[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.

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.

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.

B-Vitamin status and intake in European adolescents. A review of the literature / Estado vitamínico e ingesta de vitaminas en adolescentes europeos. Revisión bibliográfica

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

Antecedentes: Las recomendaciones, tanto nacionales como internacionales, sobre el consumo de vitamina B por adolescentes, se basan en valoraciones y extrapolaciones de datos de adultos. Los adolescentes debido a su crecimiento y desarrollo, y, por ello, a la necesidad relativamente alta de energía y nutrientes, son desde el punto de vista de la nutrición un grupo vulnerable. Además, una insuficiente ingesta de varias vitaminas B se relaciona con el desarrollo de cáncer, defectos del tubo neural y enfermedades cardiovasculares Objetivo: El objetivo de este trabajo es valorar el estado vitamínico y de homocisteina y la ingesta de vitaminas B en adolescentes europeos, basándose en datos publicados Método: La base de datos Medline (www.ncvi.nlm.nih. gov), se analizó en función de términos tales como “Vitamina B” “Homocisteina”, “Europa”…, etc. Para esta revisión se analizaron estudios publicados entre junio de 1980 y diciembre de 2004. Los resultados de ingesta de vitamina B se compararon, respectivamente, con los de EAR y AI, según recomendación del Instituto de Medicina de EEUU. Debido a las lagunas de valores de referencia para adolescentes, los resultados se compararon con los diferentes umbrales para adultos. Resultados: Considerando las limitaciones de la comparación en la revisión de estudios, por ejemplo: diferentes metodologías, tamaño de muestras, grupos de edad, etc., la media de ingesta de vitamina B sobrepasa a la de EAR y AI. Los chicos están mejor proveídos de vitamina B que las chicas. La ingesta decrecía con la edad en ambos géneros. Se apreciaba una posible deficiencia de fólico y las chicas, en particular, parecían padecer más riesgos. No se observaron claras tendencias regionales en la ingesta de vitaminas. Los niveles de vitaminas B6 y B12, fólico y homocisteina en sangre se encontraron dentro de los valores de referencia. No obstante, la enorme desviación estándar de fólico incrementaba la posibilidad de un deficiente consumo en parte de la población Conclusión: Las chicas europeas parecen estar a riesgo de deficiencia de fólico. Los suplementos y alimentos enriquecidos no fueron considerados en la mayoría de los estudios publicados, lo cual desvirtuaba la ingesta real. Todavía se deben establecer métodos estandarizados de registro dietético y valores de referencia, tanto para vitaminas del grupo B como para homocisteina. Por lo tanto, son necesarias investigaciones futuras

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.

Alzheimer y la alimentación / Alzheimer´s disease and nutrition

La enfermedad de Alzheimer es la demencia senil de mayor prevalencia en la población occidental. Aunque de origen multifactorial, a medida que se profundiza en su fisiopatología, gana fuerza la hipótesis de la implicación de factores de riesgo nutricionales, como son bajos niveles de antioxidantes y de las vitaminas folato, B6 y B12, implicadas en el ciclo metabólico de la homocisteína. El diagnóstico precoz es esencial para mantener al paciente en un estado funcional el mayor tiempo posible. Hay que garantizar el aporte de energía y nutrientes, bien mediante alimentos, suplementos o alimentación enteral. Aunque es prematuro hablar de una prevención nutricional de la demencia, puede estar indicada la suplementación de vitaminas a dosis fisiológicas en los mayores de 60 años con una buena relación coste-beneficio (AU)

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.

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.

Vitamins B12, B6 and folate as determinants of homocysteine concentration in the healthy population.

The metabolism of a substrate is closely linked to that of its cofactor(s). In the case of homocysteine, the vitamins B12, B6 and folic acid are involved in its metabolism, acting as coenzymes. To evaluate the role of these vitamins as determinants of homocysteine concentration in the healthy population, only data from this group should be considered. Studies dealing with vitamin deficiency and the occurrence of elevated homocysteine levels as well as with the treatment of elevated homocysteine levels by supplementing one or more of the vitamins have to be omitted. In the healthy population with "normal" homocysteine levels and a vitamin status currently regarded as adequate, folate seems to play the most important role in determining the blood homocysteine level. This has been derived from supplementation studies as well as from statistical correlation analysis regarding the relationship of the three vitamins to homocysteine. Until now, recommended dietary allowances for folate have been defined on the basis of the absence of clinical signs of deficiency as well as morphological alterations of blood cells indicating an early stage of folate deficiency. However, these recommended dietary allowance values do not seem to be sufficient when looking at homocysteine as a functional parameter of folate status. Due to the important role of folate status as a determinant of homocysteine concentration, it may be necessary to redefine an adequate blood folate level and probably reformulate dietary allowances for this B-vitamin.

Folic acid and Vitamin B6 supplementation and plasma homocysteine concentrations in healthy young women.

Elevated plasma homocysteine levels are a risk factor for atherosclerotic disease. Elevated fasting plasma homocysteine concentrations can be reduced by vitamin supplementation with folic acid, vitamin B6 and vitamin B12, but the effect of nutritive amounts of single vitamins on homocysteine plasma levels within the normal range is not known. This study was performed to investigate the effect of folic acid supplementation (400 micrograms/d) on fasting plasma homocysteine levels in healthy young women, in comparison to vitamin B6 (2 mg/d) or a combination of both vitamins. Healthy young women with normal homocysteine levels were supplemented for four weeks either with folic acid, vitamin B6 or the combination. The combination of folic acid and vitamin B6 reduced plasma homocysteine by 17%. Supplementation with folic acid reduced plasma homocysteine levels by 11.5%. The effect of folic acid and vitamin B6 was not significantly different from the effect of folic acid alone. Vitamin B6 had no effect on plasma homocysteine concentrations. Results show that homocysteine levels within the normal range are lowered by low-dose vitamin supplementation including folic acid.

The role of homocysteine, folate and other B-vitamins in the development of atherosclerosis.

Recently, elevated homocysteine blood concentrations have been identified as an independent risk factor for the development of atherosclerotic lesions. The amino acid homocysteine is metabolized in the human body involving the vitamins folic acid, B12 and B6 as essential cofactors and coenzymes, respectively. There is an inverse relationship between the status of the relevant B-vitamins and the homocysteine blood concentration. Supplementation of these vitamins results in a significant reduction of the homocysteine level. Nutritive amounts seem to be sufficient to obtain this reduction, even in the case of elevated homocysteine levels.

[Micronutrients in pregnancy]. / Mikronährstoffe in der Schwangerschaft.

During pregnancy the demands for energy and far more for micronutrients are increased. Discrepancies between the intake of certain micronutrients such as iodine, iron and folic acid and the recommended quantities during pregnancy are to be expected. Consequences of an unsufficient supply of these micronutrients might be goitre, anemia and with special reference to folic acid the occurrence of neural tube defects. Deficiency can be prevented by careful choice of food. Supplementation with special micronutrients is necessary before respective during pregnancy however for example to prevent neural tube defects by periconceptional supplementation with folic acid.

Causes and consequences of hyperhomocyst(e)inemia.

Increased plasma concentrations of the sulfur-containing amino acid homocyst(e)ine are designated as hyperhomocyst(e)inemia. Various definitions have been used to derive cut-off levels for hyperhomocyst(e)inemia. The classification by Kang is now generally used distinguishing moderate, intermediate and severe hyperhomocyst(e)inemia. A variety of causes are discussed for the etiology of the disease which can be grouped into genetic and nongenetic factors. Severe hyperhomocyst(e)inemia is accompanied by homocystinuria and several other symptoms occurring early in life. Treatment is mandatory for normal development and prevention of premature atherosclerosis. Even less severe forms of hyperhomocyst(e)inemia imply a substantially elevated risk for vascular diseases. Etiology and severity of defect(s) leading to hyperhomocyst(e)inemia are the basis for treatment. In genetic defects, supplementation with the cofactor(s) of the affected enzyme is used to enhance enzyme activity. Alternative routes in the pathway may also be enhanced. Nongenetic hyperhomocyst(e)inemia often requires correction of suboptimal vitamin concentrations. Nutritive doses of the vitamins may be sufficient for treatment of less severe forms as well as for prevention of hyperhomocyst(e)inemia.