Vitamin B9 (folate, folic acid) is important for energy metabolism, growth and development, the formation of blood cells and immune function.
If you do not have enough Vitamin B9 in your diet, you may experience difficulty concentrating, weakness, fatigue, irritable mood, headache, heart palpitations and other signs of megaloblastic anemia.
This vitamin is especially important for pregnant and breast-feeding women to support the health of developing fetuses and infants. Being deficient can result in serious developmental problems, including neural tube defects (NTD).
According to the European Food Safety Authority, folate deficiency is very common resulting from inadequate intake of this vitamin in the diet. It may also be caused by impaired absorption of nutrients from the gastrointestinal tract.
Use of Vitamin B9 supplements is purported to promote neurological health, methylation, blood vessel health, muscle tone and the integrity of skin, hair, and the liver.
This article will discuss how vitamin B9 works in the body, common uses and health benefits, deficiency issues, safety and side effects, and possible interactions with other compounds.
What is Vitamin B9?
Vitamin B9 is one of eight B-complex vitamins; all of which are known to be important for energy production, nervous system function, and the utilization of fats and proteins.
B vitamins are also important for maintaining health in the eyes, hair, nails, skin, and liver. Vitamin B9 also has various neurological effects.
Vitamin B9 is an essential dietary nutrient that cannot be produced in the human body. Like other B vitamins, folate is water soluble and not stored in the body. [1]
This means that we must regularly consume folate in our foods and/or take folate or folic acid supplements to keep our supplies at appropriate levels.
The type of Vitamin B9 found naturally in foods is called folate. The synthetic form of this vitamin, used in supplements and to fortify certain foods, is called folic acid.
There are several other forms of this compound used in dietary supplements. Metafolin (L-5-MTHF, L-Methylfolate) is the active form of this vitamin that is purported to be better utilized by the body.
Research has shown that supplementation with folic acid or folate during pregnancy can reduce the risk of neural tube defects in babies. Some clinical research has also seen positive effects on symptoms of depression when supplementing with folic acid.
How Does Vitamin B9 Work Inside the Body?
According to the European Food Safety Authority (EFSA), dietary intake of folic acid is important for:
- Normal blood formation
- Normal homocysteine levels
- Normal immune system
- Normal metabolism
- Normal cell division
- Normal maternal tissue growth during pregnancy
- Normal amino acid synthesis
- Normal psychological functions
- Reducing tiredness and fatigue
The University of Maryland Medical Center (UMM) states that vitamin B9 is crucial for proper brain function. [1]
UMM also says that folate is involved in the synthesis of genetic material: RNA (ribonucleic acid) and DNA (deoxyribonucleic acid).
It is particularly important during periods when cells are growing rapidly, such as during pregnancy, infancy, and adolescence for instance. [1]
The UMM states that along with vitamin B12 (cobalamin), vitamin B9 is also important for producing red blood cells, and for helping the cells to utilize available iron. [1]
Folate works with vitamin B6 (pyridoxine) and vitamin B12 to control levels of an amino acid intermediary called homocysteine. This is important because high homocysteine levels are associated with increased risk for cardiovascular disease. [1]
The Linus Pauling Institute (LPI) states that vitamin B9 is critical in the production of amino acids. Low folate levels during pregnancy increase the risks of congenital anomalies, especially neural tube birth defects. [2]
According to the LPI, folate status is considered subpar in most women of childbearing age worldwide. Synthetic vitamin B9 (folic acid) is currently being studied for its effects on preventing neural tube defects and various other congenital anomalies. [2]
Some cohort studies have reported an inverse relationship between vitamin B9 status and the risk of colorectal cancer, particularly in males. However, the LPI says there is a complicated relationship here that needs significantly more exploration to understand. [2]
According to the LPI, vitamin B9 is required for proper development and performance of the brain. Mild to severe cognitive dysfunction has been associated with both low levels of folate and high levels of homocysteine.
However, more research is needed to determine if folate supplementation has effects on cognitive decline. [2]
Common Vitamin B9 Uses
People take vitamin B9 supplements for many different uses. According to the Natural Medicines Comprehensive Database (NMCD), people commonly use this vitamin for:
- Acne
- Alzheimer’s disease
- Anemia
- Cancer
- Cardiovascular health
- Cognitive function
- Depression
- Diabetes
- Healthy pregnancy
- Hyperhomocysteinemia
- Preventing neural tube defects
- Restless leg syndrome
- Ulcerative colitis [4]
The NMCD has rated vitamin B9 as Effective for folate deficiency.
It has rated this supplement as Likely Effective for:
- end stage renal disease (ESRD)
- hyperhomocysteinemia
- neural tube birth defect
- methotrexate toxicity
Vitamin B9 is also rated as Possibly Effective for:
- age related macular degeneration (AMD)
- depression
- hypertension (high blood pressure)
- phenytoin-induced gingival hyperplasia
- pregnancy-related gingivitis
The NMCD reports that there are various other health conditions that folate and folic acid are being studied for including acne, Alzhiemer’s disease, bipolar disorder, cervical cancer, esophageal cancer, peripheral neuropathy, and restless leg syndrome.
Some preliminary clinical research into these proposed uses has yielded promising results. However, more research is needed to determine the therapeutic efficacy of vitamin B9 for these uses.
A high dose (1 mg) folic acid product has been approved by the FDA as a prescription drug for the treatment of certain medical conditions.
Most folate and folic acid products sold in the United States are categorized as dietary supplements by the FDA. Dietary supplements of Vitamin B9 have not been approved by the FDA as drugs to prevent or treat any health conditions.
Vitamin B9 Health Benefits
Dr. Edward Group III states that vitamin B9 has various potential health benefits including:
- Decreases risk of AMD (age-related macular degeneration)
- Encourages cardiovascular health by breaking down homocysteine
- Helps to normalize cholesterol levels
- Improves sperm health and function
- May help to support neurological health
- Possibly reduces the risk of ischemic stroke
- Supports healthy fetal development [3]
Below, we will examine some of the known health benefits associated with vitamin B9, specifically its effects on neural tube birth defects, cardiovascular health, and cognitive function.
Neural Tube Birth Defects
Vitamin B9 is very important during fetal development. It is known that low folate levels during early pregnancy can cause neural tube defects.
This type of birth defect affects the brain, spine, and spinal cord, which can lead to possible spontaneous termination of the pregnancy (miscarriage) or lead to a condition called spina bifida where the spinal cord is exposed after birth. [3]
NMCD states that increasing folate or folic acid during pregnancy can reduce the risk of neural tube defects. You can increase your B9 levels by eating more folate-rich foods, or by taking a quality vitamin supplement. [4]
According to the NMCD, “Analyses of clinical research suggests that folic acid fortification reduces the primary incidence of neural tube defects by 41% to 46%, while folic acid supplementation reduces the primary incidence by 42% to 62%.” [4]
Use of a supplement containing folic acid can also reduce the frequency of neural tube defects by 68% to 87% as a secondary preventative measure.
According to Dr. Group, studies have found that increasing vitamin B9 from one month before conception to three months after conception can decrease the risk of neural tube defects by at least 50%.
The NMCD has rated vitamin B9 as Likely Effective for preventing neural tube birth defects.
Cardiovascular Health
Vitamin B9 is believed to contribute to cardiovascular health in a few ways. It works by helping maintain healthy blood lipid levels and by keeping levels of a nonprotein alpha amino acid called homocysteine in balance.
Dr. Group states that folate supports normal cholesterol levels. All B-complex vitamins are known to be important for keeping blood lipids like cholesterol in proper balance.
In a study from Poland involving 124 human subjects, folic acid supplementation was found to significantly reduce LDL (“bad”) cholesterol while increasing HDL (“good”) cholesterol. In this study, subjects took 0.4 mg of folic acid daily for 3 months. [3]
When folate levels are low, homocysteine levels rise. According to Dr. Andrew Weil, when homocysteine is present in high concentrations, the risks for stroke and heart attack increase. [5]
Homocysteine is transported throughout the circulatory system and causes damage to the inside of blood vessels. This is believed to contribute to the formation of arterial plaque accumulations inside blood vessels.
Arterial plaque formations constrict the flow of blood through the circulatory system. When too much arterial plaque accumulates, arteries can become clogged and harden, leading to a condition called atherosclerosis or potentially causing a heart attack (myocardial infarction).
Atherosclerosis is a primary cause of coronary artery disease (CAD), which is a leading cause of heart disease.
The NMCD reports that in multiple clinical research studies, folic acid supplements have been shown to reduce fasting homocysteine levels.
They say that oral dosages of 400 mcg to 5 mg daily reduced levels by 20% to 30% compared to baseline in study participants with normal to moderately elevated homocysteine levels.
Dosages of 800 mcg to 1 mg per day appears to promote the greatest reduction in homocysteine levels. [4]
According to a 2015 research review, “Several diseases such as renal and thyroid dysfunction, cancer, psoriasis, and diabetes as well as various drugs, alcohol, tobacco, coffee, older age and menopause, are believed to be associated with moderately elevated homocysteine concentrations.” [6]
At this time it is still unknown if elevated homocysteine levels are a cause of cardiovascular disease, or rather an effect caused by the disease. While folic acid can decrease homocysteine levels, it is still not known whether this decreases the risk of heart disease.
The majority of studies to date have not shown that vitamin B9 improves endothelial function, reduces cardiovascular events or decreases death risks in those with CAD, chronic renal disease, cardiovascular disease, or stroke. This is true in spite of its capacity to lower homocysteine. [4]
More research is still needed to determine this relationship between homocysteine and cardiovascular disease and the effects folic acid supplementation may have.
Cognitive Function
Some research suggests that vitamin B9 may help to improve neuronal health, which may be a by-product of its ability to reduce homocysteine levels.
In a study from Korea, elderly patients with dementia were found to have high levels of homocysteine, and very low folate levels. Patients without dementia were found to have higher levels of vitamin B9. [3]
Preliminary evidence suggests that elderly people who consume more folate than the RDA are less likely to develop Alzheimer’s disease, at least compared to others with lower intake levels. [4]
However, this result only indicates a correlation and does not demonstrate that increasing intake of Vitamin B9 can reduce the risk of developing memory dysfunction.
More research is still needed to determine how vitamin B9 affects neurological health and whether it can improve conditions like Alzheimer’s disease.
Mood Disorders
The NMCD reports that observational research studies have suggested that depression may be correlated with low folate levels, especially in women. [4]
While limited clinical research has shown that folic acid alone is not as effective as conventional antidepressant therapy, multiple studies have found that folic acid together with conventional antidepressants seems to greatly improve treatment response and reduction in symptom scores. [4]
Some research shows that vitamin B9 does not improve the effects of lithium therapy in those with bipolar disorder. However, other research suggests that using folic acid along with valproate for mania is advantageous compared to valproate alone. [4]
Vitamin B9 Deficiency
Dr. Weil states that vitamin B9 deficiency is associated with low birth weight, neural tube defects, cervical dysplasia, pregnancy loss, memory impairment, and depression.
He says that pregnant women, alcoholics and those who are institutionalized are the most likely to develop folate deficiency. [5]
The UMM states that those with inflammatory bowel disease (IBD), celiac disease, and other conditions that affect nutrient absorption can also be at risk of deficiency. Certain medications can cause low levels too.
The UMM states the following warning signs to look for concerning vitamin B9 deficiency:
- Chronic gingivitis
- Inflamed tongue
- Labored breathing
- Mental sluggishness
- Poor appetite
- Stunted growth
According to the UMM, a deficiency in this vitamin can also cause diarrhea, irritability, fatigue, weakness, and forgetfulness. [1]
The LPI states that severe vitamin B9 deficiency can result in a condition called megaloblastic anemia. If this is not treated properly and promptly, it can cause irreversible brain damage. [2]
The LPI also states that low folate status is associated with an increased risk for developing cancer. However, intervention trials that used high doses of folic acid have not suggested any anticancer benefits. [2]
Vitamin B9 Food Sources
According to the National Institutes of Health (NIH), some good foods for increasing vitamin B9 status include dark green leafy vegetables, nuts, beans, legumes, fruits, fruits juices, dairy products, eggs, and seafood. [7]
The NIH states that spinach, brewer’s yeast, Brussels sprouts, liver, and asparagus are some of the best foods to add to the diet.
The United States, Canada, Costa Rica, South Africa, and Chile have implemented national programs for fortifying certain foods with folic acid. Some foods that are fortified include pastas, bleached flour, cornmeal, and cereals. [7]
Many physicians, including Drs. Group and Weil, recommend that when it is possible to get necessary nutrients like vitamins and minerals primarily from organic produce foods.
Vitamin B9 Supplements
Folic acid is the synthetic form of vitamin B9 that is made in laboratories. Most supplements contain folic acid. There are some supplements that contain folate from food sources.
Folate in supplements is commonly labelled as Methyl Folate, L-methylfolate, or (6S)-5-Methyltetrahydrofolate (5-MTHF). Some trademarked names of folate include Quatrefolic and Metfolin.
Manufacturers state that this form is the most bioactive, requiring less conversion in the body for efficient absorption and utilization.
The majority of folic acid and folate supplements come in 400 micrograms (mcg), 800 mcg, and 1000 mcg serving sizes.
In B-complex multivitamins, vitamin B9 is normally included at 400 mcg per dosage. Prenatal multivitamins typically contain between 400mcg and 800 mcg of folate or folic acid, with some as high as 1000 mcg per dose.
According to NIH, most childrens multivitamins contain between 200 mcg and 400 mcg of folic acid.
Roughly 35% of adults in the US, and about 28% of children between 1 and 13 years of age, use a dietary supplement containing folic acid. Those over 50 are more likely than other groups to use supplements with vitamin B9 in them. [7]
The NMCD states that there are more than 19,000 dietary supplement products available that contain vitamin B9 as folic acid or folate.
Because of this large variety of products to choose from, it is important to do your research and purchase from a reputable source that sells high-quality products.
B-complex vitamins are known to act synergistically to enhance one another’s effects inside the body. It is generally recommended to take these compounds together in a multivitamin product that contains all eight members of the B-complex family.
Dr. Group states that single B-complex supplements should be taken only in certain instances. He says that developing an imbalanced B-complex status can cause serious health disorders.
It is typically recommended that you take a B-complex multivitamin instead of supplementing with a single B-vitamin unless you have been instructed to do so by your doctor.
Vitamin B9 Dosage Guidelines
The LPI reports the following RDAs (recommended daily allowances) for vitamin B9:
- 600 mcg/day for pregnant women
- 500 mcg/day for lactating women
- 400 mcg/day for adults
- 300 mcg/day for children between 13 and 19 years of age
- 200 mcg/day for children between 4 and 8
- 150 mcg/day for children between 1 and 3
- 80 mcg/day for babies between 6 and 12 months
- 65 mcg/day for babies between 0 and 6 months [2]
When used as a dietary supplement, common dosages for folate or folic acid range from 400-800 mcg per day. The higher end of this range is typically taken by pregnant women in their prenatal vitamins.
Various dosages of folic acid have been used in research studies including:
- Age-related macular degeneration: 2.5 mg per day for up to 7 years
- Alzheimer’s disease: 1 mg per day for 6 months
- Bipolar disorder: 3 mg/day for 3 weeks
- Folate deficiency: 100 mcg- 5 mg per day
- Hearing loss: 800 mcg per day for 3 years
- Hyperhomocysteinemia: 200 mcg to 15 mg per day for up to 3.5 years
- Peripheral neuropathy: 400 mcg per day in combination with other vitamins
- Restless leg syndrome: 5-10 mg per day [4]
Medical authorities recommend that to prevent neural tube defects, women should take at least 400 mcg per day for the first month of pregnancy.
Women with a previous pregnancy history of neural tube defects usually take up to 4 mg per day for at least one month before conception and continuing for three months following conception.
Dr. Weil recommends that pregnant and nursing women discuss the best vitamin B9 dose for them with their obstetrician or physician.
Anyone interested in taking a folic acid or folate supplement should discuss recommended dosages with their doctor to help avoid side effects.
Vitamin B9 Side Effects
The Natural Medicines Database has rated vitamin B9 as Likely Safe when used orally or parenterally (outside of the digestive tract, normally injections) and appropriately.
Vitamin B9 has been rated as Possibly Unsafe when used orally in large doses for long-term period of time.
Research has shown that doses between 800 mcg to 1.2 g per day used for 3-10 years significantly increase the risk of cancer and cardiovascular problems. [4]
The NMCD has rated vitamin B9 as Likely Safe when used orally and appropriately during pregnancy and lactation. Prenatal vitamins often contain between 300-400 mcg of folic acid to reduce the risk of neural tube defects.
The NMCD reports no adverse effects associated with dietary or supplemental vitamin B9 in doses under 1 mg daily. Using dosages of greater than 5 mg daily can cause stomach cramps, diarrhea, and rashes.
Folic acid doses greater than 15 mg daily can cause:
- Abdominal distention (swelling)
- Allergic skin reactions
- Altered sleep patterns
- Bitter taste in mouth
- Exacerbation of seizure frequency
- Impaired judgement
- Vivid dreaming
- Worsening of psychotic behavior episodes
- Zinc depletion
Doses in excess of 15 mg/day can also cause overactivity, confusion, irritability, nausea, diarrhea, and flatulence. [7]
Other side effects of vitamin B9 are possible. Talk with your doctor about how to safely use this supplement to avoid adverse reactions.
Vitamin B9 Drug Interactions
There are various medications that vitamin B9 can interact with. It may alter the effects and/or side effects of these medications. Some medications may alter the absorption of this vitamin in the body.
Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and aspirin in large therapeutic doses can disrupt folate metabolism. Routine use of NSAIDs in smaller doses does not seem to have the same effect.
Phenytoin, an anticonvulsant medication, inhibits folate absorption in the intestines. Long-term use of phenytoin, primidone, phenobarbital, and certain other anticonvulsants decreases vitamin B9 status.
Folic acid absorption may be impaired by concomitant use with certain drugs used to lower cholesterol, like colestipol and cholestyramine for instance.
Methotrexate is a drug used to treat a variety of conditions including psoriasis, arthritis, and certain forms of cancer. Some of the side effects possible with methotrexate toxicity overlap those of severe vitamin B9 deficiency.
Some other drugs that have demonstrated antifolate activities include:
- An antibiotic called trimethoprim
- An antihypertensive called triamterene;/li>
- An antimalarial called pyrimethamine
- Sulfasalazine, a drug used for ulcerative colitis
The LPI also says that certain oral contraceptives with high amounts of estrogens can affect folate status as well.
It is best to consult with a doctor before beginning to use a vitamin B9 supplement with a doctor who understands your health and health history. Your doctor will be able to determine the best dosage for your needs and help you avoid any potential interactions with current medications or supplements you are taking.
- University of Maryland Medical Center. Vitamin B9 (Folate). Accessed Dec. 26, 2016
- LINUS PAULING INSTITUTE. Micronutrient Information Center. Folate. Accessed Dec. 26, 2016
- Group. 9 Incredible Health Benefits of Folate. Published on January 8, 2014
- Natural Medicines Comprehensive Database. Folic Acid Monograph. Accessed Dec. 26, 2016
- Weil. Vitamin B9 (Folate). Accessed Dec. 26, 2016
- Ganguly, Paul, and Sreyoshi Fatima Alam. "Role of Homocysteine in the Development of Cardiovascular Disease." Nutrition Journal 14 (2015): 6. PMC. Web. 27 Dec. 2016.
- National Institutes of Health. Office of Dietary Supplements. Folate. Dietary Supplement Fact Sheet. Accessed Dec. 26, 2016
Article last updated on: June 23rd, 2018 by Nootriment