Moderate or supranormal folic acid supplementation does not exert a protective effect for homocysteinemia and methylation markers in growing rats.

BACKGROUND/AIMS: Folic acid (FA) deficiency/supplementation effects seem to be dependent on age group and/or physiological status. The aim was to evaluate changes associated with rapid growth in relation to methionine metabolism in rats. METHODS: Four groups (n = 10 each) of male Sprague Dawley rats (5 weeks old) were on diets that varied in their FA content: 0 mg FA/kg diet (deficient), 2 mg FA/kg diet (control), 8 mg FA/kg diet (moderate supplementation), 40 mg FA/kg diet (supranormal supplementation). Animals were fed ad libitum for 30 days. Biomarkers of methionine metabolism and antioxidant status were evaluated. RESULTS: Serum total homocysteine concentration increased (p < 0.01) in FA deficient animals, with no differences between the supplemented groups. The hepatic 'methylation ratio' (S-adenosylmethionine/S-adenosylhomocysteine) of the FA content groups reached similar values, which were significantly higher compared to the deficient group. The brain 'methylation ratio', however, remained unmodified independently of FA content in the diet. FA deficiency induced hepatic DNA hypomethylation, and supranormal FA supplementation exerted the most protective effect (p < 0.01). Serum folate levels increased according to FA dietary level, whereas no differences were seen for vitamin B(12) and vitamin B(6). CONCLUSIONS: FA deficiency compromises methionine metabolism whereas supplementation does not show an additional positive effect compared to the control diet in growing animals.

[Dietary food habits, nutritional status and lifestyle in menopausal women in Spain]. / Hábitos alimentarios, estado nutricional y estilos de vida en una población de mujeres menopaúsicas españolas.

AIM: To analyse the diet and the dietary food habits in a sample of 1,218 Spanish women, aged 40 to 77 years, in the menopausal or perimenopausal condition. Women were recruited nationwide and the diet was assessed using a food frequency questionnaire. RESULTS: Diet in our population group was close to the representative dietary habits of the Spanish population, except for dairy products. These were highly consumed (approximately 4 servings/day) by menopausal women. Energy, protein and cholesterol intakes, as well as most vitamins and mineral intakes, were very high, as compared to recommended dietary allowances. We only found marginal deficient intakes for folate and vitamin D. Women over 60 years consume less eggs, sweats, sugar and miscellany, and therefore less lipids and cholesterol, as well as vitamin D, than younger women. A high rate (61%) of overweight and obesity (BMI > 25) was present in our population group and was associated with a higher intake of meat, fish and eggs, as well as energy. A healthier diet (high intake of dairy products, fresh vegetables, fruits, legumes, cereals and fish) was associated with a healthier lifestyle (no smoking, physical exercise) and the use of fortified foods and vitamin/mineral supplements. A high percentage of women regularly consumed fortified food (52,7%) and micronutrient supplements (22,8%) although diets provided enough vitamins and minerals. CONCLUSION: Diet in our study group is in accordance to healthy dietary habits and physical activity recommendations. This is probably due to a greater concern for health in women close to the menopause condition.

Hábitos alimentarios, estado nutricional y estilos de vida en una población de mujeres menopáusicas españolas / Dietary food habits, nutritional status and lifestyle in menopausal women in Spain

Objetivo: Conocer la dieta y los hábitos alimentarios, a partir de un cuestionario de frecuencia de consumo de alimentos, de una muestra de 1.218 mujeres españolas en estado de menopausia-perimenopausia y edades comprendidas entre 40 y 77 años, procedentes de todas las Comunidades Autónomas. Resultados: La dieta de la muestra de estudio es equivalente a la dieta media de la población española, destacando los productos lácteos, que son consumidos en mayor cantidad por las mujeres participantes (aproximadamente 4 raciones/ día). La ingesta energética, de proteínas y de colesterol es elevada, así como de la mayoría de vitaminas y minerales. Únicamente se han encontrado ingestas deficitarias moderadas para el ácido fólico y la vitamina D. Las mujeres de mayor edad (> 60 años) consumen menos alimentos del grupo de huevos, dulces y azúcar y varios y, por tanto, de lípidos y colesterol, aunque también de vitamina D. Un IMC elevado (IMC > 25; 61% de la población) está asociado con un mayor consumo de carnes, pescados y huevos y, por tanto, de energía. Una dieta más adecuada (mayor consumo de lácteos, frutas, verduras, legumbres, cereales y pescados) está asociada a un estilo de vida más saludable (no fumar, practicar ejercicio físico) y a la ingesta de alimentos fortificados (52,7% de la muestra total) y suplementos vitamínicos y minerales (22,8% de la muestra total), aun cuando el aporte de los micronutrientes es suficiente a través de la dieta habitual. Conclusiones: En conjunto, la dieta de nuestra población de estudio se adecúa a los patrones de dieta saludable y actividad física, reflejo de la preocupación por la salud de la mujer en la etapa de la menopausia

Aim: To analyse the diet and the dietary food habits in a sample of 1,218 Spanish women, aged 40 to 77 years, in the menopausal or perimenopausal condition. Women were recruited nationwide and the diet was assessed using a food frequency questionnaire. Results: Diet in our population group was close to the representative dietary habits of the Spanish population, except for dairy products. These were highly consumed (approximately 4 servings/day) by menopausal women. Energy, protein and cholesterol intakes, as well as most vitamins and mineral intakes, were very high, as compared to recommended dietary allowances. We only found marginal deficient intakes for folate and vitamin D. Women over 60 years consume less eggs, sweats, sugar and miscellany, and therefore less lipids and cholesterol, as well as vitamin D, than younger women. A high rate (61%) of overweight and obesity (BMI > 25) was present in our population group and was associated with a higher intake of meat, fish and eggs, as well as energy. A healthier diet (high intake of dairy products, fresh vegetables, fruits, legumes, cereals and fish) was associated with a healthier lifestyle (no smoking, physical exercise) and the use of fortified foods and vitamin/mineral supplements. A high percentage of women regularly consumed fortified food (52,7%) and micronutrient supplements (22,8%) although diets provided enough vitamins and minerals. Conclusion: Diet in our study group is in accordance to healthy dietary habits and physical activity recommendations. This is probably due to a greater concern for health in women close to the menopause condition

Supranormal dietary folic acid supplementation: effects on methionine metabolism in weanling rats.

There are nationwide folic acid (FA) fortification programmes of staple foods established or under consideration in order to prevent neural tube defects. Universal FA fortification still remains controversial because of the concern that additional FA in the diets of population groups (e.g. children and elderly) not initially targeted for fortification may suffer adverse effects. However, dietary surveys regarding folate generally deal with adults and little is known about the consumption and long-term effects of fortified food and supplements in growing individuals. Recent reports from our laboratory show several effects of high-dose folate supplementation in rats. In the present work, we studied the effect of FA on the methionine cycle in weanling (3-week-old) male rats after 4 weeks of supplementation with 40 mg FA/kg diet v. control (1 mg FA/kg diet). FA supplementation resulted in a reduction of homocysteine and creatinine concentrations v. control group. FA supplementation did not alter S-adenosylmethionine/S-adenosylhomocysteine ratio, DNA methylation, enzymatic activities or concentrations of vitamins involved in the nutritional regulation of the methionine cycle, except for folate. FA supplementation of 40 mg/kg did not lead to hepatic or renal damage. In conclusion, there were no apparent adverse effects on one-carbon metabolism after FA supplementation in the studied conditions.

High-dose folic acid supplementation in rats: effects on gestation and the methionine cycle.

There is new evidence that a good folate status may play a critical role in the prevention of neural-tube defects and in lowering elevated homocysteine concentrations. This adequate folate status may be achieved through folic acid dietary supplementation. Folate is a water-soluble vitamin with a low potential toxicity. However, the possible consequences of long-term high-dose folic acid supplementation are unknown, especially those related to the methionine cycle, where folate participates as a substrate. With the aim of evaluating such possible effects, four groups of Wistar rats were classified on the basis of physiological status (virgin v. pregnant) and the experimental diet administered (folic-acid-supplemented, 40 mg/kg diet v. control, 2 mg folic acid/kg diet). Animals were fed on the diets for 3 weeks. Results showed that gestation outcome was adequate in both groups regardless of the dietary supplementation. However, there were reductions (P < 0.001) in body weight and vertex-coccyx length in fetuses from supplemented dams v. control animals. Folic acid administration also induced a higher (P < 0.01) S-adenosylmethionine: S-adenosylhomocysteine value due to increased S-adenosylmethionine synthesis (P < 0.01). However, hepatic DNA methylation and serum methionine concentrations remained unchanged. Serum homocysteine levels were reduced in supplemented dams (P < 0.05). Finally, pregnancy caused lower serum folate, vitamin B6 and vitamin B12 levels (P < 0.05). Folic acid administration prevented the effect of pregnancy and raised folate levels in dams, but did not change levels of vitamins B12 and B6. These new findings are discussed on the basis of potential benefits and risks of dietary folic acid supplementation.

High dietary folate supplementation affects gestational development and dietary protein utilization in rats.

There is new evidence that good folate status may play a critical role in the prevention of neural tube defects and in the maintenance of adequate homocysteine levels, an amino acid recently identified as a risk factor for cardiovascular disease. This has led to different folate recommendations, all of them much higher than the present dietary recommendations. Folic acid is a water-soluble vitamin with a low potential toxicity. However, the possible consequences of long-term, high folate intakes are unknown. Therefore, the present study was undertaken to determine the effects of long-term, high dietary folate supplementation on gestational and nutritional markers in pregnant and virgin rats. Four groups of Wistar rats were classified on the basis of physiological status (virgin or pregnant) and the experimental diets administered (folic acid supplemented, 40 mg/kg diet; or control diet, 2 mg folic acid/kg diet). Rats were fed their respective diets for 3 wk. Two critical periods were used for metabolic balance studies (experimental d 1-5 and 17-21), which involved the determination of fat and protein digestibilities as well as metabolic protein utilization (MPU) and net protein utilization (NPU). Gestational development (number of live fetuses) was adequate in both diet groups regardless of folate supplementation. However, body weight and vertex-coccyx length in fetuses from supplemented dams were less than (P < 0.0001) in fetuses of control dams. Fat and nitrogen digestibilities were not affected by supplementation, but MPU and NPU coefficients were significantly lower (P < 0.05) in the folic acid-supplemented groups, irrespective of physiological status, compared to control rats. These new findings of macro-micronutrient interactions caused by high folate supplementation are discussed on the basis that the vitamin may act as a xenobiotic more than as a nutrient.