Dietary predictors of plasma total homocysteine in the Hordaland Homocysteine Study

Established dietary predictors of plasma total homocysteine (tHcy) include folate, riboflavin, and vitamins B6 and B12, while information is scarce regarding other dietary components. The aim of this study was to examine the relation between a variety of food groups, food items and nutrients, and plasma tHcy in a large population-based study. The study population included 5812 men and women aged 47-49 and 71-74 years who completed a 169-item FFQ. tHcy was examined across quartiles of dietary components by multiple linear regression analyses adjusting for age, sex, energy intake, various risk factors for elevated tHcy, as well as for dietary and plasma B-vitamins. Among 4578 non-users of vitamin supplements, intake of vegetables, fruits, cereals, eggs, fish and milk, as well as chicken and non-processed meats were inversely associated with tHcy level. The estimated mean difference in tHcy per increasing quartile of intake ranged from - 0.11 (95 % CI - 0.21, - 0.01) micromol/l for milk to - 0.32 (95 % CI - 0.42, - 0.22) micromol/l for vegetables. Positive associations were found for sweets and cakes. Whole-grain bread was significantly inversely related to tHcy only after additional adjustment for dietary and plasma B-vitamins. The nutrients folate, vitamin B6, B12, and riboflavin were inversely related to tHcy. Complex carbohydrates were inversely, and fat positively associated with tHcy, also after adjustment for dietary and plasma B-vitamins. In conclusion, food items rich in B-vitamins and with a low content of fat and sugar were related to lower tHcy levels. Eggs, chicken, non-processed meat, fish and milk were inversely associated with tHcy.     

Changes in lifestyle and plasma total homocysteine: the Hordaland Homocysteine Study

BACKGROUND: Elevated plasma concentrations of total homocysteine (tHcy) are a risk factor for cardiovascular disease. tHcy is a marker of folate and cobalamin deficiencies and is also related to several lifestyle factors. OBJECTIVE: We examined whether changes in lifestyle influence tHcy over time. DESIGN: A population-based, prospective study was conducted in 7031 subjects from western Norway who constituted 2 age groups (41-42 and 65-67 y) at baseline (1992-1993). The subjects were reinvestigated in 1997-1999 ( follow-up: 6 y). RESULTS: During follow-up, median tHcy concentrations decreased 0.10 (25th and 75th percentiles: -1.24, 1.00) micromol/L in the younger subjects and increased 0.39 (25th and 75th percentiles: -0.99, 1.79) micromol/L in the older subjects. Changes in plasma vitamin status and vitamin supplement use were the strongest determinants of changes in tHcy over time. Each unit increase in plasma folate (nmol/L) and vitamin B-12 (pmol/L) was associated with reductions in tHcy concentrations of 0.2 and 0.1 micromol/L, respectively. Among the younger and older age groups, those who started to take vitamin supplements during follow-up had significant reductions in tHcy concentrations of 0.42 (95% CI: -0.65, -0.20) and 0.41 (-0.78, -0.03) micromol/L, respectively. In the younger subjects who quit smoking, tHcy concentrations decreased 0.54 (-0.91, -0.16) micromol/L. Weight changes were inversely related to tHcy. Both baseline history of cardiovascular disease or hypertension and cardiovascular events during follow-up were significantly associated with changes in tHcy. CONCLUSIONS: Changes in lifestyle factors over time influence tHcy concentrations. These changes are modest when compared with the strong associations between tHcy and lifestyle factors in cross-sectional studies.     

Plasma total homocysteine and cardiovascular and noncardiovascular mortality: the Hordaland Homocysteine Study.

BACKGROUND: Few population-based studies have assessed relations between plasma or serum total homocysteine (tHcy) and all-cause mortality. OBJECTIVE: Our goal was to study associations between plasma tHcy and all-cause, cardiovascular, and noncardiovascular mortality. DESIGN: This was a prospective cohort study of 2127 men and 2639 women aged 65-67 y in 1992-1993 when they were recruited as part of a population-based national cardiovascular screening program carried out in Hordaland County, Norway. RESULTS: During a median of 4.1 y of follow-up, 162 men and 97 women died. A strong relation was found between plasma tHcy and all-cause mortality. The association was highly significant for noncardiovascular and for cardiovascular causes of death. In a comparison of individuals having tHcy concentrations of 9.0-11.9, 12.0-14.9, 15.0-19.9, or > or = 20 micromol/L with individuals having a tHcy concentration < 9 micromol/L, adjusted mortality ratios were 1.4, 1.9, 2.3, and 3.6 (P for trend = 0.0002) for noncardiovascular and 1.3, 2.1, 2.6, and 3.5 (P for trend = 0.0002) for cardiovascular causes of death. A tHcy increment of 5 micromol/L was associated with a 49% (95% CI: 28%, 72%) increase in all-cause mortality, a 50% (95% CI: 21%, 85%) increase in cardiovascular mortality (121 deaths), a 26% (95% CI: -2%, 63%) increase in cancer mortality (103 deaths), and a 104% (95% CI: 44%, 289%) increase in noncancer, noncardiovascular mortality (33 deaths). CONCLUSION: Plasma tHcy is a strong predictor of both cardiovascular and noncardiovascular mortality in a general population of 65-72-y-olds. These results should encourage studies of tHcy in a wider perspective than one confined to cardiovascular disease.     

Plasma total homocysteine, pregnancy complications, and adverse pregnancy outcomes: the Hordaland Homocysteine study

BACKGROUND: Total homocysteine (tHcy) measured in serum or plasma is a marker of folate status and a risk factor for cardiovascular disease. OBJECTIVE: Our objective was to investigate associations between tHcy and complications and adverse outcomes of pregnancy. DESIGN: Plasma tHcy values measured in 1992-1993 in 5883 women aged 40-42 y were compared with outcomes and complications of 14492 pregnancies in the same women that were reported to the Medical Birth Registry of Norway from 1967 to 1996. RESULTS: When we compared the upper with the lower quartile of plasma tHcy, the adjusted risk for preeclampsia was 32% higher [odds ratio (OR): 1. 32; 95% CI: 0.98, 1.77; P for trend = 0.02], that for prematurity was 38% higher (OR: 1.38; 95% CI: 1.09, 1.75; P for trend = 0.005), and that for very low birth weight was 101% higher (OR: 2.01; 95% CI: 1.23, 3.27; P for trend = 0.003). These associations were stronger during the years closest to the tHcy determination (1980-1996), when there was also a significant relation between tHcy concentration and stillbirth (OR: 2.03; 95% CI: 0.98, 4.21; P for trend = 0.02). Neural tube defects and clubfoot had significant associations with plasma tHcy. Placental abruption had no relation with tHcy quartile, but the adjusted OR when tHcy concentrations >15 micromol/L were compared with lower values was 3.13 (95% CI: 1.63, 6. 03; P = 0.001). CONCLUSION: Elevated tHcy concentration is associated with common pregnancy complications and adverse pregnancy outcomes.     

Lifestyle and cardiovascular disease risk factors as determinants of total cysteine in plasma: the Hordaland Homocysteine Study

BACKGROUND: Plasma total homocysteine (tHcy) is a cardiovascular disease risk factor and is related to several components of the established cardiovascular disease risk profile. Cysteine is structurally and metabolically related to homocysteine, but data on its association with cardiovascular disease and cardiovascular disease risk factors are sparse. OBJECTIVE: Our objective was to search for the determinants of plasma total cysteine (tCys) and compare them with those of tHcy. DESIGN: In this cross-sectional study, we studied 7591 healthy men and 8585 healthy women aged 40-67 y with no history of hypertension, diabetes mellitus, coronary heart disease, or cerebrovascular disease. RESULTS: In the group aged 40-42 y, tCys was significantly higher in men (&mean;: 273 micromol/L; 2.5-97.5 percentile: 219-338 micromol/L) than in women (253 micromol/L; 202-317 micromol/L) (P < 0.001). In the group aged 65-67 y, there was no significant sex difference in tCys: men (296 micromol/L; 233-362 micromol/L) and women (296 micromol/L; 234-361 micromol/L). As with tHcy, tCys was positively associated with age, total cholesterol concentration, diastolic blood pressure, and coffee consumption. Body mass index was a strong determinant of tCys but was not related to tHcy. Several factors known to influence tHcy, including smoking status, folate and vitamin intake, heart rate, and physical activity, were not associated or were only weakly associated with tCys. CONCLUSION: Plasma tCys is strongly related to several factors that constitute the cardiovascular disease risk profile. This should be an incentive to determine the role of tCys in cardiovascular disease.     

Plasma total cysteine,pregnancy complications,and adverse pregnancy outcomes: the Hordaland Homocysteine Study

BACKGROUND: Total homocysteine (tHcy) is associated with pregnancy complications and adverse pregnancy outcomes. The associations of plasma total cysteine (tCys) with such outcomes have not been investigated in large populations. OBJECTIVE: We investigated the association between plasma tCys and pregnancy complications, congenital malformations, and other adverse pregnancy outcomes. DESIGN: The plasma tCys concentrations of 5883 women aged 40-42 y that were measured in 1992-1993 during a cardiovascular health screening were compared with the outcomes and complications of 14492 pregnancies in the same women that were registered in the Medical Birth Registry of Norway from 1967 to 1996. RESULTS: After adjustment for parity, mother's age, tHcy, total cholesterol, body mass index, smoking, and coffee drinking, high plasma tCys concentrations (above the 95th percentile) were associated with significantly higher risks of preeclampsia [n = 342; odds ratio (OR): 1.6; 95% CI: 1.1, 2.4; P = 0.03], premature delivery (n = 774; OR: 1.8; 95% CI: 1.3, 2.5; P = 0.001), and very low birth weight (n = 175; OR: 2.0; 95% CI: 1.1, 3.9; P = 0.03) than were lower plasma tCys concentrations. tCys was not associated with the risk of placental abruption. High tCys concentrations showed a weak association with congenital malformations and stillbirths with birth weight <1500 g. The associations were independent of the tHcy concentrations. CONCLUSION: High tCys concentrations were associated with risks of preeclampsia, premature delivery, and low birth weight.     

Plasma total homocysteine is influenced by prandial status in humans: the Hordaland Hhomocysteine Sstudy

Plasma total homocysteine (tHcy) is a risk factor for cardiovascular disease, adverse pregnancy outcomes and impaired cognitive function. No population-based studies on the possible influence of prandial status on tHcy have been published. The aim of this study was to investigate the variation in plasma tHcy levels in relation to time since last meal. A cross-sectional, population-based study including 18,044 individuals in Western Norway was conducted. Most subjects were in the age groups 40-42 and 65-67 y. Participants who had not eaten during the past 6 h before the blood sampling had significantly higher mean tHcy levels compared with those who had eaten; 11.7 [95% confidence interval (CI): 11.4-12.1] vs. 11.2 (95% CI: 11.1-11.3) micromol/L among men (P = 0.03) and 10.2 (95% CI: 9.9-10.6) vs. 9.7 (95% CI: 9.6-9.7) micromol/L among women (P = 0.003). In all groups except older women, tHcy concentrations were generally higher with increasing time after a meal (P-trend <0.01 in all 3 groups). These findings suggest that fasting status and time since last meal may influence levels of tHcy and should be considered in studies of tHcy as a risk factor for cardiovascular and other diseases, and when comparing tHcy values among studies.     

Selenium supplements do not increase plasma total homocysteine concentrations in men and women

Studies in rats indicate that plasma total homocysteine (tHcy) is decreased in selenium deficiency and increases with selenium supplementation. The aim of this study was to determine the effect of selenium supplements on plasma tHcy concentrations in a population that has suboptimal selenium status. Subjects from Dunedin, New Zealand (n = 189) were randomly assigned to receive a supplement containing 200 micro g selenium or placebo for 20 wk. At baseline, 67% (n = 112) of the participants had plasma selenium concentrations < 1.2 micro mol/L, a concentration believed to be that necessary for full glutathione peroxidase (Gpx) activity. At 20 wk, plasma selenium concentration and Gpx activity increased in the selenium group by 1.2 micro mol/L [95% confidence interval (CI): 1.1, 1.3] and 5.1 nkat/g protein (3.7, 6.5), respectively, changes that were significantly greater than the changes in the placebo group (P < 0.001). At 20 wk, mean changes in plasma tHcy concentrations were 0.1 micro mol/L (95% CI: -0.4, 0.5) and -0.2 micro mol/L (-0.7, 0.3) in the supplemented and placebo groups, respectively, compared to baseline. There was no difference in the mean changes in plasma tHcy between the supplemented and placebo groups (P = 0.54). These results suggest that selenium supplementation does not influence plasma tHcy concentrations in healthy populations in developed countries, whose selenium status is characterized by lower plasma selenium concentrations.     

Determinants and distributions of plasma total homocysteine concentrations among school children in Taiwan

Background: Plasma total homocysteine (tHcy) level is an independent risk factor for cardiovascular disease (CVD) even among children. The purpose of this study is to evaluate the determinants and distributions of plasma tHcy levels and the relationship between plasma tHcy, folate and vitamin B12 levels among school children in Taipei. Methods: After multi-stage sampling, we randomly selected 1234 school children (609 boys and 625 girls) with the mean age of 13 years (from 12 to 15 years) in this study. Fasting plasma tHcy levels were measured using an ABBOTT IMx analyzer (Axis Biochemicals ASA, Oslo, Norway). Plasma folate and vitamin B12 levels were measured by ACS:180 automated chemiluminescence analyzer (Bayer, Tarrytown, NY, USA). Results: The distribution of plasma tHcy levels were skewed to the right with the mean values of 10.50 and 8.95 mol/l and medians of 9.67 and 8.474 mol/l for boys and girls, respectively. Plasma tHcy concentrations were lower in younger children and progressively increased with increasing age. Boys had significantly higher plasma tHcy levels than girls (10.50 ± 4.134 vs. 8.95 ± 2.61 mol/l, p < 0.01) and lower plasma folate levels (6.05 ± 2.85 vs. 6.39 ± 2.58 nmol/l, p < 0.01), and vitamin B12 levels (444.8 ± 158.4 vs. 495.0 ± 181.5 pmol/l, p < 0.001). Plasma tHcy levels were significantly positively associated with anthropometric measures in boys; but these characteristics attenuated and became insignificant after adjusting for other potential confounders in girls. Plasma tHcy levels were negatively associated with plasma folate and vitamin B12 levels even after adjusting for BMI and other potential confounders in both genders. Conclusions: From this study, the distributions of tHcy levels were skewed to the right and the boys had higher plasma tHcy levels than girls. Plasma tHcy levels were significantly positively associated with BMI among boys. Further studies are needed to evaluate the relationship between tHcy and CVD risk factors among children for the better prevention of heart disease in early life.     

Dietary choline and betaine assessed by food-frequency questionnaire in relation to plasma total homocysteine concentration in the Framingham Offspring Study

BACKGROUND: Epidemiologic studies of choline and betaine intakes have been sparse because a food-composition database was not available until recently. The physiologic relevance of a variation in dietary choline and betaine in the general population and the validity of intake assessed by food-frequency questionnaire (FFQ) have not been evaluated. OBJECTIVE: This study was conducted to examine the physiologic relevance and validity of choline and betaine intakes measured by an FFQ. DESIGN: We examined the relations between choline and betaine intakes measured by FFQ and plasma total homocysteine (tHcy) concentrations in 1960 participants from the Framingham Offspring Study. RESULTS: Higher intakes of dietary choline and betaine were related to lower tHcy concentrations independent of other determinants, including folate and other B vitamins. For the lowest and highest quintiles of dietary choline plus betaine, the multivariate geometric means for tHcy were 10.9 and 9.9 mumol/L (P for trend < 0.0001). The inverse association was manifested primarily in participants with low folate intakes (P for interaction < 0.0001). Among participants with folate intakes < or =250 microg/d, the geometric mean tHcy concentrations in the lowest and highest quintiles of choline plus betaine intakes were 12.4 and 10.2 micromol/L (P for trend < 0.0001). Except for choline from phosphatidylcholine, individual forms of choline were inversely associated with tHcy concentrations. CONCLUSIONS: Our findings provide support for a physiologically important variation in choline and betaine intakes in the general population and for the validity of intake measured by FFQ.     

Relations of glutamate carboxypeptidase II (GCPII) polymorphisms to folate and homocysteine concentrations and to scores of cognition, anxiety, and depression in a homogeneous Norwegian population: the Hordaland Homocysteine Study

BACKGROUND: Glutamate carboxypeptidase II (GCPII) encodes for intestinal folate hydrolase and brain N-acetylated alpha-linked acidic dipeptidase. Previous studies provided conflicting results on the effect of the GCPII 1561C-->T polymorphism on folate and total homocysteine (tHcy) concentrations. OBJECTIVE: We aimed to determine the potential effects of 2 polymorphisms of GCPII on plasma folate and tHcy concentrations, cognition, anxiety, and depression in a large aging cohort of Norwegians enrolled in the Hordaland Homocysteine Study. DESIGN: DNA samples were genotyped for the GCPII 1561C-->T and 484A-->G polymorphisms, and the results were linked to plasma folate and tHcy concentrations and to scores for cognition, anxiety, and depression. RESULTS: The 2 polymorphisms were in linkage disequilibrium and were associated with concentrations of tHcy. After adjustment for covariates, persons in the CT or combined CT and TT groups of the 1561C-->T polymorphism had higher plasma folate concentrations and lower tHcy concentrations than did those in the CC group. Subjects with the TT genotype had lower Symbol Digit Modalities Test (SDMT) scores than did subjects with the CC genotype. Compared with abstainers, moderate alcohol drinkers had higher plasma folate concentrations and higher scores on the Mini Mental State Examination. However, women abstainers with the CT genotype had lower SDMT scores than did abstainers with the CC genotype or moderate drinkers with the CT genotype. CONCLUSIONS: The 1561C-->T polymorphism is associated with higher plasma folate and lower tHcy concentrations and with lower SDMT cognitive scores in women who abstain from alcohol.     

Acute effects of tea on fasting and non-fasting plasma total homocysteine concentrations in human subjects

Plasma total homocysteine concentrations (tHcy) are a putative risk factor for CVD. Tea is a rich dietary source of polyphenols and caffeine, both of which may raise tHcy. However, it is possible that much of any effect is transitory and may be influenced by the consumption of food. Our objective was to investigate the acute effect of tea, at a dose representative of ordinary population intakes, on tHcy and to determine whether consumption of a meal influences the magnitude of any effect. Measurements of tHcy were performed in twenty participants at baseline and 3.5 h after drinking three cups of black tea or hot water (consumed at time 0, 1.5 and 3 h) with and without a meal: a total of four treatments administered in random order. Drinking tea resulted in an acute increase in tHcy (0-30 (95 % CI 0.04, 0.56) micromol/l, P=0.022). The meal resulted in an acute decrease in tHcy (-0.42 (95 % CI -0.68, -0.16) micromol/l, P=0.002). There was no interaction between tea and meal on tHcy (P=0.40); that is, the effect of tea on tHcy was not different in the fasting and non-fasting state. Our results suggest that drinking black tea can cause a small acute increase in tHcy and that this effect is not enhanced in the non-fasting state. Given that results of population studies have generally shown a negative association between tea intake and tHcy, the significance of these findings to CVD risk remains uncertain.     

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.     

Developments in the measurement of plasma total homocysteine

Elevated plasma homocysteine is considered to be a graded risk factor for cardiovascular disease, and for this reason there is great interest in high-performance analytical techniques. Methods have evolved from ion-exchange chromatography to embrace high-performance liquid chromatography with fluorescence or electrochemical detection, immunoassays, gas chromatography-mass spectroscopy and liquid chromatography with tandem mass spectrometry. Immunoassays and high-performance liquid chromatography methods are currently available in kit form, fluorescence polarization immunoassay showing the best performance.     

Effect of age on plasma homocysteine concentrations in young and elderly subjects considering serum vitamin concentrations and different lifestyle factors

OBJECTIVES: The aim of this study was to investigate whether an increase in total homocysteine (tHcy) concentration with increasing age is due to diminishing serum concentrations of pyridoxal-5-phosphate (PLP), vitamin B-12, and folate. The possible influence of different lifestyle factors on tHcy concentration was considered. METHODS: Plasma tHcy, serum concentrations of pyridoxal-5-phosphate, vitamin B-12, and folate, intake of coffee and tea, alcohol, and methionine, as well as cigarette smoking, were determined in 252 elderly subjects (60-87 years old) of the longitudinal study on nutrition and health status in an aging population in Giessen (GISELA) and 99 young adults (20-34 years old) of the study on health and nutrition of young adults (GEJE). RESULTS: Mean plasma tHcy concentrations were significantly higher in elderly than in young female subjects (9.7 +/- 1.9 micromol/L vs. 9.0 +/- 1.6 micromol/L, p < 0.05), but there was no difference between elderly and young men (10.6 +/- 2.1 micromol/L vs. 10.7 +/- 2.6 micromol/L). No differences in tHcy were observed between young and elderly subjects after adjustment for serum concentrations of PLP, vitamin B-12, and folate. Multiple linear regression analysis revealed a significant influence of age only in elderly, but not in younger subjects. CONCLUSION: Higher tHcy concentrations in the elderly, in comparison to younger women, are due to lower serum concentrations of PLP, vitamin B-12, and folate, whereas within the age group of elderly subjects alone tHcy concentrations increase with age irrespective of serum vitamin concentrations.     

Sex-related differences in methionine metabolism and plasma homocysteine concentrations

BACKGROUND: Elevated fasting homocysteine concentrations are considered a risk factor for vascular disease. Homocysteine, which is produced by the transmethylation of methionine, can be either remethylated back to methionine or metabolized via transsulfuration to cystathionine. It has been speculated that the lower risk of vascular disease among premenopausal women may be related to lower homocysteine concentrations in women than in men. OBJECTIVE: This study was designed to determine whether sex-related differences exist in methionine cycle kinetics, which may account for the reportedly lower fasting homocysteine concentrations in premenopausal women. DESIGN: Eleven healthy young men and 11 premenopausal women without cardiac risk factors were studied by using stable-isotope-labeled L-[methyl-(2)H(3),1-(13)C]methionine and L-[methyl- (2)H(3)]leucine. After 3 h of tracer infusion, 100 mg unlabeled L-methionine/kg body wt was ingested. Blood and breath samples were obtained at timed intervals. Fat-free mass was estimated by dual-energy X-ray absorptiometry and muscle mass by urinary creatinine excretion. RESULTS: No significant sex-related differences were found in fasting homocysteine concentrations, responses to the oral methionine load, or rates of methionine flux based on carboxyl or methyl labels. However, women had significantly higher remethylation rates than did men (P < 0.005) and a tendency toward higher transmethylation (P < 0.10). Whereas adjustment of remethylation rates for fat-free mass tended to attenuate the sex-related effect (P = 0.08), adjustment for muscle mass did not (P < 0.04). In contrast, significant sex-related differences in leucine flux (P < 0.02) were eliminated after adjustment for either fat-free mass or muscle mass. CONCLUSION: Reported differences between men and women in homocysteine concentrations may be partially explained by differences in rates of homocysteine remethylation.     

Plasma concentration of folate as a biomarker for the intake of fruit and vegetables: the Hordaland Homocysteine Study

BACKGROUND: Nutritional biomarkers may be used to assess dietary exposure without the errors commonly associated with self-reported dietary data. OBJECTIVE: The objective was to examine the association between plasma folate and intake of folate, fruit, and vegetables in a large cohort of healthy adults consuming foods that had not been fortified with folic acid. DESIGN: The present study population included 5533 middle-aged (47-49 y) and old (71-74 y) subjects from the Hordaland Homocysteine Study. The participants completed a food-frequency questionnaire and provided blood samples for chemical analyses. RESULTS: We observed a significant difference in plasma concentrations of folate across increasing quartiles of fruit, vegetable, and orange juice consumption. The difference in plasma folate between the highest and lowest quartiles was 1.97 (95% CI: 1.86, 2.07) nmol/L for fruit intake, 1.79 (95% CI: 1.69, 1.89) nmol/L for vegetable intake, and 2.69 (95% CI: 2.51, 2.87) nmol/L for orange juice intake. A significant inverse relation was observed across increasing quartiles of milk and bread intakes. The difference between the highest and lowest quartiles was -1.03 (95% CI: -1.13, -0.92) nmol/L for milk and -1.60 (95% CI: -1.69, -1.50) nmol/L for bread. CONCLUSION: Plasma folate concentration may be a useful biomarker for the intake of fruit and vegetables in populations consuming unfortified food products. The association can be attenuated by and should be corrected for individual intake of folic acid supplements.     

Dietary folate from vegetables and citrus fruit decreases plasma homocysteine concentrations in humans in a dietary controlled trial.

Elevated total plasma homocysteine (tHcy) concentrations are considered a risk factor for neural tube defects (NTD) and cardiovascular disease. Supplementation with folic acid decreases the risk of women having children with NTD. In both sexes, it decreases tHcy levels. We investigated the efficacy of natural dietary folate in improving folate and homocysteine status. We performed a 4-wk dietary controlled, parallel design intervention trial with 66 healthy subjects (18-45 y) divided into 3 treatment groups: the dietary folate group, the folic acid group and the placebo group. Each day each group was fed a different diet. The dietary folate group received a diet high in vegetables and citrus fruit (total folate content approximately 560 microgram) plus a placebo tablet. The folic acid group received a diet naturally low in folate (approximately 210 microgram) plus 500 microgram folic acid and placebo tablet on alternate days, i.e., 250 microgram folic acid/d. And the placebo group received the same low-folate diet as the folic acid group plus a placebo tablet. After 4 wk of intervention, folate status improved, and tHcy concentrations decreased in both the dietary folate and the folic acid groups. From the amount of additional folate (350 microgram/d) and folic acid (250 microgram/d) consumed, the relative bioavailability of dietary folate compared to folic acid was calculated to be 60-98%, depending on the endpoint used. In conclusion, increasing the consumption of vegetables and citrus fruit, both good sources of folate, will improve folate status and decrease tHcy concentrations. This may contribute to the prevention of cardiovascular disease and NTD in the general population     

Dietary fat and body fat: a multivariate study of 205 adult females.

This study examined the association between diet composition, particularly dietary fat intake, and body-fat percentage in 205 adult females. Subjects completed a written questionnaire regarding lifestyle factors, such as exercise participation and smoking, demographic data, and the diet section of the National Cancer Institute's Health Habits and History Questionnaire by Block. Skinfold-thickness measures were used to ascertain the body-fat percentage of each subject. Results showed that intake of dietary fat was related significantly with adiposity, without (F = 13.65, R2 = 0.063, P = 0.0003) and with (F = 8.74, R2 = 0.033, P = 0.0035) control for multiple potential confounding factors: age, total energy intake, total exercise time per week, years of regular physical activity, consumption of other macronutrients, and smoking. Unlike dietary fat intake, protein consumption and carbohydrate intake were not significant individual predictors of body-fat percentage when the potential confounding variables were controlled. The findings suggest that dietary fat intake may play a role in obesity beyond dietary energy content.