phytoestrogens and Glucose-Intolerance

Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 1; Feces; Female; Gastrointestinal Microbiome; Gastrointestinal Tract; Genistein; Glucose Intolerance; Homeostasis; Hyperglycemia; Insulin; Male; Mice; Mice, Inbred NOD; Phytoestrogens; Sequence Analysis, DNA

Previous studies have examined whether phytoestrogens affect glucose and lipid metabolism. However, data on children and adolescents are still limited, with most of the evidence pertaining to one phytoestrogen, namely genistein. To investigate the effect of six phytoestrogens [daidezin, enterodiol, enterolactone, equol, genistein and O-Desmethylangolensin (O-DMA)] on metabolic disturbances among youths, a cross-sectional study was conducted using a sample of 2,429 children and adolescents, 6-18 years, from the 2009-2010 National Health and Nutrition Examination Surveys (NHANES). The main outcome measures were body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C) and total cholesterol (TC), fasting glucose, triglycerides and glycohemoglobin. SBP was inversely related to enterolactone and equol. Triglycerides were inversely related to daidezin, equol, genistein and O-DMA. Whereas TC and LDL-C were inversely related to equol, an HDL-C was inversely related to genistein and O-DMA. Whereas fasting glucose was associated with enterodiol (β = 0.33, 95% CI: 0.028, 0.63), a positive relationship was observed between enterodiol and risk of HDL-C ≥ 35 mg dl(-1) (β = 0.04, 95% CI: 0.01, 0.07). In conclusion, certain phytoestrogens may contribute either positively or negatively to disturbances in lipid and glucose metabolism. Large prospective cohort studies are needed to confirm our study findings.

Topics: Adolescent; Blood Glucose; Blood Pressure; Body Mass Index; Child; Cholesterol, HDL; Cholesterol, LDL; Cross-Sectional Studies; Dyslipidemias; Equol; Genistein; Glucose; Glucose Intolerance; Humans; Lipid Metabolism; Phytoestrogens; Triglycerides

Tissue-selective estrogen complex (TSEC), which combines a selective estrogen receptor modulator (SERM) with one or more estrogens, is a novel approach to menopausal therapy. It has been demonstrated that the phytoestrogen genistein (GEN) exhibits mixed estrogen receptor agonist and antagonist activity, suggesting that GEN may have potential for use as a natural SERM. We evaluated, for the first time, the effects of GEN, conjugated estrogens (CE), and their pairing effects as a TSEC treatment on estrogen-induced endometrial hyperplasia and metabolic dysfunction in ovariectomized (OVX) mice fed a high-fat diet. CE replacement prevented fat accumulation in the adipose tissue and liver, improved glucose homeostasis, and induced endometrial hyperplasia in OVX mice. GEN at 100 mg/kg showed CE mimetic effects in preventing ovariectomy-induced metabolic dysfunctions without endometrial stimulation. Combination treatments with CE and GEN prevented metabolic dysfunctions more strongly than CE alone, but at both low and high doses, GEN did not reverse CE-induced endometrial hyperplasia. In addition, we found that in a TSEC regimen, a typical SERM raloxifene maintains the metabolic benefits of CE while simultaneously protecting the endometrium in OVX mice. These findings indicate that GEN acts as an estrogen agonist in metabolic regulation, but has no SERM function in the uteri of OVX mice.

Topics: Adiposity; Animals; Diet, High-Fat; Dietary Supplements; Endometrial Hyperplasia; Endometrium; Estrogen Replacement Therapy; Estrogens; Estrogens, Conjugated (USP); Female; Genistein; Glucose Intolerance; Liver; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Ovariectomy; Overweight; Phytoestrogens; Raloxifene Hydrochloride; Random Allocation; Selective Estrogen Receptor Modulators

Curcuma comosa Roxb. (C. comosa) is an indigenous medicinal herb that has been used in Thailand as a dietary supplement to relieve postmenopausal symptoms. Recently, a novel phytoestrogen, (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol or compound 049, has been isolated and no study thus far has investigated the role of C. comosa in preventing metabolic alterations occurring in estrogen-deprived state. The present study investigated the long-term effects (12 weeks) of C. comosa hexane extract and compound 049 on insulin resistance in prolonged estrogen-deprived rats.. Female Sprague-Dawley rats were ovariectomized (OVX) and treated with C. comosa hexane extract (125 mg, 250 mg, or 500 mg/kg body weight (BW)) and compound 049 (50 mg/kg BW) intraperitoneally three times per week for 12 weeks. Body weight, food intake, visceral fat weight, uterine weight, serum lipid profile, glucose tolerance, insulin action on skeletal muscle glucose transport activity, and GLUT-4 protein expression were determined.. Prolonged ovariectomy resulted in dyslipidemia, impaired glucose tolerance and insulin-stimulated skeletal muscle glucose transport, as compared to SHAM. Treatment with C. comosa hexane extract and compound 049, three times per week for 12 weeks, markedly reduced serum total cholesterol and low-density lipoprotein levels, improved insulin sensitivity and partially restored uterine weights in ovariectomized rats. In addition, compound 049 or high doses of C. comosa hexane extract enhanced insulin-mediated glucose uptake in skeletal muscle and increased muscle GLUT-4 protein levels.. Treatment with C. comosa and its diarylheptanoid derivative improved glucose and lipid metabolism in estrogen-deprived rats, supporting the traditional use of this natural phytoestrogen as a strategy for relieving insulin resistance and its related metabolic defects in postmenopausal women.

Topics: Animals; Biological Transport; Cholesterol; Cholesterol, LDL; Curcuma; Diarylheptanoids; Dyslipidemias; Estrogens; Female; Glucose; Glucose Intolerance; Glucose Transporter Type 4; Heptanol; Insulin; Insulin Resistance; Muscle, Skeletal; Organ Size; Ovariectomy; Phytoestrogens; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley; Uterus