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Reduction of circulating homocysteine levels by folic acid suggests an additional approach to the prophylaxis of certain forms of vascular disease related to atherogenic amino acids.
Novel coupling reagents are used for the simple and sensitive spectrophotometric determination of folic acid either in pure form or in its pharmaceutical preparations. The methods are based on the probable diazotization of the p-aminobenzoylglutamic acid obtained after reductive clevage of folic acid, followed by either coupling with iminodibenzyl to give a violet product with lambda(max) of 580nm or coupling with 3-aminophenol to produce an orange yellow-colored product with lambda(max) of 460nm. Sodium molybdate and pyrocatechol are used in the third method and the pale red-colored product formed has a lambda(max) of 490nm. The methods are highly reproducible and have been applied to the determination of folic acid in tablets and the results compare favorably with the official method. Common excipients used as additives in pharmaceutical preparations do not interfere in the proposed methods.
BACKGROUND: In 1996, the Food and Drug Administration issued a regulation requiring all enriched grain products to be fortified with folic acid to reduce the risk of neural-tube defects in newborns. Fortification (140 microg per 100 g) began in 1996, and the process was essentially complete by mid-1997. METHODS: To assess the effect of folic acid fortification on folate status, we measured plasma folate and total homocysteine concentrations (a sensitive marker of folate status) using blood samples from the fifth examination (January 1991 to December 1994) of the Framingham Offspring Study cohort for baseline values and the sixth examination (January 1995 to August 1998) for follow-up values. We divided the cohort into two groups on the basis of the date of their follow-up examination: the study group consisted of 350 subjects who were seen after fortification (September 1997 to March 1998), and the control group consisted of 756 subjects who were seen before fortification (January 1995 to September 1996). RESULTS: Among the subjects in the study group who did not use vitamin supplements, the mean folate concentrations increased from 4.6 to 10.0 ng per milliliter (11 to 23 nmol per liter) (P<0.001) from the baseline visit to the follow-up visit, and the prevalence of low folate concentrations (<3 ng per milliliter [7 nmol per liter]) decreased from 22.0 to 1.7 percent (P< 0.001). The mean total homocysteine concentration decreased from 10.1 to 9.4 micromol per liter during this period (P<0.001), and the prevalence of high homocysteine concentrations (>13 micromol per liter) decreased from 18.7 to 9.8 percent (P<0.001). In the control group, there were no statistically significant changes in concentrations of folate or homocysteine. CONCLUSIONS: The fortification of enriched grain products with folic acid was associated with a substantial improvement in folate status in a population of middle-aged and older adults.
1. Human red blood cell membrane oxidase catalyzes the transformation of folic acid to pterin-6-aldehyde and p-aminobenzoyl glutamic acid provided hydrogen peroxide, a xanthine oxidase inhibitor, is present. Horseradish peroxidase produces the same product in the absence of hydrogen peroxide. 2. The oxidation of folic acid by horseradish peroxidase is accompanied by photon emission. Several lines of evidence suggest that singlet oxygen is the emitting species and is generated directly: a) the effects of singlet oxygen traps such as bilirubin, and of singlet oxygen enhancers such as 1,4-diazobicyclo 2.2.2 octane (DABCO) and eosin; b) the emission spectrum maximum of the unsensitized reaction was greater than 560 nm; c) enhancement of photon emission when the reaction was carried out in D2O, and d) no enhancement of the emission was observed when anthracenic energy acceptors were present. 3. Singlet oxygen production and the inactivation of xanthine oxidase may be important when considering folic acid metabolism by cancer cells, in view of the fact that the level of this enzyme is low in these cells.
OBJECTIVES: To investigate the levels of vitamin A, E, B12, folic acid in employees with hearing loss due to noise. PATIENTS AND METHODS: Employees in a local hydroelectric powerhouse who suffered from hearing loss due to noise were included in the study. Study and control groups were composed of 28 employees (mean age 37+/-5 years) and 30 voluntary subjects (mean age 36+/-4 years), respectively. All the subjects in patient and control groups were males. Blood samples were obtained from all subjects and vitamin A, E, B12 and folic acid levels were measured. RESULTS: Level of vitamin B12 was found low in the patient group and normal in the control group and these were found statistically significant (p<0.005). There were no significant differences between vitamin A, E and folic acid levels. CONCLUSION: We think that measurement of vitamin B12 in routine control of the people who are working in noisy environment may be useful.
Folic acid levels during pregnancy and in pre-pregnancy were determined in 51 epileptic mothers and those of matched controls. The serum folic acid (SF) levels of epileptic mothers were significantly lower than those of controls in all study periods. The SF levels of mothers of malformed offspring were significantly lower than those of mothers of normal offspring in the 1st and 2nd trimesters of pregnancy. These results suggest that SF concentrations are implicated in congenital malformations in the offspring of epileptic mothers.
BACKGROUND: Hyperhomocysteinemia is an independent risk factor of coronary artery disease, but some studies have shown that patients with hyperhomocysteinemia are not prone to atherosclerosis. The aim of this study was to test whether homocysteine increases the production of matrix metalloproteinase-2 (MMP-2) and if extracellular additional magnesium and folic acid alters MMP-2 secretion. METHODS AND RESULTS: Gelatin zymography and western blotting were used to investigate the effects of different homocysteine levels (0-5,000 micromol/L) on MMP-2 production, and the effects of different folic acid concentrations (0-10 micromol/L) and magnesium concentrations (0-3.0 mmol/L) on homocysteine-induced MMP-2 in cultured rat vascular smooth muscle cells. Furthermore, the changes in MMP-2 were compared under various treatments for 24 h, 48 h and 72 h. Homocysteine (50-1,000 micromol/L) increased the production of MMP-2 significantly in a dose-dependent manner and at a high level (5,000 micromol/L) reduced the production of MMP-2. Increased production of MMP-2 induced by homocysteine was reduced by additional extracellular folic acid in a dose-dependent manner. Magnesium also reduced the increase of MMP-2 production induced by homocysteine. Production of MMP-2 under various treatments for 72 h increased more than during 24 or 48 h. CONCLUSIONS: Homocysteine (50-1,000 micromol/L) significantly increased the production of MMP-2 in a dose-dependent manner. Added extracellular folic acid and magnesium decreased the homocysteine-induced MMP-2 secretion. These data suggest a beneficial effect of folic acid and magnesium on the pathogenesis of coronary artery disease.
The proliferation of chicken fibroblasts is strongly stimulated by folic acid, at greater than physiological concentrations, in a plasma-containing medium, or by serum in a medium of physiological folic acid concentration. Serum and plasma, however, do not appear to differ in their content of folic acid derivatives.A qualitative difference between the proliferative behaviors of normal and transformed fibroblasts is obtained when these cells are cultivated in a physiological-folate-low-calcium-plasma medium. In such a medium, transformants proliferate steadily, at a significant rate, while normal fibroblasts do not multiply at all.
Vitamin B12 malabsorption was reported earlier to occur in patients with exocrine pancreatic insufficiency, and pancreatic extracts were shown to improve the absorption of vitamin B12. We investigated serum levels of vitamin B12 and serum folate in patients with chronic pancreatitis and different degrees of pancreatic insufficiency. 137 patients (84 males, 53 females, age 34-72 years) with chronic pancreatitis (C.P.) were included in the study. 123 of 137 (89.8%) patients had a pathologic pancreatic function test result, classified into mild (n = 24), moderate (n = 61) or severe (n = 38) insufficiency. The normal range of serum vitamin B12 and folic acid was established in 58 healthy controls and was found to be 190-1020 pg/ml for serum vitamin B12 and 2.4-16.1 ng/ml for folic acid. 7 patients (5.7%) with C.P. had vitamin B12 serum levels below 190 pg/ml; 4 of these had severe and 3 had mild or moderate exocrine pancreatic insufficiency. However there was no overall correlation between the degree of pancreatic insufficiency and vitamin B12 values. Serum levels of Vitamin B12 were 512 +/- 48 pg/ml in mild, 493 +/- 52 pg/ml in moderate and 428 +/- 45 pg/ml in severe exocrine insufficiency. Serum folic acid below 2.4 ng/ml were present in 5 patients (3.6%). Folic acid serum levels were 8.34 +/- 0.76 ng/ml in mild, 6.34 +/- 0.52 ng/ml in moderate and 7.45 +/- 0.53 ng/ml in severe exocrine insufficiency. We conclude that vitamin B12 deficiency is a rare finding in chronic pancreatitis and does not strictly depend on the degree of exocrine pancreatic insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVE: We attempted to evaluate the effect of oral folic acid supplementation on the course of cervical dysplasia. STUDY DESIGN: A total of 235 subjects with grade 1 or 2 cervical intraepithelial neoplasia were randomly assigned to receive either 10 mg of folic acid or a placebo daily for 6 months. Clinical status, human papillomavirus type 16 infection, and blood folate levels were monitored at 2-month intervals. Outcome data were subjected to chi 2 analysis. RESULTS: The prevalence of human papillomavirus type 16 infection initially was 16% among subjects in the upper tertile of red blood cell folate versus 37% in the lower tertile (trend p = 0.035). After 6 months no significant differences were observed between supplemented and unsupplemented subjects regarding dysplasia status, biopsy results, or prevalence of human papillomavirus type 16 infection. CONCLUSION: Folate deficiency may be involved as a cocarcinogen during the initiation of cervical dysplasia, but folic acid supplements do not alter the course of established disease.
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OBJECTIVE: To compare the effectiveness of weekly vs daily iron and folic acid supplementation for control of anemia in adolescent Nepalese girls. DESIGN: Randomized controlled trial. SETTING: A Government Girl School in Dharan, Nepal, an urban foothill town that is 305 m above sea level. SUBJECTS: Consecutive healthy adolescent girls (n = 209, median age 15 years) randomized to 3 groups matched for age, anthropometry, and personal and sociodemographic characteristics. Of 209 subjects, 181 completed the trial. Two girls had adverse reactions to treatment and were excluded. INTERVENTION: Group A (n = 70) received a 350-mg ferrous sulfate and 1.5-mg folic acid combination once daily for 90 to 100 days. Group B (n = 67) received the tablet under supervision once a week for 14 weeks. Group C (n = 72) did not receive any drugs. OUTCOME VARIABLE: Presupplementation and postsupplementation differences in prevalence of anemia and change in hematocrit. RESULTS: Prevalence of anemia (defined as hematocrit <36%) declined from 68.6% and 70.1% in groups A and B to 20% and 13.4%, respectively, postsupplementation (P<.001), whereas the prevalence in group C changed little (68.1% to 65.3%, P =.81). There was a significant rise in the mean hematocrit of both supplemented groups (group A, 32.9% +/- 3.5% to 41.0% +/- 5.6%, P<.001; group B, 33.2% +/- 3.6% to 40.4% +/- 4.9%, P<.001) but no appreciable change in controls (34.2% +/- 2.9% to 34.1% +/- 3.3%, P =.91). Net change in mean hematocrit in both the supplementation groups was comparable (P =.57). CONCLUSIONS: The prevalence of anemia in adolescent Nepalese girls is high. Supervised iron and folic acid therapy once a week is an effective alternative to daily administration and helps lower the prevalence of anemia in adolescent girls.
OBJECTIVES: To compare the plasma levels of vitamin B12 and folic acid following resection of ileocecal or ileal segments used for orthotopic bladder substitution. METHODS: Hemoglobin, hematocrit, and plasma levels of vitamin B12 and folic acid were measured in 34 patients with ileocecourethrostomy (ICUS) and in 16 patients with ileal reservoir (IR), with a mean follow-up of 59.8 +/- 41.9 months. The results were compared with regard to both the type of operation and the length of time since surgery. RESULTS: The level of folic acid was normal in all patients. The mean level of vitamin B12 in the ICUS group was 413.67 +/- 160.45 ng/mL compared to 257.63 +/- 121.36 for the IR group. This difference was statistically significant. In the IR group, 18.75% of the patients had a level of vitamin B12 below normal. CONCLUSIONS: There is a tendency for vitamin B12 levels to fall in patients in whom the ileum is used. Resection of the ileocecal segment including the junction does not alter the level of vitamin B12.
OBJECTIVE: To determine prospectively plasma levels of vitamin B12 and folic acid in children with intestinal parasitic infection before and three months after antiparasitic treatment. METHODS: 3036 stool samples were collected from 1959 children and 939 cello-tape anal swabs were taken from 688 children for intestinal parasite investigation. Of these, 155 children were identified as having a parasitic infection; however, only 86 were followed up during this study: 26 children with Giardia lamblia infection were treated with tinidazole and metronidazole, pyrantel pamoate was used in the treatment of 40 children with Enterobius vermicularis, and 20 patients infected with Cryptosporidium parvum received only symptomatic treatment. Vitamin B12 and folic acid levels were measured by radioimmunoassay, before and three months after the completion of treatment. RESULTS: Vitamin B12 serum concentrations did not show any significant differences among the three groups. There was a significant increase in vitamin B12 serum concentrations after three months of anti-parasitic treatment (630.57+/-200.97 vs. 667.97+/-181.55 pg/dL, p = 0.002, n = 86). Paired analysis in each group showed only significant increases for vitamin B12 in the Giardia lamblia group and in the Enterobius vermicularis group. No statistically significant differences were found for folic acid serum concentrations before and three months after treatment. CONCLUSIONS: Patients with symptomatic infection by Giardia lamblia and Enterobius vermicularis have lower vitamin B12 levels than asymptomatic patients. This could reflect a more affected intestinal mucous. These results could present the opportunity to treat these parasitic infections and to use vitamin B12 supplementation in symptomatic children with Giardia lamblia and Enterobius vermicularis infection.
AIM: The purpose of this study was to investigate the relationship between cigarette smoking and the serum levels of folic acid, vitamin B(12) and some haematological variables in patients with periodontal disease. PATIENTS AND METHODS: The study base consisted of 88 volunteer patients with periodontal disease, including 45 current smokers in the age range 31-68 years and 43 non-smokers in the range 32-66 years. The clinical parameters included plaque index (PI), gingival index (GI), bleeding on probing (BOP), probing depth (PD) and clinical attachment loss (CAL). Folic acid, vitamin B(12) and haematological variables were determined from peripheral blood samples. RESULTS: PI, PD and CAL means were significantly higher in smokers than non-smokers (p<0.05). The serum folic acid concentration of smokers was lower than that of non-smokers (p<0.05), whereas the white blood cell count was higher in smokers than in non-smokers (p<0.05). CONCLUSION: The results of this study suggest that among patients with periodontal disease the serum folic acid concentration is lower in smokers compared with non-smokers.
Hyperhomocysteinemia (HHC) is a known risk factor for venous and arterial thrombosis. Thrombophilia workup includes the level of homocysteine and other related parameters such as: vitamin B(12), folic acid, and methylenetetrahydrofolate reductase (MTHFR) C677T genotype. As the levels of homocysteine, vitamin B(12), folic acid, and MTHFR C677T genotype are linked biochemically, we hypothesized that a statistical association will be found between them. The purpose of the present study was to assess the association between the four parameters in patients with a thrombotic event or recurrent fetal loss. The potential study population included 326 patients who were referred to the Thrombosis and Hemostasis Unit; 125 of these patients had at least one pathological test result of the four parameters. The correlations between homocysteine and vitamin B(12) as well as between homocysteine and folic acid were found to be weak (r = -0.236 and r = -0.209, respectively). No significant difference was revealed between the mean homocysteine level and the CC, CT, and TT MTHFR genotypes (p = 0.246). In conclusion, in the population studied, the association between homocysteine, vitamin B(12), folic acid, and MTHFR C677T is weak. The results raise doubt as to whether the current routine evaluation of HHC, as part of thrombophilia workup, truly reflects the increased risk of thrombosis.
Pittillo, Robert F. (Southern Research Institute, Birmingham, Ala.), Mary Lucas, Robert T. Blackwell, and Carolyn Woolley. Modification of radiation damage of bacteria by folic acid antagonists. J. Bacteriol. 90:1548-1551. 1965.-The folic acid analogues, 2,4-diamino-6-methylpteridine, amethopterin, and aminopterin, have been found to sensitize certain bacteria, especially Escherichia coli, to the lethal action of ionizing irradiation. Data are presented which indicate that (i) the compounds must be present during the irradiation period for maximal sensitization to be observed, (ii) the sensitizing effect can be nullified by cysteine or cysteamine, (iii) the sensitizing effect occurs in a number of diverse bacterial genera, and (iv) folic acid neither sensitizes bacteria to irradiation nor prevents the sensitization caused by these antifolic agents.