5-methyltetrahydrofolate and Body-Weight

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

Supplementation with [6S]-5-methyltetrahydrofolic acid (MTHF) is recommended as an alternative to folic acid (FA) in prenatal supplements. This study compared equimolar gestational FA and MTHF diets on energy regulation of female offspring. Wistar rats were fed an AIN-93G diet with recommended (2 mg/kg diet) or 5-fold (5X) intakes of MTHF or FA. At weaning, female offspring were fed a 45% fat diet until 19 weeks. The 5X-MTHF offspring had higher body weight (>15%), food intake (8%), light-cycle energy expenditure, and lower activity compared to 5X-FA offspring (

Topics: Animals; Animals, Newborn; Body Weight; Diet; Energy Intake; Energy Metabolism; Feeding Behavior; Female; Folic Acid; Mice; Models, Animal; Pregnancy; Rats, Wistar; Tetrahydrofolates; Vitamin B Complex

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

To investigate the efficiency of [6S]-5-methyltetrahydrofolate or Metafolin ([6S]-5-CH(3)-H(4)folate) on the recovery of folate status, we conducted a depletion-repletion rat model study using a growing-up milk as the folate carrier.. The effect of [6S]-5-CH(3)-H(4)folate was compared to that of folic acid (PGA or Pte-Glu), by feeding two groups of folate-depleted rats a diet of fortified growing-up milk containing either 1,000 microg/l (2.2655 micromol/l) of Pte-Glu or 1,041.91 microg/l (2.2655 micromol/l) of [6S]-5-CH(3)-H(4)folate over a 4-week period. At the end of the study, the folate concentration in plasma, erythrocytes and liver was measured to establish the folate status of the animals. The folate content was determined in the plasma and erythrocytes by a time-resolved fluoroimmunoassay method and in the liver by a HPLC method.. Plasma, erythrocyte and liver folate concentrations were significantly (P < 0.001) lower after a depletion period in rats fed the folate-deficient diet compared to rats fed a control diet. The folate form used significantly influenced the folate concentration in erythrocytes and liver, but not in plasma, after the rats' body folate reserves were replenished by consuming the fortified growing-up milk. Thus, rats fed [6S]-5-CH(3)-H(4)folate-fortified growing-up milk showed significantly higher folate content in erythrocytes and liver (1,100.37 ng/ml and 4.22 microg/g, respectively), than did those fed Pte-Glu-fortified growing-up milk (827.71 ng/ml and 3.04 microg/g, respectively, in erythrocytes and liver).. We conclude that the natural diastereomer [6S]-5-CH(3)-H(4)folate may adequately serve as an alternative to folic acid for the folate fortification of infant foods.

Topics: Analysis of Variance; Animals; Animals, Newborn; Body Weight; Diet; Erythrocytes; Folic Acid; Folic Acid Deficiency; Infant Formula; Limit of Detection; Liver; Male; Nutritional Status; Random Allocation; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Stereoisomerism; Tetrahydrofolates

Folate is an essential cofactor in the generation of endogenous methionine, and there is evidence that folate deficiency exacerbates the effects of a diet low in choline and methionine, including alterations in poly(ADP-ribose) polymerase (PARP) activity, an enzyme associated with DNA replication and repair. Because PARP requires NAD as its substrate, we postulated that a deficiency of both folate and niacin would enhance the development of liver cancer in rats fed a diet deficient in methionine and choline. In two experiments, rats were fed choline- and folate-deficient, low methionine diets containing either 12 or 8% casein (12% MCFD, 8% MCFD) or 6% casein and 6% gelatin with niacin (MCFD) or without niacin (MCFND) and were compared with folate-supplemented controls. Liver NAD concentrations were lower in all methyl-deficient rats after 2-17 mo. At 17 mo, NAD concentrations in other tissues of rats fed these diets were also lower than in controls. Compared with control values, liver PARP activity was enhanced in rats fed the 12% MCFD diet but was lower in MCFND-fed rats following a further reduction in liver NAD concentration. These changes in PARP activity associated with lower NAD concentrations may slow DNA repair and enhance DNA damage. Only rats fed the MCFD and MCFND diets developed hepatocarcinomas after 12-17 mo. In Experiment 2, hepatocarcinomas were found in 100% of rats fed the MCFD and MCFND diets. These preliminary results indicate that folic acid deficiency enhances tumor development. Because tumors developed in 100% of the MCFD-fed rats and because tissue concentrations of NAD in these animals were also low, further studies are needed to clearly define the role of niacin in methyl-deficient rats.

Topics: Animals; Body Weight; Choline Deficiency; Diet; Liver Neoplasms, Experimental; Male; Methionine; NAD; Niacin; Poly(ADP-ribose) Polymerases; Rats; Rats, Inbred F344; Tetrahydrofolates

This study concerns in vivo folic acid and methyltetrahydrofolic acid (MTHF) absorption by the whole intestinal surface after 20 weeks of 30% ethanol ingestion in drinking water. The results were compared with control rats fed ad libitum. The total intestinal serosal areas were similar in ethanol-fed and control rats. Significant increases in intestinal length, and decreases in tissue wet and dry weights were found in ethanol-fed rats. Serum folic acid concentrations were significantly less in the animals which had ingested ethanol than in the control rats. Intestinal folic acid absorption was significantly increased at lower substrate concentrations (0.5 and 1 microM), while no difference was observed at 2.5 microM in the ethanol-fed rats. Folic acid absorption relative to tissue wet weight showed significant increases at all tested concentrations in the ethanol-fed rats. Intestinal MTHF absorption showed no significant changes at 0.5 microM MTHF concentration, and an increase was observed in the absorption values at 1 and 2.5 microM concentrations in the ethanol-fed rats. When expressed as tissue wet weight, MTHF absorption values in ethanol-fed rats increased at 1 and 2.5 microM but did not differ at 0.5 microM substrate concentrations. The above results indicate compensatory responses in the folic acid and MTHF intestinal absorption after chronic ethanol ingestion. These effects are observed when the whole intestinal surface is evaluated.

Topics: Animals; Body Weight; Drinking; Eating; Ethanol; Folic Acid; Intestinal Absorption; Male; Rats; Rats, Wistar; Tetrahydrofolates

During a 6-wk feeding trial, effects of low dietary deoxynivalenol (DON; 0, 0.1, 1 and 10 ppm) on food consumption and weight gain were investigated in male mice. Food intake was similar in all four dietary groups. Weight gain in the group receiving 10 ppm DON was significantly (P less than 0.01) reduced. At the end of the feeding period, test animals were sacrificed and absorption of water, D-glucose, L-leucine, L-tryptophan, 5-methyltetrahydrofolic acid and iron was measured in isolated perfused jejunal segments in vitro. No effects were observed on absorption of water, leucine, tryptophan and iron. However, at a dietary DON concentration of 10 ppm, a slightly but significantly (P less than 0.05) reduced transfer of glucose was measured. Furthermore, transfer as well as tissue accumulation of 5-methyltetrahydrofolic acid in the jejunal segment were both significantly decreased up to 50%. Heavy metal and trace element content was determined in liver, kidney and small intestine. Manganese and molybdenum content in liver tissue was reduced with a DON concentration of 10 ppm in the diet. The findings indicate that subchronic ingestion of DON, in concentrations occurring in contaminated food and feed, results in an impairment of intestinal transfer and uptake of nutrients such as glucose and 5-methyltetrahydrofolic acid.

Topics: Animals; Body Weight; Diet; Glucose; Intestinal Absorption; Iron; Leucine; Male; Mice; Tetrahydrofolates; Trichothecenes; Tryptophan

Experiments were conducted with young chicks and rats to quantify the efficacy of L-homocysteine as a methionine precursor. Linear growth responses were obtained to both L-methionine and L-homocysteine when added to a methionine-deficient intact-protein diet containing a plethora of cystine. Slope-ratio multiple regression methodology indicated L-homocysteine to be 64.5% as efficacious as L-methionine in rats and 62.5% as efficacious in chicks. Plasma-free methionine also increased linearly as graded levels of either L-methionine or L-homocysteine were added to the diet of rats. At higher dosages of L-homocysteine, betaine, but not choline, showed some efficacy in enhancing the conversion of homocysteine to methionine. In the linear response surface of the growth curve, however, supplemental betaine was without effect on L-homocysteine bioefficacy, as was also the case for supplemental sarcosine and N5-methyltetrahydrofolic acid.

Topics: Animals; Betaine; Body Weight; Chickens; Choline; Diet; Homocysteine; Male; Methionine; Methylation; Rats; Rats, Inbred Strains; Sarcosine; Tetrahydrofolates

The effect of long-term ethanol supplementation on folate metabolism was studied in McCollum rats receiving approximately 30% of their caloric intake as ethanol. Ethanol did not significantly affect hepatic or plasma total folate levels. The net hepatic uptake and metabolism of a labeled folate dose to polyglutamate forms were unimpaired by ethanol administration. In fact, the ethanol-fed animals metabolized hepatic pteroylmonoglutamates to polyglutamate forms, predominantly the pentaglutamate, at a slightly faster rate than the control animals, and the net hepatic uptake of the labeled dose was higher than in the controls. Tetrahydrofolate derivatives were the predominant one-carbon form of folate in the livers of ethanol-fed and control animals, although the proportion of folate in the 5-methyltetrahydrofolate form was slightly increased after ethanol supplementation. Although hepatic metabolism of folate appears to be unimpaired in the ethanol-fed rat, an increased rate of pteroylpolyglutamate synthesis, with a resulting increase in the tissue storage of folate, might be a contributing factor to the low serum folate levels reported in alcoholics.

Topics: Alcoholism; Animals; Body Weight; Female; Folic Acid; Humans; Liver; Male; Organ Size; Pregnancy; Pteroylpolyglutamic Acids; Rats; Tetrahydrofolates