vitamin-b-12 and Polycystic-Ovary-Syndrome

This review provides a general overview of the literature on B vitamins and fertility, as well as summarizes the evidence concerning B vitamin supplementation and fertility among polycystic ovary syndrome (PCOS) women.. Studies among women conceiving with and without medical assistance provide strong evidence for a beneficial effect of B vitamins, particularly folate and vitamin B12, on fecundability and fertility. Moreover, recent work suggests that effects may be even more pronounced among women with menstrual cycle dysfunction (a common symptom of PCOS). Among PCOS women, intervention studies have demonstrated that folic acid supplementation may reduce homocysteine levels, potentially improve women's metabolic profiles, and possibly ameliorate some hallmark features of PCOS. Although none of these intervention studies have included fertility endpoints, it is possible that by reducing homocysteine levels (or other clinical/biochemical features) in PCOS women, there may be a downstream improvement in fertility outcomes.. There is growing evidence folate (and possibly vitamin B12) supplementation may be beneficial to fertility in women. Although most studies have not exclusively focused on women with PCOS, there is biological plausibility and some evidence that B vitamin supplementation may be even more important for improving reproductive health outcomes in PCOS women.

Topics: Female; Fertility; Folic Acid; Homocysteine; Humans; Polycystic Ovary Syndrome; Vitamin B 12; Vitamin B Complex

Randomized controlled trials and observational studies have yielded inconsistent results on the effects of metformin on vitamin B12 reduction. We therefore performed a systematic review to analyze the effects of metformin on vitamin B12 concentration.. PubMed, Medline, Embase, and the Cochrane central registry of controlled trials were searched to identify randomized controlled trials and observational studies exploring the association between metformin and vitamin B12 concentration in patients with type 2 diabetes mellitus or polycystic ovary syndrome. The main outcome measure was changes in serum vitamin B12 concentration after 6-208 weeks of treatment with metformin, as compared with placebo or other anti-hyperglycemic therapy.. Six randomized controlled trials met the inclusion criteria. Serum vitamin B12 concentrations were significantly lower in patients treated with metformin than in those who received placebo or rosiglitazone (mean difference [MD], -53.93 pmol/L; 95% confidence interval [CI], -81.44 to -26.42 pmol/L, P = 0.0001). Subgroup analysis identified four trials in which patients received a lower dose of metformin (<2000 mg/d) and two in which they received a higher dose (≥2000 mg/d), with MDs in vitamin B12 concentration after metformin treatment of -37.99 pmol/L (95% CI, -57.44 to -18.54 pmol/L, P = 0.0001) and -78.62 pmol/L (95% CI, -106.37 to -50.86 pmol/L, P<0.00001), respectively.. The reduction of vitamin B12 may be induced by metformin in a dose dependent manner.

Topics: Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Metformin; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic; Treatment Outcome; Vitamin B 12

Treatment with the anti-diabetic drug metformin is followed by a decline in plasma cobalamin, but it is unsettled whether this denotes an impaired cobalamin status. This study has explored changes in the markers of cobalamin status in women with Polycystic Ovary Syndrome treated with metformin (1.5-2.5 g per day) (n = 29) or placebo (n = 23) for six months. Serum samples were collected before and after two, four, and six months of treatment. We found serum cobalamin to decline and reach significant lower levels after six months of treatment (p = 0.003). Despite the decline in serum cobalamin, we observed no reductions in the physiological active part of cobalamin bound to transcobalamin (holotranscobalamin), or increase in the metabolic marker of cobalamin status, methylmalonic acid. Instead, the non-functional part of circulating cobalamin bound to haptocorrin declined (p = 0.0009). Our results have two implications: The data questions whether metformin treatment induces an impaired cobalamin status in PCOS patients, and further suggests that serum cobalamin is a futile marker for judging cobalamin status in metformin-treated patients.

Topics: Adolescent; Adult; Biomarkers; Body Mass Index; Cohort Studies; Cross-Over Studies; Female; Humans; Hypoglycemic Agents; Metformin; Middle Aged; Polycystic Ovary Syndrome; Vitamin B 12; Young Adult

Women with polycystic ovary syndrome have elevated homocysteine levels. Elevated homocysteine levels associate with pregnancy complications. Women with polycystic ovary syndrome are often treated with metformin, a drug that may increase homocysteine levels. Hence, we investigated the effect of metformin treatment on homocysteine levels in nonpregnant and pregnant women with polycystic ovary syndrome.. Two prospective randomized placebo-controlled studies included women with polycystic ovary syndrome in a university hospital setting. Sixty-three infertile women were treated with metformin 1,000 mg bid or placebo for 16 weeks and 38 pregnant women with metformin 850 mg bid or placebo from the first trimester and throughout pregnancy. All the women had polycystic ovary syndrome and all participants received diet and lifestyle advice, and oral folate and vitamin B12 substitution, and a daily oral multivitamin tablet. The main outcome measures were serum levels of homocysteine, folate, and vitamin B12.. Serum homocysteine levels were unaffected by metformin treatment both in nonpregnant and pregnant women with polycystic ovary syndrome. However, in nonpregnant women both serum folate and vitamin B12 levels decreased with treatment. At inclusion in nonpregnant women, serum homocysteine levels associated negatively with serum levels of folate and methyl malonic acid and positively with free testosterone index. No such associations were seen in pregnant women.. Metformin treatment in women with polycystic ovary does not increase serum homocysteine levels in the nonpregnant or the pregnant state.

Topics: Female; Folic Acid; Homocysteine; Humans; Hypoglycemic Agents; Metformin; Methylenetetrahydrofolate Reductase (NADPH2); Polycystic Ovary Syndrome; Polymorphism, Genetic; Pregnancy; Pregnancy Complications; Prospective Studies; Testosterone; Vitamin B 12

This study was conducted to evaluate the effects of two different oral contraceptives (OCs) on homocysteine (Hcy) metabolism in 20 women with polycystic ovary syndrome (PCOS).. Women were randomly allocated to receive either the biphasic OC containing 40/30 mug ethynylestradiol (EE)+25/125 mug desogestrel (DSG; n=10) or the monophasic OC containing 35 mug EE and 2 mg cyproterone acetate (CPA; n=10). Investigations were performed before and after 6 months of treatment. Fasting vitamin B(12), folate, Hcy and insulin sensitivity (SI), and glucose utilization independent of insulin (Sg), by the minimal model method, were evaluated.. Folate and vitamin B(12) were not significantly modified by either OC. EE/DSG decreased SI (2.53+/-0.35 vs. 1.68+/-0.45; p<.05), without modifying Hcy (9.54+/-0.7 micromol/L vs. 9.18+/-0.6 micromol/L). EE/CPA improved SI (1.47+/-0.38 vs. 3.27+/-0.48; p<.04) and decreased Hcy (9.8+/-1.9 micromol/L vs. 7.9+/-0.9 micromol/L; p<.05). This study indicates that in women with PCOS, EE/CPA, but not EE/DSG, improves IS and decreases fasting Hcy.

Topics: Adult; Blood Glucose; Contraceptives, Oral; Cyproterone Acetate; Desogestrel; Ethinyl Estradiol; Female; Folic Acid; Homocysteine; Humans; Insulin; Insulin Resistance; Polycystic Ovary Syndrome; Vitamin B 12

Elevated levels of plasma homocysteine (Hcy) have been implicated as a significant risk factor for cardiovascular disease. Although long-term treatment with metformin can increase Hcy levels in patients with type II diabetes mellitus or coronary heart disease, it is becoming an increasingly accepted and widespread medication in polycystic ovary syndrome (PCOS). In the literature, only one study has demonstrated that metformin increases Hcy levels in PCOS patients, but the effect of other insulin sensitizers on Hcy levels have not been reported previously in women with PCOS. We aimed to assess the effects of metformin and rosiglitazone on plasma Hcy levels in patients with PCOS.. Thirty women were randomized to two groups: 15 women in group 1 received 850 mg of metformin twice daily for 3 months. In group 2, 15 women received 4 mg of rosiglitazone for 3 months. In both groups, body mass index, menstrual pattern, and plasma total Hcy, insulin, glucose and lipid metabolism parameters were recorded at baseline and at 3 months.. Hcy levels increased from 8.93+/-0.49 to 11.26+/-0.86 micromol/l (P = 0.002) and from 10.70+/-0.86 to 12.36+/-0.81 micromol/l (P = 0.01) in the metformin and rosiglitazone groups, respectively. Apolipoprotein (Apo) A1 levels increased from 127.10+/-6.85 to 145.7+/-7.18 mg/dl (P = 0.018) in the metformin group. Total cholesterol (total-C), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein (a) and Apo B levels decreased in the metformin group, but the change was not significant. Total-C levels decreased from 161.15+/-8.94 to 150.23+/-8.73 mg/dl (P = 0.026), HDL-C decreased from 43.13+/-2.65 to 39.15+/-2.52 mg/dl (P = 0.005) and LDL-C levels decreased from 93.83+/-6.06 to 80.7+/-2.30 mg/dl (P = 0.021) in the rosiglitazone group.. Treatment with insulin sensitizers in women with PCOS may lead to increases in Hcy levels.

Topics: Adult; Anovulation; Blood Glucose; Body Weight; Female; Folic Acid; Homocysteine; Humans; Hypoglycemic Agents; Insulin Resistance; Lipids; Luteinizing Hormone; Metformin; Polycystic Ovary Syndrome; Rosiglitazone; Testosterone; Thiazolidinediones; Vitamin B 12

Topics: Adolescent; Female; Humans; Polycystic Ovary Syndrome; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Diabetes Complications; Diabetes Mellitus, Type 2; Disease Progression; Female; Humans; Insulin; Ischemia; Male; Metformin; Models, Biological; Models, Theoretical; Polycystic Ovary Syndrome; Prostatic Neoplasms; Vitamin B 12

To evaluate whether the administration of metformin exerts any effects on serum homocysteine (Hcy) levels in patients with polycystic ovary syndrome (PCOS) and whether supplementation with folate enhances the positive effects of metformin on the structure and function of the vascular endothelium.. A total of 50 patients affected by PCOS, without additional metabolic or cardiovascular diseases, were enrolled in a prospective nonrandomized placebo-controlled double-blind clinical study. They were grouped into two treatment arms that were matched for age and BMI. Patients were treated with a 6-month course of metformin (1,700 mg daily) plus folic acid (400 microg daily; experimental group, n = 25) or placebo (control group, n = 25). Complete hormonal and metabolic patterns, serum Hcy, folate, vitamin B12, endothelin-1 levels, brachial artery diameter at the baseline (BAD-B) and after reactive hyperemia (BAD-RH), flow-mediated dilation, and intima-media thickness in both common carotid arteries were evaluated.. After treatment, a significant increase in serum Hcy levels was observed in the control group compared with the baseline values and the experimental group. A beneficial effect was observed in the concentrations of BAD-B, BAD-RH, flow-mediated dilation, intima-media thickness, and serum endothelin-1 in both groups. However, the results were improved more significantly in the experimental group than in the control subjects.. Metformin exerts a slight but significant deleterious effect on serum Hcy levels in patients with PCOS, and supplementation with folate is useful to increase the beneficial effect of metformin on the vascular endothelium.

Topics: Adult; Body Mass Index; Brachial Artery; Double-Blind Method; Endothelin-1; Endothelium, Vascular; Exercise; Female; Folic Acid; Homocysteine; Humans; Hypoglycemic Agents; Leisure Activities; Metformin; Placebos; Polycystic Ovary Syndrome; Tunica Intima; Tunica Media; Vasodilation; Vitamin B 12; Waist-Hip Ratio

A poor quality of oocytes and embryos and a low fertilization rate have been found in polycystic ovary syndrome (PCOS) patients. An inverse association between follicular fluid homocysteine (Hcy) levels and oocyte and embryo quality has also been demonstrated. We examined the relationship between follicular fluid Hcy concentrations and oocyte and embryo quality in PCOS patients undergoing assisted reproduction.. Fifty-two PCOS patients were included in the study, and underwent GnRH agonist/recombinant FSH treatment. The Hcy, folate, vitamin B(12), malonyldialdehyde (MDA) and estradiol (E(2)) levels were measured in follicular fluid from single oocytes at time of retrieval. One follicle per ovary was sampled and 94 were analysed. Plasma hormones were also measured. Oocytes and embryos were graded (1-3) using standard approaches.. The concentrations of Hcy, E(2), vitamin B(12), folate and MDA in plasma were higher than in follicular fluid (all P < 0.001). Significant differences were observed in follicular Hcy levels between Grade 3 and Grade 2 oocytes (P < 0.001). Hcy levels were lower in Grade 1-2 embryos than that in Grade 3 embryos; follicular fluid vitamin B(12) levels were lower in patients showing high concentrations of follicular fluid Hcy (P < 0.01). The follicular fluid Hcy levels were negatively correlated with follicular fluid vitamin B(12) (r = -0.44), folate (r = -0.68) and fertilization rate (r = -0.85), and positively correlated with follicular fluid MDA (r = 0.51).. Concentrations of Hcy in follicular fluid on the dOPU may be a useful marker for fertilization rate, and oocyte and embryo quality in PCOS patients undergoing assisted reproduction.

Topics: Adult; Embryo, Mammalian; Estradiol; Female; Folic Acid; Follicle Stimulating Hormone; Follicular Fluid; Homocysteine; Humans; Infertility, Female; Malondialdehyde; Oocytes; Ovulation Induction; Polycystic Ovary Syndrome; Reproductive Techniques, Assisted; Vitamin B 12

Polycystic ovary syndrome (PCOS) shares some or most components of metabolic cardiovascular syndrome, manifested by abdominal obesity, insulin resistance, dyslipidaemia and atherosclerosis. It has been previously demonstrated that folate and vitamin B(12) treatment improved insulin resistance in patients with metabolic syndrome. This study first investigated whether PCOS patients have lower or higher vitamin B(12), folate and homocysteine concentrations when compared with healthy, age and body mass index matched controls, and, then examined associations between vitamin B(12), folate, homocysteine and insulin resistance and obesity in PCOS patients. Homocysteine concentrations and homeostasis model assessment index were higher, whereas concentrations of vitamin B(12) were lower in PCOS patients with insulin resistance compared with those without insulin resistance. Serum vitamin B(12) concentrations were significantly lower in obese PCOS women in comparison with obese control women (P < 0.05). Fasting insulin, insulin resistance and homocysteine are independent determinants of serum vitamin B(12) concentrations in PCOS patients. Insulin resistance, obesity, and elevated homocysteine were associated with lower serum vitamin B(12) concentrations in PCOS patients.

Topics: Adult; Case-Control Studies; Female; Folic Acid; Homocysteine; Humans; Insulin Resistance; Obesity; Polycystic Ovary Syndrome; Vitamin B 12

The purpose of this study was to determine whether polycystic ovary syndrome (PCOS) and nonclassic 21-hydroxylase deficiency (CAH) are related to hyperhomocysteinemia, and to investigate if there is a correlation between homocysteine levels and insulin sensitivity in women with PCOS and CAH. Fifty patients with PCOS, 50 patients with CAH and 25 control women were included in the study. Blood samplings were performed in the early follicular phase for measuring hormone profile, Vitamin B(12), folate, homocysteine levels and fasting blood glucose. Ovulatory status was assessed with timed serum progesterone measurements. Homeostasis model assessment-insulin resistance (HOMA-IR) was calculated as a measure of insulin resistance. Mean homocysteine levels were found as (8.9 + 1.9 micromol/l and 17.7 + 3.6 micromol/l) in the normal group and PCOS respectively (p<0.001), but there was no statistical significance between nonclassic 21-hydroxylase deficiency (9.0 + 2.2 micromol/l) and control group. Most of the patients in PCOS group (35 of 50) were significantly insulin resistant. However, there was no insulin resistant patient in CAH or control group. When we compare the two subgroups of PCOS women, the patients with insulin resistance had significantly higher homocysteine levels than the ones who were not insulin resistant. There were positive correlations among serum homocysteine, insulin and androgen levels in PCOS patients. There were no correlations among these parameters in CAH and control groups. Increased homocysteine levels may contribute to increased cardiovascular disease risk in patients with PCOS. The reason for hyperhomocysteinemia seems to be related to insulin resistance but not high androgen levels.

Topics: Adrenal Hyperplasia, Congenital; Adult; Blood Glucose; Cholesterol; Estradiol; Female; Follicle Stimulating Hormone; Homocysteine; Humans; Insulin Resistance; Luteinizing Hormone; Polycystic Ovary Syndrome; Progesterone; Statistics, Nonparametric; Testosterone; Thyrotropin; Thyroxine; Vitamin B 12