Bonistein Max, Douglas Labs An exclusive, patent-pending, blend of pure genistein, vitamin D3, vitamin K, and omega-3 fatty acids to help maintain bone health.* Provided in non-gelatin soft capsules BONISTEIN™-Max soft capsules provided by Douglas Laboratories® contain an exclusive patent-pending blend of pure genistein, vitamin D3, vitamin K and omega-3 fatty acids from ultra pure fish oil to help maintain bone health. BONISTEIN-Max is provided in a soft capsule shell that is composed of carrageenan (from a red seaweed extract) and vegetable starch. No animal gelatin is used in the manufacturing of this capsule. BONISTEIN-Max is also unique in that it contains BONISTEIN™, a pure form of genistein, and not a soy isoflavone extract. FUNCTIONS Bone health is rapidly becoming an increasingly important issue. It is well known that the risk of fracture increases with age and that the number of people over 50 years of age is a rapidly growing segment of the population. By the year 2020, half of all Americans will already have or will develop problems with their bone structure. Postmenopausal women are particularly at risk since the loss of estrogen production at menopause leaves bones much less protected. This is critical, as estrogen helps to maintain the balance between bone breakdown and bone formation. Specifically, estrogen is able to limit the activity of bone-resorbing osteoclasts. Genistein: The role of isoflavones in bone health has been the focus of research for many years. Specifically, the isoflavone genistein has received much of this attention. Genistein can exert an estrogen-like effect on bone metabolism by specifically binding to the same nuclear receptors to which estrogen binds. However, unlike estrogen, genistein does not bind with an equal affinity to both the alpha and beta estrogen receptors. Genistein has a relative affinity for ER-ß that is approximately 7 - 30 times greater than its affinity for ER-a, and compared with estrogen, genistein is 500 times weaker in its binding to ER-a. This is important, as reproductive tissues such as breast and uterus are rich in ER-a, whereas bone contains greater amounts of the ER-ß. When genistein binds with the estrogen receptor it has the ability to alter gene expression in ways that favor the maintenance of healthy bone formation. The maintenance of healthy bone structure results from a balance of bone resorption (by osteoclasts) coupled with bone formation (from osteoblasts). Specifically, genistein has been shown to modulate the activity of osteoblasts by down regulating interleukin-6 (IL-6) production. Genistein has also been shown to decrease production of TNF-alpha. The production of IL-6 and TNF-alpha can act to increase osteoclast activity, so limiting their production is desirable in order to support bone health. In addition to the effect of genistein on IL-6 and TNF-alpha, genistein can also exert a positive effect on bone health via its ability to modulate pathways involving nuclear factor kappa B. Nuclear factor kappa B (NF-kB) is a nuclear protein that functions as a transcription factor and can affect the expression of numerous molecules including cytokines, and growth factors and has been shown to be involved in bone metabolism. RANK (receptor activator of NF-kB) is a cell surface receptor, that when bound with its ligand, RANKL can help precursor osteoclasts develop into fully fledged osteoclasts, and therefore favor bone breakdown. Interestingly, RANKL is produced by osteoblasts, showing how these two types of bone cells communicate with each other to maintain bone health. Osteoprotegrin, another important protein produced by osteoblasts, can bind to RANKL and prevent RANK and RANKL from forming a complex. As a result osteoprotegrin can inhibit the activation of osteoclasts that results from the combining or RANK and RANKL. In fact it is now thought that the balance of osteoprotegrin and RANKL is critical for maintaining healthy bones. Dietary supplementation with pure genistein in postmenopausal women has been shown to support healthy bone structure. Until recently, genistein was only available as part of a complex with other isoflavones. BONISTEIN-Max provides pure genistein, so its benefits may be more fully realized. Omega-3 Fatty Acids: Research continues to support multiple benefits for omega-3 fatty acids for various areas of health. Recently, data have been emerging that have shown a role for omega-3 fatty acids in bone health. Diets with a low ratio of omega-6:omega-3 fatty acids help to minimize the bone loss typically seen after menopause. In fact omega-3 fatty acids may support healthy bone formation. In ovarectomized animals fed diets with different levels of omega-3 and omega-6 fatty acids, those that received the highest ratio of omega-3:omega-6 fatty acids experienced significantly less bone loss compared with other groups. This effect may be due to the action of omega-3 fatty acids on cytokines, which in turn can effect bone health. Vitamin D3: Vitamin D is well known for the role it plays in helping to regulate calcium and bone metabolism. As we age, vitamin D status declines. If given the same amount of light, a younger person can produce more vitamin D compared with an older individual. When advancing age is combined with northern latitudes one can quickly become deficient in vitamin D. Vitamin D can increase the expression of osteocalcin and other important compounds from osteoblasts to help support bone formation or it can help to breakdown bone and mobilize calcium when it is needed elsewhere in the body. Numerous scientists now feel that supplementation with vitamin D at levels greater than previously thought necessary is critical to helping maintain healthy bone remodeling as we age. Vitamin K: A growing body of literature supports the concept that increased intake of vitamin K both from food as well as supplements can have a beneficial impact on bone health. Vitamin K has been shown to decrease calcium excretion and is involved in gamma-carboxylation of osteocalcin. Osteocalcin is important for healthy bone formation, as it facilitates the binding of calcium to hydroyapatite. However, vitamin K has also been shown to affect the synthesis of IL-6, a cytokine that can negatively impact bone health. BONISTEIN-Max provides excellent bone support, as the combination of genistein, vitamins D and K, and omega-3 fatty acids has been shown to be more effective at supporting bone health then when the ingredients are used individually. INDICATIONS BONISTEIN-Max soft capsules may be a useful dietary adjunct for those wishing to support optimal bone health. SUGGESTED USE Two soft capsules per day, or as directed by a healthcare professional. WARNING This product contains vitamin K, which interferes with the prescription drugs Coumadin and Warfarin. Do not take this product if taking either of these drugs.  Supplement Facts   Container Size 60 Oblong SoftGels   Serving Size 2 SoftGels   Amount Per 2 SoftGels Content %DV     Vitamin D3 (cholecalciferol) 800 IU   Vitamin K1 (phytonadione) 100 mcg   Genistein (from Bonstein) 30 mg   Ultra-Pure Fish Oil Concentrate 1460 mg   Providing: EPA (Eicosapentaenoic acid) 535 mg   DHA (Docosahexaenoic acid) 260 mg   Total Omega-3 fatty acids 1000 mg     Other Ingredients: Medium chain triglycerides, vegetable glycerin, SeaGel® carrageenan (from red seaeed extract), beeswax, vegetable starch and water.   This product contains BONISTEIN™ BONISTEIN is a trademark of DSM Nutritional Products. SeaGel® is a registered trademark of FMC Biopolymer.   % Daily Values (DV) are based on a 2,000 calorie diet. * Daily Value (DV) not established. Product: Bonistein Max Manufacturer: Douglas Labs Item #: 99599-60X Content: 60 Oblong SoftGels