Dietary Intake of Folate,Vitamin B2, Vitamin B6, Vitamin B12, Genetic Polymorphism of Related Enzymes,and Risk of Breast Cancer: A Case-Control Study in Japan

We investigated associations among intake of folate, vitamin B2, vitamin B6, vitamin B12, and polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) genes and breast cancer risk in a Japanese population. A hospital based, case-control study was conducted in Nagano Prefecture, Japan, in 388 pairs of patients with histologically confirmed invasive breast cancer and age- and area-matched controls selected from medical checkup examinees. Energy-adjusted intakes of folate and other B vitamins were derived from a validated food frequency questionnaire. Genotyping was completed for MTHFR (C677T and A1298T) and MTR (A2756G). Odds ratios and 95% confidence intervals were calculated by the conditional logistical regression model. Median dietary folate intake (μg/day) in the control group was 438.2 (interquartile range: 354.9–542.9). Neither dietary intake of folate, vitamin B2, vitamin B6, or vitamin B12 nor polymorphisms of MTHFR or MTR genes were significantly associated with breast cancer risk. Further, no significant interaction was found among nutrients, polymorphisms, and breast cancer risk. Associations of nutrients with breast cancer risk did not differ by hormone receptors status. We conclude that dietary intake of folate and related B vitamins and genotypes of MTHFR or MTR have no overall association with breast cancer risk in Japanese women.     

Folate Intake and Prostate Cancer Risk: A Case-Control Study

Folate deficiency has been implicated in the carcinogenesis of several tumor types. The role of folate in prostate cancer remains indeterminate. We investigated folate as a risk factor for prostate cancer among 140 biopsy-confirmed prostate cancer patients, 230 age-matched clinic controls, and 250 negative prostate biopsy controls. Dietary folate intake was inversely associated with overall risk of prostate cancer as compared to clinic controls (P for a linear trend = 0.003). When stratified by disease severity, dietary folate and folate from natural sources were associated with reduced risk of high-grade cancer as compared to both clinic controls (P for a linear trend = 0.0009 and 0.02, respectively) and biopsy negative controls (P for a linear trend = 0.03 and 0.05, respectively). There was no interaction between alcohol consumption and folate intake. These analyses support an inverse association between dietary folate intake and prostate cancer risk and primarily risk of high-grade prostate cancer.     

叶酸、维生素B12和B6的补充对预防乳腺癌的作用

叶酸、维生素B12及维生素B6的补充可降低血同型半胱氨酸水平和磷酸吡哆醛水平,对肿瘤有潜在的生物学作用。本文仅就其对肿瘤的作用机制,流行病学调查和临床干预试验,综述叶酸、维生素B12和B6的补充对预防乳腺癌的作用。对肿瘤的作用机制叶酸、维生素B12及维生素B6(磷酸吡哆醛)对肿瘤的潜在生物学作用:(1)作为嘌呤和胸苷酸合成的辅酶,参与DNA合成。缺乏这些维生素可能使尿嘧啶错误结合到DNA上,导致染色体破坏和DNA修复破裂[1～3]。(2)叶酸、维生素B12参与DNA甲基化。一种维生素B12依赖的蛋氨酸合成酶,能催化一个甲基基团从甲基四氢叶…     

Folate/Vitamin B12 Supplementation Combats Oxidative Stress-Associated Carcinogenesis in a Rat Model of Colon Cancer

Folate and vitamin B12 deficiency is associated with depletion of the major intracellular antioxidant glutathione, and oxidative stress is emerging as an etiological mechanism for colon cancer. Azoxymethane (AOM), a potent carcinogen, induces colon cancer in rats by causing pathophysiological changes and oxidative stress. We investigated the synergistic effect of folate and vitamin B12 supplementation against AOM-induced carcinogenesis and oxidative stress in rat colon. Adult male rats were distributed into four groups: 1) Basal diet only; 2) AOM injection (15?mg/kg once per week in weeks 5 and 6); 3) Folate and vitamin B12 supplemented diet; 4) Folate and B12 diet with AOM injection. After 16 weeks, rats were sacrificed, colon tissue dissected, indicators of oxidative stress were measured, and immunohistochemical and ultrastructural changes were evaluated. AOM-injected rats showed oxidative stress, evident by glutathione depletion, oxidation of cellular proteins, and DNA oxidative damage. AOM increased mucosal levels of antiapoptotic and proapoptotic proteins Bcl2 and Bax and caused ultrastructure changes in colonic cell organelles. Folate and vitamin B12 supplementation decreased the level of oxidative stress and ameliorated the cytotoxic effects of AOM. In this in vivo experimental model of colon cancer, folate and vitamin B12 supplementation combats carcinogen-induced oxidative stress.     

Intakes of Folate,Vitamin B6, and Vitamin B12 in Relation to All-Cause and Cause-Specific Mortality: A National Population-Based Cohort

The evidence regarding the intake of dietary folate, vitamin B6, and vitamin B12 in relation to mortality in the general population is limited. This study aimed to examine the relationship between dietary intakes of folate, vitamin B6, and vitamin B12 in relation to all-cause and cause-specific mortality in a large U.S. cohort. This study included a total of 55,569 adults from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 1999–2014. Vital data were determined by linking with the National Death Index records through 31 December 2015. Cox proportional hazards models were used to investigate the relationships of all-cause and cause-specific mortality with dietary folate, vitamin B6, and vitamin B12 intake. Dietary intakes of folate and vitamin B6 were inversely associated with mortality from all-cause, cardiovascular disease, and cancer for men and with mortality from all-cause and cardiovascular disease for women. In men, the multivariable hazard ratios (95% confidence intervals) for the highest versus lowest quintiles of folate and vitamin B6 were 0.77 (0.71–0.85) and 0.79 (0.71–0.86) for all-cause mortality, 0.59 (0.48–0.72) and 0.69 (0.56–0.85) for CVD mortality, and 0.68 (0.56–0.84) and 0.73 (0.60–0.90) for cancer mortality, respectively. Among women, the multivariable hazard ratios (95% confidence intervals) for the highest versus lowest quintiles of folate and vitamin B6 were 0.86 (0.78–0.95) and 0.88 (0.80–0.97) for all-cause mortality and 0.53 (0.41–0.69) and 0.56 (0.44–0.73) for CVD mortality, respectively. No significant associations between dietary vitamin B12 and all-cause and cause-specific mortality were observed. In conclusion, higher dietary intakes of folate and vitamin B6 were significantly associated with lower all-cause and cardiovascular mortality. Our findings suggest that increasing the intake of folate and vitamin B6 may lower the mortality risk among U.S. adults.     

Intake of Folate,Vitamin B6 and Vitamin B12 and the Risk of CHD: The Japan Public Health Center-Based Prospective Study Cohort I

Objective: To investigate the association of dietary folate, vitamin B₆ (VB₆) and vitamin B₁₂ (VB₁₂) with the risk of coronary heart disease among middle-aged persons.

Methods: A total of 40,803 subjects aged 40–59 years living in the community who were free of prior diagnoses of cardiovascular disease and cancer and who completed a food frequency questionnaire were followed from 1990–1992 to the end of 2001 in the Japan Public Health Center-based Prospective Study.

Results: After 468,472 person-years of follow-up, 251 coronary heart disease incidents were documented. Coronary heart disease and definite myocardial infarction were inversely associated with dietary intake of folate, VB₆ and VB₁₂ after adjustment for age and sex, but the associations were attenuated after further adjustment for smoking, dietary and other cardiovascular risk factors. However, among non-multivitamin supplement users, multivariable hazard ratios (95% confidence intervals) in the highest vs. lowest quintiles of VB₆ intake were 0.60 (0.37–0.97) for total coronary heart disease and 0.52 (0.29–0.91) for definite myocardial infarction, and the inverse associations with VB₁₂ were marginally significant. The combination of below-median intake of three vitamins or of only B₆ conferred a twice excess risk of total coronary heart disease.

Conclusions: Dietary intake of VB₆ was associated with a reduced risk of coronary heart disease among middle-aged non-multivitamin supplement users. Dietary folate and VB₁₂ were also suggested to be protective factors for coronary heart disease.     

Changes in Dietary Intake of Methionine,Folate/Folic Acid and Vitamin B12 and Survival in Postmenopausal Women with Breast Cancer: A Prospective Cohort Study

Background: Previous experimental studies showed that limiting methionine in the diet of animals or in cell culture media suppresses mammary cancer cell proliferation or metastasis. However, no previous study has investigated the associations of changes in methionine intake with survival among breast cancer survivors. We aimed to examine the association between changes in dietary intake of methionine, folate/folic acid, and vitamin B12 from before to after diagnosis of breast cancer, and mortality among breast cancer survivors. Methods: We included 1553 postmenopausal women from the Women’s Health Initiative who were diagnosed with invasive breast cancer and completed a food frequency questionnaire both before and after breast cancer diagnosis. Multivariable Cox proportional hazards regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence (CIs) of all-cause and breast cancer mortality associated with changes in methionine intake and changes in folate/folic acid and vitamin B12 intake. Results: Relative to pre-diagnosis, 28% of women decreased methionine intake by ≥20%, 30% of women increased methionine intake by ≥20%, and 42% of women had a relatively stable methionine intake (±19.9%) following breast cancer diagnosis. During a mean 16.1 years of follow up, there were 772 deaths in total, including 195 deaths from breast cancer. Compared to women with relatively stable methionine intake, women with decreased methionine intake had lower risks of all-cause (HR 0.78, 95% CI 0.62–0.97) and breast cancer mortality (HR 0.58, 95% CI 0.37–0.91) in fully adjusted models. In contrast, increased methionine intake or changes in folate/folic acid or vitamin B12 intake were not associated with all-cause or breast cancer mortality. Conclusions: Among breast cancer survivors, decreased methionine intake after breast cancer diagnosis was associated with lower risk of all-cause and breast cancer mortality.     

Vitamin B12 and Folate Status of a Selected Group of Free-Living Older Persons

Vitamin B12 and folate status was determined in 50 male and 47 female free-living subjects (65-77 years) in winter and summer. The mean intake calculated from 3-day food records met the Canadian recommended intake (RNI) for both gender and season, however, probability analysis of dietary data revealed a number of subjects at risk of deficiency. Although the mean plasma levels were within the acceptable range for both vitamins, some 9 to 14% of individual subjects had folate plasma levels below normal. Fewer subjects had subnormal plasma vitamin B12 levels. Although mean values for dietary intake and plasma concentration of folate and vitamin B12 may indicate nutritional adequacy, a proportion of an older population may be at nutritional risk.     

端粒酶的激活与胃癌进展关系的研究

目的　探讨胃腺癌组织中端粒酶的活性与胃癌进展的关系。方法　采用端粒酶原位分子杂交检测法对 4 5例原发性胃腺癌及 4 0例癌旁正常黏膜组织中端粒酶活性进行原位检测。结果　 4 5例原发性胃腺癌组织中 ,38例端粒酶呈阳性表达 ,其中早期胃癌阳性率为 6 6 6 % ,中晚期为 93 3%。 4 0例癌旁正常黏膜组织中仅 2例呈阳性表达。晚期胃腺癌组织中端粒酶阳性表达率显著高于早期胃腺癌 (P <0 0 5 )。虽然胃腺组织中端粒酶的表达随分化程度的降低与浸润深度的增加而增强 ,但其表达上的差异均无显著性 (P均 >0 0 5 )。结论　虽然胃腺癌组织中端粒酶的表达与肿瘤分化程度及浸润深度无关 ,但中晚期胃腺癌中的表达水平高于早期胃癌的事实 ,提示端粒酶的高表达是胃癌发生发展过程中的中晚期事件     

Non-Linear Association between Folate/Vitamin B12 Status and Cognitive Function in Older Adults

Although folate and vitamin B12 status have long been implicated in cognitive function, there is no consensus on the threshold of folate and vitamin B12 for assessing their impacts on cognition. The goal of this study was to detail the association between folate and vitamin B12 with cognitive performance. We analyzed cross-sectional data of older adults (≥60 y; n = 2204) from the NHANES (National Health and Nutrition Examination Surveys) cohort from 2011–2014. The restricted cubic spline model was used for describing the associations between serum total folate, RBC folate, 5-methyltetrahydrofolate, and vitamin B12 and the Consortium to Establish a Registry for Alzheimer’s Disease Word Learning (CERAD-WL) and Delayed Recall (CERAD-DR) tests, the Animal Fluency (AF) test, and the Digit Symbol Substitution Test (DSST), respectively. Older adults with a different folate and vitamin B12 status were clustered by artificial intelligence unsupervised learning. The statistically significant non-linear relationships between the markers of folate or vitamin B12 status and cognitive function were found after adjustments for potential confounders. Inverse U-shaped associations between folate/vitamin B12 status and cognitive function were observed, and the estimated breakpoint was described. No statistically significant interaction between vitamin B12 and folate status on cognitive function was observed in the current models. In addition, based on the biochemical examination of these four markers, older adults could be assigned into three clusters representing relatively low, medium, and high folate/vitamin B12 status with significantly different scores on the CERAD-DR and DSST. Low or high folate and vitamin B12 status affected selective domains of cognition, and was associated with suboptimal cognitive test outcomes.     

Cervical cancer screening practices among older women: results from the Maryland Cervical Cancer Case-Control Study

Considerable evidence shows a large proportion of older women have either never had a Pap test or have significant gaps in their history of cervical cancer screening. Differences in health care utilization patterns by age, cohort differences in use of medical subspecialities, and provider reluctance to perform cancer screening within the general medical care encounter have been suggested as reasons for underscreening. Our study conducted in 1985 documents prior health care utilization patterns of 153 cases of Maryland women with invasive cervical cancer compared with a matched control group. Analysis within three age groups showed that cases were significantly less likely to have ever had a Pap test or to receive regular Pap testing, primarily due to differences in medical care utilization patterns. Never having an obstetrician-gynecology visit, a recent (less than 3 years) internist visit, or not having any out-patient visit were significant risk factors. Other risks included older age at first Pap test, reporting not being told to have routine Pap tests, and not using contraceptives. In a multiple logistic regression analysis, recent out-patient visits and lifetime use of an obstetrician-gynecologist remained significant after adjusting for age interactions with recent Pap test history, underscoring the importance of medical care utilization patterns for screening of cancer of the uterine cervix among the elderly.     

武汉市肺癌流行因素的多元Logistic回归分析

本文报道了1985年武汉市城区原发性肺癌的配对病例对照研究。共收集病例103人,对照206人。条件 Logistic 回归模型拟合结果表明,吸烟、被动吸烟、慢性支气管炎、胃病史及家族肿瘤史是肺癌发病的危险因素。吸烟量、被动吸烟量及患慢性支气管炎的年数与患肺癌的危险性之间存在着明显的剂量—效应关系。文中详细表述了各危险因素在 Logistic 模型中的回归系数、标准化回归系数及OR 值的大小。     

癌症危险因素的病例对照研究

目的探讨癌症发病的危险因素,为制定癌症的预防策略提供依据。方法将确诊的癌症患者352例作为研究病例,进行1:1配对病例-对照研究。在47个可能与癌症有关联的因素中,通过条件Logistic回归分析筛选主要危险因素。结果居住及工作环境的放射性、微波、水、空气、居室装修等检测,均在国家规定的正常范围。肿瘤家族史,吃动物内脏、动物油、烟熏食品、泡菜腌菜、油炸食品、剩菜剩饭,吸烟,压力大,经历过重大精神刺激等是癌症的危险因素(P0.05);与家人相处愉快,文化程度高,月收入高,吃绿叶蔬菜、水果、鲜肉类、奶类、过酸食物是保护因素(P0.05)。夫妻均患癌症28对。结论癌症的主要危险因素:家族遗传因素,饮食因素,吸烟,负性精神事件及不良心理因素等,提示癌症是一种生活方式疾病。改变不良生活方式是癌症预防的主要措施。     

A Longitudinal Study of Maternal Folate and Vitamin B12 Status in Pregnancy and Postpartum,with the Same Infant Markers at 6 Months of Age

Folate and vitamin B12 are involved in homocysteine metabolism and are critical to the methylation of DNA. We aimed to assess plasma vitamin B12 (pB12), plasma folate (pFol), and red cell folate (rcFol) in women and their infants during pregnancy and after birth. Maternal biomarkers were tested as predictors of infant biomarkers, including plasma homocysteine (pHcy), at age 6 months. Participants (n = 153) were recruited at the John Hunter Hospital, Australia. Maternal fasting blood samples were collected at 20 and 36 weeks gestation, and at 14 and 27 weeks postpartum. Fifty healthy, term infants provided non-fasting samples at age 6 months. Plasma homocysteine data were available for 16 infants at age 6 months. Maternal pB12 concentrations fell by 16% from 20 to 36 weeks gestation, but had recovered by 14 weeks postpartum. Maternal rcFol concentrations fell by 31% from 20 weeks gestation to 27 weeks postpartum. Infants breastfed at 6 months had lower pB12 (median 159 vs. 402 pmol/L, n = 23 vs. 18, P < 0.01) and folate (median folate z-score -0.58 vs. 0.85, n = 23 vs. 17, P < 0.01), and higher pHcy (median 11.9 vs. 7.3 μmol/L, n = 8 vs. 6, P < 0.01), than those on infant formula. Maternal pregnancy pFol, but not pB12, inversely predicted infant pHcy, after adjustment for the infant’s current pB12 (P = 0.04). Changes in maternal B12 and folate occur during pregnancy and after birth. Infant homocysteine metabolism may be regulated through maternal folate concentrations during pregnancy and postnatal feeding.     

The role of contraceptive use in cervical cancer: the Maryland Cervical Cancer Case-Control Study

Recent evidence on the importance of sexual history and sexually transmissible agents in cervical cancer has been reported. Case-control studies have frequently demonstrated increased risk of cervical cancer for women using oral contraceptives, while laboratory results have shown that vaginal spermicides inactivate various sexually transmissible agents. To determine the role of contraceptive use in cervical cancer, 153 cases of Maryland women with invasive cervical cancer and age, race, and residence-matched controls were interviewed in 1985, focusing on sexual history, health care utilization patterns, screening history, contraceptive use, and smoking. Overall, lifetime use of contraceptives was protective of cervical cancer (odds ratio (OR) = 0.38, 95% confidence interval (CI) = 0.2-0.7). Use of oral contraceptives (OR = 0.48), diaphragm (OR = 0.29), and vaginal spermicides (OR = 0.28) were more frequent in controls than cases. After adjustment for behavioral factors (age at first intercourse, smoking, gaps in Papanicolaou smear testing, and obstetrician-gynecologist visits), use of vaginal spermicides remained significant (OR = 0.30), although use of oral contraceptives and barrier methods of contraception failed to remain significant. The effectiveness of vaginal spermicides in preventing cervical cancer may be due to their antiviral action.     

Physical Activity,Diet, and Pancreatic Cancer: A Population-Based,Case-Control Study in Minnesota

Although mounting evidence suggests that insulin resistance is involved in pancreatic carcinogenesis, few epidemiologic studies have comprehensively investigated the role of lifestyle factors influencing this metabolic disorder in the etiology of pancreatic cancer. We sought to examine this problem in a case-control study conducted in 1994–1998 in Minnesota. Cases (n = 186), aged 20 yr or older, were ascertained from all hospitals in the metropolitan area of the Twin Cities and the Mayo Clinic; from the latter, only cases residing in the Upper Midwest of the United States were recruited. Controls (n = 554) were randomly selected from the general population and frequency matched to cases by age (within 5 yr) and sex. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression. After adjustment for confounders, physical activity was associated with a reduced risk, but this protective effect was confined to light activity and moderate activity only (OR = 0.55, 95% CI = 0.30–0.97, P _trend = 0.038 and OR = 0.51, 95% CI = 0.28–0.93, P _trend = 0.07, for highest vs. lowest quartile, respectively). An increased risk was found for dietary intakes of energy and fat but was statistically significant for saturated and polyunsaturated fat only. Of note, no appreciable difference in the magnitude of the associations existed between saturated, monounsaturated, and polyunsaturated fat. Compared with individuals in the lowest quartile of fiber intake, the risk was approximately halved for those in the third (OR = 0.49, 95% CI = 0.26–0.94) and the highest quartile (OR = 0.52, 95% CI = 0.21–1.30). Our study lends support to the hypothesis that dietary and other lifestyle factors influencing insulin resistance modulate pancreatic cancer risk.     

武威市食管癌发病危险因素病例对照研究

目的探讨消化道肿瘤高发区甘肃省武威市食管癌发病危险因素。方法采用病例对照研究,在当地医院调查食管癌病例400例,正常对照752例,经单因素和多因素Logistic回归分析,筛选出与食管癌发病相关的可能危险因素。结果职业为农民、进食速度快、长期饮用蓄积水、进食腌制酸菜、吸烟、饮酒、萎缩性胃炎等与食管癌发病相关(其OR值分别为1.879、1.426、1.475、1.579、1.780、1.911、2.980),可增加其发病的危险性,而习惯性饮茶和良好的口腔卫生习惯为保护性因素(其OR值分别为0.663和0.708)。结论除去已经公认的致病因素,口腔卫生习惯不良也可能是该地食管癌发病不可忽视的危险因素之一,应针对上述因素采取综合防治措施。     

Associations of Dietary Glycemic Index,Glycemic Load and Carbohydrate with the Risk of Cervical Intraepithelial Neoplasia and Cervical Cancer: A Case-Control Study

Background: The association of dietary glycemic index (GI) and glycemic load (GL) with the risk of cervical cancer has never been investigated. Thus, we aimed to find evidence of any association of GI and GL with the risk of cervical intraepithelial neoplasia (CIN) and cervical cancer. Methods: In this hospital-based case-control study, we included 1340 women (670 controls and 262, 187 and 221 patients with CIN1, CIN2/3, and cervical cancer, respectively) from the Korean human papillomavirus cohort study. Completed demographic questionnaires and semi-quantitative food-frequency questionnaires were collected. The association of dietary GI and GL with CIN and cervical cancer was estimated using a logistic regression model. Results: The multivariate odds ratios (OR) of the highest compared with the lowest quintile of GL for CIN1 were 2.8 (95% confidence interval (CI) = 1.33–5.88). Dietary GI and GL were not associated with CIN2/3 and cervical cancer. Stratified analyses by body mass index (BMI) indicated a positive association between GI and GL and CIN 1 risk among women with a BMI (in kg/m²) <23 (OR = 2.94; 95% CI = 1.32–6.53; p for trend = 0.031 for GI and OR = 3.15; 95% CI = 1.53–6.52; p for trend = 0.013 for GL), but not among those with a BMI of ≥23. A stratification analysis by menopausal status showed that the highest quintile of GI and GL was significantly associated with the risk of CIN1 (OR = 2.91; 95% CI = 1.43–5.96; p for trend = 0.005) (OR = 2.96; 95% CI = 1.53–5.69; p for trend = 0.023) among premenopausal women. Also, in HPV positive women, dietary GL showed significant CIN1 risk (OR = 2.61; 95% CI = 1.09–6.24; p for trend = 0.087). Conclusion: Our case-control study supports the hypothesized associations of dietary GI and GL with increased risk of CIN1. Thus, the consumption of low GI and GL foods plays a significant role in the prevention of cervical carcinogenesis.     

Maternal Multivitamin Intake,Plasma Folate and Vitamin B12 Levels and Autism Spectrum Disorder Risk in Offspring

Background

To examine the prospective association between multivitamin supplementation during pregnancy and biomarker measures of maternal plasma folate and vitamin B₁₂ levels at birth and child's Autism Spectrum Disorder (ASD) risk.

Methods

This report included 1257 mother–child pairs, who were recruited at birth and prospectively followed through childhood at the Boston Medical Center. ASD was defined from diagnostic codes in electronic medical records. Maternal multivitamin supplementation was assessed via questionnaire interview; maternal plasma folate and B₁₂ were measured from samples taken 2–3 days after birth.

Results

Moderate (3–5 times/week) self‐reported supplementation during pregnancy was associated with decreased risk of ASD, consistent with previous findings. Using this as the reference group, low (≤2 times/week) and high (>5 times/week) supplementation was associated with increased risk of ASD. Very high levels of maternal plasma folate at birth (≥60.3 nmol/L) had 2.5 times increased risk of ASD [95% confidence interval (CI) 1.3, 4.6] compared to folate levels in the middle 80th percentile, after adjusting for covariates including MTHFR genotype. Similarly, very high B₁₂ (≥536.8 pmol/L) showed 2.5 times increased risk (95% CI 1.4, 4.5).

Conclusion

There was a ‘U shaped’ relationship between maternal multivitamin supplementation frequency and ASD risk. Extremely high maternal plasma folate and B₁₂ levels at birth were associated with ASD risk. This hypothesis‐generating study does not question the importance of consuming adequate folic acid and vitamin B₁₂ during pregnancy; rather, raises new questions about the impact of extremely elevated levels of plasma folate and B₁₂ exposure in‐utero on early brain development.     

Nitrate Intake Relative to Antioxidant Vitamin Intake Affects Gastric Cancer Risk: A Case-Control Study in Korea

The objective of this study was to determine whether the intake of nitrate relative to antioxidant vitamin rather than absolute intake of nitrate affects the risk of gastric cancer (GC). In a case-control study in Korea using a food frequency questionnaire, trained dietitians interviewed 136 GC cases and an equal number of controls matched by sex and age. As an index of nitrate intake relative to antioxidant vitamins intake, we calculated the nitrate:antioxidant vitamin consumption ratio. The mean daily nitrate intake from foods was very high in our subjects. Higher absolute intake of nitrate was not associated with GC risk [odds ratios (OR) = 1.13; 95% confidence interval (CI) = 0.42–3.06]. However, the GC risk distinctly increased as the nitrate:antioxidant vitamin consumption ratio increased, particularly with higher nitrate:vitamin E (OR = 2.78; 95% CI = 1.01–7.67) and nitrate:folate ratios (OR = 3.37; 95% CI = 1.28–8.87). Therefore, GC risk was influenced by the intake of nitrate relative to antioxidant vitamins. Our results suggest that a decrease in the intake of nitrate relative to antioxidant vitamins is considerably more effective in reducing GC risk than either a lower absolute intake of nitrate or a higher intake of antioxidant vitamins alone.