Serum folate is a reliable indicator of hyperhomocysteinemia and borderline hyperhomocysteinemia in young adults

Cheng, Chun-Wen; Tsai, Tsung-Po; Chen, Wan-Shin; Huang, Yi‐Chia

doi:10.1016/j.nutres.2009.09.017

Cited by 8 publications

(11 citation statements)

References 45 publications

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“…1) could not be measured for multivariate adjustment. Blood vitamin B6, cystathionine b-synthase, and betaine, affect tHcy levels independently of blood folate (27), although folate is a stronger determinant for tHcy (38,39). Second, plasma folate levels are influenced by folate intake during a relatively short term, so plasma folate levels of the subjects may indicate folate intake only a few days before the health checkup.…”

Section: Discussionmentioning

confidence: 99%

“…Erythrocyte folate levels may be more appropriate to detect folate deficiency because of long-term dietary habits (6). However, it has been reported that plasma folate levels were correlated with plasma tHcy more strongly than erythrocyte folate (38). Third, Japanese dietary folate intake may be more difficult to estimate than intake in other countries (40).…”

Section: Discussionmentioning

confidence: 99%

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A Cross-Sectional Study to Find Out the Relationship of Methylenetetrahydrofolate Reductase (MTHFR) C677T Genotype with Plasma Levels of Folate and Total Homocysteine by Daily Folate Intake in Japanese

Fukuda

Hamajima

Wakai

et al. 2014

J Nutr Sci Vitaminol

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l-5-Methyl-tetrahydrofolate (THF), derived from dietary folate, is involved in the conversion of homocysteine into methionine ( Fig. 1; 1-3). Folate deficiency increases total homocysteine (tHcy) levels (4). Hyperhomocysteinemia is one of the risk factors of cardiovascular disease (4,5) and neural tube defects (NTDs) (6). Maintaining adequate blood folate levels and controlling tHcy levels are important in preventing these diseases.In the folate metabolic pathway, 5,10-methylene-THF is converted into 5-methyl-THF by the enzyme 10-methylene-THF reductase (MTHFR). In the MTHFR C677T polymorphism (rs 1801133), the T allele reduces thermostability of the enzyme and lowers its activity, which were found to be decreased by 30% in heterozygotes and by 65% in homozygotes of minor alleles compared with the CC genotype in an in vitro study (7). However, folate intake could increase blood folate levels even among those with the TT genotype. In previous observational studies, decreased tHcy levels were related to increased blood folate levels (8-11), and increased folate intake was associated with increased blood folate levels (8, 12) and decreased tHcy levels (8,13,14) in each of the MTHFR genotype. These correlations were substantially stronger among those with TT (8,9,[11][12][13][14][15] and those consuming relatively lower amounts of folate (8,12,13). In previous interventional studies using folate supplements or fortified foods, increased folate intake raised blood folate (16-21) and reduced tHcy levels (17-21).However, one study in Japan found no association of serum folate with energy-adjusted folate intake among those with the TT genotype (22). This may be partly explained by the difference in the amount of folate intake and sources of folate. The mean folate intake among Japanese aged 20 y or more was 329 mg/d for men and 189 mg/d for women and the mean intake from supplements or fortified foods among the population was only 1 mg/d in 2008 (23 (Received November 12, 2013) Summary In those with the methylenetetrahydrofolate reductase (MTHFR) 677TT genotype, enzyme activity is lowered. Therefore, these individuals might require an increased intake of folate to maintain or control blood levels of plasma folate or total homocysteine (tHcy). We examined associations of dietary folate intake with fasting plasma folate and total homocysteine (tHcy) according to genotype among 554 Japanese (207 men and 347 women aged 39-89 y) recruited in 2009. Intake of folate was estimated with a food frequency questionnaire. The MTHFR polymorphism was genotyped by a polymerase chain reaction with confronting two-pair primers. The log-transformed concentration of folate or tHcy was regressed on energy-adjusted folate intake in a linear regression analysis. Higher folate intake was associated with higher plasma folate among those with the CC (b50.165, p50.066) or CT (b50.248, p,0.001) genotypes, and with lower tHcy levels only among those with the CC (b520.141, p50.013) genotype. Plasma folate was significantly and inversely associat...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A Cross-Sectional Study to Find Out the Relationship of Methylenetetrahydrofolate Reductase (MTHFR) C677T Genotype with Plasma Levels of Folate and Total Homocysteine by Daily Folate Intake in Japanese

Fukuda

Hamajima

Wakai

et al. 2014

J Nutr Sci Vitaminol

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“…A variation of the assessment of markers against homocysteine was used by Cheng et al [ 53 ]. The study examined the ability of the markers to predict borderline increased homocysteine ( ≥ 10.2 μ mol/L) or overtly increased homocysteine ( ≥ 14.9 μ mol/L).…”

Section: Prediction Of Hyperhomocysteinaemiamentioning

confidence: 99%

“…The two markers appeared to perform similarly, with a trend toward better performance of serum folate ( Table 1 ). Regression against homocysteine Marouf et al [ 60 ] Men with venous thromboembolism 91 Significant Not significant Marouf et al [ 60 ] Women with venous thromboembolism 110 Not significant Not significant Cheng et al [ 53 ] General population 130 Significant Not significant Dierkes et al [ 61 ] General population 336 Significant Significant Golbahar et al [ 56 ] Subjects with coronary artery disease and matched controls In our own analysis, we investigated the ability of serum and red cell folate to predict elevated plasma homocysteine levels ( ≥ 15 μ mol/L) in 320 randomly selected patient samples sent to our hospital laboratory. Among patients with a normal serum vitamin B 12 concentration and eGFR, serum folate demonstrated a significantly higher area under the receiver operating characteristic curve (AUC) for predicting increased plasma homocysteine concentration.…”

Section: Prediction Of Hyperhomocysteinaemiamentioning

confidence: 99%

Red cell or serum folate: what to do in clinical practice?

Farrell¹,

Kirsch

Herrmann

2013

Clinical Chemistry and Laboratory Medicine

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Folate deficiency has been linked to diverse clinical manifestations and despite the importance of accurate assessment of folate status, the best test for routine use is uncertain. Both serum and red cell folate assays are widely available in clinical laboratories; however, red cell folate is the more time-consuming and costly test. This review sought to evaluate whether the red cell assay demonstrated superior performance characteristics to justify these disadvantages. Red cell folate, but not serum folate, measurements demonstrated analytical variation due to sample pre-treatment parameters, oxygen saturation of haemoglobin and haematocrit. Neither marker was clearly superior in characterising deficiency but serum folate more frequently showed the higher correlation with homocysteine, a sensitive marker of deficiency. Similarly, both serum and red cell folate were shown to increase in response to folic acid supplementation. However, serum folate generally gave the greater response and was able to distinguish different supplementation doses. The C677T polymorphism of methylenetetrahydrofolate reductase alters the distribution of folate forms in red cells and may thereby cause further analytical variability in routine red cell folate assays. Overall, serum folate is cheaper and faster to perform than red cell folate, is influenced by fewer analytical variables and provides an assessment of folate status that may be superior to red cell folate.

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“…All assays were carried out in laboratory of Day General Hospital, Tehran, Iran. In BC patients, highfasting plasma tHcy level was identified as measurements over 10.0 mmol/l (47). Plasma concentrations of folate 5.9 ng/ml (48), pyridoxine 10.0 mg/l (49), and cobalamin 260 pmol/l(50) were defined as reference values for deficiency status.…”

Section: Laboratory and Biochemical Analysesmentioning

confidence: 99%

Plasma Total Homocysteine Level in Association With Folate, Pyridoxine, and Cobalamin Status Among Iranian Primary Breast Cancer Patients

Pirouzpanah

Taleban

Mehdipour

et al. 2014

Nutrition and Cancer

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Recently the elevated plasma total homocysteine (tHcy) concentration has been concerned as the secondary feature of tumoral proliferation and enhances the likelihood of thrombogenesis in cancer patients. The objective of this study was to determine the associations between folate, cobalamin, and pyridoxine with fasting plasma tHcy concentration in breast cancer (BC) patients. The intake levels of nutrients were assessed using a validated food frequency questionnaire in 141 newly diagnosed BC patients. The plasma tHcy and pyridoxal-5-phosphate were measured using high performance liquid chromatography with fluorescence detector. Plasma tHcy levels were observed to be significantly higher among BC participants with Stage III where the plasma concentrations of folate was also comparatively less (P < 0.05) than other stages. Dietary pyridoxine was even being consumed less at this stage (P < 0.05). The plasma, dietary, and residual variables of folate were inversely correlated with plasma tHcy concentration (P < 0.05). Dietary cobalamin was also associated negatively with tHcy (P < 0.05). The odds ratio of comparing the highest tertile of plasma cobalamin (>394 pmol/l) and folate (>11.4 ng/ml) vs. the lowest categories were associated with reduced odds of high tHcy occurrence with 0.20 (95% confidence interval: 0.04-0.98) and 0.14 (95% confidence interval: 0.03-0.64), respectively. In conclusion, nutrition-related methyl-group insufficiency could lead to imbalance in tHcy metabolism, as a possible cancer marker.

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Serum folate is a reliable indicator of hyperhomocysteinemia and borderline hyperhomocysteinemia in young adults

Cited by 8 publications

References 45 publications

A Cross-Sectional Study to Find Out the Relationship of Methylenetetrahydrofolate Reductase (MTHFR) C677T Genotype with Plasma Levels of Folate and Total Homocysteine by Daily Folate Intake in Japanese

A Cross-Sectional Study to Find Out the Relationship of Methylenetetrahydrofolate Reductase (MTHFR) C677T Genotype with Plasma Levels of Folate and Total Homocysteine by Daily Folate Intake in Japanese

Red cell or serum folate: what to do in clinical practice?

Plasma Total Homocysteine Level in Association With Folate, Pyridoxine, and Cobalamin Status Among Iranian Primary Breast Cancer Patients

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