![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Departments of
*
Nutritional Sciences and
Statistics, Oklahoma State University, Stillwater, OK 74078
2To whom correspondence should be addressed. E-mail: arjmand{at}okstate.edu.
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
65 y of age, data were analyzed separately for men 
65 y and those <65 y of age. The response to protein supplementation was consistent in the two age groups. The effects of SP on serum IGF-I levels suggest that SP may positively influence bone in men. Longer-duration studies examining the effects of SP or its isoflavones on bone turnover and bone mineral density and content in men are warranted.
KEY WORDS: • age • bone • isoflavones • men • selective estrogen receptor modulators
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
). In the United States, men suffer from one third of all hip fractures and one half of all symptomatic vertebral fractures (2
). Although the etiology of male osteoporosis shares some commonalities with female osteoporosis (3
), it is not clear if available treatment options that are mostly directed toward postmenopausal osteoporosis are also effective in preventing or treating osteoporosis in men (1
,2
).
As is the case in women, it is becoming increasingly apparent that estrogen is an important modulator of bone metabolism in men (4
,5
). Because estrogen therapy may not be feasible in men, compounds such as selective estrogen receptor modulators (SERM), which are believed to exert estrogen-like effects on bone but not other tissues (6
,7
), could be of benefit to men. Soy protein (SP) contains a group of nonsteroidal phenolic compounds, isoflavones, referred to as natural SERM (7
,8
). Additionally, SP has been shown to increase bone mineral content and bone mineral density (BMD) of the lumbar spine in postmenopausal women (9
), attenuate bone loss from the lumbar spine in perimenopausal women (10
) and increase BMD of Ward’s triangle in young adult women (11
). Whether SP has similar effects on bone metabolism in men has not been investigated. Hence, we hypothesized that, analogous to its effects in women, SP supplementation positively influences bone in men. The present study examined the effects of SP supplementation on markers of bone turnover such as serum alkaline phosphatase (AP) activity, a nonspecific marker of bone formation (12
), serum bone-specific AP (BSAP) activity, a specific marker of bone formation (13
), and urinary deoxypyridinoline (Dpd), a specific marker of bone resorption (14
) as well as serum insulin-like growth factor-I (IGF-I), a factor associated with higher rates of bone formation (15
–17
), in men. Additionally, because the risk of osteoporosis-related fracture increases in men with age (18
) and substantial bone loss occurs in men after age 65 y (2
), we analyzed the effects of SP supplementation on bone metabolism in men 65 y of age and older separately from those younger than 65 y of age.
|
SUBJECTS AND METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
Sixty-four men (mean ± SD, 59.2 ± 17.6 y) with no known history of osteoporosis, cancer, insulin-dependent diabetes mellitus, liver and kidney diseases, thyroid and parathyroid disorders, chronic gastrointestinal disorders or allergy to milk or SP were recruited for this study. Exclusion criteria included current use of any prescription medications known to alter bone and calcium metabolism. Ethnic and racial backgrounds were not taken into consideration. However, recruited subjects were all Caucasian males with the exception of one African-American male. Subjects were asked to sign a consent form after receiving oral and written descriptions of the study. Complete medical and diet histories were obtained from all subjects before initiating the treatments. Subjects were recruited primarily from the Oklahoma State University campus (Stillwater, OK) and the surrounding communities. The study protocol was approved by the Institutional Review Board at Oklahoma State University.
Study design
Study participants were randomly assigned to consume daily either supplemental SP (SP isolate) or supplemental milk-based protein (MP; consisting of a MP isolate containing a combination of casein and whey) used as control for 3 mo in a double-blind, randomized, controlled, parallel design. The protein supplements were obtained from the same lot and were provided in monthly rations to study participants in packages for daily consumption. Each day, subjects were asked to consume 58 g of a powdered, unflavored drink mix (Protein Technologies International, St. Louis, MO). The 58 g of powdered supplement provided 40 g of either SP isolate or MP isolate and 1400 mg calcium and 5 µg vitamin D daily. The SP supplement provided 88 mg total isoflavones per day whereas the MP supplement was free of isoflavones. Subjects were asked to return any unused supplement packages and mark calendars daily as part of monitoring compliance. Subjects were free living, consumed their habitual diet and maintained their usual physical activity.
Dietary assessments
For each subject medical and nutrition histories were obtained at the beginning of the study. One-week food frequency questionnaires were obtained via interview by a registered dietitian at the beginning and at the end of the 3-mo study period. Nutrient analysis of dietary intake was performed using food analysis software (Food Processor version 7.50; ESHA Research, Salem, OR).
Urine and blood collection
Study participants were instructed to collect the urinary output for 24-h, excluding the first void of the day, just before initiation of treatment and then again on the day before the termination of the 3-mo supplementation period. Urine volume was recorded and aliquots were collected and stored at -20°C until analyses. Blood was obtained from subjects after an overnight fast at baseline and at the end of the study. Blood was centrifuged for 15 min at 1500 x g and serum was collected and stored at -80°C until it was analyzed.
Serum analyses
Radioimmunoassay kits were used to analyze serum IGF-I (Nichols Institute Diagnostics, San Juan Capistrano, CA) and estradiol (Diagnostic Systems Laboratories, Webster, TX). Serum AP activity was determined using colorimetric kits from Roche Diagnostics (Somerville, NJ). These tests were performed on a Cobas-Fara II Clinical Analyzer (Montclair, NJ). Serum BSAP activity was quantified by immunoassay in a microtiter format (Metra Biosystems, Mountain View, CA). The intra- and interassay coefficients of variation (CV) were 3 and 8.4%, 6.5 and 9.7%, 1.9 and 2.8% and 3.9 and 7.6% for IGF-I, estradiol, AP and BSAP, respectively.
Urinary analyses
Urinary creatinine was measured colorimetrically with a commercially available kit from Roche Diagnostics using a Cobas Fara II Clinical Analyzer. Urinary Dpd was measured by competitive enzyme immunoassay in a microassay stripwell format (Quidel, Mountain View, CA). The intra- and interassay CV were 1.7 and 6.3% and 4.3 and 4.6% for creatinine and Dpd, respectively.
Statistical analyses
The data were first analyzed for the overall effects of protein supplements in men irrespective of their age and then the data were stratified into two subgroups—those 65 y and those <65 y—because substantial bone loss occurs in men after age 65 (2
). Because age and average calcium and vitamin D intakes may affect bone metabolism, we examined treatment effects on serum and urine markers of bone turnover by performing analysis of covariance using PROC MIXED in PC SAS (version 8.2; SAS Institute, Cary, NC) with age and mean vitamin D and calcium intakes used as covariates. Values for all variables were normally distributed as determined using the Kolmogorov and Smirnov tests for normal distribution. Paired t tests were used to determine whether change due to each treatment was significantly different from zero. Data are reported as least square mean ± SEM; unless otherwise indicated, P < 0.05 was regarded as significant.
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
. All baseline characteristics did not differ between the two treatments for all participants and in each age group, indicating that the subjects were well matched.
|
Values after treatment and changes from baseline for serum AP and BSAP activities, as well as urinary Dpd excretion, did not differ between SP- or MP-supplemented groups in all men, those 65 y and those <65 y (data not shown). SP and MP supplements did not affect circulating estradiol concentrations (data not shown).
When serum and urine markers of bone turnover were analyzed with age and mean vitamin D and calcium intakes as covariates, there were no effects of SP or MP supplementation (data not shown).
Both protein supplements increased serum IGF-I levels relative to baseline values. However, the increase due to SP supplementation was greater (P < 0.01) than the MP treatment in all men and when they were stratified by age (Fig. 1
). This increase in serum IGF-I due to SP, but not MP, supplementation above baseline values was significantly different from zero (P < 0.0001).
|
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
–11
); however, its effects in men have not been studied. In the male rat model of osteoporosis, SP has been shown to delay the onset of age-related bone loss (19
), yet its specific effects on bone metabolism are unclear. In the present clinical study, SP did not affect urinary excretion of Dpd or serum AP or BSAP activities compared with baseline or MP, but increased serum levels of IGF-I to a greater extent than MP. Although the effect of circulating IGF-I on bone is not well established, it has been suggested to play a role in bone formation. For example, IGF-I has been reported to directly stimulate collagen synthesis in vitro by osteoblastic cells (20
) and may mediate the anabolic action of parathyroid hormone on bone (21
). In this respect, IGF-I is thought to promote the differentiation, maturation and recruitment of osteoblasts to increase their ability to rebuild bone at resorbed sites (22
,23
). Additionally, this growth factor has been associated with increased rates of bone formation in humans (24
), human marrow cells (25
) and animals (16
,26
). Serum IGF-I concentrations have also been reported to correlate positively with bone mass in premenopausal (27
), perimenopausal (28
), postmenopausal (15
) and elderly women (29
) and with bone mineral density in men (30
). Furthermore, the decline in serum IGF-I with age (31
) has been suggested to contribute to the age-associated bone loss in elderly men and women (17
,32
). The importance of serum IGF-I to bone in men is supported by observations that men with idiopathic osteoporosis have reduced circulating IGF-I levels (22
) associated with reduced lumbar spine BMD and increased bone surface erosion (22
).
Although SP significantly increased serum IGF-I, whether this had an anabolic effect on bone could not be determined in this short-duration study. Soy isoflavones have been shown to stimulate osteoblastic activity through activation of estrogen receptors (33
). However, our findings that isoflavone-containing SP can increase serum IGF-I but not BSAP is paradoxical, making the bone-forming ability of SP questionable. Furthermore, in this study, serum IGF-I levels and BSAP activity were not correlated (r2 = 0.004 and 0.08 for SP and MP, respectively, with the slopes not different from zero; Fig. 2
). Similar results showing a lack of effect of SP supplementation on markers of bone formation have also been observed in women (10
,34
–36
). However, even in women where SP supplementation has been shown to exert beneficial effects on bone, data have not been consistent (34
,36
,37
). Hence, the effects of SP supplementation on bone may best be evaluated in longer-duration studies where bone mineral content and density can be assessed.
|
,10
,38
,39
). Soy isoflavones have been referred to as naturally occurring SERM (15
,16
). Recently, the effects of a synthetic SERM, raloxifene, on markers of bone turnover were examined in men (40
). In that study (40
), similar to our findings with naturally occurring SERM, the synthetic SERM did not affect markers of bone turnover in men. However, authors of that study (40
) suggested that the SERM may be effective in men with low estradiol levels (serum total estradiol <95 pmol/L). The serum estradiol levels of men in the present study were generally around or lower than 95 pmol/L; however, the sample size was not sufficient to stratify the response to protein supplementation by estradiol level. It is possible that more pronounced effects of SP supplementation on biomarkers of bone turnover could have been detected in men with low circulating estradiol. In conclusion, the increase in circulating IGF-I concentrations attributable to SP supplementation in men of both age groups lends credence to future examinations of the effects of SP or its constituents on bone biomarkers and bone mineral density and content in men. Evaluation of the efficacy of SP on reducing osteoporosis and osteoporosis-related fracture risk in men is needed.
|
FOOTNOTES |
|---|
3 Abbreviations used: AP, alkaline phosphatase; BMD, bone mineral density; BSAP, bone-specific AP; CV, coefficient of variation; Dpd, deoxypyridinoline; IGF-I, insulin-like growth factor-I; MP, milk-based protein; SERM, selective estrogen receptor modulator; SP, soy protein.
Manuscript received 21 March 2002. Initial review completed 13 April 2002. Revision accepted 25 June 2002.
|
LITERATURE CITED |
|---|
|
TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
1. National Osteoporosis Foundation (1999) Men and Osteoporosis 1999 National Osteoporosis Foundation Washington, D.C. .
2. National Institutes of Health (1998) Osteoporosis in Men. National Institutes of Health, Osteoporosis and Related Bone Diseases 1998 National Resource Center Washington, D.C. .
3. Bilezikian, J. P., Kurland, E. S. & Rosen, C. J. (1999) Idiopathic osteoporosis in men. Orwoll, E. S. eds. Osteoporosis in Men: The Effects of Gender on Skeletal Health 4th ed. 1999:395-416 Academic Press San Diego, CA. .
4. Khosla, S., Melton, L. J., III., Atkinson, E. J. & O’Fallon, W. M. (2000) Relationship of serum sex steroid levels to longitudinal changes in bone density in young versus elderly men. J. Clin. Endocrinol. Metab. 86:3555-3561.
5. Falahati-Nini, A., Riggs, B. L., Atkinson, E. J., O’Fallon, W. M., Eastell, R. & Khosla, S. (2000) Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men. J. Clin. Invest. 106:1553-1560.[Medline]
6. Jordan, V. C., Gaptsur, S. & Morrow, M. (2001) Selective estrogen receptor modulation and reduction in risk of breast cancer, osteoporosis, and coronary heart disease. J. Natl. Cancer. Inst. 93:1449-1457.
7. Setchell, K. D. (2001) Soy isoflavones: benefits and risks from nature’s selective estrogen receptor modulators (SERMs). J. Am. Coll. Nutr. 20:354S-362S.
8. Brzezinski, A. & Debi, A. (1999) Phytoestrogens: the "natural" selective estrogen receptor modulators?. Eur. J. Obstet. Gynecol. Reprod. Biol. 85:47-51.[Medline]
9. Potter, S. M., Baum, J. A., Teng, H., Stillman, R. J., Shay, N. F. & Erdman, J. W., Jr. (1998) Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. Am. J. Clin. Nutr. 68(Suppl.):137S-139S.
10. Alekel, D. L., St. Germain, A., Peterson, C. T., Hanson, K. B., Stewart, J. W. & Toda, T. (2001) Isoflavone-rich soy protein isolate attenuates bone loss in the lumbar spine of perimenopausal women. Am. J. Clin. Nutr. 72:844-852.
11. Anderson, J. J., Boass, A. & Xiaowei, C. (2001) Isoflavone effects on bone mineral content (BMC) and bone mineral density (BMD) in young adult women. FASEB J. 15:A728.
12. Garnero, P. & Delmas, P. D. (1996) New developments in biochemical markers of osteoporosis. Calcif. Tissue. Int. 59(Suppl.):S2-S9.
13. Garnero, P. & Delmas, P. D. (1993) Assessment of the serum levels of bone alkaline phosphatase with a new immunoradiometric assay in patients with metabolic bone disease. J. Clin. Endocrinol. Metab. 77:1046-1053.[Abstract]
14. Robins, S. P., Woitge, H., Hesley, R., Ju, J., Seyedin, S. & Seibel, M. J. (1994) Direct enzyme-linked immunoassay for urinary deoxypyridinoline as a specific marker for measuring bone resorption. J. Bone Miner. Res. 9:1643-1649.[Medline]
15. Kalu, D. N., Arjmandi, B. H., Liu, C. C., Salih, M. A. & Birnbaum, R. S. (1994) Effects of ovariectomy and estrogen on the serum levels of insulin-like growth factor-I and insulin-like growth factor binding protein-3. Bone Miner 25:135-148.[Medline]
16. Danielsen, C. C. & Flyvbjerg, A. (1996) Insulin-like growth factor I as a predictor of cortical bone mass in a long-term study of ovariectomized and estrogen-treated rats. Bone 19:493-498.[Medline]
17. Boonen, S., Lesaffre, E., Dequeker, J., Aerssens, J., Nijs, J., Pelemans, W. & Bouillon, R. (1996) Relationship between baseline IGF-I and femoral bone density in women aged over 70 years: potential implications for prevention of age-related bone loss. J. Am. Geriatr. Soc. 44:1301-1306.[Medline]
18. Melton, L. J., III. (1993) Hip fractures: a worldwide problem today and tomorrow. Bone 14:S1-S8.
19. Kalu, D. N., Masoro, E. J., Yu, B. P., Hardin, R. R. & Hollis, B. W. (1988) Modulation of age-related hyperparathyroidism and senile bone loss in Fischer rats by soy protein and food restriction. Endocrinology 122:1847-1854.
20. McCarthy, T. L., Centrella, M. & Canalis, E. (1989) Regulatory effects of IGF-I and IGF-II on bone collagen synthesis in rat calverial culture. Endocrinology 124:301-309.
21. Bikel, D. D., Halloran, B. P., Leary, C., Wider, T., Nauman, E., Rosen, C. J., Laib, A. & Majumdar, S. (2000) Insulin-like growth factor-I (IGF-I) is required for the anabolic action of parathyroid hormone (PTH) on bone. J. Bone Miner. Res. 15:S215(abs.).
22. Kurland, E. S., Rosen, C. J., Cosman, F., McMahon, D., Chan, F., Shane, E., Lindsay, R., Dempster, D. & Bilezikian, J. P. (1997) Insulin-like growth factor-I in men with idiopathic osteoporosis. J. Clin. Endocrinol. Metab. 82:2799-2805.
23. Rosen, C., Donahue, L. R. & Hunter, S. J. (1994) Insulin-like growth factors and bone: the osteoporosis connection. Proc. Soc. Exp. Biol. Med. 206:83-102.[Medline]
24. Byers, R. J., Hoyland, J. A. & Braidman, I. P. (2001) Osteoporosis in men: a cellular endocrine perspective of an increasingly common clinical problem. J. Endocrinol. 168:353-362.[Abstract]
25. Thomas, T., Gori, F., Spelsberg, T. C., Khosla, S., Riggs, B. L. & Conover, C. A. (1999) Response of bipotential human marrow stromal cells to insulin-like growth factors: effect on binding protein production, proliferation, and commitment to osteoblasts and adipocytes. Endocrinology 140:5036-5044.
26. Wakisaka, A., Tanaka, H., Barnes, J. & Liang, C. T. (1998) Effect of locally infused IGF-I on femoral gene expression and bone turnover activity in old rats. J. Bone Miner. Res. 13:13-19.[Medline]
27. Romagnoli, E., Minisola, S., Carnevale, V., Scarda, A., Rosso, R., Scarnecchia, L., Pacitti, M. T. & Mazzuoli, G. (1993) Effect of estrogen deficiency on IGF-I plasma levels: relationship with bone mineral density in premenopausal women. Calcif. Tissue Int. 53:1-6.[Medline]
28. Nasu, M., Sugimoto, T., Chihara, M., Hiraumi, M., Kurimoto, F. & Chihara, K. (1997) Effect of natural menopause on serum levels of IGF-I and IGF-binding proteins: relationship with bone mineral density and lipid metabolism in perimenopausal women. Eur. J. Endocrinol. 136:608-616.
29. Langlois, J. A., Rosen, C. J., Visser, M., Hannan, M. T., Harris, T., Wilson, P. W. & Kiel, D. P. (1998) Association between insulin-like growth factor I and bone mineral density in older women and men: The Framingham Heart Study. J. Clin. Endocrinol. Metab. 83:4257-4262.
30. Janssen, J. A., Burger, H., Stolk, R. P., Grobbee, D. E., De Jong, F. H., Lamberts, S. W. & Pols, H. A. (1998) Gender-specific relationship between serum free and total IGF-I and bone mineral density in elderly men and women. Eur. J. Endocrinol. 138:627-632.[Abstract]
31. Rajaram, S., Baylink, D. J. & Mohan, S. (1997) Insulin-like growth factor-binding proteins in serum and other biological fluids: regulation and functions. Endocr. Rev. 18:801-831.
32. Boonen, S., Aerssens, J., Dequeker, J., Nicholson, P., Cheng, X., Lowet, G., Verbeke, G. & Bouillon, R. (1997) Age-associated decline in human femoral neck cortical and trabecular content of insulin-like growth factor I: potential implications for age-related (type II) osteoporotic fracture occurrence. Calcif. Tissue Int. 61:173-178.[Medline]
33. Choi, E. M., Suh, K. S., Kim, Y. S., Choue, R. W. & Koo, S. J. (2001) Soybean ethanol extract increases the function of osteoblastic MC3T3–E1 cells. Phytochemistry 56:733-739.[Medline]
34. Arjmandi, B. H. & Smith, B. J. (2002) Soy isoflavones’ osteoprotective role in postmenopausal women: mechanism of action. J. Nutr. Biochem. 13:130-137.[Medline]
35. Gallagher, J. C., Rafferty, K., Haynatzka, V. & Wilson, M. (2000) Effects of soy protein on bone metabolism. J. Nutr. 130:667S(abs.).
36. Scheiber, M. D., Liu, J. H., Subbiah, M. T., Rebar, R. W. & Setchell, K. D. (2001) Dietary inclusion of whole soy foods results in significant reductions in clinical risk factors for osteoporosis and cardiovascular disease in normal postmenopausal women. Menopause 8:384-392.[Medline]
37. Wangen, K. E., Duncan, A. M., Merz-Demlow, B. E., Xu, X., Marcus, R., Phipps, W. R. & Kurzer, M. S. (2000) Effects of soy isoflavones on markers of bone turnover in premenopausal and postmenopausal women. J. Clin. Endocrinol. Metab. 85:3043-3048.
38. Arjmandi, B. H., Getlinger, M. J., Goyal, N. V., Alekel, L., Hasler, C. M., Juma, S., Drum, M. L., Hollis, B. W. & Kukreja, S. C. (1998) The role of soy protein with normal or reduced isoflavone content in reversing ovarian hormone deficiency induced bone loss in rats. Am. J. Clin. Nutr. 68(Suppl.):1358S-1363S.[Abstract]
39. Arjmandi, B. H., Birnbaum, R., Goyal, N. V., Getlinger, M. J., Juma, S., Alekel, L., Hasler, C. M., Drum, M. L., Hollis, B. W. & Kukreja, S. C. (1998) The bone modulating effect of soy protein in ovarian hormone deficiency is related to its isoflavone content. Am. J. Clin. Nutr. 68(Suppl.):1364S-1368S.[Abstract]
40. Doran, P. M., Riggs, B. L., Atkinson, E. J. & Khosla, S. (2001) Effects of raloxifene, a selective estrogen receptor modulator, on bone turnover markers and serum sex steroid and lipid levels in elderly men. J. Bone Miner. Res. 16:2118-2125.[Medline]
This article has been cited by other articles:
|
|
 |
|
  W.-P. Koh, A. H. Wu, R. Wang, L.-W. Ang, D. Heng, J.-M. Yuan, and M. C. Yu Gender-specific Associations Between Soy and Risk of Hip Fracture in the Singapore Chinese Health Study Am. J. Epidemiol., October 1, 2009; 170(7): 901 - 909. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Vrieling, M. A. Rookus, E. Kampman, J. M.G. Bonfrer, A. Bosma, A. Cats, J. van Doorn, C. M. Korse, B. J.M. Witteman, F. E. van Leeuwen, et al. No Effect of Red Clover-Derived Isoflavone Intervention on the Insulin-Like Growth Factor System in Women at Increased Risk of Colorectal Cancer Cancer Epidemiol. Biomarkers Prev., October 1, 2008; 17(10): 2585 - 2593. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-R. Zhou, L. Li, and W. Pan Dietary soy and tea combinations for prevention of breast and prostate cancers by targeting metabolic syndrome elements in mice Am. J. Clinical Nutrition, September 1, 2007; 86(3): 882S - 888S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R J. Barnard Prostate cancer prevention by nutritional means to alleviate metabolic syndrome Am. J. Clinical Nutrition, September 1, 2007; 86(3): 889S - 893S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J Lees, J. R Kaplan, H. Chen, C. P Jerome, T. C Register, and A. A Franke Bone mass and soy isoflavones in socially housed, premenopausal macaques Am. J. Clinical Nutrition, July 1, 2007; 86(1): 245 - 250. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Vrieling, M. A. Rookus, E. Kampman, J. M. G. Bonfrer, C. M. Korse, J. van Doorn, J. W. Lampe, A. Cats, B. J. M. Witteman, F. E. van Leeuwen, et al. Isolated Isoflavones Do Not Affect the Circulating Insulin-Like Growth Factor System in Men at Increased Colorectal Cancer Risk J. Nutr., February 1, 2007; 137(2): 379 - 383. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Kerstetter, D. E. Wall, K. O. O'Brien, D. M. Caseria, and K. L. Insogna Meat and Soy Protein Affect Calcium Homeostasis in Healthy Women J. Nutr., July 1, 2006; 136(7): 1890 - 1895. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. McCarty and K. I. Block Toward a Core Nutraceutical Program for Cancer Management Integr Cancer Ther, June 1, 2006; 5(2): 150 - 171. [Abstract] [PDF]
|
|
|
|
 |
|
 F. M. Sacks, A. Lichtenstein, L. Van Horn, W. Harris, P. Kris-Etherton, M. Winston, and for the American Heart Association Nutrition Commi Soy Protein, Isoflavones, and Cardiovascular Health: An American Heart Association Science Advisory for Professionals From the Nutrition Committee Circulation, February 21, 2006; 113(7): 1034 - 1044. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-P. Bonjour Dietary Protein: An Essential Nutrient For Bone Health J. Am. Coll. Nutr., December 1, 2005; 24(suppl_6): 526S - 536S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. W. Parodi Dairy Product Consumption and the Risk of Breast Cancer J. Am. Coll. Nutr., December 1, 2005; 24(suppl_6): 556S - 568S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Devine, I. M Dick, A. F. Islam, S. S Dhaliwal, and R. L Prince Protein consumption is an important predictor of lower limb bone mass in elderly women Am. J. Clinical Nutrition, June 1, 2005; 81(6): 1423 - 1428. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. W. Voskuil, A. Vrieling, L. J. van't Veer, E. Kampman, and M. A. Rookus The Insulin-like Growth Factor System in Cancer Prevention: Potential of Dietary Intervention Strategies Cancer Epidemiol. Biomarkers Prev., January 1, 2005; 14(1): 195 - 203. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F McCarty Insulin and IGF-I as determinants of low 'Western' cancer rates in the rural third world Int. J. Epidemiol., August 1, 2004; 33(4): 908 - 910. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kreijkamp-Kaspers, L. Kok, D. E. Grobbee, E. H. F. de Haan, A. Aleman, J. W. Lampe, and Y. T. van der Schouw Effect of Soy Protein Containing Isoflavones on Cognitive Function, Bone Mineral Density, and Plasma Lipids in Postmenopausal Women: A Randomized Controlled Trial JAMA, July 7, 2004; 292(1): 65 - 74. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. M. Probst-Hensch, H. Wang, V. H. H. Goh, A. Seow, H.-P. Lee, and M. C. Yu Determinants of Circulating Insulin-like Growth Factor I and Insulin-like Growth Factor Binding Protein 3 Concentrations in a Cohort of Singapore Men and Women Cancer Epidemiol. Biomarkers Prev., August 1, 2003; 12(8): 739 - 746. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. F. Adams, K. M. Newton, C. Chen, S. S. Emerson, J. D. Potter, E. White, and J. W. Lampe Soy Isoflavones Do Not Modulate Circulating Insulin-Like Growth Factor Concentrations in an Older Population in an Intervention Trial J. Nutr., May 1, 2003; 133(5): 1316 - 1319. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
