5-methyltetrahydrofolate and Insulin-Resistance

The purpose of this study was to evaluate whether folate exerts antioxidant effects in postmenopausal women and whether this effect is related to folate-induced modification of 24-h ambulatory blood pressure (BP).. Double-blind placebo-controlled study performed in 30 apparently healthy postmenopausal women recruited at the outpatient service of University Hospital. Women, free from hormones or substances possibly interfering with the investigated parameters, were randomized to receive orally for 3 weeks placebo (n = 15) or 15 mg/day of 5-methyltetrahydrofolate (5-MTHF; n = 15). Whole-blood free oxygen radicals test (FORT), free oxygen radical defence (FORD), lipids, glucose, insulin, insulin resistance [homeostatic model assessment for insulin resistance (HOMA-IR)], homocysteine and 24-h ambulatory BP values were evaluated.. In the entire group of women, FORT was independently and inversely related to the day-night difference of diastolic (r = 0.420; p = 0.03) and mean BP (r = 0.497; p = 0.01). Placebo did not affect any biochemical or BP parameter. 5-MTHF reduced FORT (-71.5 ± 98.2; p = 0.02) and increased FORD (0.5 ± 0.9; p = 0.05), decreased insulin (p = 0.01), HOMA-IR (p = 0.0002) and homocysteine (p = 0.008). During 5-MTHF, night-time mean (p = 0.001) and diastolic BP (p = 0.002) decreased of about 5 mmHg and the day-night difference of mean (p = 0.001) and diastolic BP (p = 0.002) contemporaneously increased. FORT reduction was related to the amplification of the nocturnal decline of mean (0.697; p = 0.006) and diastolic BP (r = 0.777; p = 0.002) and to the amplification of the day-night difference of diastolic BP (r = 0.63; p = 0.015).. Present data show a clear reduction of oxidative stress during 5-MTHF administration and a strong correlation between this decrease and the nocturnal decline of BP. The possible link between the two is worthy to be explored.

Topics: Blood Glucose; Blood Pressure; Body Mass Index; Body Weight; Cholesterol, HDL; Cholesterol, LDL; Double-Blind Method; Female; Homocysteine; Humans; Insulin; Insulin Resistance; Middle Aged; Oxidative Stress; Postmenopause; Tetrahydrofolates; Triglycerides

Topics: Animals; Diet; Diet, High-Fat; Dietary Supplements; Dose-Response Relationship, Drug; Eating; Energy Metabolism; Female; Folic Acid; Gene Expression; Hypothalamus; Insulin Resistance; Lactation; Leptin; Parturition; Phenotype; Pregnancy; Rats; Rats, Wistar; Tetrahydrofolates; Weaning; Weight Gain

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine and metabolic disorder, characterized by chronic anovulation/oligomenorrhea, hyperandrogenism, and insulin-resistance. Moreover, some studies propose a possible association between insulin resistance and hyperhomocysteinemia, which is a significant long-term risk for factor for atherogenesis and chronic vascular damage, especially in situations where insulin levels are increased. Insulin-sensitizing agents are used in the treatment of PCOS: in fact, inositols were shown to have insulin-mimetic properties. Synergic action to myo-inositol is that of gymnemic acids that have antidiabetic, anti-sweetener, and anti-inflammatory activities. Gymnemic acid formulations have also been found useful against obesity due to their ability to delay the glucose absorption in the blood. L-methyl-folate increases peripheral sensitivity to insulin, maintaining folatemia stable, and thus restoring normal homocysteine levels. Unlike folic acid, L-methyl folate has a higher bioavailability, no drug/food interferences, high absorption, and it is stable to UV-A exposure. The aim of our study is to compare the clinical, endocrine, and metabolic parameters in 100 PCOS women treated with myo-inositol, gymnemic acid, and l-methylfolate (Group A) or myo inositol and folic acid only (Group B), continuously for 6 months. From a clinical point of view, it was noticed a more significant improvement of the menstrual cycle regularity and a more significant reduction of BMI in Group A. Moreover, a more significant decrease of total testosterone and increase of SHBG serum levels were noticed in Group A. The metabolic assessment found a more significant decrease of total cholesterol and homocysteine levels; OGTT glycemia and insulinemia values were significantly more improved after treatment with myo-inositol + gymnemic acid. In conclusion, we can state that a good option for the treatment of PCOS is the combined administration of myo-inositol + gymnemic acid + l-methyl-folate, especially for overweight/obese patients with marked insulin resistance and with associated hyperhomocysteinemia.

Topics: Adult; Blood Glucose; Body Mass Index; Body Weight; Drug Therapy, Combination; Female; Humans; Hyperandrogenism; Inositol; Insulin; Insulin Resistance; Menstrual Cycle; Oligomenorrhea; Polycystic Ovary Syndrome; Saponins; Tetrahydrofolates; Treatment Outcome; Triterpenes; Young Adult