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PubMed1975

Prevention of folate deficiency by food fortification. III. Effect in pregnant subjects of varying amounts of added folic acid.

Maise meal fortified with folic acid was administered to subjects in late pregnancy in a daily dose of either 500 or 300 mug of folic acid. Changes in hematological and folate nutritonal status were compared to those in subjects receiving 300 mug folic acid/day in tablet form, and also in subjects in a previous study who received unfortified maize meal (control group) or meal containing 1,000 mug folic acid/day. In all groups receiving folic acid, red cell and serum folate levels rose progressively, and the rate of rise increased with increasing doses of folic acid. Maize meal containing a daily dose of 500 mug folic acid produced an effect similar to that of 300 mug daily in tablet form. Maize containing 300 mug added folic acid daily was effective in preventing the progression of folate depletion in late pregnancy.

Dose-Response Relationship, Drug↗
PubMed1976

Effect of nutrition education on the nutritional status of low-income pregnant women of Mexican descent.

Low-income pregnant women of Mexican descent were studied to determine whether their food habits could be improved by nutrition education. Biochemical indices of nutritional status were also investigated. Twenty-four-hour dietary recalls were obtained at an initial interview and again at a final interview after a nutrition education program, which was offered to a randomly selected treatment group. At the initial interview, the mean nutrient intakes that were most often below two-thirds of the Recommended Dietary Allowance (RDA) were iron, vitamin A, thiamin, and calcium. The mean energy value of the diets was also frequently below the RDA. At the final intakes, although the mean energy values and the calcium and carbohydrate of both the control and treatment groups increased significantly, the following improvements in dietary intakes were seen only within the treatment group: 1) there were significant increases in the mean intake of protein, ascorbic acid, niacin, riboflavin, and thiamin, 2) there were significant decreases in the percentage of intakes below two-thirds of the RDA for ascorbic acid and riboflavin, and 3) there was a significant decrease in the incidence of multiple low nutrient intakes. These dietary improvements, which occurred only in the treatment group, suggest the effectiveness of the nutrition education program. The most common biochemical deficiencies were of folic acid, thiamin, and riboflavin. Except for an improvement in mean serum folate levels, the biochemical indices for the treatment group did not appear to be influenced by the nutrition education. It is possible that the vitamin and mineral supplements which were taken by 80% of the women could have obscured improvements in biochemical indices which may have been due to the education program.

Adult↗
PubMed1978

Effects of antineoplastic drugs on Lactobacillus casei and radioisotopic assays for serum folate.

Microbiologic assay, usually employing Lactobacillus casei, remains the standard assay for serum folate to date. Among its disadvantages have been falsely low results in patients receiving bacteriostatic agents such as antibiotics. This study examined whether commonly used antineoplastic drugs had similar effect. Methotrexate and 5-fluorouracil depressed microbiologic serum folate levels. No effect was found for adriamycin, bleomycin, BCNU, cyclophosphamide, cytosine arabinoside, vincristine, vinblastine, mechlorethamine, mithramycin, hydroxyurea, and hydrocortisone. None of the drugs affected radioassay except methotrexate, which produced falsely high folate results. Thus, it appears that L. casei assay for folate becomes unreliable in patients receiving 5-fluorouracil and radioisotopic assay becomes unreliable in those receiving methotrexate.

Antineoplastic Agents↗
PubMed1990

Folate status assessment.

This paper is a review of established methods of folate status assessment and the primary factors that increase the risk of folate deficiency, including physiological life cycle changes. The first stage of folate depletion can be assessed by measuring serum folate levels, which drop prior to tissue depletion, and which are paralleled by a reduction in red blood cell (RBC) folate. Functional changes associated with abnormalities in biochemical pathways can be monitored by the deoxyuridine suppression test. Cell division, including erythropoiesis, becomes impaired in the same time sequence as changes in biochemical functions, as evidenced by abnormal erythrocyte morphology and a reduction in hemoglobin concentration. In addition to inadequate dietary folate intake, key factors that may impair folate utilization and thus status include alcohol consumption, smoking, and specific drugs. Folate requirements may increase during various phases of the life cycle due to physiological stresses such as pregnancy and lactation. Folate status may also be compromised during adolescence and in senescence for diverse reasons that require special emphasis on factors such as biological maturity and socioeconomic status, as well as chronic use of alcohol, drugs, and smoking.

Adolescent↗
PubMed1987

5-Fluorouracil and high-dose folic acid treatment for metastatic colon cancer.

Twenty-two patients with metastatic colorectal cancer were treated with a regimen of 5-fluorouracil 600 mg/m2 (maximum, 1.0 g) i.v./week and folic acid 140 mg/m2 i.v. given 1 h prior to the 5-FU. This study was undertaken in an attempt to confirm the in vitro finding that inhibition of thymidylate synthetase by 5-fluorouracil is prolonged by the presence of folates. There were four partial responses (18%) with mean duration 4 months. Dose-limiting toxicity was enteritis, seen in 12 patients (58%), and causing hospitalization in seven patients. Enteritis was shown to be due to the folic acid in most patients. Two patients died from leukopenia, enteritis, and sepsis. Mean serum folate levels at the time of 5-FU injection were 36 microM. This regimen is no more effective than 5-FU alone and has significantly more serious toxicity. Further investigation of this regimen is not recommended.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Peripheral neuropathy and folate deficiency as the first sign of Crohn's disease.

A 33-year-old man developed severe sensory peripheral neuropathy associated with low serum folate levels. No systemic disease was identified on the initial evaluation, but 21/2 years later he developed clinical and radiological features of Crohn's disease, confirmed by intestinal biopsy. Thus, sensory polyneuropathy may occur as the first manifestation of Crohn's disease.

Adult↗
PubMed1986

Study of dose-dependence and urinary folate excretion produced by ethanol in humans and rats.

Acute ethanol ingestion by human alcoholic subjects produces a marked decrease in serum folate levels within 16 hr. A similar decrease occurs in rats and can be explained by a marked increase in urinary folate excretion following ethanol treatment. To assess the effects of acute ethanol ingestion on urinary folate excretion in healthy human volunteers, two studies were carried out at initial ethanol dose levels of 0.8 g/kg and 1.0 g/kg, respectively. Blood ethanol levels peaked at 70 mg/dl in the first study, but in the second study were 100 +/- 20 mg/dl through 6 hr. Only in the second study were urinary folate levels significantly increased by ethanol administration, and this 8 hr after ingestion. This increase was accompanied by a decrease in urine volume so that in neither study was the total amount of urinary folate excreted from 0-12 hr increased by ethanol ingestion. Studies with various dose levels of ethanol in rats showed that there was a linear dose-response relationship between the total urinary folate excretion and the dose of ethanol. Peak urinary ethanol levels also correlated with urinary folate excretion. These results suggest that doses of ethanol larger than 1.0 g/kg produce increases in urinary folate excretion and that the inability to observe large increases in studies in human subjects is probably related to the limited doses of ethanol chosen.

Adult↗
PubMed1983

Side effects of phenobarbital and phenytoin during long-term treatment of epilepsy.

Phenobarbital and phenytoin have good antiepileptic effect, but clinically significant untoward effects occur during their long-term use. Phenobarbital may cause hyperactivity, behavioral problems, sedation, and even dementia; these effects are dose related to some extent. Side effects of phenytoin include sedation, a cerebellar syndrome, phenytoin encephalopathy, psychosis, locomotor dysfunction, hyperkinesia, megaloblastic anemia, decreased serum folate level, decreased bone mineral content, liver disease, IgA deficiency, gingival hyperplasia, and a lupus-like hypersensitivity syndrome. Especially susceptible to the neurotoxic effects of phenytoin are epileptic children with severe brain damage who are on multiple drugs. In those children, balance disturbance may develop and be followed by gradual loss of locomotion. Among 131 mentally retarded epileptic patients, phenytoin intoxication occurred in 73 (56%), of whom 18 experienced persistent loss of locomotion. There is experimental evidence that the toxic action of phenytoin lies at the cellular level, predominantly in the cerebellum. Many experts avoid the long-term use of phenytoin because of its insidious and potentially dangerous side effects.

Abnormalities, Drug-Induced↗
PubMed1998

A prevalence study of folate deficiency in a psychiatric in-patient population.

Controlled clinical trials in the UK have shown folate deficiency in psychiatric patients, and it has been suggested that such deficiency is most likely to occur among patients with affective disorders. Studies have led to the use of folate as an adjunct to therapy in such patients. The present paper describes a preliminary investigation into the red cell folate status of psychiatric patients in a general hospital unit compared with age- and sex-matched healthy controls, using up-to-date assays and strict entry criteria and overall improved methods on previous studies. The study showed that, although there is a trend for psychiatric patients to have lower serum folate levels than controls, there is no statistically significant difference in folate levels as measured by red cell folate, a more reliable measure of folate status, between healthy controls and psychiatric patients, and all but one of the patients had normal haematological indices.

Adult↗
PubMed1976

Diverticular disease: three studies. Part III - Metabolic effect of bran in patients with diverticular disease.

Patients with diverticular disease were given about 24 g bran daily for at least six months. After treatment the oral glucose tolerance curve fell, faecal fat excretion increased, the serum lipoprotein pattern was altered, urinary calcium excretion was reduced, and the serum folate level fell. These changes were not considered to contraindicate the use of bran in the treatment of diverticular disease.

Adult↗
PubMed1969

Pigmentation in megaloblastic anaemia associated with pregnancy and lactation.

Generalized skin pigmentation in five African women with megaloblastic anaemia in the postnatal period was associated with low serum folate levels, as distinct from vitamin B(12) deficiency. It is suggested that the occurrence of pigmentation in both folate and vitamin B(12) deficiency may reflect a common abnormality of metabolism.

Anemia, Macrocytic↗
PubMed1968

Follow-up study of coeliac disease.

In 9 out of 10 adults in whom a diagnosis of coeliac disease had been made in childhood, the diagnosis was confirmed by the finding of a flat intestinal mucosa. None showed abnormal physical signs, but three had a haemoglobin concentration below 10 g./100 ml. and all those not receiving folic acid supplements showed low serum folate levels. Five had moderate to severe symptoms at the time of investigation, but none was receiving treatment with a gluten-free diet.Periodic investigation of these patients may be necessary throughout life, and if they are found to have malnutrition they should be treated with a gluten-free diet.

Adult↗
PubMed1972

Lymphocytic infiltration of epithelium in diagnosis of gluten-sensitive enteropathy.

The macroscopic appearance of the mucosa of the small intestine and the lymphocytic infiltration of the epithelium were studied in 27 patients with dermatitis herpetiformis and in 11 control subjects. The mucosa was abnormal in appearance in 13 of the patients and normal in 14 patients and in all the controls. In 25 (93%) of the patients the intraepithelial lymphocyte count was significantly raised compared with the controls. The increased lymphocytic infiltration of the epithelium in the patients probably represented an underlying immunological reaction of the small intestine to gluten, since the infiltration lessened in five out of six patients after a year on a gluten-free diet and in all of four patients after three years on a gluten-free diet.Increased lymphocytic infiltration of the epithelium of the small intestine seems a surer sign of gluten sensitivity than the macroscopic appearance of the mucosa, and a diagnosis of gluten-sensitive enteropathy may no longer be excluded when the mucosa appears normal. Further evidence of the significance of increased lymphocytic infiltration is that patients with normal-looking mucosa but with raised intraepithelial lymphocyte counts often had low serum folate levels.

Biopsy↗
PubMed1968

Absorption and utilization of polyglutamyl forms of folate in man.

Some three-quarters of folate compounds in a normal mixed diet have a chain of seven glutamic acid residues (polyglutamates). The extent to which these forms of folate are absorbed and utilized by man is of considerable nutritional importance. These studies indicate that the polyglutamate forms were absorbed and utilized to about one-third of the extent of simpler (monoglutamate) forms, as judged by the serum folate levels after oral equimolar doses, by the amount incorporated into red cells in long-term studies, by the amount excreted into the urine, and by their capacity to initiate haematological responses in patients with folate-deficient megaloblastic anaemias.

Anemia, Macrocytic↗
PubMed1970

Folic acid in folate-deficient patients with epilepsy.

A double-blind trial using folic acid 15 mg. daily and identical placebo was carried out in 51 epileptic patients having a serum folate level below 3.6 ng./ml. Treatment was for a minimum of six months and in 41 patients was for more than one year. There were no significant changes in the frequency of seizures, behaviour, and personality, or in a number of cognitive functions.

Adolescent↗
PubMed1976

Alcohol and absorption from the small intestine. 1. Impairment of absorption from the small intestine in alcoholics.

An absorption screen was performed in 10 chronic alcoholic patients within a few days of admission due to an acute alcoholic episode. Impaired absorption of d-Xylose was noted in three patients and low leucocyte ascorbic acid and serum folate levels in five. No abnormality was detected in jejunal histology. The absorption of water and electrolytes from the jejunum was studied in these patients using a triple-lumen tube perfusion system. The mean rate of absorption of water in the alcoholic subjects (50-0 +/- 2-3 ml/h) was significantly lower (P less than 0-001) than the mean value in 14 healthy control subjects (205 +/- 15-9 ml/h). A significant reduction of Na+ and Cl-absorption was also demonstrated in the alcoholic subjects. These results indicate that patients with acute-on-chronic alcoholism may have a function impairment of water and electrolyte absorption from the jejunum. This may, in part, account for some of the nutritional deficiencies in such patients and for symptoms such as diarrhoea which may be present.

Adult↗
PubMed1978

Acid microclimate in coeliac and Crohn's disease: a model for folate malabsorption.

The surface pH of human proximal jejunum was measured in biopsy samples and found to be more acid than the phosphate buffer in which they were incubated. The in vitro jejunal surface pH was 5.93 +/- 0.05 in control subjects and 6.19 +/- 0.09 in treated coeliac patients. A group of untreated coeliac patients with a surface pH of 6.56 +/- 0.14 had a significantly less acid surface pH compared to controls, as did a group of Crohn's patients with a surface pH of 6.21 +/- 0.04. These two groups with a significantly raised surface pH were subdivisible into 'high' and 'low'groups. Surface pH was found to remain low in the treated coeliac and control groups but became more acid over the incubation period reaching almost normal values in the Crohn's group and the untreated coelic initial surface pH. The raised surface pH in untreated coeliac disease and Crohn's disease would alter the amount of a weak acid available for non-ionic diffusion. Therefore the present results may help to explain the folate malabsorption known to occur in untreated coeliac disease and the frequently seen low serum folate levels in Crohn's disease.

Adolescent↗