Folic acid: benefits, side effects, dosage and interactions

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Folic acid is a natural form of vitamin B9 that the body needs to maintain red and white blood cells ( hematogenesis ), convert carbohydrates into energy (metabolism), synthesize and maintain the body's genetic components (DNA and RNA). Daily folate intake is also necessary to maintain a healthy pregnancy, normal fetal development, and prevent some serious birth defects.

Folate is found naturally in many foods, especially dark green vegetables, beans, and legumes. There are also vitamin supplements that contain a synthetic form of folate known as folic acid . In the United States and 80 other countries, breakfast cereals, flours, breads, and other foods are fortified with folate to prevent folate deficiency in the general population.

Get Medical Information / Alexandra Gordon

Folate versus folic acid

While many people use the terms folate and folic acid interchangeably, there are key differences between the two. Folate is immediately converted in the digestive tract into the active form of vitamin B9 called 5-methyl-THF (5-MTHF). Rather, folic acid must enter the bloodstream and be transported to the liver and other tissues for conversion.

Although folic acid was once thought to be better absorbed than folic acid, it is metabolized very slowly. Also, most of the folic acid you eat is not metabolized or retained in the body. In recent years, there has been concern that excessive accumulation of unmetabolized folate may promote tumor growth, although this has yet to be definitively proven.

An estimated 30% to 40% of the population have a genetic mutation known as MTHFR, which can further interfere with the ability to metabolize folic acid and is associated with high homocysteine levels.

Generally speaking, if you get enough folic acid in your diet, you don't need to take folic acid supplements. Because the body rapidly metabolizes most of the folate, it is unlikely to build up.

Health benefits

Folic acid is essential for good health. If you don't get enough folic acid or don't get enough folic acid, you can develop a folate deficiency. While this is rare in the United States, there are certain groups that are vulnerable, including pregnant women, infants, and young children (whose consumption may be insufficient due to their rapid growth) .

Folate deficiency can also be caused by certain medications (such as metformin, birth control pills, and methotrexate) and in people with heavy bleeding, liver disease, malabsorption (such as celiac disease ), and alcoholism.

Getting enough folic acid in your diet can help prevent a number of diseases, including some cases of stroke, neural tube defects, age-related macular degeneration, and even some cancers .

Cardiovascular diseases

The body uses folic acid to maintain and repair blood vessels. It also helps lower the levels of an amino acid called homocysteine , which contributes to heart disease.

Homocysteine is formed when proteins, mainly meat, begin to break down. High concentrations of homocysteine can cause hardening of the arteries ( atherosclerosis ), which increases the risk of heart attacks and strokes.

A 2010 study from Japan, which followed 23,119 men and 35,611 women for 14 years, found that higher dietary intakes of folate and vitamin B12 were associated with a lower risk of death from stroke, coronary heart disease , and heart failure

A similar study from the University of North Carolina found that young people with the highest dietary folate intake tend to have a lower risk of high blood pressure, a key factor in heart disease, later in life .

Neural tube defects

Neural tube defects (NTDs) are birth defects of the brain or spinal cord that usually occur during the first month of pregnancy. The two most common neural tube defects are spina bifida and anencephaly .

Insufficient folate and vitamin B12 levels during pregnancy are known to increase the risk of neural tube defects. Of the two, folate deficiency is much more common and is therefore of great concern.

Since neural tube defects can occur before you even know you are pregnant, it is important that you maintain good eating habits at all times, including adequate folic acid intake. This is especially true if you are of reproductive age and prone to folate deficiency.

To further reduce the risk of neural tube defects, doctors will regularly recommend folate supplements along with daily multivitamins during pregnancy. Other health experts advise women of childbearing age to take 0.4 milligrams (400 micrograms) of folic acid daily.

Women with the C677T gene mutation are at increased risk of having a baby with NTD, and some sources recommend supplementation with MTHF rather than inactive folic acid.

A 2016 study in the American Journal of Public Health concluded that adequate folic acid intake, whether through food, supplements, or fortification, reduces the risk of spina bifida worldwide.

According to the 2015 Morbidity and Mortality Weekly Report from the Centers for Disease Control and Prevention, the introduction of fortified foods resulted in a 28% reduction in spina bifida cases between 1995 and 2011.

Macular degeneration

Age-related macular degeneration (AMD) is an eye disease characterized by a progressive loss of the center of the visual field. The main cause of macular AMD is not fully understood, although some scientists believe it is the result of inflammation and oxidative stress that affect the eyes throughout life.

Chronically elevated homocysteine levels may also play a role, highlighting the role of folate in preventing AMD.

A 2013 Australian study that evaluated the health records of 1,760 adults with AMD over 10 years found that folate deficiency increased the risk of early AMD by 75 percent.

Additionally, elevated homocysteine levels correlate with a 30 percent increased risk of developing AMD .

In contrast, taking 2,500 micrograms (mcg) of folic acid per day reduces the risk of AMD by 35 to 40 percent, according to the Women's Cardiovascular Folic Acid and Antioxidant Study (WAFACS) .

Cancer

Folic acid has a controversial relationship with cancer. For one thing, chronic inadequate folic acid intake can increase the risk of cancers of the brain, breast, cervix, colon, lungs, ovaries, pancreas, and prostate. On the other hand, excessive consumption of folate can increase the risk of certain cancers, mainly prostate cancer.

There is some evidence that high dietary folate intake can significantly reduce the risk of certain cancers, especially in women .

A 2014 review of studies , which included 16 clinical trials involving 744,068 women, found that a daily dietary intake of 153 to 400 mcg of folic acid significantly reduced the risk of breast cancer.

Interestingly, a daily intake of more than 400 mcg was not associated with a reduced risk compared to women taking less than 153 mcg. Other studies have shown similar benefits for ovarian and cervical cancers.

Possible side effects.

As an essential nutrient derived from food, folate is not associated with side effects or risks. After all, you can't get too much folic acid from the foods you eat.

The same cannot be said for folic acid, which, if consumed in excess, can cause abdominal cramps, insomnia, nausea, diarrhea, and irreversible nerve damage.

Although folate in the diet cannot interact with pharmaceutical or over-the-counter medications, some medications can interfere with folate metabolism. This includes:

  • Anticonvulsants such as dilantin (phenytoin), tegretol (carbamazepine), or valproic acid.
  • Azulfidine (sulfasalazine), used to treat ulcerative colitis and rheumatoid arthritis.
  • Birth control pills
  • Dyrenium (triamterene), a diuretic used to treat fluid retention and high blood pressure.
  • Metformin , used to control blood sugar levels.
  • Methotrexate , used to treat certain types of cancer and autoimmune diseases.

Recommended consumption

The recommended daily intake of folic acid may vary depending on the age and stage of pregnancy as follows:

  • 0 to 6 months : 65 mcg per day
  • 7 to 12 months : 80 mcg per day
  • 1 to 3 years : 150 mcg per day
  • 4-8 years : 200 mcg per day
  • 9-13 years : 300 mcg per day
  • 14 years and older: 400 mcg per day
  • During pregnancy : 600 mcg per day.
  • During lactation : 500 mcg per day.

Folate is found naturally in a wide variety of foods, including vegetables (especially dark green leafy vegetables), fruits, nuts, beans, peas, shellfish, eggs, dairy products, meats, poultry, and grains. Foods especially high in folic acid include:

  • Beef liver : 215 mcg per 3-ounce serving
  • Spinach (cooked): 131 mcg per 1/2 cup serving
  • Black-eyed peas : 101 mcg per 1/2 cup serving
  • Breakfast cereals (fortified): 100 mcg per cup.
  • Asparagus : 89 mcg per 4 stalks
  • Brussels sprouts : 78 mcg per 1/2 cup serving
  • Romaine lettuce (shredded): 64 mcg per 1-cup serving
  • Avocado : 59 mcg per 1/2 cup serving
  • White rice (cooked): 54 mcg per 1/2 cup serving
  • Broccoli : 52 mcg per 1/2 cup serving
  • Mustard greens (cooked): 52 mcg per 1/2 cup serving

Other questions

How do you know if you have a folate deficiency?

The signs of folate deficiency are usually subtle. Unexplained tiredness and weakness are often the first signs. Folate deficiency anemia is usually diagnosed only after severe symptoms. It differs from other types of anemia in that a decrease in the number of red blood cells is accompanied by the appearance of large, deformed and immature red blood cells called megaloblasts.

This condition, also known as megaloblastic anemia, can cause a cascade of specific and non-specific symptoms, including:

  • Difficulty breathing
  • Muscular weakness
  • Abnormally pale skin
  • Swollen tongue ( glossitis )
  • Soft and delicate tongue
  • Loss of appetite
  • Weightloss
  • Nausea
  • Diarrhea
  • Rapid heartbeat ( tachycardia )
  • Tingling or numbness in the hands and feet ( peripheral neuropathy )
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