The National Institutes of Health has one of the most well-accepted guidelines for women’s calcium intake:

Most people need to supplement to get enough calcium because we have reduced our dairy intake. Estimating dietary sources of calcium is an important first step, before deciding how much to augment in a pill. Not counting dairy or calcium-fortified foods, you get about 250 mg of calcium per day from our grains, seeds and vegetables. If you drink milk, calcium-fortified soy milk or OJ, you rack up an additional 300 mg per 1 cup serving. That’s 250 mg + 300 mg = 550 mg per day. Let’s say you’re 51, postmenopausal and not using estrogen. You’ll need an additional 950 mg to reach the goal of 1,500 mg per day. More is not better. Taking too much may not be good for your heart or other soft tissue and may inhibit mineral absorption.

But bone is not nourished by calcium alone. Vitamin D, is probably even more important than calcium. Other nutrients that can affect bone health include magnesium, manganese, boron, zinc, folic acid, vitamin B6 and vitamin K. These different nutrients are important in one or more of the following: bone density, bone architecture and/or bone strength.

Bolland M, Barber P, Doughty R, et al. Vascular events in healthy older women receiving calcium supplementation: Randomised controlled trial. BMJ 2008;Feb 2; 336:262-266

[Click here to download fulltext PDF from BMJ]

Commentary: It is interesting and important to point out that the Women’s Health Initiative ( Circulation 2007;115:846) showed no statistically significant increase in cardiovascular events in postmenopausal women receiving calcium supplements and another study showed a non-significant but yet a trend in increased risk for ischemic heart disease. (Arch Intern Med 2006;166:869). These three studies all point to the fact that there is no definite statement or conclusion that can be made regarding calcium and cardiovascular events. That said, I am concerned that the importance of calcium supplementation in postmenopausal women, especially younger postmenopausal women, is very overplayed. And, most individuals do not estimate their dietary calcium sources, and then use a pill to supplement in addition to dietary sources to meet a total of 1,200mg-1,500 mg per day. Rather, they often take 1,000 mg to 1,500 mg per day, in addition to their dietary sources. A result of this misinterpretation of calcium guidelines might be excessive calcium and depletion of other nutrients such as copper, silicon and magnesium, all of which have cardioprotective benefits. In addition, these total daily calcium guidelines turn out to be most important to young girls and postmenopausal women 65 and older. These are the times in life when lack of bone architecture/density growth (young girls) and bone loss (elderly women) is most crucial in the prevention of osteoporosis and risk for fractures. For women in their 30’s, 40’s, 50’s and early 60’s, our bones seem to do just fine with average dietary intake.

Soybeans contain a class of compounds called phytoestrogens, comprising mostly genistein, daidzein and glycitein, all of which have a biochemical structure similar to 17 beta estradiol. The binding of isoflavones to estrogen receptors is preferential for the estrogen receptor beta and thus indicates that soy isoflavones act as selective estrogen modulators. Daidzein is similar in shape to a drug called Ipriflavone which is used in Europe to treat osteoporosis. In the U.S., Ipriflavone is available as a nutritional supplement.

Bone mineral density (BMD) is the gold standard for determining fracture risk due to nontraumatic events. Bone turnover is an independent predictor of fracture risk.

While the effects of soy on bone metabolism has been inconsistent, many positive studies do exist that suggest a role for soy in slowing bone turnover and bone density in women. Soy appears to have a pro estrogen effect on bone in some experimental evaluations. The bone density of ovariectomized rats was evaluated in which soy replaced casein in the diet, compared to another group that received estrogen. The addition of soy inhibited bone loss, although not to the same extent as was achieved with the estrogen treatment. Another study of ovariectomized rats also reported a positive effect of the soy phytoestrogen genistein in maintaining bone. These authors also reported that genistein suppresses the bone losing cells (osteoclasts), both in the test tube and in vivo. Arjmandi also did a double-blind, randomized, controlled trial using 40g of soy protein containing isoflavones over 3 months in postmenopausal women. Bone resorption was decreased, when compared to milk protein.

Several human studies have provided further insight and comfort in the possible role of soy in our bone health. A study conducted at the University of Illinois found that menopausal women had an increase in mineral levels and density in their lumbar spines after taking 55-90 mg of isoflavones for six months. The placebo group showed the lowest bone density and the greatest bone loss, while the estrogen group showed the highest bone density and the slowest bone loss. What was surprising was that the soybean diet was effective in preventing bone loss in the fourth lumbar vertebra and, although less so, in the right hip as well. Soybean seems to have more of an effect on trabecular bone (more predominant in the spine) than on cortical bone (more predominant in the hip). The soy did not show as great an ability in preventing bone loss as the estrogen group, but the positive effect it showed is encouraging.

A study of the relation of soy isoflavone intake and bone mineral density was conducted within the Study of Women’s Health Across the Nation, a US cohort study of women aged 42-52 years. For African-American and Caucasian women, average intakes of genistein was too low to pursue analyses. For Chinese women, no association between genistein and bone mineral density was found. Pre-menopausal, but not peri-menopausal, Japanese women whose intakes were greater had a higher bone density of the spine and femoral neck. Mean spinal bone density of those women in the highest group was 7.7% greater than that of women in the lowest group. Bone density of the femoral neck was 12% greater in the highest intake group versus the lowest.

Other positive studies on soy and bone density also give some credence to the role of soy and bone health. In a study estimating the daily intakes of soy isoflavones in the diets of 478 postmenopausal Japanese women who reported soy consumption, high consumption of soy products was associated with increased bone mass.

A very recent analysis of nine studies further increases our optimism about using soy to inhibit bone resorption. Nine studies with a total of 432 menopausal women were evaluated for meta-analysis. Amount of soy intake varied amongst the nine studies from 37 mg of isoflavones per day to 118 mg of isoflavones per day. Testing for urinary peptides (deoxypyridinoline) of bone turnover demonstrated that when all nine study results are combined, those who consumed isoflavones had a decrease in these biomarkers of -2.08 nmol/mmol when compared to those who did not consume isoflavones. In five of the studies, isolated soy protein was used, as a group, there was no significant effect on urinary deoxypyridinoline. In the current analysis, significant reduction in urinary deoxypyridinoline did not occur in those studies with isoflavones of less than 90 mg/day. In a review of the research in 2003, the author concluded that 90mg of isoflavones per day is required to achieve benefits on bone health.

In contrast to the positive studies, several clinical trials using a variety of soy protein isolate formulations found no clinically important effects of soy on bone metabolism and bone turnover markers. Further inconsistent research can be seen with several clinical trials using soy protein or isoflavones demonstrating a positive effect on BMD, while others have not had positive findings.

I mentioned variations in dosing, duration, soy formulations used, and different study populations as possible reasons for inconsistent results on the effects of soy isoflavones on bone turnover and bone density. But, another significant consideration may be due to how the isoflavones are metabolized in the gut. In the recent study mentioned about analyzing nine studies 10 the significant effects on urinary peptides occurred in Asian women but not Caucasian women. This may be due to the conversion of isoflavones into its active metabolite equol in intestinal flora, and that only one-third of Caucasian women can metabolize isoflavones into equol, whereas more than half of Asian women possess this ability.

Soy isoflavones may also have more of an effect in post-menopausal women than in pre or perimenopausal women. In one study, 53.3 mg of isoflavones per day was associated with an increase in bone density in postmenopausal women, but not pre-menopausal women.

An area of soy foods that may be overlooked, is the amount of calcium in some soy foods. A diet that includes greater amounts of soy products can account for a meaningful amount of calcium, and some soy foods can offer as much or more calcium than a serving of dairy products.

With the inconsistent research, it is difficult to draw confident conclusions about the role of soy in bone health. My clinical advice is to increase soy foods as part of a regular diet in prevention strategies for all pre, peri and postmenopausal women. For all women who have significant risk factors for osteoporosis, I would in addition, recommend soy supplementation so that their total daily soy isoflavone intake would deliver approximately 90 mg of soy isoflavones per day. For treatment of peri and postmenopausal women who already have osteoporosis, I would not consider soy an adequate treatment alone. In addition to the 90 mg per day of soy isoflavones and typical supplementation including calcium, vitamin D and other potential nutrients (K, boron, magnesium, manganese, and more), dietary and exercise advice, for these women who already have osteoporosis, I am in favor of proven conventional therapies to reduce fracture risk.

References

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• Setchell K. Soy isoflavones-benefits and risk from nature’s selective estrogen receptor modulators (SERMS). J Am Coll Nutr 2001; 20: 354S-362S.
• Garnero P, Hausherr E, Chapuy M, et al. Markers of bone resorption predict hip fracture in elderly women: the EPIDOS Prospective Study. J Bone Miner Res 1996; 11:1531-1538.
• Arjmandi B, Alekel L, Hollis B, Amin D, Stacwicz-Sapuntzakis M, Guo , Kukreja S. Dietary soybean protein prevents bone loss in an ovariectomized rat model of osteoporosis. J Nutr 1996;126:161-167.
• Blair H, Jordan S, Peterson T, Barnes S. Variable effects of tyrosine kinase inhibitors on avian osteoclastic activity and reduction of bone loss in ovariectomized rats. J cell Biochem. 1996;61:629-637.
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• Erdman J, Stillman R, Lee K, Potter S. Short-term effects of soybean isoflavones on bone in postmenopausal women. Program and Abstract Book, Second International symposium on the Role of Soy in Preventing and Treating Chronic Disease. Brussels, Belgium, 1996.
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• Potter S, Baum J, Teng H, et al. Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. Am J Clin Nutr 1998; 68:1375S-1379S.
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• Morabito N, Crisafulli A, Vergara C, et al. Effects of genistein and hormone-replacement therapy on bone loss in early postmenopausal women: a randomized double-blind placebo controlled study. J Bone Miner Res 2002; 17:1904-1912.
• Chen Y, Ho S, Lam S, Ho S, Woo J. Soy isoflavones have a favorable effect on bone loss in Chinese postmenopausal women with lower bone mass: a double-blind, randomized, controlled trial. J Clin Endocrinol Metab 2003;88:4740-4747.
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Lappe J, et al. Â Vitamin D and calcium supplementation reduces cancer risk: Results of a randomized trial. Â Am J Clin Nut 2007; une 85: 1586-1591

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As women age, especially after menopause, calcium requirements increase due to both reduced intestinal calcium absorption and less efficient renal kidney conservation of calcium. Even though these two mechanisms are in play, the primary influence on calcium absorption is the actual amount of calcium that is ingested, either via diet or supplementation. Selected populations of postmenopausal women may not have adequate calcium intake, including older women, women who are lactose (dairy foods) intolerant, vegans (no animal/no dairy), and women on poor diets in general. Even in the U.S., postmenopausal women have dietary intakes of calcium of about 600 mg/day, which is below the recommended amount. The National Institutes of Health (last revised in 1994) and the National Academy of Sciences (last revised in 1997) are the two most well accepted recommended guidelines for calcium intake in women:

The amount of a calcium one takes in a supplement requires first estimating what your dietary intake is. Start with assuming that you get 250 mg per day, not counting the dairy foods or the calcium fortified foods, if you eat 2-3 meals per day. Most women take in an additional 300 mg per day in the form of one serving of dairy. If you take in more than one serving per day of dairy, then add another 300 mg for each serving of dairy, or for each serving of a calcium fortified soy food. If you drink one glass of milk per day, no soy foods or other calcium fortified foods, then your average daily intake is the 250 mg + 300 mg = 550mg/day. So, if you are 55 and postmenopausal, then you need an additional 650 mg/day (totalling 1,200 mg) to 950 mg per day (totalling 1,500 mg per day which falls within the recommendations of 1,200 mg-1,500 mg per day for postmenopausal women, not yet 65 years old.

There is a great deal of confusion and controversy about which form of calcium is best. When the calcium is taken on an empty stomach, calcium citrate are absorbed better than calcium carbonate. In addition, it may be that as women age, and have lower stomach acid production, lower fat absorption, and take in less vitamin D due to less exposure to sunshine and decreased fat absorption, calcium citrate may be a better choice due to these compromising effects on calcium absorption. In most women though, especially in peri menopausal women and postmenopausal women up to age 65, there is no known truly best form. Calcium carbonate is absorbed well when taken with food. Calcium citrate can be taken with food or on an empty stomach, making it more flexible as to timing of your supplement regime.

Calcium supplementation is extremely safe and even in amounts of total calcium intake up to 1,500 mg/day, there is no increase in the risk of a kidney stone. However, in women with a history of kidney stones, calcium supplements are contraindicated until she has medical testing/assessment and supervision. Calcium intake greater than 2,500 mg per day, taking into account diet and supplement, should be avoided. Some women become constipated or have nausea and indigestion with calcium supplementation, especially calcium carbonate. In these cases, calcium citrate will less likely cause these problems.

The last evidence based consensus opinion of the North American Menopause Society (NAMS) was published in 2001. An expert panel of clinicians and researches in the field of calcium and women’s health followed evidence-based guidelines to make recommendations to the NAMS Board of Trustees.

Areas in the document that were addressed were calcium intake, menopausal status and calcium, target intake, calcium sources, calcium benefits, and calcium levels. Here are selected highlights from that document:

Calcium intake
Adequate calcium intake, in the presence of adequate vitamin D, has been shown to reduce bone loss in peri- and postmenopausal women as well as reducing fractures in postmenopausal women older than 60 who have low calcium intakes. Calcium also enhances the anti-resorptive effects of hormone therapy (HT) in postmenopausal women. Adequate calcium is an important aspect of any treatment regimen for women with osteoporosis.

Menopause status and calcium
Whatever age menopause occurs, the requirement for calcium increases. Calcium absorption and renal calcium conservation are both estrogen dependent and both decline in hypo-estrogen states.

Calcium amounts and sources
The target for calcium intake for most postmenopausal women is 1,200 mg/ day. Adequate vitamin D status is currently defined as a serum level of 30 ng/mL or more of 25-hydroxyvitamin D. It is recommended that foods be the primary source of calcium.

Dairy products are among the better sources of calcium due to the amount of calcium contained in a serving, ease of absorption, other nutrients in the dairy products and the affordable cost. One serving of a dairy product contains between 300 mg to 400 mg per serving, depending on the product. Calcium supplements and calcium fortified foods are available in order to reach the daily target amount. Calcium is best to take with meals and not more than 500 mg at a time to achieve maximal absorption. Calcium bioavailability varies from product to product and consumers are encouraged to confirm consistent bioavailability of a product.

Recommended daily elemental calcium intake for peri-and postmenopausal women:

Institute of Medicine

Aged 31-50 [1,000 mg]
Aged 51 and older [1,200 mg]

National Institutes of Health

Premenopausal women aged 25-50 [1,000 mg]
Postmenopausal women younger than age 65 and using estrogen therapy 1,000 mg
Postmenopausal women not using estrogen therapy [1,500 mg]
All women aged 65 and older [1,500 mg]

Osteoporosis Society of Canada

Menopausal women [1,500 mg]

Calcium benefits
Calcium is beneficial in protection of bone mass and slowing of bone loss, small risk reduction of colorectal cancer, hypertension, renal calculi, PMS and obesity.

Calcium levels
No accurately sensitive tests are available to assess calcium deficiency. The focus should be on the recommended guidelines and to encourage women to consume adequate calcium and/or take calcium supplements. The laboratory test for serum vitamin D is available to diagnose those women who are vitamin D deficient and thus more likely to be deficient in calcium.

The average daily dietary consumption of calcium is far below the recommended amount to achieve optimal bone health. Health care providers are encouraged to be more vigilant in advising peri- and postmenopausal women regarding calcium intake.