Folate and vitamin B12 status in relation to cognitive impairment and anaemia in the setting of voluntary fortification in the UK

Concerns about risks for older people with vitamin B12 deficiency have delayed the introduction of mandatory folic acid fortification in the UK. We examined the risks of anaemia and cognitive impairment in older people with low B12 and high folate status in the setting of voluntary fortification in the UK. Data were obtained from two cross-sectional studies (n 2403) conducted in Oxford city and Banbury in 1995 and 2003, respectively. Associations (OR and 95 % CI) of cognitive impairment and of anaemia with low B12 status (holotranscobalamin < 45 pmol/l) with or without high folate status (defined either as serum folate >30 nmol/l or >60 nmol/l) were estimated after adjustment for age, sex, smoking and study. Mean serum folate levels increased from 15.8 (sd 14.7) nmol/l in 1995 to 31.1 (sd 26.2) nmol/l in 2003. Serum folate levels were greater than 30 nmol/l in 9 % and greater than 60 nmol/l in 5 %. The association of cognitive impairment with low B12 status was unaffected by high v. low folate status (>30 nmol/l) (OR 1.50 (95 % CI 0.91, 2.46) v. 1.45 (95 % CI 1.19, 1.76)), respectively. The associations of cognitive impairment with low B12 status were also similar using the higher cut-off point of 60 nmol/l for folate status ((OR 2.46; 95 % CI 0.90, 6.71) v. (1.56; 95 % CI 1.30, 1.88)). There was no evidence of modification by high folate status of the associations of low B12 with anaemia or cognitive impairment in the setting of voluntary fortification, but periodic surveys are needed to monitor fortification.     

Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification

BACKGROUND: Historic reports on the treatment of pernicious anemia with folic acid suggest that high-level folic acid fortification delays the diagnosis of or exacerbates the effects of vitamin B-12 deficiency, which affects many seniors. This idea is controversial, however, because observational data are few and inconclusive. Furthermore, experimental investigation is unethical. OBJECTIVE: We examined the relations between serum folate and vitamin B-12 status relative to anemia, macrocytosis, and cognitive impairment (ie, Digit Symbol-Coding score < 34) in senior participants in the 1999-2002 US National Health and Nutrition Examination Survey. DESIGN: The subjects had normal serum creatinine concentrations and reported no history of stroke, alcoholism, recent anemia therapy, or diseases of the liver, thyroid, or coronary arteries (n = 1459). We defined low vitamin B-12 status as a serum vitamin B-12 concentration < 148 pmol/L or a serum methylmalonic acid concentration > 210 nmol/L-the maximum of the reference range for serum vitamin B-12-replete participants with normal creatinine. RESULTS: After control for demographic characteristics, cancer, smoking, alcohol intake, serum ferritin, and serum creatinine, low versus normal vitamin B-12 status was associated with anemia [odds ratio (OR): 2.7; 95% CI: 1.7, 4.2], macrocytosis (OR: 1.8; 95% CI: 1.01, 3.3), and cognitive impairment (OR: 2.5; 95% CI: 1.6, 3.8). In the group with a low vitamin B-12 status, serum folate > 59 nmol/L (80th percentile), as opposed to < or = 59 nmol/L, was associated with anemia (OR: 3.1; 95% CI: 1.5, 6.6) and cognitive impairment (OR: 2.6; 95% CI: 1.1, 6.1). In the normal vitamin B-12 group, ORs relating high versus normal serum folate to these outcomes were < 1.0 (P(interaction) < 0.05), but significantly < 1.0 only for cognitive impairment (0.4; 95% CI: 0.2, 0.9). CONCLUSION: In seniors with low vitamin B-12 status, high serum folate was associated with anemia and cognitive impairment. When vitamin B-12 status was normal, however, high serum folate was associated with protection against cognitive impairment.     

Selenium,Folate, and Colon Cancer

Selenium is an essential trace element that has been implicated in cancer risk; however, study results have been inconsistent with regard to colon cancer. Our objectives were to 1) investigate the association between selenium and colon cancer, 2) evaluate possible effect measure modifiers, and 3) evaluate potential biases associated with the use of postdiagnostic serum selenium measures. The North Carolina Colon Cancer Study is a large population-based, case-control study of colon cancer in North Carolina between 1996 and 2000 (n = 1,691). Nurses interviewed patients about diet and lifestyle and drew blood specimens, which were used to measure serum selenium. Individuals who had both high serum selenium (> 140 mcg/l) and high reported folate (> 354 mcg/day) had a reduced relative risk of colon cancer [odds ratio (OR) = 0.5, 95% confidence interval (CI) = 0.4–0.8). The risk of colon cancer for those with high selenium and low folate was approximately equal to the risk among those with low selenium and low folate (OR = 1.1, 95% CI = 0.7–1.5) as was the risk for those with low selenium and high folate (OR = 0.9, 95% CI = 0.7–1.2). We did not find evidence of bias due to weight loss, stage at diagnosis, or time from diagnosis to selenium measurement. High levels of serum selenium and reported folate jointly were associated with a substantially reduced risk of colon cancer. Folate status should be taken into account when evaluating the relation between selenium and colon cancer in future studies. Importantly, weight loss, stage at diagnosis, or time from diagnosis to blood draw did not appear to produce strong bias in our study.     

Poor folate status predicts persistent diarrhea in 6- to 30-month-old north Indian children

Poor micronutrient status is associated with diarrheal illness, but it is not known whether low folate and/or cobalamin status are independent risk factors for diarrhea. We measured the association between plasma folate and cobalamin and subsequent diarrheal morbidity in a prospective cohort study of 2296 children aged 6-30 mo in New Delhi, India. Plasma concentrations of folate, cobalamin, total homocysteine (tHcy), and methylmalonic acid were determined at baseline. Whether a child had diarrhea was recorded during weekly visits in a 4-mo zinc supplementation trial. Diarrhea episodes lasting <7, ≥7, and ≥14 d were classified as acute, prolonged, and persistent, respectively. There was a total of 4596 child periods with acute, 633 with prolonged, and 117 with persistent diarrhea during follow-up. Children with plasma folate concentrations in the lowest quartile had higher odds of persistent diarrhea than children in the other quartiles [adjusted OR = 1.77 (95% CI = 1.14, 2.75); P = 0.01]. This effect differed between boys [adjusted OR = 2.51 (95% CI = 1.47, 4.28)] and girls [adjusted OR = 1.03 (95% CI = 0.53, 2.01); P-interaction = 0.030]. We found a small but significant association between high plasma tHcy concentration and acute diarrhea [adjusted OR = 1.14 (95% CI = 1.04, 1.24); P = 0.006]. Plasma cobalamin concentration was not a predictor of diarrheal morbidity. In conclusion, poor folate status was an independent predictor of persistent diarrhea in this population.     

Changes in folate status in overweight/obese women following two different weight control programmes based on an increased consumption of vegetables or fortified breakfast cereals

The modification of folate status was analysed in a group of sixty-seven overweight/obese women of childbearing age (20-35 years). Subjects were randomly assigned to one of two slightly hypocaloric diets: diet V (increased consumption of vegetables) or diet C (increased consumption of breakfast cereals). Dietetic, anthropometric and biochemical data were collected at the start of the study and again at 2 and 6 weeks. At 6 weeks a weight loss of 2.0 (sd 1.3) kg was achieved in V subjects and of 2.8 (sd 1.4) kg in C subjects (P < 0.05). At the start of the study, 64.2 % of all subjects had a folate intake of < 67 % of the recommended intake; this fell to just 3 % (7.14 % of V subjects and 0 % of C subjects) by week 6. Significant increases were only seen in C subjects in serum folate concentrations (both at 2 and 6 weeks), accompanied by a significant reduction in serum homocysteine (at week 6). Some 62.1 % of all subjects had serum folate concentrations of > or = 13.6 nmol/l (associated with a very low risk of neural tube defects) at the start of the study, while 87.0 % (85.2 % of V subjects and 88.9 % of C subjects) had concentrations of > or = 13.6 nmol/l at 6 weeks (P < 0.01). Increasing the relative consumption of vegetables/cereals in the context of a slightly hypocaloric diet may therefore be a good way to lose body weight. Breakfast cereals may be of special help with respect to folate status and serum homocysteine levels in overweight/obese young women following energy restriction diets.     

Serum folate levels among women attending family planning clinics--Georgia, 2000.

Since 1998, serum folate levels have increased nationally after mandatory fortification of cereal grain products with folic acid. Whether serum folate levels have increased among all women has not been well-studied. Identifying characteristics of women with lower serum folate levels would also be helpful in designing educational campaigns. Data for this report were collected during January 2000-January 2001. During 2000, blood samples were collected from 1,059 women aged 18-45 years who attended six family planning clinics in Georgia and analyzed for serum folate levels. This sample included women aged 18-25 years (60%), black women (41%), and women who had a high school education or less (49%). The median serum folate level (8.9 ng/mL) among this population was lower than the median of women of childbearing age (13.0 ng/mL) who participated in the 1999-2000 National Health and Nutrition Examination Survey (NHANES). In logistic regression analysis, women who were black (odds ratio [OR] = 2.4; 95% confidence interval [CI] = 1.48, 3.96), who smoked (OR = 2.1; 95% CI = 1.26, 3.43), or who used Depo-Provera contraceptive injection (manufactured by Pharmacia Corporation, Peapack, New Jersey) (OR = 2.3; 95% CI = 1.15, 4.62) were more likely to be ranked in the lowest quartile (< or = 62 ng/mL) of serum folate concentrations when compared with the highest quartile (> 12.4 ng/mL). Women who consumed cereal regularly (OR = 0.4; 95% CI = 0.26, 0.62) or folic acid supplements (OR = 0.2; 95% CI = 0.09, 0.30) were the least likely to be in the lowest serum folate quartile. This study indicates that certain women are at greater risk for having lower serum folate levels, including women who are black, smokers, Depo-Provera users, and those less likely to eat cereal regularly or to take folic acid supplements. In Georgia, these data are useful in defining target populations (e.g., black women and smokers) for folic acid education campaigns because public health officials can develop contextually appropriate messages and outreach approaches for targeting women for folic acid interventions. Ongoing surveillance of serum folate status among women can guide future intervention efforts.     

A Case-Control Nutrigenomic Study on the Synergistic Activity of Folate and Vitamin B12 in Cervical Cancer Progression

The present study was designed to identify the role of folate, B12, homocysteine, and polymorphisms of methylene tetrahydrofolatereductase (MTHFR) gene in cervical carcinogenesis among 322 women from Kerala, South India. Serum folate, vitamin B12 (chemiluminescence assay), and homocysteine (EIA) along with genetic polymorphisms of MTHFR gene (polymerase chain reaction/restriction fragment length polymorphism) were analyzed for 136 control subjects, 92 low-grade squamous intraepithelial lesions (LSIL) subjects, and 94 invasive cervical cancer cases (ICC). Statistically significant associations between MTHFR polymorphisms, serum homocysteine, and folate levels with cervical carcinogenesis were not evident, but we found that these parameters acted as effect modifiers of serum vitamin B12. The risk estimates observed for B12 became prominent only when there was a deficiency in serum folate levels [LSIL–odds ratio (OR): 14.9 (95% CI: 2.65 to 84.4); ICC–OR = 8.72 (95% CI = 1.55 to 48.8)] or when MTHFR A1298C polymorphic variant was present [LSIL–OR = 9.8 (95% CI = 2.61 to 36.7); ICC–OR = 10.0 (95%CI = 2.5 to 39.3)]. The statistical significance of this effect modification was further studied using an interaction model, where only folate was observed to have an influence on B12 levels as suggested by the odds ratio of 7.11 (95% CI = 0.45 to 111.9) obtained for ICC group, implicating a synergistic role of these 2 vitamins in invasive cervical cancer.     

Reduced Kidney Function Is Associated with Increasing Red Blood Cell Folate Concentration and Changes in Folate Form Distributions (NHANES 2011–2018)

Background: Current studies examining the effects of high concentrations of red blood cell (RBC) or serum folates assume that high folate concentrations are an indicator of high folic acid intakes, often ignoring the contributions of other homeostatic and biological processes, such as kidney function. Objective: The current study examined the relative contributions of declining kidney function, as measured by the risk of chronic kidney disease (CKD), and usual total folic acid intake on the concentrations of RBC folate and serum folate (total as well as individual folate forms). Design: Cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) collected in 2-year cycles were combined from 2011 to 2018. A total of 18,127 participants aged ≥16 years with available folate measures, kidney biomarker data (operationalized as a categorical CKD risk variable describing the risk of progression), and reliable dietary recall data were analyzed. Results: RBC folate concentrations increased as CKD risk increased: low risk, 1089 (95% CI: 1069, 1110) nmol/L; moderate risk, 1189 (95% CI: 1158, 1220) nmol/L; high risk, 1488 (95% CI: 1419, 1561) nmol/L; and highest risk, 1443 (95% CI: 1302, 1598) nmol/L (p < 0.0001). Similarly, serum total folate concentrations increased as CKD risk increased: low risk: 37.1 (95% CI: 26.3, 38.0) nmol/L; moderate risk: 40.2 (95% CI: 38.8, 41.7) nmol/L; high risk: 48.0 (95% CI: 44.3, 52.1) nmol/L; the highest Risk: 42.8 (95% CI: 37.8, 48.4) nmol/L (p < 0.0001). The modeled usual intake of folic acid showed no difference among CKD risk groups, with a population median of 225 (interquartile range: 108–390) µg/day. Conclusion: Both RBC and serum folate concentrations increased with declining kidney function without increased folic acid intake. When analyzing associations between folate concentrations and disease outcomes, researchers may want to consider the confounding role of kidney function.     

Poor zinc status is associated with increased risk of insulin resistance in Spanish children

Zn plays a key role in the synthesis and action of insulin. The aim of the present work was to determine whether a poorer Zn status was associated with insulin resistance in a group of 357 Spanish schoolchildren. Zn intake was determined by using a 3?d food record (i.e. Sunday to Tuesday). The body weight, height and waist and hip circumferences of all subjects were recorded and fasting plasma glucose, insulin and Zn concentrations were determined. Insulin resistance was determined using the homoeostasis model assessment (HOMA) marker. Children (11·5?%) with Zn deficiency (serum Zn concentration 3·16 made a significantly smaller contribution to the coverage of those recommended (59·7 (sd 14·7)?%) than observed in children with lower HOMA values (73·6 (sd 18·2)?%; P?相似文献   

Low folic acid status and its association with anaemia in urban adolescent girls and women of childbearing age in Sri Lanka

Folic acid deficiency is implicated in the aetiology of nutritional anaemia and adverse pregnancy outcomes for the fetus. Data on folic acid status among adolescent girls and non-pregnant, non-lactating young women are limited. We assessed folic acid status in a random sample of 552 subjects (277 adolescent girls aged 15-18.9 years and 275 women aged 19-30 years) living in Colombo, Sri Lanka. The association of low folic acid status with anaemia was evaluated. Socio-economic, food intake and anthropometric data were obtained. Hb, serum folic acid, vitamin B12 and ferritin and plasma homocysteine concentrations were measured. Forty-three per cent of subjects studied had low serum folic acid concentrations (<3 ng/ml) and 47 % had low Fe stores (serum ferritin <20 microg/l). Overall prevalence of anaemia was 12.9 %, and 43.9 % of anaemic subjects had both low folic acid status and depleted Fe stores (serum ferritin <12 microg/l). Both low folate status and depleted Fe stores were significantly associated with anaemia (odds ratio = 2.32; 95 % CI 1.34, 4.01 and odds ratio = 5.98; 95 % CI 3.36, 10.63, respectively). Serum folic acid concentration was associated (r = 0.108, P = 0.015) with folate intake as indicated by a computed folate index. Folate index was associated inversely with household size and positively with economic status and education level. In this study population low folic acid status, besides depleted Fe stores, was associated with anaemia. The high prevalence of low folic acid status observed highlights the need for nutrition education to improve intakes of folate, Fe and other micronutrients among adolescent girls and young women.     

Association of subclinical vitamin D deficiency with severe acute lower respiratory infection in Indian children under 5 y

OBJECTIVES: To determine whether subclinical vitamin D deficiency in Indian children under 5 y of age is a risk factor for severe acute lower respiratory infection (ALRI). DESIGN: A hospital-based case-control study. SETTING: Sanjeevani Paediatrics Hospital, a private hospital in Indapur, India. PARTICIPANTS: A total of 150 children including 80 cases and 70 controls, aged 2-60 months, were enrolled. Case definition of severe ALRI as given by the World Health Organization was used for cases. Controls were healthy children attending outpatients' service for immunization. MAIN OUTCOME MEASURE: Association of serum 25-hydroxyvitamin D3 (25OHD3) with severe ALRI, controlling for demographic and other potential risk factors. RESULTS: Serum 25OHD3 increased with age. Factors significantly associated with decreased risk of severe ALRI in univariate analysis were: exclusive breastfeeding in the first 4 months (cases 35/78 (45%), controls 41/64 (64%); P=0.02); introduction of other dietary liquids than milk only after 6 months (cases 46/70 (66%), controls 31/66 (47%); P=0.03); use of liquid petroleum cooking fuel (cases 32/80 (40%), controls 40/70 (57%); P=0.04); infant not covered in swaddling cloths when exposed to sunlight before crawling (cases 11/52 (21%), controls 25/54 (46%); P=0.006); and serum 25OHD3>22.5 nmol/l (cases 16/80 (20%), controls 48/70 (69%); P<0.001). In multivariate analysis, factors associated with significantly lower odds ratio for having severe ALRI were: serum 25OHD3>22.5 nmol/l (OR: 0.09; 95% CI 0.03-0.24; P<0.001) and exclusive breastfeeding in the first 4 months of life (OR 0.42; 95% CI 0.18-0.99; P=0.046) with age and height/age as significant covariates. CONCLUSION: Subclinical vitamin D deficiency and nonexclusive breastfeeding in the first 4 months of life were significant risk factors for severe ALRI in Indian children.     

Red cell folate and predicted neural tube defect rate in three Asian cities

BACKGROUND: Periconceptional folic acid reduces neural tube defect (NTD) risk. Red blood cell folate concentration is inversely associated with NTD risk. In many countries there is a lack of information on NTD rates. Red cell folate status in women of childbearing age may be a surrogate for NTD rates and may be helpful in identifying countries or regions most likely to benefit from improved folate status. OBJECTIVE: To predict NTD rates using red cell folate concentrations in women of childbearing age living in three Asian cities Design: Cross-sectional convenience samples of non-pregnant women living in Beijing (n=220), Kuala Lumpur (n=389), and Jakarta (n=129). RESULTS: Red cell folate concentrations were highest (p<0.001) in women from Jakarta at 872 nmol/L (95% CI; 833, 910) followed by Kuala Lumpur at 674 nmol/L (95% CI: 644, 704) and lowest in Beijing at 563 nmol/L (95% CI: 524, 601). Accordingly, predicted NTD rates were highest in Beijing at 30/10000 (95% CI: 27, 33), followed by Kuala Lumpur at 24/10000 (95% CI: 22, 25), and lowest in Jakarta at 15/10000 (95% CI: 14,15). CONCLUSION: Our red blood cell folate data suggests that of the three cities improving the folate status of women in Beijing would have the greatest impact on NTD rates.     

Low serum and red blood cell folate are moderately, but nonsignificantly associated with increased risk of invasive cervical cancer in U.S. women.

Previous observational epidemiologic studies of folate and cervical cancer, as well as folate supplementation trials for cervical dysplasia, have produced mixed results. We examined the relationship between serum and RBC folate and incident invasive cervical cancer in a large, multicenter, community-based case-control study. Detailed in-person interviews were conducted, and blood was drawn at least 6 mo after completion of cancer treatment from 51% of cases and 68% of controls who were interviewed. Blood folate was measured with both microbiologic and radiobinding assays. Included in the final analyses were 183 cases and 540 controls. Logistic regression was used to control for all accepted risk factors, including age, sexual behavior, smoking, oral contraceptive use, Papanicolaou smear history and human papillomavirus (HPV)-16 serology. For all four folate measures, the geometric mean in cases was lower than in controls (e.g., 11.6 vs. 13.0 nmol/L, P < 0.01 for the serum radiobinding assay). Folate measures using microbiologic and radiobinding assays were correlated (serum: r = 0.90; RBC: r = 0.77). For serum folate, multivariate-adjusted odds ratios (OR) in the lowest vs. highest quartile were 1.3 [95% confidence interval (CI) = 0.8--2.9] and 1.6 (0.9--2.9), using the microbiologic and radiobinding assays, respectively. For RBC folate, comparable OR were 1.2 (0.6--2.2) and 1.5 (0.8--2.7). Similar risks were obtained when restricting analyses to subjects with a history of HPV infection. Thus, low serum and RBC folate were each moderately, but nonsignificantly, associated with increased invasive cervical cancer risk. These findings support a role for one-carbon metabolism in the etiology of cervical cancer.     

Folate intake, serum homocysteine and methylenetetrahydrofolate reductase (MTHFR) C677T genotype are not associated with oral cancer risk in Puerto Rico

We examined the relationships between folate and methionine intake, serum homocysteine levels (as a biomarker for folate metabolism), and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism genotype and risk of oral cancer in a population-based, case-control study in Puerto Rico. Structured questionnaires were used to collect information on demographic factors, usual adult diet, and tobacco and alcohol use. Oral epithelial cells and blood samples were collected from a subset of subjects. Analyses were conducted by logistic regression, adjusting for age, sex, lifetime smoking and lifetime alcohol intake, with the following numbers of cases/controls, respectively: dietary data (341/521); MTHFR genotype (148/149); and homocysteine (60/90). Although increased folate intake was associated with decreased oral cancer risk [adjusted odds ratio (OR) in highest vs. lowest quartile = 0.6, 95% confidence interval (CI): 0.4, 1.0, P(trend) = 0.05)], this finding was due almost entirely to folate intake from fruit (adjusted OR = 0.4, 95% CI: 0.2, 0.6; P(trend) = 0.0001), whereas other dietary folate sources showed no clear association. Methionine intake and serum homocysteine levels were not associated with oral cancer risk. Subjects with the MTHFR C677T homozygous variant (TT) genotype had a nonsignificantly lower risk, and risk patterns tended to differ by level of folate, methionine, alcohol intake and smoking, although the power to detect significant associations in subgroups of these variables was low. Risks for oral cancer are not folate specific; preventive recommendations for this disease should emphasize the importance of a healthy diet, including substantial intake of fruits.     

Case-control analysis of dietary folate and risk of bladder cancer

Dietary folate, a water-soluble B vitamin found in a variety of fruits and vegetables, is of particular interest as a chemopreventive agent due to its role in DNA methylation and DNA synthesis and repair. We hypothesized that individuals with low folate intake would be at an increased risk for bladder cancer. Using an ongoing case-control study we assessed dietary folate in 409 incident bladder cancer patients and 451 healthy control subjects. A food-frequency questionnaire was used to estimate naturally occurring food folate (microg/kcal/day), dietary folate equivalents (DFE) from food sources (microg DFE/kcal/day), and DFE from all sources (microg DFE/kcal/day). Unconditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Bladder cancer patients reported a statistically significant lower intake of folate than control subjects for food folate and DFE from food sources (P < 0.001) but not for DFE from all sources (P = 0.061). In the highest quartile of food folate intake there was a 54% reduced risk for bladder cancer (OR = 0.46; 95% CI = 0.29-0.73) after adjusting for age, gender, ethnicity, smoking, and total energy intake. Similarly, the highest quartile of intake was associated with a 59% reduced risk for DFE from food sources (OR = 0.41; 95% CI = 0.26-0.65) and a 35% reduced risk for DFE from all sources (OR = 0.65; 95% CI = 0.42-1.00). In the joint-effects analyses using never smokers with high folate intake as the reference group (OR = 1.0), heavy smokers with low food folate intake had a 2.31-fold (95% CI = 1.11-4.82) increased risk, whereas heavy smokers with high folate intake had a reduced OR of 1.31 (95% CI = 0.53-3.26). Although the ORs were not statistically significant, light smokers and high folate intake exhibited a protective effect (OR = 0.62; 95% CI = 0.20-1.94), whereas an increased risk was observed for light smoking and low folate intake (OR = 1.41; 95% CI = 0.57-3.45). These patterns were consistent for the joint effects of smoking and DFE from food sources and DFE from all sources. In summary, high intake of dietary folate was associated with an overall decrease in bladder cancer risk. These data may have important implications for cancer prevention; however, large, hypothesis-driven, population-based clinical trials will be required to confirm these findings.     

The influence of erythrocyte folate and serum vitamin B12 status on birth weight

The extent to which maternal folate and vitamin B12 modulate infant birth weight is unclear. The present study investigated mothers in early gestation (mean 11.5 (sd 5.8) weeks) and neonates, at delivery. Erythrocyte (RBC) folate (mothers: n 683; neonates: n 614) and vitamin B12 (mothers: n 534; neonates: n 614) were measured. Data on smoking habits were available for 44 % of pregnancies (n 443). The relationship between vitamin levels and birth weight standardized for gender and gestational age was investigated, using linear regression and adjusting for possible confounding variables (maternal age, parity). Results are presented as standardized regression coefficients (b). Increasing maternal age was associated with elevated RBC folate (b 0.11 (95 % CI 0.08, 0.15), P<0.001; n 674) and smoking was associated with a decrease in maternal RBC folate (b -1.38 (95 % CI -1.92, -0.86), P=0.001; n 319). Neonatal RBC folate was predicted by maternal RBC folate (b 0.08 (95 % CI 0.04, 0.11), P=0.001; n 315) and maternal vitamin B12 (b 0.08 (95 % CI 0.01, 0.16), P=0.02; n 252). Smoking influenced maternal vitamin B12 status (b -0.88 (95 % CI -1.49, -0.27), P=0.005; n 231). Using univariate regression, smoking significantly influenced infant birth weight (b -2.15 (95 % CI -3.24, -1.04), P<0.001; n 437). However, the effect of smoking on birth weight was statistically non-significant when considered in a multivariate regression model, leaving maternal RBC folate as the only significant predictor of birth weight (b 0.25 (95 % CI 0.08, 0.42), P=0.005; n 145). These findings suggest that maternal folate status is an important determinant of infant birth weight. The combined effects of smoking and reduced RBC status on birth weight require further investigation.     

叶酸与DNA甲基转移酶1在宫颈癌及癌前病变中的作用

目的 探讨叶酸和DNA甲基转移酶1(DNMT1)与宫颈癌发生发展的关系及其在宫颈癌变中的相互作用.方法 选择经病理学确诊的宫颈鳞状细胞癌(SCC)患者100例、宫颈上皮内瘤样变(CrN)患者101例和宫颈炎(CI)患者109例为研究对象.在收集全部对象人口学特征、生殖因素等相关资料的同时,检测血清叶酸水平(RIA法)、人乳头瘤病毒16的感染状况(PCR法)和DNMT1蛋白的表达量(Westernblot法).采用SPSS 16.0分析软件,进行相关资料的t检验、x2检验、因素与疾病之间关联强度指标(OR值95%CI)的计算及交互作用分析.结果 在SCC、CIN和CI组,血清叶酸含量分别为(2.60±1.61)、(3.14±2.08)和(3.32±1.74)ng/ml,DNMT1蛋白表达水平分别为2.40±0.99、1.88±0.33和0.89±0.29,随着宫颈病变的加重叶酸含量逐渐降低,DNMT1蛋白表达水平逐渐增高,两者呈负相关关系(r=-0 186,P=0001).交互作用分析显示,叶酸水平低和DNMTl蛋白高表达在CIN和SCC组均存在正相加交互作用,OR值分别为2.50(95%CI:1.21～9.22)和6.03(95%CI:2.79～21.72),交互作用指标超额危险度、交互作用归因危险比和交互作用指数在CIN组分别为0.92、0.36和2.59,在SCC组分别为2.47、0.41和1.96.结论 血清叶酸水平低及DNMT1蛋白高表达均是导致宫颈癌和癌前病变发生的危险因素,两者存在协同作用.

Abstract：

Objective To explore the effect of folic acid and DNA methyltransferase 1 (DNMT1) on cervical cancer and cervix precancerous lesion. Methods 100 patients with cervix squamouscell carcinoma (SCC), 101 patients with cervical intraepithelial neoplasm (CIN) and 109 patients with cervix inflammation (CI) diagnosed by histology were included in this study. Radioimmunoassay (RIA), polymerase chain reaction (PCR) and Western blot were used to detect the levels of serum folate, HPV16 infection and the expression of DNMT1 protein,respectively. Results The average levels of serum folate were (2.60 ± 1.61) ng/ml, (3.14 + 2.08) ng/ml and (3.32+1.74) ng/ml,and the expression of DNMT1 protein were 2.40 + 0.99,1.88 + 0.33 and 0.89 ± 0.29 in the group of SCC, CIN and CI, respectively.The relationship of folate levels and DNMT1 protein expression showed inverse correlation (r=-0.186, P=0.00l). The results in our study indicated that there was an additive interaction between low-level of serum folate and high-expressionof DNMT1 protein related to the risk of CIN and SCC, with OR value as 2.50(95%C/: 1.21-9.22) and 6.03 (95%C/: 2.79-21.72) respectively. The relative excessrisk of interaction (RERI) , attributableproportion of interaction (API) and synergy index (S) were 0.92, 0.36 and 2.59 in the CIN group while 2.47, 0.41 and 1.96 in the SCC group. Conclusion The low level of serum folate and high expression of DNMT1 protein seemed to be associated with high risk of cervical cancer and its precancerous lesion. It suggested that there might be a synergistic action between serum folate and DNMT1 in the progression of cervix carcinogenesis.     

Does the interaction between maternal folate intake and the methylenetetrahydrofolate reductase polymorphisms affect the risk of cleft lip with or without cleft palate?

Periconceptional folic acid supplementation may reduce the risk of cleft lip with or without cleft palate (CL(P)). Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene reduce availability of 5-methyltetrahydrofolate, the predominant circulating form of folate. To determine the effect of MTHFR C677T and MTHFR A1298C genotypes and haplotypes on CL(P) risk and the interaction with maternal periconceptional dietary folate and folic acid supplement intake, the authors conducted a case-control triad study in the Netherlands (1998-2000) among 179 CL(P) and 204 control families. Infant and parental MTHFR C677T and MTHFR A1298C genotypes and haplotypes were not associated with CL(P) risk in the case-control and transmission disequilibrium test analyses. Mothers carrying the MTHFR 677TT genotype and who either did not use folic acid supplements periconceptionally or had a low dietary folate intake, or both, had an increased risk of delivering a CL(P) child (odds ratio (OR) = 5.9, 95% confidence interval (CI): 1.1, 30.9; OR = 2.8, 95% CI: 0.7, 10.5; OR = 10.0, 95% CI: 1.3, 79.1, respectively). No supplement use, low dietary folate intake, and maternal MTHFR 1298CC genotype increased the risk of CL(P) offspring almost sevenfold (OR = 6.5, 95% CI: 1.4, 30.2). Thus, the detrimental effect of low periconceptional folate intake on the risk of giving birth to a CL(P) child was more pronounced in mothers with the MTHFR 677TT or MTHFR 1298CC genotype.     

Factors associated with sugar-sweetened beverage intake among United States high school students

This cross-sectional study examined associations of demographic characteristics, weight status, availability of school vending machines, and behavioral factors with sugar-sweetened beverage (SSB) intake, both overall and by type of SSB, among a nationally representative sample of high school students. The 2010 National Youth Physical Activity and Nutrition Study data for 11,209 students (grades 9-12) were used. SSB intake was based on intake of 4 nondiet beverages [soda, other (i.e., fruit-flavored drinks, sweetened coffee/tea drinks, or flavored milk), sports drinks, and energy drinks]. Nationwide, 64.9% of high school students drank SSB ≥1 time/d, 35.6% drank SSB ≥2 times/d, and 22.2% drank SSB ≥3 times/d. The most commonly consumed SSB was regular soda. Factors associated with a greater odds for high SSB intake (≥3 times/d) were male gender [OR = 1.66 (95% CI = 1.41,1.95); P < 0.05], being non-Hispanic black [OR = 1.87 (95% CI = 1.52, 2.29); P < 0.05], eating at fast-food restaurants 1-2 d/wk or eating there ≥3 d/wk [OR = 1.25 (95% CI = 1.05, 1.50); P < 0.05 and OR = 2.94 (95% CI = 2.31, 3.75); P < 0.05, respectively] and watching television >2 h/d [OR = 1.70 (95% CI = 1.44, 2.01); P < 0.05]. Non-Hispanic other/multiracial [OR = 0.67 (95% CI = 0.47, 0.95); P < 0.05] and being physically active ≥60 min/d on <5 d/wk were associated with a lower odds for high SSB intake [OR = 0.85 (95% CI = 0.76, 0.95); P < 0.05]. Weight status was not associated with SSB intake. Differences in predictors by type of SSB were small. Our findings of significant associations of high SSB intake with frequent fast-food restaurant use and sedentary behaviors may be used to tailor intervention efforts to reduce SSB intake among high-risk populations.     

A case-control nutrigenomic study on the synergistic activity of folate and vitamin B12 in cervical cancer progression

The present study was designed to identify the role of folate, B12, homocysteine, and polymorphisms of methylene tetrahydrofolatereductase (MTHFR) gene in cervical carcinogenesis among 322 women from Kerala, South India. Serum folate, vitamin B12 (chemiluminescence assay), and homocysteine (EIA) along with genetic polymorphisms of MTHFR gene (polymerase chain reaction/restriction fragment length polymorphism) were analyzed for 136 control subjects, 92 low-grade squamous intraepithelial lesions (LSIL) subjects, and 94 invasive cervical cancer cases (ICC). Statistically significant associations between MTHFR polymorphisms, serum homocysteine, and folate levels with cervical carcinogenesis were not evident, but we found that these parameters acted as effect modifiers of serum vitamin B12. The risk estimates observed for B12 became prominent only when there was a deficiency in serum folate levels [LSIL-odds ratio (OR): 14.9 (95% CI: 2.65 to 84.4); ICC-OR = 8.72 (95% CI = 1.55 to 48.8)] or when MTHFR A1298C polymorphic variant was present [LSIL-OR = 9.8 (95% CI = 2.61 to 36.7); ICC-OR = 10.0 (95%CI = 2.5 to 39.3)]. The statistical significance of this effect modification was further studied using an interaction model, where only folate was observed to have an influence on B12 levels as suggested by the odds ratio of 7.11 (95% CI = 0.45 to 111.9) obtained for ICC group, implicating a synergistic role of these 2 vitamins in invasive cervical cancer.