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Frequently Asked Questions

The U.S. Centers for Disease Control and Prevention cannot give personal advice to any woman about the risks of having a child with a birth defect. Any specific questions a woman has about health or treatment for a condition should be directed to her healthcare provider.

Folic acid, a B vitamin, is important for a baby’s very early development, often before a woman realizes she is pregnant. A woman who plans to or could become pregnant should consume 400 micrograms (mcg) of folic acid every day to ensure her baby’s proper development and growth.

What are neural tube defects?

  • Neural tube defects are serious birth defects of the brain and spinal cord. The two most common neural tube defects are spina bifida (a spinal cord defect) and anencephaly (a brain defect). Neural tube defects develop very early during pregnancy when the neural tube—which forms the early brain and the spinal cord—does not close properly.
  • The baby’s neural tube closes during the first weeks of pregnancy, often before a woman knows that she is pregnant. If a woman consumes folic acid before and during early pregnancy, it can help increase the chance of her baby’s neural tube closing properly. Waiting until the first prenatal visit (typically, the 6th to 12th week of pregnancy) to start folic acid consumption will not prevent neural tube defects. Therefore, to help prevent neural tube defects, it is important for women to start folic acid consumption before pregnancy begins.
  • Occasionally, some women will take the daily recommended amount of folic acid and still have a baby with a neural tube defect. Although the majority of neural tube defects can be prevented by getting 400 micrograms (mcg) of folic acid every day, some neural tube defects have other causes. If you have had a baby affected by a neural tube defect, be sure to discuss with your doctor or a genetic counselor your risk of having another pregnancy affected with a neural tube defect.

What is folic acid?

  • Folic acid is a B vitamin. If a woman consumes enough folic acid (400 micrograms (mcg) daily) before and during early pregnancy, it can help prevent her baby from having a neural tube defect. Women can do this by taking a vitamin supplement containing the recommended amount of folic acid or eating enough food that is fortified with folic acid. Fortified foods include enriched breads, pastas, rice, and some breakfast cereals.

Is folic acid the same as folate?

  • The terms “folic acid ” and “folate” often are used interchangeably. However, folate is a general term used to describe the many different forms of vitamin B9: folic acid, dihydrofolate (DHF), tetrahydrofolate (THF), 5, 10-methylenetetrahydrofolate (5, 10-MTHF), and 5-methyltetrahydrofolate (5-MTHF) 1.
  • Folic acid is the synthetic (that is, not generally occurring naturally) form of folate that is used in supplements and in fortified foods, such as rice, pasta, bread, and some breakfast cereals. In many scientific studies done in countries around the world, folic acid has been shown to be effective in preventing neural tube defects 2-6.
  • Natural folate can be found in foods such as leafy green vegetables, citrus fruits, and beans. A woman should eat a balanced diet rich in natural folate from food. However, it is very difficult for most women to get the daily recommended amount of folate through food alone 7 (see Table 2: http://ods.od.nih.gov/factsheets/Folate-HealthProfessional/).
  • Supplements containing forms of folate other than folic acid (such as 5-MTHF) should not be confused with the natural food folate found in fruits and vegetables. The effectiveness of these supplements in preventing neural tube defects has not been studied.

Why is folic acid used in food fortification instead of other folate forms?

  • Food fortification is the process by which vitamins and minerals are added to foods.
  • Folic acid is more heat-stable than natural food folate, which is broken down easily by heat and light; therefore, folic acid is better suited for food fortification because many fortified products, such as bread, are baked 8.
  • Folic acid has been shown to be effective in preventing neural tube defects in randomized control trials and food fortification programs 2-6.
  • Folic acid is absorbed easily by the body, and studies have shown that it can increase blood folate concentrations (the amount in the blood) across populations (including those with the MTHFR TT genetic variant) 9, 10.
  • No scientific studies exist that show that supplements containing other forms of folate [such as 5-methyltetrahydrofolate (5-MTHF)] can prevent neural tube defects.

What is blood folate concentration?

  • Blood folate concentration is the amount of folate that can be measured in the blood (many forms of folate are included in the measure). When a woman gets folic acid through fortified foods or supplements, her blood folate concentration increases. Having enough folate in the blood can reduce her risk of having a baby affected by a neural tube defect 11.
  • Once a woman starts consuming 400 micrograms (mcg) of folic acid every day, it can take several months for her to have a blood folate concentration that is high enough to help prevent neural tube defects.
  • The two most important factors that determine whether a woman has a blood folate concentration that is high enough to help prevent neural tube defects are the amount of folic acid consumed each day and 11 the length of time it is consumed before pregnancy. When taking supplements, more is not necessarily better. The Centers for Disease Control and Prevention recommends women to take 400 mcg of folic acid every day, starting at least one month before getting pregnant.

Where can I find folic acid in the United States and in what amounts?

  • In the United States, folic acid can be found in foods with mandatory or voluntary fortification, or in supplements. All products labeled as “enriched” are required by the U.S. Food and Drug Administration to be fortified (mandatory fortification) with folic acid, in addition to other micronutrients. The dietary labels on these products must specify that folic acid is included as an ingredient 12.
  • Researchers currently estimate that in the United States, people consume about 140 micrograms (mcg) of folic acid each day from mandatorily fortified foods 13.
  • Voluntarily fortified foods, such as some ready-to-eat cereals, can be fortified with up to 400 mcg of folic acid in each serving.
  • In the United States, supplements containing folic acid generally have 400 to 800 mcg of folic acid per dose, but doses up to 1,000 mcg are allowed without a prescription 14.
  • The amount of folic acid consumed from mandatorily fortified foods alone (about 140 mcg each day, on average) occurs at much lower levels than the amount consumed from supplements containing folic acid (about 400 to 1,000 mcg from each dose) or from voluntary fortification (400 mcg from each serving) 13.

 

Is folic acid safe?

  • At this time, folic acid taken at or up to the recommended amount of 400 micrograms per day (mcg/day) has not been shown to be harmful. Additional information continues to be assessed as it becomes available.
  • Some vitamins (such as vitamin D and vitamin A) can collect in fat tissues in the body, so they can be toxic if someone consumes too much. Folic acid does not collect in fat, but instead dissolves in water. This means that any amount of folic acid that is not used by the body (also called “unmetabolized folic acid”) goes through the kidneys, into the urine, and out of the body.

What is the tolerable upper intake level (UL) for folic acid?

  • The term, tolerable upper intake level (UL), is defined by the Institute of Medicine (IOM) as “the highest level of daily nutrient intake that is likely to pose no risk of adverse health effects to almost all individuals in the general population” 15.
  • In 1998, the IOM set the UL at 1,000 micrograms per day (mcg/day) of folic acid (coming from foods fortified with folic acid and from vitamin supplements).
  • Although the UL is used more broadly, it is only intended to prevent people who don’t know that they have a deficiency of vitamin B12 from consuming too much folic acid.
  • When taking supplements, more is not better. Women who can get pregnant (whether planning to or not) need just 400 mcg/day of folic acid, and they can get this amount from vitamins or fortified foods. This is in addition to eating foods rich in folate. But, your doctor might ask you to take more for certain reasons.

How was the tolerable upper intake level (UL) for folic acid determined?

  • People with a severe deficiency of another B vitamin – vitamin B12 – can develop a type of anemia called pernicious anemia, and eventually they might have nervous system damage. If people with vitamin B12 deficiency receive high doses of folic acid, the folic acid supplementation can correct the anemia; however, the nervous system damage can still occur because these people are still deficient in vitamin B12 15. This effect was seen among some patients who were given very high dosages [more than 5,000 micrograms per day (mcg/day)] of folic acid for many months 15. Based on these data, the Institute of Medicine specified a dose of 5,000 mcg/day of folic acid as the Lowest Observed Adverse Effect Level (LOAEL). The tolerable upper intake level (UL) for folic acid was established at 1,000 mcg/day (one-fifth of the LOAEL) to prevent individuals from taking so much folic acid that they reach the LOAEL risk level of 5,000 mcg/day 15.

Does folic acid mask vitamin B12 deficiency?

  • New laboratory tests can readily measure a person’s vitamin B12 status. This means that vitamin B12 deficiency can be detected and diagnosed quite easily. It also means that not being able to identify the anemia caused by vitamin B12 deficiency, as described in early case reports, is unlikely to remain an issue. A recent population-based study examined anemia among people with vitamin B12 deficiency before and after folic acid fortification and found that folic acid did not delay the identification of vitamin B12 deficiency after fortification began 16.

Is there an established tolerable upper intake level (UL) for folic acid for women of reproductive age?

  • The Institute of Medicine has not established a separate tolerable upper intake level (UL) for women of reproductive age. It states that, in general, vitamin B12 deficiency among U.S. women of reproductive age is rare, and they are unlikely to have any adverse effects from consuming supplemental folic acid at or above the UL 15.

Is there an established tolerable upper intake level (UL) for folic acid for children?

  • When the Institute of Medicine (IOM) set the tolerable upper intake level (UL) for folic acid, there were no data on any potential adverse effects for children consuming very high amounts of folic acid, nor are there any currently. Because of this, the IOM used data from adults and proposed ULs for children based on body weight. Because there is no clinical evidence that the consumption of high amounts of folic acid among children has caused any adverse effects, the age-specific ULs (based on body weight) might not be meaningful. Another reason that ULs for children might not be meaningful is that vitamin B12 deficiency is very rare among U.S. children 17.

Does taking higher dosages of folic acid cause or worsen cognitive impairment among older adults with a vitamin B12 deficiency?

  • Undiagnosed and untreated vitamin B12 deficiency can cause cognitive impairment. Many forms of dementia – such as Parkinson disease or Alzheimer disease – are made worse when vitamin B12 levels are low, regardless of a person’s folate status 18. Once a diagnosis of vitamin B12 deficiency is established, standard medical practice is to treat such individuals with vitamin B12.
  • Some studies have suggested that a higher concentration of blood folate might be related to cognitive impairment among older adults (older than 59 years of age) who have low vitamin B12 levels 19-21, while other studies have failed to confirm these findings 22-24.
  • In studies of older adults with cognitive impairment and low vitamin B12 levels who consumed higher amounts of folic acid, these adults typically took multivitamin supplements that contained both folic acid and vitamin B12. Because these multivitamins contained sufficient amounts of vitamin B12 to correct vitamin B12 deficiency under normal circumstances, these older adults were probably not able to absorb vitamin B12 from their intestines 25. Therefore, these adults likely developed cognitive impairment because they had pernicious anemia from their low vitamin B12 status, and not because they consumed vitamin supplements containing folic acid.

Will folic acid be effective for a woman with a variant in the methyltetrahydrofolate reductase (MTHFR) enzyme?

  • All women can benefit from getting 400 micrograms per day (mcg/day) of folic acid, especially before and during early pregnancy.
  • MTHFR (methyltetrahydrofolate reductase) is an enzyme that plays a role in how all people process folate. A common genetic variant of the MTHFR enzyme (also known as the MTHFR TT or CT genotypes) determines how rapidly some people can process folate. Even though women with the MTHFR TT or CT genotypes process folate more slowly, they can increase their blood folate concentrations enough to help prevent neural tube defects—some serious birth defects of the brain and spine—by consuming the recommended 400 mcg/day of folic acid 11.
    • Research studies have shown that among populations in which more people have the MTHFR TT or CT genotypes, getting 400 mcg/day of folic acid before and during early pregnancy can reduce by 85% the risk of having a baby with a neural tube defect 5.
    • Many studies have shown that consuming folic acid increases blood folate concentrations 26. For example, a research study among a population at high risk for neural tube defects showed that, after consuming 400 mcg/day of folic acid for three months, average blood folate concentrations increased to levels that would prevent neural tube defects among women with all MTHFR genotypes, including the MTFHR TT genotype 9.

What is unmetabolized folic acid?

  • Unmetabolized folic acid is any amount of folic acid that is found in the blood because it has not been converted into other forms of folate or removed from the body through urination.
  • Folic acid is absorbed by the intestines into the bloodstream, and then converted to other forms of folate by the liver. The liver is capable of processing only a certain amount of folic acid at one time. Unused folic acid in the blood goes to the kidneys and leaves the body in urine 27.

How much folic acid must someone consume in order to have leftover unmetabolized folic acid?

Does unmetabolized folic acid cause health problems?

  • Although some people have been concerned about unmetabolized folic acid in the blood, no confirmed health risks have been found 20, 33, 34.
  • A recent review found no evidence of harmful effects of unmetabolized folic acid in the blood of infants 35.

What effect does taking folic acid have on stroke?

  • Hypertension, or abnormally high blood pressure, increases the risk for having a stroke. A recent large study of adults in China with hypertension found that taking 800 micrograms of folic acid each day reduced the occurrence of stroke by 21%. An accompanying editorial in the journal that published this study stated that this reduction in stroke would likely apply to all adults 36, 37.
  • More recently, a study looking at the results of 30 randomized control trials, involving more than 80,000 people, suggested a 10% lower risk of stroke and a 4% lower risk of overall cardiovascular (heart and blood vessel) disease among those taking folic acid supplements 38.

What effect does taking folic acid have on arsenic poisoning?

  • In many countries in the world, arsenic in the water results in chronic (that is, constant) exposure of people to arsenic. A randomized control trial in Bangladesh found that taking 400 micrograms per day of folic acid for 12 weeks reduced total blood arsenic levels by 13.6%. The authors stated that taking folic acid to lower blood arsenic levels may help reduce the risk of illnesses that can result from arsenic poisoning 39.

What effect does taking folic acid have on colorectal cancer ?

  • Anyone being treated for cancer should discuss with his or her physician whether to take supplements that contain folic acid. Supplements (including those containing folic acid) can interfere with some drugs used to treat cancer. The physician should be told about any supplements the patient is taking.
  • In 2007, a randomized control trial study was published that looked at whether people who previously had a colorectal adenoma could prevent future colorectal adenomas by taking folic acid supplements of 1,000 micrograms per day; the researchers found that people taking the folic acid supplements had an increased risk of developing three or more additional adenomas after six years of follow-up 40. However, many large individual studies and the results of many additional studies combined together into a single analysis (i.e., a meta-analysis) do not find a relationship between folic acid supplementation and developing additional colorectal adenomas 41-44.
  • The Centers for Disease Control and Prevention continually monitors the latest research on the effects of folic acid on colorectal cancer.

What effect does taking folic acid have on cancer in general?

  • A recent analysis used data from randomized control trials, which included information on 50,000 individuals. This analysis showed that for people taking folic acid, there was neither an increase nor a decrease over time in the number of new cases of cancer of the large intestine, prostate, lung, breast, or any other specific site 45.

Can low blood folate concentrations cause problems other than some birth defects?

What effect does taking folic acid have on stroke?

  • Hypertension, or abnormally high blood pressure, increases the risk for having a stroke. A recent large study of adults in China with hypertension found that taking 800 micrograms of folic acid each day reduced the occurrence of stroke by 21%. An accompanying editorial in the journal that published this study stated that this reduction in stroke would likely apply to all adults 36, 37.
  • More recently, a study looking at the results of 30 randomized control trials, involving more than 80,000 people, suggested a 10% lower risk of stroke and a 4% lower risk of overall cardiovascular (heart and blood vessel) disease among those taking folic acid supplements 38.

What effect does taking folic acid have on arsenic poisoning?

  • In many countries in the world, arsenic in the water results in chronic (that is, constant) exposure of people to arsenic. A randomized control trial in Bangladesh found that taking 400 micrograms per day of folic acid for 12 weeks reduced total blood arsenic levels by 13.6%. The authors stated that taking folic acid to lower blood arsenic levels may help reduce the risk of illnesses that can result from arsenic poisoning 39.

What effect does taking folic acid have on colorectal cancer ?

  • Anyone being treated for cancer should discuss with his or her physician whether to take supplements that contain folic acid. Supplements (including those containing folic acid) can interfere with some drugs used to treat cancer. The physician should be told about any supplements the patient is taking.
  • In 2007, a randomized control trial study was published that looked at whether people who previously had a colorectal adenoma could prevent future colorectal adenomas by taking folic acid supplements of 1,000 micrograms per day; the researchers found that people taking the folic acid supplements had an increased risk of developing three or more additional adenomas after six years of follow-up 40. However, many large individual studies and the results of many additional studies combined together into a single analysis (i.e., a meta-analysis) do not find a relationship between folic acid supplementation and developing additional colorectal adenomas 41-44.
  • The Centers for Disease Control and Prevention continually monitors the latest research on the effects of folic acid on colorectal cancer.

What effect does taking folic acid have on cancer in general?

  • A recent analysis used data from randomized control trials, which included information on 50,000 individuals. This analysis showed that for people taking folic acid, there was neither an increase nor a decrease over time in the number of new cases of cancer of the large intestine, prostate, lung, breast, or any other specific site 45.

Can low blood folate concentrations cause problems other than some birth defects?

What is neural tube defects surveillance?

  • Neural tube defects surveillance or tracking is the ongoing collection of data on who is affected by neural tube defects in a population and where they are. It involves the analysis and interpretation of these data to help come up with the best medical and public health interventions for the population. These interventions, such as fortification of staple foods with folic acid, can reduce disability and death related to neural tube defects. Neural tube defects surveillance usually is done as part of a larger birth defects surveillance effort.

What are the different types of neural tube defects surveillance programs?

  • A population-based neural tube defects surveillance program records the number of pregnancies and babies with neural tube defects within the population of a defined geographical area.
  • A hospital- or facility-based neural tube defects surveillance program records the number of pregnancies and babies with neural tube defects that occur in selected facilities.

How are neural tube defects identified for a surveillance program?

  • Neural tube defects surveillance data can be collected through active case finding, passive case finding, or a combination of the two (hybrid) (see below).
    • With active case finding, data collectors regularly visit or have electronic access to databases at participating hospitals or facilities, and they review data from the multiple sources to identify pregnancies or newborn babies with a neural tube defect.
    • With passive case finding, hospital or facility personnel identify pregnancies or newborn babies with a neural tube defect and report this information directly to the surveillance program. Identification can also occur by linking hospital or facility databases with the surveillance program database. With passive case finding, the information reported to the surveillance program usually is not reviewed and checked by surveillance program personnel.
    • Hybrid case finding refers to a combination of passive and active case finding. A program can use passive case finding as a first step; then, for those cases passively reported, data collectors can verify the neural tube defects by reviewing the medical records of the cases at the hospitals or facilities

What is biomarker-based surveillance?

  • Biomarker-based surveillance measures a biomarker within people in a specified population in order to help track health outcomes related to the biomarker. An example of biomarker-based surveillance is measuring the concentration of folate in red blood cells among people in a population in order to determine the proportion of reproductive-age women in the population who have a high risk of having babies with neural tube defects

What are red blood cell (RBC) folate concentrations?

  • Blood folate concentration is the amount of folate that can be measured in the blood (many forms of folate are included in the measure). Folate concentrations can be measured in serum or plasma (the liquid part of blood) or in red blood cells (RBCs), which are the blood cells that carry oxygen throughout the body. By measuring the RBC folate concentrations among women in a population, it is possible to predict the risk within the population of having a pregnancy with a neural tube defect 11, 48.
  • In a 2015 guideline, the World Health Organization (WHO) defined the level of RBC folate concentrations in a population that is high enough to help prevent neural tube defects in the population. According to WHO’s definition, at the population level, RBC folate concentrations should be above 400 nanograms per milliliter (906 nanomoles per liter) in women of reproductive age, to achieve the greatest reduction of neural tube defects.
  • Folic acid fortification is a public health activity known as an intervention. RBC folate concentrations can be used to find out how effective this intervention is by monitoring how much folic acid is reaching women of reproductive age through staple food fortification programs.
  • Governments can use RBC folate concentrations measured in their populations to find out if their folic acid fortification programs are working and to find ways to improve efforts to prevent neural tube defects.

Flow chart: Assess, Identify, Target, Implement, Evaluate, Adjust

What is a microbiologic assay and how is it done?

 

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