Can soy prevent osteoporosis?

Postmenopausal women over 50 years of age are especially vulnerable to osteoporosis, a bone-thinning disease, as a result of the rapid and progressive bone loss associated with estrogen deficiency at menopause, followed by sustained bone loss with aging. Some women experience an early menopausal acceleration of bone loss of 1 to 3 percent a year, (1-3) followed by an age-related bone loss of approximately 0.7 to 1 percent a year. (4-6)

Osteoporosis can be defined as a systemic disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a subsequent increase in bone fragility and susceptibility to fracture. Estrogen replacement therapy (ERT) has been used effectively in stabilizing skeletal bone mineral density (BMD) and preventing vertebral fractures, (7,8) but because of undesirable side effects and potential health risks, the compliance to ERT by postmenopausal women is only 10 to 20 percent. (9) The search for alternatives is ongoing.

Phytoestrogens and Osteoporosis

Although research to date is inconclusive, results indicate that phytoestrogens may provide an alternative to ERT as a favorable therapeutic agent in the treatment of osteoporosis. Phytoestrogens, including isoflavones, are estrogen-like molecules abundant in plants. (10) One of the richest sources of isoflavones is the soybean and soy foods. Isoflavones, the most studied phytoestrogens related to bone health, possess weak estrogenic activity and have an affinity for estrogen receptors, specifically estrogen receptor-[beta] (ER-[beta]) which is present in bone, the brain, the bladder, and the vascular epithelia.

The limited amount of data on the skeletal effects of isoflavones suggests agonistic effects. Ecological studies show a lower incidence of hip osteoporosis among Asian populations consuming diets high in soy compared with Western populations. (11) Studies using the ovariectomized rat model have shown comparable bone-sparing effects of 17[beta]-estradiol and soy protein isolate, (12) genistein or daidzein, (13) or their respective succinylated products obtained after soybean fermentation. (14)

B. H. Arjmandi et al. (15) showed that feeding isolated soy protein increased messenger ribonucleic acid (mRNA) insulin growth factor I (IGF-I) biosynthesis, suggesting that IGF-I levels would increase. IGF-1 is a protein involved in the bone formation process; therefore, an increase in IGF-1 suggests increased bone formation.

In two short-term published studies of the effects of soy isoflavones on BMD in humans, soy protein isolate was used with isoflavones as the treatment. S. M. Potter et al. (16) studied 66 hypercholesterolemic postmenopausal women and L. Alekel et al. (17) studied 69 perimenopausal women. Both studies reported a positive effect with approximately 90 milligrams (mg.) of isoflavones a day on spine BMD of 1 to 2 percent relative to control women who were fed a milk protein.

Biomarkers of bone turnover are useful for determining changes in bone formation and bone resorption. An increase in markers of bone formation indicates that bone is being deposited; an increase in markers of bone resorption indicates that bone is being degraded. Bone biomarkers help in assessing metabolic bone disease and therapeutic efficacy.

K. E. Wangen et al. (18) found that markers of bone turnover were affected by soy isoflavones at 65 and 130 mg./day in both premenopausal and postmenopausal women. In premenopausal women, markers of bone resorption significantly increased on both isoflavone diets. In postmenopausal women, bone formation markers were significantly decreased with both isoflavone diets. The changes observed in this study were of small magnitude and were probably not clinically significant.

One clinical study in humans is under way to assess the effects of soy isoflavones on calcium metabolism, including kinetics. This information is essential in ascertaining the mode of action for the skeletal effects of isoflavones.

Soy Protein and Urinary Calcium

The profile of sulfur-containing amino acids determines the effect of protein on urinary calcium excretion. (19) Relative to animal protein, soybeans have a lower content of the sulfur-containing amino acids cystine and methionine. However, relative to other legumes, soybeans have a higher content of sulfur-containing amino acids. (20) Table 1 shows the amounts of sulfur-containing amino acids in some proteins.

The metabolism of sulfur-containing amino acids generates sulfate, which increases urine acidity and therefore urinary calcium excretion.

S. A. Schuette et al. (21) showed a high correlation between urinary sulfate and total renal acid excretion and urinary sulfate and urinary calcium excretion in elderly men and postmenopausal women using purified proteins (proteins isolated from whole foods).

Similarly, M. B. Zemel et al. (22) found that an addition of purified sulfur amino acids to a protein diet significantly increased urinary calcium excretion in adult males. N. A. Breslau et al. (23) further demonstrated significant urinary calcium, urinary sulfate, and net acid excretions in an animal protein-rich diet relative to ovo-vegetarian and vegetarian diets. The ovo-vegetarian and vegetarian diets contained soymilk, soy cheese, and textured vegetable protein.

Soy Foods and Calcium Bioavailability

Soybeans have high calcium content relative to other plants and high fractional absorption of calcium, despite their high content of oxalate and phytate. Both oxalate and phytate inhibit calcium absorption, but oxalate is a more potent inhibitor because of the degree of insolubility of the oxalate-calcium complex. Moreover, phytate is the storage form of phosphorus in plants, which lowers the bioavailability of calcium by forming phosphorus-calcium complexes. Phytate appears to substantially reduce calcium absorption only in phytate-concentrated wheat bran cereal. (24)

Table 2 lists examples of natural sources of calcium and the amounts necessary to equal the calcium contained in one cup of milk. The number of servings required to replace one cup of milk for absorbable calcium are approximately three servings of cooked soybeans, eight servings of pinto beans, 10 servings of red beans, and four servings of white beans.

Some calcium-fortified foods have fractional calcium absorption values (the amount of calcium that can be absorbed from these foods) that are similar to the calcium absorption value of milk. (25) For example, Table 2 shows that the fractional absorption of calcium-set tofu is 31 percent relative to 32.1 percent for milk and the milk equivalency of calcium-set bean curd (tofu) is 1.2 servings.

Soy-based meat products, calcium-fortified soy cheese, soy yogurts and ice creams, and soy nut butter as well as soymilk are most likely more conveniently substituted for milk and dairy products than cooked soybeans. With the exception of soymilk, the fractional absorption of calcium in these products relative to cow's milk is currently unknown.

Conclusion

Soy foods provide calcium essential to building and maintaining bone and may also protect against osteoporosis. However, the current understanding of the role of soy in bone health is still in its infancy. We have much more to learn about which compounds in soy protein are bioactive and at what dose, whether soy proteins have a bone-protective effect, and the mode of action on the bone tissue. Long-term randomized, controlled trials are necessary to determine the role of soy protein and soy isoflavones on BMD and fracture incidence.

References

(1.) Mazess, R.B., Barden, H.S., Ettinger, M., et al. Spine and femur density using dual-photon absorptiometry in U.S. white women. Bone Mineral 1987; 2:211-219.

(2.) Mazess, R.B., On aging bone loss. Clinicial Orthopedics and Related Research 1982; 165:239-252.

(3.) Ravn, P., Hetland, M.L., Overgaard, K., Christiansen, C. Premenopausal and post menopausal changes in bone mineral density of the proximal femur measured by dual-energy x-ray absorptiometry. Journal of Bone Mineral Research 1994; 9:1975.

(4.) Dawson-Hughes, B., Dallal, G.E., Krall, E.A. A controlled trial of the effect of calcium supplementation on bone density in postmenopausal women. New England Journal of Medicine 1990; 323:878-883.

(5.) Greenspan, S..L, Maitland, L.A., Myers, E.R., et al. Femoral bone loss progresses with age: A longitudinal study in women over age 65. Journal of Bone Mineral Research 1994; 9:1959-1965.

(6.) The Writing Group for the PEPI Trial. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The postmenopausal estrogen/progestin intervention (PEPI) Trial. Journal of the American Medical Association 1995; 273:199-208.

(7.) The Writing Group for the PEPI Trial. Effects of hormone therapy on bone mineral density. Results from the postmenopausal estrogen/progestin interventions (PEPI) trial. Journal of the American Medical Association 1996; 276:1389-1396.

(8.) Kiel, D.P., Felson, D.T., Anderson, J.J. Hip fracture and the use of estrogens in postmenopausal women. New England Journal of Medicine 1987; 317:1169-1174.

(9.) Ettinger, B. Overview of estrogen replacement therapy: A historical perspective. Proceedings of the Society for Experimental Biology and Medicine 1998; 217:2-5.

(10.) Knight, D.C., Eden, J.A. A review of the clinical effects of phytoestrogens. Obstetrics and Gynecology 1996; 87:897-904.

(11.) Knight, D.C., Lyons-Wall, P., Eden, J.A. A review of phytoestrogens and their effects in relation to menopausal symptoms. Australian Journal of Nutrition and Diet 1996; 53:5-11.

(12.) Arjmandi, B.H., Alekel, L., Hollis, B.W., et al. Dietary soybean protein prevents bone loss in an ovariectomized rat model of osteoporosis. Journal of Nutrition. 1996; 126:161-167.

(13.) Ishida, H., Uesugi, T., Hirai, K., et al. Preventative effects of the plant isoflavones, daidzein and genistein, on bone loss in ovariectomized rats fed a calcium-deficient diet. Biological and Pharmaceutical Bulletin 1998; 21:62-66.

(14.) Toda, T., Uesugi, T., Hirai, K., et al. New 6-O-acyl isoflavones glycosides from soybeans fermented with Bacillus subtilis (Natlo). 1. 6-O-Succinylated isoflavone glycosides and their preventative effect on bone loss in ovariectomized rats fed a calciumdeficient dict. Biol Pharm Bull 1999; 22:1193-1201.

(15.) Arjmandi, B.H., Birnbaum, R., Goyal, N.V., et al. Bone-sparing effect of soy protein in ovarian hormone-deficient rats is related to its isoflavone content. American Journal of Clinical Nutrition 1998 (Suppl.); 68:1364S-1368S.

(16.) Potter, S.M., Baum, J.A., Teng, H., et al. Soy protein and isoflavones: Their effects on blood lipids and bone density in postmenopausal women. American Journal of Clinical Nutrition 1998 (Suppl.); 68:1375S-1379S.

(17.) Alekel, L., St. Germain, A., Peterson, C.T., et al. Isoflavone-rich soy protein isolate attenuates bone loss in lumbar spine of perimenopausal women. American Journal of Clinical Nutrition 2000; 729:844-852.

(18.) Wangen, K.E., Duncan, A.M., Merz-Demlow, B.E., et al. Effects of soy isoflavones on markers of bone turnover in premenopausal and postmenopausal women. Journal of Clinical Endocrinology and Metabolism 2000; 85:3043-3048.

(19.) Zemel, M.B. Calcium utilization: Effect of varying level and source of dietary protein. American Journal of Clinical Nutrition 1988; 48:880-883.

(20.) Young, V.R. Soy protein in relation to human protein and amino acid nutrition. Journal of the American Dietetic Association 1991; 91:828-835.

(21.) Schuette, S.A., Zemel, M.B., Linkswiler, H.M. Studies on the mechanism of protein-induced hypercalciuria in older men and women. Journal of Nutrition 1980; 110:305-315.

(22.) Zemel, M.B., Schuette, S.A., Hegsted, M., Linkswiler, H.M. Role of the sulfur-containing amino acids in protein-induced hypercalciuria in men. Journal of Nutrition 1981; 111:545-552.

(23.) Breslau, N.A., Brinkley, L, Hill, K.D., Pak, C.Y.C. Relationship of animal protein-rich diet to kidney stone formation and calcium metabolism. Journal of Clinical Endocrinology and Metabolism 1988; 66:140-146.

(24.) Proulx, W.R., Weaver, C.M. Calcium absorption from plants. The Soy Connection. 2(2): 1-4, 1994.

(25.) Weaver, C.M., Proulx, W.R., Heaney, R. Choices for achieving adequate dietary calcium with a vegetarian diet. American Journal of Clinical Nutrition 1999; 70 (Suppl.): 543S-548S.

(26.) Heaney R.P., Weaver C.M., Fitzsimmons M.L. Influence of calcium load on absorption fraction. Journal of Bone Mineral Research 1990; 5:1135-1138.

Table 1 Sulfur-Containing Amino Acids in Various Protein Sources

Source                     Amount (mg./g.)

Legumes
  Soybeans                       30
  Black, great northern,
    kidney, navy                 26
  Chickpea                       27
  Cowpea                         25
  Lentil                         22
  Lima, baby, and large          24
Fruit                            38
Cereals                          28
Animal foods                     39
Nuts and seeds                   46

Table 2 Comparison of Other Natural Sources of Calcium with Milk

Food         Serving    Calcium   Fractional       Milk
            Size (g.)    (mg.)    Absorption   Equiv. (cup)

Milk           240        300        32.1           1.0
Beans
Pinto          86       44.7        26.7           8.1
 Red           172       40.5        24.4           9.7
 Soy            86        100       31-42           2-3
 White         110        113        21.8           3.9

Broccoli        71         35        61.3           4.5
Kale            85         61        49.3           3.2
Spinach         85        115         5.1          16.3
Tofu with      126        258        31.0           1.2
 Calcium