Population references for plasma total homocysteine concentrations for U.S. children and adolescents in the post-folic acid fortification era

Folate intake is inversely related to circulating total homocysteine (tHcy) concentrations. Elevated tHcy is a risk factor for vascular diseases. The objectives of this study were to present plasma tHcy distributions and investigate the association between tHcy and sex, age, and race-ethnicity in U.S. children and adolescents (3264 boys and 3197 girls) using data from the National Health and Nutrition Examination Surveys, 1999-2000 and 2001-2002 conducted in the post-folic acid fortification era. Plasma tHcy was higher in boys than in girls (P < 0.0001), and higher in older children (16-18 y old) than in younger children (3-15 y old) (P < 0.0001). The difference in plasma tHcy between boys and girls was greater in the 16- to 18-y-old group than in any other age group studied (P < 0.05). Age-adjusted plasma tHcy concentrations were approximately 6.8, approximately 10.5, and approximately 8.8% higher in boys than in girls in non-Hispanic White (NHW), non-Hispanic Black (NHB), and Mexican American/Hispanic (MA/H) children, respectively. Sex- and age-adjusted plasma tHcy concentrations (geometric means +/- SE) were 5.04 +/- 0.05, 5.01 +/- 0.06, and 4.99 +/- 0.06 micromol/L in the NHW, NHB, and MA/H groups, respectively. Race-ethnicity was not related to plasma tHcy in age-adjusted analysis for boys (P < 0.77) and girls (P < 0.26), and in sex- and age-adjusted analysis (P < 0.38) for all children. The plasma tHcy concentrations begin to rise between ages 8 and 11 y, and the age-related increase is greater in boys than in girls.     

Biochemical indicators of B vitamin status in the US population after folic acid fortification: results from the National Health and Nutrition Examination Survey 1999-2000

BACKGROUND: Mandatory folic acid fortification of cereal-grain products was introduced in the United States in 1998 to decrease the risk that women will have children with neural tube defects. OBJECTIVE: The objective was to determine the effect of folic acid fortification on concentrations of serum and red blood cell (RBC) folate, serum vitamin B-12, and plasma total homocysteine (tHcy) and methylmalonic acid (MMA) in the US population. DESIGN: Blood was collected from a nationally representative sample of approximately 7300 participants aged > or = 3 y in the National Health and Nutrition Examination Survey (NHANES) during 1999-2000 and was analyzed for these B vitamin-status indicators. The results were compared with findings from the prefortification survey NHANES III (1988-1994). RESULTS: The reference ranges (5th-95th percentiles) were 13.1-74.3 nmol/L for serum folate, 347-1167 nmol/L for RBC folate, and 179-738 pmol/L for serum vitamin B-12. For plasma tHcy and MMA, the reference ranges for serum vitamin B-12-replete participants with normal serum creatinine concentrations were 3.2-10.7 mumol/L and 60-210 nmol/L, respectively. The prevalence of low serum folate concentrations (<6.8 nmol/L) decreased from 16% before to 0.5% after fortification. In elderly persons, the prevalence of high serum folate concentrations (>45.3 nmol/L) increased from 7% before to 38% after fortification; 3% had marginally low serum vitamin B-12 concentrations (<148 pmol/L) and 7% had elevated plasma MMA concentrations (>370 nmol/L). Seventy-eight percent of the US population had plasma tHcy concentrations <9 micromol/L. CONCLUSIONS: Every segment of the US population appears to benefit from folic acid fortification. Continued monitoring of B vitamin concentrations in the US population is warranted.     

Demographic,health, lifestyle,and blood vitamin determinants of serum total homocysteine concentrations in the third National Health and Nutrition Examination Survey, 1988-1994

BACKGROUND: Elevated serum total homocysteine (tHcy) is an independent risk factor for vascular diseases. OBJECTIVE: Associations between serum tHcy and demographics, health and lifestyle factors, and blood vitamin concentrations were investigated. DESIGN: Data from the third National Health and Nutrition Examination Survey, 1988-1994 were used to examine associations in men (n = 2965) and women (n = 3580) between tHcy and age, sex, race-ethnicity, body mass index, systolic and diastolic blood pressures, alcohol consumption, supplement use, red blood cell (RBC) folate, and serum creatinine, folate, vitamin B-12, and cotinine (a measure of cigarette smoking). RESULTS: The unadjusted mean tHcy was 21.5% ( approximately 1.9 micro mol/L) higher in men than in women, 11.8% ( approximately 1.1 micro mol/L) higher in non-Hispanic whites than in Mexican Americans, 42% ( approximately 3.7 micro mol/L) higher in persons aged > or = 70 y than in persons aged < 30 y, and 10.9% ( approximately 1.0 micro mol/L) higher in supplement nonusers than in supplement users. The tHcy concentration was negatively associated with serum folate (P < 0.0001 for trend), RBC folate (P < 0.0001 for trend), and serum vitamin B-12 (P < 0.0036 for trend) and was positively associated with alcohol consumption (P < 0.0001 for trend), serum cotinine (P < 0.0001 for trend), and systolic blood pressure (P < 0.0001 for trend). Consumption of hard liquor (but not of beer or wine) was positively associated with tHcy concentration (P < 0.0001 for trend). CONCLUSIONS: In this population-based study, the significant predictors of tHcy concentration were sex, age, race-ethnicity, serum creatinine, systolic blood pressure, body mass index, hard-liquor consumption, smoking, supplement use, serum folate, RBC folate, and serum vitamin B-12.     

Serum total homocysteine concentrations in children and adolescents: results from the third National Health and Nutrition Examination Survey (NHANES III)

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 implications of elevated levels in children are not known. The goals of this study were to describe the distribution of tHcy among a representative sample of children and adolescents in the United States, and to test for differences in tHcy among sex, age and race-ethnicity categories. Using surplus sera from Phase 2 of the third National Health and Nutrition Examination Survey, we measured tHcy for a nationally representative sample of 942 boys and 1085 girls aged 4-19 y. The age-adjusted geometric mean tHcy concentrations were 6.2 and 5.8 micro mol/L in non-Hispanic Caucasian boys and girls, 6.4 and 6.1 micro mol/L in non-Hispanic African-American boys and girls, and 6.4 and 5.5 micro mol/L in Mexican American boys and girls, respectively. A significant interaction between age and sex (P < 0.01) reflected the divergence of tHcy concentrations at about age 10 y, with higher concentrations in boys than in girls throughout adolescence. These first data on homocysteine concentrations in a nationally representative sample of American youth suggest that sexual dimorphism of tHcy concentrations occurs earlier, at approximately 10 y of age, than previously reported on the basis of smaller nonrepresentative samples. Improved understanding of the determinants of levels during growth and development may provide important clues to the etiology of adult disease.     

Trends in serum folate, RBC folate, and circulating total homocysteine concentrations in the United States: analysis of data from National Health and Nutrition Examination Surveys, 1988-1994, 1999-2000, and 2001-2002

Folate intakes increased dramatically after folic acid fortification. We investigated the changes in serum folate, RBC folate, and total homocysteine (tHcy) concentrations utilizing data from National Health and Nutrition Examination Surveys (NHANES) 1988-2002. NHANES 1988-2002 were based on a stratified, multistage, probability sampling design conducted among civilian U.S. residents. The current study included 17,144, 17,213, and 11,415 measurements for serum folate, RBC folate, and tHcy, respectively. Overall, geometric mean serum folate concentrations were 149.6 and 129.8% higher in 1999-2000 and 2001-2002, respectively, than in 1988-1994 (P < 0.0001). Sex-, age-, and race-ethnicity-adjusted serum folate was significantly lower in 2001-2002 than in 1999-2000 (10.4%, P < 0.0002). The prevalence of low serum folate decreased from 18.4% in 1988-1994 to 0.8% in 1999-2000 and to 0.2% in 2001-2002 (P < 0.0001). RBC folate increased from 391 nmol/L in 1988-1994 to 618 nmol/L in 1999-2000, and to 611 nmol/L in 2001-2002. Consequently, the prevalence of low RBC folate decreased from 45.8% in 1988-1994 to 7.3% in 1999-2000 and to 7.1% in 2001-2002 (P < 0.0001). Although, RBC folate status improved after folic acid fortification in all race-ethnicities, the prevalence of low RBC folate ( approximately 20.5%) continues to be high in non-Hispanic blacks. Age-, sex-, and race-ethnicity-adjusted tHcy declined from 9.5 micromol/L in 1988-1994 to 7.6 mumol/L in 1999-2000 and to 7.9 micromol/L in 2001-2002. Although folic acid fortification contributed to significant improvement in folate status, serum folate concentrations have declined recently. This may be attributable to lower folic acid intakes.     

Homocysteine and cognitive function in healthy elderly community dwellers in Italy

BACKGROUND: Elevated plasma total homocysteine (tHcy) concentrations are common in the elderly and have been suggested to be a risk factor for dementia. OBJECTIVE: In an elderly population, we examined the relation between plasma tHcy and scores on the Mini-Mental State Examination (MMSE), a commonly used screening measure of cognitive impairment in general practice. DESIGN: Fasting plasma tHcy concentrations were measured in 650 healthy, cognitively normal Italian community dwellers aged > or = 65 y (x +/- SD: 72.8 +/- 6.0 y). Socioeconomic status; serum folate, vitamin B-12, and creatinine; other potential dietary and lifestyle determinants of tHcy; and conventional vascular disease risk factors were also assessed. RESULTS: Subjects with MMSE scores of 26-28 had higher plasma tHcy concentrations (12.7 micromol/L; range: 12.2-13.2 micromol/L) than did those with scores > 28 (11.9 micromol/L; 11.4-12.3 micromol/L; P < 0.01). Subjects with scores of 24-25 had higher plasma tHcy concentrations (14.5 micro mol/L; 13.5-15.6 micromol/L) than did subjects with scores of 26-28 (P < 0.01) or > 28 (P < 0.001). The risk of hyperhomocysteinemia (plasma tHcy > 15 micromol/L) was higher in subjects with scores of 24-25 (odds ratio: 3.81; 95% CI: 1.9, 7.5) or 26-28 (odds ratio: 1.96; 95% CI: 1.3, 3.0) than in those with scores > 28. The results did not change after adjustment for conventional vascular risk factors and for age, medical, dietary, and lifestyle determinants of plasma tHcy. CONCLUSION: Elevated plasma tHcy has an independent, graded association with concurrent cognitive impairment as measured with the MMSE in healthy elderly community dwellers.     

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.     

Race-ethnicity differences in folic acid intake in women of childbearing age in the United States after folic acid fortification: findings from the National Health and Nutrition Examination Survey, 2001-2002

BACKGROUND: Neural tube defects are serious birth defects of the brain and spinal cord. Up to 70% of neural tube defects can be prevented by the consumption of folic acid by women before and early during pregnancy. OBJECTIVE: The objective was to examine folic acid intake in women of childbearing age in the United States. DESIGN: We analyzed nutrient intake data reported by 1685 nonpregnant women aged 15-49 y who participated in the National Health and Nutritional Examination Survey, 2001-2002. RESULTS: The adjusted geometric mean consumption of folic acid from fortified foods was 128 microg/d (95% CI: 123, 134 microg/d) in nonpregnant women. Eight percent (95% CI: 5.8%, 11.0%) of nonpregnant women reported consuming >or=400 microg folic acid/d from fortified foods. This proportion was lower among non-Hispanic black women (5.0%) than among non-Hispanic white (8.9%) or Hispanic (6.8%) women. A smaller percentage of non-Hispanic black (19.1%) and Hispanic (21%) women than of non-Hispanic white women (40.5%) consumed >or=400 microg folic acid from supplements, fortified foods, or both, in addition to food folate, as recommended by the Institute of Medicine to reduce the frequency of neural tube defects. CONCLUSIONS: Most nonpregnant women of childbearing age in the United States reported consuming less than the recommended amount of folic acid. The proportion with low daily folic acid intake was significantly higher in non-Hispanic black and Hispanic women than in non-Hispanic white women. At the present level of folic acid fortification, most women need to take a folic acid-containing dietary supplement to achieve the Institute of Medicine recommendation.     

Serum total homocysteine concentrations in adolescent and adult Americans: results from the third National Health and Nutrition Examination Survey

BACKGROUND: The elevation of circulating total homocysteine concentrations in a fasting state is associated with an increased risk of occlusive vascular disease. OBJECTIVE: The primary goals of this study were to describe the distribution of serum total homocysteine concentrations in the United States and to test for differences in homocysteine concentrations among sex, age, and race-ethnicity categories. DESIGN: Using surplus sera from phase 2 of the third National Health and Nutrition Examination Survey, we measured serum total homocysteine concentrations for a nationally representative sample of 3766 males and 4819 females aged > or = 12 y. RESULTS: Age-adjusted geometric mean total homocysteine concentrations were 9.6 and 7.9 mmol/L in non-Hispanic white males and females, 9.8 and 8.2 mmol/L in non-Hispanic black males and females, and 9.4 and 7.4 mmol/L in Mexican American males and females, respectively. Age-adjusted geometric mean total homocysteine concentrations were significantly lower in females than in males in each race-ethnicity group (P < 0.01) and were significantly lower in Mexican American females than in non-Hispanic white and non-Hispanic black females (P < 0.01). There was a significant age-sex interaction (P < 0.01), reflecting the fact that homocysteine concentrations in females tended to diverge from those in males at younger ages and converge with those in males at older ages. CONCLUSIONS: The first data on homocysteine concentrations in a nationally representative sample of Americans confirm the age and sex differences reported previously in nonrepresentative samples. These data also indicate that differences between Mexican American and non-Hispanic females may influence circulating homocysteine concentrations.     

Dietary strategies for lowering homocysteine concentrations

BACKGROUND: Elevated plasma total homocysteine (tHcy) concentrations are associated with increased risk of vascular disease, and there is a strong inverse association between dietary and blood folate and blood tHcy concentrations. Increased folate consumption may lower the risk of tHcy-mediated cardiovascular disease. OBJECTIVES: The objective was to determine the most appropriate means of increasing dietary folate to reduce plasma tHcy. DESIGN: Sixty-five free-living subjects aged 36-71 y with tHcy concentrations >/=9 micromol/L participated in a randomized, controlled trial to compare 3 approaches for increasing dietary folate to approximately 600 microg/d: folic acid supplementation, consumption of folic acid-fortified breakfast cereals, and increased consumption of folate-rich foods. RESULTS: An intake of 437 microg folic acid/d from supplements resulted in a 27-nmol/L increase in serum folate and a 21% reduction in tHcy, relative to the change in a control group. In subjects who consumed folic acid-fortified breakfast cereal, folate intake increased by an average of 298 microg, serum folate increased by 21 nmol/L, and tHcy concentrations decreased by 24%. Increased intakes of folate-rich foods resulted in a 418-microg increase in dietary folate, a 7-nmol/L increase in serum folate, and a 9% reduction in tHcy concentrations. The decrease in tHcy was negatively correlated (r = -0.66) with the increase in serum folate. CONCLUSIONS: Daily consumption of folic acid-fortified breakfast cereals and the use of folic acid supplements appear to be the most effective means of reducing tHcy concentrations. The reduction in tHcy was significantly negatively correlated with the increase in serum folate, which may be a useful marker for measuring dietary change.     

Homocysteine concentrations in adults with trisomy 21: effect of B vitamins and genetic polymorphisms

BACKGROUND: The effects of supplementation with B vitamins and of common polymorphisms in genes involved in homocysteine metabolism on plasma total homocysteine (tHcy) concentrations in trisomy 21 are unknown. OBJECTIVES: We aimed to determine the effects of orally administered folic acid and of folic acid combined with vitamin B-12, vitamin B-6, or both on tHcy in adults with trisomy 21. The study was also intended to analyze the possible influence of gene polymorphisms. DESIGN: One hundred sixty adults with trisomy 21 and 160 healthy, unrelated subjects aged 26 +/- 4 y were included. Plasma tHcy, red blood cell folate, serum folate, and vitamin B-12 were measured. Genotyping for the common methylenetetrahydrofolate reductase (MTHFR) 677C-->T, MTHFR 1298A-->C, cystathionine beta-synthase 844Ins68, methionine synthase 2756A-->C, methionine synthase reductase 66A-->G, and reduced folate carrier 80G-->A polymorphisms was carried out. RESULTS: The mean tHcy concentration (9.8 +/- 0.7 micromol/L) of cases who did not use vitamins was not significantly different from that of controls (9.4 +/- 0.3 micromol/L). Plasma tHcy concentrations (7.6 +/- 0.3 mmol/L) in cases who used folic acid were significantly lower than in cases who did not. Folic acid combined with vitamin B-12 did not significantly change tHcy concentrations compared with those in cases who used only folic acid. Folic acid combined with vitamins B-6 and B-12 significantly lowered tHcy (6.5 +/- 0.5 micromol/L). The difference in tHcy according to MTHFR genotype was not significant. However, tHcy concentrations were slightly higher in TT homozygotes among the controls but not among the cases. CONCLUSION: This study provides information on the relation between several polymorphisms in genes involved in homocysteine and folate metabolism in adults with trisomy 21.     

Low-dose vitamin B-6 effectively lowers fasting plasma homocysteine in healthy elderly persons who are folate and riboflavin replete

BACKGROUND: Current data suggest that physiologic doses of vitamin B-6 have no significant homocysteine-lowering effect. It is possible that an effect of vitamin B-6 was missed in previous trials because of a much greater effect of folic acid, vitamin B-12, or both. OBJECTIVE: The aim of this study was to investigate the effect of low-dose vitamin B-6 supplementation on fasting total homocysteine (tHcy) concentrations in healthy elderly persons who were made replete with folate and riboflavin. DESIGN: Twenty-two healthy elderly persons aged 63-80 y were supplemented with a low dose of vitamin B-6 (1.6 mg/d) for 12 wk in a randomized, double-blind, placebo-controlled trial after repletion with folic acid (400 microg/d for 6 wk) and riboflavin (1.6 mg/d for 18 wk); none of the subjects had a vitamin B-12 deficiency. RESULTS: Folic acid supplementation lowered fasting tHcy by 19.6% (P < 0.001). After folic acid supplementation, baseline tHcy concentrations ranged from 6.22 to 23.52 micromol/L and 10 subjects had suboptimal vitamin B-6 status (plasma pyridoxal-P < 20 nmol/L). Two-way analysis of variance showed that the significant improvement in vitamin B-6 status in response to vitamin B-6 supplementation (on the basis of both pyridoxal-P: and the erythrocyte aspartate aminotransferase activation coefficient) was reflected in a significant reduction in plasma tHcy of 7.5%. CONCLUSIONS: Low-dose vitamin B-6 effectively lowers fasting plasma tHcy in healthy subjects who are both folate and riboflavin replete. This suggests that any program aimed at the treatment or prevention of hyperhomocysteinemia should include vitamin B-6 supplementation.     

Iron status: prevalence of impairment in three Hispanic groups in the United States

Little is known about the iron status of Hispanic groups in the United States. Data from the Hispanic Health and Nutrition Examination Survey were used to estimate the prevalence of impaired Fe status for persons aged 5-74 y from three Hispanic groups: Mexican Americans (MAs), Cubans, and Puerto Ricans; prevalences were also calculated for non-Hispanic whites (NHWs) and non-Hispanic blacks (NHBs) using data from the second National Health and Nutrition Examination survey. A three-variable model called the MCV model was used to assess impaired Fe status. Prevalences based on the MCV model did not differ between Hispanic groups. Differences between Hispanics and non-Hispanics occurred only among 20-44-y-old females, where MAs had a higher prevalence than NHWs or NHBs. With this exception, these Hispanic groups do not appear to be at greater risk of impaired Fe status than non-Hispanics.     

Assessment of three levels of folic acid on serum folate and plasma homocysteine: a randomised placebo-controlled double-blind dietary intervention trial

OBJECTIVE: To determine the minimum effective dose of folic acid required to appreciably increase serum folate and to produce a significant reduction in plasma total homocysteine (tHcy). DESIGN: Double-blind, randomised placebo-controlled intervention trial. SETTING: Community-based project in a New Zealand city. SUBJECTS: Seventy free living men and women with tHcy> or =10 micromol/l. Mean age (range) was 58 (29-90) y. INTERVENTIONS: Daily consumption over 4 weeks of 20 g breakfast cereal either unfortified (placebo) or fortified with 100, 200 or 300 microg folic acid. Dietary intake was determined by weighed diet records and consumption of commercially fortified products was avoided. MAIN OUTCOME MEASURES: Plasma tHcy and serum folate concentrations. RESULTS: Average serum folate concentrations (95% CI) increased significantly in the treatment groups relative to the control group by 28(9-51)%, 60(37-87)% and 79(51-114)% for supplementation with 100, 200 and 300 microg folic acid, respectively. A reduction in tHcy was observed, being 16(8-22)%, 12(4-18)% and 17(9-24)% in the three treatment groups, respectively. CONCLUSIONS: A regular intake of as little as 100 microg folic acid per day was sufficient to lower tHcy in persons at the upper end of the normal range for tHcy. Low-level fortification may also be appropriate for lowering the risk of neural tube defects given that, when aggregated from all sources, the total intake of folic acid may be sufficiently high to adequately improve the folate status of young women.     

Plasma homocysteine concentration in a Belgian school-age population

BACKGROUND: Total plasma homocysteine (tHcy) is an independent risk factor for cardiovascular disease in adults. Data for children and adolescents are lacking. OBJECTIVE: The aim of this study was to provide a reference range for tHcy and to explore the relation between tHcy and nutritional indexes in a Belgian pediatric population. DESIGN: tHcy, folate, and vitamin B-12 were measured in 647 healthy children (353 girls and 294 boys) aged 5-19 y. RESULTS: The tHcy distribution was, as in adults, skewed to the right [geometric mean (-1 SD, +1 SD): 7.41 micromol/L (5.51, 9.96)]. Concentrations were lowest in younger children and increased with age. After the tHcy distribution was examined according to age, 3 age ranges were distinguished: 5-9 y [6.21 micromol/L (5.14, 7.50)], 10-14 y [7.09 micromol/L (5.69, 8.84)], and 15-19 y [8.84 micromol/L (6.36, 12.29)]. We observed no significant differences in tHcy values between girls and boys in children aged < 15 y; in postpubertal children, however, concentrations were higher in boys than in girls. In the 3 age groups, folate was inversely correlated with tHcy; the negative relation between tHcy and vitamin B-12 was less strong. Familial cardiovascular disease was more frequent in children who had hyperhomocysteinemia. CONCLUSIONS: These observations suggest that in children, as in adults, genetic, nutritional, and endocrine factors are determinants of the metabolism of homocysteine. The significance of tHcy values in childhood and young adulthood in terms of predicting cardiovascular risk in adulthood should be investigated.     

Association between B vitamin intake and plasma homocysteine concentration in the general Dutch population aged 20-65 y

BACKGROUND: An elevated plasma total homocysteine (tHcy) concentration is associated with an increased risk of cardiovascular diseases. Folate, riboflavin, vitamin B-6, and vitamin B-12 are essential in homocysteine metabolism. OBJECTIVE: The objective was to describe the association between dietary intakes of folate, riboflavin, vitamin B-6, and vitamin B-12 and the nonfasting plasma tHcy concentration. DESIGN: A random sample of 2435 men and women aged 20-65 y from a population-based Dutch cohort examined in 1993-1996 was analyzed cross-sectionally. RESULTS: Univariately, intakes of all B vitamins were inversely related to the plasma tHcy concentration. In multivariate models, only folate intake remained inversely associated with the plasma tHcy concentration. Mean plasma tHcy concentrations (adjusted for intakes of riboflavin, vitamin B-6, vitamin B-12, and methionine and for age, smoking, and alcohol consumption) in men with low (first quintile: 161 microg/d) and high (fifth quintile: 254 microg/d) folate intakes were 15.4 and 13.2 micromol/L, respectively; in women, plasma tHcy concentrations were 13.7 and 12.4 micromol/L at folate intakes of 160 and 262 microg/d, respectively. In men, the difference in the mean plasma tHcy concentration between men with low and high folate intakes was greater in smokers than in nonsmokers (2.8 compared with 1.6 micromol/L) and greater in nondrinkers than in drinkers of >2 alcoholic drinks/d (3.5 compared with 1.4 micromol/L). In women, the association between folate intake and plasma tHcy was not modified by smoking or alcohol consumption. CONCLUSIONS: In this Dutch population, folate was the only B vitamin independently inversely associated with the plasma tHcy concentration. Changing dietary habits may substantially influence the plasma tHcy concentration in the general population.     

Serum retinol distributions in residents of the United States: third National Health and Nutrition Examination Survey, 1988-1994

BACKGROUND: Inadequate vitamin A status has been a potential nutritional problem for some segments of the US population, particularly children and the poor. OBJECTIVE: We evaluated serum retinol concentration by using population-representative data from 16058 participants aged 4 to >/=90 y in the third National Health and Nutrition Examination Survey, 1988-1994. DESIGN: We used multivariate regression to examine the simultaneous associations of sociodemographic, biologic, and behavioral factors with serum retinol concentration. RESULTS: In children, serum retinol concentrations were greater with greater age, body mass index, serum lipids, and the use of supplements containing vitamin A. In adults, male sex, serum lipids, alcohol consumption, and age were positively associated with serum retinol concentration in most racial/ethnic strata. Household income was not associated with serum retinol concentration in children; associations were inconsistent in adults. The prevalence of serum retinol <0.70 micromol/L was very low in all strata; the prevalence of serum retinol <1.05 micromol/L was 16.7-33.9% in children aged 4-8 y and 3.6-14.2% in children aged 9-13 y, depending on sex and racial/ethnic group. The prevalence of serum retinol<1.05 micromol/L was higher in non-Hispanic black and Mexican American children than in non-Hispanic white children; these differences remained significant (P < 0.0001) after covariates were controlled for. Among adults, nonwhite women were significantly (P < 0.0001) more likely than white women to have serum retinol <1.05 micromol/L after covariates were controlled for. CONCLUSIONS: Clinically low serum retinol concentration is uncommon in US residents aged > or = 4 y, although racial/ethnic and socioeconomic differences in serum retinol concentration still exist.     

High prevalence of hyperhomocysteinemia in Chinese adults is associated with low folate, vitamin B-12, and vitamin B-6 status

Elevated plasma total homocysteine (tHcy) concentrations are associated with lower folate, vitamin B-12, and vitamin B-6 status and are considered an independent risk factor for cardiovascular disease in developed countries, but data in developing countries are limited. We conducted a cross-sectional study to explore tHcy status and its association with plasma B vitamin status in 2471 Chinese men and women aged 35 to 64 y, living in the urban and rural areas of the northern and the southern regions of China. Blood samples were also collected in 2 seasons (spring and fall). The geometric mean plasma tHcy concentration was significantly higher in the north (adjusted geometric mean, 95% CI; 13.0 micromol/L, 12.6-13.3) than in the south (9.1, 8.9-9.4) after controlling for gender, area (urban and rural), age, and season (spring and fall). Twenty-eight percent of northerners and 7% of southerners had plasma tHcy concentrations>or=16.0 micromol/L, a level used to define hyperhomocysteinemia. Within each region, men had higher plasma tHcy concentrations than women (16.1 vs. 10.6 micromol/L in the north, and 10.7 vs. 7.9 micromol/L in the south) and 40% of the northern men had hyperhomocysteinemia. Generally, individuals living in the urban areas had 30% (95% CI, 1.0-1.6) greater odds of having high tHcy levels (>or=16 micromol/L) than those living in the rural areas. Low plasma concentrations of folate, vitamins B-12 and B-6, older age, being male, and living in urban areas were all independently associated with elevated tHcy, with low folate as the strongest determinant.     

Screening for vitamin B-12 and folate deficiency in older persons

BACKGROUND: Vitamin B-12 deficiency is usually accompanied by elevated concentrations of serum total homocysteine (tHcy) and methylmalonic acid (MMA). Folate deficiency also results in elevated tHcy. Measurement of these metabolites can be used to screen for functional vitamin B-12 or folate deficiency. OBJECTIVE: We assessed the prevalence of vitamin B-12 and folate deficiency in a population-based study (n = 1562) of older persons living in Oxford City, United Kingdom. DESIGN: We postulated that, as vitamin B-12 or folate concentrations declined from adequate to impaired levels, tHcy (or MMA) concentrations would increase. Individuals were classified as being at high risk of vitamin B-12 deficiency if they had low vitamin B-12 (< 150 pmol/L) or borderline vitamin B-12 (150-200 pmol/L) accompanied by elevated MMA (> 0.35 micromol/L) or tHcy (> 15.0 micromol/L). Individuals were classified as being at high risk of folate deficiency if they had low folate (< 5 nmol/L) or borderline folate (5-7 nmol/L) accompanied by elevated tHcy (> 15 micromol/L). RESULTS: Cutoffs of 15.0 micro mol/L for tHcy and 0.35 micro mol/L for MMA identified persons with normal or elevated concentrations. Among persons aged 65-74 and >or= 75 y, respectively, approximately 10% and 20% were at high risk of vitamin B-12 deficiency. About 10% and 20%, respectively, were also at high risk of folate deficiency. About 10% of persons with vitamin B-12 deficiency also had folate deficiency. CONCLUSION: Use of tHcy or MMA among older persons with borderline vitamin concentrations may identify those at high risk of vitamin B-12 deficiency who should be considered for treatment.     

Leptin concentrations in the United States: relations with demographic and anthropometric measures

BACKGROUND: Leptin is a peptide that is strongly correlated with adiposity and is a potential determinant of obesity and its complications. OBJECTIVE: Leptin concentrations from a representative sample of the US population were examined in relation to demographic and anthropometric measures. DESIGN: Fasting serum leptin concentrations were measured in 6303 women and men aged > or =20 y in the third National Health and Nutrition Examination Survey. Anthropometric measures included body mass index, 4 skinfold thicknesses, and 4 body circumferences. Ethnic groups included non-Hispanic whites and blacks and Mexican Americans. RESULTS: The mean serum leptin concentration was much higher in women (12.7 microg/L) than in men (4.6 microg/L). In a multivariate analysis, leptin concentrations were associated with the sum of 4 skinfold thicknesses, waist and hip circumferences, ethnicity, and age. These measures explained most of the variance in leptin concentrations in women (R2 = 0.69) and in men (R2 = 0.67). Triceps skinfold thickness, when substituted for the sum of skinfold thicknesses, performed nearly as well in women (R2 = 0.68) and men (R2 = 0.67). Leptin concentrations were slightly but significantly higher in non-Hispanic blacks than in non-Hispanic whites of both sexes when these anthropometric measures and age were controlled for; Mexican Americans had concentrations that were intermediate compared with the concentrations of non-Hispanic whites and blacks. CONCLUSIONS: In this large, representative sample of the US population, demographic and anthropometric measures predicted serum leptin concentrations in women and men.