folate

Foods Richest in folate

About folate

Basic description

Arguably, no conventional nutrient has undergone as much of a research renaissance in recent years as folate. Many people are familiar with the name of this B complex vitamin, and it has long been recognized as a key nutrient in human health. Low intakes of folate can have devastating effects, ranging from birth defects to blood diseases and possibly even cancers.

More recent is the understanding of this B vitamin’s many different forms in food, and its influence far beyond birth defects, blood diseases, and cancers. The Role in Health Support section covers recent developments in folate research.

If the word folate sounds like foliage to you, this is not an accident. The words share a common root (the Latin word folium, meaning “leaf”), which helps remind us that green plant foods can be among the richest sources of folate. However, as the chart and table in this article show, there are outstanding sources of folate in other food groups as well (especially legumes). .

Because of the promising role of folate in disease risk reduction, U.S. public health organizations have taken many steps to help increase intake of folate in the U.S. population. These public health programs have helped decrease the occurrence of neural tube defects associated with folate deficiency by as much as 30% over time. (Although enrichment of processed wheat flour with vitamins B1, B2, and B3 was practiced in the U.S. as early as the 1940’s, it wasn’t until 1998 that the U.S. Food and Drug Administration established guidelines for enrichment of processed wheat flour with folate.)

The adult Dietary Reference Intake (DRI) level for folate—and WHF recommended daily intake level—is 400 micrograms DFE, where “DFE” stands for “Dietary Folate Equivalents.” In the 2009-2010 National Health and Nutrition Examination Survey (NHANES), both male and female adults in the U.S. averaged well over this amount, with approximately 475 mcg DFE for adult women and 625 mcg DFE for adult men. However, a significant amount of this folate came in the form of fortified foods, enriched foods, or folate supplements rather than whole, natural foods. From a health standpoint, WHF recommendations always focus on whole, natural foods, and if you regularly enjoy our recipes, you will be likely to do just as well as the average U.S. adult in your food-based intake of folate, without resorting to fortification or enrichment. Dozens of our recipes contain more than half of the recommended daily intake level for this B vitamin.

Our profiled foods include 10 excellent sources of folate, 17 very good sources, and 24 good sources. Included in these ranked sources of folate are foods from various food groups, including vegetables, fruits, and legumes. Given this wide variety of choices, we are confident about your ability to develop a whole foods meal plan that will provide you with plenty of folate.

Role in health support

As mentioned earlier, the past decade of folate research has taught us much more about the nature of this vitamin and its critical role in support of our health. However, we would also point out that, in general, folate has been a complicated vitamin for researchers to understand, and research on folate has produced some confusion when scientific findings need to get translated into practical steps that we can take in the grocery store and in the kitchen. Our goal in these next paragraphs is provide you with a framework for simplifying key aspects of recent research on this B vitamin.

Let’s start off with the name of the vitamin itself. “Folate” is a very general name for a complicated family of nutrients found in both plant and animal foods. (At WHF, we use this very general term as our name for this B vitamin, and when we use it, we are not trying to specify any particular form of the vitamin. We just want to refer to this B vitamin in a consistent way.) To give you an idea of many different folate forms in food, consider the following list: methylfolates, dihydrofolates, monoglutamyl folates, and polyglutamyl folates. All of these vitamin forms can be found in varying amounts in whole, natural foods. By contrast, fortified and enriched foods are typically boosted in content with a single form of this vitamin, namely, folic acid. While you can find not only folic acid but many different forms of folate available in the form of dietary supplements, this vitamin gets added to food almost exclusively in the form of folic acid.

This complicated situation involving fortified foods led the National Academy of Sciences (NAS) to establish a new category for measuring dietary folate, called Dietary Folate Equivalents, or DFEs. If you consume 1 microgram of folate from a whole natural food, the NAS considers you to have consumed 1 microgram DFE. However, if you consume 1 microgram of folate from a food that has been fortified with folic acid, the NAS considers you to have consumed 1.6 micrograms DFE. Finally, if you take a folic acid supplement on an empty stomach in which no foods are simultaneously being consumed, the NAS considers you to have consumed 2 micrograms DFE. These differences in DFE calculation are based on studies measuring blood folate levels following intake of folate in various forms. The higher DFEs reflect higher blood levels associated with intake of supplemental folic acid versus natural food folate.

However, in order to more fully understand the health benefits of this vitamin, it would be a mistake to stop our discussion with consideration of supplemental folic acid, food folate, and DFEs. During the time that has passed since the NAS establishment of folate DFEs in 1998, there have been numerous advances in research on this vitamin. In comparison to the original DFE research, which showed about 50-60% bioavailability of food folate versus 85% bioavailability of supplemental folic acid, we now know that “bioavailable” can have many meanings and blood levels of folate are not always the best way to measure bioavailability. For example, we now know that polyglutamated folate found in vegetables and citrus fruits can be absorbed in the 60-98% range. We also know that a methylated form of folate (5-methyl-tetrahydrofolate) is the major form of folate in most plant cells, and that methylfolate appears to be the only form of this vitamin that crosses over the blood brain barrier and into the brain. This research has greatly increased interest in whole foods and the extent to which they naturally contain methylfolates.

Taken as a whole, these more recent research studies suggest that folate DFEs do not tell the whole story of this vitamin with respect to health benefits, and that whole, natural foods providing folate in a variety of forms are likely to be your best bet for obtaining health benefits related to this B vitamin. With this general guideline in mind, we would like to highlight specific areas in which folate health benefits have been most consistently documented in research studies.

Brain and nervous system health

Folate has long been known to help support production of nervous system function, and in particular, production of messaging molecules that are used by nerves to send signals throughout out body. More recently, however, research has broadened our understanding in this area of folate benefits.

In what has come to be named the BH4 Cycle (where is an abbreviation for tetrahydrobiopterin), researchers have verified a close connection between production of multiple neurotransmitters (with special emphasis on serotonin and dopamine) and availability of folate. In fact, part of the molecule for which this BH4 Cycle is named (dihydrobiopterin, or BH2) can itself be readily converted into a form of folate (dihydrofolate). In addition, researchers now know that BH4 cross over the blood brain barrier using the same transport mechanism as folate.

Interest in these nervous system messaging molecules and folate has been fascinating and widespread. Since much of the dopamine produced in our nerve cells begins with conversion of one amino acid (phenylalanine) into another amino acid (tyrosine), folate availability has been shown to be closely connected with this neurotransmitter pathway since BH4 is required for conversion of phenylalanine into tyrosine. Yet broader still are possible connections between two additional neurotransmitters—glutamic acid and GABA—and folate metabolism.

Glutamine is the preeminent amino acid in our central nervous system, and it is the starting point for production of both glutamic acid and GABA. While glutamic acid is widely known as an “excitatory” neurotransmitter that can stimulate and speed up nerve cell activity, it actually plays a much wider role in nervous system health that includes proper brain development, differentiation of nerve cells, and survival of nerve cells. By contrast, GABA (gamma-aminobutyric acid) is widely regarded as a primary inhibitory neurotransmitter that can decrease nerve activity in certain areas and help initiate nervous system balance needed to pave the way for activities like sleep. Researchers do not yet know exactly how folate metabolism is related to metabolism of either glutamic aid or GABA. But what researchers do know is that folate is a B vitamin that contains a “tail” comprised of glutamic acid molecules. In fact, this glutamic acid vitamin “tail” controls absorption of folate from our intestines up into the body.

Overall cardiovascular support

During the past 10 years, research on the role of folate in nervous system support has greatly overlapped with folate research as it relates to support of the cardiovascular system. In fact, it might be hard to find an area of metabolic research that has generated more excitement that this overlapping area of folated-related events critical for health of our cardiovascular and nervous systems.

The overlap begins with the ability of adequate dietary folate to help keep blood levels of homocysteine in check. Homocysteine (Hcy) is a well-documented marker for cardiovascular disease that when excessive, represents a clearly increased risk for a variety of cardiovascular problems. (Hyperhomocysteinemia is the name of the condition for high Hcy in the blood.) Optimal levels of blood folate in one particular form (5-methyltetrahydrofolate, or 5-MTHF) can directly help lower Hcy levels. By helping to keep Hcy levels in check, healthy intake of folate can help lower risk of cardiovascular disease.

The benefits of folate for lowered cardiovascular risk do not stop with Hcy, however. Balanced levels of nitric oxide (NO) in the blood are equally well-established as being important for cardiovascular health. NO helps to regulate many cardiovascular functions, and appropriate levels of NO are considered protective again high blood pressure, excessive clumping of platelet cells, and other key aspects of blood flow.

Several different forms of an enzyme called nitric oxide synthase (NOS) are responsible for helping keep NO at appropriate levels in our blood. However, NOS enzymes cannot actually generate NO unless certain molecules are present to help the NOS enzymes function properly. One such molecule is BH4 (tetrahydrobiopterin). Without enough BH4 around, the NOS enzymes not only fail to produce enough NO, but they can actually worsen our cardiovascular health by producing too much of an oxygen free radical called superoxide. How is it that the body keep enough BH4 around? Our bodies accomplish this task with the help of an enzyme called dihydrofolate reductase (DHFR). Of course, you can easily recognize the word “folate” in the name of this enzyme, because it is the same enzyme that converts folate into its most central bioactive form in the body, called tetrahydrofolate, or THF. In other words, the same enzyme that makes sure we have enough BH4 around to keep up our nitric oxide levels also makes sure that we have the most centrally active form of folate. So you can see how our folate metabolism and our cardiovascular health are so closely connected on a metabolic level.

The key role of folate in our cardiovascular health does not stop here, however. It turns out that the overall cycle used by the body to regenerate active forms of folate—called the folate cycle—is directly tied to a central cycle in cardiovascular health called the methylation cycle. The methylation cycle is our primary way of understanding blood homocysteine levels, since this cycle continually interconverts the amino acid methionine (MET) and its fellow amino acid, homocysteine (Hcy). When our folate cycle breaks down, our methylation cycle breaks down. However, the way in which our methylation cycle breaks down is important because a breakdown in our folate cycle means a breakdown in our conversion of Hcy back into MET. In other words, a breakdown in our folate cycle means excessive accumulation of Hcy and increased risk of heart disease.

As complicated as these metabolic pathways might seem, the bottom line here is straightforward: folate is a central nutrient for cardiovascular health, and its role in cardio support is wide-ranging.

Specific support of red blood cell production

It would be wrong to leave the topic of folate and cardiovascular health without making a special note about red blood cell production. Folate is one of many nutrients necessary for the production of red blood cells. These cells carry oxygen from the lungs to other parts of the body. Along with iron, copper, vitamin B12, and vitamin B6, a deficiency of folate can impair blood cell production.

Still, the deficiency of folate must be fairly severe to impair the production of red blood cells. Although this can occur, it is rare in the United States, where adults average more than the recommended daily intake level.

Reproductive health

When women deficient in dietary folate become pregnant, the developing fetus is at increased risk for neural tube defects, a developmental condition that adversely affects nervous system development in the fetus. These neural tube defects are potentially devastating and can often cause loss of pregnancy.

Adverse effects on nervous system development in the fetus can occur very early in pregnancy, even before a woman is aware that she is pregnant. Because this very early occurrence of problems can be “invisible,” it is important for women to consume enough of this nutrient before they become pregnant. From a practical standpoint, this scenario means special attention to folate intake by any woman who is considering pregnancy. As noted earlier, current evidence supports a conclusion that better folate intake by women prior to pregnancy can directly reduce risk of neural tube defects in a significant way.

Other potential health benefits

Some studies show lower risk of breast cancer in women with higher dietary intakes of folate, as well as decreased cancer risk at other sites in both men and women. However, the overall research on folate and cancer risk is both controversial and on the surface, sometimes contradictory, since some studies find an association between high folate intake and increased cancer risk. However, this important area of research is often confounded by the failure of studies fail to distinguish between supplemental folic acid and natural food folate.

Prevention and treatment of mental health problems—especially depression—are topics of special interest in relationship to folate intake, and we have seen some preliminary studies linking folate deficiency to increased risk of depression.

Summary of food sources

As the name implies, green leafy vegetables (or foliage) are among the best sources of folate. Spinach, turnip greens, bok choy, parsley, and romaine lettuce are all rated by our system as excellent sources of folate. Other vegetables can be strong sources as well, and we see asparagus, cauliflower, broccoli and beets join the excellent group.

We also see a number of the legumes do very well for this nutrient. At the top of the list here are lentils, which achieve a rating of “excellent” for folate. In fact, among all WHF, lentils rank as our best source of folate! Rating “very good” as sources of folate are garbanzo beans, navy beans, kidney beans, and pinto beans.

Some, but definitely not all, fruits are important sources of folate. Papayas and strawberries are very good sources of this nutrient, while oranges, pineapple, raspberries, kiwifruit, cantaloupe, lemons and limes all rate as “good” sources of this B vitamin.

To design a whole foods diet that contains enough folate, you’ll want to make sure to include plenty of minimally processed plant-based foods. If you are eating 5 cups’ worth of vegetables, a couple of fresh fruits, and a legume-based meal during an average day, you are quite likely to be meeting your folate needs.

Nutrient rating chart

Introduction to nutrient rating system chart

Read more background information and details of our rating system

WHF ranked as quality sources of
folate

Food

Serving
Size

Cals

Amount
(mcg)

DRI/DV
(%)

Nutrient
Density

World’s
Healthiest
Foods Rating

Lentils

1 cup

229.7

358.38

90

7.0

excellent

Asparagus

1 cup

39.6

268.20

67

30.5

excellent

Spinach

1 cup

41.4

262.80

66

28.6

excellent

Turnip Greens

1 cup

28.8

169.92

42

26.5

excellent

Broccoli

1 cup

54.6

168.48

42

13.9

excellent

Beets

1 cup

74.8

136.00

34

8.2

excellent

Romaine Lettuce

2 cups

16.0

127.84

32

36.0

excellent

Bok Choy

1 cup

20.4

69.70

17

15.4

excellent

Cauliflower

1 cup

28.5

54.56

14

8.6

excellent

Parsley

0.50 cup

10.9

46.21

12

19.0

excellent

Pinto Beans

1 cup

244.5

294.12

74

5.4

very good

Garbanzo Beans

1 cup

269.0

282.08

71

4.7

very good

Black Beans

1 cup

227.0

256.28

64

5.1

very good

Navy Beans

1 cup

254.8

254.80

64

4.5

very good

Kidney Beans

1 cup

224.8

230.10

58

4.6

very good

Papaya

1 medium

118.7

102.12

26

3.9

very good

Brussels Sprouts

1 cup

56.2

93.60

23

7.5

very good

Green Peas

1 cup

115.7

86.78

22

3.4

very good

Bell Peppers

1 cup

28.5

42.32

11

6.7

very good

Green Beans

1 cup

43.8

41.25

10

4.2

very good

Celery

1 cup

16.2

36.36

9

10.1

very good

Cabbage

1 cup

43.5

36.00

9

3.7

very good

Summer Squash

1 cup

36.0

36.00

9

4.5

very good

Strawberries

1 cup

46.1

34.56

9

3.4

very good

Tomatoes

1 cup

32.4

27.00

7

3.8

very good

Leeks

1 cup

32.2

24.96

6

3.5

very good

Fennel

1 cup

27.0

23.49

6

3.9

very good

Lima Beans

1 cup

216.2

156.04

39

3.2

good

Dried Peas

1 cup

231.3

127.40

32

2.5

good

Avocado

1 cup

240.0

121.50

30

2.3

good

Peanuts

0.25 cup

206.9

87.60

22

1.9

good

Sunflower Seeds

0.25 cup

204.4

79.45

20

1.7

good

Quinoa

0.75 cup

222.0

77.70

19

1.6

good

Winter Squash

1 cup

75.8

41.00

10

2.4

good

Oranges

1 medium

61.6

39.30

10

2.9

good

Cantaloupe

1 cup

54.4

33.60

8

2.8

good

Onions

1 cup

92.4

31.50

8

1.5

good

Collard Greens

1 cup

62.7

30.40

8

2.2

good

Pineapple

1 cup

82.5

29.70

7

1.6

good

Raspberries

1 cup

64.0

25.83

6

1.8

good

Carrots

1 cup

50.0

23.18

6

2.1

good

Beet Greens

1 cup

38.9

20.16

5

2.3

good

Mushrooms, Crimini

1 cup

15.8

18.00

5

5.1

good

Kiwifruit

1 2 inches

42.1

17.25

4

1.8

good

Kale

1 cup

36.4

16.90

4

2.1

good

Swiss Chard

1 cup

35.0

15.75

4

2.0

good

Mushrooms, Shiitake

0.50 cup

40.6

15.22

4

1.7

good

Basil

0.50 cup

4.9

14.42

4

13.3

good

Eggplant

1 cup

34.6

13.86

3

1.8

good

Mustard Greens

1 cup

36.4

12.60

3

1.6

good

Lemons and Limes

0.25 cup

13.4

12.20

3

4.1

good

World’s Healthiest
Foods Rating

Rule

excellent

DRI/DV>=75% OR
Density>=7.6 AND DRI/DV>=10%

very good

DRI/DV>=50% OR
Density>=3.4 AND DRI/DV>=5%

good

DRI/DV>=25% OR
Density>=1.5 AND DRI/DV>=2.5%

Impact of cooking, storage and processing

Like most water-soluble vitamins, folate can frequently be removed from foods during processing. You should expect there to be a substantial loss of folate in the manufacture of canned foods. The exact amount of folate lost depends on the food in question and the processing method used, but here are some practical examples. One cup of cooked garbanzo beans (prepared from dried beans) can provide you with over 275 micrograms of folate, while the same amount of canned garbanzo beans (by weight) is likely to provide you with about 75 micrograms. Or to use a folate-rich vegetable example, like asparagus: one cup of cooked asparagus (prepared from fresh form) can provide over 265 micrograms of folate, with the same amount of canned asparagus (by weight) providing about 170 micrograms. So as you can see, there is substantial loss of folate in both of these examples. The difference between canned and non-canned legumes is one you will want to keep in mind when enjoying the convenience of canned legumes. You can help maintain strong folate intake when using canned legumes by combining them with non-canned folate-rich foods like green leafy vegetables.

Our basic approach to food selection and preparation at WHF is to avoid processing as much as possible and rely instead on fresh and minimally cooked foods. Loss of folate during processing is one of the many reasons we have adopted this approach.

Occasionally, a method of food preparation can increase the level of a nutrient, and we are aware of one such example involving folate. This particular example involves conventional preparation of tofu and tempeh using microorganisms and fermentation. While folate is typically lost during the early stages of the tofu/tempeh preparation due to soaking of soybeans in water, fermentation of the soaked beans can ultimately replenish the lost folate. While neither tofu nor tempeh emerge as ranked sources of folate at WHF, both contain measurable amounts of folate in the 25-30 microgram per serving range.

One final note about fermentation here: we’ve seen studies show that fermentation of cow’s milk—as would occur in production of yogurt, and especially with live cultures remaining in the final product—can also somewhat increase the milk’s folate content.

Folate should be fairly stable to cold, at least over short periods of time. For example, one study found that Chinese cabbage did not lose a significant amount of folate over three weeks of refrigeration. Of course, we generally recommend enjoyment of fresh cabbage stored for a week or so at most in the crisper bin of the refrigerator.

Risk of dietary deficiency

As mentioned earlier, both male and female adults in the U.S. averaged well over the recommended intake level for folate in the 2009-2010 National Health and Nutrition Examination Survey (NHANES). From our perspective, however, this adequate intake of folate in terms of amount was actually inadequate in terms of food quality, since a significant amount of this folate came in the form of fortified foods, enriched foods, or folate supplements instead of whole, natural foods. We believe that your health is always better served if you are able to get the nutrients you need from whole, natural foods. If U.S. adults did not currently consume folate-fortified and folate-enriched foods, in combination with folic acid-containing supplements, they would not average adequate intake for folate! However, if you regularly enjoy our recipes, you will personally be likely to do just as well as the average U.S. adult in your food-based intake of folate, without resorting to fortification, enrichment, or supplements.

For many of our nutrients, we can design a sample daily diet to feature multiple strong sources of the nutrient and ensure good continuity over days and weeks of eating. With respect to folate, this task is especially easy. To approximate our DV of 400 mcg, you just need to have a large serving of greens . If you’d prefer, you could get within 15% of the DV by having a legume-rich meal (such as our Black Bean Chili). We have 25 recipes that rate as excellent sources of folate, most of which contain over half your DV for folate.

Other circumstances that might contribute to deficiency

Folate is more difficult to absorb and utilize than most of the other water-soluble vitamins. As such, people with bowel disease or other conditions that interfere with absorption may need to pay extra attention to folate nutrition.

Certain conditions and life stages can increase your need for folate, even when dietary supply is consistent. The most important is pregnancy. If you plan to and/or are able to become pregnant, make sure and have a look at the public health recommendations below. Breastfeeding is also a time when the need for folate increases, and it is therefore also a time of greater deficiency risk.

Many medications, including seizure medications and drugs used to treat inflammation, interfere with folate metabolism. If you are on one of these medications, you may need to work with your doctor to ensure you get enough folate.

Relationship with other nutrients

Folate is a member of the B complex vitamins, and like the others in this group, it will rely on the presence of the entire group to do its job effectively. Luckily, most of the B complex vitamins are found in the same plant foods that are rich in folate, so a diet rich in one is often rich in the others.

The most important exception to this rule is also the B vitamin whose role is most entwined with folate. Vitamin B12, which can only be made by microorganisms and which typically only accumulates in animal foods, fermented plant foods, and mushrooms works closely with folate in many of its different roles. Because folate is provided by a much larger variety of foods than B12, and because a wider variety of foods are typically fortified with folate and not B12, it is sometimes possible to get very large amounts of folate in comparison to B12. This type of imbalanced intake can be problematic since excessive amounts of folate can make deficiency of B12 more difficult to detect through standard lab tests. If left undetected, longstanding B12 deficiency can lead to sometimes irreversible health problems.

Luckily, the amounts of folate needed to create this type of problem is large and would be virtually impossible to obtain from whole, natural foods. You could, however, create this type of folate-to-B12 imbalance from a routine combination of fortified foods and supplemental folic acid. As you’ll see below in the Risk of Dietary Toxicity section, this safety factor provided by whole foods versus fortified foods and supplements is the reason that an upper limit was set by the National Academy of Sciences for intake of folate from fortified foods and supplements, but not for intake of folate found in natural, non-fortified foods.

The pathways that utilize folate and vitamin B12 are also dependent on vitamin B6 and riboflavin for proper functioning. Compared to folate and vitamin B12, however, these additional two B vitamins are less likely to be deficient to the point of creating a problem.

Risk of dietary toxicity

There is no known risk of toxicity from excessive naturally occurring folate from foods. This is good news, since the diets highest in folate tend to be those highest in vegtables, legumes, and other highly desirable foods that belong in most healthy meal plans.

It would, however, be very easy to go above the Tolerable Upper Intake Limit (UL) of 1000 mcg of added or supplemental folic acid on a regular basis. (Note: this UL is set for all individuals 19 years and older, with the exception of women under 19 years of age who are pregnant or breastfeeding. For women in that category, the UL is 800 mcg.) For example, if you take a multiple vitamin supplement that contains 400 mcg of folic acid, and on top of that you add an energy bar that contains 15 micrograms, and a breakfast cereal fortified with 30 micrograms, you’ll have 445 micrograms of folate or 45% of the UL before you start counting your primary list of foods for the day. One cup of lentils, one cup of broccoli, and 2 tablespoons of peanuts would put you over the UL at 1,059 micrograms.

The level of folate intake describe above is unlikely to cause problems on an occasional basis. However, if you plan to routinely consume folate-fortified foods and take supplements providing large amounts of folic acid, you may want to talk with a nutritionist and/or healthcare provider to help avoid possible problems with B vitamin balance given regular high intake of this B vitamin.

One additional note about the upper limits set for folate intake: for children 1-3 years of age, the UL is 300 micrograms; for children 4-8, the UL is 400 micrograms; for 9-13 year olds, it is 600 micrograms; and for 14-18 year olds, it is 800 micrograms.

Disease checklist

• Pregnancy
• Birth defects (prevention)
• Depression
• High blood pressure
• Cancer prevention
• Cognitive decline
• Anemia
• Gingivitis
• Osteoporosis
• Ulcerative colitis
• Psoriasis

Public health recommendations

In 1998, the National Academy of Sciences (NAS) published Dietary Reference Intake (DRI) guidelines for folate. These guidelines included Recommended Dietary Allowances (RDAs) for all persons one year and older. The folate recommendations were established in terms of micrograms of Dietary Folate Equivalents (or micrograms DFE) in order to adjust for intake of folate from fortified foods and supplements. For infants under one year of age, the DRIs were established as Adequate Intake (AI) levels rather than RDAs. A summary of these recommendations appears below:

• 0-6 months: 65 mcg DFE
• 6-12 months: 80 mcg DFE
• 1-3 years: 150 mcg DFE
• 4-8 years: 200 mcg DFE
• 9-13 years: 300 mcg DFE
• 14+ years: 400 mcg DFE
• Pregnant women: 600 mcg DFE
• Lactating women: 500 mcg DFE

The National Academy of Sciences also recommended that any woman who could become pregnant consume 400 mcg of folic acid daily from either a supplement or from fortified foods in addition to the naturally occurring folate in the diet. In 1991, the Centers for Disease Control (CDC) recommended women who have previously had a child with a neural tube defect should take 4000 mcg of supplemental folic acid when starting pregnancy planning.

Tolerable Upper Limits, or ULs for folate were also established by the NAS. The ULs do not apply to naturally occurring folate in food. (In other words, there was no limit set on the amount of natural food folate found to be safe.) Instead, the ULs only apply to folate obtained from fortified foods or supplements. Below is a summary of the ULs:

• Infants under 1 year of age: not established
• Children 1-3 years: 300 micrograms
• Children 4-8 years: 400 micrograms
• 9-13 year olds: 600 micrograms
• 14-18 year olds: 800 micrograms
• Individuals 19+ years: 1,000 micrograms
• Women under 19 years who are pregnant or breastfeeding: 800 micrograms

The Daily Value (DV) recommendation for folate is 400 mcg per 2000 calories. This is the value we use to calculate food rankings in all of our food and nutrient charts.

What can high-folate foods do for you?

• Support red blood cell production and help prevent anemia
• Help prevent homocysteine build-up in your blood
• Support cell production, especially in your skin
• Allow nerves to function properly
• Help prevent osteoporosis-related bone fractures
• Help prevent dementias including Alzheimer’s disease

What events can indicate a need for more high-folate foods?

• Irritability
• Mental fatigue, forgetfulness, or confusion
• Depression
• Insomnia
• General or muscular fatigue
• Gingivitis or periodontal disease

Excellent sources of folate include romaine lettuce, spinach, asparagus, turnip greens, mustard greens, calf’s liver, parsley, collard greens, broccoli, cauliflower, beets, and lentils.

WHF rich in
folate

FoodCalsDRI/DV

 Lentils23089.5%

 Pinto Beans24573.5%

 Garbanzo Beans26970.5%

 Asparagus4067%

 Spinach4165.7%

 Black Beans22764%

 Navy Beans25563.7%

 Kidney Beans22557.5%

 Turnip Greens2942.4%

 Broccoli5542.1%

For serving size for specific foods see the Nutrient Rating Chart.

• Description

• Function

• Deficiency Symptoms

• Toxicity Symptoms

• Cooking, storage and processing

• Factors that affect function

• Nutrient interaction

• Health conditions

• Food Sources

• Nutrient Rating Chart

• Public Health Recommendations

• References

Description

What is folate?

Folic acid, also called folate or folacin, is a B-complex vitamin most publicized for its importance in pregnancy and prevention of pregnancy defects. These defects involve malformation of a structure in the fetus called the neural tube. As the baby develops, the top part of this tube helps form the baby’s brain, and the bottom part unfolds to become the baby’s spinal column.

When the neural tube fails to close properly, serious brain and spinal problems result. Mothers with inadequate supplies of folic acid have been determined to give birth to a greater number of infants with neural tube defects. Beginning in the early 1980’s, researchers began to successfully use folic acid supplementation to reduce the risk of nervous system problems in newborn infants.

Folic acid is one of the most chemically complicated vitamins, with a three-part structure that puts special demands on the body’s metabolism. The three primary components of folic acid are called PABA, glutamic acid, and pteridine. (Two of these components, glutamic acid and pteridine, help explain the technical chemical name for folate, namely pteroylmonoglutamate.)

As complex as this vitamin is in its structure, it is equally as complicated in its interaction with the human body. For example, most foods do not contain folic acid in the exact form described above, and enzymes inside the intestine have to chemically alter food forms of folate in order for this vitamin to be absorbed. Even when the body is operating at full efficiency, only about 50% of ingested food folate can be absorbed.

How it functions

What is the function of folate?

Red blood cell formation and circulation support

One of folate’s key functions as a vitamin is to allow for complete development of red blood cells. These cells help carry oxygen around the body. When folic acid is deficient, the red bloods cannot form properly, and continue to grow without dividing. This condition is called macrocytic anemia, and one of its most common causes is folic acid deficiency.

In addition to its support of red blood cell formation, folate also helps maintain healthy circulation of the blood throughout the body by preventing build-up of a substance called homocysteine. A high serum homocysteine level (called hyperhomocysteinemia) is associated with increased risk of cardiovascular disease, and low intake of folate is a key risk factor for hyperhomocysteinemia. Increased intake of folic acid, particularly by men, has repeatedly been suggested as a simply way to lower risk of cardiovascular disease by preventing build-up of homocysteine in the blood.

Preliminary research also suggests that high homocysteine levels can lead to the deterioration of dopamine-producing brain cells and may therefore contribute to the development of Parkinson’s disease. Therefore, folate deficiency may have an important relationship to neurological health.

Research is now confirming a link between blood levels of folate and not only cardiovascular disease, but dementias, including Alzheimer’s disease.

One of the most recent studies, which was published in the July 2004 issue of the American Journal of Clinical Nutrition evaluated 228 subjects. In those whose blood levels of folate were lowest, the risk for mild cognitive impairment was more than tripled, and risk of dementia increased almost four fold. Homocysteine, a potentially harmful product of cellular metabolism that is converted into other useful compounds by folate, along with vitamin B6 and B 12, was also linked to dementia and Alzheimer’s disease. Individuals whose homocysteine levels were elevated had a 4.3 (more than four fold) increased risk of dementia and a 3.7 (almost four fold) increased risk of Alzheimer’s disease.

Research teams in the Netherlands and the U.S. have confirmed that low levels of folic acid in the diet significantly increases risk of osteporosis-related bone fractures due to the resulting increase in homocysteine levels. Homocysteine has already been linked to damage to the arteries and atherosclerosis, plus increased risk of dementia in the elderly. Now, in a study that appeared in the May 2004 issue of the New England Journal of Medicine, researchers at the Eramus Medical Center, Rotterdam, Holland, and another team in Boston have confirmed that individuals with the highest levels of homocysteine have a much higher risk of osteoporotic fracture.

In the Rotterdam study, which included 2,406 subjects aged 55 years or older, those with the highest homocysteine levels, whether men or women, almost doubled their risk of fracture. The Boston team found that risk of hip fracture nearly quadrupled in men and doubled in women in the top 25% of homocysteine levels.

Cell production

Cells with very short life spans (like skin cells, intestinal cells, and most cells that line the body’s exposed surfaces or cavities) are highly dependent on folic acid for their creation. For this reason, folic acid deficiency has repeatedly been linked to problems in these types of tissue.

In the mouth, these problems include gingivitis, cleft palate, and periodontal disease. In the skin, the most common folate deficiency-related condition is seborrheic dermatitis. Vitiligo (loss of skin pigment) can also be related to folic acid deficiency. Cancers of the esophagus and lung, uterus and cervix, and intestine (especially the colon) have been repeatedly linked to folate deficiency.

Nervous system support

Prevention of neural tube defects in newborn infants is only one of the nervous system-related functions of folic acid. Deficiency of folate has been linked to a wide variety of nervous system problems, including general mental fatigue, non-senile dementia, depression, restless leg syndrome, nervous system problems in the hands and feet, irritability, forgetfulness, confusion, and insomnia. The link between folate and many of these conditions may involve the role of folate in maintaining proper balance in nervous system’s message-carrying molecules. These molecules, called neurotransmitters, often depend upon folic acid for their synthesis. It’s been fascinating to see a link discovered by researchers between mothers who follow a Mediterranean-style diet and lowered risk of spina bifida (SB) in their infants. (SB is a set of conditions that include neural tube defects.) The ability of a Mediterranean-type diet to supply rich amounts of folic acid and other nervous system supportive nutrients is believed to be the reason that a Mediterranean-type diet in the lifestyle of the mother works so well in decreasing her infant’s SB risk.

Deficiency symptoms

What are deficiency symptoms for folate?

Because of its link with the nervous system, folate deficiency can be associated with irritability, mental fatigue, forgetfulness, confusion, depression, and insomnia. The connections between folate, circulation, and red blood cell status make folate deficiency a possible cause of general or muscular fatigue. The role of folate in protecting the lining of body cavities means that folate deficiency can also result in intestinal tract symptoms (like diarrhea) or mouth-related symptoms like gingivitis or periodontal disease.

Toxicity symptoms

What are toxicity symptoms for folate?

At very high doses greater than 1,000-2,000 micrograms, folate intake can trigger the same kinds of nervous system-related symptoms that it is ordinarily used to prevent. These symptoms include insomnia, malaise, irritability, and intestinal dysfunction. Primarily for these reasons, the Institute of Medicine at the National Academy of Sciences set a tolerable upper limit (UL) in 1998 of 1,000 mcg for men and women 19 years and older. This UL was only designed to apply to “synthetic folate” defined as the forms obtained from supplements and/or fortified foods.

Factors that affect function

What factors might contribute to a deficiency of folate?

In addition to poor dietary intake of folate itself, deficient intake of other B vitamins can contribute to folate deficiency. These vitamins include B1, B2, and B3 which are all involved in folate recycling. Poor protein intake can cause deficiency of folate binding protein which is needed for optimal absorption of folate from the intestine, and can also be related to an insufficient supply of glycine and serine, the amino acids that directly participate in metabolic recycling of folate. Excessive intake of alcohol, smoking, and heavy coffee drinking can also contribute to folate deficiency.

Nutrient interactions

How do other nutrients interact with folate?

Vitamins B1, B2, and B3 must be present in adequate amounts to enable folic acid to undergo metabolic recycling in the body. Excessive amounts of folic acid, however, can hide a vitamin B12 deficiency, by masking blood-related symptoms.

Health conditions

What health conditions require special emphasis on folate?

Folate may play a role in the prevention and/or treatment of the following health conditions:

• Alcoholism
• Anemias (especially macrocytic anemia)
• Atherosclerosis
• Cervical dysplasia
• Cervical tumors
• Cleft palate or cleft lip
• Crohn’s disease
• Depression
• Diarrhea
• Gingivitis
• Glossitis
• Glycogen storage disease type I
• Hyperhomocysteinemia
• Inflammatory bowel disease
• Insomnia
• Myelopathy
• Neural tube defects
• Non-senile dementia
• Ovarian tumors
• Periodontal disease
• Restless leg syndrome
• Schizophrenia
• Seborrheic dermatitis
• Tropical sprue
• Uterine tumors

Food sources

What foods provide folate?

Excellent sources of folate include romaine lettuce, spinach, asparagus, turnip greens, mustard greens, calf’s liver, parsley, collard greens, broccoli, cauliflower, beets, and lentils.

Very good sources include summer squash, black beans, navy beans, kidney beans, pinto beans, garbanzo beans, papaya, strawberries, green beans sea vegetables, cabbage, bell peppers, Brussels sprouts, leeks, fennel, tomatoes, and green peas.

What events can indicate a need for more high-folate foods?

• Irritability
• Mental fatigue, forgetfulness, or confusion
• Depression
• Insomnia
• General or muscular fatigue
• Gingivitis or periodontal disease

Excellent sources of folate include romaine lettuce, spinach, asparagus, turnip greens, mustard greens, calf’s liver, parsley, collard greens, broccoli, cauliflower, beets, and lentils.

WHF rich in
folate

FoodCals%Daily Value

Lentils23089.5%

Pinto Beans24573.5%

Garbanzo Beans26970.5%

Spinach4165.7%

Black Beans22764%

Navy Beans25563.7%

Kidney Beans22557.5%

Collard Greens4944.1%

Turnip Greens2942.4%

Lima Beans21639%

For serving size for specific foods, see Nutrient Rating Chart below at the bottom of this page.

• Description

• Function

• Deficiency Symptoms

• Toxicity Symptoms

• Cooking, storage and processing

• Factors that affect function

• Nutrient interaction

• Health conditions

• Food Sources

• Public Health Recommendations

• References

Drug-nutrient interactions

What medications affect folate?

Medications that can help deplete the body’s supply of folate include: anticancer drugs like methotrexate; cholesterol-lowering drugs like cholestyramine; anti-inflammatory drugs like sulfasalazine; biguanide drugs like buformin, phenformin, or metformin used in the treatment of diabetes; birth control pills (oral contraceptives); potassium-sparing diuretics like triamterene; and antibiotics like trimethoprim or pyrimethamine. While the anti-convulsant drug phenytoin (sold under the brand name of Dilantin or Phenytek) remains somewhat controversial in terms of its impact on folate, several animal studies have shown a lowering of the liver’s ability to make polyglutamyl forms of this vitamin following adminstration of phenytoin.

Form in dietary supplements

What forms of folate are found in dietary supplements?

Folic acid is normally found in its simple form (also called pteroylmonoglutamic acid) in dietary supplements. Folinic acid (also called 5-formyltetrahydrofolate) is also available, and can help by-pass certain biochemical steps that occur in the body once folate has been absorbed from the intestine.

Related Articles

• Adapting a Meal Plan for Little or No Grains
• Can salads be a good source of nutrients?
• Cooking and Nutrient Loss
• Do I need to eat dairy products in order to prevent osteoporosis?
• Does Healthy Eating require three meals each day?
• Feeling Great with Cruciferous Vegetables
• How to Help Avoid the Swine Flu and Seasonal Flu by Strengthening Your Immune System with the World's Healthiest Foods
• Rejuvenating Foods for Springtime
• Veggie Advisor: How does our Vegetable Advisor make personal recommendations?
• What is The Healthiest Way of Eating?
• Why are black beans so popular? Is there anything nutritionally unique about them?
• World's Healthiest Foods Menu
• World's Healthiest Foods Way of Eating

References

1. Albrecht J, Sidoryk-Wegrzynowicz M, Zielinska M, et al. Roles of glutamine in neurotransmission. Neuron Glia Biol. 2010 Nov;6(4):263-76. doi: 10.1017/S1740925X11000093. Epub 2011 Oct 21. https://doi.org/10.1017/S1740925X11000093
2. Chen P, Li C, Li X, et al. Higher dietary folate intake reduces the breast cancer risk: a systematic review and meta-analysis. Br J Cancer. 2014 Apr 29;110(9):2327-38. doi: 10.1038/bjc.2014.155. Epub 2014 Mar 25. Review. https://doi.org/10.1038/bjc.2014.155
3. Crider KS, Bailey LB, Berry RJ. Folic acid food fortification — its history, effect, concerns, and future directions. Nutrients 2011;3:370-84. https://doi.org/10.3390/nu3030370
4. Delchier N, Ringling C, Le Grandois J, et al. Effects of industrial processing on folate content in green vegetables. Food Chem 2013;139:815-24. https://doi.org/10.1016/j.foodchem.2013.01.067
5. Engelborghs S, Gilles C, Ivanoiu A, et al. Rationale and clinical data supporting nutritional intervention in Alzheimer's disease. Acta Clin Belg. 2014 Jan-Feb;69(1):17-24. doi: 10.1179/0001551213Z.0000000006. https://doi.org/10.1179/0001551213Z.0000000006
6. Feng C and Tollin G. Regulation of interdomain electron transfer in the NOS output state for NO production. Dalton Trans. 2009 Sep 14;(34):6692-700. doi: 10.1039/b902884f. https://doi.org/10.1039/b902884f
7. Food and Nutrition Board, Institute of Medicine. Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. Washington, DC: National Academy Press; 1998;58-86.
8. Fulgoni VL, Keast DR, Bailey RL, et al. Foods, fortificants, and supplements: where do Americans get their nutrients? J Nutr 2011;141:1847-54.
9. Gori T and Munzel T. Oxidative stress and endothelial dysfunction: therapeutic implications. Ann Med. 2011 Jun;43(4):259-72. doi: 10.3109/07853890.2010.543920. Epub 2011 Feb 1. Review. https://doi.org/10.3109/07853890.2010.543920
10. Gregory JF, Quinlivan EP, and Davis SR. Integrating the issues of folate bioavailability, intake and metabolism in the era of fortification. Trends in Food Science & Technology, Volume 16, Issues 6—7, June—July 2005, Pages 229-240. https://doi.org/10.1016/j.tifs.2005.03.010
11. Halsted CH, Wong DH, Peerson JM, et al. Relations of glutamate carboxypeptidase II (GCPII) polymorphisms to folate and homocysteine concentrations and to scores of cognition, anxiety, and depression in a homogeneous Norwegian population: the Hordaland Homocysteine Study. Am J Clin Nutr. 2007 Aug;86(2):514-21. https://doi.org/10.1093/ajcn/86.2.514
12. Hayden MR and Tyagi SC. Homocysteine and reactive oxygen species in metabolic syndrome, type 2 diabetes mellitus, and atheroscleropathy: the pleiotropic effects of folate supplementation. Nutr J. 2004 May 10;3:4. https://doi.org/10.1186/1475-2891-3-4
13. Mitchell ES, Conus N, and Kaput J. B vitamin polymorphisms and behavior: Evidence of associations with neurodevelopment, depression, schizophrenia, bipolar disorder and cognitive decline. Neurosci Biobehav Rev. 2014 Aug 27. pii: S0149-7634(14)00204-8. doi: 10.1016/j.neubiorev.2014.08.006. [Epub ahead of print] Review. https://doi.org/10.1016/j.neubiorev.2014.08.006
14. Kowalska M and Cichosz G. [Dairy products as source of folates].
15. Pol Merkur Lekarski. 2014 Apr;36(214):287-90. Review. Polish.
16. Mo H, Kariluoto S, Piironen V, et al. Effect of soybean processing on content and bioaccessibility of folate, vitamin B12 and isoflavones in tofu and tempe. Food Chem 2013;141:2418-25. https://doi.org/10.1016/j.foodchem.2013.05.017
17. Obeid R, Koletzko B, and Pietrzik K. Critical evaluation of lowering the recommended dietary intake of folate. Clinical Nutrition, Volume 33, Issue 2, April 2014, Pages 252-259. https://doi.org/10.1016/j.clnu.2013.12.013
18. O'Hare TJ, Pyke M, Scheelings P, et al. Impact of low temperature storage on active and storage forms of folate in choy sum (Brassica rapa subsp. parachinensis). Postharvest Biol Tec 2012;74:85-90. https://doi.org/10.1016/j.postharvbio.2012.06.020
19. Ohrvik V, Witthoft C. Orange juice is a good folate source in respect to folate content and stability during storage and simulated digestion. Eur J Nutr 2008;47:92-8. https://doi.org/10.1007/s00394-008-0701-3
20. Owen RT. Folate augmentation of antidepressant response. Drugs Today (Barc). 2013 Dec;49(12):791-8. doi: 10.1358/dot.2013.49.12.2086138. https://doi.org/10.1358/dot.2013.49.12.2086138
21. Quinlivan EP, Gregory JF. Effect of food fortification on folic acid intake in the United States. Am J Clin Nutr 2003;77:221-5. https://doi.org/10.1093/ajcn/77.1.221
22. Reynolds EH. The neurology of folic acid deficiency. Handb Clin Neurol. 2014;120:927-43. https://doi.org/10.1016/b978-0-7020-4087-0.00061-9
23. Sanhueza C, Ryan L, Foxcroft DR. Diet and the risk of unipolar depression in adults: systematic review of cohort studies. J Hum Nutr Diet 2013;26:56-70. https://doi.org/10.1111/j.1365-277x.2012.01283.x
24. Shafizadeh TB and Halsted CH. gamma-Glutamyl hydrolase, not glutamate carboxypeptidase II, hydrolyzes dietary folate in rat small intestine. J Nutr. 2007 May;137(5):1149-53.
25. Shuaibi AM, Sevenhuysen GP, and House JD. The importance of using folate intake expressed as dietary folate equivalents in predicting folate status. Journal of Food Composition and Analysis, Volume 22, Issue 1, February 2009, Pages 38-43. https://doi.org/10.1016/j.jfca.2008.08.003
26. Subar AF, Block G, James LD. Folate intake and food sources in the US population. Am J Clin Nutr 1989;50:508-16. https://doi.org/10.1093/ajcn/50.3.508
27. Tarraga Lopez PJ, Albero JS, and Rodriguez-Montes JA. Primary and secondary prevention of colorectal cancer. Clin Med Insights Gastroenterol. 2014 Jul 14;7:33-46. https://doi.org/10.4137/cgast.s14039
28. What We Eat in America. United States Department of Agriculture. 2012. Web. Accessed 5 September, 2013.
29. Winkels RM, Brouwer IA, Siebelink E, et al. Bioavailability of food folates is 80% of that of folic acid. Am J Clin Nutr 2007;85:465-73. https://doi.org/10.1093/ajcn/85.2.465
30. Bazzano LA, He J, Odgen LG et al. Dietary intake of folate and risk of stroke in US men and women:NHANES I Epidemiologic Follow-up Study. Stroke 2002 May;33(5):1183-9. 2002.
31. Beers MH, Berkow R. The Merck manual of diagnosis and therapy. Merck Research Laboratories, Whitehouse Station, New Jersey, 1999;850-870. 1999. https://doi.org/10.5694/j.1326-5377.1957.tb57521.x
32. Bower C, Stanley FJ, Nicol DJ. Maternal folate status and the risk for neural tube defects. The role of dietary folate. Ann N Y Acad Sci 1993;678:146-55. 1993. https://doi.org/10.1016/s0140-6736(05)64402-9
33. Brody T, Shane B, Stokstad ELR. Folic acid. In: Machlin LJ. (Ed). Handbook of vitamins. Marcel Dekker, New York, 1984. 1984.
34. Coombs GF. The vitamins. Academic Press, San Diego, 1992;357-376. 1992.
35. Duan W, Ladenheim B, Cutler RG et al. Dietary folate deficiency and elevated homocysteine levels endanger dopiminergic neurons in models of Parkinson's disease. J Neurochem 2002 Jan;80(1):101-10. 2002.
36. Fernstrom JD. Can nutrient supplements modify brain function?. Am J Clin Nutr 2000;71:(6 Suppl):1669S-75S. 2000. https://doi.org/10.1093/ajcn/71.6.1669s
37. Groff JL, Gropper SS, Hunt SM. Advanced Nutrition and Human Metabolism. West Publishing Company, New York, 1995. 1995.
38. Mason JB, Levesque T. Folate: effects on carcinogenesis and the potential for cancer chemoprevention. Oncology (Huntingt) 1996;10(11): 1727-1743. 1996.
39. Montes LF, Diaz ML, Lajous J, et al. Folic acid and vitamin B12 in vitiligo: a nutritional approach. Cutis 1992;50:39-42. 1992.
40. Onicescu D, Marin A, Mischiu L. Folate metabolism in normal human gingiva and in chronic marginal periodontitis. Rev Chir Oncol Radiol 1978;25(4): 257-64. 1978.
41. Pancharuniti N, Lewis CA, Sauberlich HE, et al. Plasma homocyst(e)ine, folate, and vitamin B12 concentrations and risk for early-onset coronary artery disease. Am J Clin Nutr 1994;59:940-948. 1994. https://doi.org/10.1056/nejm199707243370403
42. Quadri P, Fragiacomo C, Pezzati R, Zanda E, Forloni G, Tettamanti M, Lucca U. Homocysteine, folate, and vitamin B-12 in mild cognitive impairment, Alzheimer disease, and vascular dementia. Am J Clin Nutr. 2004 Jul;80(1):114-22. 2004. PMID:15213037. https://doi.org/10.1093/ajcn/80.1.114
43. Ristow KA, Gregory JF, Damron BL. Thermal processing effects on folacin bioavailability in liquid model food systems, liver and cabbage. J Agr Food Chem 1982;30(5):801-806. 1982. https://doi.org/10.1021/jf00113a001
44. Scholl TO, Johnson WG. Folic acid: influence on the outcome of pregnancy. Am J Clin Nutr 2000 May;71(5 Suppl):1295S-303S. 2000. PMID:10430. https://doi.org/10.1016/s0022-3565(25)30700-7
45. Steinberg SE. Mechanisms of folate homeostasis. Am J Physiol 1984;246:G319-G324. 1984. https://doi.org/10.1152/ajpgi.1984.246.4.g319
46. Terry P, Jain M, Miller AB et al. Dietary intake of folic acid and colorectal cancer risk in a cohort of women. Int J Cancer 2002 Feb 20;97(6):864-7. 2002. https://doi.org/10.1002/ijc.10138
47. Ubbink JB, Vermaak WJ, van der Merwe A, Becker PJ. Vitamin B-12, vitamin B-6, and folate nutritional status in men with hyperhomocysteinemia. Am J Clin Nutr 1993 Jan;57(1):47-53. 1993. PMID:19560. https://doi.org/10.1111/j.1471-4159.1977.tb10624.x
48. van Meurs JB, Dhonukshe-Rutten RA, Pluijm SM, van der Klift M, de Jonge R, Lindemans J, de Groot LC, Hofman A, Witteman JC, van Leeuwen JP, Breteler MM, Lips P, Pols HA, Uitterlinden AG. Homocysteine levels and the risk of osteoporotic fracture. N Engl J Med. 2004 May 13;350(20):2033-41. 2004. PMID:15141041. https://doi.org/10.1056/NEJMoa032546
49. Vujkovic M, Steegers EA, Looman CW et al. The maternal Mediterranean dietary pattern is associated with a reduced risk of spina bifida in the offspring. BJOG: An International Journal of Obstetrics and Gynaecology. Kidlington: Feb 2009. Vol. 116, Iss. 3; pg. 408-415. 2009. https://doi.org/10.1002/bdr2.1682
50. Zimmerman MB, Shane B. Supplemental folic acid. Am J Clin Nutr 1993;58:127-128. 1993. https://doi.org/10.1016/s0140-6736(07)60854-x
51. Bazzano LA, He J, Odgen LG et al. Dietary intake of folate and risk of stroke in US men and women:NHANES I Epidemiologic Follow-up Study. Stroke 2002 May;33(5):1183-9 2002.
52. Beers MH, Berkow R. The Merck manual of diagnosis and therapy. Merck Research Laboratories, Whitehouse Station, New Jersey, 1999;850-870 1999. https://doi.org/10.5694/j.1326-5377.1957.tb57521.x
53. Bower C, Stanley FJ, Nicol DJ. Maternal folate status and the risk for neural tube defects. The role of dietary folate. Ann N Y Acad Sci 1993;678:146-55 1993. https://doi.org/10.1016/s0140-6736(05)64402-9
54. Brody T, Shane B, Stokstad ELR. Folic acid. In: Machlin LJ. (Ed). Handbook of vitamins. Marcel Dekker, New York, 1984 1984.
55. Coombs GF. The vitamins. Academic Press, San Diego, 1992;357-376 1992.
56. Duan W, Ladenheim B, Cutler RG et al. Dietary folate deficiency and elevated homocysteine levels endanger dopiminergic neurons in models of Parkinson's disease. J Neurochem 2002 Jan;80(1):101-10 2002.
57. Fernstrom JD. Can nutrient supplements modify brain function. Am J Clin Nutr 2000;71:(6 Suppl):1669S-75S 2000. https://doi.org/10.1093/ajcn/71.6.1669s
58. Groff JL, Gropper SS, Hunt SM. Advanced Nutrition and Human Metabolism. West Publishing Company, New York, 1995 1995.
59. Mason JB, Levesque T. Folate: effects on carcinogenesis and the potential for cancer chemoprevention. Oncology (Huntingt) 1996;10(11): 1727-1743 1996.
60. Montes LF, Diaz ML, Lajous J, et al. Folic acid and vitamin B12 in vitiligo: a nutritional approach. Cutis 1992;50:39-42 1992.
61. Onicescu D, Marin A, Mischiu L. Folate metabolism in normal human gingiva and in chronic marginal periodontitis. Rev Chir Oncol Radiol 1978;25(4): 257-64 1978.
62. Pancharuniti N, Lewis CA, Sauberlich HE, et al. Plasma homocyst(e)ine, folate, and vitamin B12 concentrations and risk for early-onset coronary artery disease. Am J Clin Nutr 1994;59:940-948 1994. https://doi.org/10.1056/nejm199707243370403
63. Ristow KA, Gregory JF, Damron BL. Thermal processing effects on folacin bioavailability in liquid model food systems, liver and cabbage. J Agr Food Chem 1982;30(5):801-806 1982. https://doi.org/10.1021/jf00113a001
64. Scholl TO, Johnson WG. Folic acid: influence on the outcome of pregnancy. Am J Clin Nutr 2000 May;71(5 Suppl):1295S-303S 2000. PMID:10430. https://doi.org/10.1016/s0022-3565(25)30700-7
65. Steinberg SE. Mechanisms of folate homeostasis. Am J Physiol 1984;246:G319-G324 1984. https://doi.org/10.1152/ajpgi.1984.246.4.g319
66. Terry P, Jain M, Miller AB et al. Dietary intake of folic acid and colorectal cancer risk in a cohort of women. Int J Cancer 2002 Feb 20;97(6):864-7 2002. https://doi.org/10.1002/ijc.10138
67. Ubbink JB, Vermaak WJ, van der Merwe A, Becker PJ. Vitamin B-12, vitamin B-6, and folate nutritional status in men with hyperhomocysteinemia. Am J Clin Nutr 1993 Jan;57(1):47-53 1993. PMID:19560. https://doi.org/10.1111/j.1471-4159.1977.tb10624.x
68. Zimmerman MB, Shane B. Supplemental folic acid. Am J Clin Nutr 1993;58:127-128 1993. https://doi.org/10.1016/s0140-6736(07)60854-x