-
1.
Soy Isoflavone Supplementation Increases Long Interspersed Nucleotide Element-1 (LINE-1) Methylation in Head and Neck Squamous Cell Carcinoma.
Rozek, LS, Virani, S, Bellile, EL, Taylor, JMG, Sartor, MA, Zarins, KR, Virani, A, Cote, C, Worden, FP, Mark, MEP, et al
Nutrition and cancer. 2019;(5):772-780
-
-
Free full text
-
Abstract
AIM: Soy isoflavones have been suggested as epigenetic modulating agents with effects that could be important in carcinogenesis. Hypomethylation of LINE-1 has been associated with head and neck squamous cell carcinoma (HNSCC) development from oral premalignant lesions and with poor prognosis. To determine if neoadjuvant soy isoflavone supplementation could modulate LINE-1 methylation in HNSCC, we undertook a clinical trial. METHODS Thirty-nine patients received 2-3 weeks of soy isoflavone supplements (300 mg/day) orally prior to surgery. Methylation of LINE-1, and 6 other genes was measured by pyrosequencing in biopsy, resection, and whole blood (WB) specimens. Changes in methylation were tested using paired t tests and ANOVA. Median follow up was 45 months. RESULTS LINE-1 methylation increased significantly after soy isoflavone (P < 0.005). Amount of change correlated positively with days of isoflavone taken (P = 0.04). Similar changes were not seen in corresponding WB samples. No significant changes in tumor or blood methylation levels were seen in the other candidate genes. CONCLUSION This is the first demonstration of in vivo increases in tissue-specific global methylation associated with soy isoflavone intake in patients with HNSCC. Prior associations of LINE-1 hypomethylation with genetic instability, carcinogenesis, and prognosis suggest that soy isoflavones maybe potential chemopreventive agents in HNSCC.
-
2.
Pharmacokinetics and Safety of DW1029M, a Botanical Drug for the Treatment of Diabetic Nephropathy, Following Single Doses in Healthy Subjects.
Kim, Y, Jeon, JY, Kim, EY, Lim, CH, Jang, HB, Kim, MG
Clinical pharmacology in drug development. 2017;(5):499-507
Abstract
DW1029M is a botanical extract of Morus albalinne root bark and Puerariae radix that is used for the treatment of diabetic nephropathy. This study evaluated the safety and pharmacokinetics of DW1029M following its administration in healthy Korean subjects. We conducted a randomized, open-label, single-dose, crossover phase 1 clinical study. During each period, subjects received 300, 600, or 1200 mg oral doses of DW1029M. Plasma concentrations of puerarin, daidzin, and daidzein were analyzed using a liquid chromatography-tandem mass spectrometry. Six healthy male subjects completed the study. The maximum concentration of the drug in the plasma (Cmax ) and area under the plasma drug concentration-time curve to the last measurable concentration (AUClast ) for puerarin, daidzin, and daidzein were assessed after oral administration of DW1029M. No serious adverse events or clinically or statistically significant adverse events associated with any of the drug levels were observed. The results of the measurement of vital signs, electrocardiogram, laboratory tests, and physical examinations indicated that no clinically significant changes occurred during this study. The DW1029M tablet was safe and well tolerated over a single dose range of 300-1200 mg. This pharmacokinetic study of a botanical drug may aid in the development of DW1029M.
-
3.
Profiling of Phenolic Metabolites in Feces from Menopausal Women after Long-Term Isoflavone Supplementation.
Guadamuro, L, Jiménez-Girón, AM, Delgado, S, Flórez, AB, Suárez, A, Martín-Álvarez, PJ, Bartolomé, B, Moreno-Arribas, MV, Mayo, B
Journal of agricultural and food chemistry. 2016;(1):210-6
Abstract
Phenolic compounds were screened by UPLC-ESI-MS/MS in the feces of 15 menopausal women before and after long-term isoflavone treatment. In total, 44 compounds were detected. Large intertreatment, interindividual, and intersample variations were observed in terms of the number of compounds and their concentration. Four compounds, the aglycones daidzein and genistein and the daidzein derivatives dihydrodaidzein and O-desmethylangolensin, were associated with isoflavone metabolism; these were identified only after the isoflavone treatment. In addition, 4-ethylcatechol, 3-hydroxyphenylacetic acid, and 3-phenylpropionic acid differed significantly in pre- and postintervention samples, whereas the concentration of 4-hydroxy-5-phenylvaleric acid showed a trend toward increasing over the treatment. The phenolic profiles of equol-producing and -non-producing groups were similar, with the exceptions of 3-hydroxyphenylacetic acid and 3-phenylpropionic acid, which showed higher concentrations in equol-non-producing women. These findings may help to trace isoflavone-derived metabolites in feces during isoflavone interventions and to design new studies to address their biological effects.
-
4.
Consumption of soy isoflavone enriched bread in men with prostate cancer is associated with reduced proinflammatory cytokines and immunosuppressive cells.
Lesinski, GB, Reville, PK, Mace, TA, Young, GS, Ahn-Jarvis, J, Thomas-Ahner, J, Vodovotz, Y, Ameen, Z, Grainger, E, Riedl, K, et al
Cancer prevention research (Philadelphia, Pa.). 2015;(11):1036-44
-
-
Free full text
-
Abstract
We hypothesized that soy phytochemicals may have immunomodulatory properties that may affect prostate carcinogenesis and progression. A randomized, phase II trial was conducted in 32 patients with prostate cancer with asymptomatic biochemical recurrence but no measurable disease on standard staging studies. Patients were randomized to two slices of soy bread (34 mg isoflavones/slice) or soy bread containing almond powder daily as a source of β-glucosidase. Flow cytometry and bioplex assays were used to measure cytokines or immune cell phenotype in blood at baseline (day 0) and following intervention (day 56). Adequate blood samples were available at enrollment and day 56 and evaluated. Multiple plasma cytokines and chemokines were significantly decreased on day 56 versus baseline. Subgroup analysis indicated reduced TH1 (P = 0.028) and myeloid-derived suppressor cell (MDSC)-associated cytokines (P = 0.035). TH2 and TH17 cytokines were not significantly altered. Phenotypic analysis revealed no change in CD8(+) or CD4(+) T cells but showed increased CD56(+) natural killer (NK) cells (P = 0.038). The percentage of cells with a T regulatory cell phenotype (CD4(+)CD25(+)FoxP3(+)) was significantly decreased after 56 days of soy bread (P = 0.0136). Significantly decreased monocytic (CD33(+)HLADR(neg)CD14(+)) MDSC were observed in patients consuming soy bread (P = 0.0056). These data suggest that soy bread modulates systemic soluble and cellular biomarkers consistent with limiting inflammation and suppression of MDSCs. Additional studies to elucidate impact on the carcinogenic process or as a complement to immune-based therapy are required.
-
5.
Effect of whole soy and purified isoflavone daidzein on renal function--a 6-month randomized controlled trial in equol-producing postmenopausal women with prehypertension.
Liu, ZM, Ho, SC, Chen, YM, Tang, N, Woo, J
Clinical biochemistry. 2014;(13-14):1250-6
Abstract
OBJECTIVES The aim of the study was to examine the long-term effect of commonly used whole soy foods (soy flour) and purified daidzein (one major isoflavone and the precursor of equol) on renal function among prehypertensive postmenopausal women who are also equol producers, a population most likely to benefit from soy intervention. DESIGN AND METHODS This was a 6-month double-blind, randomized, placebo-controlled trial. Two hundred seventy eligible Chinese women were randomized to either one of the three treatments: 40 g soy flour (whole soy group), 40 g low-fat milk powder + 63 mg daidzein (daidzein group) or 40 g low-fat milk powder (placebo group) daily each for 6 months. Fasting blood and 24-h urine samples were collected at the beginning and end of trial. Serum creatinine, cystatin C, urea, angiotensin-converting enzyme, minerals and 24-h urinary creatinine and minerals were analyzed. Estimated glomerular filtration rate (eGFR) was calculated with the Cockcroft-Gault and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. RESULTS Two hundred fifty-three subjects completed the study according to the protocol. Urinary isoflavones indicated good compliance of participants. No significant changes were observed in most of renal parameters, however, there was a less decrease in eGFRcockcroft in 6-month change (p=0.044) and %change (p=0.031) with whole soy intake relative to milk placebo. Subgroup analysis among women with lowered renal function suggested whole soy consumption tended to improve markers of renal function relative to control. CONCLUSIONS Six-month consumption of whole soy tended to have a modest improvement of renal function in prehypertensive postmenopausal women with lowered renal function. Future trials in subjects with more declined renal function are necessary. TRIAL REGISTRATION The trial was registered in ClinicalTrials.gov with identifier of NCT01270737. (URL: http://clinicaltrials.gov/ct2/show/NCT01270737).
-
6.
Soy isoflavone supplementation for breast cancer risk reduction: a randomized phase II trial.
Khan, SA, Chatterton, RT, Michel, N, Bryk, M, Lee, O, Ivancic, D, Heinz, R, Zalles, CM, Helenowski, IB, Jovanovic, BD, et al
Cancer prevention research (Philadelphia, Pa.). 2012;(2):309-19
-
-
Free full text
-
Abstract
Soy isoflavone consumption may protect against breast cancer development. We conducted a phase IIB trial of soy isoflavone supplementation to examine its effect on breast epithelial proliferation and other biomarkers in the healthy high-risk breast. One hundred and twenty-six consented women underwent a random fine-needle aspiration (rFNA); those with 4,000 or more epithelial cells were randomized to a double-blind 6-month intervention of mixed soy isoflavones (PTIG-2535) or placebo, followed by repeat rFNA. Cells were examined for Ki-67 labeling index and atypia. Expression of 28 genes related to proliferation, apoptosis, and estrogenic effect was measured using quantitative reverse transcriptase PCR. Hormone and protein levels were measured in nipple aspirate fluid (NAF). All statistical tests were two-sided. Ninety-eight women were evaluable for Ki-67 labeling index. In 49 treated women, the median Ki-67 labeling index was 1.18 at entry and 1.12 post intervention, whereas in 49 placebo subjects, it was 0.97 and 0.92 (P for between-group change: 0.32). Menopausal stratification yielded similar results between groups, but within premenopausal soy-treated women, Ki-67 labeling index increased from 1.71 to 2.18 (P = 0.04). We saw no treatment effect on cytologic atypia or NAF parameters. There were significant increases in the expression of 14 of 28 genes within the soy, but not the control group, without significant between-group differences. Plasma genistein values showed excellent compliance. A 6-month intervention of mixed soy isoflavones in healthy, high-risk adult Western women did not reduce breast epithelial proliferation, suggesting a lack of efficacy for breast cancer prevention and a possible adverse effect in premenopausal women.
-
7.
The effect of soy-derived isoflavones over hot flushes, menopausal symptoms and mood in climacteric women with increased body mass index.
Chedraui, P, San Miguel, G, Schwager, G
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2011;(5):307-13
Abstract
BACKGROUND Risk-benefit issues raised after the WHI have significantly increased the use of alternative treatments for the menopause. Despite this, data regarding the effect of soy isoflavones over mood and menopausal symptoms in high risk populations is still lacking. OBJECTIVE To evaluate the effect of soy derived isoflavones over hot flushes, menopausal symptoms and mood in climacteric women with increased body mass index (BMI). METHODS Fifty symptomatic climacteric women aged 40 to 59 with increased BMI (≥ 25) were recruited to receive oral 100 mg/day of soy derived isoflavones (Climasoy) for 3 months. Hot flushes (frequency/intensity), menopausal symptoms (Menopause Rating Scale [MRS]) and mood (Hamilton Depressive Rating Scale [HDRS]) were evaluated at baseline and at 90 days. RESULTS A total of 45 women completed the study. After 3 months of soy isoflavone supplementation hot flushes significantly decreased in percentage, number and severity (100% to 31.1%; 3.9 ± 2.3 to 0.4 ± 0.8 and 2.6 ± 0.9 to 0.4 ± 0.8, respectively, p < 0.001). MRS scores (total and for subscales) reflecting general menopausal symptoms also significantly decreased compared to baseline. Regarding mood, after three months total HDRS scores and the rate of women presenting depressed mood (scores ≥ 8) significantly decreased (16.3 ± 5.4 to 6.9 ± 5.2 and 93.3% to 28.9%, respectively, p < 0.05). There was no effect on blood pressure levels or BMI values after treatment. CONCLUSION In this high risk climacteric population, soy derived isoflavone treatment improved mood as well as vasomotor and general menopausal symptoms. More research is required to determine if the positive effect over mood is a direct or an indirect one through hot flush alleviation.
-
8.
Oxidative and antioxidant status in plasma of runners: effect of oral supplementation with natural antioxidants.
Di Giacomo, C, Acquaviva, R, Sorrenti, V, Vanella, A, Grasso, S, Barcellona, ML, Galvano, F, Vanella, L, Renis, M
Journal of medicinal food. 2009;(1):145-50
Abstract
Aerobic exercise increases free radical production as a consequence of enhanced oxygen consumption. If free radical formation exceeds antioxidant capacity, lipids, proteins, and DNA may be oxidized. Oxidative stress is widely recognized as a factor in many degenerative human diseases. The role of dietary antioxidants in protection against disease is a topic of continuing interest. In fact, there is epidemiological evidence correlating a higher intake of nutrients possessing antioxidant abilities with a lower incidence of various human diseases. This study was directed at investigating whether changes in plasma antioxidant capacity and oxidative stress markers occur in voluntary wheel runners, before and after oral supplementation with lycopene and isoflavones. For this purpose, plasma antioxidant capacity and oxidative stress markers were assessed in long distance runners at the end of a 60-minute run. Comparisons were made between runners before and after 60 days of supplementation with lycopene and isoflavones. DNA damage in blood cells of the same samples was also evaluated by comet assay. This investigation shows that oral supplementation with lycopene and soy-derived isoflavones significantly reduced lipid peroxidation and enhanced plasma nonproteic antioxidant defense.
-
9.
Phase II trial of isoflavone in prostate-specific antigen recurrent prostate cancer after previous local therapy.
Pendleton, JM, Tan, WW, Anai, S, Chang, M, Hou, W, Shiverick, KT, Rosser, CJ
BMC cancer. 2008;:132
Abstract
BACKGROUND Data exist that demonstrate isoflavones' potent antiproliferative effects on prostate cancer cells. We evaluated the efficacy of isoflavone in patients with PSA recurrent prostate cancer after prior therapy. We postulated that isoflavone therapy would slow the rate of rise of serum PSA. METHODS Twenty patients with rising PSA after prior local therapy were enrolled in this open-labeled, Phase II, nonrandomized trial (Trial registration # NCT00596895). Patients were treated with soy milk containing 47 mg of isoflavonoid per 8 oz serving three times per day for 12 months. Serum PSA, testosterone, lipids, isoflavone levels (genistein, daidzein, and equol), and quality of life (QOL) were measured at various time points from 0 to 12 months. PSA outcome was evaluated. RESULTS Within the mixed regression model, it was estimated that PSA had increased 56% per year before study entry and only increased 20% per year for the 12-month study period (p = 0.05). Specifically, the slope of PSA after study entry was significantly lower than that before study entry in 6 patients and the slope of PSA after study entry was significantly higher than before study entry in 2 patients. For the remaining 12 patients, the change in slope was statistically insignificant. Nearly two thirds of the patients were noted to have significant levels of free equol in their serum while on therapy. CONCLUSION Dietary intervention with isoflavone supplementation may have biologic activity in men with biochemical recurrent prostate cancer as shown by a decline in the slope of PSA. This study may lend support to the literature that nutritional supplements have biologic activity in prostate cancer and therefore, further studies with these agents in randomized clinical trials should be encouraged.
-
10.
Proteomic biomarkers of peripheral blood mononuclear cells obtained from postmenopausal women undergoing an intervention with soy isoflavones.
Fuchs, D, Vafeiadou, K, Hall, WL, Daniel, H, Williams, CM, Schroot, JH, Wenzel, U
The American journal of clinical nutrition. 2007;(5):1369-75
-
-
Free full text
-
Abstract
BACKGROUND The incidence of cardiovascular diseases increases after menopause, and soy consumption is suggested to inhibit disease development. OBJECTIVE The objective was to identify biomarkers of response to a dietary supplementation with an isoflavone extract in postmenopausal women by proteome analysis of peripheral blood mononuclear cells. DESIGN The study with healthy postmenopausal woman was performed in a placebo-controlled sequential design. Peripheral mononuclear blood cells were collected from 10 volunteers after 8 wk of receiving daily 2 placebo cereal bars and after a subsequent 8 wk of intervention with 2 cereal bars each providing 25 mg of isoflavones. The proteome of the cells was visualized after 2-dimensional gel electrophoresis, and peptide mass fingerprinting served to identify proteins that by the intervention displayed altered protein concentrations. RESULTS Twenty-nine proteins were identified that showed significantly altered expression in the mononuclear blood cells under the soy-isoflavone intervention, including a variety of proteins involved in an antiinflammatory response. Heat shock protein 70 or a lymphocyte-specific protein phosphatase and proteins that promote increased fibrinolysis, such as alpha-enolase, were found at increased intensities, whereas those that mediate adhesion, migration, and proliferation of vascular smooth muscle cells, such as galectin-1, were found at reduced intensities after soy extract consumption. CONCLUSION Proteome analysis identified in vivo markers that respond to a dietary intervention with isoflavone-enriched soy extract in postmenopausal women. The nature of the proteins identified suggests that soy isoflavones may increase the antiinflammatory response in blood mononuclear cells that might contribute to the atherosclerosis-preventive activities of a soy-rich diet.