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Treatment of hyperhomocysteinemia in children on dialysis by folic acid.

Adult patients with renal failure have a high total homocysteine concentration in plasma. Hyperhomocysteinemia is an independent risk factor for cardiovascular diseases. Folic acid lowers the homocysteine concentrations in plasma in hyperhomocysteinemia. Whether this results in a reduced risk for cardiovascular diseases remains to be proven by intervention studies. In the present study we investigated: (1) if homocysteine concentrations are elevated in the plasma of children with renal failure and (2) the influence of folic acid administration on the plasma homocysteine concentration. The plasma homocysteine concentration was measured in 21 children, 9 on hemodialysis and 12 on peritoneal dialysis, before and 4 weeks after treatment with 2.5 mg folic acid daily. Healthy children (234) constituted the control group. In controls the median homocysteine concentration was 9.1 micromol/l (range 4.3-20.0 micromol/l). The median plasma homocysteine concentration in patients before folic acid treatment was 20.0 micromol/l (Q1-Q3 13.7-26.0; Q, quartile). After 4 weeks of folic acid treatment the median plasma homocysteine concentration was 12.0 micromol/l [Q1-Q3 9.8-14.3 (P<0.0001 Wilcoxon signed rank test)]. There was no significant difference between hemodialysis and peritoneal dialysis patients. Children with renal failure treated with hemodialysis or peritoneal dialysis have elevated plasma homocysteine concentrations, but this is significantly reduced after administration of 2.5 mg folic acid daily for 4 weeks. It is suggested that folic acid be added to the treatment of children with renal failure, although a beneficial effect still has to be proven. The required dose needs further study.

Child↗

Folic acid and Vitamin B6 supplementation and plasma homocysteine concentrations in healthy young women.

Elevated plasma homocysteine levels are a risk factor for atherosclerotic disease. Elevated fasting plasma homocysteine concentrations can be reduced by vitamin supplementation with folic acid, vitamin B6 and vitamin B12, but the effect of nutritive amounts of single vitamins on homocysteine plasma levels within the normal range is not known. This study was performed to investigate the effect of folic acid supplementation (400 micrograms/d) on fasting plasma homocysteine levels in healthy young women, in comparison to vitamin B6 (2 mg/d) or a combination of both vitamins. Healthy young women with normal homocysteine levels were supplemented for four weeks either with folic acid, vitamin B6 or the combination. The combination of folic acid and vitamin B6 reduced plasma homocysteine by 17%. Supplementation with folic acid reduced plasma homocysteine levels by 11.5%. The effect of folic acid and vitamin B6 was not significantly different from the effect of folic acid alone. Vitamin B6 had no effect on plasma homocysteine concentrations. Results show that homocysteine levels within the normal range are lowered by low-dose vitamin supplementation including folic acid.

Adult↗

Reduction of plasma homocysteine by folic acid in children with chronic renal failure.

Hyperhomocysteinemia is a well-known independent risk factor for cardiovascular disease and is a prevalent abnormality in chronic renal failure. However, studies on this abnormality in children with chronic renal failure, before renal replacement therapy, are scarce. In this study, we measured the plasma homocysteine levels of 27 children (mean age 8.9+/-4.8 years) with predialytic chronic renal failure, and analyzed the effect of folic acid supplementation (1 mg daily for 4 weeks) on the homocysteine levels in 14 of these children. The baseline homocysteine concentration of the patients (12.5+/-6.0 micro mol/l) was higher than that of the control group (5.9+/-1.8 micro mol/l, P<0.001), and correlated positively with age and negatively with folic acid concentration. Folic acid and vitamin B(12) concentrations were not below normal in any patient. The homocysteine concentration was decreased from 13.2+/-6.6 micro mol/l (pretreatment) to 9.3+/-4.2 micro mol/l by folic acid supplementation in the 14 patients. Folic acid supplementation also lowered the prevalence of hyperhomocysteinemia from 64.3% to 42.9%. According to these results, we recommend that folic acid supplementation be started in children with chronic renal failure early in the disease course.

Adolescent↗

Occurrence of Crithidia factors and folic acid in various bacteria.

Crithidia factors and folic acid were found to be widely distributed in culture fluids and in cells of 27 species of bacteria, when cultured under aerobic conditions into the stationary phase. Most bacteria excreted more Crithidia factors and folic acid than they retained in their cells. One Crithidia factor produced by Serratia indica and one produced by Bacillus cereus differed from biopterin in their chromatographic behavior. The factor excreted by S. indica appeared to be a 2-amino-4-hydroxy-6-substituted pteridine on the basis of KMnO(4) oxidation and ultraviolet absorption spectra. One of the folate compounds excreted by this organism was shown to be identical to 5,10-methylidynetetrahydrofolic acid by bioautography.

Bacteria↗

[Interrelations between serum folic acid and hematologic changes in psychiatric patients].

Changes in the blood picture as well as in the content of folic acid and iron in the serum were investigated in 223 patients treated in a psychiatric clinic because of psychoses and dementia. Psychopharmaka of the phenobarbiturate type, dihydrophenytoine as well as primidone were administered in 29 cases. As anaemia could be identified in 32 patients; 3 of them turned out to be a hyperchronic anaemia, 25 a normochromic anaemia and 4 a hypochromic type one. In 78.1% of the anaemic patients there was a lowered folic acid level. All four cases with hypochromic anaemia showed a lowered serum level. A hypersegmentation of neutrophilic granulocytes could be identified in 48 patients (28.4%), with a lowered folic acid content in the serum being present in all cases. A lowered folic acid content in the serum could be found in 76.2% of the patients. All patients treated with psychopharmaka showed a subnormal folic acid content. On the other hand, a lowered iron content in the serum could only be identified in 8.1% of the cases. The final evaluation of all findings gathered results in the recommendation to attach greater importance to a direct determination of folic acid concentration in the serum in those cases of disease particularly exposed.

Adolescent↗

Folic acid supplements in vitamin tablets: a determinant of hematological drug tolerance in maintenance therapy of childhood acute lymphoblastic leukemia.

Methotrexate (MTX) is an antifolate that inhibits cell division by reducing intracellular amounts of reduced tetrahydrofolates. Of 53 children with acute lymphoblastic leukemia (ALL) in maintenance treatment with MTX and 6-mercaptopurine (6-MP), 25 had received daily folic acid supplements in vitamin tablets containing 75-200 micrograms folic acid for at least the preceding 3-month period. Experimental data have shown that increased folate concentrations intracellularly inhibit MTX metabolism and toxicity. Therefore we found it relevant to investigate the extent to which folic acid supplements affect hematological tolerance to MTX and 6-MP in children during maintenance therapy for ALL. The erythrocyte folate (ery-folate) concentration was significantly higher in children who received extra folic acid than in those who did not (p less than 0.001). The ery-folate in MTX-treated children was only marginally reduced compared with the controls. The erythrocyte methotrexate (ery-MTX) concentration correlated with the weekly dose of MTX but not with any of the investigated hematological parameters. Children who received vitamin tablets containing folic acid had higher thrombocyte counts (p = 0.0056), higher leukocyte counts (p = 0.06), higher neutrophil counts (p = 0.05), and lower erythrocyte mean cell volumes (p = 0.05) than children who received no folic acid. We conclude that folic acid supplements of 75-200 micrograms/day affect the proliferative capacity of the bone marrow. Since none of the children was folate deficient as judged by the ery-folate, we recommend that vitamins given to children in maintenance treatment with MTX and 6-MP for ALL should not contain folic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗

Prevention of neural tube defects with periconceptional folic acid.

A body of convincing evidence demonstrates that periconceptional folic acid supplements are associated with a reduction in the risk for first occurrences of neural tube defect and for recurrence of neural tube defects among women with a previously affected pregnancy. The mechanism(s) of this protective effect are unknown, and although the effect can be seen with folate doses between 0.4 and 4 mg, the optimal dose remains unknown. The optimal method of ensuring that all women of child-bearing age receive this dose of folate remains in question; supplementation offers the advantage of targeting only the population at risk, whereas food fortification offers the advantage of ensuring compliance in virtually all of the population at risk. The use of periconceptional folic acid can be expected to reduce, but not abolish, the incidence of neural tube defects. Research into the mechanism(s) of the protective effects of folic acid and the underlying biology of neural tube defects is required to address the problem of how to develop therapeutic strategies to further reduce the impact of neural tube defects.

Diet↗

Chemical binding of folic acid and methotrexate to bovine fibrinogen.

The binding of folic acid as a model compound and methotrexate as a representative of antifolates to bovine fibrinogen with the aid of 1-ethyl-3-(3-dimethylamino-propyl)-carbodiimide was investigated in order to study the possibility of using fibrinogen as a drug carrier. Soluble modified fibrinogen derivatives containing 0.03-0.1 mg of folic acid or methotrexate per mg of protein were obtained under optimal conditions. These derivatives retained the ability to form fibrin clot by the action of thrombin and to copolymerize with native fibrinogen to the three dimensional fibrin network. At higher concentrations of water soluble carbodiimide, higher temperature and low pH highly cross-linked derivatives of fibrinogen and folic acid (or methotrexate) were formed which were insoluble in water and salt solutions (pseudofibrin). The modified fibrin was extensively proteolytically cleaved by plasmin, pepsin, trypsin and cathepsin D, whereas the proteolysis of insoluble pseudofibrin was very slow.

Animals↗

Trace nutrients. 3 Magnesium, copper, zinc, vitamin B6, vitamin B12 and folic acid in the British household food supply.

1. Intakes of magnesium, copper, zinc, vitamin B6, vitamin B12 and folic acid in Britain were calculated by applying the values selected for the 4th edition of McCance and Widdowson's The Composition of Foods (Paul & Southgate, 1978) to the amounts of food recorded in the National Food Survey made during 1976 (Ministry of Agriculture, Fisheries and Food, 1977). 2. National average intakes were (/person per d): Mg 249 mg, Cu 1.51 mg, Zn 9.1 mg, vitamin B6 1.36 mg, vitamin B12 6.6 micrograms free folic acid 105 microgram and total folic acid 190 micrograms. Corresponding intakes (/person) in families with four or more children were 10-20% lower. 3. A comparison of intakes with those recommended in Canada (Department of National Health and Welfare, 1976) and the USA (National Research Council, 1974) or by WHO (1973) indicated that for folic acid average values were particularly low, and only for vitamin B12 were the recommendations significantly exceeded. 4. Contributions from alcoholic drinks and confectionery were also calculated and found, on average, to be significant for cu, vitamin B12 and folic acid. 5. The losses of B-vitamins which might occur on cooking are discussed.

Alcoholic Beverages↗

Bacteriophage T4 baseplate components. I. Binding and location of the folic acid.

Two different proteins with high affinities for the pteridine ring of folic acid have been used to determine the location of this portion of the folate molecule in the tail plate of T4D and other T-even bacteriophage particles. The two proteins used were (i) antibody specific for folic acid and (ii) the folate-binding protein from bovine milk. Both proteins were examined for their effect on various intact and incomplete phage particles. Intact T2H was weakly inactivated by the antiserum but not by the milk protein. No other intact T-even phage, including T4D, was affected by these two proteins. When incomplete T4D particles were exposed in an in vitro morphogenesis system, it was found that neither of the two proteins affected either the addition of the long tail fibers to fiberless particles or the addition of tail cores to tail plates. On the other hand, these two proteins specifically blocked the addition of T4D gene 11 product to the bottom of T4D baseplates. After the addition of the gene 11 protein, these two reagents did not inhibit the further addition of the gene 12 protein to the baseplate. It can be concluded that the phage folic acid is a tightly bound baseplate constituent and that the pteridine portion of the folic acid is largely covered by the gene 11 protein.

Animals↗

Zinc status is not adversely affected by folic acid supplementation and zinc intake does not impair folate utilization in human subjects.

Changes in zinc status in response to folic acid supplementation and the effect of zinc intake on folate utilization were evaluated in 12 men (20-34 y old) consuming a diet containing 3.5 or 14.5 mg zinc/d for two 25-d intervals. Deuterium-labeled folic acid (800 micrograms/d) or a placebo was administered orally during each phase. No differences in plasma zinc, erythrocyte zinc, urinary zinc, erythrocyte metallothionein or serum alkaline phosphatase, due to supplemental folic acid, were detected at either level of zinc intake. Differences in the response to folic acid supplementation, due to the level of zinc intake, were not detected for serum, erythrocyte or urinary (labeled and unlabeled) folate. Within the constraints of this short-term folic acid supplementation study, adverse effects on zinc status were not observed and our data suggest that folic acid utilization was not influenced by level of zinc intake.

Administration, Oral↗

[Recommended dietary allowance of folic acid is insufficient for optimal homocysteine levels].

OBJECTIVE: To determine the effect of short term supplementation of vitamin B6 (pyridoxine) followed by folic acid in apparently healthy volunteers on the fasting plasma homocysteine concentrations (hyperhomocysteinaemia is an independent risk factor for premature atherosclerosis). DESIGN: Prospective, descriptive. SETTING: Academic Hospital Groningen, the Netherlands. METHODS: Apparently healthy Dutch volunteers, aged 20-75 years, were supplemented with vitamin B6 1 mg/kg/day during 7 days followed by folic acid 5 mg/day during another 7 days. On days 0, 7 and 14 the fasting plasma homocysteine concentrations were measured. A change of an individual's plasma homocysteine level was considered statistically significant if the change in percentage exceeded 2.8 times the sum of the analytical and the intraindividual biological variation. RESULTS: There were 103 participants, 45 males and 58 females, with average ages of 43 and 44 years, respectively (on day 7, data were available on 101 participants). Baseline folic acid concentrations of all participants were above the lower limit of the reference range. Eight and two of them had vitamin B6 and vitamin B12 concentrations below the reference range, respectively. Plasma homocysteine was inversely related to plasma levels of folic acid and vitamin B12 at that moment. During vitamin B6 supplementation the mean plasma homocysteine level did not change; one participant exhibited a significant plasma homocysteine decrease. During folic acid supplementation the mean plasma homocysteine decreased from 11.7 mumol/l (SD: 5.6) to 9.1 (SD: 3.4); 40 participants (40%) exhibited significant plasma homocysteine decreases. At the end of the study plasma homocysteine was still related to plasma vitamin B12. CONCLUSION: The folic acid status of the participants at baseline was not associated with the lowest plasma homocysteine levels. Since atherosclerosis risk may increase continuously with increasing plasma homocysteine, it may be wise to keep plasma homocysteine levels as low as possible. To reach this goal, the recommended dietary allowance of folic acid may have to be increased.

Adult↗

Serum concentrations and clearances of folic acid and pyridoxal-5-phosphate during venovenous continuous renal replacement therapy.

OBJECTIVE: To determine to what extent hydrosoluble vitamins are removed by continuous renal replacement therapy (CRRT); to evaluate clearances, removal rates, and evolution of serum concentrations of folic acid and pyridoxal-5'-phosphate (P-5'-P), the active moiety of vitamin B6 during CRRT. DESIGN: A prospective, non-interventional, descriptive study on vitamin losses induced by CRRT. SETTING: Medical and surgical intensive care units in a tertiary university-affiliated hospital. PATIENTS: A total of ten critically ill patients in oligoanuric acute renal failure (five treated by continuous venovenous hemofiltration and five by continuous venovenous hemodiafiltration) with a mean effluent rate of 1801 +/- 468 ml/h. Nutritional support was not modified and additional vitamin supplements were not provided during study periods. MEASUREMENTS AND RESULTS: Concentrations of folic acid and P-5'-P were determined daily during CRRT. Samples for folic acid, P-5'-P, urea, and creatinine were taken simultaneously from the blood at the dialyzer inlet and from the effluent, at CRRT initiation, and daily thereafter over an average of 3.4 +/- 1.2 days. Samples were processed by immunochemiluminescence for folic acid and by radioenzymatic assay for P-5'-P determinations with normal ranges above 6.8 nmol/l and from 11.5 to 179.3 nmol/l, respectively. Marked decreases in serum folic acid and P-5'-P concentrations were noticed over time with mean daily reductions of 12.6 and 13.7%. Serum folic acid concentrations decreased from 42.7 to 16.0 nmol/l and serum P-5'-P decreased from 14.4 to 5.0 nmol/l in the blood coming in to the dialyzer over the study period. Clearances and removal rates were determined from the effluent side. During CRRT, mean (+/- SEM) folic acid and P-5'-P clearances were 20.5 +/- 6.3 ml/min (n = 34) and 13.2 +/- 10.6 ml/min (n = 22), whereas mean urea clearance was 27.1 +/- 5.1 ml/min (n = 26). Folic acid and P-5'-P removal rates were 27.0 +/- 34.2 and 3.4 +/- 2.0 nmol/h, corresponding to mean daily losses of nearly 650 and 80 nmol/day respectively. CONCLUSION: Significant losses of folic acid and P-5'-P (and most likely of other hydrosoluble vitamins) occur during CRRT. Considering that stores of most hydrosoluble vitamins are relatively low in critically ill patients, supplementation should be provided to patients treated similarly.

Aged↗

Rates of twinning before and after fortification of foods in the US with folic acid, Texas, 1996 to 1998.

Several investigators have reported a 40% increase in the prevalence of twinning among women who have taken folic acid or multivitamins containing folic acid at the time of conception. Given that infant morbidity and mortality are greatly increased among twins, such a large increase in twinning could have serious implications. We undertook this study to determine if US fortification of enriched cereal-grain products with folic acid was associated with an unexpected increase in the prevalence of twinning in the state of Texas. We examined 1 003 207 deliveries conceived in Texas, between 1 January 1996 and 31 December 1998. We compared the prevalence of twin deliveries conceived before, during and after fortification with folic acid, mandated to begin on 1 January 1998. Comparing pregnancies conceived in 1997 with those conceived in 1996, we observed a 2.4% yearly increase in twinning, 1.024 [0.98, 1.07]. Comparing pregnancies conceived in 1998 with those conceived in 1997, we observed a 4.6% yearly increase in twinning, 1.046 [1.00, 1.09]. These increases were adjusted for maternal age, race, education, parity and season of conception. The size and pattern of these increases are consistent with the ongoing increase in twinning of 1-4% per year which began in the US prior to fortification.

Adolescent↗

Study of wheat breakfast rolls fortified with folic acid. The effect on folate status in women during a 3-month intervention.

BACKGROUND: Folate has come into focus due to its protective role against child birth defects such as neural tube defects (NTD). Swedish authorities recommend all fertile women to increase their folate intake to 400 microg/day by eating folate-rich foods. Because not all women follow these recommendations, there is a discussion today about whether Sweden should introduce folic acid fortification in wheat flour and sifted rye flour. This decision needs knowledge about the bioavailability of folic acid from fortified foods. AIM OF THE STUDY: To investigate effects of two folic acid fortification levels on folate status in healthy female volunteers and to study the folic acid stability during the baking procedure and storage of the fortified breakfast rolls. METHOD: Twenty-nine healthy women were recruited. Folic acid-fortified wheat breakfast rolls were baked with the purpose to contain 200 microg folic acid/roll (roll L) and 400 microg folic acid/roll (roll H). Fourteen women were given one roll/day of roll L (group L) and 15 one roll/day of roll H (group H) during 12 weeks of intervention. Fasting venous blood samples were collected on days 0, 30, 60 and 90. Serum homocysteine concentrations were determined using an immunoassay. Serum and erythrocyte folate concentrations were analysed using a protein-binding assay with fluorescent quantification. The folic acid concentration in the breakfast rolls was analysed by HPLC on days 0, 30, 60 and 90. Total folate concentration was measured with microbiological assay on day 45. RESULTS: Group L Group L had initially an average erythrocyte folate concentration of 577 +/- 93 nmol/L. After 90 days of intervention, an increase of 20 % (p < 0.05) was observed. At day 0, mean serum folate concentrations were 16.9 +/- 4.3 nmol/L. The mean serum folate concentrations increased by 30 % (p < 0.001) after 90 days. At day 0, mean serum homocysteine concentrations were 9.1 +/- 2.0 micromol/L, which decreased by 20 % (p < 0.01) after 30 days. Group H Group H had an initial erythrocyte folate concentration of 784 +/- 238 nmol/L. After 90 days, an increase of 26 % (p < 0.05) was observed. Serum folate increased at least 22 % after 30 days, from a level of 18.7 +/- 4.8 nmol/L at day 0. Thereafter, all women of group H had serum concentrations at or above the upper limit of quantification (23 nmol/L). At day 0, mean serum homocysteine concentrations were 8.4 +/- 1.7 micromol/L, which decreased by 16 % (p < 0.05) after 30 days. The baking procedure resulted in 20-25 % loss of fortified folic acid in the rolls used in the present study. The size of the rolls affected the retention of folic acid during baking. No significant loss was seen in folic acid concentration in the rolls during the intervention period. CONCLUSION: The present study showed that in healthy women, subjected to a 12-week intervention with breakfast rolls fortified with either 166 microg or 355 microg folic acid, serum homocysteine concentration decreased (p < 0.05) and erythrocyte folate increased (p < 0.05). The lower level of fortification seems to be sufficient to improve the folate status. Together with the average daily intake of natural folates, these women reach the recommended intake of 400 microg/day. Folic acid is stable in fortified bread for 90 days storage at -20 degrees C.

Adult↗

Enzyme histochemistry of rat folic acid nephropathy.

One hour after a single i.v. dose of 250 mg/kg folic acid, the straight portion of distal tubules in the outer medulla of rat kidneys showed a distinct reduction in succinate dehydrogenase, NADH2-diaphorase, glutamate dehydrogenase, cytochrome oxydase, Na+/K+-ATPase, and acid phosphatase activity. In contrast, the proximal tubules exhibited only a reduction in glutamate dehydrogenase and alkaline phosphatase activity. At this time the straight portion of the distal tubules, whose enzyme activity had changed, showed partly regressive epithelial changes. 24 hours after folic acid administration an even greater reduction in enzyme activity had occurred in the straight portion of distal tubules; these structures also became dilated. The adjacent collecting tubules and the corresponding proximal tubules were also severely dilated, the proximal tubules showing a loss in enzyme acitivities similar to those observed in the distal tubules. 48 hours after folic acid administration the changes largely resembled those observed after 24 hours, but were more pronounced. At this time a tubular regeneration was observed. 72 hours after folic administration extensive normalization of the histological and histochemical changes had occured. It is postulated that a disturbance of the hairpin counter-current mechanism occurs as a result of a direct, concentration-dependent effect of folic acid on the enzymes of the energy supplying metabolism. A dilation in the region of the loop of Henle and the collecting tubules occurs subsequently.

Acid Phosphatase↗

Folic acid awareness and intake survey in the United Arab Emirates.

OBJECTIVE: The aim of this study was to determine the level of knowledge and use of periconceptional folic acid supplementation in a sample of postpartum women recruited from three hospitals. DESIGN: Cross-sectional survey in which a structured questionnaire was used in a face-to-face encounter between the subject and a trained nurse. SETTINGS: Two teaching hospitals associated with Faculty of Medicine and Health Sciences and one private hospital. SUBJECTS: Postpartum women in the three hospitals were recruited during a 40-day period in November 1999. Women who did not agree to participate, had complicated labor, delivered babies with congenital malformations, or were too exhausted or difficult to examine, were excluded. RESULTS: Univariate analyses showed that overall 46.4% of the respondents had heard about folic acid and only 8.7% knew that it prevented birth defects. 45.5% of respondents took folic acid in the first trimester. The percentage of women who had ever heard about folic acid was higher in those with higher education, and those who were not UAE nationals. Use of folic acid was associated with non-UAE nationality. CONCLUSION: Awareness of the value of periconceptional folic acid was very low and use of folic acid was less prevalent among women of UAE nationality.

Adult↗

Effects of multivitamin and folic acid supplementation in malnourished children.

OBJECTIVE: To study the effect of multivitamin and folic acid supplementation on serum folate level and weight gain. MATERIAL AND METHOD: A prospective randomized controlled study was conducted in malnourished children at the Nutrition Clinic, Queen Sirikit National Institute of Child Health from February to June 2000. History taking, weight-height measurement, and blood testing for complete blood count (CBC) and serum folate level were done. Patients were randomly by assigned into 2 groups. The study group was supplemented daily with multivitamins (MVD) along with a folic acid tablet while the control group was supplemented daily with MVD only, for 6 weeks. RESULTS: Twenty-nine malnourished children were enrolled in the present study. They were randomly by assigned into 2 groups, 14 children in the study group and 15 children in the control group. There were 11 boys (38%) and 18 girls (62%). Mean age was 36.3 months. Anemia and low serum folate level were found in 24 per cent and 21 per cent respectively. There was no significant difference in the data of both groups, except that anemia was more common in the study group (p = 0.018). After 6 weeks of supplementation, increases in weight and serum folate level were significantly higher in the study group, but there was no significant difference in weight increased between both groups. CONCLUSION: Folate deficiency may be found in malnourished children. Efficacy of folic acid supplement is good. Folic acid needs to be supplemented in malnourished children.

Chi-Square Distribution↗