Human Health. Weaver, C.M. and Heaney, RP., eds. Humana Press. Pp 65-81, 2006.<br /> <p><br /> Weaver, C.M. and Heaney, RP. Ch.9 Calcium In: Modern Nutrition in Health Disease. 10th Ed. M.E. Shils, M. Shike, AC. Ross, B. Caballero, RJ. Cousins, eds. Lippincott Williams & Wilkins Pp 194-210, 2006.<br /> <p><br /> Weaver, C.M. and Heaney, RP., editors. Calcium in Human Health, Humana Press. Totowa, New Jersey 2006.<br /> <p><br /> Weaver, C.M. and Heaney, RP. Ch. 9 Food Sources, Supplements and Bioavailability. In: Calcium in Human Health. Weaver, C.M. and Heaney, RP., eds. Humana Press. 129-142, 2006.<br /> <p><br /> Winzerling, Joy J, and Daphne Q.-D. Pham (2004) Ferritin. In Comprehensive Insect Physiology, Biochemistry, Pharmacology and Molecular Biology. Biochemistry and Molecular Biology, Ed: Lawrence I. Gilbert,Kostas Iatrou,and Sarjeet Gill. Elsevier.<br /> <p><br /> Winzerling, Joy J, and Daphne Q.-D. Pham (2004) Ferritin. In Comprehensive Insect Physiology, Biochemistry, Pharmacology and Molecular Biology. Biochemistry and Molecular Biology, Ed: Lawrence I. Gilbert,Kostas Iatrou,and Sarjeet Gill. Elsevier.<br /> <p><br /> Theses/Dissertations Directed<br /> <p><br /> Aldaous, S.A. 2005. Development Of Extruded Wild Blueberry Confection. M.S. Thesis, University of Maine, Orono, ME.<br /> <p><br /> Michelle Braun. Bone mineral metabolism in adolescents, as assessed by metabolic balance studies, Ph.D. thesis, Purdue University<br /> <p><br /> Jennifer Cheong. Effects of phytochemicals on bone turnover & validation of a novel method to assess bone turnover, Ph.D. thesis, Perdue University<br /> <p><br /> Yong Jiang. Phytochemicals and bone, M.S. thesis, Purdue University<br /> <p><br /> Lora KR. Vitamin B-6 status of a group of 4-8 y old children of Latino immigrants in rural Nebraska. M.S. Thesis. University of Nebraska-Lincoln. December, 2004.<br /> <p><br /> Nunn MD. The effects of various cooking methods on the sensory qualities and carotenoid retention in selected vegetables. M.S. Thesis: University of Nebraska-Lincoln. December, 2004.<br /> <p><br /> Oberholtzer, A.S. 2005. Development and Evaluation of a New Salmon Jerky Snack Product. M.S. Thesis, University of Maine, Orono, ME.<br /> <p><br /> Parelman M. 2005. Marginal iron restriction negatively impacts bone. MS Thesis, Kansas State University<br /> <p><br /> Yongdong Zhao. Calcium bioavailability of functional foods and discovery of bone biomarkers using serum proteomic approach, Ph.D. thesis, Purdue University<br /> <p><br /> <p><br /> Abstracts<br /> <p><br /> Lora KR, Giraud DW, Davy SR, Driskell JA. Vitamin B-6 status of 4-8 year old Latino children in rural Nebraska. FASEB J 2005;19(4):A433-434. <br /> <p><br /> Driskell JA, Giraud DW, Davy SR, Lora KR. Vitamin E, vitamin C, and carotenoid status of children, 4-8 y, of Latino immigrants. FASEB J 2005;19(4):A475. <br /> <p><br /> Presentations<br /> <p><br /> Bailey B, Deyhim F, Stoecker BJ. Effects of vitamin E supplementation on bone quality. Experimental Biology 06, San Francisco, 2006. <br /> <p><br /> Blake, P., Mayo, J.J., Kohlhepp, P. and Winzerling, J.J. (2003) Screening a Genomic Library for Aedes aegypti Ribonucleotide Reductase-R1 Subunit. Center for Insect Science University of Arizona, Tucson, AZ. <br /> <p><br /> Camire, M.E. Anthocyanins: are they the fountain of youth? Kemin Foods, Des Moines IA. Oct. 5, 2005.<br /> <p><br /> Camire, M.E., Guthrie, K., Bolton, J., Jordan, J.J., Kelley, S., Oberholtzer, A., Qiu, X., and Dougherty, M.P. Does color affect consumer attitudes about whole wheat baked products? AACC International Annual Meeting, Sept. 11-14, 2005, Orlando, FL.<br /> <p><br /> Camire, M.E. Healthy Foods Laboratory Research. Wild Blueberry Health Summit, August 11-12 2005, Bar Harbor, ME.<br /> Camire, M.E., Dougherty, M.P., and The, Y.H. Frozen wild blueberry-soy desserts. Institute of Food Technologists Annual Meeting, July 16-20, 2005, New Orleans, LA. <br /> <p><br /> Camire, M.E., Potter, R.M., Aldaous, S., Halteman, W., and Dougherty, M.P. Characteristics and sensory quality of wild blueberry soy beverages. Institute of Food Technologists Annual Meeting, July 16-20, 2005, New Orleans, LA. <br /> <p><br /> Camire, M.E. Supplements for Men's Health. Togus Veterans Hospital, Augusta, ME. June 24, 2005.<br /> <p><br /> Camire, M.E. Understanding the role of functional and nutraceutical food ingredients and the impact on anti-obesity formulations. 2nd Marcus Evans Ingredients-Based Obesity Symposium. Schaumburg, IL. June 8, 2005.<br /> <p><br /> Camire, M.E. Complementary Medicine: Research and Education Challenges for the Nutrition Professional. Maine Nutrition Council Quarterly Meeting. Augusta, January 26, 2005.<br /> <p><br /> Daniel, H. (presented by Camire, M.E.). Assessing the market for a blueberry and soy beverage. AACC International Annual Meeting, Sept. 11-14, 2005, Orlando, FL.<br /> <p><br /> Garcia-Bañuelos, M., Luz Vazquez-Moreno1, Alfonso A. Gardea and Joy Winzerling. (2005) Differential Expression in Dormancy and Release of Dormancy in Apple (Malus domestica) shoots. American Society for Biochemistry and Molecular Biology. San Diego, CA.<br /> <p><br /> Geiser, D.L., Jonathan J. Mayo, Meng-Chieh Shen and Joy J. Winzerling. (2005) Pilot Study: The Regulation by Iron of a Putative Divalent Metal Transporter in Anopheles gambiae Larval Cells, MOS55. American Society for Biochemistry and Molecular Biology. San Diego, CA. Student Travel Award Presentation.<br /> <p><br /> Geiser, D. L., Jonathan J. Mayo, Meng-Chieh Shen and Joy J. Winzerling. (2005) Pilot Study: The Regulation by Iron of a Putative Divalent Metal Transporter in Anopheles gambiae Larval Cells, MOS55. Southwestern and Rocky Mountain Region of AAAS. Tucson, AZ. <br /> <p><br /> Geiser, D., Mayo, J, Zhang, D., Kohlhepp, P. and Winzerling, J.J. (2002) Response of Aedes aegypti Larval Cells To Iron. Center for Insect Science Ninth Annual Poster Hexapodium. Tucson, AZ.<br /> <p><br /> Geiser, D., Mayo, J, Zhang, D., Kohlhepp, P. and Winzerling, J.J (2002) Response of Aedes aegypti Larval Cells To Iron. Fourth International Symposium on Molecular Insect Science. Tucson, AZ.<br /> <p><br /> Geiser, DL, Chavez, C, Pham, D. Q-D., Zhang, D., and Winzerling J.J. (2003) Response of Aedes aegypti Larval Cells To Iron. American Society of Biochemistry and Molecular Biology Annual Meeting. San Diego, CA <br /> <p><br /> Mayo, J.J., Kohlhepp, P., Goodman, N. and Winzerling, J.J. (2003) Cigarette Smoke Influences Intracellular Iron Metabolism in A549 Lung Cells. College of Agriculture and Life Sciences, University of Arizona, Tucson, AZ. <br /> <p><br /> Mayo, J.M.,,Kos, P., Shaffer, J., Pham, D.Q.-D. and Winzerling J. J. (2004) Characterization of Ribonucleotide Reductase in the Mosquito Aedes aegypti. 8th Annual American Society for Biochemistry and Molecular Biology Conference, Boston, MA (2004).<br /> <p><br /> Mayo, J. J., Meng-Chieh Shen, Dawn L. Geiser and Joy J. Winzerling. (2005) Localization and Secretion of Ferritin in Cultured Aedes aegypti Larval Cells.: American Society for Biochemistry and Molecular Biology. San Diego, CA. Student Travel Award Presentation<br /> <p><br /> Mayo, J. J., Meng-Chieh Shen, Dawn L. Geiser and Joy J. Winzerling. (2005) Localization and Secretion of Ferritin in Cultured Aedes aegypti Larval Cells. Southwestern and Rocky Mountain Region of AAAS. Tucson, AZ. <br /> <p><br /> Meng-Chieh Shen, Jonathan J. Mayo, Dawn L. Geiser and Joy J. Winzerling. (2005) Localization and Secretion of Ferritin in Cultured Aedes aegypti Larval Cells . BIO5: Research Frontiers. The University of Arizona, Tucson, AZ 85721.<br /> <p><br /> Morrow R, Deyhim F, Patil BS, Stoecker BJ. Feeding orange pulp improves bone microarchitecture in orchidectomized rats. Experimental Biology 06, San Francisco, 2006.<br /> <p><br /> Parelman M, Stoecker B, Baker A, Medeiros DM. Marginal iron deficiency negatively impacts bone. Experimental Biology, San Diego, CA, 2005<br /> <p><br /> Ramos-Clamont, G., Roberto Guzman Z. Joy Winzerling and Luz Vázquez-Moreno. (2005) Escherichia coli K88 Interaction with Serum Porcine IgA Oligosaccharides. Affinity 2005. Uppsala, Sweden. Young Investigators Award of Excellence. <br /> <p><br /> Rickleffs K, Klaahsen DL, Medeiros DM. Copper deficiency and mitochondrial biogenesis: the role of transcriptional factors PPAR-alpha, PGC1-alpha, and NFKappaB1. Experimental Biology, San Francisco, 2005<br /> <p><br /> Shane, B. Folate metabolism and retention: effect of dosage, Ortho-McNeil Pharmaceuticals, New Jersey, December 2004<br /> <p><br /> Shane, B. Models for phenotypic characterization of nutrient  gene polymorphism interactions: studies on the euchromatic histone methyltransferase, methionine synthase and MTHFR mouse knock-outs, Fred Hutchinson Cancer Research Center, Seattle, Washington, April 2005<br /> <p><br /> Shane, B. Gowland Hopkins Lecture - Molecular-genetic models for investigating the regulation of one-carbon metabolism, Thirteenth International Symposium on Chemistry and Biology of Folates and Pteridines, Egmond aan Zee, Netherlands, June 2005<br /> <p><br /> Shane, B. Folate and vitamin B12 metabolism, Technical consultation on folate and vitamin B12, Department of Nutrition for Health and Development, WHO, Geneva, Switzerland, October 2005.<br /> <p><br /> Winzerling, J.J. (2003) Iron-Binding Proteins in Insects. Department of Life Sciences. Presented at University of Wisconsin- Parkside, Parkside, WI. <br /> <p><br /> Grants <br /> <p><br /> Enhancing Obesity and Osteoporosis Research in Maine, USDA NRICGP <br /> <p><br /> Can anthocyanin-rich foods prevent diabetes?, Gustavus and Louise Pfeiffer Research Foundation<br /> <p><br /> Extruded Salmon Snack Utilizing Processing By-products, USDA NRICGP<br /> <p><br /> Iron Metabolism of Mosquitoes, USPHS NIH GM56812. (2004)<br /> <p><br /> Transcriptional Control of Ribonucleotide Reductase of Mosquitos, USPHS NIH (2003) <br /> <br />

Impact Statements

1. Work carried out in the current year has provided new information on nutrient bioavailability and metabolism and the impact of phytochemicals on these processes. These studies, which have been reported in peer reviewed publications, have also suggested new dietary guidelines for the maintenance of optimal health and for the reduction of chronic disease risk.
2. UC-Davis, UC-Berkeley & OSU (OR), Cellular, metabolic and kinetic effects of genetic polymorphisms on folate metabolism and dietary intervention strategies for the prevention and chemoprevention of cancer: This work will form the basis for future work and larger trials to identify effective dietary intervention strategies that are broadly applicable for nutrition recommendations that will significantly reduce the burden of prostate cancer.
3. KSU (KS), OSU (OK) & UA (AZ), Copper and iron metabolism influences factors involved in oxidative stress and bone health: Findings may provide insight into the mechanisms that could promote lung cancer, a primary form of cancer in the US and could lead to modified dietary recommendations for iron intake for smokers.
4. WSU (WA), Whey proteinases and generation of ACE inhibitory proteins. This research brings novel application to the dairy industry, the utilization of whey proteins in a beverage with potential use as a dietary treatment for hypertension.
5. UM (ME), UN (NE), Purdue and UC (CT), Availability and absorption of nutrients and phytonutrients from food sources: Findings provide the a basis for specific dietary recommendations regarding the inclusion of eggs and green tea in diets for the prevention and treatment of certain diet-related diseases and disorders. Additional findings indicate that soy isoflavones did not affect calcium absorption or bone resorption or turnover in postmenapausal women.

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Participants

Brief Summary of Minutes

Tammy Bray (admin), Ann Bock (NM, by proxy), Richard Bruno (CT, application pending to group), Andy Clifford (UC-D), Emily Ho (OR), Barry Shane (UC-B), Barbara Stoecker (OK), Cyndi Thomson (AZ), Connie Weaver (IN), Joy Winzerling (AZ), Etta Saltos (USDA).

Accomplishments

Short term outcomes and activities:<br /> University of California, Oregon State University, University of Arizona and Washington State University: Phytochemicals and chronic disease prevention: Studied performed in the Clifford lab (UC-Davis) have investigated the relationships between wine consumption, wine composition and cancer. They found that red wine (the residue from red wine remaining after removal of alcohol and water), delayed tumor onset in a mouse model in a positive, linear relationship when incorporated into the diet at levels of 0.5-4 mmol/kg diet. They also found that consumption the wine did alter distribution of PhlP in the rat tissues compared to control animals and animals fed other potential dietary chemopreventive agents, including phenylethyl isothiocyanate and sulforaphane. <br /> In order to improve measures of cruciferous vegetable exposure the Thomson lab (Arizona) developed and validated a cruciferous vegetable food frequency food questionnaire using urinary biomarkers of cruciferous vegetable exposure, dithiocarbamate, (JADA, 2007) and have recently described cruciferous vegetable intake in a large population of breast cancer survivors (Nutr and Cancer, in press, 2007). Along these lines we have assessed the effect of a plant-based diet on plasma carotenoid concentrations in breast cancer survivors (Ca Epidem Biomarkers Prev, 2006) and also explored measurement error associated with self-report instruments (Amer J Epi, 2006). They also have developed database programming to more fully describe citrus and d-limonene exposure in breast cancer survivors participating in the Womens Healthy Eating and Living study which will position us for assessing effects of citrus on recurrence in the near future. Further, assessment of dietary influences on breast mammographic density, a biomarker of breast cancer risk, suggests that greater vegetable and fruit intake is associated with reduced density in non-Hispanic whites, while in Hispanic women, dairy foods are associated with protection against high breast density (Menopause, 2006). The Ho laboratory (Oregon) recently reported on a novel mechanism of chemoprotection by SFN in human colon cancer cells and prostate epithelial cells, namely the inhibition of histone deacetylase (HDAC). When SFN was consumed in the diet at an average daily dose of 7.5 umol per animal for 21 days, SFN suppressed the growth of human PC-3 prostate cancer cells by 40% in male nude mice. There was a significant decrease in HDAC activity in the xenografts, as well as in the prostates and mononuclear blood cells (MBC) of mice treated with SFN, compared to controls. There also was a trend towards increased global histone acetylation in the xenografts, prostates and MBC. In human subjects, a single dose of 68 g BroccoSprouts inhibited HDAC activity significantly in PBMC, 3 and 6 h following consumption. These findings provide evidence that one mechanism through which SFN acts as a cancer chemopreventive agent in vivo is through the inhibition of HDAC activity. Moreover, the data suggest that HDAC activity in PBMC may be used as a biomarker for assessing exposure to novel dietary HDAC inhibitors in human subjects. This work suggests that phytochemicals may have the ability to alter epigenetic events that lead to disease prevention. A recent collaboration between Oregon and Arizona has begun and a joint NIH grant on vegetable intake and breast cancer recurrence has been submitted by the Ho and Thomson laboratories.<br /> <br /> <br /> At UC-Berkeley, the Shane laboratory has continued studies on the metabolic and nutritional effects of common polymorphisms in human folate-related genes that have been shown to influence disease risk. They have identified a gene-gene interaction that influences the risk of heart disease and are developing cell culture models to mimic this interaction. They have continued to evaluate two new genetic mouse models to mimic the effects of these polymorphisms and to evaluate their effects on metabolism and how this is modified by nutritional status. These new animal models have gene interruptions that disturb mitochondrial folate metabolism and histone methylation, a process involved in regulation of gene expression. They have continued to study one carbon metabolic fluxes and DNA methylation in these animals and in embryonic fibroblasts. The data indicate that disturbances in mitochondrial folate metabolism result in early embryonic lethality. They have investigated the influence of folate and vitamin B12 status in our experimental animals using cDNA array technology and have identified a number of genes that are responsive to vitamin status. They have continued to evaluate genetic risk factors for neural tube defects. This project aligns well with the study of epigenetic alterations and disease risk in the Ho lab and future work proposed by the Zempleni lab (Nebraska), a future participant in this multistate.<br /> <br /> At Washington State University, natural compounds and their effects on hypertension have been examined in the Shultz lab. Hypertension is a major controllable risk factor associated with cardiovascular disease events, such as myocardial infarction, stroke, and heart failure. Cleavage of angiotensinogen by rennin produces angiotensin I, which is subsequently hydrolyzed by angiotensin-I-converting enzyme (ACE) to angiotensin II (a potent vasoconstrictor). It has been reported that in vitro incubation of milk proteins with proteinase preparations can result in the release of ACE inhibitory peptides. We examined three commercial proteases, Validase BNP L, Validase FP II, and Multifect Neutral for digestion of 20% solutions of whey protein concentrate 80 (WPC80) for production of ACE inhibitory activity. Validase FP II produced 61% inhibition with an IC50 value of 4.1 mg/mL, Validase BNP L 46% inhibition with an IC50 value of <br /> 5.7 mg/mL, and Multifect Neutral 32% with an IC50 value of 8.1 mg/mL.<br /> <br /> Also at University of Arizona, the Winzerling laboratory has shown the first evidence that ferritin, the primary iron storage protein, decreases in lung cells exposed to cigarette smoke. This occurs at a time when individuals are exposed to iron in smoke and could promote oxidative stress and lung cell damage. Further, they have found that the expression of another protein involved in cell growth is altered by iron. This could have implications for the role of iron in growth, development and inflammation. <br /> <br /> University of Connecticut, University of Massachusetts, University of California, University of Nebraska: Bioavailability of nutrients. <br /> The Decker laboratory (U. Mass) continues work on omega-3 fatty acids. Numerous forms of omega-3 fatty acids are now commercially available. These include liquid oils, encapsulated powders and oil-in-water emulsions. In addition, many new technologies (e.g. nanotechnologies) are being proposed to deliver omega-3 fatty acids. The Decker lab has found that delivery of omega-3 fatty acids in the form of emulsions increases their bioavailability compared to oils in gelatin capsules (Garaiova, 2007). This data suggest that delivery systems could be used to increase omega-3 fatty acid bioavailability. However, very little is known about how these delivery systems will impact bioavailability once they are incorporated into foods. These studies were conducted in in situ digestions models and animal studies.<br /> <br /> The Driskell laboratory (Nebraska) has conducted studies examining vitamin status in Korean children. They found approximately 60% of vitamin A intakes of Korean young children came from provitamin A carotenoids. Plasma retinol concentrations of 2.4% of subjects were indicative of vitamin A deficiency; 42.3% had concentrations potentially indicative of marginal vitamin A status. Two-thirds of subjects had plasma ±-tocopherol concentrations indicative of inadequate vitamin E status. Many urban adult American Indians indicated having problems purchasing foods, with lack of money the primary reason. Many were overweight or obese, 32% had had nutrition education in the last 6-mo, and 39% indicated having a problem with alcoholism. Excessive intakes of cholesterol, saturated fats, sugars, and sodium were prevalent for those in all tribes. <br /> <br /> University of Connecticut-Storrs. Work done in the Koo laboratory (CT) provide evidence that: 1) the plasma level of lutein increases after egg consumption suggesting that egg can be a dietary vehicle of bioavailable carotenoids. This increase was associated with change in total cholesterol but diminishes with obesity. The plasma response to dietary lutein is related to lipoprotein size but not number and 2) the plasma triglyceride-lowering effect of green tea is mediated partly via its inhibitory effect on liver synthesis and release of fat by suppressing the expression of SREBP1c and its responsive genes. <br /> The Clifford laboratory (UC-Davis) also conducted a feasibility study which determined the fate of a true tracer dose of 14C-RRR-alpha-tocopherol and of 14C-all-rac-alpha-tocopherol in a crossover design. Mass balances, and kinetic modeling of the dataset revealed that fractional absorption of 14C-RRR-alpha-tocopherol and 14C-all-rac-alpha-tocopherol were each the same at 0.775 (as expected) while vitamin E catabolism and elimination involved -CPHC), transferring to alpha-CEHC (and some returning to liver, being converted to plasma, and being rapidly eliminated in urine, rather than in enterohepatic circulation as occurs for reverse cholesterol transfer. <br /> Kansas State University, Purdue Univesity, Oklahoma State University: Nutrient influences on bone health. The Medeiros (Kansas), Weaver (Purdue) and Stoecker (Oklahoma) labs have continued collaborations on studies investigating specific nutrients and their effects on bone health. At Kansas State University, work in the Medeiros lab previously reported that severe iron deficiency negatively impacts bone microarchitecture. Here they determined whether marginal iron restriction that reflects some human consumption patterns could have similar consequences. Thirty-two weanling female, rats were randomly divided into four groups and fed the following diets for 10 weeks: 1) iron adequate, calcium adequate (FeA:CaA), 2) calcium restricted (FeA:CaR), 3) iron restricted (FeR:CaA), and 4) both calcium and iron restricted (FeD:CaR). DEXA analysis revealed that CaR decreased bone mineral density (BMD), and FeR decreased whole body bone mineral content (BMC). Iron restricted and calcium restricted groups had lower BMD than their adequate counterparts. All treatment restricted groups had lower BMD in the 4th lumbar (L-4) vertebrae than the FeA:CaA group. Vertebrae BMD was lower in all treatment groups compared to the control group and for BMC, the CaR groups were lower than the CaA groups and the FeR groups were lower that the FeA groups.and BMC were lower in iron and calcium restricted groups. The microarchitecture of the L-4 vertebrae was compromised in FeA:CaR, FeR:CaA, and FeR:CaR: 1) the connectivity density was reduced by FeR and by CaR; and 2) trabecular number was decreased and trabecular separation was increased by FeR ; Cortical thickness of the femur was reduced by both FeR and CaR. The microarchitecture work by microCT, was performed in collaboration with the Stoecker laboratories (Oklahoma). Finite element analysis revealed that L-4 vertebrae from the FeR:CaA group had greater internal stress with an applied force than the FeA:CaA group, thus would be more likely to break. Chelation of iron in cultured osteoblast cells impaired mineralization, but had no impact upon Type I collagen deposition. Iron depletion, similar to that occurring among some human populations reduced bone strength and microarchitecture based on in vivo and in vitro results reported here. Impaired mineralization with iron depletion appears to be a possible mechanism for the observed bone abnormalities.<br /> <br /> Suppression of bone resorption in postmenopausal women by various commercial preparations of isoflavones was tested in the Weaver laboratory (Purdue) with a novel method using calcium-41. Phytoestrogens are being marketed as an alternative to estrogen therapy for preventing bone loss in postmenopausal women without sufficient evidence of efficacy. Isoflavone preparations from soy cotyledon, soy germ, kudzu, and red clover were compared to estradiol and bisphosphonate for suppressing bone resorption. The soy cotyledon preparation suppressed bone resorption by 18% compared to approximately 25% suppression by estradiol and the bisphosphonate. No other product was effective at reducing bone loss.<br /> <br /> Outputs- Major outputs are book chapters and peer-reviewed publications. Website has also been maintained by Ann Bock at New Mexico State University. New collaborative projects have also been established with joint papers and joint grants.<br /> <br /> Milestones- Prepare renewal of multi-state project by Fall 2007. Continue with collaborative studies and submit joint grants Fall 2007.<br />

Publications

Anguera, M. C., Field, M. S., Perry, C., Ghandour, H., Chiang, E.-P., Selhub, J., Shane, B. and Stover, P. J. (2006). Regulation of folate-mediated one-carbon metabolism by 10-formyltetrahydrofolate dehydrogenase. J. Biol. Chem. 281:18335-18342.<br /> <br /> Braun M.M., Martin, B.R., Kern, M., McCabe, G.P., Peacock, M., Jiang, Z., Weaver C.M. Calcium Retention in Adolescent Boys on a Range of Controlled Calcium Intakes, Am. J. Clin. Nutr. 84:414-418, 2006.<br /> <br /> Braun, M. and Weaver, C.M. A call to evaluate the impact of calcium-fortified foods and beverages. Nutr. Today 41:40-47, 2006.<br /> <br /> Cheong, J.M.K., Martin, B.R., Jackson, G.S., Elmore, D., McCabe, G.P., Nolan, J.R., Barnes, S., Peacock, M., Weaver, C.M. Soy isoflavones do not affect bone resorption in postmenopausal women: A dose response study using a novel approach with 41Ca. J. Clin. Endocrin. Metab. 92:577-585, 2007.<br /> <br /> Clark, R.M., Balakrishnan, A., Waters, D., Aggarwal D., Owen, K.Q., Koo, S.I. L-Carnitine increases liver ±-tocopherol and lowers liver and plasma triglycerides in aging ovariectomized rats. J. Nutr. Biochem. [Epub ahead of print] March 16, 2007.<br /> <br /> Daphne Q.-D. Pham, Peter J. Kos, Jonathan J. Mayo and Joy J. Winzerling. (2006) Regulation of the ribonucleotide reductase small subunit (R2) in the yellow fever mosquito, Aedes aegypti. Gene. 372:182-90. <br /> <br /> Dashwood, RH, Myzak, MC and Ho, E. (2006) Dietary HDAC inhibitors: Time to rethink weak ligands for cancer prevention. Carcinogenesis, Feb;27(2):344-9.<br /> <br /> Davy SR, Benes BA, Driskell JA. Sex differences in dieting trends, eating habits, and nutrition beliefs of a group of Midwestern college students. J Am Diet Assoc 2006;106:1673-7. <br /> <br /> Dawn L. Geiser, Dianzheng Zhang and Joy J. Winzerling. (2006) Ferritin secretion: Mosquito cell respond to an iron load. Insect Biochemistry and Molecular Biology. 36(3):177-87 <br /> <br /> de Moura FF, Burri BJ, and Clifford AJ, 2006. Accelerator mass spectrometry in the study of vitamins and mineral metabolism in humans. Handbook of Vitamins. Eds McCormick DB, Rucker RB, Suttie JW, Zempleni J; Marcel Dekker, NY.<br /> <br /> Drewel BT, Giraud DW, Davy SR, Driskell JA. Less than adequate vitamin E status observed in a group of preschool boys and girls living in the United States. J Nutr Biochem 2006;17:132-8. <br /> <br /> Driskell JA and Wolinsky I, Ed. Sports Nutrition: Vitamins and Trace Elements, 2nd ed. Boca Raton, FL: CRC Press, 2006. <br /> <br /> Driskell JA, Nunn,MN, Giraud DW, Hamouz FL. Effects of induction, conventional, and microwave cooking on sensory qualities and carotenoid retention in selected vegetables. J Am Diet Assoc 2006;106(8):A-42. <br /> <br /> Driskell JA. Summary - Vitamins and trace elements in sports nutrition. In: <br /> <br /> Driskell JA, Wolinsky I, ed. Sports Nutrition: Vitamins and Trace Elements, 2nd ed. Boca Raton, FL: CRC Press, 2006. <br /> <br /> Ebeler SE, Dingley KH, Ubick E, Abel S, Mitchell AE, Burns SA, Steinberg FM, and Clifford AJ, 2005. Animal models and analytical approaches for understanding the relationships between wine and cancer. Drugs Exp Clin Res;31:19-27.<br /> <br /> Gabriela Ramos-Clarmont M., Evelia Acedo-Felix, Joy Winzerling and Luz Vazquez-Moreno (2007) Escherichia coli K88 Interaction with IgA Oligosaccharides. EXCLI Journal, 6:10  22. <br /> <br /> Garaiova I, Guschina IA, Plummer SF, Tang J, Wang D, Plummer NT. A randomised cross-over trial in healthy adults indicating improved absorption of omega-3 fatty acids by pre-emulsification. Nutr J. 2007 25;6:4.<br /> <br /> Getachew G, Burri BJ, Kelly P, Haack KW, Ognebene TJ, Buchholz BA, Vogel JS, and Clifford AJ, 2006. How to convert biological and environmental carbon to graphite for AMS. Radiocarbon;48:325-336.<br /> <br /> Hennig, B., Ettinger, A., Jandacek, R.J., Koo, S.I., McClain, C., Seifried, H., Silverstone, A., Watkins, B., and Suk, W.A. Using nutrition for intervention and prevention against environmental chemical toxicity and associated diseases. Environ. Health. Perspect. 493-495, 2007.<br /> <br /> Joy J. Winzerling and Daphne Q.-D. Pham (2006) Iron Metabolism in Mosquitos: Mining the Anopheles gambiae database. Insect Biochemistry and Molecular Biology. 36:310-321.<br /> <br /> Kim Y-N, Driskell JA. Anthropometric measurements, selected nutrient intakes, and hemoglobin, hematocrit, and serum cholesterol values of 2-6 y old children in Republic of Korea. FASEB J 2006;20(5):A1051-2. <br /> <br /> Kim Y-N, Lora KR, Giraud DW, Driskell JA. Nonsupplemented children of Latino immigrants have low vitamin E intakes and plasma concentrations and normal vitamin C, selenium, and carotenoid intakes and plasma concentrations. J Am Diet Assoc 2006;106:385-91. <br /> <br /> Koo, S.I. and Noh, S.K. Green tea as inhibitor of the intestinal absorption of lipids: Potential mechanism for its lipid-lowering effect. J. Nutr. Biochem. 18:179-183, 2007.<br /> <br /> Lora KR, Giraud DW, Davy SR, Driskell JA. Children of Latino immigrants, 4-8 years, in rural Nebraska are adequate in vitamin B-6. Int J Vit Nutr Res 2006;76(2):47-56. <br /> <br /> Lora KR, Giraud DW, Morse KL, Driskell JA. Anthropometric characteristics and selected nutrient intakes of Latino immigrant children, 4-8 y, in rural Nebraska. FASEB J 2006;20(4):A621. <br /> <br /> Myzak, MC, Hardin, K. Dashwood, RH and Ho, E. (2006) Sulforaphane Inhibits Histone Deacetylase Activity in BPH-1, LnCaP, and PC-3 Prostate Epithelial Cells. Carcinogenesis, 27 (4): 811-819. <br /> <br /> Nijhout, H. F., Reed, M. C., Lam, S.-L., Shane, B., Gregory, J. F. III and Ulrich, C. M. (2006). In silico experimentation with a model of hepatic mitochondrial folate metabolism. Theoret. Biol. Med. Mod. 3:40-50.<br /> <br /> Pierce JP, Natarajan L, Sun S, Al-Delaimy W, Flatt SW, Kealey S, Rock CL, Thomson CA, Newman VA, Ritenbaugh C, Gold E and Caan BJ.for the Womens Healthy Eating and Living (WHEL) Study Group*. Increase in Plasma Carotenoid Concentrations in Response to a Major Dietary Change in the Women's Healthy Eating and Living (WHEL) study. Cancer Epi Biomarkers Prev 15;1886-92, 2006.<br /> <br /> Reed, M. C., Nijhout, H. F., Neuhouser, M. L., Gregory III, J. F., Shane, B., James, S. J., Boynton, A. and Ulrich, C. M. (2006). A mathematical model gives insights into nutritional and genetic aspects of folate-mediated one-carbon metabolism. J. Nutr. 136:2653-2661.<br /> <br /> Reinwald, S. and Weaver, C.M. Soy isoflavones and bone health: a double-edged sword? J. Natural Products. 69:450-459, 2006.<br /> <br /> Ritzenthaler, K.L., McGuire, M.K., Shultz, T.D., McGuire, M.A., Koepp, A.E., Luedecke, L.O., Hanson, T.W., Dasgupta, N. & Chew, B.P. (2005) Consumption of conjugated linoleic acid (CLA) from CLA-enriched cheese does not alter milk fat or immunity in lactating women. J.Nutr. 135:422-430.<br /> <br /> Shane, B. Folate, vitamin B12 and vitamin B6. (2006) In Biochemical, Physiological, Molecular Aspects of Human Nutrition, Stipanuk, M. H., ed., second edition, pp. 693-732, Saunders, New York.<br /> <br /> Thomson CA, Newton TR, Graver EJ, Jackson K, Reid PM, Hartz VL, Cussler EC, Hakim IA. Cruciferous Vegetable Intake Questionnaire Improves Cruciferous Vegetable Intake Estimates. Journal of the American Dietetic Association. (April, 2007).<br /> <br /> Thomson CA, Rock CL, Caan BJ, Flatt SW, Al-Delaimy WA, Newman VA, Hajek RA, Chilton RJ, Pierce JP. Increase in Cruciferous Vegetable Intake in Women Previously Treated for Breast Cancer Participating in a Dietary Intervention Trial. Nutrition and Cancer 2006 (Accepted).<br /> <br /> Wang, S., Noh, S.K. and Koo, S.I. Epigallocatechin gallate and caffeine differentially inhibit the intestinal absorption of cholesterol and fat in ovariectomized rats. J. Nutr. 136: 2791-2796, 2006.<br /> <br /> Wang, S., Noh, S.K. and Koo, S.I. Green tea catechins inhibit pancreatic phospholipase A2 and intestinal absorption of lipids in ovariectomized rats. J. Nutr. Biochem. 17: 492-498, 2006.<br /> <br /> Weaver, C.M. Ch. 29 Calcium. In: Present Knowledge in Nutrition. 9th Ed, ILSI, Washington, DC 2006.<br /> <br /> Weaver, C.M., Rothwell, A.P., Wood, K.V. Measuring calcium absorption and utilization in humans. Current Opinion in Clinical Nutrition and Metabolic Care 9:568-574, 2006.<br /> <br />

Impact Statements

1. University of California, Oregon State University, University of Arizona. Projects offer insight into mechanisms by which foods, nutrients and phytochemicals such as sulforaphane, cruciferous vegetables, iron and whey proteins impact chronic diseases such as cancer and heart disease. Identification of nutrient gene interactions may emerge as important factors contributing to risk of disease and the studies may indicate whether this risk can be modified by dietary changes. These studies demonstrate the feasibility of these approaches for studying the chemopreventive potential of dietary components at physiologic levels in humans.
2. University of Connecticut, University of Massachusetts, University of California, University of Nebraska. Work done in these laboratories have significant impact on establishing metabolic fate and dietary recommendations of specific nutrients for optimal health in the population. For example, data may be used as a basis for specific dietary recommendations regarding the inclusion of eggs and green tea in diets to increase plasma lutein and lower blood triglyceride (fat), respectively. Consumption of omega-3 fatty acids can have a major impact on health because they have numerous physiological roles. The kinetic modeling of vitamin E metabolism is likely to settle the controversy regarding the relative potencies of the various forms of vitamin E for humans. Finally, Korean children need to be encouraged to consume more foods that are rich in vitamins A and E.
3. Kansas State University, Purdue Univesity, Oklahoma State University Collaborative work will help establish risk factors for osteoporosis and other bone disorders. Marginal diet iron intake compromises bone integrity. This could be a factor in many human bone conditions given the high level of insufficient iron many people consume. The relationship between calcium intake and calcium retention in adolescent boys was studied and compared to girls studied previously. The large skeleton of boys is achieved by more efficient use of calcium rather than higher calcium requirements.

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Report Information

Participants

Bray, Tammy - Oregon State University; Ho, Emily - Oregon State University; Weaver,Connie - Purdue University; Winzerling, Joy - University of Arizona; Thomson, Cynthia - University of Arizona; Stoecker, Barbara - Oklahoma State University; Shane, Barry - Berkeley; Zempleni, Janos - University of Nebraska; Bruno, Rick - University of Connecticut; Clifford, Andy - University of California, Davis

Brief Summary of Minutes

Accomplishments

<p><br /> Short Term Outcomes & Activities<br /> <p><br /> Research at Oregon State University has found that sulforaphane, a chemical found cruciferous vegetables is also an HDAC inhibitor, increases acetylated histone levels and has anti-cancer properties in the prostate. Sulforaphane (SFN) is an isothiocyanate found in cruciferous vegetables such as broccoli. This anticarcinogen was first identified as a potent inducer of Phase 2 enzymes, but evidence is mounting that SFN acts through other cancer chemopreventive mechanisms. They recently reported on a novel mechanism of chemoprotection by SFN in human colon cancer cells and prostate epithelial cells, namely the inhibition of histone deacetylase (HDAC). In human subjects, they report that a single dose of 68 g BroccoSprouts® inhibited HDAC activity significantly in peripheral mononuclear cells, 3 and 6 h following consumption. They have also developed HPLC-mass spec methods for identifying SFN and its metabolites in plasma and urine. A significant increase in urinary and plasma SFN and metabolites can be found following broccoli sprout consumption. Sustained consumption of broccoli sprouts for 7 days resulted in increased acetylated histones for up to 72hrs. These findings provide evidence that one mechanism through which SFN acts as a cancer chemopreventive agent in vivo is through the inhibition of HDAC activity. Moreover, the data suggest that HDAC activity in PBMC may be used as a biomarker for assessing exposure to novel dietary HDAC inhibitors in human subjects.<br /> <p><br /> Also in the area of diet, phytochemicals and cancer prevention, work from the Thomson laboratory at University of Arizona has provided strong data in support of the use of bioactive food components for cancer prevention. They have completed the following: 1) Submission of a competitive grant application to the USDA Bioactive Food Compounds funding mechanism January, 2007 titled, "Role of vegetables in reducing oxidative stress and inflammation in overweight, post-menopausal women: a Dose-response study". Funding to begin December 1, 2007. 2) Completed a randomized, placebo-controlled green tea study in overweight breast cancer survivors. Preliminary results presented in abstract form at AICR, Washington, DC November 2-3, 2007. Primary results paper submitted to Amer J Clin Nutr November, 2007. 3) Completed a randomized, controlled, crossover feeding study of standard and high lycopene tomatoes among healthy adults. Preliminary results presented in abstract-poster form at the New Frontiers in Nutrition Science meeting, Tucson, AZ, October, 2007; primary results paper under development. 4) Participated as a co-investigator in the 8 year high fruit and vegetable intervention among breast cancer survivors  the Womens Healthy Eating and Living Study  final study results were published in JAMA July 17, 2007. 5) Lead author on the Womens Health initiative paper analyzing dietary associations with other cancer outcomes  published in JNCI October, 2007. A recent collaboration between Oregon and Arizona has begun and a joint NIH grant on vegetable intake and breast cancer recurrence will be re-submitted by the Ho and Thomson laboratories.<br /> <p><br /> In Nebraska, dietary intakes and plasma concentrations of folate of 54 seemingly healthy Korean children, aged 2-6 years, were determined. Over half of the subjects consumed < Korean Estimated Average Requirements for folate. One subject was found to have a plasma folate concentration indicative of folate deficiency, while 24% of subjects had concentrations representative of marginal folate status. Anthropometric indices and selected nutrient intakes of 136 of these Korean young children were determined. Two percent of the subjects were obese and 8%, overweight. The energy intakes of over half the subjects were < Korean Estimated Average Requirements. The vitamin E intakes of 65% of subjects were < Korean Adequate Intake and about half the subjects consumed < Korean Estimated Average Requirement for calcium and for folate, but all consumed > Korean Estimated Average Requirement for protein. The vitamin and mineral supplementation habits of 61 homebound elderly subjects living in Omaha, Nebraska were determined. Forty-seven percent of the subjects reported taking vitamin and mineral supplements. The predominate reason given for use and non-use of these supplements was because they were prescribed or recommended. The most frequently used individual vitamin or mineral supplements were calcium, vitamin D, vitamin E, and vitamin C. Most subjects received their information regarding supplements from a health care professional, most often a physician.<br /> <p><br /> Also at University of Arizona, the Winzerling laboratory is contributing this year in the area of comparative iron metabolism in insect disease vectors (mosquitoes) and in the area of prebiotics. Their work in mosquitoes is directed toward evaluating the role of ferritin in these animals. Female mosquitoes blood feed to complete their lifecycle and thereby receive a high iron load. They have developed mechanisms that allow use of the iron load for egg development while avoiding oxidative stress. This year we reported that the majority of iron absorbed from a blood meal is loaded into ferritin in gut membranes. The iron-loaded ferritin is subsequently secreted into hemolymph (blood) and the iron delivered to the ovaries and eggs. Preliminary studies using RNA interference showed a decrease in egg production with knockdown of the ferritin heavy chain subunit, while ambition of ferritin secretion from mosquito cells resulted in decreased cell viability following iron challenge. These data support the hypothesis that secretion of iron-loaded ferritin is a mechanism whereby mosquito cells prevent iron overload following iron challenge and that secreted ferritin is a primary iron transport protein in these animals.<br /> <p><br /> In Oklahoma, the Stoecker lab is provided data in support of the potential for certain dietary components to ameliorate inflammation and the effects of contaminants on bone quality. For example, cadmium (Cd) has detrimental effects on bone; however, Cd toxicity may be affected by other dietary components. We examined dietary supplementation effects of potassium phosphate (KPhos) and/or dried plum (DP) on Cd-induced bone damage. Fifty, 90 day-old ovariectomized Sprague-Dawley rats were assigned to five treatments (n=10): 1) control, 2) 50 mg Cd/kg diet, 3) 50 mg Cd and 12 g potassium phosphate/kg diet (KPhos), 4) 200 mg Cd/kg, and 5) 200 mg Cd and 12 g KPhos/kg diet. After 45 days, half the rats in each treatment had 15% DP added to diets for 3 more months. Femora and L4 vertebra were scanned using microcomputed tomography (uCT) to assess cortical bone and microarchitecture of the trabecular bone respectively. Bone strength was evaluated using finite element analysis. Cortical thickness was decreased by Cd and by KPhos (p < 0.0001) but increased by DP (p<0.003). Several parameters of trabecular bone microarchitecture, including bone volume fraction, trabecular separation and connectivity density were impaired synergistically by Cd and by high KPhos. Dried plum provided little improvement in trabecular microarchitecture in the presence of high dietary phosphorus; however, with higher dietary Ca/P ratios, DP frequently maintained trabecular microarchitecutre in rats fed 50 ppm Cd but not in those fed 200 ppm Cd. Force to compress L4 trabecular bone was consistent with microarchitectural parameters in showing significant detrimental effects of Cd and KPhos and beneficial effects of DP in the Cd-0 and Cd-50 groups when high KPhos was not fed. In international work, bioavailability of zinc and the effects of zinc status on cognition are being investigated in women in Ethiopia who are severely zinc deficient. The relation between zinc status and cognitive function was examined in a cross-sectional study in the Sidama area of the Southern Nations and Nationalities Peoples Region (SNNPR) of Ethiopia. Pregnant women >24 weeks of gestation from three adjacent rural villages volunteered to participate. Mean (± SD) plasma Zn of 89 women was 6.99 (± 1.09) µmol/l [well below the 2.5 percentile for stage of gestation]. The Ravens Coloured Progressive Matrices (CPM) test was administered individually. Scores for the Ravens scale A, which is the simplest scale, ranged from 4 to 10 of a possible 12. Women with plasma zinc > 7.6 µmol/l had significantly higher Ravens CPM scale A scores than women with plasma zinc concentrations < 7.6 µmol/l. Plasma zinc and age predicted 16% of the variation in Ravens CPM scale A scores. We conclude that zinc deficiency is associated with impaired cognition. A NIH-funded studied of effects of zinc on maternal and infant cognition is beginning in 2008. <br /> <p><br /> At Purdue, postmenopausal women are being screened for their ability to produce the active metabolite, equol, to evaluate the effect on bone resorption. They are screening women to enroll 10 equol producers and 10 non-equol producers to a study testing calcium absorption and bone resorption in response to soy isoflavone consumption.<br /> <p><br /> At University of Connecticut, collaborative work between the Bruno and Koo laboratories are being conducted to determine whether, green tea catechins, EGCG and EC, inhibit the absorption of CH and other lipids and compare their relative inhibitory effects with green tea extract (GTE). Male rats with lymph cannula were infused at 3.0 mL/h for 8 h via a duodenal catheter with a lipid emulsion containing 14C-CH, triolein (OA), alpha-tocopherol (TP), and Na-taurocholate in PBS buffer (pH, 6.0), with 153 micromol EGCG, EC, 207 mg GTE containing 153 micromol EGCG, or no catechin (control). The absorption of 14C-CH was significantly lower in rats infused with EGCG (27.7% dose), EC (29.9%), and GTE (19.5 %) than in those infused with the lipid emulsion alone (39.4%). EGCG and EC did not significantly affect the lymphatic outputs of TP, whereas GTE markedly lowered its output (EGCG, 17.0%; EC, 19.5%; GTE, 5.5%) compared with control (22.1% dose). Similarly, the lymphatic outputs of OA and phosphatidylcholine also were significantly lowered by GTE, but not affected by EGCG or EC. The results indicate that both EGCG and EC, when singly administered, inhibit the intestinal absorption of CH with little effect on other lipids. However, GTE is effective in inhibiting the absorption of all lipids tested, indicating that catechins and other constituents, as present in GTE, have a synergistic and more potent inhibitory effect on intestinal lipid absorption. Study 2: This study was conducted to determine the effect of GTE on lipid metabolism in fructose-fed OX rats. OX rats were assigned to the following groups with 7 each: 1) a starch (S) group fed the AIN-93G diet with corn starch as the major carbohydrate source; 2) a fructose (F) group fed the same diet but with 60% F; 3) a group fed the F diet containing 0.5% GTE; and 4) another group fed the F diet containing 1% GTE. At 6 wk, plasma and liver TG and cholesterol (CH), plasma HDL-C, and expression of liver SREBP1c and related genes were determined. Fructose feeding significantly elevated plasma TG and TC compared with the S control. GTE at 0.5 and 1.0% markedly lowered plasma TG and liver TG and CH. GTE at 1.0% increased plasma CH with an increase in HDL-C, compared with the F control. Fructose feeding significantly increased the abundance of liver SREBP1c, fatty acid synthase (FAS), and stearoyl-CoA desaturase (SCD1) mRNAs compared with the S control, whereas GTE decreased SREBP1c and FAS mRNAs and tended to decrease SCD1 mRNA. GT at 0.5% significantly decreased HMG-CoA reductase mRNA compared with the F control. GT did not alter the expression of intestinal NPC1L1, SR-B1, and ABCA1. The results, coupled with our earlier findings, suggest that the TG-lowering effect of GTE is mediated partly via its inhibition of intestinal absorption and liver synthesis of lipids involving SREBP1 and its responsive genes.<br /> <p><br /> In addition, the Bruno laboratory found that dietary supplementation of green tea extract (GTE), comprised of 30% polyphenolic catechins, protected against the development of hepatic steatosis in obese (ob/ob) mice, a mouse model highly vulnerable to the development of NAFLD. Histologic evidence clearly indicated that obese mice fed GTE at 1 or 2% (w/w), the equivalent of 7-14 cups of green tea in humans, reduced the severity of macrovesicular hepatic steatosis compared to obese mice fed no GTE. Concomitantly, GTE reduced hepatic total lipid and triglyceride accumulation and both were highly correlated (p < 0.05) with histologic hepatic steatosis scores thereby providing compelling evidence of the protective effect of GTE against NAFLD. Moreover, GTE protected against hepatic injury as suggested by 30-41% and 22-33% reductions in serum alanine aminotransferase and aspartate aminotransferase activities, respectively. The mechanism for the protective effect of GTE is being actively investigated, but was likely mediated in part by the body-weight lowering actions of GTE. Indeed, the body weights of obese mice fed GTE at 1 or 2% were 22-25% lower (p < 0.05) than obese controls and occurred in the absence of unaltered food intake suggesting that GTE regulated hepatic lipid accumulation independent of food intake. It was expected that the improvement in body mass would have restored serum adiponectin, but serum adiponectin was lower in obese mice compared to lean littermates and was unaffected by GTE in either genotype. Hepatic ±-tocopherol, vitamin C, and uric acid were evaluated to determine the potential GTE antioxidant mechanism. Surprisingly, GTE did not improve hepatic antioxidant concentrations and GTE tended to reduce (p = 0.06) hepatic ±-tocopherol concentrations consistent with hepatic lipid lowering effects of GTE. Thus, the findings of this project suggest that GTE protects against NAFLD by limiting hepatic lipid accumulation and injury without affecting hepatic antioxidant status and adiponectin-mediated lipid metabolism. Further study is underway to define the events by which GTE protects against obesity-triggered NAFLD.<br /> <p><br /> In California, the Shane laboratory at UC Berkeley have continued studies on the metabolic and nutritional effects of common polymorphisms in human folate-related genes that have been shown to influence disease risk. They have continued to develop mouse models to evaluate the interaction of B12-dependent methionine synthase (MS) and methylene-tetrahydrofolate reductase (MTHFR) polymorphisms and on their effects on metabolism and how this is modified by nutritional status. One carbon metabolic fluxes and DNA and histone methylation has been evaluated in these animals and in embryonic fibroblasts. We have investigated the influence of folate and vitamin B12 status in our experimental animals using cDNA array technology and have identified a number of inflammatory response genes that are responsive to vitamin status. They continue to evaluate genetic risk factors for neural tube defects. They are attempting to identify modifier genes which influence folate status, homocysteine levels, and methylation potential using a number of mouse strains, and are evaluating the interaction between iron and folate status. Mathematical models are being developed to better understand regulatory aspects of one carbon metabolism.<br /> At UC Davis, the Clifford laboratory is continuing modeling work with folate metabolism and SNPs. At the end of the project we will have kinetic models of the interactions of SNPs on 5-MTHF versus FA metabolism in humans that will clarify inter-individual responses for the development of improved strategies to minimize the risk of NTDs, age-related diseases and poor folate status. They may also have newly identified SNPs of the RFC1 that affect folate homeostasis. In summary we will know whether the main and interactive effects of genetic polymorphisms in folate relevant enzymes are significant determinants of the dynamic and kinetic behavior of folate (natural versus synthetic folate) metabolism as it might occur in vivo in humans. <br /> <p><br /> Outputs<br /> <p><br /> Major outputs are the generation of research data, book chapters, peer-reviewed publications and presentations at scientific meetings Website has also been maintained by Ann Bock at New Mexico State University for outreach purposes. New collaborative projects have also been established with joint papers and joint grants.<br /> <p><br /> Milestones<br /> <p><br /> Renewal multistate project for 2008. Continue with collaborative studies and submit joint grants through Fall 2008. Researchers will continue with publication of peer-reviewed articles, with an increase in joint publications between collaborative stations.<br /> <br />

Publications

Abebe Y, Bogale A, Hambidge KM, Stoecker BJ, Arbide I, Teshome A, Krebs NF, Westcott JE, Bailey KB, Gibson RS. Inadequate intakes of dietary zinc among pregnant women from subsistence households in Sidama, Southern Ethiopia. Public Health Nutr, July 5, 1-8 [EPub ahead of print], 2007.<br /> <p><br /> Abebe Y, Bogale A, Hambidge M, Stoecker BJ, Bailey K, Gibson RS. Phytate, zinc, iron and calcium content of selected raw and prepared foods consumed in rural Sidama, Southern Ethiopia, and implications for bioavailability. J Food Comp Anal,20:161-168, 2007. <br /> <p><br /> Braun M, Palacios C, Wigertz K, Jackman LA, Bryant RJ, McCabe LD, Martin BR, McCabe GP, Peacock M, Weaver CM. Racial differences in skeletal calcium retention in adolescent girls on a range of controlled calcium intakes. Am J Clin Nutr, 85:1657-63, 2007.<br /> <p><br /> Bruno RS, Dugan CE, Smyth JA, DiNatale DA., and Koo SI. Green tea extract protects against hepatic steatosis and injury in leptin deficient, spontaneously obese mice. J Nutr, (in press), 2007.<br /> <p><br /> Bu SY, Lerner M, Stoecker BJ, Boldrin E, Brackett DJ, Lucas EA, Smith, BJ. Dried plum polyphenols inhibit osteoclastogenesis under oxidative stress and inflammatory condition. (Submitted to Bone, 2007).<br /> Caire-Juvera G, Arendell LA, Maskarinec G, Thomson CA, Chen Z. Associations between mammographic density and body composition in Hispanic and Non-Hispanic White women by menopausal status. Menopause, (accepted June 2007).<br /> <p><br /> Camporeale G, Oommen AM, Griffin JB, Sarath G, Zempleni J. K12-biotinylated histone H4 marks heterochromatin in human lymphoblastoma cells. J Nutr Biochem. 11:760-8, 2007. [Epub 2007 Apr 16]. <br /> Camporeale G, Zempleni J, Eissenberg JC.Susceptibility to heat stress and aberrant gene expression patterns in holocarboxylase synthetase-deficient Drosophila melanogaster are caused by decreased biotinylation of histones, not of carboxylases. J Nutr 2007 137(4):885-9, 2007.<br /> <p><br /> Carlstrom J, Symons JD, Wu TC, Bruno RS, Litwin E, Jalili T. A quercetin supplemented diet does not prevent cardiovascular complications in spontaneously hypertensive rats. J Nutr, 137(3):628-33, 2007.<br /> <p><br /> Cheong JMK, Martin BR, Jackson GS, Elmore D, McCabe GP, Nolan JR, Barnes S, Peacock M, Weaver, CM. Soy isoflavones do not affect bone resorption in postmenopausal women: A dose response study using a novel approach with 41Ca. J Clin Endocrin Metab, 92:577-585, 2007.<br /> <p><br /> Chew YC, Sarath G, Zempleni J.An avidin-based assay for histone debiotinylase activity in human cell nuclei. J Nutr Biochem, 18(7):475-81, 2007. [Epub 2006 Dec 6]. <br /> <p><br /> Clifford AJ, de Moura FF, Ho CC, Chuang JC, Follett J, Fadel JG, Novotny JA. A feasibility study quantifying in vivo human alpha-tocopherol metabolism. Am J Clin Nutr, 84(6):1430-41, 2006. <br /> <p><br /> Dashwood RH and HoE. Dietary Histone Deacetylase Inhibitors: From Cells to Mice to Man. Seminars in Cancer Biology, 17(5):363-9, 2007.<br /> <p><br /> Driskell JA, Meckna BR, Scales NE. Differences exist in the eating habits of university men and women at fast-food restaurants. Nutr Res, 26:524-530, 2006.<br /> <p><br /> Droke EA, Hager KA, Lerner MR, Lightfoot SA, Stoecker BJ, Brackett DJ, Smith BJ. Soy isoflavones avert chronic inflammation-induced bone loss and vascular disease. J Inflammation, (Lond) (In Press, 2007).<br /> <p><br /> Geiser DL, Mayo JJ, Shen M-C and Winzerling J. The unique regulation of Aedes aegypti larval cell ferritin by iron. Insect Biochemistry and Molecular Biology, 37(5):418-29, 2007.<br /> <p><br /> Geiser DL, Zhang D and Winzerling J. Ferritin secretion: Mosquito cell respond to an iron load. Insect Biochemistry and Molecular Biology, 36(3):177-87, 2006.<br /> <p><br /> Gibson RS, Abebe Y, Stabler S, Allen RH, Westcott J, Stoecker BJ, Krebs NF, Hambidge KM. Zinc, gravida, infection and iron but not B-12 or folate status predict hemoglobin during pregnancy in southern Ethiopia. (Submitted to Journal of Nutrition, 2007).<br /> <p><br /> Gregory-Mercado K, Staten LK, Gillespie C, Thomson CA, Ranger-Moore J, Giuliano A, Will J, Ford E, Marshall J. Ethnicity and nutrient inadequacies among Arizona WISEWOMAN participants. J Womens Health (Larchmt), May 2007.<br /> <p><br /> Gunther CW, Legowski, PA, McCabe LD, McCabe GP, Peacock M, Lyle RM, Weaver CM, Teegarden, D. Parathyroid hormone is associated with decreased fat mass in young health women. Int J Obesity, 30:94-99, 2006.<br /> <p><br /> Herring TA, Cuppett SL, Zempleni J. Genomic implications of H(2)O (2) for cell proliferation and growth of Caco-2 cells. Dig Dis Sci,52(11):3005-15, 2007. [Epub June 28, 2007].<br /> <p><br /> Ho CC, de Moura FF, Kim SH, Clifford AJ.Excentral cleavage of beta-carotene in vivo in a healthy man. Am J Clin Nutr, 85(3):770-7, 2007.<br /> <p><br /> Hollis N, Cussler E, Rock C, Flatt SW, Pierce JP and Thomson CA. Plasma carotenoids are associated with reduced oxidative stress in women previously treated for breast cancer. Cancer Epidemiol Biomarkers Prev, 16:2008-15, 2007. <br /> <p><br /> Hong S, Bardwell WA, Natarajan L, Flatt S, Rock CL, Newman V, Madlensky L, Mills PJ, Dimsdale JE, Thomson CA, Hajek RA, Chilton JA, Pierce JP. Correlates of Physical Activity Level in Breast Cancer Survivors Participating in the Womens Healthy Eating and Living Study (WHEL). Breast Cancer Research & Treatment, 101(2):225-232, 2007.<br /> <p><br /> Kennedy TS, Thomas DG, Wogene T, Abebe Y, Hubbs-Tait L, Stoecker BJ, Hambidge KM. Growth and visual information processing in infants in southern Ethiopia. J Applied Develop Psych, (In Press, 2007). <br /> <p><br /> Kim Y-N, Giraud DW, and Driskell JA. Tocopherol and carotenoid contents of selected Korean cooked combination foods consumed by young Korean children. Nutr Sci, 9:323-329, 2006.<br /> <p><br /> Kim Y-N, Giraud DW, Driskell JA. Tocopherol and carotenoid contents of selected Korean fruits and vegetables. J Food Compos Anal, 20:458-465, 2007.<br /> <p><br /> Kim Y-N, Lee J-Y, Driskell JA. Marginal folate inadequacy observed in a group of young children in Kwangju, Korea. Nutr Res Practice, 2:120-125, 2007.<br /> <p><br /> Koo SI and Noh SK. Green tea as inhibitor of the intestinal absorption of lipids: Potential mechanism for its lipid-lowering effect. J Nutr Biochem, 18:179-183, 2007.<br /> <p><br /> Krebs NF, Abebe Y, Hambidge KM, Westcott JE, Stoecker BJ. Zinc intake from human milk and complementary foods in 7 mo old Ethiopian infants. (Submitted to Eur J Clin Nutr, 2007).<br /> <p><br /> Lawrance AK, Deng L, Brody LC, Finnell RH, Shane B and Rozen R. Genetic and nutritional deficiencies in folate metabolism influence tumorigenicity in Apcmin/+ mice. J Nutr Biochem, 18:305-312, 2007.<br /> <p><br /> Lora KL, Morse KL, Gonzalez-Kruger GE, Driskell JA. High saturated fat and cholesterol intakes and abnormal plasma lipid concentrations observed in a group of 4- to 8-year-old children of Latino immigrants in rural Nebraska. Nutr Res, 27:483-491, 2007.<br /> <p><br /> Margolis KL, Rodabough RJ, Thomson CA, Lopez AM, McTiernan A. Prospective Study of Leukocyte Count as a Predictor of Incident Breast, Colorectal, Endometrial and Lung Cancer and Mortality in Postmenopausal Women. (For the WHI Research Group). Arch of Int Med, 167(17):1837-1844, 2007.<br /> <p><br /> Martin B, Davis S, Campbell W, and Weaver CM. Exercise and calcium supplementation: Effects on calcium homeostasis in sportswomen. Med Sci Sports Exerc, 39:1481-1486, 2007.<br /> <p><br /> Maurer J, Thomson, C, Ranger-Moore J, Teixeira PJ, Lohman TG, Taren D, Cussler E, Going S, Houtkooper L. The Psychosocial and Behavioral Profile and Predictors of Self-Reported Energy Underreporting in Obese Middle-Aged Women. Journal of the American Dietetic Association. (accepted May 2007).<br /> <p><br /> Mulugeta A, Hagos F, Kruseman G, Linderhof V, Stoecker BJ, Abraha Z, Yohannes M, Samuel GG. Factors contributing to child malnutrition in Tigray, Northern Ethiopia. (Submitted to East African Medical Journal, 2007).<br /> <p><br /> Mustachich D, Bruno RS, Traber MG. Vitamin E. Vitam Horm, 76:1-21, 2007. (Invited Review).<br /> <p><br /> Myzak MC, Tong P, Dashwood WM, Dashwood RH and Ho E. Sulforaphane retards the growth of human PC-3 prostate cancer xenografts and inhibits HDAC activity in human subjects. Exp Biol Med, 232(2):227-34, 2007.<br /> <p><br /> Nesaretnam K, Koon TH, Selvaduray KR, Bruno RS, Ho E. Modulation of cell growth and apoptosis response in human prostate cancer cells supplemented with tocotrienols. European Journal of Lipid Science and Technology, accepted pending revisions.<br /> <p><br /> Nielsen FH, Stoecker BJ. Dietary boron and fish oil have different but synergistic effects beneficial to strength and trabecular microarchitecture of bone. (Submitted to Bone, 2007).<br /> <p><br /> Nunn MD, Giraud DW, Parkhurst AM, Hamouz FL, Driskell JA. Effects of cooking methods on sensory qualities and carotenoid retention in selected vegetables. J Food Qual, 29:445-457, 2006.<br /> <p><br /> Owens JE, Holstege DM, Clifford AJ.Comparison of two dietary folate intake instruments and their validation by RBC folate. J Agric Food Chem, 55(9):3737-40, 2007. [Epub 2007 Mar 31]. <br /> <p><br /> Owens JE, Holstege DM, Clifford AJ.High-throughput method for the quantitation of total folate in whole blood using LC-MS/MS. J Agric Food Chem, 55(9):3292-7, 2007. [Epub 2007 Mar 31].<br /> <p><br /> Pham DQD, Kos PJ, Mayo JJ, Winzerling JJ. Regulation of the ribonucleotide reductase small subunit (R2) in the yellow fever mosquito, Aedes aegypti Gene, 372:182-90, 2006.<br /> <p><br /> Pham DQD, Perez VH, Berzin EL, Mayo JJ and Winzerling JJ. Regulation of the ribonucleotide reductase genes in the yellow fever mosquito, Aedes aegypti. Insect Biochemistry and Molecular Biology, Submitted 2007.<br /> <p><br /> Pierce JP, Hollenbach K, Caan BJ, Thomson CA, Stefanick M, Karanja N, Gold EB, Jones LA, Hajeck R, Rock CL, Flatt S, Newman V, Faerber S, Wasserman L, Ritenbaugh C, Bardwell WA, Natarajan L, Kealey S, Madlensky L, Parker BA, Wael, Grove KM, Emond J, Marshall J. Telephone counseling helps maintain long-term adherence to a high vegetable dietary pattern. J Nutrition, 137:2291-2296, 2007. <br /> <p><br /> Pierce JP, Natarajan L, Caan BJ, Parker BA, Greenberg ER, Flatt SW, Rock CL, Kealy S, Al-Delaimy WK, Bardwell WA, Carlson R, Emond JA, Faerber S, Gold EB, Hajek RA, Hollenbach K, Jones LA, Karanja N, Madlensky L, Marshall J, Newman VA, Ritenbaugh C, Thomson CA, Wasserman L, Stefanick ML. The influence of a very high vegetable-fruit-fiber, low-fat diet on prognosis following treatment for breast cancer: The Womens Healthy Eating and Living (WHEL) Randomized Trial. Journal of the American Medical Association, 298(3):289-298, 2007.<br /> <p><br /> Pierce JP, Newman VA, Natarajan L, Flatt SW, Al-Delaimy WK, Caan BJ, Emond JA, Faerber S, Gold EB, Hajek RA, Hollenbach K, Jones LA, Karanja N, Kealey S, Madlensky L, Marshall J, Ritenbaugh C, Rock CL, Stefanick ML, Thomson CA, Wasserman L, Parker BA. Telephone counseling helps maintain long-term adherence to a high-vegetable dietary pattern. Journal of Nutrition, 137:2291-2296, 2007.<br /> <p><br /> Pierce JP, Stefanick ML, Flatt SW, Natarajan L, Sternfeld B, Madlensky Al-Delaimy W, Thomson CA, Kealey S, Hajek R, Parker BA, Newman VA, Caan B, Rock CR. For the WHEL Study Group. Greater Survival in Physically Active Women with High Vegetable-Fruit Intake Regardless of Obesity in Breast Cancer Cohort. Journal of Clinical Oncology, 25(17):2345-2351, 2007.<br /> <p><br /> Prentice RL, Thomson CA, Caan BJ, Hubbell FA, Anderson GL, Beresford SA, Pettinger M, Lane DS, Lessin L, Yasmeen S, Singh B, Khandekar J, Shikany JM, Satterfield S, Chlebowski RT. Low-Fat Dietary Pattern and Cancer Incidence in the Womens Health Initiative Dietary Modification Trial. JNCI, 99:1-10, 2007.<br /> <p><br /> Ramos-Clarmont G, Acedo-Felix ME, Winzerling J and Vazquez-Moreno L. Escherichia coli K88 Interaction with IgA Oligosaccharides. EXCLI Journal, 6:10-22, 2007.<br /> <p><br /> Reinwald S. A longitudinal study of the effect of genistein on bone mass and bone architexture in an innovative perimenopausal mouse model. Doctoral Dissertation, Purdue University, December 2006.<br /> Schernhammer E, Wolpin B, Rifai N, Cochrane B, Manson J, Ma J, Giovannucci E, Thomson CA, Stampfer MJ, Fuchs C. Plasma folate, vitamins B6, B12, and homocysteine and pancreatic cancer risk in four large cohorts. Cancer Research, 67(11); 5553-60, 2007.<br /> <p><br /> Smith EM, Hoi JT, Eissenberg JC, Shoemaker JD, Neckameyer WS, Ilvarsonn AM, Harshman LG, Schlegel VL, Zempleni J. Holocarboxylase synthetase regulates expression of biotin transporters by chromatin remodeling events at the SMVT locus. J Nutr Biochem, 2007.<br /> <p><br /> Smith EM, Hoi JT, Eissenberg JC, Shoemaker JD, Neckameyer WS, Ilvarsonn Am, Harshaman LG, Schlegel VL, Zempleni J. Feeding Drosophila a biotin-deficient diet for multiple generations increases stress resistance and lifespan and alters gene expression and histone biotinylation patterns. J Nutr, 137(9):2006-12, 2007.<br /> <p><br /> Soliman AF, Stoecker BJ, Soung DY, Devareddy L, Arjmandi BH. Effects of dietary components on cadmium-induced bone loss in an ovariectomized rat model of osteoporosis (Submitted to Calcified Tissue International, 2007). <br /> <p><br /> Stoecker BJ, Abebe Y, Hubbs-Tait L, Kennedy TS, Gibson RS, Krebs NF, Hambidge KM. Zinc status and cognitive function of pregnant women in southern Ethiopia. (Submitted to European Journal of Clinical Nutrition, 2007).<br /> <p><br /> Thomson CA, Newton TR, Graver EJ, Jackson K, Reid PM, Hartz VL, Cussler EC, Hakim IA. Cruciferous Vegetable Intake Questionnaire Improves Cruciferous Vegetable Intake Estimates. Journal of the American Dietetic Association, 107(4):631-643, 2007.<br /> <p><br /> Thomson CA, Rock CL, Caan BJ, Flatt SW, Al-Delaimy WA, Newman VA, Hajek RA, Chilton RJ, Pierce JP. Increase in Cruciferous Vegetable Intake in Women Previously Treated for Breast Cancer Participating in a Dietary Intervention Trial. Nutrition and Cancer, 57(1):11-19, 2007.<br /> <p><br /> Villarreal A, Stoecker BJ, Garcia C, Garcia K, Rios R, Gonzales C, Mandadi K, Faraji B, Patil BS, Deyhim F. Cranberry juice improved antioxidant status without affecting bone quality in orchidectomized male rats. Phytomedicine, 14:815-820, 2007.<br /> <p><br /> Weaver CM, Cheong J, Jackson G, Elmore, D, McCabe G, Martin, B. 3H-tetracycline as a proxy for 41Ca for measuring dietary perturbations of bone resorption. Nuclear Instruments and Methods in Physics Research, 259:1, 790-795, 2007.<br /> <p><br /> Weaver CM, McCabe LD, McCabe GP, Novotny R, Van Loan M, Going S, Matkovic V, Boushey C, Savaiano DA, ACT research team. Bone Mineral and Predictors of Bone Mass in White, Hispanic, and Asian Early Pubertal Girls. Calcif Tissue Int (in press 2007).<br /> <p><br /> Zhao Y, Fleet JC, Adamec J, Terry DE, Zhang X, Kemeh S, Davisson VJ. and Weaver CM. Effects of hindlimb unloading and bisphosphonates on the serum proteome of rats. Bone (accepted 2007). <br /> <p><br /> Zhou G, Kohlhepp P, Geiser DL, Frasquillo C, Vazquez-Moreno L and Winzerling JJ. Fate of blood meal iron in mosquitoes. Journal of Insect Physiology, 53(11):1169-78, 2007.<br />

Impact Statements

1. Insight into mechanisms by which foods, nutrients and phytochemicals such as sulforaphane, cruciferous vegetables, iron and folate impact chronic diseases such as cancer. Findings based on identification of nutrient gene interactions, which appear to be important factors contributing to increased risk of disease, may aid in discovery of dietary based remedies resulting in reduction of health care costs and reduced personal burden by individuals and their support systems.
2. Establishing metabolic fat and dietary recommendations of specific nutrients for optimal health. Findings may result in specific dietary recommendations designed to encourage lower blood triglyceride (fat) levels and reduce obesity induced chronic disease, provide an understanding of the relative potencies of the various forms of folate for humans, and clarify the impact of polymorphisms on vitamin B requirements.
3. Collaborative work will help establish risk factors for osteoporosis and other bone disorders related to diet. The ability to examine microarchitecture of bone allows us to evaluate which dietary components ultimately affect bone and establishes a basis for mechanistic studies.

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