Note: before anyone pooh-poohs this article for being in a blog mostly about weather and climate, note the description on the masthead. Note also that I have recently experienced cancer in my family as I’m sure many readers have at some time, therefore it is relevant to me, and may be helpful to others, and that’s all that matters. – Anthony
Guest post by David Archibald
Before starting out in climate science in 2006, my main hobby was cancer research. To that end, I had co-invented a cancer drug with two professors from Purdue University, Professor Jim Morre and his wife Professor Dorothy Morre. I went on to lodge a patent on a benign prostatic hyperplasia (BPH) drug myself. I still operate in that space. Early in that journey, I was given the draft manuscript of a book on how isoflavones from soy and other legumes modulate the human female hormone system.
That was in 1998. The manuscript had been written by Dr Graham Kelly who had founded a company to commercialise isoflavone supplementation in men and women. Dr Kelly’s journey in cancer research started in the 1980s when a friend with bowel cancer asked him to look into the science of it. Dr Kelly was intrigued by the epidemiological differences in cancer rates between populations. For example, Japanese who migrate to the US go to the US breast cancer rate in a generation. The US breast cancer rate is five times the Japanese breast cancer rate. The difference in cancer rate is not genetic, it is obviously dietary. So what is the difference in diet that is causing the difference in cancer incidence? A big difference is isoflavone consumption. Amongst the Japanese, it is an average of 40 mg per day. The US average is 3 mg per day.
In Western countries, breast cancer and prostate cancer have the same incidence. In women, 11% get diagnosed with breast cancer in their lifetime and 5% die of it. In men, 11% get diagnosed with prostate cancer in their lifetime and 5% die of it. There are very big epidemiological differences in prostate cancer rates. As the following graph shows, the Vietnamese prostate cancer rate is one fortieth of the Western prostate cancer rate:
Defeating the scourge of a lot of common cancers is as simple as changing your diet. It is a bit like Vitamin C. If you don’t get any Vitamin C in your diet, you die of scurvy within three years. Pigs and dogs make their own Vitamin C, and presumably some precursor ape to humans had the ability to make it. Humans must have lost the ability for an evolutionary advantage. There are probably a large number of other plant molecules which we evolved to rely upon in our diet. We might not die in the near term if we don’t get them in our diet, but we suffer an increased incidence of degenerative diseases if we don’t. With respect to the dietary components that might cause the low Vietnamese prostate cancer rate, the national dish of Vietnam is called pho. It is a bowl of noodles and meat with three side dishes – bean sprouts, chillis and mint. The anticancer effect would be the result of synergistic blocking of the tNOX molecule on the external membrane of cancer cells by sulforaphane from the bean sprouts with capsaicin from the chilli peppers, stopping the overproduction of anti-apoptotic proteins and allowing the death receptors to trigger the apoptotic cascade of the caspases.
Back to Dr Kelly’s book, “Hormones with Harmony”. It is 70,000 words and goes into highly readable detail on how the daughter metabolites of isoflavones become human hormones in the body. They then become very useful in evening out the peaks and troughs of the body’s estrogenic hormones: estradiol, estrone and estriol. The book goes into detail on how the plant-derived hormones are beneficial in pms, mastalgia, endometriosis, uterine fibroids, uterine cancer, ovarian cancer, menopausal symptoms, osteoporosis, cardiovascular disease, cataracts, senile dementia and breast cancer. Without being overly technical, it does not talk down to its readers. Earlier this year, I undertook to get it published and it is now available on Kindle for $5 per copy. I do recommend it.
Further to the subject of prostate cancer, there are a number of plant molecules that have an effect on it and BPH. All cancers have tNOX molecules on their external membranes. tNOX is the tumour variant of cNOX, or normal constituent NOX. No plant molecules bind to cNOX but a number bind to tNOX. tNOX has two binding sites. If both are bound to simultaneously, the effect is synergistic. For example, the combination of sulforaphane with capsaicin has twenty times the effect of sulforaphane alone. Another example of synergism is curcumin from turmeric with piperine from black pepper.
David Archibald
December 2012
This article is the worst kind of Junk Science. No controlled population studies. No controlling for age, genetics, socio economic status, different diagnostic techniques, and a myriad of other cofounding factors. This is hippie New Age crap. This is the same kind of lazy thinking that lead to the the Alar ban, the DDT ban, believing that that Sandy was caused by AGW, and a thousand other lazy thinking correlations. The lack of skepticism except by a few commenters above is an embarrassment. This is an article about modern hippie snake oil and most of you are waiting in line to buy it.
That said, there is nothing wrong with exploring nutrition as a means to better health and well-being but it is not a panacea for cancer prevention.
I’m going with “David, UK” and anyone who says there is no money to be made in selling a cure. Plenty is made selling treatments that will carry on over a lifetime.
Far more money is made when even more drugs have to be prescribed to balance off side effects of the previous drugs.
Can you imagine the effect on US tax revenues, exports, share values on Pharma and red faces fit to murder if a couple of cheap, common items were found to be a prevention never mind a cure?
Michael Tremblay says:
December 12, 2012 at 12:02 pm
Although I agree with the premise that diet can directly affect cancer rates, I do not, and would not, dismiss the genetic connection.
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The good doctor said, “For example, Japanese who migrate to the US go to the US breast cancer rate in a generation. The US breast cancer rate is five times the Japanese breast cancer rate. The difference in cancer rate is not genetic, it is obviously dietary.”
Note that he did not say that Americans who migrate to Japan go to the Japanese breast cancer rate in a generation. Without this, the “difference in cancer rate is not genetic” is mere speculation.
Forget isoflavones, and look into Paleo.
Aren’t there aboriginal tribes that still live that way, or did until they were encountered by Western Civilization? There is no record of aboriginal peoples living so long. Childbirth and it’s complications is a major cause of death for women where modern medicines do not exist. In those societies, most people don’t live into adulthood. In the days before vaccines and antibiotics, diseases and infections killed many people.
I recall an article about research into heart disease and cholesterol that implied the particle size of a person’s cholesterol.
From the Mayo Clinic: http://www.mayoclinic.org/news2011-mchi/6264.html
Low carb diets and cholesterol size: http://lowcarbdiets.about.com/od/faq/f/carbcholesterol.htm
When Japanese women go live in the US they are five times more likely to develop breast cancer.
And so the conclusion is that it must be the diet. Not differences in smoking, drinking, drug use, drug abuse, obesity, lack of exercise, diffences in medical surveillance, pollution levels, all sorts of stuff in the food…etc. No. It’s soy. Just like we had the infamous “french paradox” in the past, we now have the “asian paradox”. Likely the latter will prove as much based on shoddy statistics as the former.
For a list of veggies: Foods With Sulforaphane
Guess I will be dumping bok choi and broccoli flowers in the chicken soup I am making. (I normally use just bok choi instead of potatoes)
I normally toss in turmeric, looks like I will be adding ginger and cayenne pepper too.
Thanks David.
The various “health foods” may not help but the junk food certainly HURTS so modifying the diet makes sense.
The easiest way to add massive amounts of turmeric to your diet is by realizing that Gulden’s brand already has some in it, but not enough, so just quickly stir in more and use it to flavor your favorite comfort foods.
I salute you, Anthony, for going off topic with a vital topic such as cancer. The Linus Pauling Institute at Oregon State University provides a comprehensive and interesting summary on isoflavonoids; a key point is that the effects of soy isoflavones are strongly influenced by their metabolism, which is dependent on the activity of bacteria that colonize the human intestine (2). For example, the soy isoflavone daidzein may be metabolized in the intestine to equol, a metabolite that has greater estrogenic activity than daidzein, and to other metabolites that are less estrogenic. Studies that measure urinary equol excretion after soy consumption indicate that only about 33% of individuals from Western populations metabolize daidzein to equol (3). Thus, individual differences in the metabolism of isoflavones could have important implications for the biological activities of these phytoestrogens. Also, there is much information on this topic that inconsistent.
Here is a partially abridged version of what is published at http://lpi.oregonstate.edu/infocenter/phytochemicals/soyiso/ :
Soy Isoflavones
Summary
Isoflavones are a class of phytoestrogens—plant-derived compounds with estrogenic activity. Soybeans and soy products are the richest sources of isoflavones in the human diet. (More Information)
The results of randomized controlled trials suggest that substituting 50 g/day of soy protein for animal protein results in only a modest 3% reduction of LDL cholesterol. Isolated soy isoflavone supplements do not appear to have favorable effects on serum lipid profiles. (More Information)
Consumption of soy isoflavones, at doses of <90 mg/day, may inhibit bone resorption and stimulate bone formation (More Information)
Overall, the results of numerous observational studies do not support the idea that high soy isoflavone intakes in adults are protective against breast cancer. Limited research suggests that higher intakes of soy foods early in life may decrease the risk of breast cancer in adulthood. (More Information)
Although scientists are interested in the potential for soy isoflavones to prevent or inhibit the progression of prostate cancer, evidence from observational studies that soy isoflavones are protective against prostate cancer is limited and inconsistent. (More Information)
To date, studies on the effect of soy isoflavone consumption on menopausal symptoms have reported mixed results. (More Information)
Some health effects of soy isoflavones may be dependent on whether or not the isoflavone metabolite, equol, is produced. (More Information)
Although diets rich in soy or soy-containing products appear safe and potentially beneficial, the long-term safety of high doses of soy isoflavone supplements is not yet known. (More Information)
At present, there is no convincing evidence that infants fed soy-based formula are at greater risk for adverse effects than infants fed cow’s milk-based formula. (More Information)
Introduction
Isoflavones are polyphenolic compounds that are capable of exerting estrogen-like effects. For this reason, they are classified as phytoestrogens—plant-derived compounds with estrogenic activity (1). Legumes, particularly soybeans, are the richest sources of isoflavones in the human diet. In soybeans, isoflavones are present as glycosides (bound to a sugar molecule). Fermentation or digestion of soybeans or soy products results in the release of the sugar molecule from the isoflavone glycoside, leaving an isoflavone aglycone. Soy isoflavone glycosides are called genistin, daidzin, and glycitin, while the aglycones are called genistein, daidzein, and glycitein (chemical structures of isoflavone aglycones). Unless otherwise indicated, quantities of isoflavones specified in this article refer to aglycones—not glycosides.
Metabolism and Bioavailability
The biological effects of soy isoflavones are strongly influenced by their metabolism, which is dependent on the activity of bacteria that colonize the human intestine (2). For example, the soy isoflavone daidzein may be metabolized in the intestine to equol, a metabolite that has greater estrogenic activity than daidzein, and to other metabolites that are less estrogenic. Studies that measure urinary equol excretion after soy consumption indicate that only about 33% of individuals from Western populations metabolize daidzein to equol (3). Thus, individual differences in the metabolism of isoflavones could have important implications for the biological activities of these phytoestrogens.
Biological Activities
Estrogenic and Anti-Estrogenic Activities
Soy isoflavones are known to have weak estrogenic or hormone-like activity. Estrogens are signaling molecules that exert their effects by binding to estrogen receptors within cells (chemical structures of endogenous estrogens). The estrogen-receptor complex interacts with DNA to change the expression of estrogen-responsive genes. Estrogen receptors are present in numerous tissues other than those associated with reproduction, including bone, liver, heart, and brain (4). Soy isoflavones and other phytoestrogens can bind to estrogen receptors, mimicking the effects of estrogen in some tissues and antagonizing (blocking) the effects of estrogen in others (5). Scientists are interested in the tissue-selective activities of phytoestrogens because anti-estrogenic effects in reproductive tissue could help reduce the risk of hormone-associated cancers (breast, uterine, and prostate), while estrogenic effects in other tissues could help maintain bone density and improve blood lipid profiles (cholesterol levels). The extent to which soy isoflavones exert estrogenic and anti-estrogenic effects in humans is currently the focus of considerable scientific research.
Estrogen Receptor-Independent Activities
Soy isoflavones and their metabolites also have biological activities that are unrelated to their interactions with estrogen receptors (6). By inhibiting the synthesis and activity of certain enzymes involved in estrogen metabolism, soy isoflavones may alter the biological activity of endogenous estrogens and androgens (7-9). Soy isoflavones have also been found to inhibit tyrosine kinases (10), enzymes that play critical roles in the signaling pathways that stimulate cell proliferation. Additionally, isoflavones can act as antioxidants in vitro (11), but the extent to which they contribute to the antioxidant status of humans is not yet clear. Plasma F2-isoprostanes, biomarkers of lipid peroxidation in vivo, were significantly lower after two weeks of daily consumption of soy protein containing 56 mg of isoflavones than after consumption of soy protein providing only 2 mg of isoflavones (12). However, daily supplementation with 50-100 mg of isolated soy isoflavones did not significantly alter plasma or urinary F2-isoprostane levels (13, 14).
Disease Prevention
Cardiovascular Disease
Serum Cholesterol
Although controlled clinical trials conducted prior to 1995 suggested that substituting 25-50 g/day of soy protein for animal protein lowered serum LDL cholesterol by about 13% (15), more recent and better controlled trials indicate that the LDL cholesterol-lowering effect of soy protein is much more modest. A recent review of 22 randomized controlled trials concluded that substituting 50 g/day of soy protein for animal protein lowered LDL cholesterol by only about 3% (16). There is limited evidence that soy protein containing isoflavones is more effective than soy protein without isoflavones in lowering LDL cholesterol (17,18), but the consumption of soy isoflavones alone (as supplements or extracts) does not appear to have favorable effects on serum lipid profiles (16, 19-21). For more information on soy protein and cholesterol, see the article on Legumes.
Effects on Arterial Function
The preservation of normal arterial function plays an important role in cardiovascular disease prevention. The ability of arteries to dilate in response to nitric oxide produced by the endothelial cells that line their inner surface (endothelium-mediated vasodilation) is compromised in people at high risk for cardiovascular disease (22). To date, results of randomized controlled trials on the effect of soy isoflavones on arterial function have been mixed. However, most placebo-controlled trials found no significant improvement in endothelium-mediated vasodilation when postmenopausal women were supplemented with up to 80 mg/day of soy isoflavones (23-25) or up to 60 g/day of soy protein containing isoflavones (26-30). Arterial stiffness is another measure of arterial function. Measurements of arterial stiffness assess the distensibility of arteries, and a strong association between arterial stiffness and atherosclerosis has been observed (31). In placebo-controlled clinical trials, supplementation of postmenopausal women with 80 mg/day of a soy isoflavone extract for five weeks significantly decreased arterial stiffness (32), as did supplementation of men and postmenopausal women with 40 g/day of soy protein providing 118 mg/day of soy isoflavones for three months (29). Although most studies have not found supplementation with soy protein or isoflavones to improve endothelium-mediated vasodilation, preliminary research suggests that soy isoflavone supplementation may decrease arterial stiffness. However, a recent randomized controlled, cross-over trial in hypertensive individuals found that supplementation with soy protein containing 118 mg/day of isoflavones for six months did not improve measures of arterial function, including arterial stiffness (33). More research is needed to determine whether supplementation with soy isoflavones improves arterial function.
Hormone-associated Cancers
Breast Cancer
Breast cancer incidence in Asia, where average isoflavone intakes from soy foods range from 25-50 mg/day (34), is lower than breast cancer rates in the Western countries where average isoflavone intakes in non-Asian women are less than 2 mg/day (35, 36). However, many other hereditary and lifestyle factors could contribute to this difference. Epidemiological studies of dietary soy and breast cancer have reported conflicting results (see the article on Legumes). A few studies suggest that a higher soy intake during adolescence may lower risk of developing breast cancer later in life (37, 38). At present, there is little evidence that taking soy isoflavone supplements decreases risk of breast cancer. See the article on Legumes for more information about soy consumption and breast cancer risk.
Endometrial Cancer
Because the development of endometrial (uterine) cancer is related to prolonged exposure to unopposed estrogens (estrogen not counterbalanced with the hormone progesterone), it has been suggested that high intakes of phytoestrogens with anti-estrogenic activity could be protective against endometrial cancer (39). In support of this idea, three retrospective case-control studies found that women with endometrial cancer had lower intakes of soy isoflavones from foods compared to cancer-free control groups (39-41). However, supplementation of postmenopausal women with soy protein providing 120 mg/day of isoflavones for six months did not prevent endometrial hyperplasia induced by the administration of exogenous estradiol (42). Although limited evidence from case-control studies suggests an inverse relationship between consumption of soy foods and endometrial cancer, there is no evidence from intervention trials that taking soy isoflavone supplements decreases endometrial cancer risk.
Prostate Cancer
Mortality from prostate cancer is much higher in the U.S. than in Asian countries, such as Japan and China (43). However, epidemiological studies do not provide consistent evidence that high intakes of soy foods are associated with reduced prostate cancer risk. See the article on Legumes for more information about soy foods and prostate cancer risk. The results of cell culture and animal studies suggest a potential role for soy isoflavones in limiting the progression of prostate cancer (44). Although soy isoflavone supplementation for up to one year did not significantly decrease serum concentration of prostate specific antigen (PSA) in men without confirmed prostate cancer (45-47), soy isoflavone supplementation appeared to slow the rising serum PSA concentration associated with prostate tumor growth in two small studies of prostate cancer patients (48, 49). One small, short-term (60 years, found that neither supplemental soy protein (18 g/day) nor isoflavones (105 mg/day), alone or in combination, significantly affected BMD over a one-year period (75). To date, results of studies are conflicting, but a recent meta-analysis of nine randomized controlled trials (trial duration, one to 12 months) concluded that soy isoflavones, at doses of <90 mg/day, inhibit bone resorption and stimulate bone formation (76). Some authors have proposed that the effect of soy isoflavones on bone health may be dependent on whether or not the individual produces the isoflavones metabolite, equol (see Metabolism and Bioavailability above) (77-80). This could possibly explain disparate results among clinical trials. Thus, while there is some evidence that isoflavone-rich diets have bone-sparing effects, it is not known whether increasing soy isoflavone intake appreciably decreases the risk of osteoporosis or osteoporotic fracture.
Cognitive Decline
Scientific research on the effect of soy isoflavones on cognitive function is limited. An observational study that examined the relationship between soy intake and cognitive function found that Hawaiian men who reported consuming tofu at least twice weekly during midlife were more likely to have poor cognitive test scores 20-25 years later than those who reported consuming tofu less than twice a week (81). In an Indonesian study of elderly men and women, consumption of tofu was associated with worse memory, while consumption of tempe was associated with improved memory (82). In contrast, the results of several small clinical trials in postmenopausal women suggest that increasing soy isoflavone intake may result in modest improvements in performance on some cognitive tests for up to six months. Postmenopausal women given soy extracts, providing 60 mg/day of soy isoflavones for 6-12 weeks, performed better on cognitive tests of picture recall (short-term memory), learning rule reversals (mental flexibility), and a planning task compared to women given a placebo (83, 84). In a longer trial, postmenopausal women given supplements that provided 110 mg/day of soy isoflavones for six months performed better on a test of verbal fluency than women given placebos (85). In a cross-over trial lasting six months, women receiving 60 mg/day of soy isoflavones experienced significant improvements in cognitive performance and overall mood compared to when the women were given a placebo (86). However, in larger placebo-controlled trials, postmenopausal women receiving 80 mg/day of isoflavones for six months or 99 mg/day of isoflavones for one year did not affect performance on a battery of cognitive function tests, including tests for memory, attention, verbal fluency, motor control, and dementia (67, 87). A recent review of eight trials, seven of which were conducted in postmenopausal women, found half reported that soy isoflavone treatment was associated with improvements in cognitive function (88).
Disease Treatment
Menopausal Symptoms
Hot flushes (flashes) are the primary reason that women seek medical attention for menopausal symptoms (89). Concern over potential adverse effects of hormone replacement therapy (90, 91) has led to increased interest in the use of phytoestrogen supplements by women experiencing menopausal symptoms (92). The effects of increasing soy isoflavone intake on the frequency of hot flushes have been examined in a number of randomized controlled trials (93-95). To date, at least four reviews of such trials have been published. A review published in 2002 found that only one out of eight randomized controlled trials of soy foods reported a significant reduction in the frequency of hot flushes, while three out of five controlled trials of soy isoflavone extracts reported a significant reduction in hot flush frequency (96). In general, any reductions observed were modest (10-20%) compared to placebo. A 2004 systematic review that examined ten randomized controlled trials found that only four trials reported beneficial effects of soy preparations in the treatment of menopausal symptoms like hot flushes (95). More recently, another systematic review and meta-analysis of 12 randomized controlled trials found that soy isoflavone supplementation was associated with a small reduction in the number of hot flushes; this analysis found that women with a higher number of daily flushes experienced the greatest benefit from isoflavone therapy (94). One review that analyzed various trials according to the specific isoflavones contained in the supplements found that use of supplements containing primarily genistein reduced symptoms of hot flushes (97). Interestingly, a recent study found that only women who produced the isoflavone metabolite, equol (see Metabolism and Bioavailability above), which was detected in the urine, experienced improvements in menopausal symptoms like hot flushes following soy isoflavone supplementation (98). Breast cancer survivors in particular may experience more frequent and severe hot flushes related to therapies aimed at preventing breast cancer recurrence (99). However, none of the randomized controlled trials in breast cancer survivors found that soy isoflavone supplementation was significantly more effective than a placebo in decreasing the frequency or severity of hot flushes (100-103). To date, studies on the effect of soy isoflavone consumption on menopausal symptoms have reported mixed results.
Sources
Food Sources
Isoflavones are found in small amounts in a number of legumes, grains, and vegetables, but soybeans are by far the most concentrated source of isoflavones in the human diet (104, 105). Recent surveys suggest that average dietary isoflavone intakes in Japan, China, and other Asian countries range from 25-50 mg/day (34). Dietary isoflavone intakes are considerably lower in Western countries, where studies have found average isoflavone intakes to be as low as 2 mg/day (35, 36). Traditional Asian foods made from soybeans include tofu, tempeh, miso, and natto. Edamame refers to varieties of soybeans that are harvested and eaten in their green phase. Soy products that are gaining popularity in Western countries include soy-based meat substitutes, soy milk, soy cheese, and soy yogurt. The isoflavone content of a soy protein isolate depends on the method used to isolate it. Soy protein isolates prepared by an ethanol wash process generally lose most of their associated isoflavones, while those prepared by aqueous wash processes tend to retain them (106). Some foods that are rich in soy isoflavones are listed in the table below along with their isoflavone content (107). Because the isoflavone content of soy foods can vary considerably between brands and between different lots of the same brand (106), these values should be viewed only as a guide. Given the potential health implications of diets rich in soy isoflavones, accurate and consistent labeling of the soy isoflavone content of soy foods is needed. More information on the isoflavone content of foods is available from the USDA nutrient data laboratory.
(See link for Tables of Total Isoflavone, Daidzein and Genistein Aglycone Content of Selected Foods* (107); the table does not copy well)
*Isoflavone content of soy foods can vary considerably between brands and between different lots of the same brand (106); therefore, these values should be viewed only as a guide.
Supplements
Soy isoflavone extracts and supplements are available as dietary supplements without a prescription in the U.S. These products are not standardized, and the amounts of soy isoflavones they provide may vary considerably. Moreover, quality control may be an issue with some of these products (108). When isoflavone supplements available in the U.S. were tested for their isoflavone content by an independent laboratory, the isoflavone content in the product differed by more than 10% from the amount claimed on the label in approximately 50% of the products tested (109).
Infant Formulas
Soy-based infant formulas are made from soy protein isolate and contain significant amounts of soy isoflavones. In 1997, the total isoflavone content of soy-based infant formulas that were commercially available in the U.S. ranged from 32-47 mg/liter (~ 34 fluid ounces) (110).
Safety
Soy isoflavones have been consumed by humans as part of soy-based diets for many years without any evidence of adverse effects (105). The 75th percentile of dietary isoflavone intake has been reported to be as high as 65 mg/day in some Asian populations (111). Although diets rich in soy or soy-containing products appear safe and potentially beneficial, the long-term safety of very high supplemental doses of soy isoflavones is not yet known. One study in older men and women found that 100 mg/day of soy isoflavones for six months was well tolerated (112). Yet, long-term studies are needed to evaluate the safety of isoflavones.
Adverse Effects
Safety for Breast Cancer Survivors
The safety of high intakes of soy isoflavones and other phytoestrogens for breast cancer survivors is an area of considerable debate among scientists and clinicians (99, 113). The effects of high intakes of soy isoflavones on breast cancer recurrence and survival of breast cancer patients have not been well studied. The results of cell culture and animal studies are conflicting, but some have found that soy isoflavones can stimulate the growth of estrogen receptor positive (ER+) breast cancer cells (114, 115). High intakes of the soy isoflavone, genistein, interfered with the ability of tamoxifen to inhibit the growth of ER+ breast cancer cells implanted in mice (116), but it is not known if a similar effect would be seen in humans. A recent prospective study in 5,042 female breast cancer survivors in China, who were followed for a median of 3.9 years, found that consumption of isoflavone-rich soy foods was significantly associated with a 29% lower risk of death and a 32% lower risk of cancer recurrence (117). In this study, soy isoflavone consumption was associated with a nonsignificant, 21% reduction in risk of death and a significant, 23% reduction in risk of cancer recurrence (117). Very limited data from clinical trials suggest that increased consumption of soy isoflavones (38-45 mg/day) can have estrogenic effects in human breast tissue (118, 119). However, a study in women with biopsy-confirmed breast cancer found that supplementation with 200 mg/day of soy isoflavones did not increase tumor growth over the next 2-6 weeks before surgery when compared to a control group that did not take soy isoflavones (120). Given the available data, some experts think that women with a history of breast cancer, particularly ER+ breast cancer, should not increase their consumption of phytoestrogens, including soy isoflavones (99). However, other experts argue that there is not enough evidence to discourage breast cancer survivors from consuming soy foods in moderation (113), and the recent study mentioned above (117) indicates that moderate consumption of soy foods (11 g/day of soy protein) may even be beneficial to breast cancer survivors. Due to conflicting results, more research is needed to determine the safety of high soy isoflavone intake in breast cancer survivors.
Soy-based Infant Formulas
Infant formula made from soy protein isolate has been commercially available since the mid-1960s (121). As much as 25% of the infant formula sold in the U.S. is soy-based formula (122). Since infants fed soy-based formulas are exposed to relatively high levels of isoflavones, which they can absorb and metabolize, concern has been raised regarding potential long-term effects on growth, development, as well as reproductive and immune function (110, 123). The results of at least six clinical trials comparing infants fed soy-based formula with infants fed cow’s milk-based formula indicate that soy-based formula supports normal growth and development in the first year of life (124). A prospective study evaluating growth and development in children fed breast milk, cow's milk-based formula, or soy-based formula is currently under way at the Arkansas Children's Nutrition Center. After five years into the study, adverse effects of soy formula have not been observed, and no differences in growth and development among the various groups have been noted (125). In addition, one retrospective study of 811 men and women at 20-34 years of age found no differences in height, weight, time of puberty, general health, or pregnancy outcomes between those fed soy-based formula as infants and those fed cow’s milk-based formula, although women fed soy-based formula reported significantly greater use of asthma or allergy drugs than women fed cow’s milk formula (126). The American Academy of Pediatrics recently published a report that reviews the indications and contraindications for the use of soy-based formulas (122). At present, there is no convincing evidence that infants fed soy-based formula are at greater risk for adverse effects than infants fed cow’s milk-based formula. However, long-term studies on the growth and development of infants fed soy-based formulas are currently ongoing (127, 128).
Thyroid Function
In cell culture and animal studies, soy isoflavones have been found to inhibit the activity of thyroid peroxidase, an enzyme required for thyroid hormone synthesis (129, 130). However, high intakes of soy isoflavones do not appear to increase the risk of hypothyroidism as long as dietary iodine consumption is adequate (131). Since the addition of iodine to soy-based formulas in the 1960s, there have been no further reports of hypothyroidism in soy formula-fed infants (132). Several clinical trials, mostly in premenopausal and postmenopausal women with sufficient iodine intakes, have not found increased consumption of soy isoflavones to result in clinically significant changes in circulating thyroid hormone levels (133-137).
Pregnancy
To date, studies have not examined the effect of an isoflavone-rich diet on fetal development or pregnancy outcomes in humans, and the safety of isoflavone supplements during pregnancy has not been established.
Drug interactions
Because colonic bacteria play an important role in the metabolism of soy isoflavones, antibiotic therapy could decrease their biological activity (138). Some evidence from animal studies suggests that high intakes of soy isoflavones, particularly genistein, can interfere with the antitumor effects of tamoxifen (Nolvadex) (116). Until more is known about potential interactions in humans, those taking tamoxifen or other selective estrogen receptor modulators (SERMs) to treat or prevent breast cancer should avoid soy protein supplements or isoflavone extracts (see Safety for Breast Cancer Survivors). High intakes of soy protein may interfere with the efficacy of the anticoagulant medication warfarin. There is one case report of an individual on warfarin who developed subtherapeutic INR (prothrombin time) values upon consuming ~16 ounces of soy milk daily for four weeks (139). INR values returned to therapeutic levels two weeks after discontinuing soy milk. The amount of levothyroxine required for adequate thyroid hormone replacement has been found to increase in infants with congenital hypothyroidism fed soy formula (132, 140). Taking levothyroxine at the same time as a soy protein supplement also increased the levothyroxine dose required for adequate thyroid hormone replacement in an adult with hypothyroidism (141).
NormanS
Jim Rose says:
December 12, 2012 at 7:45 am
This post is a bit over-simplified due to space considerations. Sulforaphane comes from cruciferous vegetables. It is stored in the plant as glucoraphannin. It is released by being cleaved by the enzyme myrosinase. Bean sprouts contain a range of compounds apart from the isoflavones, such as coumestrol, depending upon the species of plant. Glucoraphannin is formed in the seed and is diluted as the plant grows. Mature broccoli heads contain one fiftieth of the concentration of sprouts.
PaulID says:
December 12, 2012 at 8:01 am
My opinion is that the best meal to have is Thai salad – mostly raw green vegetables, sprouts, chilli and some animal protein. Better than pho in that if you don’t get much exercise, you should try to back out carbohydrates.
I think this is an excellent post.
Leland H Hartwell, Tim Hunt and Sir Paul Nurse won the Nobel Prize in Physiology in 2001 for discovering key regulators of the cell cycle. This was a well deserved Nobel (unlike the Gore/IPCC/EU nonsense) as it greatly improves our understanding of life and cancer.
It’s commonly known that when a cell in the body duplicates itself the DNA separates into two parts. Cancer starts when cells begin to grow abnormally. Recently Dr Mark Petronczki and his team of reaearchers have made significant progress in discovering more about the division of cells and had a paper published in Nature this year.
http://www.nature.com/nature/journal/v492/n7428/full/nature11773.html
A belt forms around the middle of the cell and tightens to split the cell into two. The research team discovered that a protein is a key part of this process. Understanding cell division and why it goes wrong is essential for the development of treatments for cancer and finding ways to prevent cells dividing uncontrollably in the first place.
http://scienceblog.cancerresearchuk.org/wp-content/uploads/2012/06/LRI-image.jpg
Survival rates for cancer have greatly improved over the years but far more money needs to be put into research into the different cancers to make significant progress.
If the money wasted on CAGW had been spent on medical research doctors would probably by now have better treatments for all types of cancer and other diseases, as well as replacements for antibiotics which are increasingly becoming becoming less effective.
Concerning food (apologies if already mentioned) onions and garlic are thought to contain powerful anti-cancer properties:
“Like many vegetables, onions and garlic contain antioxidants that can block highly reactive free radicals from damaging cell DNA and starting the cancer process. Laboratory studies have shown that onion and garlic compounds can increase enzymes that deactivate carcinogens in the body, enhancing our ability to eliminate carcinogens before they do any damage.
“Furthermore, in the laboratory onion and garlic compounds slow the growth and stimulate the self-destruction of cancer cells that form. Given this protective potential, the challenge now is to identify amounts that will provide optimal effects.
“Some research hints garlic and onion’s protective compounds may work more effectively when combined with other compounds that work through different pathways. For example, animal studies show even greater reduction in cancer development from garlic and tomato than from either alone.
“The protective effects of onion and garlic seem related to wherever cancer cells grow in the body and not to any specific tissue, such as breast or thyroid. That leads many scientists to say that although research offers more proof of onion and garlic’s impact on some cancers than others, they are likely to offer protection against a wide range of cancers.”
http://preventcancer.aicr.org/site/News2?page=NewsArticle&id=11136&news_iv_ctrl=0&abbr=pr_hf_
Michael Palmer says:
December 12, 2012 at 8:20 am
Agreed. There is a host of other molecules from things like green tea, wasabi, ginger.
Matt Skaggs says:
December 12, 2012 at 8:29 am
There are four isoflavones: genistein, daidzein, formononotin and biochannin A. Your gut flora converts them to daughter metabolites. There is plenty of literature on anti-cancer effects of the daughter metabolites. Soy contains genistein and daidzein while chick peas have all four. The chick pea isoflavone profile is slightly better for osteoporosis than soy.
GoneWithTheWind says:
December 12, 2012 at 8:50 am
Yes, the Japanese are known for their high stomach cancer rate which apparently is due to high consumption of white rice. It is the lack of fiber that is the cause. Eating white rice is not much different to eating sugar granules.
Stuart says:
December 12, 2012 at 9:09 am
I consider BPH to be a neoplastic condition. As for treatments, things like saw palmetto are merely five alpha reductase inhibitors. The current main commercial treatment is a smooth muscle relaxant. These things treat the symptoms but not the underlying cause. The most effective treatment for BPH that I have come across is sulforaphane, taken as glucoraphanin in broccoli sprouts or seed extract. There are a few other plants that are also quite effective. A friend of mine uses the weed purslane, Portulaca oleraca. It has come up in my garden self-sown. These days I water it instead of pulling it out.
So that’s why I like mustard (turmeric) on my pastrami sandwich (black pepper crust)!
😉
Seriously, though, plants matter. Even the phosphorus compounds in rice bran change cancer profiles. Brown rice keeps the bran, so keeps the particular compound, and reduces bowl cancer rates.
The subject is obviously an important one, I’m glad that David wrote it, and that Anthony went forward with it.
That said — although the isoflavone hypothesis may have some merit — human bodies are very complex, and there are many more differences between Asian and North American diets, among them the amounts of food we eat here, the amounts of refined sugars, and as a consequence, the climbing rates of diabetes and the high rates of heart disease. I seem to recall a couple of decades ago that the hypothesis at the time for differences in cancer rates (and rates of other diseases) was that Americans eat more meat, especially steak, often (at the time) in the form of hamburgers. Which of the many dietary differences (other than soy consumption) might also explain the much higher rates of hormone-related cancers (e.g., breast and prostate cancers)? I don’t know, but I wouldn’t want to say that we only have to eat more soy, or more fermented soy, and the problem goes away.
@John Robertson:
This one?: http://chiefio.wordpress.com/2012/08/24/you-are-what-you-eat/
about how some food switch genes on and off…
I also found that a soak in a tub with Epsom’s Salts and some added Boraxo helped feel better too. Raises blood Mg levels via absorption and assures you have a bit of Boron as well (that is just being recognized as needed…)
On Japanese Cancers:
Don’t forget that they also consume high salt diets, and various things with other ‘odd’ chemical compositions (fermented et. al.) some of which correlate with intestinal cancers. Not to mention the very high smoking rate (and not just smoked fish…)
In general, if you eat whole fruits and grains and fish you are better off.
On Vit. C:
The Eskimo tradition includes a very careful division of, IIRC, the adrenal cortex. That is high in Vit. C levels.
It’s not just a carbohydrate thing. It’s also knowing your food source very intimately and acting wisely.
BTW, avoid Bear Liver unless you want to die from Vitamin D overdose and ALWAYS cook bear like pig. It has tricinosis in it too…
@Oldseadog:
One of the interesting things I learned (the slightly hard way…) is that BOTH acetaminophen and ibuprofen (Tylenol and Advil) can “blow out your liver” if consumed with a bit of alcohol. I knew about Tylenol, but was washing down Advil with some wine when the wife noticed my eyes a bit yellow the next day… (Good things liver regenerates…)
Along the way, found out that Asprin doesn’t have those problems BUT also is specifically protective against the metabolic cascade that results in liver damage. And not just from the NSAIDS, but also from Alcohol…
So all these years of folks saying to save your liver by stopping the drinking could more effectively have been dealt with by “Take an aspirin for your hangover before you start drinking”… Which just makes me wonder what the level of French aspirin consumption might be…
http://chiefio.wordpress.com/2012/05/27/apirin-good-advil-ibuprofen-tylenol-acetaminophen-bad/
at least when mixed with wine…
@Steve From Rockwood:
Cholesterol is a product of an animal metabolism, not a disease agent.
The whole ‘saturated fats bad / unsaturated oils good’ is based in part on bad studies. Trans-Fats were treated as ‘saturated fat’ since both were solids at room temperature and they figured it wouldn’t matter. So the early studies did not distinguish between lard and hydrogenated vegetable shortening with trans fats.
In a more recent study straight tri-stearate ( ‘perfect’ cow fat if you will) was tested and did exactly NOTHING to cholesterol levels.
Trans-fats have been tested and found quite evil.
A few years back we started religiously avoiding any food with the word “Hydrogenated” on the label (since our FDA lets trans-fat be in food labeled as zero trans-fat as long as it’s less than 1/2 gram / serving … when one gram is enough to bolix up your works and one cookie can be one serving…) Since then, I eat all I want, but end up not eating all that much as the fat we do eat is metabolized for energy, not stored due to a trans-fat gummed up set of enzymes.
Basically, where before a box of “Oreos” could be eaten and still ‘feel hungry’ due to plugged up fat metabolism, I now can have one piece of toast and real butter and not be hungry for hours…
FWIW, my Dad ‘blew off’ the saturated fat idea and we were raised on bacon and butter. When he died (lung cancer, 40 years of unfiltered Camels) at autopsy they said he had no circulatory problems… HIS Dad died at about 90 something. Lived on a farm eating Amish style cooking (Mom was Amish). For those who don’t know, it’s essentially all fat all the time. There are dishes that are things like “Pile of toast soaked in butter with melted cheese poured over it eggs on top and bacon in layers”… If out of butter, you can use bacon grease instead… No, that’s not an overstatement. You raise pigs, eggs, and dairy; so most of what you eat are pigs, eggs, and dairy… I remember a “mayonnaise sandwich” and then there were those fried chicken with potatoes drenched in butter AND pan gravy heavy on the chicken fat… With bread with a thick layer of butter on it…
In short, if it can be buttered, gravied, or have bacon and cheese added, you do. If not, it’s a desert and gets mayonnaise or cream in it.. 😉
IMHO the whole ‘cholesterol and fat’ diet thing is another scientific cockup. It’s the transfat.
@Duster:
Also note that corn is a grain, so has more omega-6 fatty acids in the oils. Grasses (the leaves part) have more omega-3. BOTH go through the same enzyme to make some prostaglandins that have an effect on inflammation rates. (IIRC it is a protaglandin..)
So the 3 vs 6 ratio determines those hormone ratios via competition. That we’ve skewed by from about 1:1 over to about 20:1… toward the ‘more inflammation’ side.
Short form: AVOID Omega-6 oils (mostly seed oils – soy, corn) and ADD Omega-3 oils (flax, some specialty oils) or REPLACE with mono-unsaturates and saturateds ( Olive, safflower, coconut, palm, butter ).
An old Indian (India) proverb is that “Ghee is the key to longevity”. It’s clarified butter.
BTW, one of the ‘hotspots’ of longevity is in N. Italy. They eat a LOT of sheep’s milk cheeses and grass fed lamb. The short chain fatty acids matter… (Cocoa butter is in the same class)
So if you want to live a long happy healthy life, eat the way folks traditionally did. That includes things like Sheep’s milk cheeses (Pecorino Romano) and wine and butter and whole wheat pasta with olive oil and garlic … and chocolate … not just a Japanese diet..
And avoid the ‘hydrogenated’ anything…
Diet and neutraceuticals raise complex questions that will not be resolved for a long time. My first exposure to the public health domain was a year in Nha Trang, as an Army health inspector during the war. Things have improved in the last half century, but one still cannot be confident about any statistic from a ‘third world’ regime.
On nutrition in general as preventive medicine, both extreme opinions are wrong — there are strong critiques for both the mainstream and alternative medical cultures. It would take a long time to go into that aspect. The short version is: The mainstream has conflicts of interest, regulatory capture, little or no support for substances that cannot be protected by a composition-of-matter patent, and a culture that is generally uneconomic. The alternative types are not doing appropriate research and sometimes lack educational qualification.
There is a lot of free information, however. For example, on Medline, enter
altern med rev [jour]
and get 507 hits, of which 478 are free pdf files that you can download. If the search term is neutraceuticals and the limitation or filter is free full text, there are still more than 10,000 hits. If you google the word ‘pubmed’ the first hit should have a link to the Medline search page.
There are also controversial or dissident doctors (regular MDs) who defend neutraceuticals. Two who are working today are Julian Whitaker and Jonathan V. Wright, see the wiki articles.
The classical dispute is ascorbate in high or massive IV doses. Antiviral effects were claimed in the mid-XXth century by Fred Klenner, MD, and a google search could find some of his early papers. They are too early for Medline, which also refuses to index papers from the journal of orthomolecular medicine. That can also be found through google, however. The late R. F. Cathcart, MD (d. 2007), still has a website
http://orthomed.com/
which has lots of links — and anger about the mainstream exclusion. Note the Belfield-Stone paper on animal therapy.
Dr. Thomas E. Levy has recently published a book on the extreme-dose ascorbate approach; the customer reviews on Amazon are mostly positive.
http://www.amazon.com/Curing-Incurable-Vitamin-Infectious-Diseases/dp/1401069630/ref=cm_cr_pr_product_top
There are other situations where a disease is said to be stabilized or a chronic inflammation mitigated by a neutraceutical. For example, one might try to stabilize Alzheimer’s Disease with a combination of alpha-lipoic acid and low-dose lithium, according to information that one can find on Medline or the Wright and Whitaker dissident websites. At the mainstream level, there are now Phase III trials of IV immunoglobulin, (IVIg, gamma globulin therapy), and there is preliminary evidence of efficacy. This approach would be very expensive — but, then, that is the idea.
Finally, the real disaster on a worldwide scale is the developmental and general health effects of micronutrient deficiency. The Copenhagen Consensus organized by the climate semi-skeptic, Lomborg, concluded that the best bang-for-the-buck in world improvement would be micronutrient supplements:
https://en.wikipedia.org/wiki/Copenhagen_Consensus
About two billion people out of the ~7 billion world population are brain damaged by micronutrient deficiency, my reading suggests. See also the Flynn Effect in the wikipedia and apply Occam’s razor to the fancier explanations.
Logan
David Archibald says:
December 12, 2012 at 3:06 pm
My opinion is that the best meal to have is Thai salad – mostly raw green vegetables, sprouts, chilli and some animal protein. Better than pho in that if you don’t get much exercise, you should try to back out carbohydrates.
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Pho?
Mostly raw green vegetables and sprouts will do you little good. Humans can’t digest plant cell walls, and our mastication is limited, so little nutrition will be derived from uncooked vegetables.
David Archibald says:
December 12, 2012 at 3:19 pm
Matt Skaggs says:
December 12, 2012 at 8:29 am
There are four isoflavones: genistein, daidzein, formononotin and biochannin A. Your gut flora converts them to daughter metabolites. There is plenty of literature on anti-cancer effects of the daughter metabolites. Soy contains genistein and daidzein while chick peas have all four. The chick pea isoflavone profile is slightly better for osteoporosis than soy.
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I am very happy to hear that. A favorite dish is TURKISH MOUSSAKA which contains chick peas.
Cinnamon BTW is thought to improves blood glucose, triglyceride, total cholesterol, HDL cholesterol, and LDL cholesterol levels in people with type 2 diabetes.
I found it gets rid of the after meal crash common in hypoglycemia. It seems to “stabilize” blood sugar levels and also aids in weight loss when a low carb. diet quit working.
This is an interesting resource in what is in various veggies: http://www.phenol-explorer.eu/reports/40#onion-family vegetables
One of the main reasons human are such a successful species is that they can survive and reproduce on just about anything which is edible, and any combination of them.
Discussions on nutrition are always fun. Soy is bad! No, says someone else, it is the elixir of life! Humbug, says a third person, it is OK but only if it is fermented. Sheesh.
So-called ‘nutritional science’ is about on a level with phrenology. It is often based on ideology (going back to some alleged golden era is a popular theme, although the eras identified as golden vary widely). Personal anecdotes, wildly contradictory from person to person, abound.
It may be that David Archibald, or E.M. Smith, or one of the millions of other diet enthusiasts who spruik their views, are on to something. But there are uncountable competing theories out there, and none of them passes the tests of scientific rigour that we require of – oh, I don’t know – climate science. Anecdotes, invalid epidemiological studies, inter-country comparisons that are not statistically valid, fads and fashions – we have those in abundance. Facts are thin on the ground, and the ones that most people do accept are at a very simple level of understanding – like that consuming Vitamin C prevents scurvy. Why this is so, how much V.C. is needed, and why people who eat little or no food containing it can survive are still subject to debate.
All the guff about ‘superfoods’ in the popular media is typical of the ignorant and superstitious level on which we still operate when it comes to food. It is no better than (arguably worse than) modern witchcraft. That goes for ‘bad’ things like cholesterol and oxidants as well. They are today’s evil spirits, but don’t stand up to a lot of objective scrutiny.
Food evangelists are tedious bores when one is dining with them, and often at other times as well. Eat, drink and be merry, folks. Your friends and relatives will like you more, and you will be happier as well.
E.M.Smith says:
December 12, 2012 at 4:32 pm
>>>>>>>>>>>>>>>>>>>>>>>>>>>
I agree whole heartedly. (So does my more recent blood work)
Animal fat also turns off hunger so you just do not eat as much. I think the rotten dietary habits are the main problem for Americans. Since WWII we have been eating more and more junk food. They even have candy and coke machines in the schools now and then want to put kids on Ritalin because they are bouncing off the walls.
Glad to hear about the lamb but I do not think my ram lambs will.