Understanding Soy

1. Understanding Soy • Soy has been consumed by Asian cultures for thousands of years. • Soy is a legume that is so nutritionally complete that it sustained Eastern populations through drought and famine. • Composed of: • Protein - Carbohydrate • Fat - Fiber • Phytonutrients - Isoflavones • Other isoflavone rich foods include garbanzo beans and sprouts (Red Clover)

2. The forms of soy • Soy has been used and studied in various forms: • Whole soybeans-raw and cooked • Protein isolates-with balanced and unbalanced isoflavone content • Balanced isoflavone isolates • Single isoflavone isolates • The more imbalanced the isoflavones the greater the chance for negative affects.

3. Why is their confusion around soy? • Negative articles regarding soy typically focus on only one particular study. • Thorough evaluation of existing research will reveal the positive health benefits of soy. • Also, certain companies and/or individuals are exploiting negative research as a marketing tactic.

4. Frequently Asked Questions about Soy • Is GMO soy is used in Metagenics products? • Do Metagenics soy products have the proper balance of isoflavones? • Is soy beneficial for tissue health? Menopause? Bone health? • Do you think people are eating too much soy? • Do soy products compromise male reproduction? • Isn’t it better to use a more complete protein? • Do I have to use fermented soy products to achieve therapeutic benefits? • Does soy inhibit thyroid function? • How common is soy allergy?

5. Is GMO soy is used in Metagenics products? • NO. We use only DNA identified soy to guarantee the purity of our ingredients. • We test every batch to ensure we are using only the purest soy protein. • Our “Identity Preserved” soy allows us to trace the source of the raw material and ensure it is not genetically modified. • Being certified by regulatory agencies of NNFA, NSF and TGA shows how seriously we take the quality of all of our products. • Over $2 million spent in 2005 on QC/QA

6. Do Metagenics soy products have a natural balance of isoflavones? • Yes. Our soy products are evaluated to verify they have natural ratios of the isoflavones Genistein and Daidzein. • Isoflavones from soy are 100 to 1000 times weaker than estradiol. • Collins. Steroids 1997;62:365 • Our soy products carry a 1:1 ratio of these isoflavones which is identical to what is found in tofu. • Our 35 full-time scientists led by Dr. Jeffrey Bland are involved in every aspect of product formulation, research and testing. • Over $5 million spent in 2005.

7. Is soy beneficial for tissue health? • Yes. Soy contains various beneficial agents for tissue health • Kennedy AR. The evidence for soybean products as cancer preventive agents. J Nutr 1995;125(3 Suppl):733S-43S. • Cultures that eat soy have shown an improvement in colon and specific hormone-related tissue health issues. • Shu XO, Jin F, Dai Q, et al. Soyfood intake during adolescence and subsequent risk of breast cancer among Chinese women. Cancer Epidemiol Biomarkers Prev 2001;10(5):483-88. • Lamartiniere CA, Moore JB, Brown NM, Thompson R, Hardin MJ, Barnes S. Genistein suppresses mammary cancer in rats. Carcinogenesis 1995;16(11):2833-40. • Human trials involving post-menopausal women demonstrate a significant shift in healthy estrogen metabolism. • Xu X, Duncan AM, Merz BE, Kurzer MS. Effects of soy isoflavones on estrogen and phytoestrogen metabolism in premenopausal women. Cancer Epidemiol Biomarkers Prev 1998;7(12):1101-08. • Xu X, Duncan AM, Wangen KE, Kurzer MS. Soy consumption alters endogenous estrogen metabolism in postmenopausal women. Cancer Epidemiol Biomarkers Prev 2000;9(8):781-86.

8. Is soy beneficial for breast health? • Research is far from conclusive on this issue and researchers are urging caution for women • However, a distinction should be made between the clear benefit of soy protein for cardiovascular health and the inconclusive role of isoflavones for breast tissue health. • Henkel J. U.S. Food and Drug Administration. Soy: Health claims for soy protein, questions about other components. Available at: http://www.fda.gov/fdac/features/2000/300_soy.html. Accessed August 4, 2004. • Messina M, Erdman J Jr, Setchell KD. Introduction to and perspectives from the Fifth International Symposium on the Role of Soy in Preventing and Treating Chronic Disease. J Nutr 2004;134(5):1205S-06S. • Xu X, Duncan AM, Merz BE, Kurzer MS. Effects of soy isoflavones on estrogen and phytoestrogen metabolism in premenopausal women. Cancer Epidemiol Biomarkers Prev 1998;7(12):1101-08. • Xu X, Duncan AM, Wangen KE, Kurzer MS. Soy consumption alters endogenous estrogen metabolism in postmenopausal women. Cancer Epidemiol Biomarkers Prev 2000;9(8):781-86.

9. Does soy benefit menopausal women? • Yes. The research shows a great correlation with reducing hot flashes and other menopausal issues by consuming soy products. • Consumption of soy protein containing isoflavones decreased the intensity of hot flashes. • Washburn S, Burke GL, Morgan T, Anthony M. Effect of soy protein supplementation on serum lipoproteins, blood pressure, and menopausal symptoms in perimenopausal women. Menopause 1999;6(1):7-13. • The majority of studies in menopausal women have shown improvement of hot flashes following soy consumption. • The role of isoflavones in menopausal health: consensus opinion of The North American Menopause Society. Menopause 2000;7(4):215-29. • Eden J. Phytoestrogens and the menopause. Baillieres Clin Endocrinol Metab 1998;12(4):581-87. • Dalais FS, Rice GE, Wahlqvist ML, et al. Effects of dietary phytoestrogens in postmenopausal women. Climacteric 1998;1(2):124-29.

10. Is soy beneficial for bone health? • Yes. Studies have shown that the isoflavones that are found in soy stimulate bone formation and reduce bone breakdown. • Soy isoflavones have been found to have a positive effect on bone health. • Migliaccio S, Anderson JJ. Isoflavones and skeletal health: are these molecules ready for clinical application? Osteoporos Int 2003;14(5):361-68. • Isoflavones stimulate osteoblastic bone formation and inhibit osteoclastic bone breakdown. • Brynin R. Soy and its isoflavones: a review of their effects on bone density. Altern Med Rev 2002;7(4):317-27.

11. Do you think people are eating too much soy? • Americans eat very little soy products when compared to Asian populations. • While Asian populations consume an average of 10 to 50 grams of soy per day, Americans generally consume only 1 to 3 grams daily. • Limer JL, Speirs V. Phyto-oestrogens and breast cancer chemoprevention. Breast Cancer Res 2004;6(3):119-27. • In fact, one-quarter of Americans reported consuming soy foods once a week or more, while 38% admitted to never consuming soy products. • United Soybean Board. National Report, 2004-2005. Consumer attitudes about nutrition – Insights into nutrition, health, and soyfoods. Available at: http://www.talksoy.com/pdfs/ConsumerAttitudes2004.pdf. Accessed August 5, 2004.

12. Do soy products compromise male reproduction? • NO. Studies done with balanced soy isoflavones do not show negative impact on male reproduction. • These studies done with one isoflavone or by injecting isoflavones directly into the blood create much of the negative concern on soy. • Genistein was shown in cell cultures to negatively impact human sperm's ability to fertilize the female egg. • Professor Lynn Fraser of King's College London, European Society for Human Reproduction and Embryology • Only when plant estrogens are injected, leading to high blood levels are adverse effects seen in research animals. • US Center for the Evaluation of Risks to Human Reproduction (CERHR) or the National Institute of Environmental Health Services and National Toxicology Program; March 20, 2006.

13. Do soy products compromise male reproduction? • Four published clinical trials investigating the effects of soy isoflavone consumption in men and reported that there are no adverse effects of soy isoflavone consumption on sperm quality. • Persky VW, Turyk ME, Wang L, et al. Effect of soy protein on endogenous hormones in postmenopausal women. Am J Clin Nutr 2002;75(1):145-53. • Consumption of isoflavone supplements at the level of 40 mg daily had no effect on semen quality. • Mitchell JH, Cawood E, Kinniburgh D, Provan A, Collins AR, Irvine DS.Publication: Clin Sci (Lond). 2001 Jun;100(6):613-8. • There is no evidence of increased rates of fertility disorders among the Asian population due to soy consumption. • Medical foods with soy deliver 17mg of balanced isoflavones.

14. Should soy be used for prostate health? • Yes. Research shows overwhelming evidence of the positive benefits in supporting prostate health without adverse effects. • Peterson G, Barnes S. Genistein and biochanin A inhibit the growth of human prostate cancer cells but not epidermal growth factor receptor tyrosine autophosphorylation. Prostate 1993;22(4):335-45. • Geller J, Sionit L, Partido C, et al. Genistein inhibits the growth of human-patient BPH and prostate cancer in histoculture. Prostate 1998;34(2):75-79. • Barnes S. Effect of genistein on in vitro and in vivo models of cancer. J Nutr 1995;125(Suppl):777S-83S. • Adlercreutz CH, Goldin BR, Gorbach SL, et al. Soybean phytoestrogen intake and cancer risk. J Nutr 1995;125(3 Suppl):757S-70S. • Nagata C, Takatsuka N, Shimizu H, Hayashi H, Akamatsu T, Murase K. Effect of soymilk consumption on serum estrogen and androgen concentrations in Japanese men. Cancer Epidemiol Biomarkers Prev 2001;10(3):179-84. • Habito RC, Montalto J, Leslie E, Ball MJ. Effects of replacing meat with soyabean in the diet on sex hormone concentrations in healthy adult males. Br J Nutr 2000;84(4):557-63. • Mitchell JH, Cawood E, Kinniburgh D, Provan A, Collins AR, Irvine DS. Effect of a phytoestrogen food supplement on reproductive health in normal males. Clin Sci 2001;100(6):613-18. • Hussain M et al. Soy isoflavones in the treatment of prostate cancer Nutr Cancer 2003;47(2):111-7.

15. Isn’t it better to use a more complete protein? • Early studies suggested that soy was not a complete protein source. These early findings have been shown to be inaccurate. • Soy has the same score as egg white and milk protein. • Protein Digestibility Corrected Amino Acid Score (PDCAAS), which has been adopted by both the FDA and World Health Organization (WHO) • Sarwar G, McDonough FE. Evaluation of protein digestibility-corrected amino acid score method for assessing protein quality of foods. J Assoc Off Anal Chem 1990;73(3):347-56. • FAO/WHO/UNU Expert Consultation. Energy and Protein Requirements. Geneva: World Health Organization; 1985 (WHO technical report, series 724). • U.S. Food and Drug Administration. Federal Register. 21 CFR, Part 101, et al. Part III. Food Labeling, 1991.

16. Does soy inhibit thyroid function? • Well-designed human clinical studies have demonstrated that soy has a minimal effect on overall thyroid function in healthy individuals. • Duncan AM, Underhill KE, Xu X, Lavalleur J, Phipps WR, Kurzer MS. Modest hormonal effects of soy isoflavones in postmenopausal women. J Clin Endocrinol Metab 1999;84(10):3479-84. • Persky VW, Turyk ME, Wang L, et al. Effect of soy protein on endogenous hormones in postmenopausal women. Am J Clin Nutr 2002;75(1):145-53. • UltraMeal Medical Food Program: Containing soy protein (15 grams) with a comprehensive vitamin/mineral blend • Patients using the UltraMeal product had no change in their TSH levels after 10 weeks. Patients using the popular retail product showed a significant elevation (150% above baseline) in their TSH levels. • Bland JS, DiBase F, Ronzio R. Physiological effects of a doctor-supervised versus and unsupervised over-the-counter weight-loss program. J Nutr Med 1992;3:285-93

17. Does soy inhibit thyroid function? • Amounts greater than 200 mg of isoflavones per day may inhibit thyroid hormone synthesis in susceptible people. (thyroid issues/low iodine) • Certain studies suggest that soy and soy isoflavones inhibit the production of thyroid hormones in individuals with thyroid issues. • Chang HC, Doerge DR. Dietary genistein inactivates rat thyroid peroxidase in vivo without an apparent hypothyroid effect. Toxicol Appl Pharmacol 2000;168(3):244-52. • Approximately 10 million Americans or 3% of the population have thyroid issues. • Alternatives to soy based medical foods are available for these individuals.

18. Isn’t soy more allergenic than other proteins? • Soy proteins tend to be less reactive than many other food proteins. In fact, soy has been used as an alternative for infants with allergies to cow’s milk. • Cordle CT. Soy protein allergy: incidence and relative severity. J Nutr 2004;134(5):1213S-19S. • A meta-analysis of 17 studies of allergy patterns of high-risk infants revealed soy allergy occurring in 3% to 4% of subjects versus 25% for cow’s milk. • Cantani A, Lucenti P. Natural history of soy allergy and/or intolerance in children, and clinical use of soy-protein formulas. Pediatr Allergy Immunol 1997;8(2):59-74.

19. Do I have to use fermented soy products to achieve therapeutic benefits? • No. The majority of studies around the world show beneficial effects of soy. • Our research studies confirm those findings for areas including: • Blood Sugar • Body composition • Preserving muscle mass during weight loss • Cardiovascular risk reduction

20. The Functional Medicine Research Center • We are the only company in the professional market to operate a patient clinic. • In 2004-2005 the FMRC conducted over 5,000 patient visits. • It allows us to test our products for safety and efficacy before they reach your patients. • Many companies use your patients to test their products.

21. UltraGlycemX medical food positively affects blood sugar • UltraGlycemX Medical Food • Contains soy protein (15 grams) with a comprehensive vitamin/mineral blend • Clinically Shown to: • Significantly improve • fasting and 2-hour postprandial insulin • Triglycerides and cholesterol levels • Body composition • Study lasted 8 weeks and 37 insulin resistant patients participated

22. UltraMeal medical food positively affects body composition • UltraMeal Medical Food • Contains soy protein (15 grams) with a comprehensive vitamin/mineral blend • Published Peer Review Study: • A 10 week study with 34 patients showed Patients on UltraMeal lost an average of 13 lbs with zero muscle lost. • Compared to a popular retail product in which patients lost similar weight but lost 85% of it as muscle. • Bland JS, DiBase F, Ronzio R. Physiological effects of a doctor-supervised versus and unsupervised over-the-counter weight-loss program. J Nutr Med 1992;3:285-93

23. UltraMeal medical food positively affects body composition • UltraMeal Medical Food • Published Peer Reviewed Study: • A University of Oregon study showed significant change in body composition over 7 weeks. • 34 patients lost an average of 14.1 lbs of fat while gaining 0.9 lbs of muscle. • Hackman RM, Ellis BK, Brown RL. Phosphorous magnetic resonance spectra and changes in body composition during weight loss. J Am Coll Nutr 1994; 13(3)243-250

24. UltraMeal Plus program affects body composition and cardiovascular health • UltraMeal Plus Medical Food • Incorporates soy protein and phytosterols with a comprehensive vitamin and mineral blend • Published Peer Reviewed Study: • 42 post-menopausal women were studied for 12 weeks and the results showed statistically significant improvement in 14 independent cardiovascular risk markers • Lukaczer D, Liska DJ, Lerman RH. et al. Effect of a low glycemic index diet with soy protein and phytosterols on CVD risk factors in postmenopausal women. Nutrition 2006 104-113

25. UltraMeal Plus shows significant changes in key cardiovascular markers • Weight -14.8 lbs • Lean Muscle +2.28 lbs • Total Cholesterol -16% • LDL Cholesterol -15% • HDL Cholesterol +6% • tChol/HDL -20% • TG/HDL -56% • hsCRP -34% • HA1C -3.4% • Insulin -26%

26. We support the use of soy

27. We have options to benefit every type of patient • Many companies just say why one protein or ingredient is better than another. • Thyriod issues and soy allergy patients • UltraMeal Whey • UltraMeal Rice • UltraClear Medical Food • UltraClear Plus Medical Food • UltraInflamX Medical Food • Breast tissue health options • Estrium Medical Food • UltraMeal Whey • UltraMeal Rice • UltraClear Medical Food • UltraClear Plus Medical Food • UltraInflamX Medical Food

28. Decisions must be based on a balanced review of research • Metagenics will always select the best ingredients and method of delivery to meet the needs of your patients • Variety of proteins in our medical foods • Use of powders, tablets, capsules and liquids in different products to ensure effectiveness as well as improved compliance.

29. At Metagenics, we're in the health business - Not the pill business • In the health business, safety and effectiveness are top priority because there is a lot riding on the quality of the products we make: • Your patient’s health. • The success of the nutritional therapy you recommend. • Your credibility as a health professional.

30. “Genetic Potential Through Nutrition” • We invest more in research and quality than anyone else in our industry. • Our medical foods are just one example of how we distinguish ourselves in this industry. • Always True to Our MissionSince our inception in 1983, we have never deviated from our founding idea - "the patient's best interests must be served."