[Polymedication in institutionalized elderly and its effect on vitamin B12, folate, and homocysteine levels]. / La polimedicación en mayores institucionalizados: su efecto sobre los niveles de vitamina B12, folato y homocisteína.

AIM: To determine drug consumption in institutionalized elderly living in the Region of Madrid (Spain) and to assess the relationship between drug intake and biochemical parameters for vitamin B12 (Cobalamin and Holotranscobalamin), serum folate (SF) and homocysteine (Hcy). METHODS: 167 subjects (32% men), mean age 83 ± 7 years, were classified according to biochemical parameter levels (in or out of reference range) and drugs were classified according to ATC system. The relationship between drug intake and biochemical levels was studied by means of the Fisher exact test. RESULTS: The daily mean drug intake was 5. Psicoleptic and antiacid drugs were the most consumed (both 53%). Cobalamin (median 158.2 pg/mL; 10.7% of individuals), SF (5.3 ng/mL; 52.1%) and holotranscobalamin (11.76 pmoL/L; 7.8%) deficiencies were observed. Hyperhomocysteinaemia (19.4 µmoL/L) was present in 65% of population. Antiaenemic drug intake normalized cobalamin, urologic drug and corticosteroids SF and psicoanaleptics holotranscobalamin levels. Drugs against pulmonar obstruction increased Hcy concentration (all p < 0.05). CONCLUSION: There is a high prevalence of SF deficiency and hyperhomocysteinaemia in the studied population. The elevated number of drugs taken simultaneously by each subject makes it difficult to analyze which drugs are responsible for those alterations.

Micronutrients in pregnancy: current knowledge and unresolved questions.

Micronutrient status is increasingly recognized to play an important role in the health and well-being of pregnant women and in the development and long-term health of the offspring. On 26th - 28th February 2009, The Child Health Foundation invited leading experts in this area to a scientific workshop at Obergurgl, Austria to review and critically discuss current knowledge, to identify issues that may need to be addressed in future recommendations, and to highlight priorities and opportunities for future research. This report summarizes updated key conclusions of the workshop with regards to micronutrients' intake and physiological role related to mother, placenta and fetus, as well as relevance for adverse pregnancy and long-term outcomes.

[6S]-5-methyltetrahydrofolate increases plasma folate more effectively than folic acid in women with the homozygous or wild-type 677C-->T polymorphism of methylenetetrahydrofolate reductase.

BACKGROUND AND PURPOSE: 5,10-Methylenetetrahydrofolate reductase (MTHFR) is responsible for the synthesis of 5-methyltetrahydrofolate (5-MTHF). The 677C-->T mutation of MTHFR reduces the activity of this enzyme. The aim of this study was, first, to compare pharmacokinetic parameters of [6S]-5-MTHF and folic acid (FA) in women with the homozygous (TT) and wild-type (CC) 677C-->T mutation, and second, to explore genotype differences. The metabolism of [6S]-5-MTHF and FA was evaluated by measuring plasma folate derivatives. EXPERIMENTAL APPROACH: Healthy females (TT, n= 16; CC, n= 8) received a single oral dose of FA (400 microg) and [6S]-5-MTHF (416 microg) in a randomized crossover design. Plasma folate was measured up to 8 h after supplementation. Concentration-time-profile [area under the curve of the plasma folate concentration vs. time (AUC)], maximum concentration (C(max)) and time-to-reach-maximum (t(max)) were calculated. KEY RESULTS: AUC and C(max) were significantly higher, and t(max) significantly shorter for [6S]-5-MTHF compared with FA in both genotypes. A significant difference between the genotypes was observed for t(max) after FA only (P < 0.05). Plasma folate consisted essentially of 5-MTHF irrespective of the folate form given. Unmetabolized FA in plasma occurs regularly following FA supplementation, but rarely with [6S]-5-MTHF. CONCLUSIONS AND IMPLICATIONS: These data suggest that [6S]-5-MTHF increases plasma folate more effectively than FA irrespective of the 677C-->T mutation of the MTHFR. This natural form of folate could be an alternative to FA supplementation or fortification.

Sampling and processing of fresh blood samples within a European multicenter nutritional study: evaluation of biomarker stability during transport and storage.

INTRODUCTION: Analysis of several biological markers improves the quality and physiologic comprehension of data obtained in epidemiological nutritional studies. AIM: To develop a methodology that guarantees the centralized analysis and quality assurance of the most relevant blood parameters from fresh blood samples in adolescents in a European multicenter study. MATERIALS AND METHODS: Stability of selected nutrients and biomarkers (vitamins, fatty acids, iron metabolism and immunological parameters) chosen with respect to time and temperature of sample transport and storage was evaluated as part of the pilot study of the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) project. RESULTS: Routine biochemistry and iron status parameters included in the HELENA Cross-Sectional Study (CSS) protocol could be analyzed within 24 h from fresh blood samples without any stability problems (coefficient of variation (CV)<5%, P<0.05). However, stability tests for lymphocyte subpopulations, vitamin C and fatty acids showed that they are very unstable at room temperature without any treatment. Therefore, a special handling for these samples was developed. Vitamin C was stabilized with metaphosphoric acid and transported under cooled conditions (CV 4.4%, recovery rate >93%, P>0.05). According to the results, a specific methodology and transport system were developed to collect blood samples at schools in 10 European cities and to send them to the centralized laboratory (IEL, Bonn, Germany). To guarantee good clinical practice, the field workers were instructed in a training workshop and a manual of operation was developed. CONCLUSION: The handling and transport system for fresh blood samples developed for the European multicenter study HELENA is adequate for the final part of the HELENA-CSS and will provide, for the first time, reference values for several biological markers in European adolescents.

Vitamin B6 status, deficiency and its consequences--an overview.

BACKGROUND: Vitamin B6 is thought to be a most versatile coenzyme that participates in more than 100 biochemical reactions. It is involved in amino acid and homocysteine metabolism, glucose and lipid metabolism, neurotransmitter production and DNA/RNA synthesis. Vitamin B6 can also be a modulator of gene expression. Nowadays, clinically evident vitamin B6 deficiency is not a common disorder, at least in the general population. Nevertheless, a subclinical, undiagnosed deficiency may be present in some subjects, particularly in the elderly. OBJECTIVE: This review gives a complete overview over the metabolism and interactions of vitamin B6. Further, we show which complications and deficiency symptoms can occur due to a lack of vitamin B6 and possibilities for public health and supplemental interventions. METHODS: The database Medline (www.ncvi.nlm.nih.gov) was searched for terms like "vitamin B6", "pyridoxal", "cancer", "homocysteine", etc. For a complete understanding, we included studies with early findings from the forties as well as recent results from 2006. These studies were summarised and compared in different chapters. RESULTS AND CONCLUSION: In fact, it has been proposed that suboptimal vitamin B6 status is associated with certain diseases that particularly afflict the elderly population: impaired cognitive function, Alzheimer's disease, cardiovascular disease, and different types of cancer. Some of these problems may be related to the elevated homocysteine concentrations associated to vitamin B6 deficiency, but there is also evidence for other mechanisms independent of homocysteine by which a suboptimal vitamin B6 status could increase the risk for these chronic diseases.

[Homocysteine as a cardiovascular marker and risk factor]. / Homocystein als kardiovaskulärer Marker und Risikofaktor.

In context of cardiovascular secondary prevention the D.A.C.H.-Liga (union of scientists from Germany, Austria, and Switzerland doing research on the topic homocysteine) demands that the homocysteine level should be measured and recommends a substitution of folic acid above a value of 10 micromol/l. Numerous studies have proven the therapy's positive effect. Although a threshold could not be acquired in any study there seems to be an association between the homocysteine level and an increased cardiovascular risk. Homocysteine is not only a marker, but also a reason of cardiovascular mortality and morbidity. Further detailed statements concerning homocysteine therapy can be made after completing of current research.

B-vitamin status and intake in European adolescents. A review of the literature.

BACKGROUND: National and international recommendations for the intake of B vitamins in adolescents consist of estimates and extrapolations from adult values. Due to increasing growth and therefore relatively high energy and nutrient requirements adolescents are a vulnerable group from the nutritional point of view. In addition, a deficient intake of several B vitamins is strongly connected with the development of cancer, neural tube defects and cardiovascular diseases. OBJECTIVE: The aim of this work is to assess dietary intake and status of B vitamins and homocysteine of European adolescents on the basis of published data. METHODS: The database Medline (www.ncvi.nlm.nih.gov) was searched for terms like "Vitamin B", "homocysteine", "Europe", etc. Studies published between June 1980 and December 2004 were analysed for this review. Results of the intake of B vitamins were compared with the EAR or AI, respectively, as recommended by the U.S. Institute of Medicine. Due to lacking reference values for adolescents results of blood status as well as homocysteine were compared to different thresholds for adults. RESULTS: Considering the limitations of the comparability between the reviewed studies e.g. by different methodologies, sample size, age groups, the average intake of B vitamins surpassed the EAR and AI. Boys were better supplied with B vitamins than girls. The intake decreased with increasing age in both genders. A possible deficiency of folate was noticed and girls in particular seemed to be more at risk. Clear regional tendencies for the vitamin intake could not be observed. Results of vitamin B6, B12, folate in blood, and homocysteine were levelled in-between the thresholds. Though the great standard deviation of folate increased the probability of a deficient supply in parts of the population. CONCLUSIONS: European girls seem to be at risk of folate deficiency. Supplements and fortified food were not taken into consideration by most of the published studies which additionally distorts the real intake. Standardized methods of dietary surveys and reference values for B vitamins as well as homocysteine still must be established. Hence, further investigations are of great relevance. folate increased the probability of a deficient supply in parts of the population. CONCLUSIONS: European girls seem to be at risk of folate deficiency. Supplements and fortified food were not taken into consideration by most of the published studies which additionally distorts the real intake. Standardized methods of dietary surveys and reference values for B vitamins as well as homocysteine still must be established. Hence, further investigations are of great relevance.

Research goals for folate and related B vitamin in Europe.

In the past decade, the understanding of folate bioavailability, metabolism and related health issues has increased, but several problems remain, including the difficulty of delivering the available knowledge to the populations at risk. Owing to the low compliance of taking folic acid supplements, for example, among women of child-bearing age who could lower the risk of having a baby with a neural tube defect, food-based strategies aimed at increasing the intake of folate and other B-group vitamins should be a priority for future research. These should include the development of a combined strategy of supplemental folate (possibly with vitamin B(12)), biofortification using engineered plant-derived foods and micro-organisms and food fortification for increasing folate intakes in the general population. Currently, the most effective population-based strategy to reduce NTDs remains folic acid fortification. However, the possible adverse effect of high intakes of folic acid on neurologic functioning among elderly persons with vitamin B(12) deficiency needs urgent investigation. The results of ongoing randomized controlled studies aimed at reducing the prevalence of hyperhomocysteinemia and related morbidity must be available before food-based total population approaches for treatment of hyperhomocysteinemia can be recommended. Further research is required on quantitative assessment of folate intake and bioavailability, along with a more thorough understanding of physiological, biochemical and genetic processes involved in folate absorption and metabolism.

Clinical use and rational management of homocysteine, folic acid, and B vitamins in cardiovascular and thrombotic diseases.

About half of all deaths are due to cardiovascular disease and its complications. The economic burden on society and the healthcare system from cardiovascular disability, complications, and treatments is huge and becoming larger in the rapidly aging populations of developed countries. As conventional risk factors fail to account for part of the cases, homocysteine, a "new" risk factor, is being viewed with mounting interest. Homocysteine is a sulfur-containing intermediate product in the normal metabolism of methionine, an essential amino acid. Folic acid, vitamin B(12), and vitamin B(6) deficiency and reduced enzyme activities inhibit the breakdown of homocysteine, thus increasing the intracellular homocysteine concentration. Numerous retrospective and prospective studies have consistently found an independent relationship between mild hyperhomocysteinemia and cardiovascular disease or all-cause mortality. Starting at a plasma homocysteine concentration of approximately 10 micromol/l, the risk increase follows a linear dose-response relationship with no specific threshold level. Hyperhomocysteinemia as an independent risk factor for cardiovascular disease is thought to be responsible for about 10 percent of total risk. Elevated plasma homocysteine levels (> 12 micromol/l; moderate hyperhomocysteinemia) are considered cytotoxic and are found in 5 to 10 percent of the general population and in up to 40 percent of patients with vascular disease. Additional risk factors (smoking, arterial hypertension, diabetes, and hyperlipidemia) may additively or, by interacting with homocysteine, synergistically (and hence overproportionally) increase overall risk. Hyperhomocysteinemia is associated with alterations in vascular morphology, loss of endothelial antithrombotic function, and induction of a procoagulant environment. Most known forms of damage or injury are due to homocysteine-mediated oxidative stresses. Especially when acting as direct or indirect antagonists of cofactors and enzyme activities, numerous agents, drugs, diseases, and life style factors have an impact on homocysteine metabolism. Folic acid deficiency is considered the most common cause of hyperhomocysteinemia. An adequate intake of at least 400 microg of folate per day is difficult to maintain even with a balanced diet, and high-risk groups often find it impossible to meet these folate requirements. Based on the available evidence, there is an increasing call for the diagnosis and treatment of elevated homocysteine levels in high-risk individuals in general and patients with manifest vascular disease in particular. Subjects of both populations should first have a baseline homocysteine assay. Except where manifestations are already present, intervention, if any, should be guided by the severity of hyperhomocysteinemia. Consistent with other working parties and consensus groups, we recommend a target plasma homocysteine level of < 10 micromol/l. Based on various calculation models, reduction of elevated plasma homocysteine concentrations may theoretically prevent up to 25 percent of cardiovascular events. Supplementation is inexpensive, potentially effective, and devoid of adverse effects and, therefore, has an exceptionally favorable benefit/risk ratio. The results of ongoing randomized controlled intervention trials must be available before screening for and treatment of hyperhomocysteinemia can be recommended for the apparently healthy general population.

Alcohol consumption and its relation to cardiovascular risk factors in Germany.

OBJECTIVE: To analyse the association of alcohol consumption and blood lipids, haemostatic factors, and homocysteine in German adults by gender and age groups. DESIGN: Cross-sectional population-based survey. SETTING: Data from the German National Health Interview and Examination Survey 1998, representative for age, gender, community size, and federal state. SUBJECTS: From a sample of 7124 Germans between 18 and 79 y old, 2420 women and 2365 men were selected. Only individuals who were not currently receiving medical treatment or did not have disorders related to cardiovascular disease were selected for this study. RESULTS: Using analyses of variance, mean blood levels of total cholesterol, HDL cholesterol, HDL/total cholesterol ratio, total glycerides, fibrinogen, antithrombin III, and homocysteine adjusted for age, socioeconomic status, East/West Germany residence, body mass index, tobacco use, sports activity, and coffee consumption, if appropriate are presented by alcohol consumption groups (0, >0-10, >10-20, >20-30 and >30 g/day). The HDL/total cholesterol ratio increased with higher alcohol groups up to 10-20 g/day (+15%) for women and >30 g/day (+18%) for men, showing the strongest rise among men aged 55-79 y. Fibrinogen decreased with higher alcohol groups up to 10-20 g/day for women and 20-30 g/day for men. Among women, homocysteine levels showed a U-shaped curve with a minimum of 8.49 mmol/l at 10-20 g alcohol/day (-8%, reference: nondrinking), whereas an inverse association was observed for men. CONCLUSIONS: Moderate alcohol consumption is associated with favourable levels of several cardiovascular risk factors. The most favourable cardiovascular risk factor profile among women was observed among those drinking 10-20 g alcohol/day. Beneficial effects seem to be more pronounced among older men.

Beneficial role for folate in the prevention of colorectal and breast cancer.

Folate is involved in the synthesis of nucleotides and amino acid metabolism such as methylation of homocysteine to methionine. Methionine is activated by adenosine triphosphate (ATP) to produce S-adenosylmethionine (SAM), the primary intracellular methyl donor. Thus, folate is essential for the synthesis, methylation, and repair of DNA. With regard to its biochemical function it has been hypothesized that a diminished folate status may contribute to carcinogenesis by alteration of gene expression and increased DNA damage. Animal and human studies support this hypothesis, particularly with respect to colorectal cancer. Epidemiological evidence for the association between folate status and cancer was first observed among ulcerative colitis patients. Several case-control studies demonstrated reduction in colorectal cancer risk with better folate status. Two large, prospective cohort studies support the concept that high folate intake is protective against colon cancer. In contrast to colorectal cancer, the potential association of folate status and risk has been less investigated in breast cancer. Recently, convincing epidemiological data establishing a positive effect of folate status on breast cancer risk were published. This review summarizes the epidemiological evidence for the association between folate status and colorectal and breast cancer risk. In addition, a short overview is given on the discussed mechanism(s) by which folate might be involved in carcinogenesis.

Total plasma homocysteine and related amino acids in end-stage renal disease (ESRD) patients measured by gas chromatography-mass spectrometry--comparison with the Abbott IMx homocysteine assay and the HPLC method.

Increased concentrations of homocysteine probably contribute to the high cardiovascular morbidity and mortality in hemodialysed end-stage renal disease (ESRD) patients and are determined by a variety of factors such as age, residual renal function, and vitamin status. Fasting plasma concentrations of total homocysteine, methionine, cysteine, and cystathionine were determined by gas chromatography-mass spectrometry (GC-MS) in 131 ESRD patients receiving daily oral folate (160-320 microg) and vitamin B6 (10-20 mg) supplements. Concentrations of homocysteine determined by GC-MS were compared with those measured by high-performance liquid chromatography (HPLC) and an immunofluorescence method (IMx analyzer) using Passing-Bablok regression analysis. Mean plasma concentration of total homocysteine determined by GC-MS (28.7+/-11.9 micromol/l [mean+/-SD]) was significantly lower than that determined by HPLC (34.0+/-14.5 micromol/l; p<0.001) or IMx (32.4+/-13.9 micromol/l; p<0.001). A close correlation existed between GC-MS and HPLC (r=0.931; y=1.203 x+0.279) and GC-MS and IMx (r=0.896; y=1.105 x+0.766). Linear regression analysis showed positive correlations between plasma concentrations of homocysteine and cysteine (r=0.434; p<0.001) and homocysteine and cystathionine (r=0.187; p=0.032). Plasma concentrations of homocysteine correlated negatively with folate (r=-0.281; p=0.001) and vitamin B12 (r=-0.229; p=0.009). GC-MS proved to be a sensitive and reliable method for the determination of total plasma homocysteine and related amino acids. Despite vitamin supplementation, ESRD patients requiring chronic maintenance hemodialysis, have high plasma concentrations of homocyst(e)ine which seems to be metabolized mainly within the transsulfuration pathway, while remethylation to methionine seems to be disturbed.

Nutrition and cognitive impairment in the elderly.

As the number of older people is growing rapidly worldwide and the fact that elderly people are also apparently living longer, dementia, the most common cause of cognitive impairment is getting to be a greater public health problem. Nutrition plays a role in the ageing process, but there is still a lack of knowledge about nutrition-related risk factors in cognitive impairment. Research in this area has been intensive during the last decade, and results indicate that subclinical deficiency in essential nutrients (antioxidants such as vitamins C, E and beta-carotene, vitamin B(12), vitamin B(6), folate) and nutrition-related disorders, as hypercholesterolaemia, hypertriacylglycerolaemia, hypertension, and diabetes could be some of the nutrition-related risk factors, which can be present for a long time before cognitive impairment becomes evident. Large-scale clinical trials in high-risk populations are needed to determine whether lowering blood homocysteine levels reduces the risk of cognitive impairment and may delay the clinical onset of dementia and perhaps of Alzheimer's disease. A curative treatment of cognitive impairment, especially Alzheimer's disease, is currently impossible. Actual drug therapy, if started early enough, may slow down the progression of the disease. Longitudinal studies are required in order to establish the possible link of nutrient intake--nutritional status with cognitive impairment, and if it is possible, in fact, to inhibit or delay the onset of dementia.

Effect of folic acid supplements on homocysteine concentration in plasma of gestating sows.

An experiment comprising 19 German Landrace sows was established to evaluate the effect of folic acid supplements (10 mg/kg concentrate) on homocysteine and folic acid concentration in plasma and serum, respectively, of highly pregnant sows as compared to an unsupplemented control (basal diet contained 0.62 mg folic acid/kg concentrate). Blood samples were taken between day 75 and 110 of gestation for homocysteine analysis and on day 100 of gestation for folic acid determination. Due to the folic acid supplements serum folic acid concentration increased significantly (104 nmol/l in controls and 140 nmol/l in supplemented sows). In contrast, homocysteine concentration in the plasma was not significantly influenced by folic acid supplements (16.6 mumol/l in controls and 15.2 mumol/l in supplemented sows). Further investigations seem to be necessary to clarify the physiology of homocysteine metabolism in swine.

Lowering of homocysteine concentrations in elderly men and women.

B-vitamin supplementation has previously been shown to lower the concentration of plasma total homocysteine, a risk factor for cardiovascular disease. Little is known about the homocysteine-lowering effects of low-dose B-vitamins in elderly individuals, who are prone to higher homocysteine levels due to advanced age and a greater frequency of impaired vitamin status. We aimed to identify if and to what extent B-vitamins lower total homocysteine and its subfractions in elderly individuals. Men and women (> or = 60 years) received either B-vitamins (400 micrograms folic acid + 1.65 mg pyridoxine + 3 micrograms cyanocobalamin) or a placebo daily for 4 weeks. Subjects in the vitamin group showed a significant decrease in plasma total homocysteine during the first 2 weeks; thereafter, total homocysteine only slightly decreased further resulting in a geometric mean reduction of -16.3% (95% CI: -11.3% to -21.0%) over the entire treatment period. Free homocysteine decreased as well. However, the observed higher ratio of free/total homocysteine after 4 weeks of supplementation suggest a more pronounced reduction in protein-bound homocysteine. Low-dose B-vitamin supplementation is effective in lowering homocysteine in elderly individuals. Further studies are needed to be able to depict the effect of B-vitamin supplementation on different homocysteine sub-fractions in plasma.

Availability of food folate in humans.

The aim of our study was to determine whether the area-under-the-plasma-response-curve method with the positive area (AUC+) as primary analysis variable is suitable to evaluate the availability of food folate in humans. Healthy volunteers (n = 20) received four test meals in a randomized, four-period cross-over design as follows: meal A, 600 g spinach; meal B, 300 g spinach; meal C, 0.4 mg folic acid in water; meal D, folate-free control meal. Blood samples were drawn before administration of the test meals and up to 10 h postprandially. Plasma folate was significantly increased for up to 6 h after uptake of spinach and folic acid (P < 0.007), whereas the response curve after the control meal decreased slightly but significantly (P < 0.007). To calculate the net increase of plasma folate, the values were corrected by the individual predose concentrations. The AUC+ was calculated with these corrected values. The mean AUC+ was highest after consumption of meal A (71.2 +/- 24.0 h x nmol/L) followed by meal C (61.8 +/- 23. 8 h x nmol/L) and meal B (41.4 +/- 19.4 h x nmol/L). The AUC+ after meal B was significantly lower than after the other two meals (P < 0. 05). The results suggest that the AUC method with multiple blood sampling is useful for assessing the availability of food folate in humans.

Influence of feeding different vegetables on plasma levels of carotenoids, folate and vitamin C. Effect of disruption of the vegetable matrix.

Carotenoids, folate and vitamin C may contribute to the observed beneficial effects of increased vegetable intake. Currently, knowledge on the bioavailability of these compounds from vegetables is limited. We compared the efficacy of different vegetables, at the same level of intake (i.e. 300 g/d), in increasing plasma levels of carotenoids, folate and vitamin C and we investigated if disruption of the vegetable matrix would enhance the bioavailability of these micronutrients. In an incomplete block design, sixty-nine volunteers consumed a control meal without vegetables and three out of four vegetable meals (i.e. broccoli, green peas, whole leaf spinach, chopped spinach; containing between 1.7 and 24.6 mg beta-carotene, 3.8 and 26 mg lutein, 0.22 and 0.60 mg folate and 26 and 93 mg vitamin C) or a meal supplemented with synthetic beta-carotene (33.3 mg). Meals were consumed for 4 d and fasting blood samples were taken at the end of each period. Consumption of the spinach-supplemented meal did not affect plasma levels of beta-carotene, although the beta-carotene content was 10-fold those of broccoli and green peas, which induced significant increases in plasma beta-carotene levels (28 (95% CI 6.4, 55)% and 26 (95% CI 2.6, 54)% respectively). The beta-carotene-supplemented meal increased plasma concentrations of beta-carotene effectively (517 (95% CI 409, 648)%). All vegetable meals increased the plasma concentrations of lutein and vitamin C significantly. Broccoli and green peas were, when expressed per mg carotenoid consumed, also more effective sources of lutein than spinach. A significant increase in plasma folate concentration was found only after consumption of the spinach-supplemented meal, which provided the highest level of folate. Disruption of the spinach matrix increased the plasma responses to both lutein (14 (95% CI 3.7, 25)%) and folate (10 (95% CI 2.2, 18)%), whereas it did not affect the response to beta-carotene. We conclude that the bioavailabilities of beta-carotene and lutein vary substantially among different vegetables and that the bioavailabilities of lutein and folate from spinach can be improved by disruption of the vegetable matrix.

Effects of folic acid and combinations of folic acid and vitamin B-12 on plasma homocysteine concentrations in healthy, young women.

BACKGROUND: Elevated plasma homocysteine concentrations are considered to be a risk factor for vascular disease and fetal malformations such as neural tube defects. Recent studies have shown that plasma homocysteine can be lowered by folic acid in amounts corresponding to 1-2 times the recommended dietary allowance. Preliminary evidence indicates that vitamin B-12 may be beneficial when included in supplements or in a food-fortification regimen together with folic acid. OBJECTIVE: We aimed to compare the homocysteine-lowering potential of a folic acid supplement with that of 2 supplements containing different doses of vitamin B-12 in addition to folic acid. DESIGN: Female volunteers of childbearing age (n = 150) received a placebo for 4 wk followed by a 4-wk treatment with either 400 microg folic acid, 400 microg folic acid + 6 microg vitamin B-12, or 400 microg folic acid + 400 microg vitamin B-12. RESULTS: Significant reductions (P < 0.001) in plasma homocysteine were observed in all groups receiving vitamin treatment. The effect observed with the combination of folic acid + 400 microg vitamin B-12 (total homocysteine, -18%) was significantly larger than that with a supplement containing folic acid alone (total homocysteine, -11%) (P < 0.05). Folic acid in combination with a low vitamin B-12 dose (6 microg) affected homocysteine as well (-15%). CONCLUSIONS: These results suggest that the addition of vitamin B-12 to folic acid supplements or enriched foods maximizes the reduction of homocysteine and may thus increase the benefits of the proposed measures in the prevention of vascular disease and neural tube defects.