Nutritional anaemia during pregnancy. A comparative study of two socio-economic classes.
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Anemia↗
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Results for “Serum Folate Level”
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Pilot phase IIA study for evaluation of the efficacy of folic acid in the treatment of laryngeal leucoplakia.
BACKGROUND: It has been previously observed that patients with head and neck squamous cell carcinoma or with laryngeal leucoplakia present a significant reduction in plasma folate levels. The current Phase IIA pilot study assessed the effectiveness of folic acid as a chemopreventive agent in patients affected by glottic laryngeal leucoplakia. METHODS: Forty-three untreated patients affected by glottic laryngeal leucoplakia were enrolled in the Ear, Nose, and Throat Department (Universita Cattolica del Saco Cuore, Rome, Italy). Glottic leucoplakia was initially diagnosed by indirect laryngoscopy and successively confirmed by diagnostic direct microlaryngoscopy with a biopsy for histologic assessment. Folic acid (Folina, Schwarz Pharma, Germany) was administered orally (5 mg every 8 hours) for 6 months. Patients were monitored every 30 days by videolaryngoscopy. RESULTS: Twelve (28%) patients had no response, 19 (44%) had a partial response, and 12 (28%) had a complete response. The mean increase in serum folate levels (10.06 +/- 0.53) and the mean decrease in homocysteine serum (3.65349 +/- 0.85526) at the end of the study were highly significant (P = .0001). CONCLUSIONS: The larynx is 1 of the sites of major interest and a good model for the development of chemopreventive agents, but so far the proposed agents have shown no clear efficacy on precancerous lesions or on the development of second malignancies.
Adult↗
Folate levels and cancer morbidity and mortality: prospective cohort study from Busselton, Western Australia.
PURPOSE: To test a community population for the hypothesis that carcinogenesis is related to blood folate levels. METHODS: Prospective analysis of cancer mortality data for a cohort of 964 men (person-time follow up: 20,254 years) and 1024 women (person-time follow up: 24,970 years) and morbidity data for a subcohort, all of whom participated in the 1969 Busselton (Western Australia) Health survey. Outcome measures were adjusted hazard ratios according to baseline folate levels for total cancer mortality and morbidity and site specific mortality and morbidity for colorectal, lung, breast, and prostate cancers. RESULTS: In total, there were 278 cancer deaths--45 from colorectal cancer, 44 from lung cancer, 15 from breast cancer, and 31 from prostate cancer. Decreased serum folate levels showed an independent association with increased prostate cancer mortality risk, the adjusted hazard ratio per decrease of 2 microg/L was 1.56 (CI: 1.05, 2.38), men whose levels were in the lowest quartile had an adjusted hazard ratio of 4.79 (CI: 1.56, 14.43) for subsequent death from prostate cancer. The morbidity subcohort data showed that decreased red blood-cell folate was significantly associated with increased events due to breast cancer, the adjusted hazard ratio per decrease of 100 mug/L was 1.96 (CI: 1.22, 3.12), women in the lowest quartile of red cell folate levels had an adjusted hazard ratio of 6.46 (CI: 1.19, 35.07) for a subsequent breast cancer event. Mortality and morbidity from colorectal or lung cancers were not associated with folate levels. CONCLUSIONS: Independent associations, assessed over periods greater than 20 years, were demonstrated between decreased folate levels and increased risks of prostate cancer mortality and breast cancer morbidity.
Adult↗
Folate bioavailability in humans: effects of wheat bran and beans.
The effect of wheat bran or California small white beans in the diet on absorption of monoglutamyl (PteGlu) and heptaglutamyl folic acid (PteGlu7) was studied in six men confined to a metabolic unit. Relative folate absorption was determined by measuring 24-h urinary folate excretion and serum folate levels at 0, 1, and 2 h after ingestion of a formula meal containing 1.13 mumol PteGlu or PteGlu7 (500 micrograms PteGlu equivalent). Serum data showed PteGlu absorption was more rapid than PteGlu7 absorption. Urinary excretion of PteGlu7 was 63% (50 less than or equal to mean less than or equal to 76%) of PteGlu excretion. Addition of 30 g wheat bran to the formula meal accelerated PteGlu absorption whereas PteGlu7 absorption was not significantly affected by either food. Effects of the two foods were qualitatively different. Wheat bran increased the absorption of PteGlu relative to PteGlu7 whereas beans minimized the difference between PteGlu and PteGlu7 serum areas.
Adult↗
Risk factors in phenytoin-induced gingival hyperplasia.
A survey was carried out into the degree of gingival hyperplasia in 68 patients receiving phenytoin in a hospital for the mentally handicapped. Comparisons of degree of gingival hyperplasia exhibited by the patients were made with a range of parameters by analysis of variance and Chi square tests. The severity of the hyperplasia increased with increasing dose, increasing dose per unit body weight and serum levels of phenytoin and also with decreasing age and weight of the patients. No significant relationship (P less than 0.2) was found between serum folate levels and degree of hyperplasia. Poor oral hygiene predisposed patients to hyperplasia.
Adolescent↗
Relationship between total homocysteine and folate levels in pregnant women and their newborn babies according to maternal serum levels of vitamin B12.
OBJECTIVE: To determine total homocysteine and folate levels in pregnant women according to vitamin B12 (B12) levels, and to analyse the impact of maternal B12 levels on the nutritional status of their newborn babies. DESIGN: Cross sectional observational study. SETTING: Two public hospitals in Jundiai City, São Paulo, Brazil. SAMPLE: Sixty-nine pregnant women and their respective newborn babies at the time of delivery. METHODS: Maternal blood was collected up to 8 hours before delivery. Umbilical cord blood was collected after the expulsion of the placenta. Total homocysteine was measured by high perfomance liquid chromatography, folate by ion capture methodology and B12 by enzyme immunoassay. MAIN OUTCOME MEASURES: Relationship between low maternal vitamin B12 levels and total homocysteine and folate levels in pregnant women and newborn babies. RESULTS: There was a significant correlation between maternal and neonatal B12 levels, but not between maternal B12 and neonatal red blood cell (RBC) folate. There was a weak correlation between maternal B12 levels and neonatal serum folate. However, there were significant correlations between maternal and neonatal total homocysteine levels and between neonatal B12 and neonatal total homocysteine levels. Mean (+/- SD) umbilical cord blood B12, RBC folate, serum folate and total homocysteine levels were 1.7 +/- 0.8, 1.8 +/- 0.8, 2.2 +/- 0.8 and 0.9 +/- 0.3 times higher than maternal B12, RBC folate, serum folate and total homocysteine values, respectively. CONCLUSIONS: These data suggest that pregnant women with low B12 levels are unable to provide the necessary amount of B12 to their fetuses. The clinical consequences could be the presence of neurological abnormalities as well as the lack of utilisation of homocysteine for methionine transformation.
Adolescent↗
Assessment of the potential effect of incremental increases in folic acid intake on neural tube defects in Australia and New Zealand.
OBJECTIVE: To estimate the number of neural tube defects that could be prevented in Australia and New Zealand by increasing levels of folic acid intake. METHODS: Available data on prevalence of neural tube defects in Australia and New Zealand, folic acid supplement use and serum folate were used in a published model to estimate the number of neural tube defects that could be prevented in Australia and New Zealand for increments of folic acid intake from 0.1 mg daily to 1 mg daily. RESULTS: An increase of 0.2 mg folic acid per day was estimated to result in the prevention of 49 (95% CI 27-84) neural tube defects per year in Australia and 11 (95% CI 6-18) in New Zealand. A separate estimation for Indigenous Australians found that 0.2 mg of folic acid daily could prevent 7 (95% CI 4-11) neural tube defects in Indigenous infants per year. CONCLUSIONS: These data should be useful in considering primary preventive strategies for neural tube defects, including the possible introduction of mandatory fortification of food with folic acid. The estimates are imprecise because of limitations in the data used in the model. IMPLICATIONS: More representative and precise data on neural tube defects, serum folate levels and use of folic acid supplements from all Australian States and New Zealand are needed to refine the output from the model and to provide a baseline assessment of folate status against which to measure the effects of any future interventions to prevent neural tube defects.
Australia↗
Folate status of adult males living in a metabolic unit: possible relationships with iron nutriture.
Folate and iron status was monitored at monthly intervals in 40 adult males who were living in a metabolic unit for 2 to 8 months and consuming diets containing 150 to 250 micrograms of folate per day. There were significant (p less than 0.02) declines in hematocrit, serum folate, and serum ferritin. Men who participated in studies for 6 months or more or those with initial serum folate levels more than 10.5 ng/ml and erythrocyte folate levels more than 481 ng/ml also exhibited a highly significant (p less than 0.001) decline in red blood cell folate. Men with erythrocyte folate below 480 ng/ml or serum folate below 10 ng/ml and who participated in the studies for less than 5 months showed little or no change in folate status. The findings may reflect adjustments in body folate to reflect dietary intakes. Also a folate intake of 200 +/- 68 micrograms/day appeared to be adequate for maintenance of folate stores in adult males. A correlation between iron stores and folate status was also observed. However, this relationship may be coincidental.
Adult↗
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↗
Decreased vitamin B12 and folate levels in cerebrospinal fluid and serum of multiple sclerosis patients after high-dose intravenous methylprednisolone.
Twenty-one patients (15 women, 6 men) with definite multiple sclerosis (MS) were treated with 1000 mg intravenous methylprednisolone-succinate (MP) daily for 10 days. Before MP treatment there was a negative correlation (r = 0.59, P = 0.0084) between serum vitamin B12 and progression rate, defined as the ratio of the score on Kurtzke's Expanded Disability Status Scale and disease duration. A significant decrease was demonstrated in the cerebrospinal fluid (CSF) and serum levels of folate and in the CSF level of vitamin B12 after MP treatment. The decrease in serum B12 was not statistically significant. After MP treatment all median levels of vitamin B12 and folate were below the reference medians. We hypothesize that low or reduced vitamin B12/folate levels found in MS patients may be related to previous corticosteroid treatments. Otherwise a more causal relationship between low vitamin B12/folate and MS cannot be excluded. Further studies may be required to clarify the vitamin B12 and folate metabolism in patients with MS.
Adult↗
Pyrimethamine alone as prophylaxis for cerebral toxoplasmosis in patients with advanced HIV infection.
Prophylaxis for toxoplasma encephalitis was performed with pyrimethamine alone (50 mg daily) in 56 patients with advanced HIV infection. Thirty-eight patients were at high risk for toxoplasma encephalitis (CD4+ counts < or = 200/microliter, and presence of serum IgG antibodies to Toxoplasma gondii). The overall treatment period was 697 months (mean 12.5 +/- 12.1). During prophylaxis, only one patient developed toxoplasma encephalitis, four patients discontinued treatment due to adverse reactions. Steady state pyrimethamine plasma concentrations were measured by gas chromatography. Mean plasma level was 1,887 +/- 1,161 ng/ml, during liver enzyme-inducing comedication plasma levels were significantly (p = 0.0001) reduced (1,488 +/- 884 ng/ml versus 1,978 +/- 1,196 ng/ml without comedication). All patients received a folinic acid supplement of 7.5 mg daily. Serum folate levels ranged from 5.7-105 (43.7 +/- 29.2) nmol/l; severe hematological side effects did not occur.
AIDS-Related Opportunistic Infections↗
Interrelationships between the B-vitamins in B12-deficiency neuromyelopathy. A possible malabsorption-malnutrition syndrome.
Five patients presenting clinically with a form B12-deficiency neuromyelopathy, with cord involvement in all and proximal muscle weakness in two of them, were investigated for their neurologic, hematologic and vitamin status. Megaloblastosis and achlorhydria were present in all, and impaired absorption of 57Co vitamin B12 and of D-xylose was detected in four. Total cyanide extracted vitamin B12 (A) was lowered in all cases and noncyanide extractable (B) in four of the five, being zero in three. All five responded to injections of hydroxocobalamin. In two patients sequential estimations showed that both A and B, especially the latter, rose steeply initially, normalizing at 50% of A after some weeks. Moiety B is suggested to be physiologically the more active and dissociable form of vitamin B12. Markedly elevated initial serum folate levels, and their subsequent fall under treatment with B12, indicated the operation of the "methyltetrahydrofolate trap". Blood levels of thiamin, nicotinic acid and pantothenic acid were within normal limits. However, serum riboflavin (B2) total vitamin B6 and pyridoxal were reduced in all where tested. Vitamin B6 deficiency could have resulted from its own malabsorption and have contributed to be B12 deficiency. Vitamin B2 and B6 levels also corrected themselves on B12 therapy. The B-vitamin deficiencies in our patients probably resulted from intestinal malabsorption, with a possible factor of malnutrition consequent to their strictly vegetarian diet.
Achlorhydria↗
Improved pregnancy outcome in epileptic women in the last decade: relationship to maternal anticonvulsant therapy.
The prevalence of abnormal pregnancy outcomes in the offspring of 103 epileptic women, followed prospectively during pregnancy between 1982 and 1989, was compared with that in the previous study of 119 pregnancies by Dansky et al from the same institution. Our results have shown a significant decrease in the prevalence of major malformations, as compared with the previous study: 8.8% vs 24.1% (P < 0.01). Monotherapy was more frequent and the mean number of drugs used during pregnancy was significantly smaller in the present study. Phenytoin, phenobarbital and primidone were prescribed less frequently in the present study, whereas carbamazepine and valproic acid were used more frequently. Plasma levels of valproic acid during pregnancy were higher in mothers of malformed babies. In the present study, plasma folate levels were significantly higher, and more patients were taking folate supplements during pregnancy. In conclusion, the type and number of drugs used during pregnancy, as well as the plasma concentrations and serum folate levels, may determine the frequency of abnormal outcomes.
Abnormalities, Drug-Induced↗
Homocysteine concentrations and methionine loading in patients on antiepileptic drugs.
OBJECTIVES: A few reports have shown elevated fasting total plasma homocysteine (tHcy) in patients taking antiepileptic drugs (AEDs). In this study we determined the influence of AEDs on plasma tHcy levels prior to and following methionine loading. MATERIAL AND METHODS: Thirty-four patients on different AEDs and 34 matched controls were recruited. Blood samples were drawn prior to and 6 h post-methionine loading (6h-PML). RESULTS: The patients on AEDs inducing the cytochrome P450 (carbamazepine, phenytoin, phenobarbital, primidone), had higher fasting and 6h-PML plasma tHcy concentrations than the controls (P = 0.01 and P<0.001). Patients on AED inhibiting the cytochrome P450 (valproate [VPA]), had lower 6h-PML p-tHcy concentrations than controls (P = 0.01). CONCLUSIONS: Our data indicate that not only fasting but also 6h-PML tHcy levels should be determined in order to identify hyperhomocysteinemia among patients on AEDs. Inducer AEDs seem to have an opposite effect than the inhibitor VPA on plasma tHcy, erythrocyte folate and serum folate levels.
Adult↗
Chronic diuretic therapy with moderate doses of triamterene is not associated with folate deficiency.
The diuretic drug triamterene has previously been shown to be a competitive inhibitor of folate absorption in the rat intestine (J Lab Clin Med 1986;108:272-6). We therefore investigated whether human subjects who are taking the drug on a long-term basis are at increased risk of folate deficiency. In each of two free-living populations, a study was performed to compare the folate status of triamterene users with those not taking the drug. The first population consisted of 272 elderly individuals not living in institutions who were participants in a nutrition status survey and who were taking a variety of antihypertensive medications; 32 of these individuals were daily users of triamterene. The hemoglobin concentration, red blood cell (RBC) count, and mean corpuscular volume (MCV) values were not significantly different between the triamterene users and nonusers. The female triamterene users had a slightly higher serum folate level than the female nonusers (p less than 0.04); a similar pattern was observed among the men, although the difference was not statistically significant. The second population consisted of 27 individuals attending a hypertension clinic; 18 subjects were taking 50 to 150 mg of triamterene per day and nine were taking antihypertensive drugs other than triamterene. The hemoglobin concentration, RBC count, MCV, serum folate values, and RBC folate values were found to not differ significantly between the triamterene users and the hypertensive controls (p greater than 0.05). These data suggest that chronic triamterene administration in individuals not living in institutions, at the doses examined in this study, is not associated with indications of folate deficiency.
Aged↗
Serum homocysteine, folate and risk of stroke: Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study.
BACKGROUND: Homocysteine and folate have been suggested to have opposite effects on the risk of stroke, although the results are controversial. DESIGN AND METHODS: The purpose of this study was to assess the effects of serum total homocysteine (tHcy) and serum folate levels on the risk of stroke in a prospective cohort study. The subjects were 1015 men aged 46-64 years and free of prior stroke, examined in 1991-1993 in the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. RESULTS: At baseline the mean serum tHcy concentration was 10.9 micromol/l (SD 3.4). During an average follow-up time of 9.6 years, 49 men experienced a stroke, of which 34 were ischaemic. In Cox proportional hazards models, men in the highest tHcy third had a risk factor-adjusted hazard rate ratio (RR) of 2.77 [95% confidence interval (CI): 1.23-6.24] for any stroke and 2.61 (95% CI: 1.02-6.71) for ischaemic stroke, compared with men in the lowest third. The mean baseline serum folate concentration was 10.4 nmol/l (SD 4.1). Men in the highest third of serum folate (>11.2 nmol/l) had an adjusted RR for any stroke of 0.35 (95% CI: 0.14-0.87) and for ischaemic stroke of 0.40 (95% CI: 0.15-1.09), compared with men in the lowest third. CONCLUSION: Elevated serum tHcy is associated with increased risk of all strokes and ischaemic strokes in middle-aged eastern Finnish men free of prior stroke. On the other hand, high serum folate concentration may protect against stroke.
Age Factors↗
Increased urinary folate excretion and decreased plasma folate levels in the rat after acute ethanol treatment.
A common complication of chronic alcohol abuse is folic acid deficiency, which can result from poor dietary intake and from a direct effect of ethanol on folate metabolism, such as the acute decrease in serum folate levels. Ethanol (4 g/kg body weight) was administered orally to male Sprague-Dawley rats to study the rat as a suitable animal model for the acute effects of ethanol. The concentration of folate in the urine, determined by Lactobacillus casei assay, as well as the amount of urinary folate excretion were markedly increased 4 hr after ethanol administration. After 14 hr, the total plasma folate level was significantly depressed to 50% of control levels. No significant changes were observed in the total folate levels in the liver and red cell nor in the levels of individual hepatic folate monoglutamate derivatives determined by high pressure liquid chromatography assay. These results indicate that acute ethanol administration to rats produces a marked increase in the urinary excretion of folate compounds, which leads to a decrease in plasma folate levels. The acute decrease in plasma folate levels in ethanol-treated rats is similar to that seen in humans and suggests that the rat is an appropriate model for the study of the acute effects of ethanol on folate metabolism.
Alcoholic Intoxication↗
Fasting plasma homocysteine as a sensitive parameter of antifolate effect: a study of psoriasis patients receiving low-dose methotrexate treatment.
We have investigated the effect of low-dose methotrexate (25 mg weekly) on plasma homocysteine in 13 patients who had psoriasis. Total, free, and protein-bound homocysteine were determined both during fasting and after methionine loading. Psoriasis patients had significantly higher basal plasma homocysteine levels than age-matched control subjects. In addition, the methionine loading test was abnormal in four of the patients, but this was not significant. Psoriasis patients, although not folate deficient, did have lower serum folate levels than control subjects. There was a significant and transient increase in fasting plasma homocysteine levels within 48 hours after administration of low-dose methotrexate. This response was repeated after each administration and was observed eight to 20 times in three patients whose progress was monitored for 2 to 6 months. Notably, methotrexate did not affect the plasma profile for homocysteine after methionine loading. This study showed the level of fasting plasma homocysteine to be a sensitive and responsive parameter of antifolate drug treatment.
Adult↗