Serum Total Homocysteine Concentrations Research Articles

The Association between Hyperhomocysteinemia and Thoracoabdominal Aortic Aneurysms in Chinese Population.

Objective To shed light on the association between hyperhomocysteinemia (HHcy) and thoracoabdominal aortic aneurysms (TAAAs). Methods From July 2013 to March 2017, we conducted a matched case–control study involving individuals who presented to the Chinese People's Liberation Army General Hospital and underwent thoracoabdominal magnetic resonance angiography or computed tomography angiography. A total of 73 patients with TAAAs were enrolled in the case group, and 219 sex-matched subjects without TAAAs were included in the control group. We then examined the relationship between HHcy and TAAAs by logistic regression models and subgroup as well as interaction analyses. Results Serum total homocysteine (tHcy) concentrations and the proportion of HHcy were significantly higher in the patients with TAAAs than in those without TAAAs (P < 0.001). Furthermore, the multivariate logistic regression models indicated that participants with HHcy had a 2.14-fold higher risk of TAAAs than those with a normal serum tHcy level (adjusted odds ratio (OR), 2.14; 95% confidence interval, 1.00–4.56). Similarly, each 1 μmol/L increase in the serum tHcy concentration was associated with a 4% higher risk of TAAAs (adjusted OR, 1.04; 95% confidence interval, 1.00–1.07). Subgroup analyses indicated that HHcy tended to be associated with a greater risk of TAAAs in all stratified subgroups (adjusted ORs > 1). Furthermore, the interaction analyses revealed no interactive role in the association between HHcy and TAAAs. Conclusions The present case–control study suggests that HHcy is an independent risk factor for TAAAs. Larger prospective cohort studies are warranted to validate these findings.

Circulating amino acids are associated with bone mineral density decline and ten-year major osteoporotic fracture risk in older community-dwelling adults.

With aging, poor bone mineral density (BMD) and accelerated decrease in BMD are strong risk factors for fracture. Reports of the associations of dietary protein intake with bone strength are inconsistent, possibly owing to differences in protein sources and amino acid (AA) composition. We examined the associations of serum AA with 4-year hip BMD loss and subsequent fracture risk within 10 years in older community-dwelling adults, and further addressed whether lifestyle, dietary protein intake and its source, and body composition would affect the associations. In 1424 men and 1573 women (mean age 72 years), using binary logistic regression, higher serum valine, leucine, isoleucine and tryptophan concentrations were associated (or approaching a borderline significance in case of the last three ones) with less hip BMD decline (defined as BMD loss ≥ 2.8 times the precision error of the BMD measurement at femoral neck) in 4 years later, with the OR (95%CI) /SD of AA increase, ranging from 0.83 (0.75, 0.91) to 0.92 (0.87, 0.98) after multiple adjustments for baseline age, gender, BMI, BMD, estimated glomerular filtration rate (eGFR), dietary protein intake (animal- and plant-derived protein intakes), calcium intake, established lifestyles (physical activity level, smoking and alcohol drinking status), osteoporosis medications, and changes of body fat and lean muscle mass. Higher serum total homocysteine (tHcy) concentration was independently associated with BMD decline 4 years later (OR (95%CI) /SD of 1.16 (1.05, 1.27)). Using multivariate Cox regression, higher serum tryptophan concentration potentially predicted low risk of incident major osteoporotic fractures (MOFs) (HR/SD (95%CI)=0.86 (0.75, 0.98)) after multiple adjustments. Higher serum tHcy was associated with MOFs (HR/SD (95%CI)=1.29 (1.12, 1.50)) risk after multiple adjustments in men. These findings suggest that a specific AA profile correlates with greater BMD and lower subsequent fracture risk, independent of diet and lifestyle factors.

Association of Hyperhomocysteinemia with Acute Myocardial Infarction in Kurdish Patients

Cardiovascular disease (CVD) is the main cause of death worldwide. Among multiple cardiovascular risk factors, such as age, blood pressure, diabetes, smoking and hyperlipidemia, hyperhomocysteinemia has recently emerged to have an important role in increasing risk of CVD by impairing oxidative stress-induced endothelial dysfunction and inducing atherothrombosis. However, the association between high circulating level of homocysteine and increasing the risk of CVD in human remains controversial and has not been consistently observed. OBJECTIVES: The aim of this study is to evaluate the association between serum total homocysteine (tHcy) concentrations with increased risk of CAD in patients with acute myocardial infarction (MI) in Kurdish population. In addition, correlations of classical risk factors including hypertension, smoking, diabetes and hyperlipidemia with hyperhomocysteinemia in MI patients were studied. Its role in in development of CVD could be pivotal. METHODS: In a case-control study, a total of 74 patients (51 male; 23 female; aged 22-80 years) who had diagnosed with acute CAD on angiography were enrolled in this study and 74 gender and age matched non-CAD individuals were included as the control group. The serum tHcy level was measured by enzymatic immunoassay. Hyperhomocysteinemia (HHcy) was defined as Hcy>15 µmol/l. RESULTS: the mean ± standard deviation (SD) of serum total homocysteine (tHcy) level in acute myocardial infarction patients was 22.8 ± 1.30 µmol/l, which was significantly higher compared to that of control group being 15.1 ± 1.33 µmol/l (P < 0.001), indicating that a high homocysteine level may promote pathogenesis of atherosclerosis. 51 (68.9%) MI cases had hyperhomocysteinemia; of these 35 MI patients (47.3%) had mild hyperhomocysteinemia (15-30µmol/L), and 16 MI patients (21.6%) had moderate levels of hyperhomocysteinemia (30-100 µmol/L). No significant correlation between tHcy levels and MI risk factors such as hypertension, hyperlipidemia, and diabetes mellitus, was observed. The tHcy levels were significantly higher in smoker patients than in non-smokers. CONCLUSIONS: These findings confirm that in patients with acute myocardial infarction, elevated homocysteine levels are associated with development of MI independent of other risk factors. A strong association between elevated levels of serum tHcy in MI patients was observed in Kurdish population. This study concludes that Hcy is considered as a strong emerging cardiovascular risk factor for development of myocardial infarction. Moreover, the measurement of Homocysteine levels might act as a surrogate laboratory marker and as one of the effective ways to diagnose patients with myocardial infarction in hospitals.

Vitamin D3 prevents cardiovascular diseases by lowering serum total homocysteine concentrations in overweight reproductive women: A randomized, placebo-controlled clinical trial

Obesity and overweight are associated with vitamin D deficiency and hyperhomocysteinemia, all of which are contributing factors for developing cardiovascular disease (CVD). Therefore, we hypothesized that improving serum 25-hydroxyvitamin D [25(OH)D] levels may decrease the body weight and total homocysteine concentrations among overweight reproductive women. To test our hypothesis, a randomized, double-blind placebo-controlled clinical trial, registered under ClinicalTrials.gov Identifier No. NCT03310307, was conducted on 100 overweight reproductive women that were allocated into two groups, namely, the treatment group (n = 50), which received 50 000 IU vitamin D3 per week, and the placebo group (n = 50), and followed for 2 months. Participants' 25(OH)D, homocysteine, parathyroid hormone, calcium, phosphorus, body weight and body mass index (BMI) were measured and compared before and after treatment. The results showed that there was a significant decrease in homocysteine levels after the first and second months of vitamin D3 intervention in the treatment group, and no significant changes were seen in the placebo group throughout the period of follow up. Statistically significant (P ≤ .05) reductions in homocysteine concentration, body weight, BMI, and parathyroid hormone levels were noticed in the treatment group compared to the placebo. Meanwhile, 25(OH)D, calcium and phosphorus levels were statistically significantly (P ≤ .05) increased in the treatment group. In conclusion, vitamin D3 intervention with a treatment dose of 50 000 IU per week for at least 2 months can help decrease BMI and homocysteine levels, which in turn will help prevent or minimize the risk of CVD among overweight women of reproductive age.

Effect of B9 and B12 vitamin intake on semen parameters and fertility of men with MTHFR polymorphisms.

The methylenetetrahydrofolate reductase (MTHFR) gene codes a crucial enzyme which involve in folate metabolism. The effect of MTHFR gene polymorphisms on male fertility status is uncertain and controversial. We evaluated the effect of B vitamin family intake on total homocysteine content and semen parameters of men with MTHFR gene polymorphisms. MTHFR genotypes frequency and serum total homocysteine concentration were measured among 280 men with impaired spermatogenesis (asthenospermia, oligospermia, severe oligospermia and azoospermia) and 85 control participants. B vitamin family dietary intakes were assessed using a semi-quantitative food-frequency questionnaire. In addition, concentrations of vitamins B9 and B12 were evaluated in serum samples of some participants (n=60). We observed significantly higher frequency of TC or TT genotypes in C677T polymorphism among oligospermic, severe oligospermic and azoospermic men. CC genotype of A1298C polymorphism was significantly higher only in azoospermic men. Also, we observed critical effect of vitamin B9 and B12 intake on decreasing of total homocysteine and improving of semen parameters among the men with T allele of MTHFR C677T polymorphism. Our investigation showed that sufficient consumption of vitamins B9 and B12 influences sperm parameters of men with different MTHFR polymorphisms, especially genotypes with T allele.

Association between the MTHFR C677T polymorphism, blood folate and vitamin B12 deficiency, and elevated serum total homocysteine in healthy individuals in Yunnan Province, China

BackgroundAn increased serum total homocysteine (tHcy) concentration is typically associated with genetic defects involved in Hcy metabolism or related nutritional deficiencies. In this study, the combined effects of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and folate and vitamin B12 deficiency on serum total Hcy (tHcy) levels were evaluated in a healthy Chinese population in Yunnan Province, China. MethodsThe MTHFR C677T polymorphism was genotyped in 330 volunteers (164 men and 166 women) using polymerase chain reaction-restriction fragment length polymorphism analysis. Folate, vitamin B12, and tHcy concentrations were determined by corpuscle immune chemiluminescence assays. The tHcy concentration was determined using an enzymatic assay. ResultsSignificant negative correlations (p<0.001) were observed between the serum levels of tHcy and folate (r=−0.252) and vitamin B12 (r=−0.243). Men had significantly higher serum tHcy concentrations than women (p<0.001). Individuals with the MTHFR TT genotype had significantly higher serum tHcy concentrations than individuals with the CC and CT genotypes (p<0.001). The folate level of red blood cells was significantly increased in individuals with the TT genotype than in individuals with the CC genotype (p<0.05). Moreover, in the low vitamin group, the serum tHcy level was significantly correlated with the levels of folate (r=−0.334, p=0.001) and vitamin B12 (r=−0.212, p=0.046). ConclusionThe MTHFR C677T polymorphism, folate deficiency, and B12 deficiency were significantly associated with elevated serum tHcy levels. Among these three factors, folate deficiency had the greatest contribution to the serum tHcy concentration, followed by (in order of decreasing effect) MTHFR C677T and vitamin B12 deficiency. Thus, folic acid and vitamin B12 supplementation could help prevent diseases associated with tHcy accumulation, especially in individuals with the MTHFR 677TT genotype.

Hyperhomocysteinemia induced by methionine dietary nutritional overload modulates acetylcholinesterase activity in the rat brain.

Methionine is the only endogenous precursor of homocysteine, sulfur-containing amino acid and well known as risk factor for various brain disorders. Acetylcholinesterase is a serine protease that rapidly hydrolyzes neurotransmitter acetylcholine. It is widely distributed in different brain regions. The aim of this study was to elucidate the effects of methionine nutritional overload on acetylcholinesterase activity in the rat brain. Males of Wistar rats were randomly divided into control and experimental group, fed from 30th to 60th postnatal day with standard or methionine-enriched diet (double content comparing to standard, 7.7 g/kg), respectively. On the 61st postnatal day, total homocysteine concentration was determined and showed that animals fed with methionine-enriched diet had significantly higher serum total homocysteine concentrations comparing to control rats (p < 0.01). Acetylcholinesterase activity has been determined spectrophotometrically in homogenates of the cerebral cortex, hippocampus, thalamus, and nc. caudatus. Acetylcholinesterase activity showed tendency to decrease in all examined brain structures in experimental comparing to control rats, while statistical significance of this reduction was achieved in the cerebral cortex (p < 0.05). Brain slices were stained with haematoxylin and eosin (H&E) and observed under light microscopy. Histological analysis of H&E-stained brain slices showed that there were no changes in the brain tissue of rats which were on methionine-enriched diet compared to control rats. Results of this study showed selective vulnerability of different brain regions on reduction of acetylcholinesterase activity induced by methionine-enriched diet and consecutive hyperhomocysteinemia.

Association between High Serum Homocystine and Preeclampsia

Background: Hyperhomocysteinemia is an important biological marker for adverse outcome of pregnancy. Objective: The aim of the present study was to see the association of high serum homocysteine with preeclampsia (PE). Methodology: This cross sectional study was carried out in the Department of Obstetrics and Gynaecology at Sir Salimullah Medical College &amp; Mitford Hospital, Dhaka. All pregnant women with or without eclampsia admitted at the hospital were included in this study. Pregnant women with diabetes mellitus, chronic hypertension, multiple pregnancies, chronic renal disease and patients taking anti-folate drugs were excluded from this study. Fasting serum total homocysteine (tHomocysteine) concentration was estimated by Fluorescence Polarization Immunoassay (FPIA) method. Result: A total number of 50 PE patient [Severe PE (23) &amp; Mild PE (27)] and 50 pregnant women without PE were selected purposively. Fasting serum total homocysteine (tHomocysteine) concentration was estimated by fluorescence polarization immunoassay (FPIA) method. Mean serum homocysteine concentration in severe PE, mild PE and pregnant women without PE were 11.5 4.58 mol/L, 10.43 5.12 and 5.70 1.30 respectively. Serum homocysteine was significantly increased in severe PE and mild PE in comparison to without PE group . Howere severe PE and mild PE group cases did not differ with respect to serum homocysteine. Conclusion: Significant positive correlation was found between serum homocysteine concentration and urinary total protein, uric acid level, systolic blood pressure and diastolic blood pressure. DOI: http://dx.doi.org/10.3329/jssmc.v5i1.16200 J Shaheed Suhrawardy Med Coll, 2013;5(1):21-25

Serum homocysteine and lipid profile levels in type 2 diabetes mellitus patients

Serum total homocysteine (tHcy) concentration is associated with increased risk factor for coronary heart diseases (CHD). The relation between type2 diabetes mellitus compared to the non diabetics is not clear. The current study represents an association between tHcy and cardiovascular disease is stronger in diabetics than in nondiabetic subjects.

The Association between Serum Homocysteine Levels and Retinopathy of Prematurity

To evaluate the relationship between serum total homocysteine levels and retinopathy of prematurity (ROP). This prospective case-control study involved premature infants diagnosed with ROP 4 weeks after birth (cases); controls were premature infants not developing ROP during follow-up. Fasting serum total homocysteine concentrations were determined in all participants 4 weeks after birth, using high performance liquid chromatography. A total of 45 and 35 infants were included in the case and control groups, respectively. The mean ± SD (range) serum total homocysteine levels were 10.36 ± 1.72 μmol/l (7.45-14.84) in infants with ROP and 8.41 ± 2.12 μmol/l (5.56-13.90) in controls. This difference was statistically significant. Mean ± SD total homocysteine levels were higher in infants with more severe ROP (11.45 ± 1.76 μmol/l) compared with mild ROP (9.92 ± 1.56 μmol/l). Elevated serum total homocysteine levels are associated with the development of ROP in premature infants. Further studies with larger patient populations are required, to improve understanding of the relationship between homocysteine and ROP development.

Plasma malondialdehyde, bilirubin, homocysteine and total antioxidant capacity in patients with angiographically defined coronary artery disease

Oxidative stress has been implicated in coronary artery disease (CAD). Malondialdehyde (MDA) is lipid peroxidation end product. Bilirubin may act as an antioxidant that suppresses lipid oxidation. The role of MDA and antioxidant capacity and their inter-relationship in patients with and without CAD was investigated. Thirty-eight consecutive patients with angiographically diagnosed CAD were compared with 60 age, and sex-matched controls. The controls had completely normal coronary arteries in angiograms. Plasma MDA, serum bilirubin, total homocysteine and total antioxidant capacity (TAC) levels were measured. Risk factors of CAD were determined for all subjects using National Cholesterol Education Program (NCEP)-Adult Treatment Panel (ATP)-III criteria. Serum MDA and total homocysteine concentration were significantly higher, but TAC, total bilirubin and direct bilirubin levels were lower in CAD patients when compared to the controls. Age, and sex-adjusted plasma MDA levels had negative correlations with TAC (r = -0.30, p = 0.001) and total bilirubin (r = -0.30, p = 0.002) concentrations. In multivariate analysis by the multiple logistic regression method, serum MDA was significantly associated with CAD (OR = 1.15, 95% CI, 1.25 to 1.82; p < 0.0001)) after adjustment for lipid status parameters and traditional risk factors in this study population. Increased serum MDA concentration, as a biomarker of lipid peroxidation, low serum bilirubin and antioxidant capacity were observed in patients with angiographically defined CAD. The significant inverse correlation of the serum bilirubin and MDA levels demands further in-depth investigations to clarify the association between them in the development of CAD. Key words: Oxidative stress, bilirubin, malondialdehyde, coronary artery disease, antioxidant capacity, homocysteine.

SIGNIFICANT DECREASE IN HOMOCYSTEINE AND ox‐LDL IN HEALTHY HEAVY SMOKERS AFTER NUTRACEUTICAL SUPPLEMENTATION

Nutraceuticals may attenuate some negative effects of cigarette smoking. We evaluated effects of two different encapsulated formulas, consisting primarily of mixed juice powder concentrate (Juice Plus+®), in a randomized placebo controlled, double‐blind study on 101 heavy smokers (&gt;20 cigarettes/d, duration ≥10y, median age 47; 41–57 y, 63 M, mean capsule compliance 85.2%). Smokers were divided into 3 groups: A‐placebo, B‐fruit/vegetable, C‐fruit/vegetable/berry. Serum and erythrocyte folate (s‐fol and ery‐fol, respectively) and total homocysteine (tHcy) concentrations were measured before and after 3‐m supplementation. In 75 (46 M) compliant (&gt;95%) subjects, lipid panel parameters (total Cholesterol, tChol; LDL‐c; oxidized‐LDL, ox‐LDL) were evaluated. Median values were compared (t‐test for paired data); data are reported as mean delta values (± standard deviation). Intervention with both nutraceutical formulations resulted in reduction in ox‐LDL and tHcy compared to placebo.Support: NSA, Collierville, TN A (placebo) B (fruit/veg) C (fruit/veg/berry) tChol (mg/dL) 9.3 (±18.4) −11.6 (±22.9)* −6.3 (±25.5)* LDL‐c (mg/dL) 16.8 (±17.6) −8.1 (±17.9)* −0.8 (±20.5)* ox‐LDL (U/L) −2.3 (±11.3) −13.8 (±12.5)* −11.2 (±12.2)* tHcy (μM) −0.14 (±1.4) −2.38 (±2.3)# −3.20 (±5.2)# s‐fol (nM) 2.8 (±5.5) 13.7 (±9.9)# 16.6 (±9)# ery‐fol (nM) 194 (±178.3) 488.2 (±349)# 646.3 (±362.1)#

Moderate or Supranormal Folic Acid Supplementation Does Not Exert a Protective Effect for Homocysteinemia and Methylation Markers in Growing Rats

Background/Aims: Folic acid (FA) deficiency/supplementation effects seem to be dependent on age group and/or physiological status. The aim was to evaluate changes associated with rapid growth in relation to methionine metabolism in rats. Methods: Four groups (n = 10 each) of male Sprague Dawley rats (5 weeks old) were on diets that varied in their FA content: 0 mg FA/kg diet (deficient), 2 mg FA/kg diet (control), 8 mg FA/kg diet (moderate supplementation), 40 mg FA/kg diet (supranormal supplementation). Animals were fed ad libitum for 30 days. Biomarkers of methionine metabolism and antioxidant status were evaluated. Results: Serum total homocysteine concentration increased (p < 0.01) in FA deficient animals, with no differences between the supplemented groups. The hepatic ‘methylation ratio’ (S-adenosylmethionine/S-adenosylhomocysteine) of the FA content groups reached similar values, which were significantly higher compared to the deficient group. The brain ‘methylation ratio’, however, remained unmodified independently of FA content in the diet. FA deficiency induced hepatic DNA hypomethylation, and supranormal FA supplementation exerted the most protective effect (p < 0.01). Serum folate levels increased according to FA dietary level, whereas no differences were seen for vitamin B₁₂ and vitamin B₆. Conclusions: FA deficiency compromises methionine metabolism whereas supplementation does not show an additional positive effect compared to the control diet in growing animals.

Thrombophilia and abdominal vessel thrombosis in a Greek University hospital: A five year experience

Thrombophilia, either congenital or acquired, has foremost consequences in the abdominal vessels. We review here the cases of patients admitted with abdominal vessel thrombosis over a five-year period. Our data focused on gender and age at diagnosis, site of thrombosis, previous thromboembolic events, underlying conditions, and family history. Investigations included measurement of protein C, protein S, activated PC resistance, and antithrombin, and screening for factor V Leiden, prothrombin G20210A, the C677T variant of the methylenetetrahydrofolate reductase gene, and V617F JAK2 mutation, r lupus anticoagulant, antiphospholipid antibodies and paroxysmal nocturnal hemospherinouria, and also serum folate, vitamin 12, and total homocysteine concentrations. Twenty-nine patients were admitted and 18 of their family members also underwent the same thrombophilia investigations. Eighteen patients (62.1%) presented with portal vein thrombosis (PVT), five patients (17.2%) with mesenteric vein thrombosis (MVT), four patients (13.8%) with splenic vein thrombosis (SVT), and two (6.9%) patients with hepatic vein thrombosis (HVT). There was a high incidence of congenital thrombophilia (37.9%), acquired thrombophilic conditions (27.6%), or both (20.7%). Sixteen of 18 patients with PVT, four of five patients with MVT, all four patients with SVT, and one of two patients with HVT had one or more thrombophilic risk factors. In 13.8% of the patients no underlying condition was identified. We concluded that thrombophilia may have major implications in the pathogenesis of abdominal vessel thrombosis in adult life, and a thorough thrombophilia investigation should be performed in all these patients.

Red Clover (Trifolium pratense) Isoflavones and Serum Homocysteine in Premenopausal Women: A Pilot Study

There is limited information on the effect of isoflavones on homocysteine concentrations, a risk factor for a number of chronic diseases. Twenty-three premenopausal women participated in a double-blind, randomized, parallel study for four menstrual cycles. Subjects consumed either placebo or purified red clover (Trifolium pratense) isoflavone (86 mg/day) tablets. Blood samples were collected weekly during cycles 1, 3, and 4 for determination of serum folate and total homocysteine concentrations. Dietary intake was monitored monthly. Concentrations of folate and homocysteine in serum did not change significantly in either group, and there were no significant differences observed between the follicular and luteal phases of the menstrual cycle. The participants' dietary records indicated that nutrient intake was constant, and compliance was confirmed by analysis of urinary isoflavone concentrations and tablet counts in returned containers. These results suggest that in the absence of any dietary modification, supplementation with purified isoflavones that are predominantly methoxylated has no effect on serum homocysteine or folate in premenopausal women.

Urinary methylmalonic acid levels in patients with acute ischemic stroke

Objectives Vitamin B-12 and folate deficiency are common, especially in people aged 55 or over, and accompanied by elevated methylmalonic acid (MMA) and homocysteine concentrations. The aims of the study were to investigate the relationship between serum vitamin B-12, homocysteine, folate, erythrocyte folate and urinary MMA in patients with ischemic stroke, and to develop a simple screening HPLC method for the measurement of urinary MMA. Design and methods Twenty-eight patients aged 55 years and over with ischemic stroke and 23 age- and sex- matched healthy controls were included in the study. Serum vitamin B-12 and folate were measured by immunoassay; serum total homocysteine and urinary MMA concentrations by HPLC. Results There was no significant difference in vitamin B-12, folate and homocysteine concentrations between the patient and control groups. Urinary MMA concentrations and erythrocyte folate levels were significantly higher in patients than controls. There was a significantly negative correlation between vitamin B-12 and MMA. Conclusions Increased urinary MMA excretion is associated with ischemic stroke and it may more robustly reflect vitamin B-12 deficiency in patients with ischemic stroke. The method used in this study is eligible for routine urinary MMA measurements.

Folate contents in human milk and casein-based and soya-based formulas, and folate status in Korean infants

We assessed folate nutritional status from birth to 12 months in fifty-one infants who were fed human milk (HM; n 20), casein-based formula (CBF; n 12) or soya-based formula (SBF; n 19). Folate contents in ninety-five HM samples obtained from twenty mothers for the first 6-month period and twelve CBF and nineteen SBF samples were measured by bioassay after trienzyme extraction. Folate intake was estimated by weighing infants before and after feeding in the HM group and by collecting formula intake records in the formula-fed groups. After solid foods were introduced, all foods consumed were included to estimate folate intake. Serum folate and total homocysteine (tHcy) concentrations were determined at 5 and 12 months of age, and infant growth was monitored for the first 12 months. Mean HM folate contents ranged from 201 to 365 nmol/l with an overall mean of 291 nmol/l, and the contents peaked at 2 months postpartum. HM folate contents were higher than those reported in North America. Folate contents in CBF and SBF were markedly higher than those in HM and those claimed on the product labels. The overall folate intakes in formula-fed infants were significantly higher than those in HM-fed infants, and this was associated with significantly higher folate and lower tHcy in formula-fed infants than HM-fed infants at 5 months. At 12 months, serum folate was significantly higher in the SBF group than the other groups, whereas serum tHcy and overall growth were similar among all groups.

Prevalence and effects of gene-gene and gene-nutrient interactions on serum folate and serum total homocysteine concentrations in the United States: findings from the third National Health and Nutrition Examination Survey DNA Bank

BackgroundAbnormalities of folate and homocysteine metabolism are associated with a number of pediatric and adult disorders. Folate intake and genetic polymorphisms encoding folate-metabolizing enzymes influence blood folate and homocysteine concentrations, but the effects and interactions of these factors have not been studied on a population-wide basis. ObjectiveThe objective was to assess the prevalence of these genetic polymorphisms and their relation to serum folate and homocysteine concentrations. DesignDNA samples from 6793 participants in the third National Health and Nutrition Examination Survey (NHANES III) during 1991–1994 were genotyped for polymorphisms of genes coding for folate pathway enzymes 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C→T and 1298A→C, methionine synthase reductase (MTRR) 66A→G, and cystathionine-β-synthase 844ins68. The influence of these genetic variants on serum folate and homocysteine concentrations was analyzed by age, sex, and folate intake in 3 race-ethnicity groups. ResultsFor all race-ethnicity groups, serum folate and homocysteine concentrations were significantly related to the MTHFR 677C→T genotype but not to the other polymorphisms. Persons with the MTHFR 677 TT genotype had a 22.1% (95% CI: 14.6%, 28.9%) lower serum folate and a 25.7% (95% CI: 18.6%, 33.2%) higher homocysteine concentration than did persons with the CC genotype. Moderate daily folic acid intake (mean: 150 μg/d; 95% CI: 138, 162) significantly reduced the difference in mean homocysteine concentrations between those with the MTHFR 677 CC and TT genotypes. We found a significant interaction between MTHFR 677C→T and MTRR 66A→G on serum homocysteine concentrations among non-Hispanic whites. ConclusionsThe MTHFR 677C→T polymorphism was associated with significant differences in serum folate and homocysteine concentrations in the US population before folic acid fortification. The effect of MTHFR 677C→T on homocysteine concentrations was reduced by moderate daily folic acid intake.

Serum Total Homocysteine Concentrations in Children and Adolescents in Jos, Nigeria

Although the elevation of circulating total serum homocysteine (tHcy) concentration in a fasting state is associated with an increased risk of occlusive vascular disease in adults, the levels in children in Nigeria are not known. The goals of this study were to describe the distribution of tHcy among a representative sample of children and adolescents in Jos, Nigeria, and to test for differences in tHcy among sex and age categories. The sampling scheme, which included persons aged 10 to 19 years, was a stratified, multistage probability design. This cross sectional study involved 182 school children drawn from secondary schools in Jos, Nigeria between January and July 2003. Fasting venous samples were collected and assayed for tHcy, Total protein and Albumin. Anthropometric measurements were taken. The mean tHcy concentrations were 2.7 +/- 2.4 (95% CI 2.4-2.9), 3.5 +/- 3.2 (3.3-3.8) and 3.6 +/- 3.2 (3.3-4.1), 4.1 +/- 3.6 (4.0-4.4) micromol/l for the girls and boys aged 10-14 and 15-19 years, respectively. Albumin levels correlate positively with plasma total homocysteine, tHcy (r = 0.45, P = 0.03). This study provided age-specific data regarding tHcy concentrations between 10-19 years population in Jos, Nigeria. The tHcy concentration increased as a function of age in both sexes.

Serum total homocysteine concentrations and risk of mortality from stroke and coronary heart disease in Japanese: The JACC study

Evidence for association between serum total homocysteine (tHcy) level and cardiovascular disease is limited in Asian populations. We conducted a nested case–control study under JACC Study. A total of 39,242 subjects aged 40–79 years provided serum samples at baseline surveys between 1988 and 1990. Control subjects were selected by matching for sex, age, community and year of serum storage. Serum tHcy levels were measured by high-performance liquid chromatography. During the 10-year follow-up, there were 444 deaths due to total cardiovascular disease, including 310 total stroke (131 hemorrhage and 101 ischemic strokes) and 134 coronary heart diseases. The risks of mortality from ischemic stroke, coronary heart disease, and total cardiovascular disease were significantly higher in individuals with the highest serum tHcy quartile (≥15.3 μmol/L) than in those with the lowest quartile (<10.5 μmol/L); the respective multivariable odds ratios (95% CI) were 4.35 (1.12–16.9), 3.40 (1.17–9.86), and 1.68 (1.02–2.77). The multivariable odds ratios associated with a 5-μmol/L increase in tHcy were 1.49 (1.01–2.18), 2.01 (1.21–3.35), and 1.15 (1.00–1.32), respectively. High serum tHcy levels were associated with increased mortality from ischemic stroke, coronary heart disease and total cardiovascular disease among Japanese.