Since about half of all pregnancies in the United States are unplanned 1 , experts recommend all women get enough folic acid even if you are not trying to get pregnant. To keep the blood healthy by helping red blood cells form and grow.
Not getting enough folic acid can lead to a type of anemia called folate-deficiency anemia. Folate-deficiency anemia is more common in women of childbearing age than in men. How do I get folic acid? You can get folic acid in two ways. Through the foods you eat. Folate is found naturally in some foods , including spinach, nuts, and beans.
Folic acid is found in fortified foods called "enriched foods" , such as breads, pastas, and cereals. Look for the term "enriched" on the ingredients list to find out whether the food has added folic acid.
As a vitamin. Check the label to make sure. How much folic acid do women need? If you: Amount of folic acid you may need daily 2 Could get pregnant or are pregnant — micrograms. Your doctor may prescribe this amount. Research shows taking this amount may lower the risk of having another baby with spina bifida. Have spina bifida and want to get pregnant 4, micrograms. Women with spina bifida have a higher risk of having children with the condition.
Take medicines to treat epilepsy , type 2 diabetes , rheumatoid arthritis , or lupus Talk to your doctor or nurse. Folic acid supplements can interact with these medicines. Are on dialysis for kidney disease Talk to your doctor or nurse.
Have a health condition, such as inflammatory bowel disease or celiac disease , that affects how your body absorbs folic acid Talk to your doctor or nurse. Are some women at risk for not getting enough folic acid? Spanish-speaking Mexican-American women often do not get enough folic acid. However, Mexican-Americans who speak English usually get enough folic acid.
What can happen if I do not get enough folic acid during pregnancy? These include: Spina bifida. As a result, the nerves that control the legs and other organs do not work. Children with spina bifida often have lifelong disabilities. They may also need many surgeries. Anencephaly an-en-SEF-uh-lee. Almost all babies with this condition die before or soon after birth. Do I need to take folic acid every day even if I'm not planning to get pregnant?
By the time you find out you are pregnant, it might be too late to prevent the birth defects. You need to take folic acid every day because it is a water soluble B-vitamin. Water soluble means that it does not stay in the body for a long time.
Your body metabolizes uses folic acid quickly, so your body needs folic acid each day to work properly. All of these defects happen during the first 28 days of pregnancy — usually before a woman even knows she's pregnant. That's why it's so important for all women of childbearing age to get enough folic acid — not just those who are trying to become pregnant.
Half of all pregnancies are not planned, so any woman who could become pregnant should make sure she gets enough folic acid. It's not clear why folic acid has such a profound effect on the prevention of neural tube defects.
But experts do know that it's vital to the development of DNA. As a result, folic acid plays a large role in cell growth and development, as well as tissue formation.
How can women of childbearing age — and especially those who are planning a pregnancy — get enough folic acid every day? The U. Isolated folate deficiency is uncommon; folate deficiency usually coexists with other nutrient deficiencies because of its strong association with poor diet, alcoholism, and malabsorptive disorders [ 4 ]. Megaloblastic anemia, which is characterized by large, abnormally nucleated erythrocytes, is the primary clinical sign of folate or vitamin B12 deficiency [ 1 , 4 ].
Its symptoms include weakness, fatigue, difficulty concentrating, irritability, headache, heart palpitations, and shortness of breath [ 2 ].
Folate deficiency can also produce soreness in and shallow ulcerations on the tongue and oral mucosa; changes in skin, hair, or fingernail pigmentation; gastrointestinal symptoms; and elevated blood concentrations of homocysteine [ 1 , 2 , 4 , 32 ]. Women with insufficient folate intakes are at increased risk of giving birth to infants with NTDs [ 2 ].
Inadequate maternal folate status has also been associated with low infant birth weight, preterm delivery, and fetal growth retardation [ 1 , 33 ]. Frank folate deficiency is rare in the United States, but some individuals might have marginal folate status.
The following groups are among those most likely to be at risk of folate inadequacy. People with alcohol use disorder People with alcohol use disorder frequently have poor-quality diets that contain insufficient amounts of folate. Moreover, alcohol interferes with folate absorption and hepatic uptake, accelerates folate breakdown, and increases its renal excretion [ 1 , 4 , 9 ]. Even moderate alcohol consumption of ml 8 fluid ounces red wine per day or 80 ml 2.
Women of childbearing age All women capable of becoming pregnant should obtain adequate amounts of folate to reduce the risk of NTDs and other birth defects [ 2 , 36 , 37 ].
However, some women of childbearing age get insufficient amounts of folate even if they take dietary supplements [ 29 ]. Pregnant women During pregnancy, demands for folate increase because of its role in nucleic acid synthesis [ 33 ]. This level of intake might be difficult for some women to achieve through diet alone. The American College of Obstetricians and Gynecologists recommends a prenatal vitamin supplement for most pregnant women to ensure that they obtain adequate amounts of folic acid and other nutrients [ 38 ].
People with malabsorptive disorders Several medical conditions increase the risk of folate deficiency. Diminished gastric acid secretion associated with atrophic gastritis, gastric surgery, and other conditions can also reduce folate absorption [ 4 ]. 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 ].
Autism spectrum disorder Autism spectrum disorder ASD is a neurodevelopmental disorder characterized by difficulty communicating and interacting with other people, limited interests, and repetitive behaviors. The causes of ASD are not clear, but genetic and environmental factors including infections and prenatal exposure to certain drugs, pollutants, and pesticides are believed to play a role [ ].
Emerging evidence suggests that periconceptional folic acid supplementation might reduce the risk of ASD or mitigate the potentially increased risk of ASD from prenatal exposure to certain drugs and toxic chemicals.
For example, the prospective Norwegian Mother and Child Cohort Study that included 85, children aged 3. Conversely, a longitudinal, population-based cohort of 35, pregnant Danish women and their children found no association between periconceptional folic acid or multivitamin use and ASD [ 52 ].
Periconceptional use of folic acid might mitigate the potentially increased risk of ASD in children exposed to certain drugs and neurotoxins in utero [ ]. An analysis of data from the Norwegian Mother and Child Cohort Study, which included , children, found that children exposed to antiepileptic drugs known to reduce folate in vivo in utero were 5.
In addition, the severity of autistic traits was inversely associated with both maternal plasma folate concentrations and folic acid doses. Similarly, in a U. The risk of ASD was even higher 2. However, most, if not all, of the currently available data are observational, and confounding weakens the ability to demonstrate causal inference. Additional research and validation in other studies are needed before firm conclusions can be drawn.
Cancer 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 , 53 , 54 ]. Evidence also indicates that folate might play a dual role in cancer initiation and progression [ 56 ]. That is, folate might suppress some types of cancer during the early stages of development, whereas high doses of folic acid taken after preneoplastic lesions have been established might promote cancer development and progression.
Results from clinical trials involving folic acid supplementation have been mixed. In addition, most trials have included other B-vitamins frequently at doses well above RDA levels and sometimes other nutrients, making it difficult to disentangle the effects, if any, of folic acid alone. For example, in a trial in France, 2, people with a history of cardiovascular disease received daily supplements of mcg folic acid, 3 mg vitamin B6, and 20 mcg vitamin B12 for 5 years [ 57 ].
The researchers found no association between B-vitamin supplementation and cancer outcomes. Several epidemiological studies have found inverse associations between high dietary folate intakes and the risk of colorectal adenoma and cancer [ ]. Other studies, however, have found no significant associations between dietary folate intakes [ 64 , 65 ] or circulating folate concentrations [ 66 , 67 ] and colorectal cancer risk.
Several clinical trials have examined whether supplemental folic acid sometimes in combination with other B-vitamins reduces the risk of colorectal adenoma in individuals with or without a history of adenoma.
A pooled analysis of three large clinical trials one in Canada, one in both the United States and Canada, and one in both the United Kingdom and Denmark found that folic acid supplementation for up to 3. Folic acid supplementation also had no effect on the risk of all cancer types combined in the pooled analysis of three clinical trials cited above [ 69 ].
Similarly, a meta-analysis of 13 randomized trials showed no statistically significant effects of folic acid supplementation median daily dose of 2, mcg over an average treatment period of 5. Some research has found associations between folic acid supplementation and increased cancer risk. In a randomized clinical trial investigating osteoporotic fracture incidence in 2, participants aged 65 years or older with elevated homocysteine levels, those who received mcg folic acid plus mcg vitamin B12 and IU vitamin D3 for 2 years reported a significantly higher cancer incidence, especially of colorectal and other gastrointestinal cancers, than those who received only IU vitamin D3 [ 72 ].
In addition, a prospective study found that folic acid intake from fortified foods and supplements was positively associated with a risk of cancer recurrence among patients with non—muscle-invasive bladder cancer, whereas natural folate intakes showed no significant association [ 73 ]. A secondary analysis of the study by Cole and colleagues [ 70 ] found that folic acid supplementation significantly increased the risk of prostate cancer [ 75 ].
Subsequent research has shown an association between increased cancer cell proliferation and higher serum folate concentrations in men with prostate cancer [ 76 ]. The mixed findings from clinical trials, combined with evidence from laboratory and animal studies indicating that high folate status promotes tumor progression, suggest that folate might play dual roles in cancer risk, depending on the dosage and timing of the exposure.
Modest doses of folic acid taken before preneoplastic lesions are established might suppress cancer development in healthy tissues, whereas high doses taken after the establishment of preneoplastic lesions might promote cancer development and progression [ 9 , 59 , ].
This hypothesis is supported by a prospective study that found an inverse association between folate intake and risk of colorectal cancer only during early pre-adenoma stages [ 82 ]. A expert panel convened by the National Toxicology Program and the National Institutes of Health Office of Dietary Supplements concluded that folic acid supplements do not reduce cancer risk in people with adequate baseline folate status.
The panel also determined that the consistent findings from human studies that supplemental folic acid has an adverse effect on cancer growth justify additional research on the effects of folic acid supplementation on cancer risk [ 83 ]. Several important questions about these effects remain, including the dose and timing of folic acid supplementation that might exert tumor-promoting effects and whether this effect is specific to synthetic folic acid or other forms of folate [ 56 ].
Overall, the evidence to date indicates that adequate dietary folate intake might reduce the risk of some forms of cancer. However, the effects of supplemental folic acid on cancer risk are unclear, especially among individuals with a history of colorectal adenomas or other forms of cancer. 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. Cardiovascular disease and stroke An elevated homocysteine level has been associated with an increased risk of cardiovascular disease [ 1 , 2 ].
Folate and other B vitamins are involved in homocysteine metabolism, and researchers have hypothesized that these micronutrients reduce cardiovascular disease risk by lowering homocysteine levels [ 1 , 84 ]. Folic acid and vitamin B12 supplements lower homocysteine levels. However, these supplements do not actually decrease the risk of cardiovascular disease, although they appear to provide protection from stroke [ ].
For example, in 5, U. In a substudy of participants, the supplementation also had no significant effects on biomarkers of vascular inflammation [ 90 ], but it did lower homocysteine levels by a mean of Another clinical trial included 5, patients aged 55 years or older with vascular disease or diabetes from various countries including the United States and Canada that had a folic acid fortification program and some that did not [ 87 ].
Patients received 2, mcg folic acid plus 50 mg vitamin B6 and 1 mg vitamin B12 or placebo for an average of 5 years. Compared with placebo, treatment with B vitamins significantly decreased homocysteine levels but did not reduce the risk of death from cardiovascular causes or myocardial infarction. In a large trial in regions of China without folic acid fortification among 20, adults with hypertension but no history of stroke or myocardial infarction, supplementation with mcg folic acid plus 10 mg enalapril used to treat high blood pressure for a median of 4.
The effect was more pronounced in participants with the lowest baseline levels of plasma folate. These findings suggest that folic acid supplementation might primarily benefit those with insufficient folate levels, which are less common in countries, such as the United States, with folic acid fortification [ 95 ].
Likewise, the authors of the third update of a Cochrane review of the effects of homocysteine-lowering interventions on cardiovascular events concluded that folic acid supplementation alone or in combination with vitamin B6 and vitamin B12 does not affect the risk of myocardial infarction or death from any cause, but it does reduce the risk of stroke [ 96 ].
Three other meta-analyses have also found that folic acid is effective for preventing stroke, especially in populations exposed to no or partial folic acid fortification [ 93 , 97 , 98 ]. Overall, the available evidence suggests that supplementation with folic acid alone or in combination with other B-vitamins reduces the risk of stroke, especially in populations with low folate status, but does not affect other cardiovascular endpoints. Scientists hypothesize that elevated homocysteine levels might have a negative effect on the brain via numerous mechanisms, including cerebrovascular ischemia leading to neuronal cell death, activation of tau kinases leading to tangle deposition, and inhibition of methylation reactions [ ].
In one randomized, double-blind, placebo-controlled trial in the Netherlands, people aged 70 years or older with no or moderate cognitive impairment received mcg folic acid plus 1 mg vitamin B12; 1 mg vitamin B12; or placebo for 24 weeks [ ].
In another clinical trial in older adults mean age After an average of 1. However, in a subset of women with a low baseline dietary intake of B vitamins, supplementation significantly slowed the rate of cognitive decline. A secondary analysis of a study in Australia which did not have mandatory folic acid fortification at the time of the study found that daily supplementation with mcg folic acid plus mcg vitamin B12 for 2 years improved some measures of cognitive function, particularly memory, in adults aged 60 to 74 years who had depressive symptoms [ ].
Another meta-analysis included 11 randomized controlled trials in over 20, older adults mean age 60—82 years that administered to 2, mcg folic acid plus 20—1, mcg vitamin B12 in 10 trials and 3—50 mg vitamin B6 in 8 trials for 0.
The supplementation significantly lowered homocysteine levels but did not affect cognitive aging, global cognitive function, or specific cognitive domains including memory, speed, and executive function [ ]. Several large reviews have evaluated the effect of B vitamins on cognitive function. Most of the authors concluded that supplementation with folic acid alone or in combination with vitamins B12 or B6 does not appear to improve cognitive function in individuals with or without cognitive impairment [ ].
Some noted, however, that when researchers took baseline homocysteine and B-vitamin status into account, B-vitamin supplementation slowed cognitive decline in individuals at high risk of cognitive decline [ , ]. Additional clinical trials are needed to better understand the effects of folic acid supplementation on cognitive function and cognitive decline. Depression Low folate status has been linked to depression and poor response to antidepressants in some, but not all, studies.
However, secondary factors linked to depression, such as unhealthy eating patterns and alcohol use disorder, might also contribute to the observed association between low folate status and depression [ ]. In an ethnically diverse population study of 2, people aged 15 to 39 years in the United States, serum and erythrocyte folate concentrations were significantly lower in individuals with major depression than in those who had never been depressed [ ].
An analysis of NHANES data found that higher serum concentrations of folate were associated with a lower prevalence of depression in 2, adults aged 20 or older [ ]. The association was statistically significant in females, but not in males. However, another analysis showed no associations between folate intakes from both food and dietary supplements and depression among 1, healthy Canadians aged 67—84 years [ ].
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 [ ]. A few studies have examined whether folate status affects the risk of depression during pregnancy or after childbirth.
A systematic review of these studies had mixed results [ ]. One study included in the review among women in Singapore found that compared with women with higher plasma folate concentrations mean Another study of 2, women in the United Kingdom found no significant associations between red blood cell folate levels or folate intakes from food and dietary supplements before or during pregnancy and postpartum depressive symptoms [ ].
More recently, a cohort study of 1, Chinese women found a lower prevalence of postpartum depression in women who took folic acid supplements for more than 6 months during pregnancy than in those who took them for less time [ ]. Studies have had mixed results on whether folic acid supplementation might be a helpful adjuvant treatment for depression when used with traditional antidepressant medications.
In a clinical trial in the United Kingdom, patients with major depression were randomly assigned to receive either mcg folic acid or placebo in addition to 20 mg of fluoxetine daily for 10 weeks [ ]. Although the effects in men were not statistically significant, women who received fluoxetine plus folic acid had a significantly greater improvement in depressive symptoms than those who received fluoxetine plus placebo. Another clinical trial in the United Kingdom randomized adults with moderate to severe depression who were taking antidepressant medications to either 5, mcg folic acid or placebo daily for 12 weeks in addition to their antidepressants [ ].
Measures of depression did not improve in participants taking folic acid compared with those taking placebo. The authors noted, however, that this conclusion was based on low-quality evidence.
Another meta-analysis of four clinical trials found that —10, mcg folic acid per day for 6—12 weeks as an adjunctive treatment did not significantly affect measures of depression compared with placebo [ ]. Other studies have examined the effects of 5-methyl-THF supplementation as an adjuvant treatment to antidepressants, and results suggest that it might have more promise than folic acid [ ]. Additional research is needed to fully understand the association between folate status and depression.
Although limited evidence suggests that supplementation with certain forms and doses of folate might be a helpful adjuvant treatment for depressive disorders, more research is needed to confirm these findings. In addition, many of the doses of folate used in studies of depression exceed the UL and should be taken only under medical supervision. 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 [ , ].
The prevalence rate of spina bifida and anencephaly the two most common types of NTDs in the United States is 5. Because of its role in the synthesis of DNA and other critical cell components, folate is especially important during phases of rapid cell growth [ ].
Although the mechanism has not been fully established, clinical trial evidence shows that adequate periconceptional folic acid consumption by women prevents a substantial proportion of NTDs [ 3 , 80 , , , , ]. However, significant racial and ethnic disparities persist. Federal Register. Final rule, 5 March Folate and neural tube defects.
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