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Folate levels in pregnant women who smoke: an important gene/environment interaction.

OBJECTIVE: The objective of this study was to determine whether serum and red blood cell folate levels were decreased in pregnant women who smoke and whether total plasma homocysteine levels were elevated. STUDY DESIGN: In this cross-sectional study, serum folate, red blood cell folate, and homocysteine were measured in pregnant first- and early second-trimester pregnant women who smoked (case subjects) and pregnant women who did not smoke (control subjects). In addition, vitamin B(12), albumin, creatinine, cotinine, and hematocrit levels and methylenetetrahydrofolate reductase status were determined and compared between groups. RESULTS: Pregnant women who smoked had significantly lower concentrations of serum folate (22.7 vs 29.4 nmol/L; P =.001) and lower concentrations of red blood cell folate (766 vs 900 nmol/L; P =.038 [not significant]) than pregnant women who did not smoke. Dietary folate intake was not significantly different between pregnant women who smoked and pregnant women who did not smoke. Homocysteine levels were also not significantly different between the groups. For each genotype of methylenetetrahydrofolate reductase, lower levels of serum folate were observed in pregnant women who smoked, with the lowest folate levels seen in homozygous mutant methylenetetrahydrofolate reductase 677TT (18.6 nmol/L in pregnant women who smoked vs 24.2 nmol/L in pregnant women who did not smoke). CONCLUSION: Both serum folate and red blood cell folate are lower in pregnant women who smoked than in pregnant women who did not smoke, although homocysteine levels are not significantly different. There is an important gene environment interaction between methylenetetrahydrofolate reductase gene activity and tobacco exposure on serum folate levels. Lower levels of serum folate may account for the higher rate of miscarriage, stillbirth, abruptio placentae, and fetal anomalies that are observed in pregnant women who smoke. Pregnant women who smoke may benefit from higher doses of folic acid periconceptionally.

Adult↗

Serum ferritin, folate and cobalamin levels and their correlation with anemia in normal full-term pregnant women.

Serum ferritin, folate, cobalamin and hemoglobin concentrations were determined by radioimmunoassay, radioisotopic assay, radioassay and an automated hematology analyser respectively, and then analysed in 221 normal full-term pregnant women in order to evaluate the incidence and the prevalence of nutritional anemia in pregnancy. None of them had received any hematonic during their pregnancy. Their mean age was 27.68 years and the mean duration of pregnancy was 39.51 weeks. Twenty-three (10.41%) of these previously non-anemic pregnant women had clinical anemia after full-term pregnancy. Of the 23 women, 11 (47.83%) had iron-deficiency anemia, with serum ferritin less than 12 micrograms/l; another 11 women had some degree of iron depletion, with serum ferritin less than 20 micrograms/l. So in 22 of the 23 anemic women (95.65%) the cause of anemia may correlate to iron depletion. The remaining one had folate-deficiency anemia. No pure cobalamin deficiency anemia was found in this study. Among the 198 non-anemic normal full-term pregnant women, 92 (46.46%) had iron depletion (serum ferritin less than 20 micrograms/l), of whom 35 (17.68%) had severe iron deficiency, with serum ferritin less than 12 micrograms/l. Another 3 had folate deficiency and 3 had cobalamin deficiency. By including all the anemic and non-anemic pregnant women, 114 (51.58%) of them had some degree of iron depletion. In other words, pregnancy can produce a considerable degree of iron depletion in more than half of the previously non-anemic women.

Adult↗

[A case-control study on the association between folate and cervical cancer].

OBJECTIVE: To evaluate the possible effects of folate on cervical carcinogenesis and the interaction of folate and human papillomaviruses 16 (HPV16). METHODS: A hospital-based case-control study was conducted. 111 hospitalized cases who were pathologically diagnosed of having cervical cancer and 111 controls identified with hysteromyoma that frequency-matched to cases on age, birth place and residential area. A 60-item food-frequency questionnaire (FFQ) were administered to estimate the consumption of dietary folate. HPV16 DNA in exfoliated cervical cell and serum folate were detected by special PCR and radioimmunoassay respectively. RESULTS: HPV16 infection rate in cases (61.26%) was significantly higher than that in controls (28.83%), with adjusted OR of 4.95(95% CI:2.49-9.83).The levels of dietary folate in cases (5.00 microg/kcal +/- 0.41 microg/kcal) were significantly lower than that in controls (5.14 microg/kcal +/- 0.35 microg/kcal), but the adjusted OR showing no statistical significance. However, serum folate in cases (1.79 ng/ml +/- 1.42 ng/ml) was significantly lower than that in controls(2.59 ng/ml +/- 2.81 ng/ml),and there were significantly increasing trend in the risk of cervical cancer with reducing level of serum folate (chi-squared trend test of P = 0.000). Meanwhile, low-level of serum folate and HPV16-infection showed significant interaction in the development of cervical cancer, with likelihood ratio test of G = 5.56, P = 0.02. CONCLUSION: Results indicated that low levels of folate might increase the risk of cervical cancer, and potential synergistic action might exist between low level of serum folate and HPV16 in the development of cervical cancer.

Case-Control Studies↗

Serum and erythrocyte folates in combined iron and folate deficiency.

A high incidence of iron and folate deficiency was found in 80 female subjects living in a private institution. Iron therapy in individuals with low serum iron values resulted in a significant increase in hemoglobin levels. An improvement in serum and RBC folate levels was also found following iron therapy but this could not be attributed to treatment since a similar increase was observed in untreated control subjects, probably due to an increased dietary intake of folates during the study period. In subsequent studies small amounts of pteroylglutamic acid were given to all patients and their response to therapy was related to initial serum and RBC folate values. No correlation between serum folate levels and response to folate therapy could be demonstrated. Red cell folate levels on the other hand correlated well with response to therapy. A significant increase in hemoglobin was found following folate therapy in patients with low RBC folates, but not increase in subjects with normal RBC folates. Conversely, the increase in hemoglobin following iron therapy in subjects with normal RBC folates was three times as much as in patients with low RBC folates. Thus, unlike serum folate determinations, RBC folate measurements are a reliable index of tissue folate stores, and useful in the prediction of response to folate therapy in both the iron-deficient and iron-replete states.

Adult↗

Changes in folate supplementation, and in serum and red cell folate levels in antenatal patients over the course of a health promotion project for the prevention of neural tube defects.

We assessed the use of folic acid supplements and changes in serum and red cell folate levels in pregnancy over the course of a health promotion project in Western Australia by 4 cross-sectional studies of women attending a public antenatal outpatient clinic in 1992 (before the launch of the health promotion project), 1993, 1994, and 1995. A short questionnaire was completed and blood taken for estimation of serum and red cell folate. There was an increase in the proportion of women taking folic acid supplements in the first trimester (51.9% in the final phase) and before pregnancy (15% in the final phase of the study), and no change in the proportion taking other vitamin supplements. Serum and red cell folate levels increased significantly over the study period in both women taking and not taking folic acid supplements. The proportion of women who had seen the pamphlet used in the health promotion project rose to 35.4% in the third phase, and fell to 27.8% in the final phase. Coincident with the health promotion project, there was an increase in folate status in early pregnancy. However, most women were not taking folic acid supplements before they became pregnant and, hence may not have had sufficient folate at the time of normal neural tube closure.

Erythrocytes↗

An Ontario-wide study of vitamin B12, serum folate, and red cell folate levels in relation to plasma homocysteine: is a preventable public health issue on the rise?.

BACKGROUND: Plasma homocysteine has been reported to be useful in the evaluation of patients with suspected vitamin B12 or folate deficiency. In November 1998, Canada began its mandatory fortification of all flour, and some corn and rice products, with folic acid. We evaluated the status of folate and vitamin B12 in Ontario since this fortification program began, and also studied the role of plasma homocysteine in the assessment of vitamin B12 deficiency since that time. METHODS: A retrospective cross-sectional study design was performed using a community database of all Ontario samples analyzed by MDS Laboratories, a major provider of diagnostic laboratory services in Canada. All consecutive single-patient fasting samples for plasma homocysteine collected between January 1 and September 30, 1999 were included, as well as corresponding red cell folate and serum B12 concentrations. Data for serum folate were included when available. Descriptive statistics included the arithmetic and geometric means for each measure, as well as the lower and upper centile values. After excluding cases with a concomitant serum creatinine > 120 micromol/L or red cell folate < 215 nmol/L, we established the test properties of a plasma homocyteine level of 15 micromol/L or greater for the diagnosis of "low" (< 120 pmol/L) or "indeterminate" (i.e., between 120 and 150 pmol/L) serum vitamin B12 concentrations. RESULTS: The mean age of all subjects was 58.4 years (95% CI 57.4 to 59.4). Plasma homocysteine samples were obtained from 403 males (56.7%) and 308 females. The geometric mean homocysteine concentration for the entire population was 8.3 micromol/L, and was significantly higher among males (9.3 micromol/L) than females (8.3 micromol/L) (unpaired t-test: 2-p < 0.0001). The geometric mean serum folate concentration was significantly higher in females (35.8 nmol/L) than males (33.6 nmol/L) (2-p < 0.0001), as were the mean red cell folate levels (females 966.8 nmol/L, males 949.3 nmol/L; 2-p < 0.0001). Serum vitamin B12 concentrations were available for 692 subjects, with a geometric mean of 322.0 pmol/L. Again, mean vitamin B12 was higher in females (332.5 pmol/L) than males (314.3 pmol/L) (2-p < 0.0001). The fifth centile for vitamin B12 was 134.6 pmol/L. A plasma homocysteine concentration > 15 micromol/L did not discriminate between cobalamin concentrations below versus above 120 pmol/L (positive and negative predictive values 7.4% and 97.2%, respectively), nor did it discriminate "indeterminate" B12 levels between 120 and 150 pmol/L (positive and negative predictive values 6.3% and 94.0%, respectively). CONCLUSION: In a large select group of Ontarians, serum and red cell folate concentrations appear to be higher than expected, possibly due to a recent national folate fortification programme; cobalamin levels are no higher than expected. Given our inability to detect mild B12 deficiency using such indicators as plasma homocysteine, and considering the substantial growth in the elderly segment of the Canadian population, occult cobalamin deficiency could become a common disorder. Accordingly, we recommend either consideration of the addition of vitamin B12 to the current folate fortification programme, and/or the development of better methods for the detection of cobalamin deficiency.

Age Factors↗

Molecular genetic analysis of the human dihydrofolate reductase gene: relation with plasma total homocysteine, serum and red blood cell folate levels.

Disturbances in folate metabolism may increase the risk of certain malignancies, congenital defects and cardiovascular diseases. The gene dihydrofolate reductase (DHFR) is primarily involved in the reduction of dihydrofolate, generated during thymidylate synthesis, to tetrahydrofolate in order to maintain adequate amounts of folate for DNA synthesis and homocysteine remethylation. In order to reveal possible variation that may affect plasma total homocysteine (tHcy), serum folate and red blood cell (RBC) folate levels, we sequenced the DHFR coding region as well as the intron-exon boundaries and DHFR flanking regions from 20 Caucasian individuals. We identified a 9-bp repeat in the 5'-upstream region that partially overlapped with the 5'-untranslated region, and several single-nucleotide polymorphisms, all in non-coding regions. We screened subjects for the 9-bp repeat (n=417), as well as the recently reported 19-bp deletion in intron 1 (n=330), and assessed their associations with plasma tHcy, serum and RBC folate levels. The 19-bp del/del genotype was associated with a lower plasma tHcy (-14.4% [95% confidence interval: -23.5 to -4.5], P=0.006) compared with the wild-type genotype. This may suggest that intracellular folate levels are affected.

5' Flanking Region↗

Cerebrospinal fluid folate activity in patients with Plasmodium falciparum cerebral malaria.

Serum and CSF folate levels were determined simultaneously in 28 patients with P. falciparum cerebral malaria. Both mean values were found to be significantly lower than those of normal subjects reported earlier. Ten (35%) and nine (32%) patients showed low serum and CSF folate respectively. Altogether seven patients had low folate levels in both serum and CSF. After being treated in the hospital for one week, both serum and CSF folate levels increased in nine convalescent subjects. The CSF folate levels were statistically significantly higher than those of the acute malarial stage. These findings indicated that both serum and CSF folate levels were depressed in patients with cerebral malaria and increased after recovery.

Adolescent↗

Tobacco smoke exposure and decreased serum and red blood cell folate levels: data from the Third National Health and Nutrition Examination Survey.

The aim of this cross-sectional study was to determine the effects of smoke exposure on serum and red blood cell folate levels. Data collected as part of the Third National Health and Nutrition Examination Survey were analyzed. Serum and red blood cell folate levels were measured in active smokers and nonsmokers with high, moderate, and low exposure to environmental tobacco smoke. After adjusting for dietary intake of folate and other covariates, we found that both smokers and nonsmokers with high smoke exposure had lower red blood cell folate levels than did nonsmokers with low smoke exposure (-86 nmol/l [95% confidence interval, CI, -101 to -71 nmol/l] for smokers; -50 nmol/l [95% CI -69 to -31 nmol/l] for nonsmokers with high smoke exposure, compared with nonsmokers with low smoke exposure). Similarly, after adjustment of dietary intake of folate and other covariates, the log serum folate level also was decreased (-0.29 log nmol/l [95% CI -0.33 to -0.25 log nmol/l] for smokers; -0.16 log nmol/l [95% CI -0.20 to -0.12 log nmol/l] for nonsmokers with high smoke exposure, compared with nonsmokers with low smoke exposure). Tobacco smoke exposure is associated with decreased folate levels, which may be a mechanism for some of the health effects of active and passive smoking.

Adolescent↗

Nutrition following gastric operations for morbid obesity.

Nutritional status after 238 gastric operations designed to reduce caloric intake and body weight to within 30% of ideal was assessed by measuring body composition using the multiple isotope dilution technique. Body cell mass (BCM) and body fat were quantitated before and at 24 months after operation. Malnutrition was defined as a total exchangeable sodium (Nae) to total exchangeable potassium (Ke) ratio greater than 1.22. Data were collected on 96 patients. All had lost a mean of 26% of preoperative weight by 24 months. Significant malnutrition occurred in 47 patients whose Nae/Ke ratio ranged from 1.23 to 2.17 (1.45 +/- 0.03). There was a 34% reduction in body fat. The malnourished patients lost 10% more BCM by 24 months than did the normally nourished group. Malnutrition resolved as the stoma enlarged in 19 patients, and dietary counselling helped eight patients. Eighteen patients required reoperation to establish a larger orifice, and endoscopic dilatation was successful in two patients. Administration of a liquid diet via the gastrostomy was required for prolonged periods in some malnourished patients. Seventeen patients who had lost weight rapidly over a short time had low vitamin B12, thiamine, and serum and RBC folate levels. One patient had a markedly decreased serum thiamine level with neuropathy. Symptoms of weakness, easy fatigability, and lassitude were found in the malnourished patients. Low thiamine and serum folate levels were also seen in patients ingesting a liquid diet of 750 kcal with a standard multivitamin supplement. Malnutrition was not seen in these patients. In the 49 patients who remained well nourished, BCM decreased by 19%, but the Nae/Ke remained normal. Weight loss was well tolerated, and no patients required reoperation or supplemental liquid diet to increase caloric or protein intake. The degree of malnutrition in patients after gastric operations is as great as following intestinal bypass but is not associated with liver failure. Malnutrition with vitamin deficiency is a great potential hazard in patients who undergo intake-limiting operations, especially if the goal of the operation is to restore near-normal weight. Current operations are successfully designed to maintain a small orifice size, so that the risks of malnutrition are likely to increase in the future.

Adult↗

Serum folate and Vitamin B12 levels in women using modern oral contraceptives (OC) containing 20 microg ethinyl estradiol.

OBJECTIVE: The effects of modern oral contraceptives (OC) on serum concentrations of folate and cobalamin are controversial. STUDY DESIGN: Case-control study on the cobalamin and folate status of 71 healthy female nulligravidae using "low dose" OC for >or=3 months and 170 controls. Factors interfering with vitamin metabolism were thoroughly controlled. Serum concentrations were measured by commercial assays. The results were evaluated using Mann-Whitney's U-test and chi(2) analysis. RESULTS: OC-users showed significantly lower concentrations of cobalamin than controls. The rates of women with reduced, normal, and elevated levels differed significantly. Nine users but no control had frank cobalamin deficiency without clinical symptoms. Folate levels did not differ between the groups. Vegetarian diet, smoking or obesity did not have a significant influence. CONCLUSIONS: Routine measurement of cobalamin or folate in women using "low dose" OC is not warranted. Vitamin supplementation or different contraceptive methods should be considered in women with pre-existing cobalamin deficiency or restrictive dietary habits.

Adolescent↗

[Study of oral contraceptives action on blood folate levels (author's transl)].

In 95 women taking reduced-level-oral contraceptives and in 24 same-aged women controls, the measure of erythrocyte and serum folate led to the following conclusions: 1) Folate levels in women consuming the pill were generally found to be of the same range as those of controls. 2) No significant difference could be shown between results for different kinds of contraceptives.

Adult↗

Do serum and red blood cell folate levels indicate iron response in hemodialysis patients?

The relationship among iron status, ferritin, and folate levels, and the possible contribution of folate measurement in the prediction of iron response in hemodialysis patients, have not been assessed. In addition to serum ferritin and transferrin saturation (TSAT), serum and red blood cell (RBC) folate levels were evaluated as indices for intravenous iron therapy responsiveness in 60 hemodialysis patients. Patients were classified as iron responders or nonresponders depending on whether they exhibited a rise in hemoglobin above 1 g/dl after administration of 1 g of iron sucrose. An inverse relation between serum ferritin concentration and RBC folate levels was found in iron responders (n=26, r=-0.62, p<0.001) but not in nonresponders (n=34, r=0.07, p=nonsignificant). Only serum and RBC folate levels could predict iron response in patients with ferritin levels above 150 microg/l (n=25), with a sensitivity of 83.3% and a specificity of 94.7%. Our findings suggest that RBC folate concentration is inversely related with ferritin levels in iron-responsive but not in non-responsive hemodialysis patients. Serum and RBC folate concentration seems to predict response to iron administration better than serum ferritin or TSAT in patients with ferritin levels above 150 microg/l; therefore, in these patients, it might be used to guide iron management.

Anemia, Iron-Deficiency↗

Elevated homocysteine levels with weight loss after Lap-Band surgery: higher folate and vitamin B12 levels required to maintain homocysteine level.

OBJECTIVE: To investigate homocysteine levels and their relationship with serum folate and vitamin B12 concentrations with weight loss after the Lap-Band form of gastric restrictive surgery, with the view to minimizing risk. METHODS: We measured levels of fasting plasma homocysteine (tHcy), folate (serum and RBC) and vitamin B12 in two groups. The study group was 293 consecutive patients at 12 (n=192) or 24 (n=101) months review after surgery. The controls were 244 consecutive patients presenting for this surgery. RESULTS: The group losing weight had higher geometric mean tHcy levels: 10.4 (95% CI, 9.8-10.8) micromol/l compared with 9.2 (95% CI, 8.9-9.7) in controls (P<0.001). This occurred with higher folate levels and unchanged vitamin B12 levels. Levels of folate and B12 together explained 35% (r (2)) of the homocysteine variance in the weight loss group compared with only 9% (r (2)) in controls (P<0.001). Those taking regular multivitamin supplements had lower tHcy levels: 9.6 (9.1-10.0) micromol/l vs 12.3 (11.4-13.3) in those not taking supplements (P<0.001). A low normal plateau of tHcy levels occurred at levels of folate >15 ng/l and B12)600 ng/ml. A curvilinear relationship exists between these cofactors and tHcy levels, with the dose-response relationship shifted to the right in the weight loss group. CONCLUSION: This study shows elevated tHcy levels with weight loss, without lower serum folate or vitamin B(12) levels. There is an altered dose-response relationship with higher serum B(12) and folate levels required to maintain recommended tHcy levels. Patients losing weight have significant health benefits; however, they may be at greater risk of vascular events or fetal abnormality in association with raised tHcy levels. Multivitamin supplementation is effective in lowering tHcy levels.

Adult↗

Serum folate, vitamin B12, and homocysteine in major depressive disorder, Part 1: predictors of clinical response in fluoxetine-resistant depression.

OBJECTIVE: In the present study, we assessed the relationship between serum folate, vitamin B12, and homocysteine levels and clinical response in patients with major depressive disorder (MDD) who had previously failed to respond to open treatment with fluoxetine 20 mg/day and were enrolled in a 4-week, double-blind trial of either (1) fluoxetine dose increase, (2) lithium augmentation of fluoxetine, or (3) desipramine augmentation of fluoxetine. METHOD: Fifty-five outpatients (mean +/- SD age = 41.7 +/- 10.6 years; 50.9% women) with MDD as assessed with the Structured Clinical Interview for DSM-III-R who were enrolled in the double-blind trial had serum folate, vitamin B12, and homocysteine measurements completed at baseline (prior to fluoxetine treatment initiation). Folate levels were classified as either low (< or = 2.5 ng/mL) or normal. Vitamin B12 levels were classified as either low (< or = 200 pg/mL) or normal. Homocysteine levels were classified as either elevated (> or = 13.2 micromol/L) or normal. With the use of a logistic regression, we then assessed the relationship between (1) low or normal folate levels, (2) normal or low B12 levels, and (3) elevated or normal homocysteine levels and clinical response to double-blind treatment. The study was conducted from November 1992 to January 1999. RESULTS: Low serum folate levels (chi2=3.626, p =.04), but not elevated homocysteine (p >.05) or low vitamin B12 levels (p >.05), were associated with poorer response to treatment. The response rates for patients with (N = 14) and without (N = 38) low folate levels were 7.1% versus 44.7%, respectively. CONCLUSION: Low serum folate levels were found to be associated with further treatment resistance among patients with fluoxetine-resistant MDD.

Adult↗

Homocysteine: relationship to serum cobalamin, serum folate, erythrocyte folate, and lobation of neutrophils.

Serum levels of total homocysteine were studied in the following: 26 healthy adults; 79 hospitalised patients in whom serum cobalamin, serum folate, and erythrocyte folate were greater than 230 pmol/L, 12 nmol/L, and 600 nmol/L, respectively; 32 hospitalised patients whose serum cobalamin was less than 147 pmol/L, compared to 25 patients whose serum cobalamin was greater than 147 pmol/L but unmatched in any other parameter; and 194 patients in whom samples were sent for determination of cobalamin and folate from a neurological service. None of this last group had megaloblastic anaemia. There was a relationship between the elevated concentrations of total homocysteine in serum and low concentrations of serum cobalamin and of erythrocyte folate. This relationship was most evident in samples with serum cobalamin < 86 pmol/L and erythrocyte folate < 335 nmol/L, although elevated homocysteine levels were found in some samples where serum cobalamin and erythrocyte folate levels were greater than these. Serum folate correlated poorly with serum total homocysteine. There was only a poor-to-fair correlation of neutrophil lobe counts to total serum homocysteine.

Adult↗

Factors associated with hyperhomocysteinemia after renal transplantation.

Recent studies show that clinically stable renal transplant recipients have an increased prevalence of hyperhomocysteinemia (hyperHcy), but the mechanism of this disorder has not yet been elucidated. The aim of the present study was to evaluate the factors associated with hyperHcy after a successful renal transplantation. In 106 stable renal transplant recipients, total serum Hcy level (tHcy), folate, total protein, serum creatinine concentration, creatinine clearance, lipid status, body weight (BW), body mass index (BMI), and body fat (BF) were determined. The mean doses of cyclosporine, prednisolone, and azathioprine (mg/kg/day) were recorded. The mean serum tHcy level was significantly higher in renal transplant patients than in healthy controls (22.02 +/- 8.02 versus 13.0 +/- 3.3 micromol/ L; p < 0.001), and the incidence of patients with hyperHcy was 82%. Comparison of the group of 20 patients with tHcy level <15 micromol/L and the group of 86 patients with tHcy level >15 micromol/L revealed that the latter was significantly older, heavier, had been longer on dialysis before renal transplantation, and had older donors and poorer renal graft function. Significant correlation was found between tHcy level and recipient age, dialysis duration, BW, creatinine clearance, serum creatinine, and folate concentration. However, multivariate analysis indicated that creatinine clearance (p = 0.025) and BW (p = 0.03) were the only determinants of elevated total Hcy level in renal transplant recipients. HyperHcy persists after successful kidney transplantation in the majority of renal transplant recipients, and its appearance is primarily associated with creatinine clearance and body weight.

Adult↗

Effect of vitamin B12, folate, and dietary supplements on breast carcinoma chemotherapy--induced mucositis and neutropenia.

BACKGROUND: Although patients with malignant disease frequently use dietary supplements, the effects of these agents with regard to chemotherapy are unclear. Therefore, the authors investigated the influence of vitamin B12, folate, and nutritional supplements on chemotherapy-induced toxicity. METHODS: Women with breast carcinoma were asked to complete a questionnaire that recorded their use of dietary supplements. Blood samples were obtained for the assessment of serum vitamin B12 and folate levels before and after the first cycle of chemotherapy and for weekly complete blood counts. Toxicity was evaluated by measuring absolute neutrophil counts and the frequency and severity of oral mucositis. RESULTS: Of the 49 women who submitted questionnaires, 35 (71%) took a combined total of 165 supplements. Compared with patients in a previous study (performed in 1990), patients in the current study had dramatically increased serum folate levels. Initial neutrophil count, but not type of chemotherapy, patient age, or serum vitamin B12 level, was predictive of nadir absolute neutropenia and the decrease from initial neutrophil count to nadir (Nfall). After adjusting for initial neutrophil count, Nfall was found to be lower for women who were taking supplements compared with women who were not taking supplements (P = 0.01) and for women who were taking multivitamins (P = 0.01) or vitamin E (P = 0.03). Women with serum folic acid levels < 20 ng/mL had a smaller decrease in neutrophil count after chemotherapy than did women with higher folate levels (P = 0.04). No significant association between oral mucositis and initial neutrophil count, nadir neutrophil count, Nfall, age, vitamin B12 level, or folate level was found. CONCLUSIONS: The decrease in neutrophil count caused by chemotherapy was ameliorated by dietary supplementation with a multivitamin or vitamin E. In contrast, high serum folate levels were associated with the exacerbation of this decrease in neutrophil count.

Adult↗