Dietary Intake of Folate and Assessment of the Folate Deficiency Prevalence in Slovenia Using Serum Biomarkers

Folate deficiency is associated with various health issues, including anemia, cardiovascular disease, and birth defects. Low folate intake and suboptimal folate status were found in several countries; however, this topic has not yet been investigated in Slovenia. Dietary folate intake and serum folate status were investigated through the nationally representative food consumption study SI.Menu/Nutrihealth. Folate intake was estimated using a sample of N = 1248 subjects aged 10–74 years, stratified in three age groups (adolescents, adults, elderly population), through two 24 h-dietary recalls and food propensity questionnaire. Data on serum folate and homocysteine was available for 280 participants. Very low folate intake (<300 µg/day) was observed in 59% of adolescents, 58% of adults and 68% of elderlies, and only about 12% achieved the WHO recommended level of 400 µg/day. Major dietary contributors were vegetables and fruit, and cereal products. Living environment, education, employment status and BMI were linked with low folate intake in adults; BMI, and sex in adolescents; and sex in elderlies. Considering low serum folate (<7 nmol/L) and high serum homocysteine (>15 nmol/L), folate deficiency was found in 7.6 and 10.5% in adults and elderlies, respectively. Additional public health strategies should be employed to promote the consumption of folate-rich foods. With current folate intakes, supplementation with folic acid is relevant especially in specific vulnerable populations, particularly in women planning and during pregnancy.     

The Effect of Folate Fortification of Cereal-Grain Products on Blood Folate Status,Dietary Folate Intake,and Dietary Folate Sources among Adult Non-Supplement Users in the United States

Objective: Since January 1998, the Federal Drug Administration has required folic acid fortification of all enriched cereal-grain products in the U.S. This program intended to increase folic acid intake among women of childbearing age in order to decrease their risk of pregnancies affected by neural tube defects. The aim of this study was to explore the changes in serum and erythrocyte folate status of the adult U.S. population following folic acid fortification of enriched cereal-grain products and to explore accompanying changes in food sources and dietary total folate intake.

Methods: We compared data from two National Health and Nutrition Examination Surveys (NHANES): NHANES III, conducted during 1988 to 1994, reflecting the time prior to folate fortification, and NHANES 1999–2000, reflecting the time period after fortification.

Results: Mandatory folic acid fortification led to significant increases in both serum and erythrocyte folate concentrations in all sex and age groups. In the overall study population the mean serum folate concentration increased more than two-fold (136%), from 11.4 nmol/L to 26.9 nmol/L, and the mean erythrocyte folate concentration increased by 57 percent, from 375 nmol/L to 590 nmol/L. Less than 10% of women of childbearing age reached the recommended erythrocyte folate concentration of greater than 906 nmol/L that has been shown to be associated with a significant reduction in neural tube defect (NTD) risk. After fortification, the category “bread, rolls, and crackers” became the single largest contributor of total folate to the American diet, contributing 15.6% of total intake, surpassing vegetables, which were the number one folate food source prior to fortification. Dietary intake of total folate increased significantly in almost all sex and age groups, except in females over 60 years of age. The mean dietary total folate intake of the study population increased by 76 μg/d (28%), from 275 μg/d to 351 μg/d.

Conclusions: The fortification of enriched cereal-grain products with folic acid lead to a significant improvement of blood folate status of the overall adult, non-supplement using, US population. However, women of childbearing age may take folic acid supplements to reach erythrocyte folate levels that have been associated with decreased risk of NTDs.     

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.     

Dietary Folate,Alcohol Consumption,and Risk of Non-Hodgkin Lymphoma

Dietary deficiency of folate and other micronutrients involved in the one-carbon metabolism (i.e., vitamins B ₂ , B ₆ , B ₁₂ , and methionine) have been related to several diseases, including cancers, but results on non-Hodgkin lymphoma (NHL) are controversial. A hospital-based case-control study was conducted in Italy, in 1999–2002. Cases were 190 incident, histologically confirmed NHL aged 18–84 years. Controls were 484 subjects admitted to hospitals for acute, non-neoplastic diseases supposed to be unrelated to alcohol consumption or to diet modification. Dietary habits, including alcohol drinking, were assessed by a validated food-frequency questionnaire. Nutrient intakes were computed using the Italian food composition database. Odds ratios (ORs) and corresponding 95% confidence intervals for tertiles of nutrients' intake were computed using the energy-adjusted residual models. No significant association emerged between NHL risk and intakes of folate (OR = 0.9), vitamin B ₂ (OR = 0.9), vitamin B ₆ (OR = 0.8), and methionine (OR = 0.7). However, a significant inverse association was observed for all the nutrients examined among abstainers and former drinkers, whereas no relations between one-carbon nutrients and NHL risk emerged among current alcohol drinkers. Our findings support the possibility of an antagonist effect of alcohol on the one-carbon metabolism in NHL etiology. However, the lack of an overall effect for one-carbon nutrients and the small sample size suggested caution in interpreting our results.     

SOCS-1和RIZ1基因启动子区CPG岛甲基化与胃癌发病的关系

目的检测细胞因子信号转导抑制因子(SOCS-1)和Rb结合锌指结构基因(RIZI)启动子区甲基化状态,初步探讨其甲基化状态与胃癌发生的关系。方法收集南京市原发性胃癌患者96例为胃癌组,采用1:1病例-对照研究方法 ,随机选取非消化系统疾病、非肿瘤患者96例为对照组,采用甲基化特异性PCR(MSP)检测胃癌组及对照组外周血DNA的SOCS-1和RIZl基因基因启动子区甲基化状态。结果胃癌组SOCS-I(OR=4.845,P<0.001,95%CI:2.506～9.367)和RIZI基因(OR=3.338,P=0.01,95%CI:1.591～7.003)启动子区甲基化率均高于对照组,且有统计学意义。在胃癌组中,发现SOCS-1基因甲基化异常与年龄、性别、Lauren分型、胃癌发生部位、TNM分期等无统计学关联(P>0.05),而与肿瘤淋巴有无转移有一定关联(P=0.002);RIZI基因甲基化异常与年龄、性别、Lauren分型、胃癌发生部位、TNM分期、淋巴结转移均未见统计学关联(P>0.05)。结论 SOCS-1和RIZI基因启动子区异常甲基化可能具有肿瘤特异性,检测SOCS-1和RIZI基因甲基化状态对于胃癌的早期诊断和治疗有一定意义。     

Low Folate Status Enhanced Benzene-Induced Cytogenetic Damage in Bone Marrow of Mice: A Relationship Between Dietary Intake and Tissue Levels of Folate

We examined the protective effect of dietary folate on benzene-induced chromosomal damage in bone marrow of mice regarding folate levels in diet and tissue. Male mice were fed either a deficient, basal, or high folate diet (0, 2, or 8 mg/kg diet, respectively) for 4 wk followed by a single dose of benzene. Plasma folate levels corresponded to those of dietary intake. Meanwhile, bone marrow, erythrocyte, and liver folate were decreased to 40% in the deficient group and almost saturated in the high group. Plasma homocysteine levels negatively correlated to levels of tissue folate. Chromosomal damage, evaluated by micronucleus assay, was not affected by folate status alone but was markedly enhanced by benzene, particularly in the deficient group (P < 0.05 vs. the basal and high groups). The activities of hepatic drug-metabolizing enzymes did not enhance benzene metabolism in the deficient groups, indicating that enhanced chromosomal damage was solely due to the low folate status. These results suggest that a low folate status can increase the risk of benzene-induced chromosomal damage in bone marrow, but excess folate intake does not enhance protection, as it is saturated in tissue.     

Nutrient and Fiber Intake and Risk of Renal Cell Carcinoma

This study examines the association between nutrient and fiber intake and the risk of renal cell carcinoma (RCC). Between 1994 and 1997 in 8 Canadian provinces, mailed questionnaires were completed by 1,138 incident, histologically confirmed cases of RCC and 5,039 population controls. Measurement included information on socioeconomic status, lifestyle habits, and diet. A 69-item food frequency questionnaire provided data on eating habits 2 yr before data collection. Odds ratios (ORs) and 95% confidence intervals were derived through unconditional logistic regression. Intakes of total fat, saturated fat, monounsaturated fat, trans-fat, and cholesterol were associated with the risk of RCC; the ORs for the highest vs. the lowest quartile were 1.67, 1.53 and 1.46, 1.31, and 1.48, respectively. The positive association was apparently stronger in women, overweight or obese, and never smokers. Sucrose was related to the risk of RCC. High fiber intake was inversely associated with RCC risk. No association was found with intake of total protein and polyunsaturated fat, n-3 and n-6 polyunsaturated fatty acids, and total carbohydrates. The results were consistent across strata of sex, tobacco, and BMI. The findings suggest that a diet low in fats and cholesterol and rich in fiber could favorably affect the risk of RCC.     

Dietary and Supplemental Folate and the Risk of Left- and Right-Sided Colorectal Cancer

Epidemiological evidence suggests that folate may lower the risk of colorectal cancer (CRC) although studies have been inconsistent and some have indicated differences in the effects of naturally occurring dietary folate and the synthetic form of this vitamin, folic acid. Most studies to date have considered CRC as a single disease; however, cancers that develop on the left and right sides of the colorectum display important phenotypic differences, suggesting they may also have different risk factors. A population-based case-control study was conducted in Western Australia to examine the relationship between intake of both natural dietary folate and supplements containing folic acid and the risk of left- and right-sided CRC. Data were available for 850 cases (575 left-sided and 275 right-sided) and 958 controls. Odds ratios were calculated using multinomial logistic regression models. There was no association between natural dietary folate intake and risk of either left-or right-sided CRC. Supplement use similarly had no significant effect on right-sided CRC. However, long-term supplement users (4+ yr) were at lower risk of left-sided CRC than those who had not taken supplements (OR = 0.65, 95% CI, 0.50–0.86) and there was a significant trend in risk reduction as duration of use increased (P < 0.01).     

Association between Dietary Intake of Flavonoids and Cancer Recurrence among Breast Cancer Survivors

Intake of flavonoids is associated with the incidence of breast cancer, but the association between the intake of flavonoids and cancer recurrence is unclear. This study aimed to investigate the hypothesis that intake of flavonoids and flavonoid-rich foods is negatively associated with cancer recurrence. Among 572 women who underwent breast cancer surgery, 66 patients had a cancer recurrence. Dietary data were collected using a structured 24-h dietary recall, and intake of flavonoids was calculated based on the Korea Rural Development Administration flavonoid database. Among overweight and obese patients, disease-free survival was associated with intake of flavonoids (p = 0.004) and flavonoid-rich foods (p = 0.003). Intake of flavonoids (hazard ratio (HR) = 0.249, 95% confidence interval (CI): 0.09–0.64) and flavonoid-rich foods (HR = 0.244, 95% CI: 0.09–0.66) was negatively associated with cancer recurrence after adjusting for confounding factors in overweight and obese patients. Consumption of flavonoids and flavonoid-rich foods was lower in overweight and obese patients with cancer recurrence than those without recurrence and in normal-weight patients. This study suggests that intake of flavonoids and flavonoid-rich foods could have beneficial effects on cancer recurrence in overweight and obese breast cancer survivors.     

Dietary Ruminant and Industrial Trans-Fatty Acids Intake and Colorectal Cancer Risk

As colorectal cancer (CRC) is largely due to modifiable lifestyle habits, the awareness on its risk factors is highly important. Dietary fatty acids have been linked to CRC risk. We explored the association between dietary trans fatty acids (TFAs) intake and CRC risk. We analyzed 865 CRC cases (434 in colon and 404 in rectum) and 3206 controls of the IROPICAN study, with data collected by trained interviewers using validated questionnaires. TFAs intake (industrial and ruminant types) was categorized into quartiles. Multivariate logistic regression models were built to calculate the odds ratios (OR) for the association between CRC and TFAs. We observed a positive association between industrial TFAs and colon cancer (OR for highest vs lowest quartile [OR_Q4vsQ1] = 1.28, 95% confidence interval 1.07–1.54). A higher association was observed between industrial TFAs and CRC, occurring after 50 years of age. In addition, elaidic acid was associated with an increased risk of colon (OR_Q4vsQ1 = 1.58, 1.24–2.02) and specifically of proximal colon cancer (OR _Q4vsQ1 = 2.12, 1.40–3.20), as well as of rectum cancer (OR_Q4vsQ1 = 1.40, 1.07–1.83). An inverse association was observed between ruminant TFAs intake and colon cancer risk (OR_Q4vsQ1 = 0.80, 0.67–0.97). Industrial TFAs, such as semisolid/solid hydrogenated oils, may increase the risk of CRC, especially colon and proximal colon cancer. In contrast, ruminant TFAs do not appear to be associated with CRC. Awareness programs and regulatory actions regarding hydrogenated oils are warranted, given their high consumption through ultra-processed foods in more developed and less developed countries.     

Dietary Intake of B Vitamins and Methionine and Colorectal Cancer Risk

B vitamins are involved in 1-carbon metabolism, which is necessary for DNA replication, DNA repair, and regulation of gene expression. Recent studies suggest inverse associations between folate and vitamin B6 intakes and colorectal cancer risk but associations with other B vitamins and methionine have not been widely studied. After following 14,645 men and 22,467 women for 15 yr on average, we ascertained 910 incident colorectal cancers. Dietary intakes were estimated using a 121-item food frequency questionnaire. Hazard ratios (HRs) and 95% confidence intervals were estimated using Cox regression. We found some evidence of a U-shaped relationship between colon cancer risk and vitamin B6 and an inverse U-shaped relationship between rectal cancer risk and B12 (test for the quadratic trend, P = 0.005 and P = 0.0005 respectively). For colon cancer, we observed a reduced risk associated with low methionine/high folate, HR = 0.63 (0.49, 0.80) and an increased risk associated with high methionine/high folate, HR = 1.36 (1.06, 1.74) (P interaction < 0.0001). Our study suggests a U-shaped association between colon cancer risk and vitamin B6 intake and an inverse U-shaped association between rectal cancer risk and vitamin B12. Adequate folate intake might protect against colon cancer risk in those with low methionine intake.     

Dietary Fat Intake and KRAS Mutations in Colorectal Cancer in a Moroccan Population

Epidemiologic data support an association between diet and mutations in the Kirsten-ras (KRAS) gene involved in colorectal cancer (CRC) development. This study aimed to explore the associations between fat intake and KRAS mutations in codons 12 and 13 in cases of CRC in the Moroccan population. A multicenter case-series study nested in a large-scale Moroccan CRC case-control study was conducted. Among all CRC cases recruited, 151 specimens were available for the DNA mutation analysis. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (Cis) for KRAS mutation status according to the fat intake variables. A KRAS mutation was detected in the CRC tumor of 34.4% of the patients among whom 65.4% had a single mutation at codon 12 and 34.6% had a single mutation at codon 13. Compared to low levels of consumption, a positive association was observed between high polyunsaturated fatty acids (PUFA) consumption (>16.9 g/day) and prevalence of KRAS mutations (OR = 2.15, 95% CI = 1.01–4.59). No statistically significant associations were observed for total fat, monounsaturated fatty acids, saturated fatty acids and KRAS mutations. The results of this study suggest that PUFA may be relevant in the etiology of CRC, possibly through the generation of G > A transitions at the KRAS oncogene. Further studies are needed to verify and explain this finding.     

Paternal Dietary Folate,B6 and B12 Intake,and the Risk of Childhood Brain Tumors

It is biologically plausible that a paternal preconception diet low in nutrients related to DNA integrity could affect sperm DNA and subsequently risk of cancer in the offspring. The aim of this analysis was to investigate whether paternal preconception dietary folate, B6, or B12 intake was associated with the risk of childhood brain tumors (CBT) in an Australian case-control study. Cases <15 years of age were recruited from 10 Australian pediatric oncology centers between 2005 and 2010, and controls from random-digit dialing, frequency-matched to cases on age, sex, and state of residence. Paternal dietary information was obtained by food-frequency questionnaires. Nutrient values were energy adjusted and divided into tertiles for analysis by unconditional logistic regression. In fathers with relevant data (237 cases and 629 controls), no association with dietary folate and B6 and risk of CBT was seen; high B12 intake was associated with an increased risk of CBT (odds ratio highest vs. lowest tertile: 1.74, 95% confidence interval: 1.14, 2.66) without an increasing trend. These results do not support the hypothesis that paternal dietary folate intake influences the risk of CBT. The increased OR observed between dietary B12 intake and risk of CBT is without any certain explanation.     

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.     

Prospective Study of Dietary Phytoestrogen Intake and the Risk of Colorectal Cancer

Dietary phytoestrogen intake has been inversely associated with the risk of prostate and breast cancer and might also affect the risk of colorectal cancer. We evaluated the associations between dietary lignan intake, dietary isoflavonoid intake, dietary coumestrol intake, and dietary enterolignans and equol intake, and risk of colorectal cancer. Data from the Women's Lifestyle and Health (WLH) Cohort study was used. The WLH study is a prospective population-based cohort study including 48,268 Swedish women aged 30–49 years at the time of enrolment in 1991–92. Follow-up for colorectal cancer incidence, death, and emigration until the end of 2010 was performed through record linkage to the Swedish Cancer Registry and Total Population Register. During follow-up 206 incident colorectal cancer cases were identified. Cox proportional hazards models were fitted to estimate adjusted risk ratios with 95% confidence intervals. We found no statistically significant association between the intake of dietary lignans, dietary isoflavonoids, coumestrol, or enterolignans and equol, and risk of colorectal cancer. We found no association between dietary phytoestrogen intake and the risk of colorectal cancer. However, since the number of cancer cases was small, our results need to be confirmed. Future studies should investigate colon and rectal cancer separately.     

Overall Dietary Intake and Prognosis after Breast Cancer: A Systematic Review

Breast cancer survivors often seek information about how lifestyle factors, such as diet, may influence their prognosis. Previous studies have reviewed evidence around single nutrients, individual foods or food groups. We reviewed studies examining relationships between overall dietary intake and prognosis in breast cancer survivors. A systematic search was conducted to identify studies, published until June 2016, which assessed associations between overall dietary intake (i.e., quality; score; pattern) and mortality and/or recurrence in breast cancer survivors. We identified seven eligible studies. Studies were heterogeneous regarding diet assessment timing (before/after diagnosis); mean age and menopausal status; and dietary intake measure (statistically derived/a priori defined indices). Better overall dietary intake (i.e., better quality; healthy/prudent pattern; less inflammatory diet) was associated with decreased risk of overall and non-breast cancer mortality, in most studies. Insufficient evidence is available to draw conclusions regarding breast cancer-specific survival and disease recurrence. Following breast cancer diagnosis, better overall dietary intake may independently improve overall and non-breast cancer survival. Survivors may improve prognosis by adopting more healthful dietary patterns consistent with dietary guidelines and/or prudent diet. Future adequately powered studies should consider measuring dietary intake consistently to better understand the role of diet in disease-specific outcomes.     

Dietary Polyamines Intake and Risk of Colorectal Cancer: A Case-Control Study

Polyamines (including putrescine, spermidine, and spermine) are small, cationic molecules that are necessary for cell proliferation and differentiation. Few studies have examined the association of dietary polyamines intake with colorectal cancer risk. The aim of this study was to evaluate total polyamines, putrescine, spermidine, and spermine intake in relation to colorectal cancer risk in China. In total, 2502 colorectal cancer cases and 2538 age-(5-year interval) and sex-matched controls were recruited from July 2010 to April 2019. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated by multivariable unconditional logistic regression after adjustment for various potential confounding factors. Higher intake of total polyamine, putrescine and spermidine was significantly associated with reduced risk of colorectal cancer. The adjusted ORs for the highest compared with the lowest quartile of intake were 0.60 (95% CI 0.50, 0.72; P_trend < 0.001) for total polyamines, 0.35 (95% CI 0.29, 0.43; P_trend < 0.001) for putrescine and 0.79 (95% CI 0.66, 0.95; P_trend = 0.001) for spermidine, respectively. However, higher intake of spermine was associated with increased risk of colorectal cancer, with an adjusted OR of 1.58 (95% CI 1.29, 1.93; P_trend < 0.001). This data indicate that higher intake of total polyamines, putrescine and spermidine, as well as lower intake of spermine, is associated with a decreased risk of colorectal cancer.     

Growth,Dietary Intake,and Vitamin D Receptor (VDR) Promoter Genotype in Indonesian School-Age Children

Nutrition has been known as a predominant factor associated with stunting. However, some studies have discovered a genetic contribution in calcium absorption that will affect growth, known as the VDR gene. The aim of this study was to assess the association between VDR gene polymorphism and dietary intake towards height-for-age z-score (HAZ) of elementary school children in Malang District, East Java. This study analyzed the baseline of a randomized trial in East Java, Indonesia. School children aged 8–10 years old (n = 142) were included in this study. Energy, protein, calcium, and vitamin D intakes were obtained using 4-day 24-h dietary recalls. Two SNPs located in the promoter region of VDR gene were selected (rs11568820 and rs4516035) and analyzed using Real-Time PCR. The result showed a significant correlation between energy and protein intake with HAZ of the children (p = 0.030 and p = 0.016, respectively). The association between VDR gene and HAZ was not found (p > 0.05). Adjusted by other factors, protein intake was significantly correlated with HAZ (β = 0.034, 95% CI 0.015–0.052, p < 0.001, adj. R² = 0.089). The children in our study had a favorable VDR gene genotype, however the effect of VDR gene promoter activity might not be revealed due to very low vitamin D and calcium intake to stimulate intestinal calcium absorption which in turn affects HAZ.