PubMed Health⌕ Search

Biomedical subjects

G Varela-Moreiras

Publications and source records attributed to G Varela-Moreiras.

At least 19 recordsLinked to original sources
PubMed2006

Research goals for folate and related B vitamin in Europe.

In the past decade, the understanding of folate bioavailability, metabolism and related health issues has increased, but several problems remain, including the difficulty of delivering the available knowledge to the populations at risk. Owing to the low compliance of taking folic acid supplements, for example, among women of child-bearing age who could lower the risk of having a baby with a neural tube defect, food-based strategies aimed at increasing the intake of folate and other B-group vitamins should be a priority for future research. These should include the development of a combined strategy of supplemental folate (possibly with vitamin B(12)), biofortification using engineered plant-derived foods and micro-organisms and food fortification for increasing folate intakes in the general population. Currently, the most effective population-based strategy to reduce NTDs remains folic acid fortification. However, the possible adverse effect of high intakes of folic acid on neurologic functioning among elderly persons with vitamin B(12) deficiency needs urgent investigation. The results of ongoing randomized controlled studies aimed at reducing the prevalence of hyperhomocysteinemia and related morbidity must be available before food-based total population approaches for treatment of hyperhomocysteinemia can be recommended. Further research is required on quantitative assessment of folate intake and bioavailability, along with a more thorough understanding of physiological, biochemical and genetic processes involved in folate absorption and metabolism.

Biological Availability↗
PubMed2002

High dietary folate supplementation: effects on diet utilization and methionine metabolism in aged rats.

BACKGROUND: Folate supplementation or food fortification is being nowadays recommended because of its effect on the prevention of neural tube defects and the lowering of homocysteine levels. We have previously reported a negative effect of high dose folate supplementation on dietary metabolic protein utilization in pregnant and virgin rats. OBJECTIVES: To determine the effects of such folate supplementation on nutritional and some biochemical markers in aged rats. DESIGN: Aged male Wistar rats were given free access either to a folate supplemented diet (40 mg/kg diet) or a control diet (1 mg/kg diet) for 29 days following a week adaptation period. Two critical periods were used for metabolic balance studies (experimental days 1 to 8 and 22 to 29), involving the determination of digestive and metabolic protein utilization. Several biochemical markers involved in the methylation cycle were also determined. RESULTS: Data show that long term high folate supplementation reduces nitrogen digestive function in aged rats (P<0,03) during the second metabolic period (days 22 to 29). However, supplementation did not alter metabolic protein utilization. Plasma homocysteine and serum vitamin B6 and B12 levels, hepatic S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) concentrations -and thus methylation ratio, SAM/SAH-, were neither affected by folate supplementation. CONCLUSION: Folate supplementation at high doses may have a negative effect on diet utilization, related to protein status.

Aging↗
PubMed2001

Nutritional regulation of homocysteine: effects of drugs.

Homocysteine plays a critical regulation role at the intersection of two metabolic pathways: remethylation and transsulfuration. Both are nutritionally regulated per se, and this issue constitutes the main goal of the present short review. In addition, several factors (i.e., drugs) may change the nutritional modulation, altering the normal functioning of the methionine/methylation cycle. The metabolism of a substrate is closely linked to that of it cofactors: in the case of homocysteine, there are three vitamins acting as cofactors or coenzymes: B6, B12 and folate. Vitamin B6 is involved in the formation of cystathionine from homocysteine (transsulfuration pathway). It is also critical for the formation of 5,10-methylentetrahydrofolate from tetrahydrofolate (folic acid derivatives), and therefore is closely related to the metabolism of folate. The latter is in conjunction with vitamin B12 involved in the remethylation of homocysteine to methionine. This reaction is B12-dependent. Different animal and human studies have proved the existence of a relation between vitamin status and homocysteine. Other dietary components as methionine content, riboflavin, alcohol or coffee consumption are being investigated in relation to homocysteine concentration. Drugs may interfere with the utilization of nutrients. This fact may be of special importance for vitamins (i.e., folate). Administration of drugs in populations with adequate vitamin intake is not usually a problem, but the existence of risk groups (the elderly, adolescents, smokers, dieters, etc.) may lead to specific vitamin deficiencies which may lead to elevated homocysteine. The case of folate is analysed since this vitamin shows the most reported number of interactions with drugs.

Acetaminophen↗
PubMed2000

Comparative study of two techniques for assessing fat intake in a Mediterranean diet. The influence of culinary oils changes.

The diet usually consumed by a community of 18 normolipemic monks was studied. It included olive oil as cooking fat (basal period BP). This diet was modified by substituting olive oil for sunflower oil during a 21-day period (experimental period EP). The precise individual weighing technique was utilised for the determination of intake, and by means of the food composition tables (FCTs) the energy and nutrient of the diet were calculated. By chemical analysis of the duplicate sample (CA) of the cooked dishes the lipid intake was also determined. Total serum cholesterol HDL and LDL cholesterol, serum triglycerides, AI and B-100 apolipoproteins and Lp(a) were also analysed. Similarly the absolute and relative values for SFA, MUFA and PUFA obtained by both techniques were also different and these were maintained when the (PUFA + MUFA)/SFA ratio was calculated by both techniques and in the two periods. The correction of the lipid intake by means of the CA technique did not improve either the correlation between the intake or the plasma lipid concentration or the cholesterolemia prediction (r = 0.83 for FCT and CA).

Adult↗
PubMed2000

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.

Animals↗
PubMed2000

Drugs-nutrient interactions: a potential problem during adolescence.

The concept of drug-nutrient interactions is not new, but it has only recently gained currency in medicine. Although the elderly are normally considered to be at particular risk, other groups may also be at risk: infants, adolescents, pregnant women, alcohol and tobacco users, etc. In infants and adolescents there are several factors that may influence the possible interactions: firstly, nutrient needs are usually higher, mainly micronutrients; systems for detoxification of anutrients are not complete; the tendency to restricted diets (especially girls) that are unable to cover the actual recommended intakes for a number of micronutrients (i.e. vitamins); and the dangerous increase in alcohol consumption either in males or females. Administration of drugs in population with adequate vitamin intake is usually not a problem, but administration of drugs in those with borderline intake of vitamins or in patients with low nutritional status can result in symptomatic vitamin deficiency states. The groups at risk of poor vitamin status are smokers (a high proportion of adolescents are active smokers); dieters (skipping meals and dieting to lose weight frequently compromise micronutrient intake, and it should be considered that it is extremely difficult to meet all the requirements at intakes of less than 1,200 calories per day), oral contraceptive users, and pregnant and lactating women, excessive alcohol users, etc. The chapter also focuses on the case of folate: rapidly dividing tissues during the adolescent growth spurt increase requirements for folate. Because of this increased need, folate status appears to be of concern during the age of this rapid growth. A variety of drugs are known to interfere with vitamin utilization by blocking or altering transformation of the vitamin to its metabolically active form. Serum folate levels are known to be low in a high percentage of patients with rheumatoid arthritis, suggesting that aspirin alters the transport of folate by competition for binding sites on serum proteins. Methotrexate, a drug commonly used at low doses for the treatment of psoriasis, rheumatoid arthritis and certain liver disorders, limits the availability of methyl groups derived from one-carbon metabolism by inhibiting competitively a key enzyme in the intracellular folate metabolism. In humans, the antiepileptic drug valproic acid (VPA) is associated with two major adverse effects: teratogenicity and folate deficiency. The mechanisms by which VPA exerts the teratogenic or antifolate effect remain unclear, but an alteration in the methionine cycle is the strongest hypothesis proposed.

Adolescent↗
PubMed2000

S-adenosylmethionine prevents hepatic tocopherol depletion in carbon tetrachloride-injured rats.

In various experimental models, S-adenosylmethionine (SAMe) has been shown to reduce liver injury by preventing depletion of glutathione, one of the antioxidant systems that plays a critical role in defence against oxidative stress. On the other hand, alpha-tocopherol may be decreased in liver diseases, and treatment with this vitamin reduces liver injury in CCl(4)-treated rats. Since there is a close relationship among the different antioxidant systems (mainly glutathione, alpha-tocopherol and ascorbic acid), we have assessed whether, as well as restoring hepatic glutathione content, SAMe has any effect on liver alpha-tocopherol and ascorbic acid levels in CCl(4)-injured rats. Four groups of seven male Wistar rats treated for 9 weeks were studied: rats induced to cirrhosis with CCl(4), rats induced to cirrhosis plus SAMe administration (10 mg x kg(-1) x day(-1)) and their respective controls. Liver samples were obtained for measuring levels of glutathione, alpha-tocopherol, ascorbic acid and thiobarbituric acid-reactive substances (TBARS), and hydroxyproline concentration as an index of collagen content. The hydroxyproline content was higher in CCl(4)-injured rats than in the control group (4.4+/-1.8 and 1.1+/-0.3 micromol/g respectively; P<0.05). In CCl(4)-injured rats, SAMe administration decreased collagen content (2.7+/-1.0 microl/g; P<0.05) and TBARS, and corrected glutathione depletion. alpha-Tocopherol was significantly lower in CCl(4)-injured rats than in controls (17.3+/-4.9 and 23.0+/-4.0 micromol/g respectively; P<0.05). By contrast, alpha-tocopherol levels were similar (23.8+/-5.1 micromol/g) in CCl(4)-injured rats receiving SAMe and in controls. In CCl(4)-injured rats, liver ascorbic acid was decreased in comparison with controls (4.9+/-1.8 and 8.2+/-1.0 micromol/g respectively; P<0.05), levels which were not replenished by SAMe (4.6+/-0.4 micromol/g). In conclusion, SAMe not only decreases fibrosis and protects against hepatic glutathione depletion, but has a further antioxidant effect of preventing alpha-tocopherol depletion in CCl(4)-injured rats.

Animals↗
PubMed1999

Impaired methionine synthesis and hypomethylation in rats exposed to valproate during gestation.

BACKGROUND: The antiepileptic drug valproic acid (VPA) may be teratogenic. The mechanism of teratogenicity remains unclear, but it has been hypothesized that VPA interferes with folate metabolism. OBJECTIVE: To study the effect of VPA on the methionine cycle and transmethylation reactions in pregnant rats. METHODS: Wistar rats were treated with VPA (300 mg/kg/day) on gestation days 8, 9, and 10, alone or in combination with folinic acid (FOL, 4 mg/kg/day) on gestation days 8, 9, and 10 or S-adenosylmethionine (SAM, 10 mg/kg/day) throughout gestation days 1 to 10. RESULTS: VPA induced a reduction in maternal methionine serum concentration (p < 0.05) caused by a 24% reduction of methionine synthase activity in liver. This provoked hepatic DNA hypomethylation, although the methylation ratio (S-adenosylmethionine/S-adenosylhomocysteine) was not altered. Homocysteine, folate, and vitamin B12 serum concentrations, as well as methionine adenosyltransferase and betaine homocysteine methyltransferase hepatic activities, did not change. In fetuses exposed to VPA, no effect was observed in hepatic methionine content, but the methylation ratio was reduced (p < 0.01), leading again to hepatic DNA hypomethylation. Coadministration of FOL prevented VPA-induced alterations in methionine synthesis and corrected fetal DNA hypomethylation. By contrast, SAM did not exert a protective effect on fetal DNA methylation. CONCLUSION: Impaired methionine synthesis and DNA hypomethylation may be involved in VPA-induced teratogenesis.

Analysis of Variance↗
PubMed1999

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.

Animals↗
PubMed1996

Brain folates and DNA methylation in rats fed a choline deficient diet or treated with low doses of methotrexate.

In a recent study we have demonstrated that induced changes in several parameters of one-carbon metabolism in livers of rats fed either a choline deficient diet or treated with low doses of methotrexate may be reversed through restoration of an adequate choline diet and discontinuing of methotrexate (MTX) administration. The present study was aimed at comparing these two treatments for their effect on brain: total folate was 0.69 +/- 0.35 nmol/g in the control group and was significantly lower in the other two groups (0.25 +/- 0.06 in the MTX and 0.45 +/- 0.24 nmol/g in the choline deficient groups, p < 0.01). Both treatments were associated with elongations of the glutamate chains of the folate molecules: the proportion of hepta- and octaglutamyl folates increased from 16% to 31% in the MTX treated and to 33% in the choline deficient group, accompanied with concomitant decreases in the concentrations of tetra- and pentaglutamyl folates. MTX could not be detected in brain tissue in contrast to previous observations of significant amounts found in liver. DNA was significantly (p < 0.05) undermethylated in both treated groups compared to controls. Results are discussed on the basis of the possibility that choline deficiency and MTX treatment appear to impair the capacity of tissues, either a peripheral one as liver or a central one as brain, to incorporate folate.

Animals↗
PubMed1995

Choline deficiency and methotrexate treatment induces marked but reversible changes in hepatic folate concentrations, serum homocysteine and DNA methylation rates in rats.

OBJECTIVE: The study compared the effects of feeding rats a choline deficient (CD) diet or injecting low doses of methotrexate (MTX) on hepatic folate concentration and distribution, homocysteine (Hcy) concentration and DNA methylation. METHODS: Thirty rats were divided into three groups and were fed either a choline sufficient (CS) or deficient diet (CD), or injected with low doses of MTX (0.1 mg/kg/day) for 2 weeks. Half the animals of each group were sacrificed and the remaining CD and MTX animals were fed repletion diets without methotrexate administration for two additional weeks. RESULTS: CD or MTX resulted in a significantly lower folate concentrations (25-50%) compared to the control group. Folate distribution in the treated animals was associated with elongation of the glutamate chains: higher proportion of hexa (from 14%, control, to 35%, choline, p < 0.05), hepta (from 5% to 16%, p < 0.05), and appearance of octaglutamyl folates. MTX administration resulted in a similar pattern of hepatic folate distribution. Two weeks following the MTX administration and the restoration of an adequate choline diet for 2 weeks restored the hepatic folate levels to the control animals. CONCLUSIONS: Results are discussed based on the possibility that CD and MTX treatment appear to impair the capacity of tissues to incorporate folate in only 2 weeks and affect other biomarkers of one-carbon metabolism such as Hcy concentration and DNA methylation. This adverse picture was partially reversed in a relative short time by simply feeding an adequate CS diet and discontinuing MTX injections.

Animals↗
PubMed1995

Carbon tetrachloride-induced hepatic injury is associated with global DNA hypomethylation and homocysteinemia: effect of S-adenosylmethionine treatment.

Carbon tetrachloride (CCl4) administration to rats produces hepatic cirrhosis and supplementation with S-adenosylmethionine (SAM) can partially prevent CCl4-induced liver injury. These effects are thought to be caused by oxidative stress and the subsequent formation of free radicals, but the mechanism whereby this occurs and the accurate nature of the mechanisms by which SAM exerts its protective action are not well understood. The effect of short-term administration of CCl4 on hepatic DNA methylation and on SAM and S-adenosylhomocysteine (SAH) were assessed. CCl4 administration to rats for 3 weeks resulted in hypomethylation of liver DNA, determined by comparing the extent to which DNA from livers of control or treated animals could be methylated in vitro using [3H-methyl] SAM as methyl donor. This CCl4 effect on DNA methylation was corrected by the administration of SAM (10 mg/kg/d, intramuscularly), with values of methyl groups incorporation comparable with those observed in the control animals. hepatic SAM was decreased by CCl4 (65.3 +/- 5.27 vs. 102.2 +/- 4.89 nmol/g; P < .05) and SAH was increased (69.5 +/- 14.6 vs. 29.4 +/- 3.83 nmol/g; P < .05). This led to a marked reduction of the SAM/SAH ratio (the methylation ratio) from 3.47 in control rats to 0.94 in CCl4-treated animals (P < .05). SAM treatment partially prevented (P < .05) the reduction of the ratio SAM/SAH induced by CCl4. CCl4 also induced a marked elevation of serum homocysteine levels (more than 20-fold; P < .001), which was partially prevented by SAM administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Effects of ageing on folate metabolism in rats fed a long-term folate deficient diet.

The present study was focused on the effects of feeding to young (2 mo. old) and aged (30 mo. old) rats either a folate repleted or a folate deficient diet for seven weeks on several markers of folate metabolism. Serum and liver folate contents were determined, and hepatic distribution of folates based on glutamic acid chain length and pteridine ring was obtained. In addition, liver s-adenosylmethionine (Ado Met) and s-adenosylhomocysteine (AdoHcy) concentrations, as well as serum homocysteine concentration have been also determined. Ageing itself seems not to be associated with lower hepatic folate content, but in serum a 50% decrease was observed. Feeding the folate deficient diet did result in significant lower (p < 0.001) liver folate content in both age groups, and in marked decreases in serum folates. These quantitative changes in the folate deficient groups were associated with an elongation of the glutamate chain length, mostly represented by a significant decrease in the proportion of pentaglutamyl derivatives, an increase of hexaglutamyl, and appearance of hepta and octaglutamyl folate derivatives. However, there were no important modifications in the pteridine ring distribution regardless of the age and level of dietary folate. In the present study, ageing seems to be associated with a significantly lower AdoMet/AdoHc ratio (65% decrease, p < 0.05), irrespective of the folic acid included in the diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1994

Effects of prolonged aspirin or acetaminophen administration to rats on liver folate content and distribution. Relation to DNA methylation and S-adenosylmethionine.

The study was aimed at determining the effects of longterm administration to rats of aspirin or acetaminophen (ACAP) on liver folate content and distribution as well as whether or not hepatocyte DNA was methylated at the end of the treatments. In addition, S-adenosylmethionine and S-adenosylhomocysteine hepatic concentrations were determined. In liver, aspirin or ACAP administration were not associated with important changes in total folate content or glutamic acid chain length distribution. DNA methylation assessed by comparing the extent to which DNA from livers of control or treated animals could be methylated in vitro using (3H-methyl)S-Ado Met as methyl donor, resulted in similar [3H] methyl incorporation into DNA regardless of the drug. The long-term administration of the analgesics did not result in significant changes in S-AdoMet/S-AdoHcy ratios.

Acetaminophen↗
PubMed1992

Long-term folate deficiency alters folate content and distribution differentially in rat tissues.

We fed rats a defined amino acid, folate-free diet that did not contain sulfathiazole for 25 wk and examined the effects upon the content and distribution of folates in various tissues, based on the glutamic acid chain length and pteridine ring distribution. Compared with controls, rats fed the folate-deficient diet had lower folate concentrations in liver (11.10 +/- 1.04 vs. 27.11 +/- 2.72 nmol/g, P less than 0.001), kidney (4.79 +/- 0.65 vs. 11.69 +/- 1.40 nmol/g, P less than 0.01) and spleen (1.29 +/- 0.12 vs. 3.74 +/- 0.52 nmol/g, P less than 0.001), but not in brain (0.60 +/- 0.09 vs. 0.65 +/- 0.04 nmol/g, P greater than 0.1). The folate-deficient diet also resulted in changes in folate distribution reflected mostly by longer glutamate chains. In livers of the animals fed the folate-deficient diet the relative concentration of pentaglutamyl folates was lower and that of hexaglutamyl folates was higher, and there were also considerable amounts of hepta and octaglutamyl derivatives. Similar changes in folate distribution were observed in kidney and spleen. Brain folate distribution, however, was the same in the folate-deficient and folate-replete rats. The folate-deficient diet was without effect on the pteridine ring structure distribution in the various tissues except for small changes in the kidney. These results are discussed with respect to the relationship between tissue folate depletion and glutamic acid chain elongation and the possibility that folate conservation is different in the brain than in other tissues.

Animals↗
PubMed1992

Effects of yogurt and fermented-then-pasteurized milk on lactose absorption in an institutionalized elderly group.

In the present study we evaluated lactose malabsorption (LM) after ingestion of three dairy products in 53 healthy institutionalized elderly people. A preliminary screening with milk (250 ml, 11 g lactose) was carried out to select the LM subjects using the H2 breath test. The effect of consuming an equivalent amount of lactose contained in yogurt and fermented-then-pasteurized milk (FPM) was then assessed in LM subjects. Results indicated that 36% of the elderly population studied was considered as LM and that breath H2 excretion was significantly higher after ingestion of milk than after ingestion of yogurt. This beneficial effect was partially eliminated when FPM was tested. Moreover, breath H2 excretion was significantly higher (p less than 0.05) 3 hours after ingestion of FPM compared to the normal yogurt. These results demonstrate a high prevalence of LM in the elderly and confirm the positive effect of yogurt on lactose absorption, whereas pasteurized yogurt did not cause the same effect.

Aged↗