Study Shows Soy Protein Reduced Progression Of Clogged Arteries In Women Within 5 Years Of Menopause

This large scale, first-of-a-kind study will be published in the November issue of Stroke

A new study published in the November 2011 issue of Stroke reveals some promising data on the positive effects of soy protein reducing the progression of clogged arteries in women who were within five years of menopause. This study was the largest and longest randomized controlled human study conducted to-date that directly investigated the efficacy of isolated soy protein consumption on the progression of atherosclerosis (lipid deposition in the artery walls).

“These results are consistent with what we have learned through research conducted over the past decade,” said Howard N. Hodis, MD, USC Keck School of Medicine and lead author of the study. “The literature demonstrates that there is a ‘window of opportunity’ of a potential beneficial effect on coronary heart disease for products that bind to the estrogen receptor including hormone-replacement therapy, soybean isoflavones or selective estrogen receptor modulators (SERMs) when initiated in women within 5-6 years of menopause.”

The progression rate of carotid artery intima-media thickness (CIMT) trended to be 16 percent lower on average in the isoflavone-containing soy protein group compared with the placebo group. However, in women who had experienced menopause within the past five years, isolated soy protein consumption was associated with a significant 68 percent reduction in CIMT progression compared to those consuming the placebo.

Excellent compliance was observed for this study as determined by package and bar count (86.5 percent for placebo and 91.0 percent for isolated soy protein). Compliance was confirmed by plasma and urine isoflavone measurements.

“The high compliance suggests that the clinical study products provided by Solae were very palatable and were not associated with any significant adverse effects as confirmed by the data,” said Elaine Krul, PhD, nutrition discovery lead, Solae.

Subjects in this study were ‘healthy’ with no previous signs of cardiovascular disease which may explain the lack of significant reduction in plasma lipids that is seen in persons with higher plasma lipid levels.

“This study also showed a significant increase in HDL (“the good”) cholesterol in participants consuming isolated soy protein,” said Krul. “The results of this study reinforce that soy protein can provide health benefits for the healthy aging market segment.”



Hodis HN, Mack WJ, Kono N, Azen SP, Shoupe D, Hwang-Levine J et al; for the Women’s Isoflavone Soy Health Research Group. Isoflavone Soy Protein Supplementation and Atherosclerosis Progression in Healthy Postmenopausal Women: A Randomized Controlled Trial. Stroke 2011 Sep 8. [Epub ahead of print]


Is Estrogen Going to Your Head?

Growing deposits of bone in the skull means your hormones are out of whack, warns researcher Prof. Israel Hershkovitz at Tel Aviv University 

Girls are growing up faster than ever — and not only when it comes to their taste in fashion and music. Their bodies are reaching puberty at an increasingly earlier age, and this trend to rapid maturity continues through women’s adult lives. That’s bad news, according to Tel Aviv University researchers. Women today are more likely to develop Hyperostosis Frontalis Interna (HFI), a hormonal condition once typically found in post-menopausal women, earlier and more frequently than the female population a century ago.

Women’s hormonal balances are changing and taking a physical toll, says  and his graduate student Hila May of TAU’s Sackler Faculty of Medicine, together with Dr. Natan Peled of Carmel Medical Center in Haifa. That balance is being affected by the hormones we now consume in our food and by our changing fertility patterns, such as having children later in life. Women today are 2.5 times more likely to develop HFI than they were 100 years ago, the study found.

Their research recently appeared in the American Journal of Human Biology 

Prof. Israel Hershkovitz

Sounding the alarm

HFI occurs when a hormonal imbalance leads to the growth of lesions, or bone masses, in the inner skull. This may lead to symptoms such as chronic headaches, weight gain, and thyroid irregularities, and is suspected to have multiple causes, including lifestyle, fertility habits, nutrition, and environment.

To track the growing prevalence of HFI, Prof. Hershkovitz and fellow researchers compared 992 historic female skulls from museum collections aged 20 to 90 years with CT scans of 568 living female participants ranging from 20 to 103 years old. Not only was prevalence of HFI found to be 2.5 times higher in the latter group, but the researchers also discovered that the average age of women who suffered from HFI had fallen drastically.

An age-dependent condition, HFI was once known to primarily strike post-menopausal women, who had then been exposed moderate levels of estrogen throughout their lives. Now it is appearing as well in pre-menopausal women, who have been exposed to higher levels of estrogen earlier in their lifetimes.

Their survey found that only 11 percent of 19-20th century women in the age range 30-39 had HFI. However, in the modern sample, 40 percent of women in that age group were found to be developing the condition. Any number of factors could be to blame, May says. Hormones added to food are one culprit, but not the only one. Women are now having fewer children and getting pregnant later in life. The period of time women breastfeed has also been shortened considerably, from three to four years a century ago to an average of less than six months today. Women are also consuming additional amounts of hormones through birth control medications. It’s now common for girls to be on “the pill” in their early teenage years.

There is currently no cure for HFI, but detection of the condition remains important, says Prof. Hershkovitz, who was among the first scientists to investigate the development of HFI in the human skull. “It’s an alarm within the human body, telling you that your body is out of balance and there is a pathological process going on,” he explains. It can also be a symptom of metabolic diseases.

Not just for women

Although most frequently found in the female population, HFI is not an exclusively female condition. Prof. Hershkovitz points to the case of Farinelli, a famous male opera singer in the 18th century, who suffered from HFI probably as a result of castration to preserve his falsetto voice.

Prof. Hershkovitz, Dr. Peled and May discovered a high prevalence of HFI in men who have been treated for prostate cancer. One of the treatments for prostate cancer, explains Prof. Hershkovitz, is chemical castration. Since the cancer itself feeds on testosterone, this treatment option literally starves the disease, but leads to higher levels of estrogen in the body.

Prof. Hershkovitz does not counsel against the prostate treatment, however — it is part of the physiological “cost-benefit” balance of the body. “If you treat one system in the body, another must pay,” he says. In this case, he says, it’s worth the price.



May H, Peled N, Dar G, Abbas J, Hershkovitz I. Hyperostosis frontalis interna: What does it tell us about our health? Am J Hum Biol 2011; 23 (3): 392-397.


Mother’s Diet Influences Baby’s Allergies — New Research

A possible link between what a mother eats during pregnancy and the risk of her child developing allergies has been identified in new research published in this month’s The Journal of Physiology.

The research found that if a mother’s diet contains a certain group of polyunsaturated fatty acids (PUFAs) – such as those found in fish, walnut oil or flaxseed – the baby’s gut develops differently. The PUFAs are thought to improve how gut immune cells respond to bacteria and foreign substances, making the baby less likely to suffer from allergies.

Until now, several clinical trials have shown that fish and walnut oil supplementation in pregnant women reduces the risk of allergy in their children, but the mechanism was unknown.

“There is intense research interest in maternal diet during pregnancy. In the western diet, the group of polyunsaturated fatty acids that we have shown to help gut function are actually disappearing – our dietary intake of fish and nut oils is being replaced by corn oils which contain a different kind of fatty acid”. Said Dr Gaëlle Boudry, of the INRA research institute in Rennes, France.

“Our study identifies that a certain group of polyunsaturated fatty acids – known as n-3PUFAs – causes a change in how a baby’s gut develops, which in turn might change how the gut immune system develops. These changes are likely to reduce the risk of developing allergies in later life.”

The team found that supplementing a mother’s diet with n-3PUFA caused the new-born’s gut to become more permeable. A more permeable gut enables bacteria and new substances to pass through the lining of the gut into the bloodstream more easily. These new substances then trigger the baby’s immune response and the production of antibodies.

“The end result is that the baby’s immune system may develop and mature faster – leading to better immune function and less likelihood of suffering allergies,” added Dr Boudry.

This research adds to previous studies which have shown that an intake of n-3 PUFAs during pregnancy increases gestational length and maturation of the central nervous system of a baby and that their performance on mental tasks also seemed to be improved in childhood.

“Other studies have found that a diet containing fish or walnut oil during pregnancy may make your baby smarter – our research adds to this, suggesting such supplements also accelerate the development of a healthy immune system to ward off food allergies.”

In terms of next steps, the team’s findings were based on piglets so research will continue to see if they translate to humans. The porcine intestine is an excellent model of the human gut however, so they are hopeful that the findings can be extrapolated. The team also plans to investigate whether the apparent gut function-boosting effects of n-3PUFA that they have identified in new-borns extends into later life.



De Quelen F, Chevalier J, Rolli-Derkinderen M, Mourot J, Neunlist M, Boudry G. n–3 polyunsaturated fatty acids in the maternal diet modify the postnatal development of nervous regulation of intestinal permeability in piglets J Physiol 2011; 589 (17): 4341-4352.


Role Of Soy In Menopausal Health Reported

Discussion of a scientific review of soy protein, soy isoflavones and soy metabolites for peri- and postmenopausal women at North American Menopause Society (NAMS)/Wulf H. Utian Translational Science Symposium:


Soy has recently been reviewed and supported for introduction into general medical practice as a treatment for distressing vasomotor symptoms of menopause, such as hot flashes, but its use in other medical areas, such as heart health, requires further research, according to a new report reviewing the risks and benefits of soy protein, isoflavones and metabolites in menopausal health from The North American Menopause Society (NAMS)/Wulf H. Utian Translational Science Symposium, published in the July Menopause, the peer-reviewed NAMS journal.

“Although a significant amount of scientific research about soy and soy isoflavones exists, the adoption of soy isoflavones into the care of women in menopause has to date been recommended mainly by physicians and health care practitioners involved in integrative medicine. We believed that facilitating a robust review of the current scientific evidence about the benefits and risks of soy could yield a document useful to physicians to help them make decisions about soy use with their patients, particularly those in menopause,” said Belinda H. Jenks, Ph.D., director of Scientific Affairs & Nutrition Education at Pharmavite LLC. Otsuka Pharmaceutical Co., Ltd., Pharmavite LLC and the Allmen Foundation supported the development of the symposium and report via an unrestricted educational grant.

The report focuses on a review of soy’s mechanism of action and processing within the body (bioavailability and pharmacokinetics), as well as on several therapeutic areas, concluding that use of soy isoflavones for hot flashes is reasonable and that soy food consumption is associated with lower risk of breast and endometrial cancer. The report also recommended more research to further characterize the effects of soy isoflavones on bone and cardiovascular health as well as cognition, which involves thinking, reasoning, or remembering.

The report, approved by the NAMS Board of Trustees, was authored by 22 clinicians and well-respected scientific research experts in women’s health and botanicals who participated in the symposium in October 2010. They examined basic and clinical research findings from more than two hundred key published controlled trials as well as laboratory studies of the soy isoflavones genistein and daidzein and the daidzein metabolite, S-equol. A supplement containing Natural S-equol for the management of menopausal symptoms is in development by Pharmavite LLC, the makers of Nature Made® vitamins and minerals and a subsidiary of Otsuka Pharmaceutical Co., Ltd.

About Soy Isoflavones and S-Equol

Soy isoflavones are compounds that can bind to estrogen receptors. The isoflavones genistein and daidzein are primarily found in whole soybeans and soy products. S-equol [7-hydroxy-3-(4′-hydroxyphenyl)-chroman] is a compound resulting — when certain bacteria are present in the digestive tract — from the metabolism, or conversion, of daidzein.

S-equol binds to the same estrogen receptors as naturally occurring, endogenous estrogen, but with a stronger affinity for the estrogen beta receptor. On binding to these receptors, S-equol mimics some, but not all, activities of endogenous estrogen. Because of these actions, it has been proposed that S-equol alleviates some of the symptoms caused by diminished estrogen production during menopause.

However, not everyone can produce S-equol after soy consumption, as the production depends on the types of bacteria present in the large intestine and may be influenced by the amount of soy consumed. About 50 percent of Asians and 20 to 30 percent of North Americans and Europeans, who in general consume less soy than Asians, have the ability to produce high levels of S-equol. Controlled clinical trials have documented that a supplement containing Natural S-equol reduces the frequency of hot flashes as well as muscle discomfort associated with menopause, in women both in Japan and the United States.

Soy Isoflavone Bioavailability and Pharmacokinetics

Not all soy foods or supplements contain the same amount or percentage of the three primary isoflavones genistein, daidzein or glycetein. Soyfoods and supplements can vary in soy isoflavone amounts and forms which, in turn, may impact the way the body will metabolize the isoflavones and subsequently can impact their effectiveness in health care, the report states.

For example, the rates of absorption in the body of the isoflavones daidzein and genistein depend on their form. As glycosides, which have an attached sugar molecule, both isoflavones can reach a peak plasma concentration in four to 10 hours. However, the human body cannot use this form, and during digestion the sugar is removed. This resulting aglycone form can be absorbed faster. When consumed as aglycosides, both daidzein and genistein can achieve peak concentrations in just one hour, or up to three hours if eaten with a meal. When the daidzein metabolite S-equol is consumed, its peak plasma rate rapidly occurs in just one to two hours.

The time needed for the total plasma concentration of either isoflavone to decrease by half typically is six to 12 hours and for S-equol, six to eight hours. However, genistein takes significantly longer to leave the body than daidzein. S-equol is excreted almost exclusively in urine, with 75 percent excreted within 12 hours after consumption.

Soy-isoflavones Reasonable for Menopausal Symptoms

The NAMS report advises that in postmenopausal women with distressing vasomotor symptoms, such as hot flashes, initial treatment with soy isoflavones is reasonable because of demonstrated modest effectiveness in early post-menopausal women who have at least four hot flashes daily. The report recommends a starting dose of 50 milligrams (mg) or more daily for at least 12 weeks. If a woman responds, the treatment can continue with monitoring for side effects, but for women who do not respond after 12 weeks, other treatment options should be discussed, the authors suggest.

However, the report points to increasing evidence that women whose gut bacteria have little or no capacity to covert daidzein to S-equol may continue to suffer from severe hot flashes despite daidzein supplementation. The report suggests that dietary supplements providing higher proportions of genistein or S-equol may provide more relief of menopausal symptoms than the modestly effective relief recognized by soy isoflavones alone. Also, the report recommends a supplement containing natural S-equol may be effective for some women who do not have the capacity to produce S-equol, which occurs only when certain bacteria are present in the digestive tract.

The authors’ menopause symptom treatment recommendations were based on a review of 14 studies that included data on soy isoflavone content and dosing, at least 12 weeks of treatment, women who experienced natural (not induced) menopause and the women’s average age, their prevalence of hot flashes at study start and their magnitude of symptom improvement.

Potential Protection for Breast and Endometrial Cancer

Soy foods, in populations that typically consume them, appear to protect against breast cancer. Therefore, the NAMS report advises that moderate life-long dietary soy consumption is recommended as part of a healthy lifestyle. The best evidence indicates that there are no adverse effects from this diet and it has potential for prevention of breast and endometrial cancer, the report states.

However, the authors note that specific recommendations regarding soy food or soy isoflavone consumption by breast cancer survivors cannot be made at this time, although such studies in humans indicate either no effect or a protective effect, but in contrast laboratory and rodent studies indicate a potential for risk.

The authors recommend studies of endometrial risk should focus on long-term, postmenopausal exposures to soy. The authors’ breast and endometrial cancer recommendations were based on a review of at least 18 studies.


Further Research about Soy Effects on Women’s Health

The NAMS report identifies several areas for further research on soy in midlife women. Specifically, the authors call for more studies that compare outcomes among women whose intestinal bacteria have the ability to convert daidzein to S-equol with those that do not to determine if equol producers derive greater benefits from soy supplementation. Also, larger studies are needed in younger postmenopausal women, as is more research to understand soy isoflavone supplement use in women. The authors also propose studies on the relationships of other dietary components as well as prescription and over-the-counter medications on soy isoflavones, consumed as a part of the diet or as a supplement, and S-equol production. And finally, the authors request greater standardization and documentation of clinical trial data regarding soy.



North American Menopause Society. The role of soy isoflavones in menopausal health: report of The North American Menopause Society/Wulf H. Utian Translational Science Symposium in Chicago, IL (October 2010). Menopause 2011; 18 (7): 732-53.

Natural S-equol. A scientific advancement for menopause therapy.


Vitamin D Can Help Elderly Women Survive

Giving vitamin D3 (cholecalciferol) to predominantly elderly women, mainly in institutional care, seems to increase survival. These women are likely to be vitamin D deficient with a significant risk of falls and fractures. This is the key conclusion in a systematic review published in the latest edition of The Cochrane Library.

Up until now there has been no clear view on whether there is a real benefit of taking vitamin D. “A Cochrane meta-analysis published only a couple of years ago found that there was some evidence for benefit, but it could not find an effect on mortality. We were, however, aware that more trials had been published and wanted to assess the effects of vitamin D when you added all the data together,” said Dr Goran Bjelakovic, who works at Department of Internal Medicine – Gastroenterology and Hepatology, at the University of Nis, in Serbia and at The Cochrane Hepato-Biliary Group at The Copenhagen Trial Unit in Copenhagen, Denmark.

The eight-strong international team of researchers identified 50 randomised trials that together had 94,148 participants. They had a mean age of 74 years, and 79% were women. “Our analyses suggest that vitamin D3 reduces mortality by about 6%. This means that you need to give about 200 people vitamin D3 for around two years to save one additional life,” says Bjelakovic.

There were no significant benefits of taking other forms of vitamin D such as vitamin D2, and the active forms of the vitamin, alfacalcidol or calcitriol. However, the researchers point out that they could only find much less data relating to these types of vitamin D and so these conclusions should be taken with caution. “We need to have more randomised trials that look specifically to see whether these forms of vitamin D do or don’t have benefits,” says Bjelakovic. His team did conclude that alfacalcidol and calcitriol significantly increased the risk of hypercalcaemia, and vitamin D3 combined with calcium significantly increased the risk of kidney stones.

There have been reports and comments that taking vitamin D can reduce the risk of getting cancer, but this work showed no evidence that vitamin D reduced cancer-related mortality.

“Previous reviews of preventive trials of vitamin D have not included as much information and have not examined the separate influence of different forms of vitamin D on mortality. By taking data from a larger number of trials we have been able to shed much more light on this important issue,” says Bjelakovic.


Vitamin D Supplements Found To Be Safe For Healthy Pregnant Women

Use of vitamin D supplements during pregnancy has long been a matter of concern but now researchers writing in theJournal of Bone and Mineral Research report that even a high supplementation amount in healthy pregnant women was safe and effective in raising circulating vitamin D to a level thought by some to be optimal. The study also found no adverse effects of vitamin D supplementation, even at the highest amount, in women or their newborns.

The research team, led by Dr. Bruce Hollis from the Medical University of South Carolina in Charleston, used a randomized controlled trial with healthy expectant mothers to discover how varying dosages of daily supplements could safely sustain a circulating vitamin D level of at least 32 nanograms per milliliter.

“Vitamin D supplementation during pregnancy remains controversial largely due to severe misconceptions about the potential harm it may cause to the fetus,” said Dr Hollis. “Surprisingly the scientific debate has made little progress since Dr. Gilbert Forbes made a recommendation of 200 IU (international units) per day in 1963, which was based on a hunch.”

While the threat of vitamin D during pregnancy has remained little known, it has been established that the vitamin plays a role in homeostasis, the body’s internal regulation, during pregnancy and that a deficiency can effect immune, pancreatic and cardiovascular systems.

Dr Hollis’ team monitored the pregnancies of 350 women, from a variety of ethnic and socio-economic backgrounds, who were all between 12 and 16 weeks into gestation. The women were randomly assigned to one of three groups. One group received 400 IU of vitamin D per day, the second group received 2,000 IU per day and the third received 4,000 IU daily.

The team found that women who received the highest level of supplementation (4,000 IU per day) were more likely to achieve and sustain the desired level of circulating levels of vitamin D throughout their pregnancy. Moreover, the researchers found that pregnant women who received lower levels of vitamin D supplementation did not attain the threshold circulating level of the vitamin.

“In our study subjects, a daily dosage of up to 4,000 IU of vitamin D was required to sustain normal metabolism in pregnant women,” concluded Dr Hollis. “Furthermore, following decades of speculation into its safety our research has demonstrated vitamin D supplementation to be both safe and effective.”


Full citation:
Hollis. B, Johnson. D, Hulsey. T, Ebeling. M, Wagner. L, “Vitamin D Supplementation during Pregnancy: Double Blind, Randomized Clinical Trial of Safety and Effectiveness”, Journal of Bone and Mineral Research, Wiley-Blackwell, June 2011: DOI