Plasma Isoflavone Concentrations Research Articles

A Soy Protein Isolate Rich in Genistein and Daidzein and Its Effects on Plasma Isoflavone Concentrations, Platelet Aggregation, Blood Lipids and Fatty Acid Composition of Plasma Phospholipid in Normal Men

The effects of consuming a soy protein isolate beverage powder (60 g/d for 28 d) vs. a casein supplement was evaluated in 20 male subjects who were randomly allocated into the two groups. A dramatic rise in plasma isoflavone concentrations was observed after supplementation in the soy protein group, the levels reaching 907 ± 245 nmol/L for genistein (a 110-fold increase) and 498 ± 102 nmol/L for daidzein (a 150-fold increase) as measured by isotope dilution gas chromatography - mass spectrometry. These concentrations are higher than previously reported for the plasma of Japanese subjects consuming a traditional diet (276 nmol/L and 107 nmol/L, respectively). No significant differences in collagen- or 9,11-dideoxy-11α, 9α-epoxymethanoprostaglandin F2α (U46619)-induced platelet aggregation were observed in platelet-rich plasma from the two groups; the increase in plasma isoflavonoids from soy protein supplementation is not sufficient to significantly inhibit platelet aggregation ex vivo. Similarly, plasma total and HDL-cholesterol were not affected by protein supplementation, possibly because the men were normo-cholesterolemic at entry. Analysis of plasma phospholipid polyunsaturated fatty acid composition showed no differences between soy protein and casein supplementation. Previous investigations reported a significant alteration in fatty acid status in animals fed soy protein relative to those fed casein. The present studies indicate that although soy protein supplementation to a typical Western diet can increase plasma concentrations of isoflavones, this may not necessarily be sufficient to counter heart disease risk factors such as high plasma cholesterol and platelet aggregation.

Effects of a low-fat dietary regimen enriched with soy in children affected with heterozygous familial hypercholesterolemia

Familial hypercholesterolemia (FH) is an inheritable, autosomal dominant disorder leading to pathologically increased levels of low-density-lipoprotein cholesterol (LDL-C). Dietary treatment remains an important tool in the management of affected children even after the decision for the initiation of pharmacotherapy is made. However, little evidence is available regarding the optimal dietary regimen for the treatment of children affected with FH. We present results from a randomized controlled trial in paediatric patients affected with heterozygous FH, assessing the effect of a soy-enriched fat modified diet (soy group) compared to fat modified diet (Control group) alone on LDL-C over a period of 13 weeks. Furthermore, we monitored isoflavone levels in plasma and urine as markers of adherence to the dietary treatments. LDL-C decrease was statistically significantly greater in the soy group compared to the control group at week 7 (Control group 176.3±27.8mg/dl, soy group 154.7±29.2mg/dl, p=0.038), and showed a trend towards significant at week 13 (Control group 179.9±41.8mg/dl, soy group 155.0±30.2mg/dl, p=0.089). Relative LDL-C decrease correlated significantly with the following plasma isoflavone concentrations measured in week 7: daidzein (p<0.004, r=0.576) and genistein (p<0.017, r=0.490). We provide evidence from a small randomized-controlled trial for the effectiveness and safety of a dietary treatment with soy in paediatric patients affected with heterozygous FH. The decrease in LDL-C was highly correlated with isoflavone levels, further highlighting a direct effect of soy ingestion. This study was registered under ClinicalTrials.gov Identifier No. NCT03563547.

Abstract 2276: Effect modification by isoflavones on the association between salt intake and gastric cancer risk: A case-cohort study within the Korean multi-center cancer cohort

Abstract Backgrounds: Attenuation by genistein, an isoflavone abundant in soybean, of gastric carcinogenesis induced by sodium chloride was reported in an animal study. Up to date, role of isoflavone as an effect modifier on the association between salt intake and gastric cancer risk is not clearly established. Methods: We randomly selected 640 subcohort subjects without cancer history at enrollment from the Korean multi-center cancer cohort participants. Ninety-nine gastric cancer cases were identified from the inside (N=8) and the outside (N=91) of the subcohort after the 12.2 years of median follow-up time. To estimate individual’s salt intake, we measured 24-hour urinary sodium excretion from spot urine using the Tanaka’s equation. Three isoflavone plasma concentrations (Genistein, daidzein, and equol) of 167 subjects among case-cohort subjects had been measured using time-resolved fluoroimmunoassay. Cubic spline curve for gastric cancer risk according to urinary sodium level was used to define optimal cut-off points of urinary sodium excretion concentration. Weighted Cox proportional hazard regression was used to calculate hazard ratios (HRs) and their 95% confidence intervals (CIs). Stratified analysis by isoflavone level was conducted to assess effect modification by isoflavone on the association between salt intake and gastric cancer. Results: Gastric cancer risk in the high salt intake group (urinary sodium excretion ≥6,000mg/day) was significantly increased (HR, 1.69; 95% CI, 0.99-2.90) compared to the reference group (urinary sodium excretion 4500-5,999mg/day). Magnitudes of gastric cancer risk by high salt intake were more strengthened in the group with low plasma isoflavone concentrations (One or no genistein, diadzein or equol levels over the median concentrations) (HR, 6.92; 95% CI, 1.80-26.56). Contrary to the low isoflavone group, no significant differences in gastric cancer risk according to salt intake levels were found in the group with high isoflavone concentration. Conclusions: High salt intake is associated with gastric cancer risk, but this association can be attenuated by high concentration of isoflavones. We suggest that sufficient intake of soybean products, the rich sources of isoflavone, may give protection against gastric cancer in the population with high salt intake. Citation Format: Jieun Jang, Yunji Hwang, Choonghyun Ahn, Kwang-Pil Ko, Aesun Shin, Keun-Young Yoo, Sue K. Park. Effect modification by isoflavones on the association between salt intake and gastric cancer risk: A case-cohort study within the Korean multi-center cancer cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2276. doi:10.1158/1538-7445.AM2017-2276

Combined bioavailable isoflavones and probiotics improve bone status and estrogen metabolism in postmenopausal osteopenic women: a randomized controlled trial

Background: Female age-related estrogen deficiency increases the risk of osteoporosis, which can be effectively treated with the use of hormone replacement therapy. However, hormone replacement therapy is demonstrated to increase cancer risk. Bioavailable isoflavones with selective estrogen receptor affinity show potential to prevent and treat osteoporosis while minimizing or eliminating carcinogenic side effects.Objective: In this study, we sought to determine the beneficial effects of a bioavailable isoflavone and probiotic treatment against postmenopausal osteopenia.Design: We used a novel red clover extract (RCE) rich in isoflavone aglycones and probiotics to concomitantly promote uptake and a favorable intestinal bacterial profile to enhance isoflavone bioavailability. This was a 12-mo, double-blind, parallel design, placebo-controlled, randomized controlled trial of 78 postmenopausal osteopenic women supplemented with calcium (1200 mg/d), magnesium (550 mg/d), and calcitriol (25 μg/d) given either RCE (60 mg isoflavone aglycones/d and probiotics) or a masked placebo [control (CON)].Results: RCE significantly attenuated bone mineral density (BMD) loss at the L2-L4 lumbar spine vertebra (P < 0.05), femoral neck (P < 0.01), and trochanter (P < 0.01) compared with CON (-0.99% and -2.2%; -1.04% and -3.05%; and -0.67% and -2.79, respectively). Plasma concentrations of collagen type 1 cross-linked C-telopeptide was significantly decreased in the RCE group (P < 0.05) compared with CON (-9.40% and -6.76%, respectively). RCE significantly elevated the plasma isoflavone concentration (P < 0.05), the urinary 2-hydroxyestrone (2-OH) to 16α-hydroxyestrone (16α-OH) ratio (P < 0.05), and equol-producer status (P < 0.05) compared with CON. RCE had no significant effect on other bone turnover biomarkers. Self-reported diet and physical activity were consistent and differences were nonsignificant between groups throughout the study. RCE was well tolerated with no adverse events.Conclusions: Twice daily RCE intake over 1 y potently attenuated BMD loss caused by estrogen deficiency, improved bone turnover, promoted a favorable estrogen metabolite profile (2-OH:16α-OH), and stimulated equol production in postmenopausal women with osteopenia. RCE intake combined with supplementation (calcium, magnesium, and calcitriol) was more effective than supplementation alone. This trial was registered at clinicaltrials.gov as NCT02174666.

Plasma isoflavones in Malaysian men according to vegetarianism and by age.

Epidemiological studies indicate lower prevalences of breast and prostate cancers and cardiovascular disease in Southeast Asia where vegetarianism is popular and diets are traditionally high in phytoestrogens. This study assessed plasma isoflavones in vegetarian and non-vegetarian Malaysian men according to age. Daidzein, genistein, equol (a daidzein metabolite), formononetin, biochanin A, estrone, estradiol and testosterone were measured by validated liquid chromatography tandem mass spectrometry (LCMSMS). Plasma isoflavone and sex hormone concentrations were measured in 225 subjects according to age (18-34, 35-44 and 45-67 years old). In all age groups, vegetarians had a higher concentration of circulating isoflavones compared with non-vegetarians especially in the 45-67 year age group where all isoflavones except equol, were significantly higher in vegetarians compared with omnivores. By contrast, the 18-34 year group had a significantly higher concentration of daidzein in vegetarians and significantly higher testosterone and estrone concentrations compared with non-vegetarians. In this age group there were weak correlations between estrone, estradiol and testosterone with some of the isoflavones. This human study provides the first Malaysian data for the phytoestrogen status of vegetarian and nonvegetarian men.

Tracking Isoflavones in Whole Soy Flour, Soy Muffins and Plasma after Consumption of Muffins by Healthy Adults

The cardio‐protective effect of soy may be related to isoflavones. Research is needed to determine how isoflavones change during processing and digestion from a raw food ingredient to the biological fluid in order to better understand the relationship between isoflavone form, the food matrix, and the health effects conferred. This study tracked the abundance and transformation of soy isoflavones in: de‐fatted whole soy flour; a baked soy muffin; and plasma after regular consumption of soy muffins in a human clinical trial. Isoflavones were identified and quantified in soy flour and muffins by HPLC, and in plasma by LC‐MS/MS after participants (n=162) consumed soy muffins at doses of either 12.5g or 25g soy protein daily for 6 weeks. Soy muffins were sampled from 7 different production days (n=14) and analyzed for individual isoflavone isoforms and total isoflavone. Mean (±SEM) isoflavone content was 4.14±1.29 mg/g (DW) in soy flour and 1.10±0.04 mg/g (DW) in soy muffins. Soy flour and muffins contained similar proportions of isoflavone isoforms, but soy muffins contained overall lower absolute isoflavone content. Median total plasma isoflavone concentrations at week 6 for the low dose soy and the high dose soy groups were 91.0 and 333.7 ng/mL, respectively. Baking soy flour does not result in major changes in the relative proportion of isoflavones isoforms. Regular consumption of soy results in a dose‐related increase in plasma isoflavones with an approximate 4‐fold increase with a doubling of the dose. Funded through the Government of Canada Growing Forward I Science substantiation Program (RBPI#1746).

Plasma isoflavones and risk of primary liver cancer in Japanese women and men with hepatitis virus infection: a nested case-control study.

Evidence suggests that estrogen plays a preventive role in primary liver cancer development, and it might be thought that isoflavones, which are structurally similar to estrogens and bind to estrogen receptors, are associated with the risk of liver cancer. We investigated this suspected association by measuring plasma concentrations of isoflavones in a nested case-control study of a population-based prospective cohort in Japan. From 18,628 target participants ages 40 to 69 years who returned the baseline questionnaire and provided blood samples, we selected those with either hepatitis B or hepatitis C virus infection at baseline (n = 1,544). Among these, 90 (28 women and 62 men) were newly diagnosed with primary liver cancer from 1993 through 2006; they were matched with 175 controls (54 women and 121 men). Plasma concentrations of isoflavones (genistein, daidzein, glycitein, and equol) were measured using triple quadrupole tandem liquid chromatography-mass spectrometry. The ORs of liver cancer development based on plasma concentrations were estimated with a conditional logistic regression model. Basically, distributions of plasma isoflavone concentrations did not differ between the cases and controls. No statistically significant associations of genistein, daidzein, glycitein, and equol with primary liver cancer risk were found in either women or men. In middle-aged Japanese women and men with hepatitis virus infection, plasma isoflavones were unassociated with the occurrence of primary liver cancer. The role of isoflavones in liver carcinogenesis merits further study using both biomarkers and data on dietary intake of isoflavones. Cancer Epidemiol Biomarkers Prev; 24(3); 532-7. ©2014 AACR.

Plasma isoflavone concentration is associated with decreased risk of type 2 diabetes in Korean women but not men: results from the Korean Genome and Epidemiology Study

To examine the association between soybean products and risk of type 2 diabetes, we measured four isoflavone biological markers--genistein, daidzein, glycitein and equol--in a nested case-control study. The study population was composed of 693 cases (316 women and 377 men) and 698 matched controls (317 women and 381 men) within the Korean Genome and Epidemiology Study. The concentrations of isoflavone biomarkers were measured using HPLC-MS/MS on plasma samples that were collected at baseline. A stratified analysis was undertaken to examine the association between plasma isoflavone concentrations and risk of type 2 diabetes according to sex and equol production. Logistic regression models were used to compute ORs and 95% CIs adjusted for confounders. In women, compared with the lowest quartile of plasma concentration of genistein, the highest quartile exhibited a significantly decreased risk of diabetes (OR 0.58, 95% CI 0.35, 0.95). When stratified by equol-producing status in women, the OR for diabetes in the highest vs the lowest quartile of genistein concentration was 0.31 (95% CI 0.16, 0.60) in equol producers, but genistein concentration was not associated with risk of diabetes in equol non-producers (p for interaction = 0.013). In men, isoflavone concentrations were not associated with risk of diabetes, regardless of equol-producing status. High plasma concentrations of genistein were associated with a decreased risk of type 2 diabetes in women. This inverse association was prominent in equol-producing participants. These results suggest a beneficial effect of a high intake of soybean products on risk of type 2 diabetes in women.

Large inter-individual variation in isoflavone plasma concentration limits use of isoflavone intake data for risk assessment.

Background/objectives:Isoflavones are present in soy foods and soy-based supplements. Despite low plasma isoflavone concentrations in the general Western population, concentrations in supplement users exceed those suggested to be beneficial for health in Asian populations, raising concerns for adverse effects. To aid risk assessment, quantification of the relation between isoflavone intake and plasma concentrations is essential.Subjects/methods:Plasma samples were collected from postmenopausal women in three placebo-controlled crossover studies with 8-week periods for supplements (two studies, ~100 mg isoflavones/day, n=88) or 4-week periods for soy foods (one study, ~48 mg isoflavones/day, n=15). Plasma isoflavone concentrations (daidzein, equol, genistein and glycitein) were quantified using high-performance liquid chromatography and electrochemical detection. The association between plasma concentrations and isoflavone intake, equol producer status, intake–producer interaction and background dietary intake was assessed based on the assumption of a log-linear relation.Results:Median plasma total isoflavone concentrations after the soy food and supplement interventions were respectively 2.16 and 3.47 μmol/l for equol producers and 1.30 and 2.39 μmol/l for non-producers. Regression analysis showed that doubling isoflavone intake increased plasma concentrations by 55–62% (±s.e. 1–2%, R2>0.87) for daidzein, genistein, equol (only for producers) and total isoflavones; for glycitein the association was weaker (15±1%, R2=0.48). Adjustments for energy, carbohydrate and fat intake did not affect these estimates. Inter-individual variation, estimated based on repeated measures in one of the studies, was 30–96%.Conclusions:Although the relation between isoflavone intake and plasma concentrations was adequately quantified, the use of isoflavone intake data for risk assessment needs caution due to large inter-individual variation in plasma concentrations.

Effect of synbiotic fermented milk on oral bioavailability of isoflavones in postmenopausal women

The purpose of this study was to investigate the effect of synbiotic fermented milk, containing Lactobacillus paracasei and inulin, on oral bioavailability and pharmacokinetics of isoflavones in healthy postmenopausal women. The study was a one-group pre-post treatment study. Twelve subjects were assigned to consume a single oral dose of 375 mL of soy beverage. Blood samples were collected immediately before and at various time points until 32 hours after the administration of the soy beverage. After a washout period, subjects were requested to consume 180 mL of synbiotic fermented milk after breakfast and dinner for 14 days, followed by a single oral dose of 375 mL of soy beverage on the next day. Collection of blood samples after the administration of the soy beverage were performed at the same time points as the former phase. Plasma isoflavone concentrations were measured by using high-performance liquid chromatography (HPLC) technique. In conclusion, this study highlighted that continuous consumption of synbiotic fermented milk followed by a single oral administration of soy beverage significantly enhanced oral bioavailability of isoflavones compared with a single oral dose of soy beverage alone.

Abstract P189: Acculturation Status is Associated with Selected Plasma Nutrient Biomarkers of Dietary Intake and CVD Risk in Adult Chinese Americans

The demographic changes anticipated in the U.S. over the next decade magnify the importance of addressing health disparities among minority populations. Chinese Americans are a fast growing minority subgroup, yet there is limited and inconsistent data on the impact of dietary acculturation and subsequent cardiovascular disease (CVD) risk in this population. This discrepancy could be related to the subjective nature of the assessment tools used to collect dietary data along with cultural/linguistic barriers to the implementation of these methods. We hypothesized that higher acculturation status will be associated with dietary patterns that more closely resemble the typical U.S. diet and subsequently with a higher risk of CVD in Chinese Americans (N=225). Dietary intake was evaluated using plasma concentrations of validated objective plasma nutrient biomarkers: phylloquinone for green leafy vegetables/vegetable oils and partially-hydrogenated fat; phospholipid concentrations of 15:0 and 20:4n-6 for dairy and meat, omega 3 for fish, trans (18:1n-9T, 18:1n-7T) for partially-hydrogenated fat; carotenoids for fruit and vegetables (F&amp;V) including carotene (green/yellow/orange F&amp;V), cryptoxanthin (orange/red F&amp;V), lutein/zeaxanthin (green leafy vegetables), lycopene (tomatoes, mainly from pizza and pasta sauce); and isoflavones (genistein, diadzein) for soy containing foods. The biomarker data was then correlated with acculturation status (assessed using the Stephenson Multigroup Acculturation scale) as well as the CVD risk factor data. Results (for all r values, p&lt;0.05) indicate that higher dominant culture identification was associated with higher 15:0, 18:1n-7T and lycopene intakes (r=0.11, r=0.14 and r=0.15, respectively), while higher ethnic culture identification was associated with higher plasma phylloquinone (r=0.12) and isoflavone (r=0.34) concentrations. With regard to CVD risk factors, plasma LDL-cholesterol was positively associated with 20:4n-6 (r=0.13) and inversely associated with lutein (r=-0.13) and zeaxanthin (r=-0.12) concentrations. Plasma triglyceride was positively associated with carotene (r=0.14); plasma insulin was also positively associated with carotene (r=0.15), lycopene (r=0.120 and 15:0 (r=0.11); while plasma glucose was positively associated with 18:1n-9T (r=0.16), 18:1n-7T (r=0.12) and zeaxanthin (r=0.20) concentrations. These results indicate that higher acculturation status is associated with dietary patterns that more closely resemble the typical U.S. diet, as reflected by higher concentrations of dietary biomarkers for meat, dairy and tomato based products and partially-hydrogenated fat intake; and lower fruit, vegetable and soy intake and subsequently an unfavorable CVD risk profile.

Plasma Isoflavone Concentrations Are Not Associated with Gastric Cancer Risk among Japanese Men and Women1,2

The incidence of gastric cancer throughout the world is ∼2–3 times higher in men than in women. Previous research suggested that isoflavones, which are structurally similar to 17β-estradiol, may prevent gastric cancer. Based on a large, population-based, prospective study, we recently reported a null association between dietary isoflavone intake and gastric cancer. However, epidemiologic studies using blood concentrations of isoflavones might better reflect the effect of isoflavones on gastric cancer carcinogenesis than dietary assessment. We therefore conducted a nested case-control study within the Japan Public Health Center-Based Prospective Study. Participants were followed-up from 1990 to 2004. Among 36,745 participants who answered the baseline questionnaire and provided blood samples, 483 gastric cancer cases matched to 483 controls were used in the analysis. ORs and 95% CIs were estimated with a conditional logistic regression model. The overall distribution of plasma isoflavone concentrations was not associated with the development of gastric cancer. Compared with groups with the lowest plasma concentrations (reference groups), the groups with the highest daidzein and genistein concentrations had adjusted ORs and 95% CIs of 1.11 (0.74–1.66; P-trend = 0.6) and 0.96 (0.64–1.44; P-trend = 0.9), respectively. The results did not change when analysis was based on sex, subsite, or histological type. We found no association of plasma isoflavone concentrations with gastric cancer risk. Our data support the previously observed null association between isoflavone intake and gastric cancer risk.

Plasma pharmacokinetics and urinary excretion of isoflavones after ingestion of soy products with different aglycone/glucoside ratios in South Korean women

Asian populations are thought to receive significant health benefits from traditional diets rich in soybeans due to high isoflavone contents. However, available epidemiologic data only weakly support this hypothesis. The present study was carried out to assess the pharmacokinetics of isoflavones in South Korean women after ingestion of soy-based foods. Twenty-six healthy female volunteers (20-30 y old) consumed three different soy products (i.e., isogen, soymilk, and fermented soybeans) with different aglycone/glucoside ratios. Plasma and urine isoflavone concentrations were measured by high-performance liquid chromatography (HPLC) after ingestion of one of the soy products. Pharmacokinetic parameters were determined using the WinNonlin program. The area under the curve (AUC) for plasma daidzein levels of the soymilk group (2,101 ± 352 ng · h/mL) was significantly smaller than those of the isogen (2,628 ± 573 ng · h/mL) and fermented soybean (2,593 ± 465 ng · h/mL) groups. The maximum plasma concentration (Cmax) of daidzein for the soymilk group (231 ± 44 ng/mL) was significantly higher than those of the isogen (160 ± 32 ng/mL) and fermented soybean (195 ± 35 ng/mL) groups. The half-lives of daidzein and genistein in the soymilk group (5.9 and 5.6 h, respectively) were significantly shorter than those in the individuals given isogen (9.6 and 8.5 h, respectively) or fermented soybean (9.5 and 8.2 h, respectively). The urinary recovery rates of daidzein and genistein were 42% and 17% for the isogen group, 46% and 23% for the fermented soybean group, and 33% and 22% for the soymilk group. In conclusion, our data indicated that soy products containing high levels of isoflavone aglycone are more effective for maintaining plasma isoflavone concentrations. Additional dose-response, durational, and interventional studies are required to evaluate the ability of soy-based foods to increase the bioavailability of isoflavones that positively affect human health.

Influence of Fructooligosaccharide on Pharmacokinetics of Isoflavones in Postmenopausal Women

The objective of the present paper was to determine the influence of fructooligosaccharide (FOS) on the pharmacokinetics of isoflavones in healthy postmenopausal women. The study was a fixed-sequence, two-phase, crossover study. Twelve subjects received a single oral dose of 300 mL of a soy beverage. Blood samples were collected before the dose and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, and 32 h after the administration of the soy beverage. After a washout period of at least 1 week, subjects were assigned to receive oral doses of FOS, 5 g each time, twice a day (after breakfast and dinner) for 14 days, followed by a single oral dose of the same soy beverage on the next day. Blood samples were then collected at the same time points mentioned previously. Plasma isoflavone concentrations were determined by HPLC. Continuous oral administrations of FOS followed by a single oral administration of soy beverage caused significant increases in C max, AUC0–32, and AUC0–∞ of genistein and AUC0–32 of daidzein, comparing to those obtained following a single oral dose of soy beverage alone. Other pharmacokinetic parameters (T max and t 1/2 of both aglycones and AUC0–∞ of daidzein) between both regimens were not significantly different.

Highlights of This Issue

In breast cancer patients, studies have shown that obesity is associated with both an increased risk of dying from breast cancer and increased risk of distant metastasis. In this pilot study, Pilie and colleagues focused on the potential differences in protein expression patterns of mammary epithelial cells obtained from obese versus nonobese women. They found that vimentin protein expression was significantly different between obese and nonobese women. Differential protein expression analysis may enhance the understanding of breast cancer initiation and progression in obese women.Epidemiologic studies have established an inverse association between isoflavone intake and breast and prostate cancer risks and an inverse association with lung cancer risk has also been suggested. To help clarify the association of isoflavone intake and lung cancer risk, Shimazu and colleagues examined plasma isoflavone concentrations and lung cancer risks in a population of Japanese women. An inverse association was indeed found between plasma levels of the isoflavone genistein and lung cancer risk, supporting the previously observed association between isoflavone intake and lung cancer risk.The evidence linking the acute phase inflammatory response marker C-reactive Protein (CRP) and cancer remains inconclusive. To address this, Van Hemelrijck and collleagues performed a prospective cohort study using repeated measurements of CRP and leukocyte levels to evaluate their association with cancer risk. They report a positive trend between CRP and cancer and found that the associations between leukocytes and cancer were slightly stronger than CRP. These encouraging results are evidence that the use of CRP for early cancer detection may have merit.Experimental evidence suggests that long-chain omega-3 and omega-6 fatty acids may modify early skin carcinogenesis, but it is not known if this effect exists in the general population. To explore this, van der Pols and colleagues used p53 expression as a biomarker of early UV-induced carcinogenesis and monitored serum omega-3 and omega-6 fatty acids as well as p53 immunoreactivity in dorsal hand punch biopsies. They report an inverse association between total serum omega-3 (but not omega-6) fatty acid and p53 immunoreactivity in the whole epidermis as well as basal layer. These results add to the growing evidence that long-chain fatty acids may modify early skin carcinogenesis.

Genistein and genistein-containing dietary supplements accelerate the early stages of cataractogenesis in the male ICR/f rat

Cataract-related loss of vision affects large numbers of people in today’s aging populations and presents a healthcare burden to many nations. The role of dietary supplements within the lens is largely unknown, although benefits from dietary anti-oxidants are expected. In this study, the effects of genistein as its aglycone, a genistein-containing dietary supplement (Novasoy ®200), and a genistein-containing food (soy protein isolate, PRO-FAM 932) on the development of lens opacity were examined in the hereditary cataractous ICR/f rat. These studies were carried out in a background diet of semi-purified, isoflavone-free AIN-76A with casein as its protein source. The amount of genistein for the experimental diets was standardized to its concentration (as genistein aglycone as well as simple and complex β-glucoside conjugates) in the soy protein isolate supplement. Also tested was a high-dose genistein diet containing an 11-fold higher amount of genistein aglycone. The composition of each diet was verified by reverse-phase HPLC and blood plasma isoflavone concentrations were determined by LC-tandem mass spectrometry. The development of opacity in each lens was monitored and digitally recorded using slit-lamp examination over the course of the study. Each of the genistein-containing diets caused a significantly more rapid development of fibrous opacification in the anterior cortical region and development of apparent water clefts or vacuoles in the posterior subcapsular region than the AIN-76A control diet; however, the establishment of dense lens opacification was not significantly different between each of the diets. There was also no significant difference observed between the low-dose and high-dose genistein aglycone groups. These data suggest that genistein-containing dietary supplements accelerate the early stages of cataractogenesis in the male ICR/f rat, with no dose-dependent effects.

Biomarkers of Dietary Exposure Are Associated with Lower Risk of Breast Fibroadenomas in Chinese Women ,

Fibroadenomas are the most common benign breast condition among women and account for up to 50% of all breast biopsies being performed. Although considered a benign condition, fibroadenomas utilize substantial resources for management and treatment to rule out potential malignancies. Dietary factors may influence benign fibrocystic breast conditions, but little is known of their association with fibroadenomas. We examined possible associations between a broad spectrum of circulating biomarkers of dietary intake and risk of fibroadenomas. Participants were women in a breast self-examination trial in Shanghai, China who were diagnosed with fibroadenomas (n = 258) and 1035 controls. Conditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% CI. Isoflavone concentrations were inversely associated with risk of fibroadenomas. Adjusted OR (95% CI) for the highest versus the lowest quartile of plasma concentration were 0.36 (0.16–0.79; P-trend < 0.001) for daidzein and 0.39 (0.19–0.84; P-trend = 0.010) for genistein. We also observed inverse associations between higher percentages of the RBC (n-3) fatty acids, eicosapentaenoic acid (EPA) ([0.38 (0.19–0.77); P-trend = 0.007] and docosapentaenoic acid (DPA) [0.32 (0.15–0.70); P-trend = 0.024], and fibroadenoma risk. Circulating concentrations of carotenoids, vitamin C, retinol, and ferritin were not associated with fibroadenoma risk. The inverse associations between plasma isoflavone concentrations and RBC EPA and DPA and fibroadenoma risk suggest that higher intakes of soy foods and fatty fish may lower the risk of fibroadenomas. J. Nutr. 140: 1302–1310, 2010.

Emerging Research on Equol and Cancer1–

Mechanisms of action of equol described using in vitro studies suggest possible effects of this compound in relation to cancer risk. However, experimental data are lacking with regard to the effects of S-(-)-equol (a gut bacterial product of daidzein), racemic equol, or even daidzein on tumorigenesis in vivo. Rodent studies, using racemic equol or daidzein in equol-producing animals, suggest that equol exposure does not stimulate mammary tumor growth, but there is little evidence that it is protective either. Racemic equol has been shown to inhibit skin carcinogenesis in hairless mice. Epidemiologic studies of associations between urinary or plasma isoflavone concentrations and breast cancer risk in women have reported no association nor increased risk associated with higher equol measures in low-soy–consuming populations but have reported a trend toward decreased cancer risk with increased equol in Asian populations. These population-based differences have been reported for prostate cancer too. Several studies in Asian men report lower equol concentrations or a lower prevalence of equol-producers among men with prostate cancer compared with controls, whereas studies in European populations report no association. Studies using intermediate biomarkers of cancer risk and susceptibility in humans also have examined the effects the equol-producer phenotype in relation to soy intake with varying results. Overall, the role of equol in relation to cancer remains unclear. With the availability of R- and S-equol, animal studies of carcinogenesis and human intervention studies addressing effects of the equol enantiomers on intermediate biomarkers may help to ascertain the role of equol in cancer risk. J. Nutr. 140: 1369S–1372S, 2010.

INTERVENSI ISOFLAVON KEDELAI TIDAK BERPENGARUH TERHADAP STATUS INFLAMASI DAN IMUNITAS PADA REMAJA DENGAN KEGEMUKAN

&lt;p class="MsoNormal" style="margin: 0cm 12.8pt .0001pt 14.2pt; text-align: justify; text-indent: 21.8pt;"&gt;&lt;span style="font-size: 10pt;"&gt;Overweight/obesity is a condition that has been proven to be interrelated with chronic inflammation and compromised immune system due to disregulation of adipocytokine. The aim of the present study was to evaluate the effect of soy isoflavone on the markers of inflammation and immunity of overweight or obese teenagers. Eighteen overweight or obese teenagers, 9 boys and 9 girls each sex were randomized to one of three intervention groups; 0 ml, 150 ml and 300 ml soy milk, equal to 0 g, 25 g and 50 mg isoflavone everyday for 30 days. The data collected were food consumption, plasma isoflavone concentration, plasma IL6 as indicator of inflammation, and lymphocyte and NK cell count as indicator of immunity. The study showed that nutrient intake of samples were still relatively low. The soy milk intervention significantly increased plasma isoflavone concentration, but not significantly had contribution to the plasma IL6 concentration and lymphocyte and NK cell count. Several kind of food consumed by samples had contribution to the plasma isoflavone concentration, and lymphocyte count. Based on the results, it was suggested that soy isoflavone intervention does not affect the inflammation status and immunity of overweight/obese teenagers.&lt;/span&gt;&lt;/p&gt;

Effects of isoflavone supplements vs. soy foods on blood concentrations of genistein and daidzein in adults

The objective of this investigation was to examine the pharmacokinetics of isoflavone concentrations over a 24-h period among healthy adults consuming either soy foods or soy isoflavone tablets at different doses. This randomized, cross-over trial was conducted with 12 generally healthy adults. The three phases of the intervention included isoflavone tablets at (1) 144 mg/day or (2) 288 mg/day and (3) soy foods designed to provide a calculated 96 mg isoflavones/day (doses in aglycone equivalents). Doses were spread out over three meals per day. After 6 days on each study phase, plasma isoflavone concentrations were determined on the seventh day at 0, 4, 8, 10, 12 and 24 h. Average levels of total isoflavone concentrations at 8, 10 and 12 h were >4 μmol/L for the soy food phase and for the higher dose tablet phase. Genistein concentrations were higher overall in the soy food vs. both the lower and the higher dose supplement phases of the study ( P<.05). When comparing plasma concentrations for the two doses of tablets, saturation appeared more evident for genistein than for daidzein at the higher dose level. In conclusion, we observed important differences in the pharmacokinetics of genistein and daidzein contrasting the sources and doses of isoflavones when administered three times daily, including a possible advantage for increasing serum concentrations of isoflavones from consuming soy foods relative to isoflavone supplements.