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Isoflavone Research

February 13, 2010 Written by JP       [Font too small?]

Within every living flower, plant and seed there is a complex factory fast at work. The goods manufactured have one basic goal in mind – to ensure survival. In this way, human beings are quite similar to the inhabitants of the botanical world. But, when we think of ourselves, we tend to focus on the external characteristics or feelings and thoughts that we experience. Rarely do we contemplate the broad array of natural substances that travel through the bloodstream, reside in organs and otherwise populate the inner metropolis that is our physiology. That specific type of curiosity is almost exclusively the domain of physicians and scientists.

Isoflavones are chemicals produced by plants in order to repel fungi and microorganisms that can endanger their existence. But these very same substances, often referred to as “phytoestrogens”, can affect the human body in a much different way. Over the past few decades scientists have been investigating the role that these plant-based estrogens may play in the prevention of cancer, cardiovascular disease and much more.

Ever since the early days of research into isoflavones there’s been a certain level of controversy associated with their use. Some physicians believe that such phytoestrogens may disrupt the normal processes of the body if used in larger quantities. Other authorities take the position that isoflavones are perfectly healthy in the context of a well balanced diet, but shouldn’t be used in abnormally concentrated amounts. Finally, there are some experts in the field of natural medicine and nutrition who are true advocates of phytoestrogen therapy. They believe that plant derived estrogen is a gentler and safer way to assist the body in coping with hormonal changes/imbalance as compared to conventional hormone replacement therapy. (1,2,3)

Because this is an ever evolving field of study, I’ve decided to update my current understanding of this topic. In order to do so, I’ll be reviewing some of the most recent human and animal studies involving isoflavones from a variety of dietary sources.

Let’s begin with a study presented in the January edition of the journal Metabolism. This clinical trial helps clarify the effects of soy isoflavones on cholesterol levels. 11 men and 12 women took part in this experiment that examined the impact of three different dietary interventions on lipid levels. All of the participants were classified as having high cholesterol (hyperlipidemia) at the start of the study.

  • The volunteers were asked to consume 3 different diets, in separate trials each lasting 4 weeks.
  • Diet 1 involved the consumption of “a low-fat dairy diet and 10g/d prebiotic (oligofructose-enriched inulin)”.
  • Diet 2 consisted of “a soy food-containing diet (30g/d soy protein, 61 mg/d isoflavones) and 10g/d placebo (maltodextrin)”.
  • Diet 3 provided the same soy food diet along with 10g/d of the prebiotic inulin used in the first diet.

A group of researchers, from the University of Toronto, analyzed the results of the experiment and determined that the combination of soy isoflavones + the prebiotics yielded the greatest cholesterol lowering effect. Specifically, a significant drop in LDL (“bad”) cholesterol and a hike in HDL (“good”) cholesterol was documented. These same benefits were not reported when the participants were using the dairy + prebiotics or soy + placebo diets. The authors of the study speculate that the fermentation provoked by the prebiotics may have enhanced the absorption and activity of the isoflavones naturally present in soy. (4)

Another trial from December 2009 concluded that isoflavones in red clover could effectively alter the cardiovascular risk profile in 40 healthy postmenopausal women. Over the course of 12 months, the women demonstrated a statistically relevant decline in LDL, total cholesterol and trigylceride levels. Like the previously mentioned study on soy + prebiotics, the volunteers using red clover isoflavones also found an elevation in HDL cholesterol. According to the scientists involved, no significant side-effects were observed over the course of the 1 year trial period. (5)

The combination of soy isoflavones and prebiotics was also the spotlight of the February 2010 edition of the Journal of Medicinal Food. However this time, the focus was on bone health. Researchers from Florida State University discovered that a blend of genistin, an isoflavone found in soy, and a prebiotic known as fructooligosaccharides (FOS) was more effective than soy alone in promoting enhanced bone density in a group of menopausal (ovariectomized) rats. This news is particularly welcome at this time because the most recent human study examining soy found relatively disappointing results. In that case, only a small gain in neck bone mineral density was reported based on a 3 year trial period. It’s not guaranteed, but it’s possible that the addition of prebiotics to soy could improve the outcome for women hoping to benefit from soy isoflavones in relation to osteopenia and osteoporosis. (6,7)

There’s an interesting side note to the isoflavone-bone connection. A group of scientists from the Department of Food Science & Technology at the University of California recently announced that beers rich in hops may assist in promoting a healthy skeletal system. The reasoning behind this speculative claim is that such beers are a rich source of the trace mineral silicon. Beyond that, the form of silicon found in hops-rich brews is a particularly bioavailable form known as orthosilicic acid. But there’s another reason why hops-based beverages and extracts may support bone integrity – hops are a plentiful source of isoflavones. (8,9,10)

A quick survey of the current isoflavone landscape reveals one seemingly positive development and few disappointments. On the positive side, a new Australian and Japanese study both suggest that regular consumption of dietary isoflavones may help protect against chronic obstructive pulmonary disease (COPD) and lung cancer. The COPD investigation involved a total of 618 patients – 278 with COPD and 340 healthy “controls”. A careful analysis of the participants’ dietary patterns revealed that those with COPD “had significantly lower habitual intakes of isoflavones”. A much larger study that included over 76,000 older men and women looked for a correlation between diet and lung cancer incidence over the course of 11 years. Researchers from the National Cancer Center in Tokyo, Japan observed that the men and women who did not smoke and regularly ate soy were much less likely to develop cancer than those who didn’t smoke but infrequently consumed isoflavones. This conclusion was based on the results of a food frequency questionnaire that included 138 food items. (11,12)

I’m sorry to report that supplementing with soy isoflavones does not appear to reduce appetite or promote fat loss in postmenopausal women. A new study in the February 2010 issue of Menopause bursts that bubble. 229 healthy, older women were given either a placebo, 80mg or 120mg of soy isoflavones for 12 months. No changes were detected with regard to body composition (lean body and fat mass) or in the levels of appetite-related hormones (adiponectin, ghrelin, insulin or leptin). Speaking of insulin, soy protein doesn’t seem to improve the health of those with type 2 diabetes either. So says a recent Canadian paper published in the British Journal of Nutrition. Soy protein was not found to be superior to milk protein in a crossover study conducted on 29 type 2 diabetics. No meaningful differences in fasting blood sugar, HbA1C and insulin resistance or sensitivity were uncovered. However it’s worth noting that some experts believe that fermented soy products may be more successful in the natural management of diabetes than conventionally processed soy. (13,14,15)

Soy Isoflavones Tend to Concentrate in the Prostate Gland
Source: Prostate 2009 May 15; 69(7): 719-726 (link)

One of the most popular uses of soy extracts is in the management of menopausal symptoms. The most recent trial that examined this issue took place in the Gynecology and Obstetrics Department of San Raffaele Hospital in Milano, Italy. 180 women with ages ranging from 40-65 took part in the study. All of the participants reported having at least 5 episodes of hot flashes within the 7 days preceding the start of the trial. Half of the female volunteers were given 80mg of isoflavones (containing 60mg of genistein) or a placebo for 12 weeks. The women receiving the soy extract reported a 36.2% reduction in “moderate-to-severe hot flashes” at the 6 week mark and a 41.2% decline by week 12. There was also a relatively high response rate in the placebo group (24% and 29.3% respectively). However, the researchers conducting the experiment still felt that the soy isoflavones should be considered for “the management of hot flashes in postmenopausal women not treated with hormone replacement therapy due to their superior efficacy to placebo and a very good safety profile”. (16)

The most intriguing discovery I made while researching isoflavones has to do with coffee – a favorite subject of mine. It turns out that coffee can be a bountiful source of isoflavones. New research out of Portugal explains that the way coffee is brewed, roasted and the species of coffee used are all important determinants of isoflavone concentrations. For instance, 30 mL of “100% arabica” espresso contains about 40 mcg of isoflavones. The same amount of “100% robusta” espresso yields roughly 7 times that amount. In general, it was found that espresso contained larger quantities of isoflavones such as daidzein, genistein and formononetin than “press-pot coffee” or “filtered coffee”. (17,18)

So far today, I’ve mostly focused on soy’s potential in female related health issues. However, the coffee/isoflavone issue may also be particularly relevant for men. Some evidence suggests that dietary phytoestrogens tend to concentrate in prostatic tissue – the significance being that isoflavones may possess direct and indirect anti-cancer properties. If you couple this understanding with a recent report that linked heavy coffee intake with a “60% lower risk of aggressive prostate cancer”, it really makes you wonder whether coffee may one day assume a leading role in the natural fight against prostate cancer. (19,20,21)

What I’ve found in compiling today’s column is similar to the discoveries I’ve made in the past about isoflavones. These phytochemicals cannot be easily classified as dangerous across the board, largely ineffective or outright panaceas. Authorities who espouse any of those positions are simply not looking hard enough for the facts. I’m sure that there are people out there who ought to avoid phytoestrogens altogether. I’m also convinced that you can live a perfectly healthy life without trying to include plenty of isoflavones in your menu plan. But I’m equally certain that isoflavones can provide a therapeutic effect under select circumstances as well. I think the best plan of action is to continue to research these complex substances in order to scientifically identify how and when to best utilize them. Thankfully, I’m not alone in this point of view. As I type this, there are multiple studies currently under way that will undoubtedly help clarify many of the questions we all have about isoflavones. I’ll make sure to keep an eye and ear out for what that research reveals and you can count on me to report whatever I discover right here.

Note: Please check out the “Comments & Updates” section of this blog – at the bottom of the page. You can find the latest research about this topic there!

Be well!

JP

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10 Comments & Updates to “Isoflavone Research”

  1. Nina K. Says:

    Morning JP :-)

    I’m always interested in natural soy isoflavones. I have read a lot about it and I’m very insecure if soy products are healthy or not. Theres a big controversy: a few say its healthy others say its not because it impairs the thyroid gland etc…

    One manufacturer of soy products (all organic) makes a really good deep smoked tofu, i eat it sometimes cause of the delicious taste, but i know its a high processed food :-( .

    The picture above looks like young soybeans called edamame, there are a lot of commercials for edamame at the moment. I’m curious to try them but theres again the voice in my head….be carefull….i also would like to try high protein spaghetti made of soy….it is really difficult.

    Do you know JP how much soy consumption is necessary to impair the thyroid function and other hormonal cycles?

    One story of our live: we lived in Bavaria for about 3 years. They consume a lot of hops (beer!) In fact you can see that the male Bavarians have a less risk for osteoporosis because the look very female – cause of high beer consumption most of them at any age have growing breasts!! I have never seen that before in such a degree :-) I think hops i really good but in a moderate amount ;-)

    Greetings

    Nina K.

  2. JP Says:

    Nina,

    I don’t thinks there’s currently an “upper limit” established for soy. Soy can indeed impact sex hormone levels and possibly affect thyroid function in select populations:

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2691652/?tool=pubmed

    http://www.ncbi.nlm.nih.gov/pubmed/18624607

    http://jn.nutrition.org/cgi/content/full/138/6S-I/1244S

    My personal position is that it’s probably best for most people to avoid eating soy on a regular basis – unless they’re using it for a strategic purpose. Certain sensitive individuals, such as though with hypothyroidism, should likely stay away from soy altogether or consume it infrequently.

    For those who do eat soy, I generally recommend that they opt for fermented versions when possible or at least organic (unfermented) soy as the next best choice. I think they should consider supplementing with digestive enzymes, pre- and/or probiotics to enhance absorption and digestion of the desirable phytochemicals. Finally, I would pay close attention to ensure optimal amounts of dietary or supplemental iodine when eating soy regularly. This may support proper thyroid function.

    I think this plan of action will likely remove much of the downside associated with this legume. Still, I choose to mostly avoid them – mainly because I don’t have a good enough reason to include soy in my wellness regime.

    re: the top-heavy men

    Excess alcohol, from any source, can bring about this kind of effect! Moderation is definitely the key! ;)

    http://www.ncbi.nlm.nih.gov/pubmed/562605

    Be well!

    JP

  3. anne h Says:

    Many, many years I was a Vegan.
    Then for many more, a vegetarian.
    I never really got any of the reported good benefits of soy.
    Except I was very popular with the “shabby chic” Bohemian crowd!
    That, and reading “A Course In Miracles” would have gotten me a date quick!
    Except for I was celibate then, as well!

  4. Sai Says:

    Good Day JP!

    Edamame is one of my favorites and we add it to the veggie fried rice frequently. Next time i will add it with confidence! Yes, Soy has been one of the controversial foods, but as long as it is in moderation and with the help of these type of articles we have to make careful progress. The only problem is i think it is still not safe for very young girls approaching puberty. I would appreciate your comments on that.

    Best Regards

    Sai.

  5. JP Says:

    Anne,

    I was all those things too – at one point or another. ;)

    Be well!

    JP

  6. JP Says:

    Good day, Sai! :)

    I personally think soy should be eaten in moderation, if at all, in growing boys and girls. There’s really no sense in risking any possibility of endocrine disruption, in my opinion:

    http://www.ncbi.nlm.nih.gov/pubmed/17546252

    http://www.bprcem.com/article/S1521-690X%2805%2900076-X/abstract

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1415269/?tool=pubmed

    Be well!

    JP

  7. JP Says:

    Updated 08/24/15:

    http://link.springer.com/article/10.1007/s00404-015-3849-0/fulltext.html

    Arch Gynecol Obstet. 2015 Aug 21.

    Low-dose isoflavone aglycone alleviates psychological symptoms of menopause in Japanese women: a randomized, double-blind, placebo-controlled study.

    PURPOSE: Many studies have demonstrated the effectiveness of isoflavones on menopausal symptoms; however, these mostly used high dosages. Because high-dose isoflavone may result in endometrial hyperplasia, we investigated whether low-dose isoflavone aglycone alleviates menopausal symptoms similarly to high dosages.

    METHODS: We conducted a randomized, double-blind, placebo-controlled study in 90 healthy women aged 40-60 years who had at least one menopausal symptom on the Menopausal Symptom Scale (MSS). The participants were randomized to receive active tablets containing ultralow-dose (12.5 mg/day; n = 30) or low-dose (25 mg/day; n = 30) isoflavone aglycone, or placebo (n = 30) tablets, for 8 weeks. Their menopausal symptoms were evaluated using MSS, Hospital Anxiety and Depression Scale (HADS), and Athens Insomnia Scale (AIS) before, and 4 and 8 weeks after treatment.

    RESULTS: Eighty-seven women (97 %) completed the 8-week treatment. In the low-dose group, significant improvement was observed from baseline, in the following parameters: (1) HADS-depression subscale score, (2) AIS score, (3) MSS-somatic symptom score after 4 and 8 weeks of treatment, and (4) MSS-vasomotor symptom score after 8 weeks of treatment. The changes in scores on HADS-depression subscale and AIS from baseline to 8 weeks were significantly higher in the low-dose group than in the placebo group.

    CONCLUSIONS: Low-dose (25 mg/day) isoflavone aglycone significantly alleviated symptoms of depression and insomnia in Japanese middle-aged women.

    Be well!

    JP

  8. JP Says:

    Updated 08/24/15:

    http://cancerpreventionresearch.aacrjournals.org/content/early/2015/08/13/1940-6207.CAPR-14-0464.abstract

    Cancer Prev Res (Phila). 2015 Aug 14.

    Consumption of soy isoflavone enriched bread in men with prostate cancer is associated with reduced pro-inflammatory cytokines and immunosuppressive cells.

    We hypothesized that soy phytochemicals may have immunomodulatory properties that may impact prostate carcinogenesis and progression. A randomized, phase II trial was conducted in 32 prostate cancer patients with asymptomatic biochemical recurrence but no measurable disease on standard staging studies. Patients were randomized to 2 slices of soy bread (34 mg isoflavones/slice) or soy bread containing almond powder daily as a source of β-glucosidase. Flow cytometry and bioplex assays were used to measure cytokines or immune cell phenotype in blood at baseline (day 0) and following intervention (day 56). Adequate blood samples were available at enrollment and day 56 and evaluated. Multiple plasma cytokines and chemokines were significantly decreased on Day 56 versus baseline. Subgroup analysis indicated reduced Th1 (p=0.028) and MDSC-associated cytokines (p=0.035). Th2 and Th17 cytokines were not significantly altered. Phenotypic analysis revealed no change in CD8+ or CD4+ T cells, but showed increased CD56+ NK cells (p=0.038). The percentage of cells with a T regulatory cell phenotype (CD4+CD25+FoxP3+) were significantly decreased after 56 days of soy bread (p=0.0136). Significantly decreased monocytic (CD33+HLADRnegCD14+) MDSC were observed in patients consuming soy bread (p=0.0056). These data suggest that soy bread modulates systemic soluble and cellular biomarkers relevant to immunomodulation consistent with limiting inflammation and suppression of MDSCs. Additional studies to elucidate impact on the carcinogenic process or as a complement to immune-based therapy are required.

    Be well!

    JP

  9. JP Says:

    Updated 08/24/15:

    http://cancerpreventionresearch.aacrjournals.org/content/early/2015/08/13/1940-6207.CAPR-15-0125.abstract

    Cancer Prev Res (Phila). 2015 Aug 14.

    Double-blind randomized 12-month soy intervention had no effects on breast MRI fibroglandular tissue density or mammographic density.

    Soy supplementation by breast cancer patients remains controversial. No controlled intervention studies have investigated the effects of soy supplementation on mammographic density in breast cancer patients. We conducted a double-blind, randomized, placebo-controlled intervention study in previously treated breast cancer patients (n=66) and high-risk women (n=29). We obtained digital mammograms and breast magnetic resonance imaging (MRI) scans at baseline and after 12 months of daily soy (50 mg isoflavones per day) (n=46) or placebo (n=49) tablet supplementation. The total breast area (MA) and the area of mammographic density (MD) on the mammogram was measured using a validated computer-assisted method, and mammographic density percent (MD% = 100 × MD/MA) was determined. A well-tested computer algorithm was used to quantitatively measure the total breast volume (TBV) and fibroglandular tissue volume (FGV) on the breast MRI, and the FGV percent (FGV% = 100 × FGV/TBV) was calculated. On the basis of plasma soy isoflavone levels, compliance was excellent. Small decreases in MD% measured by the ratios of month 12 to baseline levels, were seen in the soy (0.95) and the placebo (0.87) groups; these changes did not differ between the treatments (P=0.38). Small decreases in FGV% were also found in both the soy (0.90) and the placebo (0.92) groups; these changes also did not differ between the treatments (P=0.48). Results were comparable in breast cancer patients and high-risk women. We found no evidence that soy supplementation would decrease mammographic density and that MRI might be more sensitive to changes in density than mammography.

    Be well!

    JP

  10. JP Says:

    Updated 06/30/17:

    https://www.ncbi.nlm.nih.gov/pubmed/28661316

    Br J Nutr. 2017 May;117(10):1403-1413.

    Effects of isoflavone-containing soya protein on ex vivo cholesterol efflux, vascular function and blood markers of CVD risk in adults with moderately elevated blood pressure: a dose-response randomised controlled trial.

    Emerging CVD risk factors (e.g. HDL function and central haemodynamics) may account for residual CVD risk experienced by individuals who meet LDL-cholesterol and blood pressure (BP) targets. Recent evidence suggests that these emerging risk factors can be modified by polyphenol-rich interventions such as soya, but additional research is needed. This study was designed to investigate the effects of an isoflavone-containing soya protein isolate (delivering 25 and 50 g/d soya protein) on HDL function (i.e. ex vivo cholesterol efflux), macrovascular function and blood markers of CVD risk. Middle-aged adults (n 20; mean age=51·6 (sem 6·6) years) with moderately elevated brachial BP (mean systolic BP=129 (sem 9) mmHg; mean diastolic BP=82·5 (sem 8·4) mmHg) consumed 0 (control), 25 and 50 g/d soya protein in a randomised cross-over design. Soya and control powders were consumed for 6 weeks each with a 2-week compliance break between treatment periods. Blood samples and vascular function measures were obtained at baseline and following each supplementation period. Supplementation with 50 g/d soya protein significantly reduced brachial diastolic BP (-2·3 mmHg) compared with 25 g/d soya protein (Tukey-adjusted P=0·03) but not the control. Soya supplementation did not improve ex vivo cholesterol efflux, macrovascular function or other blood markers of CVD risk compared with the carbohydrate-matched control. Additional research is needed to clarify whether effects on these CVD risk factors depend on the relative health of participants and/or equol producing capacity.

    Be well!

    JP

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