DOCSLIB.ORG

Genetic Variation of Folate-Mediated One-Carbon Transfer Pathway Predicts Susceptibility to Choline Deficiency in Humans

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Genetic Variation of Folate-Mediated One-Carbon Transfer Pathway Predicts Susceptibility to Choline Deficiency in Humans Genetic variation of folate-mediated one-carbon transfer pathway predicts susceptibility to choline deficiency in humans Martin Kohlmeier, Kerry-Ann da Costa, Leslie M. Fischer, and Steven H. Zeisel* Department of Nutrition, School of Public Health and School of Medicine, University of North Carolina, Chapel Hill, NC 27599 Edited by Bruce N. Ames, University of California, Berkeley, CA, and approved September 14, 2005 (received for review May 25, 2005) Choline is a required nutrient, and some humans deplete quickly Little is understood about the factors that influence dietary when fed a low-choline diet, whereas others do not. Endogenous requirements for choline in humans. Endogenous production of choline synthesis can spare some of the dietary requirement and choline during phosphatidylcholine biosynthesis (through the requires one-carbon groups derived from folate metabolism. We methylation of phosphatidylethanolamine by phosphatidyleth- examined whether major genetic variants of folate metabolism anolamine N-methyltransferase) is most active in liver but has modify susceptibility of humans to choline deficiency. Fifty-four been identified in many other tissues, including the brain and the adult men and women were fed diets containing adequate choline mammary gland (10–12). This synthesis of choline provides and folate, followed by a diet containing almost no choline, with some but not all of the choline required to sustain normal organ or without added folate, until they were clinically judged to be function in humans (4). The use of choline as a methyl-group choline-deficient, or for up to 42 days. Criteria for clinical choline donor also influences the dietary requirement for choline. The deficiency were a more than five times increase in serum creatine metabolism of choline, methionine, and methylfolate are closely kinase activity or a >28% increase of liver fat after consuming the interrelated and intersect at the formation of methionine from low-choline diet that resolved when choline was returned to the homocysteine (Fig. 1). Betaine:homocysteine methyltransferase diet. Choline deficiency was observed in more than half of the catalyzes the remethylation of homocysteine by using the choline participants, usually within less than a month. Individuals who were carriers of the very common 5,10-methylenetetrahydrofolate metabolite betaine as the methyl donor (13, 14). In an alternative dehydrogenase-1958A gene allele were more likely than noncar- pathway, 5-methyltetrahydrofolate:homocysteine S-methyl- riers to develop signs of choline deficiency (odds ratio, 7.0; 95% transferase (also known as methionine synthase) regenerates confidence interval, 2.0–25; P < 0.01) on the low-choline diet unless methionine by using a methyl group derived de novo from the they were also treated with a folic acid supplement. The effects of one-carbon pool (15). Perturbing the metabolism of one of the the C677T and A1298C polymorphisms of the 5,10-methylene methyl donors results in compensatory changes in the other tetrahydrofolate reductase gene and the A80C polymorphism of methyl donors because of the intermingling of these metabolic the reduced folate carrier 1 gene were not statistically significant. pathways (16–19). Rats ingesting a low-choline diet showed The most remarkable finding was the strong association in pre- diminished tissue concentrations of methionine and S- MEDICAL SCIENCES menopausal women of the 5,10-methylenetetrahydrofolate dehy- adenosylmethionine (SAM) (19) and of total folate (17). Hu- drogenase-1958A gene allele polymorphism with 15 times in- mans deprived of dietary choline have difficulty removing creased susceptibility to developing organ dysfunction on a low- homocysteine after a methionine load and develop elevated choline diet. plasma homocysteine concentrations (20). Methotrexate, which is widely used in the treatment of cancer, psoriasis, and rheu- genetic polymorphism ͉ methylene tetrahydrofolate dehydrogenase ͉ matoid arthritis, limits the availability of methyl groups by methylene tetrahydrofolate reductase ͉ reduced folate carrier ͉ competitively inhibiting dihydrofolate reductase, a key enzyme nutrient requirement in intracellular folate metabolism. Rats treated with methotrex- ate have diminished pools of all choline metabolites in liver (21). holine or its metabolites are needed for the structural Choline supplementation reverses the fatty liver caused by Cintegrity and signaling functions of cell membranes; it is the methotrexate administration (22–24). Genetically modified mice major source of methyl groups in the diet (one of choline’s with defective 5,10-methylene tetrahydrofolate reductase metabolites, betaine, participates in the methylation of homo- (MTHFR) activity become choline-deficient (25), an important cysteine to form methionine), and it directly affects cholinergic observation because many humans have genetic polymorphisms neurotransmission, transmembrane signaling, and lipid trans- that alter the activity of this enzyme (26, 27). Thus, common port͞metabolism (1). Choline is a required nutrient, and the SNPs in genes of folate metabolism could increase the demands Institute of Medicine and the National Academy of Sciences of for choline as a methyl-group donor, thereby increasing dietary ͞ the USA set an adequate intake level for choline of 550 mg day requirements for this essential nutrient. ͞ for men and 425 mg day for women (2). In this study, we examine whether SNPs in genes of folate One of the clinical consequences of dietary choline deficiency metabolism increase the susceptibility of humans to developing can be the development of fatty liver (hepatosteatosis) (3, 4), signs of organ dysfunction when fed a low-choline diet. because a lack of phosphatidylcholine limits the export of excess triglyceride from liver (5, 6). Also, choline deficiency induces hepatocyte apoptosis with leakage of alanine aminotransferase Conflict of interest statement: No conflicts declared. from liver into blood (4, 7, 8). Some people, when deprived of This paper was submitted directly (Track II) to the PNAS office. choline, develop muscle damage and increased creatine kinase Abbreviations: THF, tetrahydrofolate; MTHFD1, cytosolic 5,10-methylene tetrahydrofolate (CK) activity in blood (9). This effect may be attributable to dehydrogenase; MTHFR, 5,10-methylene tetrahydrofolate reductase; RFC1, reduced folate impaired membrane stability as a consequence of diminished carrier 1; SAH, S-adenosylhomocysteine; SAM, S-adenosylmethionine; CI, confidence inter- availability of phosphatidylcholine. The health significance of val; CK, creatine kinase. this rise in CK activity is unknown, but the rise is certainly an *To whom correspondence should be addressed. E-mail: steven࿝[email protected]. important surrogate marker for choline depletion status. © 2005 by The National Academy of Sciences of the USA www.pnas.org͞cgi͞doi͞10.1073͞pnas.0504285102 PNAS ͉ November 1, 2005 ͉ vol. 102 ͉ no. 44 ͉ 16025–16030 Downloaded by guest on September 28, 2021 Fig. 1. Three polymorphic genes are critical for folate-mediated one-carbon transfer. THF, tetrahydrofolate; MTHFR, 5,10-methylene tetrahydrofolate reductase; MTHFD1, cytosolic 5,10-methylene tetrahydrofolate dehydrogenase; RFC1, reduced folate carrier 1. Methods supplement (General Nutrition Center, Pittsburgh). The actual Subjects. Healthy adults were recruited by advertising. Both choline content of a sampling of duplicate portions was assayed males (n ϭ 31) and females (n ϭ 31) were included, with ages by our laboratory (29). Subjects were then switched to a choline- Ͻ ranging from 18 to 70 years. Inclusion was contingent on depletion diet containing 50 mg of choline per 70 kg of body age-typical good state of health as determined by physical weight per day by eliminating choline-rich foods, as confirmed by examination and standard clinical laboratory tests. Of the orig- analysis of duplicate food portions (32, 33). Details of diet inally recruited 62 subjects, 58 completed at least the initial formulations were previously published (28). Furthermore, par- baseline phase and the depletion phase. Of these 58, 1 subject ticipants were randomly assigned to receive either placebo or 400 ␮g of folic acid per day as a supplement in addition to the amount was excluded because of a 9-kg weight loss during the study, and ␮ ͞ 3 subjects were excluded because they did not comply with diet of folate consumed with food (100 g day). Diets were well restrictions, leaving 54 subjects included in all analyses. Subject tolerated. characteristics were as follows: 28 women and 26 men; 34 Periodic determinations of urinary choline and betaine con- Caucasians, 14 African-Americans, 3 Asians, and 3 of other centrations were used to confirm compliance with the dietary ethnicity; mean age was 38.7 Ϯ 15.4 (SD) years; mean body mass restrictions. Subjects remained on this depletion diet until they developed signs of organ dysfunction associated with choline index was 25.0 Ϯ 3.7 kg͞m2. The ethnicity of the participants deficiency, or for 42 days if they did not. Humans were deemed reflects the local population characteristics of the Raleigh– to have signs of organ dysfunction associated with choline Durham–Chapel Hill area of North Carolina. The criteria for deficiency if they had more than a 5-fold increase of serum CK subject selection and all details of the clinical protocol were activity while on the choline depletion diet and if this increased approved by the institutional review board of the University
Load more

Recommended publications
  • L-Carnitine, Mecobalamin and Folic Acid Tablets) TRINERVE-LC
    For the use of a Registered Medical Practitioner or a Hospital or a Laboratory only (L-Carnitine, Mecobalamin and Folic acid Tablets) TRINERVE-LC 1. Name of the medicinal product Trinerve-LC Tablets 2. Qualitative and quantitative composition Each film- coated tablets contains L-Carnitine…………………….500 mg Mecobalamin……………….1500 mcg Folic acid IP…………………..1.5mg 3. Pharmaceutical form Film- coated tablets 4. Clinical particulars 4.1 Therapeutic indications Vitamin and micronutrient supplementation in the management of chronic disease. 4.2 Posology and method of administration For oral administration only. One tablet daily or as directed by physician. 4.3 Contraindications Hypersensitivity to any constituent of the product. 4.4 Special warnings and precautions for use L-Carnitine The safety and efficacy of oral L-Carnitine has not been evaluated in patients with renal insufficiency. Chronic administration of high doses of oral L-Carnitine in patients with severely compromised renal function or in ESRD patients on dialysis may result in accumulation of the potentially toxic metabolites, trimethylamine (TMA) and trimethylamine-N-oxide (TMAO), since these metabolites are normally excreted in the urine. Mecobalamin Should be given with caution in patients suffering from folate deficiency. The following warnings and precautions suggested with parent form – vitamin B12 The treatment of vitamin B12 deficiency can unmask the symptoms of polycythemia vera. Megaloblastic anemia is sometimes corrected by treatment with vitamin B12. But this can have very serious side effects. Don’t attempt vitamin B12 therapy without close supervision by healthcare provider. Do not take vitamin B12 if Leber’s disease, a hereditary eye disease.
    [Show full text]
  • Guidelines on Food Fortification with Micronutrients
    GUIDELINES ON FOOD FORTIFICATION FORTIFICATION FOOD ON GUIDELINES Interest in micronutrient malnutrition has increased greatly over the last few MICRONUTRIENTS WITH years. One of the main reasons is the realization that micronutrient malnutrition contributes substantially to the global burden of disease. Furthermore, although micronutrient malnutrition is more frequent and severe in the developing world and among disadvantaged populations, it also represents a public health problem in some industrialized countries. Measures to correct micronutrient deficiencies aim at ensuring consumption of a balanced diet that is adequate in every nutrient. Unfortunately, this is far from being achieved everywhere since it requires universal access to adequate food and appropriate dietary habits. Food fortification has the dual advantage of being able to deliver nutrients to large segments of the population without requiring radical changes in food consumption patterns. Drawing on several recent high quality publications and programme experience on the subject, information on food fortification has been critically analysed and then translated into scientifically sound guidelines for application in the field. The main purpose of these guidelines is to assist countries in the design and implementation of appropriate food fortification programmes. They are intended to be a resource for governments and agencies that are currently implementing or considering food fortification, and a source of information for scientists, technologists and the food industry. The guidelines are written from a nutrition and public health perspective, to provide practical guidance on how food fortification should be implemented, monitored and evaluated. They are primarily intended for nutrition-related public health programme managers, but should also be useful to all those working to control micronutrient malnutrition, including the food industry.
    [Show full text]
  • DRIDIETARY REFERENCE INTAKES Thiamin, Riboflavin, Niacin, Vitamin
    Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline http://www.nap.edu/catalog/6015.html DIETARY REFERENCE INTAKES DRI FOR Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline A Report of the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline and Subcommittee on Upper Reference Levels of Nutrients Food and Nutrition Board Institute of Medicine NATIONAL ACADEMY PRESS Washington, D.C. Copyright © National Academy of Sciences. All rights reserved. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline http://www.nap.edu/catalog/6015.html NATIONAL ACADEMY PRESS • 2101 Constitution Avenue, N.W. • Washington, DC 20418 NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance. This project was funded by the U.S. Department of Health and Human Services Office of Disease Prevention and Health Promotion, Contract No. 282-96-0033, T01; the National Institutes of Health Office of Nutrition Supplements, Contract No. N01-OD-4-2139, T024, the Centers for Disease Control and Prevention, National Center for Chronic Disease Preven- tion and Health Promotion, Division of Nutrition and Physical Activity; Health Canada; the Institute of Medicine; and the Dietary Reference Intakes Corporate Donors’ Fund.
    [Show full text]
  • Does Dietary Melatonin Play a Role in Bone Mineralization?
    Syracuse University SURFACE Theses - ALL January 2017 Does Dietary Melatonin Play a Role in Bone Mineralization? Martha Renee Wasserbauer Syracuse University Follow this and additional works at: https://surface.syr.edu/thesis Part of the Medicine and Health Sciences Commons Recommended Citation Wasserbauer, Martha Renee, "Does Dietary Melatonin Play a Role in Bone Mineralization?" (2017). Theses - ALL. 120. https://surface.syr.edu/thesis/120 This Thesis is brought to you for free and open access by SURFACE. It has been accepted for inclusion in Theses - ALL by an authorized administrator of SURFACE. For more information, please contact [email protected]. ABSTRACT Introduction: Melatonin is generated as a product of normal circadian rhythm and is also is thought to play an important role in maintaining bone mineral density (BMD) by reducing chronic inflammation. Postmenopausal women are at an elevated risk of BMD loss due to declining estrogen and a natural decrease in melatonin synthesis with increasing age. Endogenous melatonin production is largely influenced by exposure to external light cues, but recent research has indicated that serum melatonin may be increased by the consumption of melatonin-rich foods. The purpose of this study was to quantify dietary-derived melatonin and examine its effects on inflammation, BMD, and sleep in a sample of postmenopausal women. Methods: Cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) was conducted to examine differences in melatonin consumption, BMD, and sleep in postmenopausal women with chronic and low-level inflammation indicated by level of C-reactive protein (CRP). Data from the years 2005-2010 was included in this study.
    [Show full text]
  • Identification of Folates by Iodine Oxidation at Acid, Neutral and Alkaline Ph
    Coppell et at.: Identification of folates by iodine oxidation 155 Pteridines Vo!' 1, 1989, pp. 155 - 157 Identification of Folates by Iodine Oxidation at Acid, Neutral and Alkaline pH By A . D . Coppell, R . J. Leeming!) Haematology Department, The General Hospital, Steelhouse Lane, Birmingham B4 6NH, Great Britain J. A. Blair Biology Division, Aston University, Birmingham B4 7ET, Great Britain (Received March 1989) Summary Oxidation by iodine at pH 1.5, pH 7.0 with and without catalase and at pH 12.5, differentiated folic acid, 5- methyltetrahydrofolic acid, 10-formylfolic acid, 10-formyltetrahydrofolic acid and 5-formyltetrahydrofolic acid, when the products were assayed with Lactobacillus casei. This method is proposed as an alternative to differential microbiological assay for identifying folates. Introduction Blakley (7). 5-Methyltetrahydrofolic acid (5- The methods commonly used for measuring folates CH3THF) was obtained from Eprova, Switzerland. in biological material a re microbiological (1) or radio­ 5-Formyltetrahydrofolic acid (5-CHOTHF) was a gift isotope dilution assays (2). The identification of in­ from Lederle. 10-Formyltetrahydrofolic acid (10- dividual folates is carried out using differential mi­ CHOTHF) was prepared by acidifying 5-CHOTHF, crobiological assays with L. casei, P. cerevisiae and leaving for one hour at 25 "C in the dark then return­ S.faecalis (3). This process is time consuming, re­ ing to neutral pH. Tetrahydrofolic acid (THF) was quiring the maintenance of three stock cultures in obtained from Eprova. The iodine solution was pre­ appropriate culture media. High performance liquid pared by saturating a 2 gi l potassium iodide solution chromatography (HPLC) using electrochemical de­ with crystalline iodine.
    [Show full text]
  • Vitamin B12 Deficiency ROBERT C
    Vitamin B12 Deficiency ROBERT C. OH, CPT, MC, USA, U.S. Army Health Clinic, Darmstadt, Germany DAVID L. BROWN, MAJ, MC, USA, Madigan Army Medical Center, Fort Lewis, Washington Vitamin B12 (cobalamin) deficiency is a common cause of macrocytic anemia and has been implicated in a spectrum of neuropsychiatric disorders. The role of B12 deficiency O A patient informa- in hyperhomocysteinemia and the promotion of atherosclerosis is only now being tion handout on vita- min B12 deficiency, explored. Diagnosis of vitamin B12 deficiency is typically based on measurement of written by the authors serum vitamin B12 levels; however, about 50 percent of patients with subclinical dis- of this article, is pro- ease have normal B12 levels. A more sensitive method of screening for vitamin B12 defi- vided on page 993. ciency is measurement of serum methylmalonic acid and homocysteine levels, which are increased early in vitamin B12 deficiency. Use of the Schilling test for detection of pernicious anemia has been supplanted for the most part by serologic testing for pari- etal cell and intrinsic factor antibodies. Contrary to prevailing medical practice, studies show that supplementation with oral vitamin B12 is a safe and effective treatment for the B12 deficiency state. Even when intrinsic factor is not present to aid in the absorp- tion of vitamin B12 (pernicious anemia) or in other diseases that affect the usual absorption sites in the terminal ileum, oral therapy remains effective. (Am Fam Physi- cian 2003;67:979-86,993-4. Copyright© 2003 American Academy of Family Physicians.) itamin B12 (cobalamin) plays manifestations (Table 1).It is a common cause an important role in DNA of macrocytic (megaloblastic) anemia and, in synthesis and neurologic func- advanced cases, pancytopenia.
    [Show full text]
  • Circulatory and Urinary B-Vitamin Responses to Multivitamin Supplement Ingestion Differ Between Older and Younger Adults
    nutrients Article Circulatory and Urinary B-Vitamin Responses to Multivitamin Supplement Ingestion Differ between Older and Younger Adults Pankaja Sharma 1,2 , Soo Min Han 1 , Nicola Gillies 1,2, Eric B. Thorstensen 1, Michael Goy 1, Matthew P. G. Barnett 2,3 , Nicole C. Roy 2,3,4,5 , David Cameron-Smith 1,2,6 and Amber M. Milan 1,3,4,* 1 The Liggins Institute, University of Auckland, Auckland 1023, New Zealand; [email protected] (P.S.); [email protected] (S.M.H.); [email protected] (N.G.); [email protected] (E.B.T.); [email protected] (M.G.); [email protected] (D.C.-S.) 2 Riddet Institute, Palmerston North 4474, New Zealand; [email protected] (M.P.G.B.); [email protected] (N.C.R.) 3 Food & Bio-based Products Group, AgResearch, Palmerston North 4442, New Zealand 4 High-Value Nutrition National Science Challenge, Auckland 1023, New Zealand 5 Department of Human Nutrition, University of Otago, Dunedin 9016, New Zealand 6 Singapore Institute for Clinical Sciences, Agency for Science, Technology, and Research, Singapore 117609, Singapore * Correspondence: [email protected]; Tel.: +64-(0)9-923-4785 Received: 23 October 2020; Accepted: 13 November 2020; Published: 17 November 2020 Abstract: Multivitamin and mineral (MVM) supplements are frequently used amongst older populations to improve adequacy of micronutrients, including B-vitamins, but evidence for improved health outcomes are limited and deficiencies remain prevalent. Although this may indicate poor efficacy of supplements, this could also suggest the possibility for altered B-vitamin bioavailability and metabolism in older people.
    [Show full text]
  • Folate and Folic Acid on the Nutrition and Supplement Facts Labels
    Folate and Folic Acid on the Nutrition and Supplement Facts Labels What is folate? Folate is a B vitamin that helps your body make healthy new cells. What foods provide folate? Folate is naturally present in many foods, including vegetables (especially asparagus, brussels sprouts, and dark green leafy vegetables such as spinach and mustard greens), fruits and fruit juices (especially oranges and orange juice), beef liver, nuts (such as walnuts), and beans and peas (such as kidney beans and black-eyed peas). Asparagus Brussels Dark leafy Oranges and sprouts greens orange juice Beef Nuts (such as Beans and peas (such liver walnuts) as kidney beans and black-eyed peas) The New What’s in it for you? June 2020 — 1 What foods provide folate? (Continued) You also get folate by eating foods fortified with folic acid. Folic acid is a form of folate that can be added to foods during the manufacturing process. Foods that are fortified with folic acid include: enriched breads, flours, pastas, rice, and cornmeal; fortified corn masa flour (used to make corn tortillas and tamales, for example); and certain fortified breakfast cereals. Folic acid is also found in certain dietary supplements. Enriched Enriched Enriched Enriched Enriched Fortified corn Fortified breads flours pastas rice cornmeal masa flour breakfast cereals How much folate do I need? The amount of folate you need depends on your age, but most adults can rely on the Daily Value (DV) to find out how much folate to consume. The Daily Values (DV) are reference amounts (in grams, milligrams, or micrograms) of nutrients to consume or not to exceed each day.
    [Show full text]
  • Melatonin As a Reducer of Neuro- and Vasculotoxic Oxidative Stress Induced by Homocysteine
    antioxidants Review Melatonin as a Reducer of Neuro- and Vasculotoxic Oxidative Stress Induced by Homocysteine Kamil Karolczak * and Cezary Watala Department of Haemostatic Disorders, Medical University of Lodz, ul. Mazowiecka 6/8, 92-215 Lodz, Poland; [email protected] * Correspondence: [email protected] Abstract: The antioxidant properties of melatonin can be successfully used to reduce the effects of oxidative stress caused by homocysteine. The beneficial actions of melatonin are mainly due to its ability to inhibit the generation of the hydroxyl radical during the oxidation of homocysteine. Melatonin protects endothelial cells, neurons, and glia against the action of oxygen radicals generated by homocysteine and prevents the structural changes in cells that lead to impaired contractility of blood vessels and neuronal degeneration. It can be, therefore, assumed that the results obtained in experiments performed mainly in the in vitro models and occasionally in animal models may clear the way to clinical applications of melatonin in patients with hyperhomocysteinemia, who exhibit a higher risk of developing neurodegenerative diseases (e.g., Parkinson’s disease or Alzheimer’s disease) and cardiovascular diseases of atherothrombotic etiology. However, the results that have been obtained so far are scarce and have seldom been performed on advanced in vivo models. All findings predominately originate from the use of in vitro models and the scarcity of clinical evidence is huge. Thus, this mini-review should be considered as a summary of the outcomes of the initial research in the field concerning the use of melatonin as a possibly efficient attenuator of oxidative Citation: Karolczak, K.; Watala, C.
    [Show full text]
  • Folate and Vitamin B12: Function and Importance in Cognitive Development Aron M
    Folate, Vitamin B12 and Brain Bhutta ZA, Hurrell RF, Rosenberg IH (eds): Meeting Micronutrient Requirements for Health and Development. Nestlé Nutr Inst Workshop Ser, vol 70, pp 161–171, Nestec Ltd., Vevey/S. Karger AG., Basel, © 2012 Folate and Vitamin B12: Function and Importance in Cognitive Development Aron M. Troen Nutrition and Brain Health Laboratory, Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel Abstract The importance of the B vitamins folate and vitamin B12 for healthy neurological develop- ment and function is unquestioned. Folate and vitamin B12 are required for biological methylation and DNA synthesis. Vitamin B12 also participates in the mitochondrial catabo- lism of odd-chain fatty acids and some amino acids. Inborn errors of their metabolism and severe nutritional deficiencies cause serious neurological and hematological pathology. Poor folate and vitamin B12 status short of clinical deficiency is associated with increased risk of cognitive impairment, depression, Alzheimer’s disease and stroke among older adults and increased risk of neural tube defects among children born to mothers with low folate status. Folate supplementation and food fortification are known to reduce incident neural tube defects, and B vitamin supplementation may have cognitive benefit in older adults. Less is known about folate and vitamin B12 requirements for optimal brain devel- opment and long-term cognitive health in newborns, children and adolescents. While increasing suboptimal nutritional status has observed benefits, the long-term effects of high folate intake are uncertain. Several observations of unfavorable health indicators in children and adults exposed to high folic acid intake make it imperative to achieve a more precise definition of folate and B12 requirements for brain development and function.
    [Show full text]
  • Nutrient Effects Upon Embryogenesis: Folate, Vitamin a and Iodine
    Hornstra G, Uauy R, Yang X (eds): The Impact of Maternal Nutrition on the Offspring. Nestlé Nutrition Workshop Series Pediatric Program, vol 55, pp 29–47, Nestec Ltd., Vevey/S. Karger AG, Basel, © 2005. Nutrient Effects upon Embryogenesis: Folate, Vitamin A and Iodine Thomas H. Rosenquista, Janee Gelineau van Waesa, Gary M. Shawb and Richard Finnellc aUniversity of Nebraska Medical Center, Omaha, Nebr.; bCalifornia Birth Defects Monitoring Project, Berkeley, Calif., and cTexas A & M University Medical Center, Houston, Tex., USA Introduction The period of human ‘embryogenesis’, the foundation of this chapter, is generally taken to include the initial 8-week period of human development, from fertilization through organogenesis. Knowledge of the effects of nutrients upon the normal development of the embryo during this period typically has been acquired by observation of the effects that accompany some perturbation of the delivery of a given nutrient; therefore this chapter will focus upon the results of ‘perturbed’ delivery of folic acid, vitamin A, and iodine. While a developmental defect may occur at virtually any time during gestation, only perturbations that occur during embryogenesis can produce major anatomical malformations of organs that develop from the neural tube and the neural crest. Defects of the neural tube and neural crest are the most common and the most devastating in terms of mortality and morbidity, stillbirths, and spontaneous abortions. These include neural tube closure defects such as spina bifida, orofacial defects, and conotruncal heart defects [1–3]. Based upon these data, it may be argued that the most important nutri- ent effects during embryogenesis are those that impact upon the development of the neural tube and the neural crest; therefore, these effects will be the principal topic of this chapter.
    [Show full text]
  • WHO Technical Consultation on Folate and Vitamin B12 Deficiencies
    Conclusions of a WHO Technical Consultation on folate and vitamin B12 deficiencies All participants in the Consultation Key words: Folate, vitamin B12 The consultation agreed on conclusions in four areas: » Indicators for assessing the prevalence of folate and Preamble vitamin B12 deficiencies » Health consequences of folate and vitamin B12 defi- Folate and vitamin B12 deficiencies occur primarily as ciencies a result of insufficient dietary intake or, especially in » Approaches to monitoring the effectiveness of inter- the case of vitamin B12 deficiency in the elderly, poor ventions absorption. Folate is present in high concentrations » Strategies to improve intakes of folate and vitamin B12 in legumes, leafy green vegetables, and some fruits, so lower intakes can be expected where the staple diet consists of unfortified wheat, maize, or rice, and when Indicators for assessing and monitoring the intake of legumes and folate-rich vegetables and vitamin status fruits is low. This situation can occur in both wealthy and poorer countries. Animal-source foods are the only Prevalence of deficiencies natural source of vitamin B12, so deficiency is prevalent when intake of these foods is low due to their high The recent review by WHO showed that the majority cost, lack of availability, or cultural or religious beliefs. of data on the prevalence of folate and vitamin B12 Deficiency is certainly more prevalent in strict vegetar- deficiencies are derived from relatively small, local ians, but lacto-ovo vegetarians are also at higher risk surveys, but these and national survey data from a for inadequate intakes. If the mother is folate-depleted few countries suggest that deficiencies of both of these during lactation, breastmilk concentrations of the vitamins may be a public health problem that could vitamin are maintained while the mother becomes affect many millions of people throughout the world.
    [Show full text]