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J Selhub

Publications and source records attributed to J Selhub.

At least 37 records · Page 2Linked to original sources
PubMed2001

Determinants of plasma total homocysteine concentration in the Framingham Offspring cohort.

BACKGROUND: Established determinants of fasting total homocysteine (tHcy) concentration include folate and vitamin B-12 status, serum creatinine concentration, and renal function. OBJECTIVE: Our objective was to examine the relation between known and suspected determinants of fasting plasma tHcy in a population-based cohort. DESIGN: We examined the relations between fasting plasma tHcy concentrations and nutritional and other health factors in 1960 men and women, aged 28-82 y, from the fifth examination cycle of the Framingham Offspring Study between 1991 and 1994, before the implementation of folic acid fortification. RESULTS: Geometric mean tHcy was 11% higher in men than in women and 23% higher in persons aged > or = 65 y than in persons aged < 45 y (P < 0.001). tHcy was associated with plasma folate, vitamin B-12, and pyridoxal phosphate (P for trend < 0.001). Dietary folate, vitamin B-6, and riboflavin were associated with tHcy among non-supplement users (P for trend < 0.01). The tHcy concentrations of persons who used vitamin B supplements were 18% lower than those of persons who did not (P < 0.001). tHcy was positively associated with alcohol intake (P for trend = 0.004), caffeine intake (P for trend < 0.001), serum creatinine (P for trend < 0.001), number of cigarettes smoked (P for trend < 0.001), and antihypertensive medication use (P < 0.001). CONCLUSIONS: Our study confirmed, in a population-based setting, the importance of the known determinants of fasting tHcy and suggested that other dietary and lifestyle factors, including vitamin B-6, riboflavin, alcohol, and caffeine intakes as well as smoking and hypertension, influence circulating tHcy concentrations.

Adult↗
PubMed2001

Hyperhomocysteinemia associated with poor recall in the third National Health and Nutrition Examination Survey.

BACKGROUND: High circulating total homocysteine (tHcy) concentrations are associated with stroke, which is a major cause of cognitive dysfunction. Blood homocysteine concentrations are inversely correlated with performance on some cognitive-function tests and a relation was recently shown between hyperhomocysteinemia and Alzheimer disease. OBJECTIVE: The objective was to evaluate the relation between serum tHcy concentrations and performance on short delayed-recall tests of elderly men and women participating in the third National Health and Nutrition Examination Survey, phase 2 (1991--1994). DESIGN: Subjects were aged > or =60 y. Subjects reported no previous stroke, completed > or =8 y of education, and took a test of delayed recall of story ideas (n = 1200) or words (n = 1270). RESULTS: After adjustment for sex, age, race-ethnicity, income, years of education, and serum creatinine concentration, subjects in the upper half of the folate distribution recalled, on average, >4 of 6 story ideas; subjects with lower folate status recalled significantly fewer ideas (P < 0.001). Of the subjects with low folate status, story recall was significantly poorer in those with serum tHcy concentrations above the 80th percentile of the distribution (13.7 micromol/L) than in those with lower tHcy concentrations (P < 0.03). The odds ratio relating hyperhomocysteinemia to recall of > or =1 of 3 previously learned words was 0.3 (95% CI: 0.2, 0.7) after adjustment for the 5 demographic factors alone and was 0.4 (0.2, 0.9) after further adjustment for serum folate concentration. CONCLUSION: Hyperhomocysteinemia is related to poor recall and this association was partially independent of folate status.

Age Factors↗
PubMed2001

COMT genotype, micronutrients in the folate metabolic pathway and breast cancer risk.

Catechol-O-methyltransferase (COMT) catalyzes the O-methylation of catechol estrogens (CEs), using S-adenosylmethionine (SAM) as a methyl donor. Several studies have indicated that the val108met COMT polymorphism, which results in a 3-4-fold decrease in activity, is associated with increased breast cancer risk. Folate, whose intake levels have also been associated with breast cancer risk, and other micronutrients in the folate metabolic pathway influence levels of SAM and S-adenosylhomocysteine (SAH), a COMT inhibitor generated by the demethylation of SAM. Because these micronutrients have been shown to alter SAM and SAH levels, we hypothesized that they could also affect COMT-catalyzed CE methylation. Although measurements of SAM and SAH were not initially collected, a secondary analysis of data from two nested case-control studies was performed to examine whether serum levels of folate, vitamin B12 (B12), pyridoxal 5'-phosphate (PLP), cysteine and homocysteine, in conjunction with COMT genotype, were associated with breast cancer risk. COMT(HH) (high activity COMT homozygote) breast cancer cases had statistically significantly lower levels of homocysteine (P = 0.05) and cysteine (P = 0.04) and higher levels of PLP (P = 0.02) than COMT(HH) controls. In contrast, COMT(LL) (low activity COMT homozygote) cases had higher levels of homocysteine than COMT(LL) controls (P = 0.05). No associations were seen between B12, COMT genotype, and breast cancer risk. An increasing number of COMT(L) alleles was significantly associated with increased breast cancer risk in women with below median levels of folate (P(trend) = 0.05) or above median levels of homocysteine (P(trend) = 0.02). These findings are consistent with a role for certain folate pathway micronutrients in mediating the association between COMT genotype and breast cancer risk.

Breast Neoplasms↗
PubMed2001

Folic acid fortification increases red blood cell folate concentrations in the Framingham study.

In 1996 the Food and Drug Administration (FDA) issued a regulation to take effect in January 1998 that all enriched cereal grain products include 140 microg of folic acid/100 g. The present cross-sectional study was undertaken to assess the effect of this fortification on RBC folate concentrations in the Framingham Offspring Cohort. Among those who did not take B-vitamin supplements, we compared RBC folate in 561 individuals who were examined before implementation of the FDA mandatory folic acid fortification (not exposed) vs. 354 individuals who were examined after implementation of fortification (exposed). We calculated the prevalence of deficient (<160 microg/L, 362.6 nmol/L) and acceptable (>200 microg/L, 453.2 nmol/L) RBC folate concentrations in both groups. Those exposed to folic acid fortification had a mean RBC folate of 450.0 microg/L (1019.7 nmol/L), a value 38% higher than the mean RBC folate of 325.3 microg/L (737.1 nmol/L) in those who were not exposed to fortification (P < 0.001). The prevalence of individuals with deficient RBC folate was 4.9% in the group not exposed to fortification compared with 1.9% in the group exposed to fortification (P < 0.02), and the prevalence of individuals with acceptable RBC folate was 87.0% in the group not exposed to fortification compared with 96.1% in the group exposed to fortification (P < 0.001). Similar results were seen in individuals who used supplements containing B-vitamins. The results of this study showed that in this cohort, the introduction of folic acid fortification significantly improved folate nutritional status measured as RBC folate.

Adult↗
PubMed2001

Renal insufficiency, vitamin B(12) status, and population attributable risk for mild hyperhomocysteinemia among coronary artery disease patients in the era of folic acid-fortified cereal grain flour.

Fortification of enriched cereal grain flour products with folic acid has drastically reduced the prevalence of deficient plasma folate status, a major determinant of plasma total homocysteine (tHcy) levels. We hypothesized that even more liberally defined "suboptimal" plasma folate status might no longer contribute importantly to the population attributable risk (PAR) for mild hyperhomocysteinemia, a putative atherothrombotic risk factor. We determined fasting plasma tHcy, folate, vitamin B(12), and pyridoxal 5'-phosphate levels, along with serum creatinine and albumin levels, in 267 consecutive patients (aged 61+/-9 [mean+/-SD] years, 76.4% men and 26.6% women) with stable coronary artery disease (CAD) who were nonusers of vitamin supplements or had abstained from supplement use for at least 6 weeks before examination. Subjects were evaluated a minimum of 3 months after the implementation of flour fortification was largely completed. Relative risk estimates for the calculation of PAR were derived from a multivariable-adjusted logistic regression model with >/=12 micromol/L tHcy as the dependent variable and with age, sex, pyridoxal 5'-phosphate (continuous), albumin (continuous), <5 ng/mL folate, <250 pg/mL vitamin B(12), and >/=1.3 mg/dL creatinine as the independent variables. The prevalence of >/=12 micromol/L plasma tHcy was 11.2% (30 of 267 patients). PAR estimates (percentage) for >/=12 micromol/L tHcy were as follows: <5 ng/mL folate (<1%), <250 pg/mL vitamin B(12) (24.5%), and >/=1.3 mg/dL creatinine (37.5%). In the era of folic acid-fortified cereal grain flour, renal insufficiency and suboptimal vitamin B(12) status (but not folate status) contribute importantly to the PAR for mild hyperhomocysteinemia among patients with stable CAD.

Adult↗
PubMed2001

Fasting plasma homocysteine levels in the insulin resistance syndrome: the Framingham offspring study.

OBJECTIVE: Insulin resistance, associated metabolic abnormalities, and elevated homocysteine levels are risk factors for cardiovascular disease (CVD). We examined relationships between homocysteine levels and features of insulin resistance syndrome (IRS). RESEARCH DESIGN AND METHODS: We measured clinical characteristics, plasma levels of fasting homocysteine, folate, B vitamins, creatinine, and fasting and 2-h insulin and glucose levels after a 75-g oral glucose tolerance test in 2,214 subjects without CVD at the fifth examination (1991-1995) of the Framingham Offspring Study. After excluding 203 subjects with diabetes, the remaining 2,011 subjects were categorized as having none, one, two, or all three of the phenotypes of IRS: impaired glucose tolerance, hypertension, and/or a central metabolic syndrome (two or more traits: obesity, dyslipidemia, or hyperinsulinemia). In addition, in 1,592 subjects attending the sixth examination (1995-1998), we measured the urine albumin/creatinine ratio (UACR). Age-, sex-, creatinine-, vitamin-, and UACR-adjusted mean homocysteine levels or proportions with homocysteine >14 micromol/l in each phenotypic category and differences between categories were assessed with regression models. RESULTS: The mean age of the subjects was 54 years (range 28-82); 55% were women, 12.3% had hyperinsulinemia, and 15.9% had two or more of the IRS phenotypes. Adjusted mean homocysteine levels were higher comparing those with hyperinsulinemia (9.8 micromol/l) and those without (9.4 micromol/l, P = 0.04) and were higher among subjects with two or more IRS phenotypes (9.9 micromol/l) compared with those with 1 or no phenotype (9.3 micromol/l, P = 0.003). Mean UACR levels were also higher among subjects with two or more IRS phenotypes (7.2 mg/g) compared with those with 1 or no phenotype (5.5 mg/g, P = 0.007). CONCLUSIONS: Hyperhomocysteinemia and abnormal urinary albumin excretion are both associated with hyperinsulinemia and may partially account for increased risk of CVD associated with insulin resistance. Because hyperhomocysteinemia and microalbuminuria also reflect endothelial injury, these observations also support the hypothesis that endothelial dysfunction is associated with expression of the IRS.

Adult↗
PubMed2001

Association of methylenetetrahydrofolate reductase polymorphism C677T and dietary folate with the risk of cervical dysplasia.

Epidemiological studies have been inconsistent regarding a role for folate in the etiology of cervical dysplasia. Methylenetetrahydrofolate reductase (MTHFR) catalyzes the synthesis of 5-methyltetrahydrofolate, which is involved in the methylation of homocysteine to methionine. A common variant of this enzyme, resulting from a 677C-->T (Ala-->Val) substitution in the gene, has been shown to have reduced activity and is associated with mild hyperhomocysteinemia. A multiethnic case-control study was used to examine the association of dietary folate and MTHFR genotype with the odds ratios (ORs) for cervical dysplasia among women identified from several clinics on Oahu, Hawaii, between 1992 and 1996. We collected blood samples for DNA extraction, cervical smears for cytological diagnosis, exfoliated cervical cells for human papillomavirus (HPV) DNA testing, and personal interviews from 150 women with squamous intraepithelial lesions (SILs) and from 179 women with cytologically normal (Pap) smears. We found a positive, monotonic trend (P = 0.02) in the ORs for cervical SILs associated with the number of variant MTHFR T alleles, after multivariate adjustment. Women with the heterozygous CT genotype had twice the risk of cervical SILs [OR, 2.0; 95% confidence interval (CI), 1.1-3.7], and women with the homozygous TT genotype had almost three times the risk of SILs (OR, 2.9; 95% CI, 1.0-8.8) compared to women with the homozygous MTHFR CC genotype. The dietary intakes of folate, vitamin B(6), and vitamin B(12) were inversely related to the ORs for cervical SILs, after adjustment for HPV DNA and other confounders. The OR among women in the highest quartile compared with women in the lowest quartile of folate intake was 0.3 (95% CI, 0.1-0.7; P for trend = 0.002). Women with the variant T allele and folate intakes below the median were at significantly elevated risk of cervical SILs (OR, 5.0; 95% CI, 2.0-12.2) compared to women with CC alleles and folate intakes above the median. HPV infection was a strong risk factor for cervical dysplasia, particularly among women with the variant T allele (OR, 46.6; 95% CI, 15.9-136.2). All associations of MTHFR genotype with the ORs for cervical SILs were independent of other risk factors under study. These findings suggest that the MTHFR T allele and reduced dietary folate may increase the risk for cervical SILs.

Adult↗
PubMed2000

Effect of dietary patterns on serum homocysteine: results of a randomized, controlled feeding study.

BACKGROUND: Elevated blood levels of homocysteine are associated with an increased risk of atherosclerotic cardiovascular disease. Although numerous studies have assessed the impact of vitamin supplements on homocysteine, the effect of dietary patterns on homocysteine has not been well studied. METHODS AND RESULTS: During a 3-week run-in, 118 participants were fed a control diet, low in fruits, vegetables, and dairy products, with a fat content typical of US consumption. During an 8-week intervention phase, participants were then fed 1 of 3 randomly assigned diets: the control diet, a diet rich in fruits and vegetables but otherwise similar to control, or a combination diet rich in fruits, vegetables, and low-fat dairy products and reduced in saturated and total fat. Between the end of run-in and intervention periods, mean change in homocysteine was +0.46 micromol/L in the control diet, +0.21 micromol/L in the fruits and vegetables diet (P=0.47 compared with control), and -0.34 micromol/L in the combination diet (P=0.03 compared with control, P=0.12 compared with the fruits and vegetables diet). In multivariable regression models, change in homocysteine was significantly and inversely associated with change in serum folate (P=0.03) but not with change in serum vitamin B(12) (P=0.64) or pyridoxal 5' phosphate, the coenzyme form of vitamin B(6) (P=0.83). CONCLUSIONS: Modification of dietary patterns can have substantial effects on fasting levels of total serum homocysteine. These results provide additional insights into the mechanisms by which diet might influence the occurrence of atherosclerotic cardiovascular disease.

Adult↗
PubMed2000

Case-control study of plasma folate, homocysteine, vitamin B(12), and cysteine as markers of cervical dysplasia.

BACKGROUND: An association between B-complex vitamins and related compounds with the development of cervical neoplasia is biologically plausible, yet to the authors' knowledge epidemiologic investigations of these potential biomarkers are limited. METHODS: A case-control study was designed to examine the relation between plasma folate, homocysteine, vitamin B(12), and cysteine and early, premalignant changes in cervical epithelial cells among women identified from several clinics on Oahu, Hawaii, between 1992 and 1996. Fasting blood samples for plasma nutrient analysis, cervical smears for cytologic diagnosis, exfoliated cervical cells for human papillomavirus DNA testing by polymerase chain reaction, and a personal interview were obtained from 185 women with atypical squamous cells of undetermined significance (ASCUS) of the cervix, 147 women with squamous intraepithelial lesions (SIL), and 191 women with cytologically normal (Papanicolaou) smears. RESULTS: Age-adjusted and ethnicity-adjusted mean plasma concentrations of cysteine, but not other nutrients, were significantly lower among ASCUS cases (P = 0.006) and SIL cases (P = 0.01) than controls. A positive trend in the odds ratio for SIL but not ASCUS was found for increased plasma homocysteine concentrations, but this finding was not statistically significant. High plasma levels of cysteine were associated with a reduced risk of ASCUS (P value for trend = 0.006), with an odds ratio of 0.3 (95% confidence interval, 0.2-0.7) for the highest compared with the lowest quartile of cysteine concentration. A weak, negative relation between cysteine and the development of low grade SIL (LSIL) but not high grade SIL (HSIL) also was found. CONCLUSIONS: The results of the current study do not support the hypothesis that folate, homocysteine, or B(12) are markers of cervical dysplasia risk. A possible inverse association between plasma cysteine concentrations and the risk of cervical dysplasia needs further study.

Adult↗
PubMed2000

Total homocysteine and estrogen status indicators in the Third National Health and Nutrition Examination Survey.

The possibility that estrogen status modulates total homocysteine concentration, a risk factor for vascular occlusion, was examined in a representative sample of the US population, the Third National Health and Nutrition Examination Survey (phase 2), 1991-1994. The geometric mean serum total homocysteine concentration was compared among population subgroups differing on inferred estrogen status, after adjusting for potential confounding by age, race-ethnicity, smoking, and the serum concentration of creatinine, folate, and vitamin B-12. Premenopausal women aged 17-54 years had a lower mean serum total homocysteine concentration (8.1 micromol/liter, 95% confidence interval (CI): 7.9, 8.2) than men in the same age range (8.9 micromol/liter, 95% CI: 8.6, 9.3). In the age range 17-44 years, pregnant women (6.0 micromol/liter, 95% CI: 5.4, 6.8), but not oral contraceptive users (7.9 micromol/liter, 95% CI: 7.6, 8.2), had a lower mean serum total homocysteine concentration than nonpregnant, non-oral-contraceptive-using women (8.1 micromol/liter, 95% CI: 7.9, 8.2). The mean serum total homocysteine concentration of estrogen-using women aged > or = 55 years (9.5 micromol/liter, 95% CI: 8.9, 10.1) was significantly decreased relative to nonestrogen users (10.7 micromol/liter, 95% CI: 10.3, 11.1) and men (10.4 micromol/liter, 95% CI: 9.8, 11.0) in the same age range. These findings suggest that higher estrogen status is associated with a decreased mean serum total homocysteine concentration, independent of nutritional status and muscle mass, and that estrogen may explain the previously reported male-female difference in total homocysteine concentration.

Adolescent↗
PubMed2000

Controlled comparison of L-5-methyltetrahydrofolate versus folic acid for the treatment of hyperhomocysteinemia in hemodialysis patients.

BACKGROUND: The hyperhomocysteinemia regularly found in hemodialysis patients is largely refractory to combined oral B-vitamin supplementation featuring supraphysiological doses of folic acid. We evaluated whether a high-dose L-5-methyltetrahydrofolate-based regimen provided improved total homocysteine (tHcy)-lowering efficacy in chronic hemodialysis patients. METHODS AND RESULTS: We block-randomized 50 chronic, stable hemodialysis patients on the basis of their screening predialysis tHcy levels, sex, and dialysis center into 2 groups of 25 subjects treated for 12 weeks with oral folic acid at 15 mg/d (FA group) or an equimolar amount (17 mg/d) of oral L-5-methyltetrahydrofolate (MTHF group). All 50 subjects also received 50 mg/d of oral vitamin B(6) and 1.0 mg/d of oral vitamin B(12). The mean percent reductions (+/-95% CIs) in predialysis tHcy were not significantly different: MTHF, 17.0% (12.0% to 22.0%); FA, 14.8% (9.6% to 20.1%); P=0.444 by matched ANCOVA adjusted for pretreatment tHcy. Final on-treatment values (mean with 95% CI) were MTHF, 20.0 micromol/L (18.8 to 21.2 micromol/L); FA, 19.5 micromol/L (18.3 to 20.7 micromol/L). Moreover, neither treatment resulted in "normalization" of tHcy levels (ie, final on-treatment values <12 micromol/L) among a significantly different or clinically meaningful number of patients: MTHF, 2 of 25 (8%); FA, 0 of 25 (0%); Fisher's exact test of between-groups difference, P=0.490. CONCLUSIONS: Relative to high-dose folic acid, high-dose oral L-5-methyltetrahydrofolate-based supplementation does not afford improved tHcy-lowering efficacy in hemodialysis patients. The preponderance of hemodialysis patients (ie, >90%) exhibit mild hyperhomocysteinemia refractory to treatment with either regimen. This treatment refractoriness is not related to defects in folate absorption or circulating plasma and tissue distribution.

Administration, Oral↗
PubMed2000

Treatment of mild hyperhomocysteinemia in renal transplant recipients versus hemodialysis patients.

BACKGROUND: Mild hyperhomocysteinemia is common among maintenance hemodialysis (HD) patients and renal transplant recipients (RTR) and may contribute to the excess incidence of arteriosclerotic outcomes experienced by both patient groups. Relative to their RTR counterparts, the hyperhomocysteinemia of HD patients seems to be considerably more refractory to treatment with high-dose folic acid (FA)-based B-vitamin supplementation regimens, although controlled comparison data are lacking. METHODS: We compared the relative responsiveness of (n=10) RTR and (n=39) HD patients with equivalent baseline total homocysteine (tHcy) levels (i.e., RTR range=14.2-23.6 micromol/L; HD range=14.4-24.9 micromol/L) to 12 weeks of tHcy-lowering treatment. The RTR received 2.4 mg/day of FA, 50.0 mg/day of vitamin B6, and 0.4 mg/day of vitamin B12, while the HD patients received 15 mg/day of FA or an equimolar amount (17 mg/day) of the reduced folate, L-5-methyltetrahydrofolate, in addition to 50.0 mg/day of vitamin B6, and 1.0 mg/day of vitamin B12. RESULTS: The mean percent (%) reductions (+/-95% confidence interval) in tHcy were: RTR=28.1% (16.2-40.0%); HD=12.1% (6.6-17.7%), P=0.027 for comparison of between-groups differences by analysis of covariance adjusted for baseline tHcy levels. Moreover, (50.0%) of 10 of the RTR versus only (5.1%) of 39 of the HD patients had final on-treatment tHcy levels <12 micromol/L; P=0.002 for comparison of between-groups differences by Fisher's exact test. CONCLUSION: Relative to RTR with comparable baseline tHcy levels, the mild hyperhomocysteinemia of maintenance HD patients is much more refractory to tHcy-lowering B-vitamin treatment regimens featuring supraphysiological amounts of FA or the reduced folate, L-5-methyltetrahydrofolate. Accordingly, RTR are a preferable target population for controlled clinical trials testing the hypothesis that tHcy-lowering B-vitamin intervention may reduce arteriosclerotic cardiovascular disease event rates in patients with chronic renal disease.

Adult↗
PubMed2000

Plasma total homocysteine levels in subjects with hyperinsulinemia.

OBJECTIVES: Hyperhomocysteinemia as well as insulin resistance are considered to be risk factors for the development of coronary artery disease. This study was aimed at determining whether any relationship between plasma insulin and glucose levels and total plasma homocysteine (tHcy) concentrations exists in a population based survey performed 10 years apart. DESIGN AND SETTING: A cross-sectional study was undertaken during the years 1986-87 to examine risk factors for diabetes and for coronary artery disease (CAD) in the Jewish population of Jerusalem. Ten years later two groups of individuals were invited for re-examination. SUBJECTS: Two groups of individuals were examined: the first one consisted of nondiabetic subjects (n = 86), who had hyperinsulinemia 10 years previously (at the first visit), the second group consisted of normoinsulinemic nondiabetic individuals (n = 265) who had initially normal glucose and insulin levels. MAIN OUTCOME MEASURES: Metabolic, biochemical and anthropomorphic features were determined. Fasting and post load glucose, as well as insulin concentrations on fasting and 2 h post glucose load were measured at the first and second visits. Plasma tHcy and folic acid were determined only at the second visit. RESULTS: The results demonstrated a significant negative correlation between plasma tHcy levels and insulin levels at the second visit. No difference was found in folic acid levels between these two groups. CONCLUSIONS: In general, hyperinsulinemia and hyperhomocysteinemia are both related to an increased incidence of CAD. In our population most of the subjects examined had tHcy levels within the normal range and only a few demonstrated very high levels. However, negative association between insulin levels and tHcy concentrations was found. Possible explanations for this finding are discussed.

Adult↗
PubMed2000

Determinants of plasma total homocysteine levels in Korean chronic renal transplant recipients.

OBJECTIVE: Study the determinants of plasma total homocysteine (tHcy) levels, such as fasting levels of serum creatinine (SCr), albumin, plasma tHcy, folate, B(12), and pyridoxal-5'-phosphate (PLP) in chronic Korean renal transplant recipients (RTR). DESIGN: Cross-sectional study. SETTING: Nephrology & Transplant Service in Catholic University Kangnam St. Mary's Hospital, Seoul, Korea. PARTICIPANTS: Ninety-one chronic Korean RTR with stable renal function who were > or =6 months post-transplant. MEASURES: Used medical record review and anthropometric measurements, and overnight (10 to 14 hours) fasting blood samples were measured for plasma tHcy, PLP, folate, B(12), SCr, and albumin. RESULTS: The prevalence of hyperhomocysteinemia (tHcy > 12 micromol/L) was 56%, and 47% had low plasma folate levels (<3 ng/mL). Linear modeling with analysis of covariance adjusted for age, sex, albumin, SCr, and plasma B-vitamin status revealed that only SCr (standard regression coefficient R = +0.663, P<.001), plasma folate (R = -0.276, P =.001), and B(12) (R = -0.149, marginal, P =.08) were independent determinants of fasting tHcy levels in this patient population. CONCLUSION: Renal function is the major independent determinant of the fasting tHcy levels among chronic, stable Korean RTR, and that B-vitamin status plays a secondary role among such patients.

Adult↗
PubMed2000

Plasma vitamin B-12 concentrations relate to intake source in the Framingham Offspring study.

BACKGROUND: Low vitamin B-12 status is prevalent among the elderly, but few studies have examined the association between vitamin B-12 status and intake. OBJECTIVE: We hypothesized that vitamin B-12 concentrations vary according to intake source. DESIGN: Plasma concentrations and dietary intakes were assessed cross-sectionally for 2999 subjects in the Framingham Offspring Study. The prevalence of vitamin B-12 concentrations <148, 185, and 258 pmol/L was examined by age group (26-49, 50-64, and 65-83 y), supplement use, and the following food intake sources: fortified breakfast cereal, dairy products, and meat. RESULTS: Thirty-nine percent of subjects had plasma vitamin B-12 concentrations <258 pmol/L, 17% had concentrations <185 pmol/L, and 9% had concentrations <148 pmol/L, with little difference between age groups. Supplement users were significantly less likely than non-supplement-users to have concentrations <185 pmol/L (8% compared with 20%, respectively). Among non-supplement-users, there were significant differences between those who consumed fortified cereal >4 times/wk (12%) and those who consumed no fortified cereal (23%) and between those in the highest and those in the lowest tertile of dairy intake (13% compared with 24%, respectively), but no significant differences by meat tertile. Regression of plasma vitamin B-12 on log of intake, by source, yielded significant slopes for each contributor adjusted for the others. For the total group, b = 40.6 for vitamin B-12 from vitamin supplements. Among non-supplement-users, b = 56.4 for dairy products, 35.2 for cereal, and 16.7 for meat. Only the meat slope differed significantly from the others. CONCLUSIONS: In contrast with previous reports, plasma vitamin B-12 concentrations were associated with vitamin B-12 intake. Use of supplements, fortified cereal, and milk appears to protect against lower concentrations. Further research is needed to investigate possible differences in bioavailability.

Adult↗
PubMed2000

B vitamins, homocysteine, and neurocognitive function in the elderly.

Evidence of the importance of the B vitamins folic acid, vitamin B-12, and vitamin B-6 for the well-being and normal function of the brain derives from data showing neurologic and psychologic dysfunction in vitamin deficiency states and in cases of congenital defects of one-carbon metabolism. The status of these vitamins is frequently inadequate in the elderly and recent studies have shown associations between loss of cognitive function or Alzheimer disease and inadequate B vitamin status. The question that arises is whether these B vitamin inadequacies contribute to such brain malfunctions or result from aging and disease. From a theoretical standpoint, these inadequacies could give rise to impairment of methylation reactions that are crucial to the health of brain tissue. In addition or perhaps instead, these inadequacies could result in hyperhomocysteinemia, a recently identified risk factor for occlusive vascular disease, stroke, and thrombosis, any of which may result in brain ischemia. Advances in the understanding of this putative relation between inadequate vitamin status and loss of cognitive function in the elderly are likely to be slow and may depend on the outcomes of both prospective studies and longitudinal studies in which nutritional intervention is provided before cognitive decline occurs.

Aging↗
PubMed2000

Analysis of factors influencing the comparison of homocysteine values between the Third National Health and Nutrition Examination Survey (NHANES) and NHANES 1999+.

Two important changes occurred in the time between the Third National Health and Nutrition Examination Survey (NHANES III) (1991-1994) and the later survey (NHANES 1999+) regarding total homocysteine (tHcy), i.e., a change in matrix from serum to plasma and a change in analytical methods. The goals of this study were to determine the magnitude of potential differences between plasma and serum with regard to tHcy concentrations, and between the two analytical methods used in these surveys. Optimally prepared plasma, serum allowed to clot for 30 and 60 min at room temperature and serum allowed to clot for 30 and 60 min and subjected to four freeze-thaw cycles, prepared from blood samples collected from 30 healthy people, were analyzed by both methods. Serum samples had significantly higher tHcy concentrations than plasma samples, and the difference increased with longer clotting time. Freeze-thaw cycles had little or no effect on the variability or bias in the serum sample results. The tHcy results produced by the two analytical methods were significantly different, but consistent across sample types. On average, the results of the method used in NHANES III were lower by 0.64 micromol/L; however, the relative bias varied with tHcy concentration. The tHcy results determined in surplus serum from NHANES III overestimated tHcy concentrations by approximately 10% compared with optimally prepared plasma. The average method bias was 6% between the two analytical methods. On the basis of changes in matrix and methodology, direct comparison of tHcy results between the two surveys is inappropriate.

Adult↗