US study links reduced death rates to higher intake of foods rich in flavonoids (fruits, vegetables, tea, soy, chocolate, herbs); Results lend credence to controversial breast-health claims for soy
by Craig Weatherby
Worldwide, more than one million women are diagnosed with breast cancer every year, with the highest rates occurring in the US and the Netherlands.
The National Cancer Institute estimates that 13 percent of American women will develop breast cancer during their lives, with most being diagnosed after menopause.
Evidence from research in animals and human cancer cells shows that high concentrations of flavonoids—common dietary antioxidants abundant in most plant foods—curb the growth of many cancers.
However, epidemiological studies have generally failed to find that diets high in flavonoids offer people significant protection from cancer. The exceptions have been some results suggesting that flavonoids may reduce the risk of lung and breast cancer.
Flavonoids are abundant in fruits, vegetables, herbs, spices, tea, soy, chocolate, nuts, red wine and many medicinal herbs, and are divided into smaller categories such as flavonols, flavones, isoflavones, anthocyanidins, and flavan-3-ols.
Positive survival findings echo prevention findings from prior stage
As we reported last March, a team based at the University of North Carolina published positive conclusions from a breast cancer prevention study among women living on New York’s Long Island:
“…intake of flavonols, flavones, flavan-3-ols, and lignans is associated with reduced risk of… postmenopausal breast cancer.”
All flavonoids were found protective against breast tumors, with some kinds—flavones (see source list below)—reducing risk by as much as 39 percent
Lignans, which were also found protective, are fiber-like, weakly estrogenic compounds, found in a variety of seeds, whole grains, bran, berries, and vegetables. Flaxseed is the richest source, by far.
And the UNC team found that women enjoyed protective effects at flavonoid-intake levels achievable by eating the five daily servings of fruits and/or vegetables recommended in US dietary guidelines (Fink BN et al March, 2007).
(For more on this research and related prevention studies see “Food-Borne Antioxidants May Curb Breast Cancer.”)
But the effects of flavonoids on breast cancer survival rates had not been studied until the same UNC team compared participants’ flavonoid intake with their 5-year survival rates.
Second stage of Long Island study finds flavonoids enhance survival
Researchers from UNC analyzed medical and death records from participants in their previous cancer-prevention study, which involved 1,210 breast cancer patients aged 25 to 98 (Fink BN et al November, 2007).
The study encompassed the five to six years that intervened between the women’s cancer diagnoses and the end of the study in 2002.
The UNC team found that the Long Island women whose diets were richest in flavonoids were 37 to 48 percent more likely to have survived, compared to women with the lowest flavonoid intakes.
And the risk reduction was greater—from 41 to 56 percent depending on the flavonoid in question—among postmenopausal women with the highest flavonoid intakes.
Compared to the women with the lowest self-reported intakes of plant foods containing significant amounts of three kinds of flavonoids, the women reporting the highest intakes of these foods enjoyed substantial risk reductions:
- Isoflavones reduced risk of death by 48 percent
- Flavones reduced risk of death by 37 percent
- Anthocyanidins reduced risk of death by 36 percent
Where are these protective flavonoids found?
- Isoflavones are most abundant in soy beans and soy foods.
- Flavones are most abundant in parsley, celery, chili peppers, basil, and mint but also occur in beets, bell peppers, Brussels sprouts, cabbage, cauliflower, lettuces, spinach, rosemary, and thyme.
- Anthocyanidins are most abundant in blue-red-purple foods like berries, grapes, grape juice, red wine, red cabbage, and eggplant.
Americans get most of their flavonoids from tea, citrus fruits and juices, wine, apples, chocolate, and grapes.
The UNC team also found death-risk reductions among the women with the highest intake of flavan-3-ols: a type of flavonoid that Americans get primarily from tea, chocolate, grapes, and some berries and vegetables. (The potent antioxidant supplements known as pycnogenol or OPC contain mixtures of flavan-3-ols from grape seed and skin or pine bark.)
The flavonoid-density of Americans’ diets increases with age and income—with the exception of children aged two to five, most of who eat lots of fruit—and is higher in women, Caucasians, and vitamin supplement users.
Flavonoid intake is lowest in adults whose jobs involve physical labor, which fits with the correlation between higher income and higher flavonoid intake (Chun OK et al 2007; Gu L et al 2004).
The soy conundrum: Does soy raise or reduce breast cancer risk?
The results from Long Island suggest that the isoflavones in soy foods enhance survival among breast cancer patients.
Isoflavones act as “phytoestrogens”, which means that they bind to the same cell receptors as estrogen. This has led to the hypothesis that soy foods could prevent the cell proliferation that leads to breast cancer. This is how tamoxifen helps prevent re-occurrence of breast cancer.
However, the few human studies conducted to date do not support this hypothesis. And the results of animal tests suggest that one soy isoflavone (genistein) may interfere with the ability of tamoxifen to curb the growth of breast cancer cells.
Instead, research to date suggests that exposure to isoflavones in childhood or early adolescence may be protective. It appears that the cancer-preventive effects of soy foods only manifest if the developing mammary gland was exposed to dietary isoflavones during childhood and puberty.
This hypothesis would explain why Japanese women—who eat tofu from early childhood and throughout life, in modest amounts—enjoy much lower rates of breast cancer compared to western women.
It's been feared that when women only begin to consume isoflavone-rich soy foods or supplement powders later in life – especially at the time of menopause – the phytoestrogenic isoflavones in soy could actually stimulate the proliferation of endometrial and mammary gland tissues, with unknown and unpredictable risks.
So the finding that isoflavones obtained from soy foods enhanced survival rates in mature breast cancer patients offers some hope for women who only began consuming tofu, tempeh, or soy milk after their adolescence.
Andrew Weil, MD and many other observers believe that while whole soy foods may be beneficial, the very high concentrations of isoflavones in soy protein powders could be risky.
And whole soy foods are high in omega-6 fatty acids, which promote tumor growth in animals.
So, despite the positive association between high intake of soy flavonoids and enhanced breast cancer survival, consuming lots of soy foods or soy protein supplements may not be a terribly wise prevention tactic... unless the soy habit starts early in life and is practiced in moderation.
- Arts IC, Hollman PC, Bueno De Mesquita HB, Feskens EJ, Kromhout D. Dietary catechins and epithelial cancer incidence: the Zutphen elderly study. Int J Cancer. 2001;92(2):298-302.
- Arts IC, Jacobs DR, Jr., Gross M, Harnack LJ, Folsom AR. Dietary catechins and cancer incidence among postmenopausal women: the Iowa Women's Health Study (United States). Cancer Causes Control. 2002;13(4):373-382.
- Chun OK, Chung SJ, Song WO. Estimated dietary flavonoid intake and major food sources of U.S. adults. J Nutr. 2007 May;137(5):1244-52.
- De Stefani E, Ronco A, Mendilaharsu M, Deneo-Pellegrini H. Diet and risk of cancer of the upper aerodigestive tract--II. Nutrients. Oral Oncol. 1999;35(1):22-26. -Closas R, Gonzalez CA, Agudo A, Riboli E. Intake of specific carotenoids and flavonoids and the risk of gastric cancer in Spain. Cancer Causes Control. 1999;10(1):71-75.
- Duffy C, Perez K, Partridge A. Implications of phytoestrogen intake for breast cancer. CA Cancer J Clin. 2007 Sep-Oct;57(5):260-77. Review.
- Fink BN, Steck SE, Wolff MS, Britton JA, Kabat GC, Gaudet MM, Abrahamson PE, Bell P, Schroeder JC, Teitelbaum SL, Neugut AI, Gammon MD. Dietary Flavonoid Intake and Breast Cancer Survival among Women on Long Island. Cancer Epidemiol Biomarkers Prev. 2007 Nov;16(11):2285-92.
- Fink BN, Steck SE, Wolff MS, Britton JA, Kabat GC, Schroeder JC, Teitelbaum SL, Neugut AI, Gammon MD. Dietary flavonoid intake and breast cancer risk among women on Long Island. Am J Epidemiol. 2007 Mar 1;165(5):514-23. Epub 2006 Dec 11.
- Garcia R, Gonzalez CA, Agudo A, Riboli E. High intake of specific carotenoids and flavonoids does not reduce the risk of bladder cancer. Nutr Cancer. 1999;35(2):212-214.
- Garcia-Closas R, Agudo A, Gonzalez CA, Riboli E. Intake of specific carotenoids and flavonoids and the risk of lung cancer in women in Barcelona, Spain. Nutr Cancer. 1998;32(3):154-158.
- Goldbohm RA, Van den Brandt PA, Hertog MG, Brants HA, Van Poppel G. Flavonoid intake and risk of cancer: a prospective cohort study. Am J Epidemiol. 1995;41:s61.
- Gu L, Kelm MA, Hammerstone JF, Beecher G, Holden J, Haytowitz D, Gebhardt S, Prior RL. Concentrations of proanthocyanidins in common foods and estimations of normal consumption. J Nutr. 2004 Mar;134(3):613-7.
- Hertog MG, Feskens EJ, Hollman PC, Katan MB, Kromhout D. Dietary flavonoids and cancer risk in the Zutphen Elderly Study. Nutr Cancer. 1994;22(2):175-184. (PubMed)
- Higdon JV, Frei B. Tea catechins and polyphenols: health effects, metabolism, and antioxidant functions. Crit Rev Food Sci Nutr. 2003;43(1):89-143.
- Lagiou P, Samoli E, Lagiou A, et al. Flavonoids, vitamin C and adenocarcinoma of the stomach. Cancer Causes Control. 2004;15(1):67-72.
- Peterson J, Lagiou P, Samoli E, et al. Flavonoid intake and breast cancer risk: a case--control study in Greece. Br J Cancer. 2003;89(7):1255-1259.
- RA, Hertog MG, Brants HA, van Poppel G, van den Brandt PA. Consumption of black tea and cancer risk: a prospective cohort study. J Natl Cancer Inst. 1996;88(2):93-100.
- Wuttke W, Jarry H, Seidlová-Wuttke D. Isoflavones--safe food additives or dangerous drugs? Ageing Res Rev. 2007 Aug;6(2):150-88. Epub 2007 May 16. Review.