Folic Acid in a nutshell:
Folic acid is needed to make red blood cells (deficiency can result in anemia) as well as DNA (in every cell of the body). Read about Folic acid, pregnancy and teenagers in my article, “Folic acid rich foods” for other uses of this vitamin.
Folic acid is a B vitamin in which very few Americans, Canadians, or Costa Ricans are deficient, unless, ironically, they favor natural and unprocessed food (read on to find out why). Folic acid deficiency in other parts of the world is a reality for many people unless they take supplements or they pay special attention to their diets.
Folic acid; folate; folicin; dihydrofolic acid; dihydrofolate; vitamin B9; pteroyl-L-glutamic acid; pteroyl-L-glutamate; pteroylmonoglutamic acid; tetrahydrofolic acid; tetrahydrofolate.
What Is Folic Acid?
Folic acid is a water-soluble vitamin in the vitamin B family. It is vital to life in organisms ranging from bacteria to humans, although it is a “vitamin,” in the sense that it has to be obtained from food, only in higher organisms. Humans get their folic acid primarily from green leafy vegetables or supplements. Cereal grains and rice are fortified with folic acid in the Canada, Costa Rica, and the USA, although Americans who live in Hawaii and Alaska sometimes get their cereals and rice from countries that do not add vitamins to food products.
Chemically, folic acid is a compound composed of three parts. It joins glutamic acid, which is one of the most abundant amino acids in the most organisms, with para-aminobenzoic acid (PABA), and a structure called a pteridine ring. The reason it is good to know about the chemical structure of folic acid is that some unscrupulous marketers advertise that glutamic acid or PABA or some pteridine compound is a newly discovered “vitamin” that you the consumer can only get from their supplement. These claims just are not true. Bacteria and plants can use these three compounds to make a vitamin, but human beings cannot.
What Does Folic Acid Do?
When a plant manufactures folic acid, it's not because it is thinking to itself, “Someday some nice human being may want to eat me in a salad and I want to be as nutritious as possible ”. Plants make folic acid so they can transform certain amino acids into others and also so they can make DNA. Humans have to consume folic acid so their bodies can perform the same function—in every single cell.
The folic acid we get in food is an inert form of the vitamin called dihydrofolic acid. It's still a vitamin, but it has to be activated by the liver. The liver changes dihydrofolic acid into tetrahydrofolic acid. We can also get this ready-to-use form of folic acid from supplements. The the active, tetrahydrofolic acid form of the vitamin is used in any important process called methylation.
Scientists are just beginning to understand the role of methylation in preventing aging. Segments of the DNA molecules in our genes can be switched on and switched off when they are “methylated,” that is, when they receive a -CH3 group from a donor molecule. That donor molecule is usually some form of folic acid. Methylation may be “good” or “bad,” depending on the gene that is being switched on or switched off. The net effect of methylation, however, seems to be slower aging.
Converting dihydrofolic acid to tetrahydrofolic acid (it helps to think of it as connecting 2 + 2 to make 4) is just the beginning of the processes in which the body uses folic acid. Folic acid interacts with other essential nutrients in vital life processes. (Don't worry about the nomenclature. Just know that transformations of folic acid into its various forms require other vitamins to complete the process.)
- Tetrahydrofolic acid interacts with the amino acid serine to form 5,10-methylenetetrahydrofolate. This is the form of folic acid that the body uses to make DNA. Serine is an amino acid that is especially abundant in eggs (more in egg white than in the yolk), soy products, cheese, an American and Latin American snack known as pork rinds, milk, mollusks, nuts, seeds, and gelatin (Jell-O or jelly). Without serine, the body cannot use the vitamin for this purpose.
- The 5,10-methylenetetrahydrofolate made by the reaction above then reacts with vitamin B12 to make methylcobalamin. This is the nutrient that can transform a heart-harming amino acid known as homocysteine back into the useful amino acids from which it is made.
And there are many dozens more similar chemical reactions in the body that require folic acid. The important thing to know about all of these reactions is that the body always has to transform the dihydrofolic acid form food into other forms. If the liver is not healthy, the body can't use folic acid from food. The body may be able to use the folic acid from supplements.
While folic acid is vital to healthy human metabolism, it just won't work if there are shortages of other vitamins and amino acids. The body needs riboflavin (vitamin B2), niacin (vitamin B3), pyridoxine (vitamin B6), serine, vitamin C, and zinc to be able to transform folic acid into its useful forms.
Vitamin B12 is especially important for folic acid metabolism. Folic acid can only cross the outer cell membrane into a cell in the form of 5-methylenetetrahydrofolate. It can only function in the cell if it is transformed into a slightly different chemical called 5-methyltetrahydrofolate. This transformation requires vitamin B12. If there is not enough vitamin B12 in the cell, then it can't use folic acid, either. Folic acid is said to be “trapped.”
This is the problem in a condition called megaloblastic anemia. The bones can't make red blood cells because they can't use folic acid because they don't have B12. It's necessary to get B12 for the bones to be able use folic acid to form red blood cells.
What Happens When We Don't Get Enough Folic Acid?
Even more important than helping make new red blood cells, the most basic task of folic acid in the human body is making DNA. When we don't get enough folic acid, our bodies don't make enough DNA. This means it cannot make replacement cells as cells wear out. Or it cannot make replacement cells properly. The effects of folic acid deficiency on red blood cells are a good example of how folic acid deficiency causes health problems.
Red blood cells usually have a life span of about 90 days (or less, in diabetics and in people undergoing stress). Occasionally, red blood cells may live as long as 120 days. This means that bone marrow constantly has to renew the bloodstream's red blood cell supply or a kind of anemia known as megaloblastic anemia results.
As the body's supply of folic acid dwindles, red blood cells at first continue to be made, but they are large and irregularly shaped, not as capable of carrying oxygen as healthy red blood cells. The white blood cells known as neutrophils that the body uses to fight infections are formed in segments that don't have the infection-fighting power of an intact cell.
Anemia causes severe fatigue. Neutropenia (lack of neutrophils) causes vulnerability to infection. Long before other problems related to folic acid deficiency would manifest themselves, anemia and neutropenia may result in death. Or there may be a kind of starting and stopping in the process that keeps people alive but miserable for many years. When this happens, there may also be a surge in homocysteine levels that causes severe inflammation of the cardiovascular system. This inflammation spreads to the brain and central nervous system.
Are You at Risk of Folic Acid Deficiency?
It is rare for people to get so little folic acid from their diets that they develop anemia, neutropenia, or high homocysteine levels. It's more common that functional folic acid deficiency occurs when the liver cannot transform the kind of folic acid in supplements and fortified foods into the kind of folic acid that is active in the body.
Alcoholics often have issues surrounding folic acid deficiency. There are also numerous health conditions that require extra folic acid for recovery, not just the smaller amount of folic acid needed to prevent anemia. An astonishing range of health conditions respond to folic acid:
- The main reason the governments of the United States, Canada, and Costa Rica mandate the fortification of cereals with folic acid is to prevent birth defects. Mothers who avoid folic acid deficiencies almost never bear children who have cleft palate or spina bifida. Mothers who are deficient in folic acid sometimes do.
- Cervical dysplasia, a condition caused by infection with the human papillomavirus (HPV), does not always lead to cervical cancer, but it is the first step. Women who use oral contraceptives seem to be at lower risk for the progression of cervical dysplasia when they take folic acid. Some women who have cervical dysplasia may lack the enzymes needed to use serine to transform folic acid into methylenetetrahydrofolate. Women who don't have this enzyme are three times as likely to develop cervical cancer after cervical dysplasia. You can't go down to the nutritional supplements shop and buy methylenetetrahydrofolate, but you can buy another form of folic acid that bypasses this step. Look for supplements that are labeled as folic triglutamate, folic polyglutamate, pteroylglutamic acid, or pteroylglutamate. This forms of the vitamin compensate for the lack of the enzyme.
- High homocysteine levels are a risk factor for heart disease even when cholesterol levels are normal. Studies have found that taking 250 to 1000 micrograms (mcg) of folic acid a day usually lowers homocysteine levels. There have not been any long-term studies that confirm that folic acid also reduces rates of heart disease independent of any other healthy choices you make.
- Erectile dysfunction in men is often treated with drugs like Viagra, Cialis, and Levitra. These medications work by enabling the linings of blood vessels to produce a compound known as nitric oxide, or NO. Folic acid supplements assist the production of NO and help men get their erections back, but they work better when men also take vitamin B6, vitamin B12, betaine, tetrahydrobiopterin (BH4), L-arginine, and vitamin C.
- Inflammatory bowel disease often leads to colon cancer. Taking up to 500 mcg of folic acid every day lowers the average risk of colon cancer in people who have inflammatory bowel disease by 20 to 30%.
- Vitiligo is a condition that causes loss of pigment in patches of skin. A combination of folic acid, vitamin B12, and vitamin C sometimes helps improve it.
- A number of central nervous system and peripheral nervous system conditions may respond to folic acid supplementation. These include restless legs syndrome, Alzheimer's and other forms of dementia, depression, insomnia, and diabetic neuropathy. Folic acid will not cure any of these conditions, but it will help all of them.
How to Make Sure You Get Enough Folic Acid
The recommended daily intake recommendations for folic acid are just plain confusing, even though there is a reason for the way they are calculated. As described above, the kind of folic acid is (for the most part) dihydrofolic acid. The kind of folic acid the body actually uses is tetrahydrofolic acid. This is also the kind of folic acid that is found in supplements. Nutritionists calculate folic acid from supplements as being twice as active as folic acid in supplements if the supplement is taken on an empty stomach. A microgram (mcg) of supplemental folic acid is said to be worth twice as many dietary folate equivalents (DFEs) as a microgram of supplemental folic acid from food.
There's also a computation to account for the fact that taking a supplement on a full stomach does not yield as much of the vitamin in its useful form. To keep the math simple, or at least to keep it from being impossibly complicated, we'll ignore that here.
- Women who are pregnant need a daily intake of 600 mcg of folic acid.
- Women who are breastfeeding need a daily intake of 500 mcg of folic acid.
- Adults of both sexes generally need 400 mcg of folic acid.
- Teens aged 14 to 18 generally also need 400 mcg of folic acid.
- Children aged 9 to 13 generally need 300 mcg of folic acid.
- Children aged 4 to 8 generally need 200 mcg of folic acid.
- Infants and children who have not yet reached the age of 4 need up to 100 mcg of folic acid.
If you take your supplements with food, add 30% to these numbers.
In the USA, Canada, and Costa Rica, flour, cereals, milled grains, and rice usually have 1400 mcg of folic acid added to every kilogram of product. Most people get about 1000 mcg of folic acid every day from fortified foods in these countries, on the possibly optimistic assumption that people only eat three slices of bread or one bowl of cereal every day. If you don't live in the USA, Canada, or Costa Rica, or if you only consume organic grains, you will need to get your folic acid from non-fortified foods.
These foods are listed in terms of micrograms (mcg) per 3-1/2 oz (100 g) serving for use with the chart above. Don't worry about dietary folate equivalents if you use this chart.
- A serving of Quaker Frosted Oats provides about 1570 mcg of folic acid.
- A serving of Cap'n Crunch provides about 1520 mcg of folic acid.
- A serving of General Mills Cheerios provides about 1320 mcg of folic acid.
- A serving of Kellogg's All-Bran provides about 1310 mcg of folic acid.
- A serving of General Mills Rice-Chex provides about 710 mcg of folic acid.
- A serving of a typical meal replacement shake provides about 500 mcg of folic acid.
- A serving of Boo Berries, Cinnamon Grahams, Cocoa Puffs, Count Chocula, Fiber-One, Golden Grahams, Honey Crunch Corn Flakes, Marshmallow Froot Loops, or almost any other prepared cereal will provide 300 mcg of folic acid, along with lots of sugar.
- A serving of cooked spinach provides about 268 mcg of folic acid.
- A serving of lentils provides about 179 mcg of folic acid.
- A serving of asparagus provides about 134 mcg of folic acid.
- A serving of orange juice (1/2 cup) provides about 168 mcg of folic acid.
- Enriched bread, rice, macaroni, spaghetti, and peanut butter (a full 3-1/2 oz or 100 g of peanut butter) provide about 200 mcg of folic acid.
- A serving of fried chicken provides about 30 mcg of folic acid.
- A serving of baked chicken provides about 25 mcg of folic acid. (Frying dries out the chicken so folic acid becomes more concentrated).
- A serving of fish or shellfish provides 15 to 25 mcg of folic acid.
- A serving of homemade falafel provides about 15 mcg of folic acid.
In the United States, women who don't have enough money to vitamins can apply for WIC coupons that allow them to buy cereal, juice, and milk that provide more than enough folic acid and other nutrients to prevent the most common forms of birth defects. Although the program is a boon to cereal manufacturers, it also prevents cleft palate and spina bifida. Generally two servings of breakfast cereal provides more than enough folic acid for a day for a woman in pregnancy and far more than enough folic acid for anyone else. That doesn't mean that these foods are optimal nutrition.
It's easy to get folic acid from sugar-sweetened vitamin-fortified cereal. It takes more planning to get folic acid from spinach, lentils, asparagus, and orange juice. Other good sources of folic acid include bananas, beets, turnip greens, raspberries, grapefruit and grapefruit juice, pineapple juice (canned more than fresh, due to condensation in the canning process), egg yolks, sunflower seeds, liver, and sausage made with liver.
You'll need to get at least five servings of these foods a day to get your daily supply of folic acid. That can be hard to do, but because these real foods provide other nutrients as well as folic acid, they are far healthier than sugar-laden cereals and breads and pastas made from enriched white flour.
More Folic Acid in Cooked Foods (If They Are Cooked the Right Way)
Contrary to what most people expect, cooking vegetables the right way can actually increase their folic acid content. Cooking carrots in a pressure cooker increases available folic acid about 2300%. Cooking cauliflower in a pressure cooker increases available folic acid about 3200%.
On the other hand, if you are just going to boil your vegetables in an open pot, it's better to eat them raw. Boiling removes water-soluble vitamins. Pressure cooking and sous-vide cooking increase available vitamin content. (Sous-vide cooking minimizes leaching of chemicals from the plastic. Microwaving maximizes it.)
It's always best to buy the freshest vegetables you can find when you are looking for folic acid content.
There are certain vitamins that are more abundant when a plant is sick, because it makes the vitamin to protect itself. Folic acid is more abundant when a plant is healthy, because it is especially needed in rapidly growing cells. An apple that shrivels while it is still on the tree may actually contain more vitamin C than a juicy apple that has a lot more taste appeal. But tender, mouthwatering salad greens contain more folic acid than salad greens that wilted in the field or molded in the refrigerator.
Frequently Asked Questions About Folic Acid
Q. Is it true that folic acid heals stomach problems?
A. No, but people who have stomach problems usually need supplemental folic acid. If you have any take medications for heartburn or gastroesophageal reflux disease (GERD), you will probably need folic acid (and calcium) supplements because your stomach is not as able to digest nutrients out of food. If you have any kind of chronic inflammation of the bowel, you may also need supplemental folic acid.
Q. Is it possible to take too much folic acid?
A. Taking about 30 times the recommended dose can cause stomach upset. The is also a risk of not realizing you have vitamin B12 deficiency when you take folic acid without also taking vitamin B12.
That's because very high doses of folic acid can overcome the “folic acid trap” that can occur when there isn't enough vitamin B12. The brain and central nervous system still need B12 for other functions, so dangerous central nervous system problems can occur if anemia is treated with folic acid alone.
If you take folic acid, take vitamin B12, too.
Q. What is the relationship between folic acid and chemotherapy?
A. Some treatments for cancer such as methotrexate work by neutralizing the active form of folic acid. This deprives cancer cells of the folic acid they need to make the DNA they need to multiply rapidly. It also deprives non-cancerous tissues of the folic acid they need to make the DNA they need to multiply at a normal rate. The objective is to slow down the growth of the cancer long enough for the immune system to destroy it while hoping the patient does not succumb to anemia or neutropenia.
There is some disagreement about whether taking folic acid supplements would help or hurt during chemotherapy with methotrexate. Usually it is counterproductive to take supplements while still receiving chemotherapy, but helpful to receive them when chemotherapy is stopped. Your physician is best able to determine the usefulness of folic acid and other vitamin supplements in your case.