Era Of Folic Acid Fortification Research Articles

Fetal In-Utero Microneurosurgical Repair of Myelomeningocele and Myeloschisis: Neursurgical Outcome Updated

Conference presented at the Brazilian Academy of Neurosurgery Pediatric Symposium on December 9th, 2024. Myelomeningocele (MMC) is recognized as the most prevalent neural tube defect (NTD) and the most complex congenital anomaly that is still consistent with life. In the era of folic acid fortification, its incidence has been observed at 3.4 per 10,000 live births. The observed decrease in incidence is attributed to a synergy of enhanced folate supplementation, along with advancements in prenatal diagnostics, and, in certain cases, the option of selective termination. Recently, innovative technology and growing expertise have sparked considerable excitement within the scientific community regarding fetal MMC repair. In this lecture, Dr. Elbabaa shares his surgical outcomes and provides an updated overview of the current state of the art in this surgical field.

Genetic Variants Involved in One-Carbon Metabolism: Polymorphism Frequencies and Differences in Homocysteine Concentrations in the Folic Acid Fortification Era.

Folate and other B vitamins are essential co-factors of one-carbon metabolism, and genetic variants, such as polymorphisms, can alter the metabolism. Furthermore, the adoption of food fortification with folic acid showed a decrease of homocysteine concentration. The aim of this study was to investigate the frequencies of the polymorphisms of enzymes and carrier proteins involved in one-carbon metabolism, and to evaluate homocysteine concentrations in the presence of these genetic variants in a population exposed to mandatory food fortification with folic acid. Using data from a population-based cross-sectional study in São Paulo, Brazil, the study population comprised 750 participants above 12 years of age of both genders. A linear regression model was used to evaluate the homocysteine concentrations according to genetic variants and folate level. The results showed that the minor allelic frequencies were 0.33 for MTHFR (rs1801133), 0.24 for MTHFR (rs1801131), 0.19 for MTR (rs1805087), 0.42 for MTRR (rs1801394), 0.46 for RFC1 (rs1051266), and 0.47 for DHFR (19-bp deletion). The genetic variants of MTHFR 677C>T, MTRR 66A>G and RFC-1 80G>A were different according to race. The homocysteine concentrations increased in the CT and TT compared to CC genotypes of polymorphism MTHFR 677C>T in all populations, and differences between the homocysteine concentrations according to the genotypes of MTHFR 677C>T were observed regardless of folate level.

A lower degree of PBMC L1 methylation in women with lower folate status may explain the MTHFR C677T polymorphism associated higher risk of CIN in the US post folic acid fortification era.

BackgroundStudies in populations unexposed to folic acid (FA) fortification have demonstrated that MTHFR C677T polymorphism is associated with increased risk of higher grades of cervical intraepithelial neoplasia (CIN 2+). However, it is unknown whether exposure to higher folate as a result of the FA fortification program has altered the association between MTHFR C677T and risk of CIN, or the mechanisms involved with such alterations. The current study investigated the following in a FA fortified population: 1) The association between MTHFR C677T polymorphism and risk of CIN 2+; 2) The modifying effects of plasma folate concentrations on this association; and 3) The modifying effects of plasma folate on the association between the polymorphism and degree of methylation of long interspersed nucleotide elements (L1s), in peripheral blood mononuclear cell (PBMC) DNA, a documented biomarker of CIN risk.MethodsThe study included 457 US women diagnosed with either CIN 2+ (cases) or ≤ CIN 1 (non-cases). Unconditional logistic regression models were used to test the associations after adjusting for relevant risk factors for CIN.ResultsThe 677CT/TT MTHFR genotypes were not associated with the risk of CIN 2+. Women with CT/TT genotype with lower folate, however, were more likely to be diagnosed with CIN 2+ compared to women with CT/TT genotype with higher folate (OR = 2.41, P = 0.030). Women with CT/TT genotype with lower folate were less likely to have a higher degree of PBMC L1 methylation compared to women with CT/TT genotype with higher folate (OR = 0.28, P = 0.017).ConclusionsThis study provides the first evidence that the MTHFR 677CT/TT genotype-associated lower degree of PBMC L1 methylation increases the risk of CIN 2+ in women in the US post-FA fortification era. Thus, even in the post-FA fortification era, not all women have adequate folate status to overcome MTHFR 677CT/TT genotype-associated lower degree of L1 methylation.

Frequency and determinants of marginal vitamin B12 deficiency in childbearing‐aged women of South Asian and European descent in Metro Vancouver

Low maternal vitamin B12 (B12) status has been associated with an increased risk of neural tube defects (NTDs) and insulin resistance. It was estimated that 34 % of NTD cases in Canada may be linked to low B12 status in the era of folic acid fortification. Due to the early effects of B12 status on pregnancy outcome, it is crucial for women to be B‐vitamin adequate before conception. South Asians are one of the most vulnerable ethnic groups for B12 inadequacy and are one of the largest ethnic minorities in Vancouver.The objectives of this study are to assess whether South Asian women of childbearing age are more likely to be marginally B12 deficient than women of European descent in the Metro Vancouver area and to determine whether select demographic, dietary, and genetic determinants increase a woman's risk to be marginally B12 deficient.In a convenience sample of 300 healthy non‐pregnant females (19 – 35 y), B12 status is assessed using serum B12, holotranscobalamin, and plasma methylmalonic acid. Sociodemographic status, supplement use, and usual eating habits are assessed by questionnaires.The frequency of marginal B12 deficiency was estimated to be 16% with a trend for higher frequency in South Asian women. The research outcomes will aid in identifying risk factors of B12 deficiency by ethnicity and contribute to the evaluation of periconceptional supplement recommendations.Grant Funding Source: ‘FNH Vitamin Research Fund’ UBC

Following Up Folate and Its Function in Colorectal Carcinogenesis

given to women with suboptimal micronutrient intake. Because the trial was carried out during the folic acid fortification era and the women volunteering were likely to be health-conscious, with a history of vitamin supplement use, the median intake of folate, B6, and B12 at study entry was relatively high, at 108%, 167%, and 292% of the respective recommended dietary allowances (1). The lack of effect of high-dose folate/B6/B12 supplementation on adenoma risk in a well-nourished population agrees with a recent combined analysis of the three large randomized, placebocontrolled trials of folic acid supplementation, which were carried out in the United States, Canada, the United Kingdom, and Denmark among patients with an adenoma history (2632 men and women) (8). After up to 3.5 years of folic acid use, at 0.5 or 1.0 mg/day, risk of adenoma, or advanced adenoma, was not statistically significantly increased or decreased. Interestingly, folic acid was associated with non-statistically significant reductions in risk among subjects in the two lowest quartiles of circulating folate at study entry. This combined analysis is encouraging, even though more follow-up is needed. The largest of the three trials included had previously reported potentially adverse effects: a statistically nonsignificant increased risk of adenoma, especially advanced adenoma, after 3 and 6–8 years of follow-up (9). Although these randomized trials do suggest that high-dose folic acid is not a promising chemopreventive agent for colorectal cancer, they do not completely resolve the role of folate and other B vitamins in colorectal carcinogenesis. In 2010, in a pooled analysis of 13 prospective studies of folate intake and colon cancer, including 5720 incident cases and up to 7–20 years of follow-up, both dietary folate intake and total folate intake (from diet and supplements) were inversely, although modestly, associated with risk (comparing extreme quintiles, RRs = 0.92, 95% CI = 0.84 to 1.00 and 0.85, 95% CI = 0.77 to 0.95, respectively) (10). The stronger association with total folate intake might be due to an expanded range of intake, enhanced bioavailability of the synthetic folic acid in supplements, or the presence of other B vitamins in the multivitamins that provided most of the supplemental folate. More recently, in analyses of incident colorectal cancer diagnosed in the folic acid fortification era, the American Association of Retired Persons cohort reported a statistically significant 30% reduction in colorectal cancer risk comparing extremes of total folate intake (6484 incident cases) (11); and the Cancer Prevention Study II reported a statistically significant 19% reduction comparing extreme quintiles of total intake (1023 incident cases) (12). Although the strength of these associations with total folate intake

Folate-status response to a controlled folate intake in nonpregnant, pregnant, and lactating women

Folate dose-response studies in women of childbearing age who consumed a folic acid (FA)-containing multivitamin in the era of FA fortification are lacking. We sought to investigate folate-status response to a known folate dose comprising an FA-containing prenatal supplement (750 μg/d) plus natural food folate (400 μg/d) in third-trimester pregnant women, lactating women 5-15 wk postpartum, and nonpregnant women. Pregnant (n = 26), lactating (n = 28), and nonpregnant (n = 21) women consumed the study folate dose under controlled intake conditions for 10-12 wk. Blood, urine, and breast milk were collected at baseline, study midpoint, and study end. Study-end serum total folate concentrations averaged ~30 ng/mL and did not differ by physiologic group (P = 0.876). Study-end urinary folate excretion represented ~9-43% of total folate intake and ranged from 100 to 500 μg/d. Third-trimester pregnant women excreted less urinary folate than did lactating (P = 0.075) and nonpregnant (P < 0.001) women. Lactating women excreted less (P < 0.001) urinary FA than did nonpregnant women. Breast-milk total folate concentrations remained constant (P = 0.244; 61.8 ng/mL at study end), whereas breast-milk FA concentrations increased (P = 0.003) to 24.1 ng/mL at study end. The consumption of the study folate dose yielded a supranutritional folate status regardless of the physiologic state. Based on urinary folate excretion, folate use was greatest to least: pregnant > lactating > nonpregnant women. Breast-milk folate species were responsive to maternal folate intake, and FA made up ~40% of breast-milk total folate at study end. These findings warrant revisiting prenatal supplement FA formulation in populations exposed to FA-fortification programs.

Folate intake and risk of colorectal cancer and adenoma: modification by time

Experimental and observational studies have suggested that folate may play dual roles in colorectal cancer risk depending on the timing and dose. We examined the latency between folate intake and the incidence of colorectal cancer. We prospectively examined associations between folate intake assessed every 2 to 4 y by using validated food-frequency questionnaires and risk of colorectal cancer and adenoma in the Nurses' Health Study and Health Professionals Follow-Up Study, which included 2299 incident colorectal cancers and 5655 colorectal adenomas from 1980 to 2004. There was an association between total folate intake 12-16 y before diagnosis and lower risk of colorectal cancer (relative risk: 0.69; 95% CI: 0.51, 0.94; ≥800 compared with <250 μg folate/d), but there was no association between intake in the recent past and colorectal cancer risk. Long- and short-term intakes of total folate were associated with a lower risk of colorectal adenoma, with a strong association with intake 4-8 y before diagnosis (odds ratio: 0.68; 95% CI: 0.60, 0.78; ≥800 compared with <250 μg folate/d). The current use of multivitamins for >15 y, but not a shorter duration of use, was associated with lower risk of colorectal cancer; and a shorter duration of use was related to lower risk of adenoma. We did not observe an adverse effect of total folate or synthetic folic acid on risk of colorectal cancer or adenoma even during the folic acid fortification era. Folate intake is inversely associated with risk of colorectal cancer only during early preadenoma stages.

Choline and Risk of Neural Tube Defects in a Folate-fortified Population

Folic acid is known to reduce risk of neural tube defects (NTDs). Even so, NTDs continue to occur despite individual supplementation or population fortification with folic acid. We investigated other nutrients related to one-carbon metabolism that may affect NTD risk. This prospective study included data from more than 180,000 pregnant women in California from 2003 through 2005. Midpregnancy serum specimens were linked with delivery information regarding the presence of a NTD, another structural malformation, or no malformation in the fetus. We identified 80 NTD-affected pregnancies (cases) and we randomly selected 409 pregnancy controls. Serum specimens were tested for methylmalonic acid, homocysteine, cysteine, methionine, total choline, betaine, cystathionine, vitamin B6, folate, vitamin B12, riboflavin, and creatinine. We observed elevated NTD risks associated with lower levels of total choline, and reduced risks with higher levels of choline. Specifically, we observed an odds ratio of 2.4 (95% confidence interval = 1.3-4.7) associated with the lowest decile and an odds ratio of 0.14 (0.02-1.0) associated with the highest decile, both relative to the 25th-74th percentiles of the control distribution. These data did not show meaningful differences between cases and controls for any other analytes. This is the first study to investigate total choline in NTD-affected pregnancies. Our findings for choline, for which low levels were a risk factor and higher levels were a protective factor for NTDs, may offer a useful clue toward understanding the complex etiologies of NTDs in an era of folic acid fortification of the food supply.

Lower Risk of Cervical Intraepithelial Neoplasia in Women with High Plasma Folate and Sufficient Vitamin B12 in the Post-Folic Acid Fortification Era

The purpose of this study was to determine the influence of plasma folate and vitamin B12 concentrations on cervical cancer risk in the U.S. after the folic acid fortification era. The study included 376 premenopausal women of childbearing age who tested positive for infections with high-risk (HR) human papillomaviruses (HPVs) and were diagnosed with cervical intraepithelial neoplasia (CIN) grade 2 or higher (CIN 2+, cases) or <or=CIN 1 (noncases). CIN 2+ (yes/no) was the dependent variable in logistic regression models that specified plasma folate concentrations combined with plasma B12 concentrations as the independent predictors of primary interest, adjusting for age, race, education, smoking, parity, number of life-time male sexual partners, use of contraceptives, waist circumference, physical activity, healthy eating index, and circulating concentrations of vitamins A, C, tocopherol, and total carotene. Women with supraphysiologic concentrations of plasma folate (>19.8 ng/mL) who also had sufficient plasma vitamin B12 (>or=200.6 pg/mL) had 70% lower odds of being diagnosed with CIN 2+ (P = 0.04) when compared with women with plasma folate of <or=19.8 ng/mL and plasma vitamin B12 of <200.6 pg/mL. Our results do not corroborate the concern that supraphysiologic plasma folate concentrations seen in the post-U.S. folic acid fortification era increase the risk of CIN in premenopausal women of childbearing age. In fact, higher folate is associated with significantly lower risk of CIN, especially when vitamin B12 is sufficient, demonstrating the importance of vitamin B12 in the high-folate environment created by the folic acid fortification program.

Sources of Folate Intake in Women at Risk for Cervical Cancer (CC) in an Era of Folic Acid Fortification

A comprehensive evaluation of folate intake from different sources has not been documented among women at risk for CC in the US Post Folic Acid Fortification Era. The study objectives were to identify different sources of folate intake and document determinants of folate intake from these sources in 273 women of child bearing age tested positive for high‐risk human papillomaviruses (HR‐HPVs). Folate intake was assessed using the Block 98.2 semi‐quantitative food frequency questionnaire (FFQ). Daily folate equivalents (DFE) were calculated by multiplying synthetic folic acid (SFA) intake from fortified food and supplements with the correction factor of 1.7. The median intakes of natural folate (NF), SFA and total folate DFE were 175, 224 and 442 µg/d respectively. Higher DFE was associated with higher folate intake from SFA. Forty three percent of the women had folate intakes below the RDA (&lt; 400 µg/d of DFE) and 8% of the women had intakes &gt; 1000 µg/d of DFE, beyond the maximum safe amount. Women with lower education were less likely to have intakes &gt; 175 µg/d of NF and &gt; 224 µg/d of SFA (P=0.02 &amp; P=0.04 respectively) while AA women and women in the highest tertile of HEI were more likely to have intakes &gt; 175 µg/d of NF (P=0.003 &amp; P=0.05 respectively). Current smokers were more likely to consume &gt; 224 µg/d of SFA (P=0.003). Women with higher calories from alcohol were less likely to have an intake &gt; 224 µg/d of SFA and &gt; 400 µg/d of DFE (P=0.004 &amp; P=0.02 respectively). These results demonstrated that race, level of education, HEI, smoking and alcohol consumption influences folate intake from different sources. Overall, however, below RDA consumption rather than exceeding intakes over 1000 µg/d is of concern in women at risk for developing CC. The study is supported by RO1 CA105448.

Folate Status of Young Canadian Women after Folic Acid Fortification of Grain Products

Women of childbearing age are advised to consume folic acid–containing supplements. Whether this remains necessary after folic acid fortification of the food supply in North America has yet to be determined. The objectives of this study were to assess folate intakes and the contribution of folic acid to the diets of women of childbearing age in the post–folic acid fortification era. Using a cross-sectional study design, fasting blood samples were obtained from 95 women (aged 18 to 25 years), and the samples were analyzed for serum and red blood cell folate, as well for total homocysteine. Dietary and supplemental folate intakes were assessed. The biochemical evidence showed that no women were folate deficient, but only 14% reached red blood cell folate concentrations associated with significant reductions in neural tube defect risk. Mean dietary intake of food folic acid was 96±64 μg/day, supplemental folic acid was 94±189 μg/day, natural folate was 314±134 μg/day, and the total intake, as dietary folate equivalents, was 646±368 μg dietary folate equivalents/day. Therefore, intakes of folic acid from fortified foods are within the level originally predicted for the fortification efforts; however, only 17% of participants met the special recommendation for women capable of becoming pregnant (400 μg folic acid daily from supplements, fortified foods, or both in addition to consuming food folate from a varied diet). These data suggest that women of childbearing age are achieving positive folate status in the postfortification era, but it may not be sufficient to achieve red blood cell folate concentrations associated with a significant reduction in neural tube defect risk. Even with food fortification, women of childbearing age should be advised to take a folic acid–containing supplement on a daily basis.

Homocysteine and Folate Status in an Era of Folic Acid Fortification: Balancing Benefits, Risks, and B-vitamins

Mandatory folic acid (vitamin B9) fortification of flour products to a level of 140–150 μg/100g was implemented in the US and Canada in 1998. The rationale was to improve folate status in women of childbearing age and thereby decrease the incidence of neural tube defects (NTDs). Studies with complete ascertainment of prenatally diagnosed NTD cases indicate that fortification has prevented up to 50% of NTDs(1). Fortification has therefore been highly successful in achieving its primary objective. Folate concentration in serum and erythrocytes is a marker of folate status, which is inversely associated with the plasma concentration of total homocysteine (tHcy). Cobalamin (vitamin B12) status and renal function are also strong determinants of plasma tHcy(2), and moderate hyperhomocysteinemia is associated with an increased risk of chronic diseases, including cardiovascular disease, dementia, and impaired cognition(3). In this issue of Clinical Chemistry , Pfeiffer and colleagues(4) report on concentrations of tHcy in approximately 26 000 participants in the National Health and Nutrition Examination Survey (NHANES) from 1991 through 1994, and from 3 postfortification surveys (1999–2004). When comparing the postfortification to the prefortification period, Pfeiffer and colleagues found a tHcy decrease of approximately 10%, and a pronounced decrease in the prevalence of individuals with elevated tHcy (>13 μmol/L). These observations complement recent data published by the same authors, which demonstrate an increase in serum and erythrocyte folates, and no change in serum cobalamin in NHANES samples during the same time period(5). Results from these recent studies by Pfeiffer et al. confirm previous studies on folate and homocysteine in NHANES(6)(7) and the Framingham cohort(8). A slight decrease in blood folate between the first (1999–2000) and third (2003–2004) postfortification periods(5 …

Vitamin B12, homocysteine and carotid plaque in the era of folic acid fortification of enriched cereal grain products

Vitamin B12, homocysteine and carotid plaque in the era of folic acid fortification of enriched cereal grain products

The role of folate receptor α in cancer development, progression and treatment: Cause, consequence or innocent bystander?

Folate receptor alpha (FRalpha) is a membrane-bound protein with high affinity for binding and transporting physiologic levels of folate into cells. Folate is a basic component of cell metabolism and DNA synthesis and repair, and rapidly dividing cancer cells have an increased requirement for folate to maintain DNA synthesis, an observation supported by the widespread use of antifolates in cancer chemotherapy. FRalpha levels are high in specific malignant tumors of epithelial origin compared to normal cells, and are positively associated with tumor stage and grade, raising questions of its role in tumor etiology and progression. It has been suggested that FRalpha might confer a growth advantage to the tumor by modulating folate uptake from serum or by generating regulatory signals. Indeed, cell culture studies show that expression of the FRalpha gene, FOLR1, is regulated by extracellular folate depletion, increased homocysteine accumulation, steroid hormone concentrations, interaction with specific transcription factors and cytosolic proteins, and possibly genetic mutations. Whether FRalpha in tumors decreases in vivo among individuals who are folate sufficient, or whether the tumor's machinery sustains FRalpha levels to meet the increased folate demands of the tumor, has not been studied. Consequently, the significance of carrying a FRalpha-positive tumor in the era of folic acid fortification and widespread vitamin supplement use in countries such as Canada and the United States is unknown. Epidemiologic and clinical studies using human tumor specimens are lacking and increasingly needed to understand the role of environmental and genetic influences on FOLR1 expression in tumor etiology and progression. This review summarizes the literature on the complex nature of FOLR1 gene regulation and expression, and suggests future research directions.

Vitamin B12, homocysteine and carotid plaque in the era of folic acid fortification of enriched cereal grain products

Carotid plaque area is a strong predictor of cardiovascular events. High homocysteine levels, which are associated with plaque formation, can result from inadequate intake of folate and vitamin B12. Now that folic acid fortification is widespread in North America, vitamin B12 has become an important determinant of homocysteine levels. We sought to determine the prevalence of low serum levels of vitamin B12, and their relation to homocysteine levels and carotid plaque area among patients referred for treatment of vascular disease since folic acid fortification of enriched grain products. We evaluated 421 consecutive new patients with complete data whom we saw in our vascular disease prevention clinics between January 1998 and January 2002. We measured total carotid plaque area by ultrasound and determined homocysteine and serum vitamin B12 levels in all patients. The patients, 215 men and 206 women, ranged in age from 37 to 90 years (mean 66 years). Most were taking medications for hypertension (67%) and dyslipidemia (62%). Seventy-three patients (17%) had vitamin B12 deficiency (vitamin B12 level < 258 pmol/L with homocysteine level > 14 mumol/L or methylmalonic acid level > 271 nmol/L). The mean area of carotid plaque was significantly larger among the group of patients whose vitamin B12 level was below the median of 253 pmol/L than among those whose vitamin B12 level was above the median: 1.36 (standard deviation [SD] 1.27) cm2 v. 1.09 (SD 1.0) cm2; p = 0.016. Vitamin B12 deficiency is surprisingly common among patients with vascular disease, and, in the setting of folic acid fortification, low serum vitamin B12 levels are a major determinant of elevated homocysteine levels and increased carotid plaque area.

Plasma folate concentrations are associated with depressive symptoms in elderly Latina women despite folic acid fortification

A relation between low folate status and depression has been recognized since the 1960s. Since 1998, flour in the United States has been fortified with folic acid, and the prevalence of folate deficiency has decreased dramatically. We investigated whether, in this era of folic acid fortification, low folate status is a determinant of depressive symptoms in a cohort of elderly Latinos (aged >/=60 y) participating in the Sacramento Area Latino Study on Aging (SALSA). In a cross-sectional logistic regression analysis of data from SALSA (n = 627 M, 883 F), odds ratios (ORs) were ascertained for elevated depressive symptoms [Center for Epidemiologic Studies Depression Scale (CES-D) score >/=16] among tertiles of plasma folate. Depressive symptoms were assessed by using the CES-D. Plasma folate concentrations were determined by radioassay. The prevalence of folate deficiency (plasma folate </= 6.8 nmol/L) in the SALSA population was <1%. For men, no significant association between folate tertile and high CES-D score was observed. The adjusted OR for high CES-D score in women in the lowest tertile of folate was 2.04 (95% CI: 1.38, 3.02), which was significantly different from that in women in the highest tertile of folate (P < 0.001). These data indicate that, despite folic acid fortification, low folate status is associated with depressive symptoms in elderly Latina women (but not elderly Latino men).

Folate, Cognition, and Depression in the Era of Folic Acid Fortification

ABSTRACT: It has long been recognized that folate deficiency is associated with impaired cognitive function, particularly in older adults. Moreover, folate deficiency contributes to the symptoms of clinical depression and negatively influences the efficacy of antidepressant medications. The pathophysiological mechanisms by which folate deficiency influences cognition and depressive mood are not clearly understood, but may be mediated by decreased intracellular concentration of the methyl donor S‐adenosylmethionine in the brain and increased concentration of the putative vascular toxin homocysteine in the blood (hyperhomocysteinemia). Folic acid fortification of flour in the United States, intended to reduce the risk of neural tube defects, has been in effect since January 1, 1998. The program has proven to be highly successful having lowered the prevalence of folate deficiency and hyperhomocysteinemia, as well as the incidence of neural tube defects. An important question is whether associations between folate status, cognition, and depression remain significant. In this presentation, the evidence supporting the relationships between folate status, cognition, and depression will be summarized. In addition, epidemiological data will be presented from the Sacramento Area Latino Study on Aging (SALSA), a community‐based cohort study of physical and cognitive function in Latino Americans age 60 years and older, that indicate folate status remains a significant determinant of cognitive function and depressive mood despite the success of folic acid fortification.

Heterogeneity in the prevalence of methylenetetrahydrofolate reductase gene polymorphisms in women of different ethnic groups

Objective To determine the prevalence of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms in women of different ethnic groups and to relate these common mutations to plasma homocysteine, red cell folate, and serum folate. Design A one-time fasting blood sample was obtained for MTHFR genotype (C677T and A1298C) determinations (n=433). Serum folate, red cell folate, and homocysteine analyses were performed in nonfolic acid supplement users (n=215). Subjects/setting This study involved 433 women from four ethnic groups, including 193 Hispanic women of Mexican descent, 139 white women, 53 Asian women of mixed descent, and 48 African American women. Statistical Analyses Performed χ2, t Test, and analysis of variance were used. Results Mexican women (18.1%) had a higher frequency of the 677 TT genotype compared with white (7.2%), Asian (3.8%), and African American (0%) women. White women (7.9%) had a higher frequency of the 1298 CC genotype than the other ethnic groups (range=1.9% to 2.6%). The frequency of compound heterozygosity (677 CT + 1298 AC) was higher in Mexican (17.6%) and white (15.1%) women than Asian and African American (∼4% to 6%) women. In the era of folic acid fortification, neither genotype, independently or together, was associated with homocysteine or blood folate concentrations when ethnic groups were combined. In Mexican women, however, a linear trend (P≤.05) was detected for the C677T variants with the lowest red cell folate in the TT genotype. Applications/conclusions These data demonstrate ethnic differences in genetic polymorphisms that are diet responsive and may be useful when investigating ethnic variations in chronic disease, developmental anomalies, and folate requirements. J Am Diet Assoc. 2003;103:200-207.

Validation of Homocyst(e)ine-Lowering Treatment in the Era of Folic Acid Fortification of Cereal Grains

Validation of Homocyst(e)ine-Lowering Treatment in the Era of Folic Acid Fortification of Cereal Grains