Ask ODS The most commonly used cutoff value for elevated homocysteine levels is 16 micromol/L, although slightly lower values of 12 to 14 micromol/L have also been used [2]. In another clinical trial in older adults (mean age 74.1 years) with elevated homocysteine levels, supplementation with 400 mcg folic acid plus 500 mcg vitamin B12 and 600 IU vitamin D3 for 2 years lowered homocysteine levels but did not affect cognitive performance compared with 600 IU vitamin D3 alone [107]. This potent B vitamin, folic acid, plays a crucial role for adults, especially women of child-bearing age, who want to keep their heart functioning . However, most, if not all, of the currently available data are observational, and confounding weakens the ability to demonstrate causal inference. As an essential nutrient sourced from food, folate is not associated with side effects or risks. The U.S. Public Health Service and CDC have published similar recommendations [36]. [, Venn BJ, Green TJ, Moser R, et al. Depression Association of folic acid supplementation during pregnancy with the risk of autistic traits in children exposed to antiepileptic drugs in utero. Plasma folate, vitamin B-6, and vitamin B-12 and breast cancer risk in BRCA1- and BRCA2-mutation carriers: a prospective study. U. S. Preventive Services Task Force, Bibbins-Domingo K, Grossman DC, et al. Am J Clin Nutr 2000;71:1295S-303S. According to observational studies, folic acid supplementation might increase mean gestational age and lower the risk of preterm birth [1,144]. [, Linnebank M, Moskau S, Semmler A, et al. 2009;169(4):335-41. doi:10.1001/archinternmed.2008.574, He H, Shui B. Folate intake and risk of bladder cancer: a meta-analysis of epidemiological studies. 2014;65(3):286-292. doi:10.3109/09637486.2013.866641, Chen P, Li C, Li X, Li J, Chu R, Wang H. Higher dietary folate intake reduces the breast cancer risk: a systematic review and meta-analysis. Pediatrics 2005;116:580-6. Folate Deficiency. Buy Solgar Folate 1,333 mcg DFE, 100 Tablets - 800 mcg Bio-Active Metafolin - Heart Health - Non-GMO, Vegan, Gluten Free, Dairy Free, Kosher - 100 Servings on Amazon.com FREE SHIPPING on qualified orders [, DeVilbiss EA, Gardner RM, Newschaffer CJ, et al. On the other hand, some research has found a potential tumor-promoting effect with folic acid supplementation. Meta-analysis of B vitamin supplementation on plasma homocysteine, cardiovascular and all-cause mortality. It is differentiated from other types of anemia in that the reduced red blood cell count will be accompanied by the appearance of large, misshapen, immature red blood cells called megaloblasts. [, Molloy AM, Kirke PN, Brody LC, et al. A systematic review of these studies had mixed results [121]. In vitamin B12 deficiency, higher serum folate is associated with increased total homocysteine and methylmalonic acid concentrations. Int J Clin Pract. Lancet. Am J Clin Nutr 2011;94:666S-72S. Erythrocyte folate concentrations provide a longer-term measure of folate intakes; a concentration above 140 ng/mL indicates adequate folate status [2,3,7,9]. Neural tube defects (NTDs) are congenital disabilitiesof the brain or spinal cord that typically occur during the first month of pregnancy. Centers for Disease Control and Prevention. In a 2015 study published in JAMA, researchers evaluated whether folic acid therapy could reduce the risk of first-time stroke. Although this is rare in the United States, deficiency can occur in people with certain risk factors. Am J Clin Nutr 2011;94:303S-12S. Size: 100 Count (Pack of 1) However, researchers did not observe a difference in folic acid levels between AMD participants and controls. If you buy through links on this page, we may earn a small commission Heres our process. A daily multivitamin may offer a modest benefit to cognitive function among older adults, according to a new study. This polymorphism results in less biologically available 5-MTHF and, thus, reduced methylation potential, leading to elevated homocysteine levels and an increased risk of NTDs [1,3,20,40]. Treatment with folic acid plus vitamin B12 reduced homocysteine concentrations by 36% but did not improve cognitive function. [, Liu S, Joseph KS, Luo W, et al. Evidence also indicates that folate might play a dual role in cancer initiation and progression [57]. The activity of dihydrofolate reductase varies greatly among individuals [3]. JAMA 2008;300:795-804. The mcg DFE is the unit of measure for folate on the new Nutrition Facts or Supplement Facts label. Sulfasalazine Folate 1,333 MCG DFE (800 MCG FOLIC ACID) Tablets. JAMA Neurol 2018;75:160-8. Am J Clin Nutr 2015;102:848-57. High concentrations of folate and unmetabolized folic acid in a cohort of pregnant Canadian women and umbilical cord blood. Any mention in this publication of a specific product or service, or recommendation from an organization or professional society, does not represent an endorsement by ODS of that product, service, or expert advice. To avoid toxicity, be aware of the appropriate dosage (above) and keep the safe upper intake levels in mind. Results from a study of 52 men and women with major depressive disorder showed that only 1 of 14 participants with low serum folate levels responded to antidepressant treatment compared with 17 of 38 with normal folate levels [120]. However, for some people, such as those who are pregnant, supplements are an easy way to ensure adequate vitamin B9 intake. Based on the metabolic interactions between folate and vitamin B12, the FNB established a UL for the synthetic forms of folate available in dietary supplements and fortified foods (Table 3) [2]. Is high homocysteine level a risk factor for cognitive decline in elderly? Available In. Additional research and validation in other studies are needed before firm conclusions can be drawn. Arch Intern Med 2012;172:540-7. While folate immediately converts in the digestive tract into the active form of vitamin B9, called 5-methyl-THF (5-MTHF), folic acid needs to enter the bloodstream and reach the liver and other tissues for conversion. https://www.federalregister.gov/documents/2016/05/27/2016-11867/food-labeling-revision-of-the-nutrition-and-supplement-facts-labels#h-126, https://www.efsa.europa.eu/en/efsajournal/pub/7452. [, Morris MS, Jacques PF, Rosenberg IH, Selhub J. Higher plasma folate concentrations have also been associated with an increased risk of breast cancer in women with a BRCA1 or BRCA2 mutation [75]. Environ Health Perspect 2017;125:097007. Therefore, 0.5 mg supplementary folic acid on an empty stomach is equal to 1 DFE (or 2x as potent as food folate)[1]. [. Med Hypotheses. For a general overview of Folate, see our consumer fact sheet on Folate. This essential nutrient is known for its ability to prevent neural tube (precursor to the brain and spinal cord) birth defects in pregnant women who consume adequate amounts (400 mcg or >). An analysis of data from the Norwegian Mother and Child Cohort Study, which included 104,946 children, found that children exposed to antiepileptic drugs (known to reduce folate in vivo) in utero were 5.9 to 7.9 times more likely to have autistic traits at ages 18 and 36 months if their mothers did not take folic acid periconceptionally than if they did [44]. Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial. Additional research is needed to fully understand the extent to which maternal consumption of folic acid might affect the risk of these adverse birth outcomes. The researchers found no association between B-vitamin supplementation and cancer outcomes. [, Clarke R, Halsey J, Lewington S, et al. In April 2016, FDA approved the voluntary addition of up to 154 mcg folic acid/100 g to corn masa flour [15]. Folate is absorbed across the human colon: evidence by using enteric-coated caplets containing 13C-labeled [6S]-5-formyltetrahydrofolate. MTHFR Gene, Folic Acid, and Preventing Neural Tube Defects. Always speak with a healthcare provider before taking a supplement to ensure that the supplement and dosage are appropriate for your individual needs. Am J Clin Nutr 2008;88:1602-10. Effect of homocysteine lowering treatment on cognitive function: a systematic review and meta-analysis of randomized controlled trials. In: Shils M, Shike M, Ross A, Caballero B, Cousins RJ, eds. NTDs result in malformations of the spine (spina bifida), skull, and brain (anencephaly). Centers for Disease Control and Prevention. For some people, supplementation with 5-MTHF might be more beneficial than with folic acid (see "People with an MTHFR polymorphism" below) [20,21]. Although studies conducted since that time do not demonstrate a clear protective association (possibly because of food fortification effects, study design flaws, or inadequate sample sizes) [142], the U.S. Preventive Services Task Force recommends that all women who are planning to become or capable of becoming pregnant take a daily supplement containing 400 to 800 mcg folic acid starting least 1 month before conception and continuing through the first 2 to 3 months of pregnancy [37]. [, Venn BJ, Green TJ, Moser R, et al. JAMA 2013;309:570-7. Folate and cancer: a tale of Dr. Jekyll and Mr. Hyde? The ratio of mg to mcg is 1:1000. Int J Cancer 2015;137:930-9. [, Green TJ, Liu Y, Dadgar S, et al. 2015;37(5):430-438. doi:10.1016/S1701-2163(15)30258-9, Xu L, Huang Z, He X, Wan X, Fang D, Li Y. J Am Acad Dermatol 1993;28:466-9. Am J Psychiatry 2012;169:1267-74. Supplementation did, however, significantly reduce the risk of stroke by 25%. Individuals taking these medications on a regular basis should discuss their folate intakes with their health care providers. Modern Nutrition in Health and Disease. Am J Epidemiol 2013;178:1028-37. J Affect Disord 2000;60:121-30. Yet, this process is slow and inefficient in some people. Pregnant women [, Lamers Y. Folate recommendations for pregnancy, lactation, and infancy. High intake of folic acid may lead to increased blood levels of unmetabolized folic acid. Folate, methionine, and alcohol intake and risk of colorectal adenoma. 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. FDA approves folic acid fortification of corn masa flour. Concentrations of unmetabolized folic acid and primary folate forms in pregnant women at delivery and in umbilical cord blood. Total Folic Acid intake should not exceed 1000 mcg (1,667 mcg DFE) per day. Bethesda (MD): National Center for Biotechnology Information (US); 2012-. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: Section 5. Int J Food Sci Nutr 2014;65:286-92. Centers for Disease Control and Prevention. [, Ebbing M, Bleie O, Ueland PM, et al. *These statements have not been evaluated by the Food and Drug Administration. In addition, the severity of autistic traits was inversely associated with both maternal plasma folate concentrations and folic acid doses. [, Ho RC, Cheung MW, Fu E, et al. Maternal folate status as a risk factor for autism spectrum disorders: a review of existing evidence. Antiepileptic medications, such as phenytoin (Dilantin), carbamazepine (Carbatrol, Tegretol, Equetro, Epitol), and valproate (Depacon), are used to treat epilepsy, psychiatric diseases, and other medical conditions. Although most people consume adequate amounts of folate, certain groups, including women of childbearing age and non-Hispanic black women, are at risk of insufficient folate intakes. It is usually only after symptoms are severe that healthcare providers identify folate deficiency anemia. Mean concentrations in this age group range from 211 to 294 ng/mL depending on age, dietary habits, and supplement use. Some groups are at risk of taking excess folate, including older adults and children who take supplements and eat fortified foods. In addition, women with the 677C>T MTHFR polymorphismwhich is more common in Hispanics than Caucasians, Asians, and African Americansmight have an increased risk of NTDs [1,3,27,40]. A secondary analysis of the study by Cole and colleagues [71] found that folic acid supplementation significantly increased the risk of prostate cancer [76] . Therefore, it is important to talk to your healthcare provider about any supplements you plan to take and check in about any potential interactions with other supplements or medications. Symptoms include: In addition to symptoms of megaloblastic anemia, other symptoms associated with folate deficiency include: Your provider may recommend you take folate if you are pregnant, breastfeeding, or deficient. Little is known about the long-term effects of high folic acid doses in children [7]. Do not use if outer bottle seal is missing or damaged. 1). [, Kong X, Huang X, Zhao M, et al. Folate's role in neurotransmitter (chemical messengers) synthesis and homocysteine metabolism has prompted research on its potential effect on depression. Unraveling the complex relationship between folate and cancer risk. Keep out of reach of children. Its used in supplements and added to processed food products, such as flour and breakfast cereals. EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA), et al. [, Clarke R, Bennett D, Parish S, et al. Foods providing 20% or more of the DV are considered to be high sources of a nutrient, but foods providing lower percentages of the DV also contribute to a healthful diet. Instead, it needs to be converted in your liver or other tissues (6). Researchers found that spina bifida was lower in places that mandated folic acid fortification than in those where it was voluntary. The role of dietary supplements in inflammatory bowel disease: a systematic review. [, Figueiredo JC, Grau MV, Haile RW, et al. [, Crider KS, Bailey LB, Berry RJ. Folic acid food fortification-its history, effect, concerns, and future directions. Folic Acid and Pregnancy: How Much Do You Need? [, Smith AD, Refsum H. Homocysteine, B vitamins, and cognitive impairment. Another meta-analysis of four clinical trials found that 50010,000 mcg folic acid per day for 612 weeks as an adjunctive treatment did not significantly affect measures of depression compared with placebo [128]. Proc Natl Acad Sci U S A 2007;104:19995-20000. But is there any evidence that folic acid is a hair-growth treatment? Questions about this possibility still remain, but the focus of concern has shifted to the potential for large amounts of folate to precipitate or exacerbate the anemia and cognitive symptoms associated with vitamin B12 deficiency [2,85,148-153]. Eur J Clin Nutr. National Library of Medicine. Contributions of enriched cereal-grain products, ready-to-eat cereals, and supplements to folic acid and vitamin B-12 usual intake and folate and vitamin B-12 status in US children: National Health and Nutrition Examination Survey (NHANES), 2003-2006. [, Roffman JL. More research is needed to fully understand how dietary folate and supplemental folic acid affect cancer risk and whether their effects differ by timing of exposure. Folate supplementation: too much of a good thing? The risk of ASD was even higher (2.5 times) if the women were exposed to indoor pesticides and had daily folic acid intakes of less than 800 mcg, suggesting that folic acid might attenuate the potentially increased risk of ASD from pesticide exposure. Can J Psychiatry 2016;61:576-87. Folate is a B vitamin that helps your body make healthy new cells. NTDs Folate: a magic bullet or a double edged sword for colorectal cancer prevention? If you are prenant, nursing, taking any medications or have any medical condition, please consult your healthcare practitioner before taking any dietary supplement. Effects of folate and vitamin B12 deficiencies during pregnancy on fetal, infant, and child development. To meet this need, the FNB increased the folate RDA from 400 mcg DFE/day for nonpregnant women to 600 mcg DFE/day during pregnancy [2]. Converting Units of Measure for Folate, Niacin, and Vitamins A, D, and Am J Clin Nutr 2006;84:361-70. For folic acid, 1,000 mcg is equivalent to 1,667 mcg DFE because 0.6 mcg folic acid = 1 mcg DFE [11,164]. In a clinical trial in 148 adults with major depressive disorder, supplementation with 7,500 mcg/day 5-MTHF for 30 days followed by 15,000 mcg/day for another 30 days, both in conjunction with SSRI treatment, did not improve measures of depression compared with SSRI treatment plus placebo [131]. Serum folate, vitamin B12, and homocysteine in major depressive disorder, Part 1: predictors of clinical response in fluoxetine-resistant depression. Solgar Folate 1,333 MCG DFE (800 MCG Folic Acid) - The Healthy Place [. Am J Clin Nutr 2014;100:657-66. The suggested adult dosage is one tablet per day, preferably . Obeid R, Holzgreve W, Pietrzik K. Is 5-methyltetrahydrofolate an alternative to folic acid for the prevention of neural tube defects? They are the most common major congenital malformations of the central nervous system and result from a failure of the neural tube to close at either the upper or lower end on days 21 to 28 after conception [132,133]. In the United States and most other developed nations, breakfast cereals, flour, bread, and other foods are fortified with folic acid to prevent folate deficiency within the general population. Several epidemiological studies have suggested an inverse association between folate intakes and status and the risk of colorectal, lung, pancreatic, esophageal, stomach, cervical, ovarian, breast, bladder, and other cancers [1,9,54,55]. Folate Augmentation of Treatment--Evaluation for Depression (FolATED): randomised trial and economic evaluation. For example, the prospective Norwegian Mother and Child Cohort Study that included 85,176 children aged 3.3 to 10.2 years found that children of mothers who took up to 400 mcg per day folic acid during all of part of the time from 4 weeks before to 8 weeks after the start of pregnancy were 39% less likely to have autistic disorder than those whose mothers did not take the supplements [50]. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. [, Halsted CH, Gandhi G, Tamura T. Sulfasalazine inhibits the absorption of folates in ulcerative colitis. Am J Clin Nutr 2014;100:1578-86. [, Trujillo J, Vieira MC, Lepsch J, et al. Folic acid supplements may cause some common side effects, including: Severe side effects are primarily associated with excessive supplementation. 2014;110(9):2327-2338. doi:10.1038/bjc.2014.155, Wien TN, Pike E, Wislff T, Staff A, Smeland S, Klemp M. Cancer risk with folic acid supplements: a systematic review and meta-analysis. Effects of homocysteine-lowering with folic acid plus vitamin B12 vs placebo on mortality and major morbidity in myocardial infarction survivors: a randomized trial. J Nutr 2002;132:3353-5. However, consuming a supplement like folate may have potential side effects. Adequate Intake (AI): Intake at this level is assumed to ensure nutritional adequacy; established when evidence is insufficient to develop an RDA. The measure of mcg DFE is used because the body has an easier time absorbing folic acid than folate. How Do I Know If I Have a Folate Deficiency? Intake recommendations for folate and other nutrients are provided in the Dietary Reference Intakes (DRIs) developed by an expert committee of the Food and Nutrition Board (FNB) at the National Academies of Sciences, Engineering, and Medicine [2]. Measures of depression did not improve in participants taking folic acid compared with those taking placebo. Cognitive impairment is associated with elevated serum homocysteine levels among older adults. 1 Folate is shown as mcg DFE and as a %DV, 2 Folic acid is shown in parenthesis and is important for individuals who could become pregnant. Several studies indicate that chronically elevated levels of unmetabolized folic acid may have adverse health effects, including increased cancer risk. Annu Rev Nutr 2017;37:269-91. Am J Clin Nutr 2009;89:702S-6S. Whether this policy change has affected the disparities in NTD rates between Hispanic women and other populations is not yet known. Intakes of folate, vitamin B6 and B12 and risk of depression in community-dwelling older adults: the Quebec Longitudinal Study on Nutrition and Aging. The .gov means its official.Federal government websites often end in .gov or .mil. It can be purchased at many drug stores, as well as online. Amazon's Choice in Vitamin B9 (Folic Acid) Supplements by Solgar. Folic acid is also essential for the metabolism of homocysteine and other importan doi:10.2105/AJPH.2015.302902. Our team thoroughly researches and evaluates the recommendations we make on our site. The ULs do not apply to individuals taking high doses of supplemental folate under medical supervision [2]. Effects of homocysteine lowering with B vitamins on cognitive aging: meta-analysis of 11 trials with cognitive data on 22,000 individuals. Folic acid supplementation reduced homocysteine concentrations by 26% and significantly improved global cognitive function, memory, and information processing speed compared with placebo, but it did not affect sensorimotor speed, complex speed, or word fluency. Cancer Am J Gastroenterol 1997;92:485-9. The information contained herein is for informational purposes only and does not establish a doctor-patient relationship. Methotrexate We use tools, such as cookies, to provide you with the best user experience. Please be sure to consult your physician before taking this or any other product. Am J Clin Nutr 2011;94:1053-62. General information about NTDs, folic acid, and folate. About half of the population cannot make this conversion efficiently, due to genetic variation (more about that here). In addition, a 2018 prospective study found that folic acid intake from fortified foods and supplements was positively associated with a risk of cancer recurrence among 619 patients with nonmuscle-invasive bladder cancer, whereas natural folate intakes showed no significant association [74]. Dietary folate, methionine, riboflavin, and vitamin B-6 and risk of sporadic colorectal cancer. Conversion of calciumlmethylfolate and (6S)5methyltetrahydrofolic acid glucosamine salt into dietary folate equivalents.. Sulfasalazine (Azulfidine) is used primarily to treat ulcerative colitis. [, Pitkin RM. [, Andreeva VA, Touvier M, Kesse-Guyot E, et al. Since high levels of homocysteines can contribute to heart disease and stroke, some research has looked at the connection between folate and heart disease. The possible mechanisms are unclear but might be related to folates role in methylation reactions in the brain, neurotransmitter synthesis, and homocysteine metabolism [117,118]. [, Mason JB, Tang SY. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. Dementia, cognitive function, and Alzheimers disease So, if you have both, high folate intake can sometimes mask B12 deficiency until it's too late to correct it. Researchers observed that folate deficiency was associated with an increased risk of early and any AMD by 75% to 89%. in Store, Avoiding the Use of Artificial Ingredients or Fillers. Subsequent research has shown an association between increased cancer cell proliferation and higher serum folate concentrations in men with prostate cancer [77]. 2016;70(3):380-385. doi:10.1038/ejcn.2015.202, Shere M, Bapat P, Nickel C, Kapur B, Koren G. Association between use of oral contraceptives and folate status: A systematic review and meta-analysis. The mechanism of these potential benefits is unknown, but it might be related to folic acids role in DNA methylation, which, in turn, can affect neurodevelopment [47-49]. J Nutr Biochem 1999;10:66-88. These doses exceed the UL and should be taken only under medical supervision [143]. Summary. The underlying cause of macular AMD is not well understood. In addition, researchers concluded it was particularly effective in populations without folate food fortification. J Nutr 2013;143:867-71. [, Cole BF, Baron JA, Sandler RS, et al. That's because NTDs can occur before a person knows they are pregnant. [, Tomaszewski JJ, Cummings JL, Parwani AV, et al. DRI is the general term for a set of reference values used for planning and assessing nutrient intakes of healthy people. 15 Healthy Foods That Are High in Folate (Folic Acid), Sarsaparilla: Benefits, Risks, and Side Effects, Taking a Daily Multivitamin May Protect Your Memory Later in Life. Supplemental 5-MTHF is available in the form of levomefolate calcium or levomefolate magnesium. [, Papakostas GI, Petersen T, Mischoulon D, et al. Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50,000 individuals. Low levels of vitamin B9 are associated with an increased risk of several health conditions, including: For these reasons, supplementing with vitamin B9 is common. For example, one trial in the Netherlands administered either 800 mcg folic acid or placebo daily for 3 years to 818 participants aged 5070 years with elevated homocysteine levels (13 micromol/L or higher) and normal vitamin B12 levels [116].