Jeong-Hwa Choi

Contemporary Issues Surrounding Folic Acid Fortification Initiatives

The impact of folate on health and disease, particularly pregnancy complications and congenital malformations, has been extensively studied. Mandatory folic acid fortification therefore has been implemented in multiple countries, resulting in a reduction in the occurrence of neural tube defects. However, emerging evidence suggests increased folate intake may also be associated with unexpected adverse effects. This literature review focuses on contemporary issues of concern, and possible underlying mechanisms as well as giving consideration the future direction of mandatory folic acid fortification. Folate fortification has been associated with the presence of unmetabolized folic acid (PteGlu) in blood, masking of vitamin B12 deficiency, increased dosage for anti-cancer medication, photo-catalysis of PteGlu leading to potential genotoxicity, and a role in the pathoaetiology of colorectal cancer. Increased folate intake has also been associated with twin birth and insulin resistance in offspring, and altered epigenetic mechanisms of inheritance. Although limited data exists to elucidate potential mechanisms underlying these issues, elevated blood folate level due to the excess use of PteGlu without consideration of an individual’s specific phenotypic traits (e.g. genetic background and undiagnosed disease) may be relevant. Additionally, the accumulation of unmetabolized PteGlu may lead to inhibition of dihydrofolate reductase and other enzymes. Concerns notwithstanding, folic acid fortification has achieved enormous advances in public health. It therefore seems prudent to target and carefully monitor high risk groups, and to conduct well focused further research to better understand and to minimize any risk of mandatory folic acid fortification.

Vitamin D, folate, and potential early lifecycle environmental origin of significant adult phenotypes

Solar radiation early in pregnancy interacts with light sensitive vitamins to influence an embryos genetic profile. This influences both adult disease risk and may play a role in the evolution of skin colour.

TAS2R38 bitter taste genetics, dietary vitamin C, and both natural and synthetic dietary folic acid predict folate status, a key micronutrient in the pathoaetiology of adenomatous polyps

Taste perception may influence dietary preferences and nutrient intakes contributing to diet-related disease susceptibility. This study examined bitter taste genetics and whether variation in the TAS2R38 gene at three polymorphic loci (A49P, V262A and I296V) could alter dietary and systemic folate levels and dietary vitamin C intake, and whether a nutrigenetic circuit existed that might link bitter taste, folate/antioxidant status and risk for a colonic adenomatous polyp. TAS2R38 diplotype predicted bitter taste (PROP) phenotype (p value <0.00001) and red cell folate status (p=0.0179) consistent with the diplotype that has the broadest range of bitter perception (AVI/PAV) also possessing the highest average red cell folate value. However, TAS2R38 diplotype did not predict dietary intake of methylfolic acid, pteroylmonoglutamic acid or total folic acid. Neither did it predict dietary intake of vitamin C. Despite this, intake of dietary folate predicts red cell folate with analysis pointing to a key nutrient-nutrient interaction between vitamin C intake and systemic folate status. Analysis of 38 patients with an adenomatous polyp and 164 controls showed that individually, dietary nutrient intake, nutrient status and taste diplotype did not influence polyp risk. However, red cell folate status (in individuals below the population median value) did interact with bitter taste diplotype (AVI/PAV) to predict polyp risk (p=0.0145). Furthermore, synthetic folic acid (below median intake) was statistically associated with adenoma occurrence (p=0.0215); individuals with adenomatous polyps had a 1.77× higher intake than controls. Additionally, stepwise regression taking account of all dietary nutrients showed a tight relationship between methylfolic acid (but not pteroylmonoglutamic acid) intake and red cell folate level in those with a low folate status and occurrence of an adenomatous polyp (p=0.0039). These findings point to a role for folate in the pathoaetiology of adenomatous polyps, with the natural and synthetic vitamers not necessarily having the same biological effect.

Dietary Patterns and Risk for Metabolic Syndrome in Korean Women: A Cross-Sectional Study

AbstractDietary patterns are a risk factor for metabolic syndrome (MetS). The prevalence of MetS has increased in Korea, and this condition has become a public health issue. Therefore, the present cross-sectional study aimed to identify the associations between dietary patterns and the risk of MetS among Korean women.The data of 5189 participants were analyzed to determine dietary intake and lifestyle. A principal components analysis was employed to determine participant dietary patterns with regard to 106 food items. MetS was diagnosed using the National Cholesterol Education Program, Adult Treatment Panel III. Logistic regression analyses were applied to evaluate the associations between dietary pattern quintiles and MetS and to generate odds ratios (ORs) and 95% confidence intervals (CIs) after adjusting for potential confounders.Three dietary patterns were identified: “traditional,” “western,” and “prudent.” The “prudent” dietary pattern consisted of a high intake of fruits and fruit products as well as nuts, dairy, and a low consumption of grains; this pattern was negatively associated with the risk of MetS. The highest quintile of the “prudent” dietary pattern was significantly less likely to develop MetS (OR: 0.5, 95% CI: 0.36–0.68, P for trend <0.001) compared with the lowest quintile. This pattern was also negatively associated with all of the MetS diagnostic criteria: abdominal obesity (OR: 0.52, 95% CI: 0.41–0.65), blood pressure (OR: 0.72, 95% CI: 0.59–0.87), triglycerides (OR: 0.67, 95% CI: 0.52–0.85), fasting glucose (OR: 0.64, 95% CI: 0.43–0.95), and high-density lipoprotein cholesterol (OR: 0.53, 95% CI: 0.42–0.68). However, the “traditional” and “western” dietary patterns were not associated with the risk of MetS.The “prudent” dietary pattern was negatively associated with the risk of developing MetS among Korean women.

Methylation diet and methyl group genetics in risk for adenomatous polyp occurrence

Purpose The aim of this study is to explore whether a methylation diet influences risk for adenomatous polyps (AP) either independently, or interactively with one-carbon metabolism-dependent gene variants, and whether such a diet modifies blood homocysteine, a biochemical phenotype closely related to the phenomenon of methylation. Methods 249 subjects were examined using selective fluorescence, PCR and food frequency questionnaire to determine homocysteine, nine methylation-related gene polymorphisms, dietary methionine, 5-methyltetrahydrofolate, vitamins B6 and B12. Results 1). Both dietary methionine and 5-methyltetrahydrofolate intake are significantly associated with plasma homocysteine. 2). Dietary methionine is related to AP risk in 2R3R-TS wildtype subjects, while dietary B12 is similarly related to this phenotype in individuals heterozygous for C1420T-SHMT, A2756G-MS and 844ins68-CBS, and in those recessive for 2R3R-TS. 3). Dietary methionine has a marginal influence on plasma homocysteine level in C1420T-SHMT heterozygotes, while B6 exhibits the same effect on homocysteine in C776G-TCN2 homozygote recessive subjects. Natural 5-methyltetrahydrofolate intake is interesting: Wildtype A1298C-MTHFR, heterozygote C677T-MTHFR, wildtype A2756G-MS and recessive A66G-MSR individuals all show a significant reciprocal association with homocysteine. 4). Stepwise regression of all genotypes to predict risk for AP indicated A2756G-MS and A66G-MSR to be most relevant (p = 0.0176 and 0.0408 respectively). Results were corrected for age and gender. Conclusion A methylation diet influences methyl group synthesis in the regulation of blood homocysteine level, and is modulated by genetic interactions. Methylation-related nutrients also interact with key genes to modify risk of AP, a precursor of colorectal cancer. Independent of diet, two methylation-related genes (A2756G-MS and A66G-MSR) were directly associated with AP occurrence.

Genetic Variation in the TAS2R38 Bitter Taste Receptor and Gastric Cancer Risk in Koreans.

The human TAS2R38 gene encodes a bitter taste receptor that regulates the bitterness perception and differentiation of ingested nutritional/poisonous compounds in the oral cavity and gastrointestinal tract. TAS2R38 gene variants are associated with alterations in individual sensitivity to bitter taste and food intake; hence, these genetic variants may modify the risk for diet-related diseases, including cancer. However, little is known about the association between TAS2R38 polymorphisms and gastric cancer susceptibility. The present case-control study examined the influence of TAS2R38 polymorphisms on food intake and determined whether they predict gastric cancer risk in Koreans. A total of 1,580 subjects, including 449 gastric cancer cases, were genotyped for TAS2R38 A49P, V262A, I296V and diplotypes. Dietary data were analysed to determine the total consumption of energy, fibre, vegetables, fruits, sweets, fats, alcohol and cigarettes. TAS2R38 diplotype was not associated with food, alcohol or cigarette consumption, either independent or dependent of gastric cancer phenotype. However, the PAV/AVI diplotype significantly increased gastric cancer risk (adjusted odds ratio: 1.513; 95% confidence interval: 1.148–1.994) independent of dietary intake. Findings suggest that TAS2R38 may be associated with the risk for gastric cancer in Koreans, although the TAS2R38 diplotype did not influence dietary intake.

Optimization of far-infrared vacuum drying conditions for Miang leaves (Camellia sinensis var. assamica) using response surface methodology

Far-infrared (FIR) vacuum is an advanced drying technique that has recently been applied in food processing. Optimal drying conditions for processing tea from Miang leaves using FIR vacuum drying were investigated. Response surface methodology with a central composite design was used to design, analyze, and predict the optimal time and temperature conditions for FIR vacuum drying, taking into account the physicochemical properties of Miang leaves. When the temperature increased from 50 to 65°C and the time from 60 to 120 min, the amount of epicatechin, epicatechin gallate, epigallocatechin gallate, and total catechins significantly (p<0.05) increased while the moisture content and water activity significantly (p<0.05) decreased, compared with controls. The physicochemical properties of dried Miang leaves were significantly (p>0.05) influenced by time and temperature, compared with controls. Drying conditions of 65°C for 120 min are recommended for optimization of drying.

Variations in the bitterness perception-related genes TAS2R38 and CA6 modify the risk for colorectal cancer in Koreans

Bitterness perception is known to be an important factor in individuals’ dietary behaviors and is also associated with the sensing of nutritious/noxious molecules for subsequent metabolic responses in multiple organs. Therefore, the genetic variation in bitterness sensing may be associated with diet-related diseases, including colorectal cancer (CRC). We investigated the influence of variations in the bitterness-sensing genes taste receptor type 2 member 38 (TAS2R38) and carbonic anhydrase 6 (CA6) on the consumption of food, tobacco and alcohol and the risk of CRC in Koreans. The study population consisted of 681 cases and 1361 controls, and their intake of vegetables, fruits, fiber, fat-food and sweets was analyzed. The genotypes for TAS2R38 A49P, V262A and I296V and CA6 rs2274333 A/G were assessed using the MassArray technique. Our findings suggested that the TAS2R38 diplotype, CA6 rs2274333 and their combined genotype had a negligible influence on dietary and alcohol intake. The combined TAS2R38-CA6 AVI/AVI-AA genotype was associated with higher tobacco consumption than the other genotypes in CRC cases only. However, the genetic variations were a significant risk factor for CRC. The TAS2R38 AVI/AVI diplotype and CA6 G allele were associated with a reduced risk of CRC. Moreover, when the combined genotypes of the subjects were analyzed, possessing both the variant diplotype/variant allele (AVI/AVI+G*) was associated with a greater reduction in the risk of CRC (adjusted OR = 0.49; 95%CI: 0.34–0.74). In summary, variations in the bitterness perception genes TAS2R38 and CA6 did not influence the examined food intake in Koreans. However, those genetic variants were a decisive modifying factor of CRC susceptibility.

Variations in TAS1R taste receptor gene family modify food intake and gastric cancer risk in a Korean population

SCOPE Human taste receptor type 1 (TAS1R, T1R) gene family mediates the perception of umami and sweet tastes and regulates metabolism. This study investigated whether variants in the TAS1R are associated with food intake and susceptibility to gastric cancer (GC). METHODS AND RESULTS A total of 1131 Koreans including 377 GC cases were analyzed to determine the dietary intake and genotype for 25 variants in TAS1R genes. Among the genotyped polymorphisms, six loci with a minor allele frequency >0.05 were tested for an association with dietary intake and GC risk. Findings suggest that TAS1R polymorphisms were associated with a variety of food intake that is beyond the known T1R-taste association. Furthermore, differential consumption for cigarettes and citrus fruits by TAS1R genetic variants may be linked to GC risk in males and females, respectively. Additionally, in males, TAS1R1 rs34160967 heterozygote showed an increased risk of GC (odds ratio: 1.52, 95% confidence interval: 1.10-2.09), independent of dietary intake. However, this GC-risk effect of TAS1R variants was not evident in females. CONCLUSIONS Genetic variants in TAS1R were associated with dietary consumption, which may be associated with GC risk. TAS1R1 rs34160967 may also modify the risk for GC independent of diet in Korean males.

Gene-Nutrient Interaction between Folate and Dihydrofolate Reductase in Risk for Adenomatous Polyp Occurrence: A Preliminary Report.

Folate and related gene variants are significant risk factors in the aetiology of colorectal cancer. Dihydrofolate reductase (DHFR) is critical in the metabolism of synthetic folic acid (pteroylmonoglutamatamic, PteGlu) to tetrahydrofolate following absorption. Therefore, the 19bp deletion variant of DHFR may lead to the alteration of folate-related colorectal disease susceptibility. This study examined the association between PteGlu and 19bp del-DHFR, and adenomatous polyp (AP) occurrence, an antecedent of colorectal cancer. A total of 199 subjects (162 controls and 37 AP cases) were analysed to determine dietary intake of total folate, natural methylfolate and synthetic PteGlu, level of erythrocyte folate and plasma homocysteine (tHcy), and genotype of 19bp del-DHFR. Dietary folate intake, erythrocyte folate, tHcy and 19bp del-DHFR variants did not independently predict the occurrence of AP. However, a gene-nutrient interaction was observed when subjects were stratified according to dietary folate intake. In subjects with a folate intake above the median value due to significant dietary PteGlu content, the presence of the 19bp-deletion allele decreased the risk for AP (OR=0.35, 95% CI: 0.13-0.97). However, such association was not evident in individuals with a folate intake below the median value. In conclusion, the finding suggests that folate nutrition and 19bp del-DHFR variation may interact to modify AP risk.