macrocarpon) Jamieson Laboratories, Toronto, Ontario, Canada. Cranberry juice .... recovery, and coefficient of variatio
NUTRITION AND CANCER, 59(2), 176–184 C 2007, Lawrence Erlbaum Associates, Inc. Copyright
Dietary Phytoestrogens, Including Isoflavones, Lignans, and Coumestrol, in Nonvitamin, Nonmineral Supplements Commonly Consumed by Women in Canada Lilian U. Thompson, Beatrice A. Boucher, Michelle Cotterchio, Nancy Kreiger, and Zhen Liu
Abstract: Twenty-one nonvitamin, nonmineral dietary supplements commonly consumed by women in Canada were analyzed for isoflavones (formononetin, daidzein, genistein, glycitein), lignans (pinoresinol, lariciresinol, secoisolariciresinol, matairesinol), and coumestrol to complement our previously published food phytoestrogen database. Supplements containing soy or red clover had the highest concentrations of total isoflavones (728.2–35,417.0 ug/g) and total phytoestrogens (1030.1–35,517.7 ug/g) followed by licorice and licorice-containing supplements (41.3– 363.3 ug/g isoflavones; 56.5–370.0 ug/g total phytoestrogens). Other supplements had considerably less isoflavones (≤19.0 ug/g) and total phytoestrogens (≤44.2 ug/g). Lignans were present in all (≤298.9 ug/g), whereas coumestrol was either not present or present in only small amounts (≤3.0 ug/g). Supplements differed in phytoestrogen profiles. The daily intake of isoflavones and lignans from some supplements may greatly exceed those from several servings of soy or vegetables. Hence, the intake of supplements should be taken into consideration in clinical or epidemiological studies for more accurate estimation of phytoestrogen intakes.
Dietary supplements may provide doses of bioactive ingredients that surpass what might be obtained from foods, suggesting the importance of their inclusion in studies of disease risk (11,12). Additionally, if not adequately regulated, supplement labels may also not reflect the actual contents or the multiplicity of bioactive constituents (4,12–14). Phytoestrogens, including isoflavones, lignans, and coumestans, are a group of bioactive compounds of particular importance to women’s health because they exhibit both estrogenic and antiestrogenic effects. Many herbal supplements have been shown to possess estrogenic or antiestrogenic activities (8,11,15,16), but except for those containing soy, red clover, licorice, or black cohosh (12,14,17–19), their phytoestrogen contents have never been elucidated. The objective of this study was to determine the phytoestrogen content of nonvitamin, nonmineral dietary supplements that are commonly consumed by women primarily for hormonal effects or conditions such as menopause. The results will complement our recently published database on phytoestrogens in foods (20) and will help in the more accurate estimation of total phytoestrogen intake (from foods and supplements) in clinical and epidemiological studies and in examining risk association with hormone-related diseases such as breast cancer.
Introduction The use of dietary supplements such as herbal and other nonvitamin, nonmineral supplements is widespread, with up to one-third of the general population reporting current use (1–3). Although intake may vary with characteristics such as age, education, ethnicity, and smoking, women report consistently high use (1–4) as do those affected by diseases such as cancer (5). Taken to improve well-being and prevent or alleviate symptoms of disease, nonvitamin, nonmineral dietary supplements are perceived as alternatives to conventional medicine with fewer side effects, although their actual risks and benefits have been scarcely evaluated (6–11).
Methods Twenty-one nonvitamin, nonmineral dietary supplements (Table 1) were selected for phytoestrogen analysis based on reports of estrogenic activity, use for premenstrual or menopausal symptoms, or presence of known phytoestrogens in food (e.g., garlic, cranberry) or supplementary forms (15–17,21–23). Analyzed items and brands were those most frequently reported in our 2003 survey of nonvitamin, nonmineral supplement use in a random sample of 478 women (24). Seventeen supplements were classified as “single” (SS)
L. U. Thompson, N. Kreiger, and Zhen Liu are affiliated with the Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada M5S 3E2. M. Cotterchio and N. Kreiger are affiliated with the Department of Public Health Sciences, University of Toronto, Toronto, Ontario, Canada M5T 3M7. B. A. Boucher, M. Cotterchio, and N. Kreiger are affiliated with Cancer Care Ontario, Toronto, Ontario, Canada M5G 2L7.
Table 1. Supplement Information on Product Labelsa Supplement (Product Name) Manufacturer, Location Single supplements Bioflavonoids (Citrus Bioflavonoids Plus Hesperidin 650 mg) Natural Factors, Burnaby, British Columbia, Canada Black cohosh (Black Cohosh 100 mg, DIN 02238886) Swiss Herbal Remedies Ltd., Richmond Hill, Ontario, Canada Blue cohosh (Blue Cohosh Tincture) Shawla Herbs, Roseneath, Ontario, Canada Chasteberry (Chasteberry Vitex agnus castus) Sundown Herbals, Boca Raton, FL Chasteberry (Vitex Fruit 400 mg) Nature’s Way Products Inc., Springville, UT Cranberry (Maximum Concentrate Cranberry Juice 500 mg, Vaccinium macrocarpon) Jamieson Laboratories, Toronto, Ontario, Canada Dong quai (Dong Quai, Angelica sinesis, Pure Root Powder 500 mg) Swiss Herbal Remedies Ltd., Richmond Hill, Ontario, Canada Evening primrose oilc (Evening Primrose Oil 500 mg, with Rosemary and Thyme, DIN 02153793) Jamieson Laboratories, Toronto, Ontario, Canada
Garlic (aged, odorless)a (KyolicR Aged Garlic ExtractTM Odorless Formula 104) Wakunaga of America Co Ltd., Jamieson Laboratories, Toronto, Ontario, Canada Garlic (odorless)c (Odorless Garlic 500 mg) Jamieson Laboratories, Toronto, Ontario, Canada Hops (Hops Flowers 310 mg) Nature’s Way Products Inc., Springville, UT Isoflavones (Estrovone Isoflavones 75 mg) Swiss Herbal Remedies Ltd., Richmond Hill, Ontario, Canada
Lecithinc (Unbleached Lecithin 1,200 mg) Swiss Herbal Remedies Ltd., Richmond Hill, Ontario, Canada
Licorice (Licorice Root 545 mg) Nature’s Way Products of Canada Ltd., Newmarket, Ontario, Canada Red clover (MenoflavonTM Formula) Jamieson Laboratories, Toronto, Ontario, Canada Red clover (PromensilTM Red Clover Tablets) Novogen, Ancaster, Ontario, Canada
Wild yam (Wild Yam Root 520 mg) Nature’s Way Products of Canada Ltd., Newmarket, Ontario, Canada Multiple supplements Estro LogicTMa , Quest, Jamieson Laboratories, Toronto, Ontario, Canada
Vol. 59, No. 2
Ingredients Per Unit (Capsule, Tablet, Drop)b
Bioflavonoid complex (lemon, orange, grapefruit) 500 mg Hesperidin 150 mg Other ingredients: magnesium stearate Black cohosh root powder (Cimicifuga racemosa) 80 mg Standardized black cohosh root extract (2.5% triterpenoids) 20 mg Other ingredients: rice bran flour Fresh wildcrafted blue cohosh root (caulophyllum thalictroides) macerated in 50% grain alcohol Chasteberry (fruit) 400 mg Vitex agnus castus (fruit) 400 mg Other ingredients: millet, magnesium stearate Cranberry juice concentrate (1:34) 500 mg (equivalent to 8 oz cranberry juice or 10 g fresh cranberries) Other ingredients: cellulose, calcium silicate, magnesium stearate Dong quai (powdered root) angelica sinensis 500 mg Other ingredients: magnesium stearate Evening primrose oil (standardized to 10% (50 mg) gamma linolenic acid) 500 mg Vitamin E natural d-α-tocopheryl acetate (in antioxidant base of rosemary and thyme) 13.6 IU Other/capsule ingredients: not identified Aged garlic extract 300 mg Lecithin 190 mg Other ingredients: magnesium stearate (vegetable source) Aged garlic powder 5 mg (equivalent to fresh garlic 500 mg) Other/capsule ingredients: soybean oil, gelatin, vegetable oil, glycerin, yellow beeswax, lecithin Hops (flower) 310 mg Other ingredients: millet, magnesium stearate NovasoyTM soy extract [standardized to contain 40% isoflavones (10 mg)] 25 mg Red clover extract [standardized to contain 8% isoflavones (4mg)] 50 mg Other ingredients: cellulose, di calcium phosphate, magnesium stearate Lucas MeyerTM premium soy lecithin (Leci-PLCTM ) 1200 mg (consisting of phosphatidylcholine, phosphatidylinositol, phosphatidylethanolamine, phosphatidylserine) Other/capsule ingredients: gelatin, glycerin, purified water Pure licorice root powder (glycyrrhiza glabra) 545 mg Red clover extract 362 mg (containing MenoflavonTM botanical isoflavone complex 40 mg) Other ingredients: water, cellulose, natural colors, lactose Isoflavones (as red clover extract) 40 mg Other ingredients: dicalcium phosphate, microcrystalline cellulose, hypromellose, soy polysaccharide, magnesium stearate, silica, mixed tocopherols, acacia gum, iron oxide Wild yam root (Dioscorea villosa) 520 mg Other ingredient : millet
Black cohosh extract (Cimicifuga racemosa) (standardized to 2.5% triterpene glycosides) 100 mg Soybean isoflavones (standardized to 40% isoflavones) 50 mg Wild yam extract (Dioscorea villosa) (standardized to 6% total saponins) 33.5 mg Sage extract (Salvia officinalis) 25 mg Chaste tree extract (Vitex agnus-castus) 12.5 mg Vervain extract (Verbena officinalis) 12.5 mg Astragalus extract (Astragalus membranaceus) 12.5 mg Motherwort extract (Leonurus cardiaca) 12.5 mg Other ingredients: microcrystalline cellulose, silicon dioxide, magnesium stearate (vegetable source)
177
Table 1. (Continued) Menopause Formula, Natural Factors, Burnaby, British Columbia, Canada
Natural HRTTM , Swiss Herbal Remedies Ltd., Richmond Hill, Ontario, Canada
PMS Formula, Life Brand, Shoppers Drug Mart, Toronto, Ontario, Canada
Black cohosh 6:1 extract (Cimicifuga racemosa) (2.5% triterpene glycosides) 40 mg Vitex (chasteberry) extract (Vitex agnus-castus) (0.6% aucubine) 80 mg Licorice root extract 4:1 (Glycyrrhiza glabra) (12% glycyrrhizin) 75 mg Wild yam 10:1 extract (Dioscorea) (10% diosgenin) 75 mg Hops 5:1 extract (Humulus lupulus) (2% essential oil compound) 25 mg Dong quai 12:1 extract (1% ligustilide) 100 mg (herbal equivalent 1200 mg) Chaste tree berry extract (0.5% agnuside) 100 mg (herbal equivalent 100 mg) Black cohosh 15:1 extract (2.5% triterpenoids) 20 mg (herbal equivalent 300 mg) Wild yam root 2:1 extract (5% diosgenin) 50 mg (herbal equivalent 100 mg) Red clover extract (8% isoflavones) 100 mg (herbal equivalent 100 mg) Burdock root 4:1 extract 50 mg (herbal equivalent 200 mg) Other ingredients: magnesium stearate Chaste tree berry (0.5% agnuside) 92 mg Burdock root 69 mg Black haw 69 mg Alfalfa 69 mg Red clover (8% isoflavones) 62.5 mg Ginko biloba (24% ginko-flavone glycosides, 6% terpene lactones) 46 mg Black cohosh (from 4.5 mg of 12:1 standardized extract with 2.5% triterpene glycosides) 54 mg Other ingredients: maltodextrin, magnesium stearate, silicon dioxide
a: All details are from label except missing manufacturer location, which was obtained from distributor (Purity Life, Acton, Ontario, Canada). b: Ingredients exclude capsule shell unless indicated. c: Analysis of oily supplements included capsule contents and shell.
because they contain primarily 1 bioactive ingredient and are labeled as such; 4 supplements were classified as “multiple” (MS) because they contain several bioactive ingredients and are bought by consumers as brand-name items. MS are marketed for women’s health or hormonal effects and contain at least 1 of the bioactive ingredients in SS. One bottle of each supplement was purchased in 2003 from major health food stores or pharmacies in Toronto, Ontario, Canada and stored at −20◦ C. Different brands of 3 SS (chasteberry, garlic, red clover) were included to investigate variation in supplement composition. Each bottle provided 30 to 180 capsules or tablets except for blue cohosh, which was in tincture form (50 ml). Each supplement was analyzed before the expiration date stated on the label. Several tablets, capsules, and 15-drop aliquots were randomly taken from each container and weighed individually to estimate the mean weight. Contents of capsules were emptied and weighed except for oily supplements whose contents could not be separated from capsule shells. Tablets were finely ground in a small coffee grinder prior to analysis. Homogenized samples were analyzed in duplicate for isoflavones (formononetin, daidzein, genistein, glycitein), lignans (matairesinol, lariciresinol, pinoresinol, secoisolariciresinol), and coumestrol by gas chromatography-mass spectrometry (GC-MS) methods. The analytical method used has previously been described in detail (20). Briefly, the lignan analysis involved extraction of duplicate samples (0.25–2.00 g) twice with 5 to 25 ml 70% methanol, alkaline hydrolysis of the extract, passing 178
through a C18 solid-phase extraction column (SPE column; Octadecyl C18/14%, 200 mg/3 ml; Applied Separations, Allentown, PA), hydrolysis with β-glucuronidase (Helix Pomatia; Sigma Aldrich, St. Louis, MO) and another C18 SPE column. An internal standard (5α-androstane-3β,17βdiol; Steraloids Inc, Wilton, NH) was added to the column eluent, and the sample was then derivatized with Tri-Sil Reagent (Pierce Co., Rockford, IL) before injection to the GC-MS (Agilent 6890 series GC system interfaced with an Agilent 5973 network mass selective detector; Agilent Technologies, Wilmington, DE). The individual phytoestrogens were quantified by comparing the peak area of each phytoestrogen with the peak area response of the internal standard and then interpolating the area ratio against calibration curves produced with different amounts (1–25,000 ng) of the individual phytoestrogens. For isoflavone and coumestrol analysis, the same procedure was followed except that the alkaline hydrolysis step was eliminated. The phytoestrogen contents (as aglycones) are presented in ug as consumed per g (wet weight), per unit (tablet, capsule, or drop), and per daily dose based on recommended usual doses given on product labels. The analytical method detection and quantitation limits, recovery, and coefficient of variation for each of the phytoestrogens are provided in Table 2. The detection limit was estimated from injections (n = 2) of various levels of standards (0.007–166.667 ug/ml) to the GC-MS. The quantitation limit in ug/g sample was calculated based on the amount of sample extracted and the detection limit of the GC-MS. The percent recovery was the mean recoveries (n = 8) of a mixture of the Nutrition and Cancer 2007
Table 2. Detection and Quantitation Limits, Recovery and Coefficient of Variation (CV) of the Analytical Methoda Variable Detection limit, ng/uLb Quantitation limit, ug/g samplec Recovery,% CV,% (within-day) CV,% (between-days)
FOR
DAI
GEN
GLY
MAT
LAR
PINO
SECO
COU
0.067 0.010 93.7 4.7 6.5
0.067 0.010 88.2 2.5 2.7
0.007 0.001 89.1 2.5 7.5
0.333 0.050 77.3 2.8 3.2
0.333 0.050 76.6 3.9 4.7
0.667 0.100 73.8 2.6 3.1
0.333 0.050 73.9 5.2 6.3
0.333 0.050 92.3 1.0 1.4
0.067 0.010 77.1 4.3 5.5
a: Abbreviations are as follows: FOR, formononetin; DAI, daidzein; GEN, genistein; GLY, glycitein; MAT, matairesinol; LAR, lariciresinol; PINO, pinoresinol; SECO, secoisolariciresinol; COU, coumestrol; GC-MS, gas chromatography-mass spectrometry. b: Amount that can be detected by the GC-MS. c: Estimated lowest concentration in sample that can be quantified using the GC-MS method.
phytoestrogen standards (5,000 ng each) in methanol added to water and carried through the whole analytical procedure. The mean coefficient of variation was estimated from analytical runs within a day (n = 4) and between days (n = 8).
Results The SS and MS ingredients listed on the labels are given in Table 1. Some SS (black cohosh, isoflavones, red clover) and MS (Estro LogicTM , Quest, Jamieson Laboratories, Toronto, Ontario, Canada; Menopause Formula, Natural Factors, Burnaby, British Columbia, Canada; Natural HRTTM (Hormone Replacement Therapy), Swiss Herbal Remedies Ltd., Richmond Hill, Ontario, Canada) have label claims relating to menopause or premenstrual symptom relief. Some SS also include broader claims relating to control of cholesterol (garlic), nervousness and irritability (hops), and for urinary tract (cranberry) and general health (chasteberry, garlic, red clover). The SS have a variety of primary bioactive ingredients (Table 1), and the largest phytoestrogen contributors are those with the highest levels of isoflavones expressed in aglycone units (Table 3). The highest amount of isoflavones was detected in SS containing red clover (18,970.8– 27,419.4 ug/g) or soy (isoflavones 9,583.3 ug/g) as primary ingredients (Table 3). Red clover supplements have successively more formononetin than genistein, daidzein, and glycitein, whereas formononetin is the least plentiful in SS, with considerably more soy extract. Licorice contained the next highest isoflavone content (363.3 ug/g), primarily as formononetin. All other SS have lower isoflavone concentrations (0.0–19.0 ug/g), with the majority containing more formononetin followed by genistein. Lecithin was analyzed, but because no or insignificant amounts of phytoestrogens (isoflavones, lignans, coumestrol) were detected, results for this SS will not be reported further. Only 7 SS contained coumestrol, and they are in low concentrations (0.1–1.2 ug/g; Table 3). On the other hand, lignans are present in all (0.1–90.0 ug/g). In the highest concentrations are lariciresinol in 6, pinoresinol in 6, secoisolariciresinol in 3, and matairesinol in 1 supplement. Matairesinol is often present in lower concentrations than other lignans. Vol. 59, No. 2
The highest total lignan levels were found in both samples of red clover, then 1 sample of chasteberry (Sundown Vitamins, Boca Raton, FL), bioflavonoids, isoflavones, and wild yam. The 2 chasteberry supplements differ in phytoestrogen content. Both have very little isoflavones (1.7–2.8 ug/g), but their total lignans are widely different (9.1 vs. 41.4 ug/g; Table 3). However, the relative amounts of their individual lignans are similar, that is, highest in pinoresinol followed by lariciresinol, secoisolariciresinol, and matairesinol. In contrast, the 2 garlic supplements did not differ much in their total isoflavone (13.2 vs. 19.0), lignan (1.5 vs. 0.1), and phytoestrogen (14.7 vs. 19.1) contents, although their phytoestrogen profiles differed. The small quantitative difference is primarily due to the higher concentration of formononetin in the odorless (not aged) garlic supplement (11.4 vs. 0.1 ug/g). The 2 red clover supplements also differed in phytoestrogen concentrations but were similar in having the highest concentration of formononetin followed by large amounts of genistein and having higher pinoresinol than the other types of lignans. Black cohosh contains both isoflavones and lignans, whereas blue cohosh contains only lignans, albeit all phytoestrogens are in low concentrations. The phytoestrogen ranking of the SS when expressed as ug/unit or ug/daily dose was similar to that based on concentration (ug/g), although the ranks often increased or decreased by 1 to 2 levels (Table 3). All 4 MS listed black cohosh and chasteberry extract as 2 main ingredients, and except for PMS Formula (premenstrual syndrome formula) (Life Brand, Shoppers Drug Mart, Toronto, Ontario, Canada), also included wild yam (Table 1). Except for Menopause Formula, they contained a known source of isoflavones (red clover or soy) and hence showed very high concentrations of total isoflavones (728.2–35,417.0 ug/g; Table 3). As with SS, those MS containing red clover (Natural HRT, PMS Formula) have a higher concentration of formononetin relative to daidzein, genistein, and glycitein, whereas concentration order is reversed for those containing soy isoflavones (Estro Logic) in which formononetin is the lowest, and genistein is the highest. Although not containing soy or red clover, Menopause Formula had significant, albeit lower amounts of isoflavones (41.3 ug/g) than the other MS. It contains licorice root extract and hops, which are not present in the other MS. 179
Table 3. Phytoestrogen Content (as Aglycone) of Supplements in ug as Consumed Per g (wet wt), Per Unit, and Per Daily Dosea Supplement and weight, per g, per unit (mg), daily dose (mg)b Single supplements Bioflavonoidsc Per g Per capsule (642) 2 capsules (1,284) Black cohoshd Per g Per capsule (399) 2 capsules (798) Blue cohoshe Per g Per drop (33) 15 drops (488) Chasteberryf Per g Per capsule (404) 6 capsules (2,424) Chasteberryg Per g Per capsule (440) 1 capsule (440) Cranberryh Per g Per capsule (603) 2 capsules (1,206) Dong quaid Per g Per capsule (514) 3 capsules (1,542) Evening primrose oilh,i Per g Per capsule (721) 4 capsules (2,884) Garlic (aged, odorless)h Per g Per capsule (481) 4 capsules (1,924) Garlic (odorless)h,i Per g Per capsule (337) 3 capsules (1,011) Hopsg Per g Per capsule (516) 2 capsules (1,032) Isoflavonesd Per g Per caplet (497) 3 caplets (1,491) Lecithind,i Per g Per capsule (1,699) 3 capsules (5,097) Licoricej Per g Per capsule (436) 6 capsules (2,616) Red clover (Menoflavon)h Per g Per capsule (463) 1 capsule (463)
180
FOR
DAI
GEN
GLY
MAT
LAR
PINO
SECO COU
Total ISO Total LIG Total PE
0.4 0.3 0.5
0.7 0.5 0.9
3.4 2.2 4.4
0.0 0.0 0.0
0.2 0.1 0.3
30.3 19.5 38.9
0.1 0.1 0.1
0.5 0.3 0.6
0.0 0.0 0.0
4.5 2.9 5.8
31.1 20.0 39.9
35.6 22.9 45.7
0.2 0.1 0.2
0.6 0.2 0.5
0.7 0.3 0.6
4.6 1.8 3.7
0.0 0.0 0.0
1.8 0.7 1.4
0.4 0.2 0.3
nd nd nd
0.0 0.0 0.0
6.1 2.4 4.9
2.2 0.9 1.8
8.3 3.3 6.6
0.1 0.0 0.1
0.0 0.0 0.0
0.0 0.0 0.0
0.0 0.0 0.0
0.7 0.0 0.3
0.3 0.0 0.2
0.1 0.0 0.1
3.5 0.1 1.7
0.0 0.0 0.0
0.1 0.0 0.1
4.6 0.2 2.2
4.7 0.2 2.3
1.1 0.4 2.7
0.6 0.2 1.5
0.8 0.3 1.9
0.3 0.1 0.7
nd nd nd
13.7 5.5 33.2
23.9 9.7 57.9
3.8 1.5 9.2
0.0 0.0 0.0
2.8 1.1 6.8
41.4 16.7 100.4
44.2 17.9 107.1
0.7 0.3 0.3
0.1 0.0 0.0
0.6 0.3 0.3
0.3 0.1 0.1
nd nd nd
3.0 1.3 1.3
5.2 2.3 2.3
0.9 0.4 0.4
0.1 0.0 0.0
1.7 0.8 0.8
9.1 4.0 4.0
10.9 4.8 4.8
0.5 0.3 0.6
0.2 0.1 0.2
0.9 0.5 1.1
0.1 0.1 0.1
0.9 0.5 1.1
3.2 1.9 3.9
3.1 1.9 3.7
0.9 0.5 1.1
0.1 0.1 0.1
1.7 1.0 2.1
8.1 4.9 9.8
9.9 6.0 11.9
3.7 1.9 5.7
0.6 0.3 0.9
0.7 0.4 1.1
0.2 0.1 0.3
nd nd nd
nd nd nd
0.4 0.2 0.6
1.7 0.9 2.6
0.0 0.0 0.0
5.2 2.7 8.0
2.1 1.1 3.2
7.3 3.8 11.3
0.0 0.0 0.0
0.0 0.0 0.0
0.0 0.0 0.0
0.3 0.2 0.9
0.2 0.1 0.6
nd nd nd
0.0 0.0 0.0
nd nd nd
0.0 0.0 0.0
0.3 0.2 0.9
0.2 0.1 0.6
0.5 0.4 1.4
0.1 0.1 0.2
3.6 1.7 6.9
9.1 4.4 17.5
0.4 0.2 0.8
nd nd nd
0.8 0.4 1.5
0.3 0.1 0.6
0.4 0.2 0.8
0.0 0.0 0.0
13.2 6.4 25.4
1.5 0.7 2.9
14.7 7.1 28.3
11.4 3.8 11.5
1.3 0.4 1.3
6.3 2.1 6.4
0.0 0.0 0.0
0.0 0.0 0.0
nd nd nd
0.1 0.0 0.1
nd nd nd
0.0 0.0 0.0
19.0 6.4 19.2
0.1 0.0 0.1
19.1 6.4 19.3
2.1 1.1 2.2
0.6 0.3 0.6
1.4 0.7 1.4
0.2 0.1 0.2
1.0 0.5 1.0
1.7 0.9 1.8
3.1 1.6 3.2
2.0 1.0 2.1
0.3 0.2 0.3
4.3 2.2 4.4
7.8 4.0 8.1
12.4 6.4 12.8
221.7 110.2 330.6
2,450.9 1,218.1 3,654.3
6,605.4 3,282.9 9,848.7
305.3 151.7 455.2
0.3 0.2 0.5
12.6 6.3 18.8
8.9 4.4 13.3
5.5 2.7 8.2
0.8 0.4 1.2
9,583.3 4,762.9 14,288.7
27.3 13.6 40.7
9,611.4 4,776.9 14,330.6
0.0 0.0 0.0
0.0 0.0 0.0
0.0 0.0 0.0
nd nd nd
nd nd nd
nd nd nd
nd nd nd
nd nd nd
0.0 0.0 0.0
0.0 0.0 0.0
nd nd nd
0.0 0.0 0.0
341.0 148.7 892.1
11.7 5.1 30.6
10.3 4.5 26.9
0.3 0.1 0.8
0.9 0.4 2.4
3.8 1.7 9.9
0.4 0.2 1.1
0.4 0.2 1.1
1.2 0.5 3.1
363.3 158.4 950.4
5.5 2.4 14.4
370.0 161.3 967.9
23,764.3 11,002.9 11,002.9
1,515.7 701.8 701.8
2,126.4 984.5 984.5
13.0 6.0 6.0
23.7 11.0 11.0
12.6 5.8 5.8
36.0 16.7 16.7
17.7 8.2 8.2
1.0 0.5 0.5
27,419.4 12,695.2 12,695.2
90.0 41.7 41.7
27,510.4 12,737.3 12,737.3
Nutrition and Cancer 2007
Table 3. (Continuted) Supplement and weight per g per unit (mg), daily dose (mg)b Red clover (Promensil)k Per g Per tablet (535) 1 tablet (535) Wild yamj Per g Per capsule (546) 2 capsules (1,092) Multiple supplements Estro Logich Per g Per capsule (376) 2 capsules (752) Menopause Formulac Per g Per capsule (302) 2 capsules (604) Natural HRTd Per g Per capsule (451) 2 capsules (902) PMS Formulal Per g Per capsule (464) 2 capsules (928)
FOR
DAI
GEN
GLY
MAT
LAR
PINO
14,693.1 7,860.8 7,860.8
978.3 523.4 523.4
3,264.2 1,746.4 1,746.4
2.5 1.4 2.7
1.1 0.6 1.2
24.4 9.2 18.4
SECO COU
Total ISO Total LIG Total PE
35.2 18.8 18.8
0.6 0.3 0.3
3.7 2.0 2.0
37.4 20.0 20.0
4.1 2.2 2.2
0.9 0.5 0.5
18,970.8 10,149.4 10,149.4
45.8 24.5 24.5
19,017.5 10,174.4 10,174.4
1.7 0.9 1.9
0.1 0.1 0.1
0.0 0.0 0.0
0.6 0.3 0.7
4.6 2.5 5.0
11.0 6.0 12.0
0.0 0.0 0.0
5.4 3.0 5.9
16.2 8.9 17.7
21.6 11.8 23.6
8,325.9 3,130.5 6,261.1
26,101.4 9,814.1 19,628.3
965.3 363.0 725.9
1.1 0.4 0.8
42.3 15.9 31.8
36.1 13.6 27.2
19.5 7.3 14.7
1.7 0.6 1.3
35,417.0 13,316.8 26,633.6
99.0 37.2 74.5
35,517.7 13,354.7 26,709.3
38.6 11.7 23.3
1.8 0.5 1.1
0.6 0.2 0.4
0.3 0.1 0.2
0.0 0.0 0.0
5.2 1.6 3.1
3.5 1.1 2.1
6.5 2.0 3.9
0.0 0.0 0.0
41.3 12.5 25.0
15.2 4.6 9.2
56.5 17.1 34.1
4,725.1 2,131.0 4,262.0
598.8 270.1 540.1
281.8 127.1 254.2
3.1 1.4 2.8
0.4 0.2 0.4
6.7 3.0 6.0
8.5 3.8 7.7
5.9 2.7 5.3
0.3 0.1 0.3
5,608.8 2,529.6 5,059.1
21.5 9.7 19.4
5,630.6 2,539.4 5,078.8
414.0 192.1 384.2
85.8 39.8 79.6
227.5 105.6 211.1
0.9 0.4 0.8
2.8 1.3 2.6
97.5 45.2 90.5
122.3 56.8 113.5
76.3 35.4 70.8
3.0 1.4 2.8
728.2 337.9 675.8
298.9 138.7 277.4
1,030.1 478.0 955.9
a: Abbreviations are as follows: FOR, formononetin; DAI, daidzein; GEN, genistein; GLY, glycitein; MAT, matairesinol; LAR, lariciresinol; PINO, pinoresinol; SECO, secoisolariciresinol; COU, coumestrol; ISO, isoflavones; LIG, lignans; PE, phytoestrogens; nd, below quantitation limit (0.001 ug/g, GEN; 0.010 ug/g, FOR, DAI, COU; 0.050 ug/g GLY, MAT, PINO, SECO; 0.100 ug/g LAR); 0.0, >0.01 but
