Bone Health: Soy and Isoflavones

Soy has many positive associations with bone health and the research to back it up. In 2008, researchers investigated the effect of soybean and isoflavone intake on BMD and its change among 34 young Korean women over two years.¹² During the study period, BMD increased significantly for lumbar spine and Ward's triangle (WT). The average daily intake of soybeans and isoflavones was 39 g and 8 mg, respectively. Soybean intake and total isoflavone intake had positive correlation on femoral neck (FN) and WT. BMD increased 0.26 percent per 1 mg of isoflavone intake per year in the FN and 0.31 percent for WT (P = .05 and .008). Researchers concluded, “Soybean and isoflavone intake have a positive effect on the change of BMD on the FN and WT among young Korean women.”

In July 2008, dried plum and fructooligosaccharides (FOS) or their combination in a soy protein-based diet and their ability to restore bone mass in ovarian hormone deficient rats was evaluated.¹³ Three-month-old female Sprague-Dawley rats (n=72) were divided into six groups and either ovariectomized (Ovx, five groups) or sham-operated (sham, one group). The rats were maintained on a semi-purified standard diet for 45 days after surgery to establish bone loss. Thereafter, the rats were placed on one of the following dietary treatments for 60 days: casein-based diet, soy-based diet or soy-based diet with dried plum, FOS, and combination of dried plum and FOS. Soy protein in combination with the test compounds significantly improved whole-body BMD. All test compounds in combination with soy protein significantly increased femoral BMD but the combination of soy protein, dried plum and FOS had the most pronounced effect in increasing lumbar BMD. Similarly, all of the test compounds increased ultimate load, indicating improved biomechanical properties. Data from a separate 2008 study, pointed to the “beneficial bone effects of a soy diet in rapidly growing animals and the potential for early soy consumption to increase peak bone mass.”¹⁴

However, a study published in the European Journal of Nutrition that randomized lactating rats to one of four diets supplemented with different levels of soy isoflavones (0, 2, 4, 8 mg aglycone isoflavone/g protein) found consuming soy isoflavones, in levels readily attained through soy foods, had neither protective effects on bone nor deleterious effects on milk quality or quantity during lactation.¹⁵

An interesting fact about soybeans is they contain a large amount of menaquinone-7, or vitamin K, which may also help prevent the development of osteoporosis. Vitamin K mediates the synthesis of proteins regulating bone metabolism. Natto is a fermented product made out of soybeans and researchers from a study published in the Journal of Nutrition said, “Natto intake may help prevent postmenopausal bone loss through the effects of menaquinone 7 or bioavailable isoflavones, which are more abundant in natto than in other soybean products.”¹⁶ A paper published in Blood compared the absorption and efficacy of vitamin K1 and natural long-chain menaquinone-7 (MK-7; as MenaQ7™ from PL Thomas) in healthy adults.¹⁷ Both K1 and MK-7 were absorbed well, with peak serum concentrations at four hours after intake. A major difference between the two vitamin K species was the very long half-life time of MK-7, resulting in much more stable serum levels and accumulation of MK-7 to higher levels (7- to 8-fold) during prolonged intake. MK-7 induced more complete carboxylation of osteocalcin. Researchers did warn hematologists to be aware that preparations supplying 50 mu/gamma g/d or more of MK-7 may interfere with oral anticoagulant treatment in a clinically-relevant way.

Additionally, a randomized clinical intervention study gave 325 postmenopausal women either a placebo or 45 mg/d of vitamin K2 (MK-4, menatetrenone) for three years in which vitamin K2 helped maintain bone strength in the femoral neck by improving bone mineral content (BMC) and femoral neck width (FNW) with little effect on DXA-BMD.¹⁸ The vitamin K2-treated group experienced no change in hip bone strength, whereas in the placebo group, bone strength decreased significantly. And in concert with this study, a significant correlation between hip fracture incidence and vitamin K intake, as well as regional variations in food patterns, suggest that increasing intake of vegetables and legumes might lead to a decrease in hip fracture incidence in the future.¹⁹ Accumulating evidence suggests the requirements for other functions than blood coagulation may be higher.

One study looked at vitamin K in children. In 307 healthy, peripubertal children (mean age 11.2 years), BMC of the total body, lumbar spine and femoral neck were determined at baseline and two years later.²⁰ Vitamin K status (undercarboxylated (ucOC) to carboxylated (cOC) fractions of osteocalcin; UCR) was also measured at both points. Improvement of vitamin K status over two years (n=281 children) was associated with a marked increase in total body BMC. The ratio of UCR was associated with pubertal stage, markers of bone metabolism, sex hormones and vitamin D status. A better vitamin K status was associated with more pronounced increase in bone mass in healthy, peripubertal children.

In addition to vitamin K, genistein, an isoflavone, is found mainly in soy. A presentation by DSM Nutritional Products on bone health and its trademark genistein, Bonistein™, said genistein has the ability to bind to certain estrogen receptors in the cell nucleus possibly helping to replace estrogen in postmenopausal women, helping with bone loss and development. In fact, a 2008 Italian study compared the effects of genistein with alendronate, raloxifene and oestradiol.²¹ Six months after ovariectomy, 96 ovariectomized (OVX) rats with osteoporosis were divided into eight equal groups, randomized to treatments (genistein aglycone (1 and 10 mg kg(-1) s.c.); alendronate (0.003 and 0.03 mg kg(-1) s.c.); raloxifene hydrochloride (0.05 and 0.5 mg kg(-1) s.c.); and 17-alpha-ethinyl oestradiol (0.003 and 0.03 mg kg(-1) s.c.)) for 12 weeks. Untreated OVX (n=12) and sham OVX (n=12) were used as controls. Genistein (10 mg kg(-1)) showed a greater increase in both BMD and BMC than all the other treatments. Genistein significantly increased breaking strength, bone quality, bone-alkaline phosphatase and osteoprotegerin, and reduced C-telopeptide and soluble receptor activator of nuclear factor-kappaB ligand compared with the other treatments at all dose levels. Collectively, these results strongly suggest genistein aglycone may serve as a therapy for the management of postmenopausal osteoporosis women.

Additionally, researchers at the University of Messina, Italy, said, “After three years of treatment, genistein exhibited a promising safety profile with positive effects on bone formation in a cohort of osteopenic, postmenopausal women.”²²

In Germany, dietary intake of genistein resulted in bone protection without stimulating uterine wet weight; however, an isoflavone-rich diet did appear to be more effective in bone protection than administration of pure genistein.²³

SoySelect®, Indena’s standardized extract from soy, features a double standardization of its active ingredients (including isoflavones glycosides genistin and daidzin). According to the company’s pharmacological reports, in a rat OVX model of menopause it produced a bone-sparing effect associated with the slowing down of the increased bone turnover.

Ipriflavone (IP), a synthetic isoflavone, is another natural approach to preventing osteoporosis. IP has been found to influence bone metabolism²⁴ and serve as a clinical treatment in osteoporosis.²⁵ Companies such as TSI Health Sciences offer it as a dietary supplement, i.e., Ostivone®.

A Japanese study divided 15 rabbits, after two titanium caps were placed into their calvarial bone for guided bone regeneration (GBR), into three groups: the No-IP (no intake of IP), Post-IP (10 mg/kg/d of IP after GBR) and Pre-IP (IP intake beginning before GBR).²⁶ One cap was removed from each rabbit after three months and the remaining site was a control. Researchers concluded the daily intake of IP before or after GBR inhibits the resorption of augmented tissue and would be useful for improving the quality of newly-generated bone beyond the skeletal envelope.

At Oklahoma State University, 48 90-day-old female Sprague-Dawley rats were divided into four groups: one sham-operated (sham) and three ovariectomized groups.²⁷ The OVX groups were either control (OVX), supplemented with IP (100 mg/kg body weight/d) via gavaging (OVX+IP) or injected with 17beta-estradiol (E(2) (10 mcg/kg body weight) (OVX+E(2)). Animals were fed diets containing 0.4 percent calcium, 0.3 percent phosphorus and 0.195 nmol vitamin D(3)/g for 35 days from the date of surgery. Calcium uptake by duodenal cells was significantly greater in the IP and E(2)-treated animals compared with the OVX control group. In addition, calcium uptake by the ileal and colonic cells of the E(2)-treated animals was significantly greater compared with all the other groups leading researchers to infer IP, although less potent than estrogen, significantly enhances calcium uptake in the duodenum, the active site of calcium absorption.

However, a study at Texas A&M evaluated whether ipriflavone was able to restore bone mass in osteopenic OVX rats.²⁸ Seventy-two, 90-day-old Sprague-Dawley rats were divided into six groups (sham two groups; ovariectomized four groups). Thirty-five days from the date of surgery, one sham and one OVX group were killed to verify the occurrence of bone loss. The remaining four groups were sham, OVX, OVX + IP (100 mg[sol]kg body weight/d), or OVX + 17beta-estradiol (10 microg[sol ]kg body weight/d) for a period of 65 days. IP was ineffective in restoring bone density and unlike estrogen, did not prevent bone resorption as evidenced by increased (P<0.05) urinary excretion of hydroxyproline and serum tartrate-resistant acid phosphatase activity. But IP did increased (P<0.05) the expression of IGF-I in the femur.

This article is part of a larger feature: Naturally Battling for Better Bone Health

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