Influence of Nutritonal Intake on 6-Year Mortality in an Italian Elderly Population

Many observations agree on the existence, in older ages, of nutritional deficiencies secondary to dietary intake. This study investigated to what extent dietary intake of calories, protein, iron and vitamins influences the 6-year mortality in an elderly population living at home. To prevent the confounding effect of non-dietary factors, such as gender, functional and health status, socioeconomic conditions and health risk habits, these variable have also been considered. The dietary intake was calculated comparing the content of nutrients in self-reported, 24-hour diet, with the 1980 Recommended Dietary Allowances (RDA) obtaining a percentage for each nutrient. The percentage difference from the RDA was tested on 6-year mortality using a bivariate regression model. The intake of protein, vitamin A, thiamin, niacin, vitamin Bg and folate was significantly related to mortality: subjects with a lower dietary intake of those nutrients had a higher risk of death. When nutrient intake was tested in a multiple regression model, adjusted for non-dietary potential confounders, only folate was an independent predictor of mortality. This study shows that most of the dietary nutrient's intake is related to socioeconomic and physical factors.     

Folate, vitamin B6, vitamin B12, and methionine intakes and risk of stroke subtypes in male smokers

The associations of dietary folate, vitamin B(6), vitamin B(12), and methionine intakes with risk of stroke subtypes were examined among 26,556 male Finnish smokers, aged 50-69 years, enrolled in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Dietary intake was assessed at baseline by using a validated food frequency questionnaire. During a mean follow-up of 13.6 years, from 1985 through 2004, 2,702 cerebral infarctions, 383 intracerebral hemorrhages, and 196 subarachnoid hemorrhages were identified from national registers. In analyses adjusting for age and cardiovascular risk factors, a high folate intake was associated with a statistically significant lower risk of cerebral infarction but not intracerebral or subarachnoid hemorrhages. The multivariate relative risk of cerebral infarction was 0.80 (95% confidence interval: 0.70, 0.91; p(trend) = 0.001) for men in the highest versus lowest quintile of folate intake. Vitamin B(6), vitamin B(12), and methionine intakes were not significantly associated with any subtype of stroke. These findings in men suggest that a high dietary folate intake may reduce the risk of cerebral infarction.     

Intakes of vegetables and related nutrients such as vitamin B complex, potassium, and calcium, are negatively correlated with risk of stroke in Korea

Consumption of vegetables and fruits is associated with a reduced risk of stroke, but it is unclear whether their protective effects are due to antioxidant vitamins or folate and metabolically related B vitamins. The purpose of the study was to test the hypothesis that intake of fruits and vegetables, which are major sources of antioxidant and vitamin B complex vitamins, reduces the risk of stroke. Cases consisted of patients diagnosed with first event of stroke (n = 69). Controls (n = 69) were age-, sex-, and body mass index-matched to cases. Multivariable-adjusted regression analysis showed that subjects who ate four to six servings of vegetable per day had a 32% reduction in the risk of stroke, and those with more than six servings per day had a reduction of 69% after adjusting for age, sex, BMI, and family history of stroke. Intakes of total fat, plant fat, calcium, potassium, vitamin B₁, vitamin B₂, vitamin B₆, niacin, and folate were significantly and negatively associated with the risk of stroke. Although the trend was not significant, stroke risk was reduced in the second quartile (1.21-2.66 servings per week) of fish intake. However, intake of fruits (average daily intake of 1.0 serving) and antioxidant vitamins such as carotene, vitamin C, and vitamin E was not associated with the risk of stroke. In conclusion, our observational study suggests that intake of fat and vegetables, rich sources of vitamin B complex, calcium, and potassium may protect against stroke.     

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.     

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.     

Dietary intake of B-vitamins in mothers born a child with a congenital heart defect

Background Periconceptional use of multivitamins reduces the risk of a child with a congenital heart defect (CHD). Data on the impact of maternal diet, however, are lacking. Aim of the study We investigated the association between the maternal dietary intake of B-vitamins and having a child with a CHD. Methods A case-control study was performed in 192 mothers of a child with a CHD and 216 mothers of a healthy child. Mothers filled out food frequency questionnaires covering the current dietary intake, and general questionnaires at 17 months after the index-pregnancy. Maternal blood samples were taken to determine B-vitamin and plasma total homocysteine (tHcy) concentrations as nutritional biomarkers. Pregnant and lactating mothers and those with another diet compared with the preconceptional period were excluded for analysis. Case-mothers and controls were compared using the Mann-Whitney U test and logistic regression. Results The dietary intake of macronutrients and B-vitamins was comparable between both groups, but all mothers had a substantially lower median folate intake (cases 161 μg, controls 175 μg) than the Dutch recommended dietary allowance of 300 μg. Within the case-group, the intake of proteins and vitamin B₆ and the concentrations of serum vitamin B₁₂ and folate were significantly lower in hyperhomocysteinemics (tHcy ≥ 14.5 μmol/l) than in normohomocysteinemics. The maternal educational level was positively associated with B-vitamin intake, except for vitamin B₁₂ in controls. Low educated case-mothers showed a significantly lower median vitamin B₁₂ intake than controls (2.8 μg and 3.8 μg, P = 0.01). The CHD risk doubled if vitamin B₁₂ intake in these mothers reduced by 50% (OR 2.0; 95% CI: 1.1–3.5). Conclusions A diet low in vitamin B₁₂ is associated with an increased risk of a child with a CHD, especially in low educated women. A disbalance in the maternal intake of proteins and low folate intake may play a role as well, but needs further investigation. As hyperhomocysteinemia is a strong risk factor for adult cardiovascular disease, these data may imply that the hyperhomocysteinemic mothers and their children should be targeted for nutritional interventions.     

Diet,Physical Activity,and Cardiovascular Disease Risk Factors Among Older Chinese Americans Living in New York City

Cardiovascular disease (CVD) is the leading cause of death in the US and affects Chinese Americans disproportionately compared to other ethnic groups in the American population. However, few studies have examined CVD risk factors, including diet and physical activity, in Chinese Americans. This investigation used a cross-sectional design to evaluate the dietary intake, dietary supplement use, and physical activity of 125 older Chinese Americans aged 50–98 years, and to determine how these behaviors may be related to obesity and other CVD risk factors. Sociodemographic information, CVD risk factors, dietary intake, and physical activity were obtained from all participants recruited from health fairs conducted in New York City (NYC). The findings revealed that older Chinese American adults living in NYC had a high prevalence of overweight and obesity, borderline hypertension, pre-diabetes, and diabetes. Many participants did not meet their daily requirements calcium, potassium, folate, vitamin B6, and vitamin B12, several minerals and vitamins important for cardiovascular health. Although most participants consumed an adequate numbers of servings of foods from the main food groups, most did not meet the recommended number of servings of dairy foods and only one in four adults took a multivitamin supplement daily. After adjusting for potential confounders, daily consumption of oil/sweets and dairy foods was positively associated with waist circumference. Also, daily consumption of oils/sweets, meats, and grains was positively associated with systolic blood pressure. The majority of the participants reported at least 30 min of moderate intensity physical activity per day. Dietary intake or supplement use did not show protective effects but performing vigorous physical activity may reduce risk of CVD in this population.     

The Role of Diet,Alcohol, BMI,and Physical Activity in Cancer Mortality: Summary Findings of the EPIC Study

Evidence on the impact of diet, alcohol, body-mass index (BMI), and physical activity on mortality due to cancer and other cancer-related outcomes is still scarce. Herein, we reviewed the contribution of the European Prospective Investigation into Cancer and Nutrition (EPIC) study to the current state of the art on the role of these factors in cancer mortality. We identified 45 studies using a rapid systematic review methodology. Dietary factors associated with reduced cancer mortality included raw vegetable intake; dietary fiber intake; the Mediterranean diet; other dietary scores; other diet patterns including low meat eaters, vegetarians/vegans, or fish eaters; dietary intake (or biomarkers) of some vitamins (e.g., vitamin D, vitamin K2, or Vitamin C); and intake of lignans. Physical activity and following healthy lifestyle recommendations also reduced cancer mortality risk. In contrast, dietary factors associated with higher cancer mortality risk included poor diet quality, consumption of alcohol and soft drinks including juice, and, to a lesser extent, intake of some fatty acids. Excess weight and obesity also increased the risk of cancer mortality. The EPIC study holds valuable information on diet and lifestyle factors and offers a unique opportunity to identify key diet-related factors for cancer mortality prevention.     

Diet, serum homocysteine levels and ischaemic heart disease in a Mediterranean population

Homocysteine (Hcy) is recognised as a risk factor for IHD. Serum Hcy is negatively correlated with serum folate levels, the main sources of which are fruits, vegetables and legumes. The present case-control study was designed to examine the relationship between serum Hcy levels and IHD and to assess the role of dietary factors in the southern Mediterranean population of Crete, Greece. Serum Hcy, folate, vitamin B12, creatinine and glucose levels and a full lipid profile were measured in 152 patients with established IHD, median age 64 (range 33-77) years, and 152 healthy control subjects, age- and sex-matched. Dietary data were assessed using a 3 d food intake record. Compared with controls, patients with IHD had significantly higher daily intakes of vitamin B12 and MUFA and significantly lower intakes of carbohydrate, fibre, folate, cholesterol, n-3 fatty acids and total trans unsaturated fatty acids. Moreover, patients had significantly higher serum Hcy, vitamin B12 and creatinine levels, but significantly lower folate. Serum folate concentrations in both groups had a significant positive correlation with dietary fibre consumption and a significant inverse correlation with vitamin B12 intake. IHD patients should be encouraged to increase their daily dietary intake of fibre, folate and n-3 fatty acids, which are significant components of the traditional Cretan Mediterranean diet. Where dietary folate intake is inadequate, folate supplements are recommended to reduce elevated Hcy levels.     

Depression and Vegetarians: Association between Dietary Vitamin B6, B12 and Folate Intake and Global and Subcortical Brain Volumes

Deficiency of vitamin B6 and vitamin B12, mostly in vegetarians, is found to be associated with depression and adverse neurological function. We investigated whether vitamin B6, B12, and folate have an effect on brain structure, especially among depressed people who follow a specific diet. The study sample comprised 9426 participants from the UK Biobank cohort with a mean age of 62.4 years. A generalized linear model controlling for age, sex, body mass index, ethnicity, town send deprivation index, educational qualification, smoking, and alcohol intake was used to test the association between study groups and structural brain volumes. Depression was more prevalent, and intake of vitamin B6 and B12 was lower among vegetarians, while non-vegetarians had a lower intake of folate. Overall, no significant association was observed between vitamin B6, B12, and folate intakes and both global and subcortical brain volumes among participants with depression. However, vitamin B12 intake was positively associated with right pallidum among non-depressed participants, and a significant interaction between vitamin B12 intake and depression status on the right pallidum was observed. Also, a significant interaction between folate intake and depression status on grey matter (GM) volume and left thalamus was observed. Upon diet stratification, folate intake is associated with total brain volume and GM volume among vegetarians with depression. Furthermore, no significant associations were observed for subcortical regions. Our findings suggest that dietary intake of vitamin B6 and B12 might have an effect on brain structure. Vegetarians, particularly those who suffer from depression may benefit from supplementing their diets with vitamins B6, B12, and folate to ensure brain health. Further studies, especially with a larger sample size and longitudinal design, are needed to confirm these findings.     

Serum homocysteine concentration as a marker of nutritional status of healthy subjects in Crete, Greece

BACKGROUND: Dietary habits are an important determinant of serum homocysteine (tHcy), which may be a marker rather than a cause of progression of the atherosclerotic process. The aim of the present study was to evaluate the nutritional status, and to determine the serum tHcy concentrations in healthy subjects who live in rural areas of Crete, and who theoretically follow a contemporary Mediterranean-style diet. METHODS: Serum tHcy, folate, vitamin B(12), creatinine, glucose, and the lipid profile, were measured in 203 (141 men and 62 women) healthy subjects, aged 33-78 years. The major risk factors for cardiovascular disease such as age, gender, cigarette smoking, obesity were recorded and dietary data were assessed using a 3-day weighed food intake record. RESULTS: Our population had high serum tHcy, low serum folate concentrations and lower than the traditional Cretan dietary folate intake [median (range): 12.0 (3.6-44.7) micromol L(-1), 7.9 (1.9-15.5) ng mL(-1) and 241 (68-1106) microg, respectively]. Dietary intake of fibre, omega-3, and mono- or/ polyunsaturated fatty acids was also low. An inverse relation was observed between serum tHcy concentrations and serum folate (r = -0.28; P < 0.01) and vitamin B(12) levels (r = -0.33; P < 0.001). CONCLUSIONS: Nowadays, the Cretan diet has changed towards a more westernized eating pattern. Given the analytic difficulties in determining the amount of folate in food and the inverse correlation between serum tHcy and folate levels, serum tHcy concentrations may be a useful marker for nutritional status, especially folate deficiency, in healthy subjects.     

Folate, vitamin B6, multivitamin supplements, and colorectal cancer risk in women

The authors evaluated associations between intakes of folate and vitamin B(6) and colorectal cancer risk among women enrolled in a randomized trial on aspirin and vitamin E in disease prevention. At baseline (1992-1995), 37,916 US women aged >or=45 years who were free of cancer and cardiovascular disease provided dietary information. During an average of 10.1 years of follow-up (through February 20, 2004), 220 colorectal adenocarcinoma cases were documented. Total folate and vitamin B(6) intakes were not significantly associated with the risk of colorectal cancer. However, dietary intakes of folate and vitamin B(6) were significantly inversely associated with colorectal cancer risk among women who were not taking supplements containing folate and vitamin B(6). Multivariable relative risks among women in the highest quintiles of intake versus the lowest were 1.16 (95% confidence interval (CI): 0.76, 1.79) for total folate, 1.14 (95% CI: 0.77, 1.69) for total vitamin B(6), 0.46 (95% CI: 0.26, 0.81) for dietary folate, and 0.69 (95% CI: 0.41, 1.15) for dietary vitamin B(6). The use of multivitamin supplements was not related to colorectal cancer risk. These findings suggest that higher dietary intakes of folate and vitamin B(6) may reduce the risk of colorectal cancer in women. An alternative explanation is that other factors related to dietary intakes of folate and vitamin B(6) account for the inverse associations.     

The use of B vitamin supplements and peripheral arterial disease risk in men are inversely related

Peripheral arterial disease (PAD) causes morbidity and is associated with mortality. B vitamin intake has been inversely associated with coronary heart disease, but their effects on PAD are not known. We examined prospectively the relationships between dietary folate, vitamin B-6 and B-12 and PAD risk in 51529 male U.S. health professionals, aged 40 to 75 y, who answered a detailed 131-item questionnaire to assess diet and vitamin supplement use. The study population consisted of 46036 men free of PAD, cardiovascular disease and diabetes at baseline followed for 12 y during which we documented 308 incident PAD cases. For every 400 microg/d increment of folate intake, the multivariate adjusted PAD risk decreased by 21% [relative risk (RR) = 0.79, 95% CI 0.64-0.96]. Men in the top category of folate intake (median = 840 micro g) were at 33% lower risk of PAD than men in the bottom category (median = 244 microg) (RR = 0.67, 95% CI 0.45-0.96, P-value, test for trend = 0.03) after multivariate adjustment. There were weak inverse associations between intake of vitamin B-6 and PAD risk (RR = 0.70, 95% CI 0.48-1.02, P-value, test for trend = 0.06) and B-12 (RR = 0.77, 95% CI 0.54-1.11, P-value, test for trend = 0.12). These results suggest that higher consumption of folate may contribute to the prevention of PAD.     

Dietary folate, vitamin B6, vitamin B12 and methionine intake and the risk of breast cancer by oestrogen and progesterone receptor status

Few studies have evaluated the relationship between the consumption of dietary folate and one-carbon metabolism-related nutrients and breast cancer risk defined by oestrogen receptor (ER) and progesterone receptor (PR) status. The objective of the present study was to examine the associations between dietary folate, vitamin B6, vitamin B12, and methionine intake and the risk of breast cancer by ER and PR status among Chinese women in Guangdong. A hospital-based case-control study was conducted from June 2007 to August 2008, with 438 cases and 438 age (5-year interval)- and residence (rural/urban)-matched controls. Dietary intake information was assessed using a validated FFQ administered through a face-to-face interview. Unconditional logistic regression models were used to calculate multivariate-adjusted OR and 95 % CI. A significant inverse association was found between dietary folate and vitamin B6 intake and breast cancer risk. The adjusted OR of the highest v. the lowest quartile were 0·32 (95 % CI 0·21, 0·49; P(trend) < 0·001) for dietary folate and 0·46 (95 % CI 0·30, 0·69; P(trend) < 0·001) for vitamin B6. No associations were observed for vitamin B12 and methionine intake. A significant inverse association between dietary folate intake and breast cancer risk was observed in all subtypes of ER and PR status. These findings suggest that dietary folate and vitamin B6 intakes were inversely associated with breast cancer risk. The inverse association did not differ by ER and/or PR status.     

Tea as a Potential Chemopreventive Agent in PhIP Carcinogenesis: Effects of Green Tea and Black Tea on PhIP-DNA Adduct Formation in Female F-344 Rats

Disturbances in DNA methylation have been hypothesized as being involved in carcinogenesis. It has been proposed that dietary factors such as folate, alcohol, and methionine may be associated with colon cancer because of their involvement in DNA methylation processes. Data from a large retrospective population‐based case‐control study of incident colon cancer were used to evaluate whether intake of alcohol and other dietary factors involved in DNA methylation are associated with colon cancer. Dietary data were obtained using a detailed diet history questionnaire. We did not observe strong independent associations between folate, vitamin B6, vitamin B12, methionine, or alcohol and risk of colon cancer after adjusting for body size, physical activity, cigarette smoking patterns, energy intake, and dietary intake of fiber and calcium. However, when assessing the associations between colon cancer and a composite dietary profile based on alcohol intake, methionine, folate, vitamin B12, and vitamin B6 we observed a trend of increasing risk as one moved from a low‐ to a high‐risk group. This trend was modest and most marked in those diagnosed at a younger age [odds ratio (OR) for men = 1.3, 95% confidence interval (CI) = 0.9–1.9; OR for women = 1.6, 95% CI= 1.0–2.6]. We observed that associations with this high‐risk dietary profile were greater among those who took aspirin or nonsteroidal anti‐inflammatory drugs on a regular basis and were younger at the time of diagnosis (men OR = 1.7, 95% CI = 1.0–3.2; women OR = 2.2, 95% CI= 1.0–4.8) and for distal tumors (men OR = 1.4, 95% CI = 0.9–2.3; women OR = 2.0, 95% CI = 1.0–3.8). Findings from this study provide only limited support for previously reported associations between dietary factors involved in DNA methylation and risk of colon cancer.     

Folate, vitamin B12 and homocysteine in relation to birth defects and pregnancy outcome

Increased folate intake reduces the risk of neural tube defects, other malformations and also possibly, pregnancy complications. Increasing evidence suggests that the beneficial effect of folate may be related to improved function of methionine synthase, a vitamin B12-dependent enzyme that converts homocysteine to methionine. In India, the majority of the population adheres to a vegetarian diet known to be deficient in vitamin B12. In such a population, increased folate intake may offer minimal protection against birth defects, whereas vitamin B12 administration should be considered. In this review, is described the metabolism of and interrelations between folate, vitamin B12 and homocysteine. This is followed by a brief discussion of some of the proposed mechanisms for their biological effects in relation to birth defects and pregnancy outcome.     

A healthy body, a healthy mind: long-term impact of diet on mood and cognitive function

Certain dietary risk factors for physical ill health are also risk factors for depression and cognitive impairment. Although cholesterol lowering has been suggested to increase vulnerability to depression, there is better support for an alternative hypothesis that intake of n-3 long-chain polyunsaturated fatty acids can affect mood (and aggression). Possible mechanisms for such effects include modification of neuronal cell membrane fluidity and consequent impact on neurotransmitter function. Stronger evidence exists concerning a role for diet in influencing cognitive impairment and cognitive decline in older age, in particular through its impact on vascular disease. For example, cognitive impairment is associated with atherosclerosis, type 2 diabetes and hypertension, and findings from a broad range of studies show significant relationships between cognitive function and intakes of various nutrients, including long-chain polyunsaturated fatty acids, antioxidant vitamins, and folate and vitamin B12. Further support is provided by data on nutrient status and cognitive function. Almost all this evidence, however, comes from epidemiological and correlational studies. Given the problem of separating cause and effect from such evidence, and the fact that cognitive impairment and cognitive decline (and depression) are very likely to be significant factors contributing to the consumption of a poor diet, greater emphasis should now be placed on conducting intervention studies. An efficient approach to this problem could be to include assessments of mood and cognitive function as outcome measures in studies designed primarily to investigate the impact of dietary interventions on markers of physical health.     

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.     

Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, intakes of folate and related B vitamins and colorectal cancer: a case-control study in a population with relatively low folate intake

Folate is key in one-carbon metabolism, disruption of which can interfere with DNA synthesis, repair, and methylation. Efficient one-carbon metabolism requires other B vitamins and the optimal activity of enzymes including 5,10-methylenetetrahydrofolate reductase (MTHFR). We report a population-based case-control study of folate intake, related dietary factors and MTHFR polymorphisms (C677T, A1298C) and colorectal cancer in a population with relatively high colorectal cancer incidence and relatively low folate intake. A total of 264 cases with histologically confirmed incident colorectal cancer and 408 controls participated. There was no clear trend in risk with reported intakes of total, or dietary, folate, riboflavin, vitamin B12 or vitamin B6, nor were there interactions between folate intake and the other B vitamins or alcohol. For C677T, risk decreased with increasing variant alleles (multivariate OR for CT v. CC = 0.77 (95 % CI 0.52, 1.16); OR for TT v. CC = 0.62 (95 % CI 0.31, 1.24)), which, although not statistically significant, was consistent with previous studies. For A1298C, compared with AA subjects, CC subjects had modest, non-significant, reduced risk (multivariate OR = 0.81 (95 % CI 0.45, 1.49)). There were significant interactions between total folate and C677T (P = 0.029) and A1298C (P = 0.025), and total vitamin B6 and both polymorphisms (C677T, P = 0.016; A1298C, P = 0.033), although the patterns observed differed from previous studies. Seen against the setting of low folate intake, the results suggest that the role of folate metabolism in colorectal cancer aetiology may be more complex than previously thought. Investigation of particular folate vitamers (for example, tetrahydrofolate, 5,10-methylenetetrahydrofolate) may help clarify carcinogenesis pathways.