Things to Know Before Taking Folate or Folic Acid Supplement

Folate is an essential nutrient from the vitamin B complex. Having sufficient folate is crucial for maintaining general health as well as preventing and alleviating several medical conditions.

Folate and folic acid are terms that are often used interchangeably. However, they are not the same.

Folate refers to various chemical forms of folate that are found in food sources or circulate in human body. Folic acid is synthetically made and is very similar in molecular form to the naturally occurring folates. Still, there are important differences between these substances and the way they are metabolized in our bodies.

Folic acid is cheaper and obtained more easily than the folates from food sources. It is also more stable and resistant to heat or light.  That is why most nutritional supplements on the market contain folic acid and not folate. Check the label carefully to see what you are in fact getting with your daily vitamin pill.

Dosage – How Much Folate or Folic Acid Should You Take

In this section, we will explain the commonly recommended daily amounts of folic acid and folate for general population as well as recommendations for specific health conditions.  

One of the main differences between folic acid and folates is their absorption rate. Folic acid is absorbed much more easily into our bloodstream. For that reason the doses of folic acid are smaller than the doses for folates (about half of the recommended doses for folate).

To measure the difference in the absorption of folate and folic acid, scientists at Food and Nutrition Board (FNB) at the US National Academy of Medicine have created a measurement called 'Dietary folate equivalents' or DFE.

1 mcg DFE is equivalent to:

• 1 mcg of folate obtained from food sources
• 0.5 mcg of folic acid taken on an empty stomach or
• 0.6 mcg folic acid taken with a meal

You can read more about folate/folic acid daily intake recommendations in the Food and Nutrition Board Report: Dietary reference intake: Folate).

In the following section, you will found daily intake recommendations for folates and folic acid.

Recommended Daily Dosage for Folate

• Adults (male and female) 400 mcg (400 mcg DFE)
• Pregnant women: 600 mcg (600 mcg DFE)
• Breastfeeding women: 500mcg (500 mcg DFE)
• 0-6 months        65 mcg (65 mcg DFE)
• 7–12 months     80 mcg (80 mcg DFE)
• 1–3 years            150 mcg (150 mcg DFE)
• 4–8 years            200 mcg (200 mcg DFE)
• 9–13 years          300 mcg (300 mcg DFE)
• 14–18 years       400 mcg (400 mcg DFE)

Recommended Daily Dosage for Folic Acid

The dosages below apply to folic acid found in vitamin supplements.

Folic acid is better absorbed if taken on an empty stomach. If you take your supplement with meal or consume folic acid in fortified food product, the dose needs to be slightly larger to absorb the same amount (for example, the typical daily dose for a healthy adult - 200 mcg would be increased to 240 mcg).

• Adults (male and female): 200 mcg (400mcg DFE)
• Pregnant women: 300mcg (600mcg DFE)
• Breastfeeding women: 250 mcg (500mcg DFE)
• 0-6 months:       32.5 mcg (65 mcg DFE)
• 7–12 months:    40 mcg (80 mcg DFE)
• 1–3 years:           75 mcg (150 mcg DFE)
• 4–8 years:           100 mcg (200 mcg DFE)
• 9–13 years:        150 mcg (300 mcg DFE)
• 14–18 years:      200 mcg (400 mcg DFE)

Tolerable Upper Intake for Folic Acid

Studies have shown that when you take too much folic acid, some of it won't convert into the form (tetrahydrofolate) that the body can use. The same happens if you take the typically recommended amounts, but have a genetic condition that hinders the conversion of folic acid (such as MTHFR gene mutation).

The result in both cases is the same – you will be left with unconverted folic acid circulating in your bloodstream. This may lead to a range of unwanted health consequences – such as decreased action of natural killer cells and lowered immunity (1) or even a higher risk of cancer (2).

That is why the so called ‘tolerable upper intake level’ of folic acid has been set (see details for different age groups below). 

As a side note - natural folate doesn't have this limit as it doesn’t have any known adverse side effects. Also, any excess folate that is unused by the body doesn’t build up, but is excreted in urine.

Below you can see the tolerable upper intake of folic acid for different age groups.

• Adults (male, female): 1000mcg
• Pregnant women: 1000 mcg
• Breastfeeding women: 1000 mcg
• 0-12 months: not possible to establish; all folate in this age group should come from breast milk, formula or food sources
• 1–3 years:           300 mcg              
• 4– 8 years:          400 mcg              
• 9–13 years:        600 mcg              
• 14–18 years:      800 mcg

Dosages of Folate/Folic Acid for Specific Conditions

For Folate Deficiency

People with diagnosed folate deficiency typically take 400 to 1000 mcg of folic acid per day (which equals to 800 to 2000 mcg DFE daily). The dose is increased up to 5 milligrams daily if the deficiency is accompanied with severe megaloblastic anemia. The therapy for anemia can last from 4 to 6 weeks; then maintenance therapy at lower dose is started.

For Preventing Neural Tube Defects in Pregnancy

Women who are pregnant or are planning to become pregnant should consume 600 mcg of folate daily (600 mcg DFE). Ideally, this should be started a couple of months before getting pregnant. The neural tube defect happens in the first month of pregnancy, so early pregnancy is a crucial time for taking folate.

If you have a higher risk of neural tube defect (you have, for example, a family member with spina bifida) or you've had a previous pregnancy that was affected by neural tube defect, your dose should be increased. Your doctor will give you a prescription for a higher dose supplement; this can be up to 4.000 mcg of folic acid daily.

Folate and Folic Acid for Preventing Cancer

Folates that we get from food have long been known to offer some level of protection from cancer.  Good sources of dietary folates are leafy vegetables, legumes and certain fruits.

If you don’t get enough folates from your diet, you might consider a nutritional supplement. Check the label carefully to make sure that your supplement contains folates extracted from food sources.

There is no generally established folate dosage for cancer prevention. In such case, it is best if you follow the general recommended daily intake for an adult which is 400 mcg of folate daily.

 Folic acid, on the other hand, is not recommended for cancer prevention. In fact, there are even some studies that show that folic acid intake – especially in large amounts – might even contribute to the development of certain cancers. It is supposed to do that by triggering the already existing pre-cancerous growths (such s colon polyps) to turn cancerous (3). 

For Heart Disease

Folate benefits heart health by decreasing homocysteine levels, lowering high blood pressure and improving the function of blood vessel lining (countering endothelial dysfunction).

Homocysteine is an amino acid that is often increased in people with heart disease. For lowering homocysteine levels, people in different studies have taken between 200 mcg to 5 milligrams of folic acid daily.  Doses between 800 mcg to 1.000 mcg have had best results on homocysteine levels.

For decreasing high blood pressure and improving the function of blood vessel lining doses, people have taken between 400 mcg to 10 milligrams of folic acid.

In 2009, there was a meta-analysis of 8 clinical trials of folic acid in hypertension (4). People in these studies have taken either 5 or 10 milligrams of folic acid daily. 

The results have shown that folic acid – even in these extremely high doses – provides only a slight decrease in blood pressure. On the other hand, the improvement in the functioning of the blood vessel lining has been significant (as measured by percentage of FMD – flow-mediated dilation of blood vessels).

For Reducing the Risk of Stroke

Regular folate intake reduces the overall risk of stroke. The mechanisms behind this are supposed to be the same as the ones that provide benefits for the heart and blood vessels.

A meta-analysis of 8 randomized trials has shown that folate can decrease the risk of stroke by as much as 18% (5).  The dosages in these studies ranged from 0 (control group) to 500 mcg folic acid and up to 15 milligrams folic acid daily.  Longer supplementation has been related with larger decrease in risk. This is in line with HOPE2 trial that didn't show beneficial effect of folic acid supplementation on stroke risk until 36 months of taking supplemental folate.

The results were also more significant in countries that don't have grain fortification programs. One likely explanation for this would be that supplementation works better for people that start off with low blood folate levels.  

For Reducing Methotrexate toxicity

Methotrexate is a drug that is taken for suppressing immune system and as a chemotherapy agent. It is used as treatment for rheumatoid arthritis and psoriasis.

Folic acid is taken for alleviating some of the symptoms of methotrexate toxicity (toxic effects of this drug on the lining of the gastrointestinal tract and mouth).  For methotrexate toxicity, 1 to 20 milligrams of folic acid have been used.

Folate/Folic Acid for Improving Depression

Folate has been shown to help people with depression that don't respond well to antidepressants. It is not meant as a substitute for antidepressants; instead, it should be taken together with SSRI medication to enhance their effects (SSRI means selective serotonin reuptake inhibitors, which are a class of antidepressant drugs).

For improving response to antidepressants, people have taken between 200 mcg and 3 milligrams of folic acid daily.

For Preventing Macular Degeneration (AMD)

Folate helps to prevent age related macular degeneration possibly through its antioxidant effect and by lowering the levels of the amino acid homocysteine.

Folate works best when taken together with 2 other vitamin from vitamin B group: vitamin B12 and vitamin B6.

One study has found that taking the combination of folic acid, B12 and B6 reduces the risk of AMD by as much as 40% (6). This study included women with several risk factors for AMD, who were taking folic acid (2.5 mg/day), vitamin B₆ (50 mg/day), and vitamin B₁₂ (1 mg/day), or placebo.

Beneficial effects of these vitamins started to show about 2 years into the treatment – so the supplementation takes a while to work.

For Vitiligo

People also take folic acid to help with the symptoms of vitiligo (skin condition where patches of skin lose their pigment). For vitiligo, up to 5 milligrams of folic acid have been taken.

For Gum Disease

People with gingivitis (inflammation of the gums) often have low blood folate levels. It has been shown that taking folate by mouth doesn't significantly affect the condition of the mouth. On the other hand, mouthwash that contains folic acid works surprisingly well for calming down gum inflammation (7).

When and How to Take Folic Acid and Folate

If you take folic acid supplements, you will get the most out of them if you take them on an empty stomach – this way their absorption rate is basically 100%.

However, this may cause stomach upset in some people. If this happens, take your supplement with meal (when taken with meal, folic acid has about 85% absorption rate).

Supplements that have food-sources folates typically don’t cause stomach problems even if you take them on an empty stomach.

Folate and folic acid supplements are best taken in combination with other B vitamins (the so called vitamin B complex). The reason for this is that B vitamins need other vitamins from the same group to work efficiently in the body.

Folic acid is also often found in multivitamins and prenatal vitamins. The typical dose in multivitamins is 400 mcg, which provides 800 mcg DFEs daily (double the recommended daily intake!). Be careful to check the label for the dose, so you won’t be taking excess folic acid.

We recommend, though, that you skip folic acid supplements altogether and get your folate as part of whole foods-based multivitamin (or whole foods-base vitamin B complex).  

Store your folate/folic acid supplement in cool, dry place that is away from direct heat or light.

Safety and Side Effects

Natural folate is needed for healthy functioning of our body and is considered safe even in high doses.

Folic acid, though, has some concerns regarding safety. That is why the so called tolerable upper intake was established. For adults, this is set at 1.000 mcg of folic acid daily. It is not advised to exceed this amount as it may lead to unwanted side effects.

Still, many studies have used fairly high doses of folic acid. If you are considering dose larger than the recommended daily intake (200 mcg of folic acid), you should talk it through with your health care provider.

High doses of folic acid may cause various side effects, including diarrhea, stomach cramps, nausea, irritability, lack of focus, seizures, and skin changes.

There is some evidence that large doses of folic acid taken for longer periods of time may lead to serious side effects. These include increased risk of cancer, lowered immunity or increased risk of heart attack.

High doses of folic acid may also mask the deficiency in vitamin B12. This deficiency typically shows in simple blood analysis, but with folic acid supplementation the blood appears normal.  At the same time, the underlying B12 deficiency is left uncorrected and the other symptoms of the condition progress unhindered. This may eventually leave you with irreversible neurological damage.

It is worth mentioning that folate - unlike folic acid - doesn’t mask the blood symptoms (pernicious anemia) of B12 deficiency.

Who Should be Cautious When Taking Folate/Folic Acid

People with a History of Cancer or Undergoing Treatment for Cancer

There is some evidence that folic acid may trigger pre-cancerous growth to turn into cancer.  That is why people who have had cancer are advised to stay away from folic acid supplements.

Some medications for cancer are folate antagonists. They work by preventing cancer cells from using folate/folic acid to create new DNA and thus inhibit cancer growth. For that reason, folate and folic acid supplements are not suited for people undergoing cancer treatment.

People Recovering from Angioplasty

Folic acid/folate supplements should not be used by people recovering from angioplasty (procedure to widen narrowed arteries).

People with B12 Deficiency

Folic acid may mask the blood signs of B12 deficiency. People with a personal history of B12 deficiency or those who have close relatives that suffer from B12 deficiency should take folic acid with caution.

Seizure Disorders

Folic acid supplements may make seizures worse or may trigger an episode. If you suffer from a seizure disorder, avoid folic acid supplements; especially in high doses.

People with Low Blood Pressure

Folate and folic acid slightly lower blood pressure. If you have low pressure, be careful when taking these supplements.

People With Low Blood Sugar or Diabetes

Folate and folic acid may lower blood sugar. People with low blood sugar or diabetes, should be cautious when taking folate/folic acid – especially if they take large doses.

Pregnant and Breastfeeding Women

Pregnant women or women who are trying to conceive should take 600mcg of folate daily. The corresponding dose for folic acid is 300 mcg (which is equivalent to 600mcg DFE).

When choosing your prenatal supplement, those containing folate should always be preferred to supplements with folic acid.  There are several reasons for that (8):

• Folate doesn't cause adverse side effects,
• It raises blood levels of the bioavailable form of folate – tetrahydrofolate - more reliably than folic acid (because folic acid first needs to go through a complex conversion process before turning into tetrahydrofolate)
• It raises blood hemoglobin levels and helps protect against anemia in pregnancy (folic acid doesn't seem to have this effect).

Children

Infants (0-12 months) should get their folate exclusively from breast milk, formula or food – no other supplements should be taken.

Older children typically take folate/folic acid as part of multivitamin for kids. It is preferable if children take folate instead of folic acid supplement since folate has no known negative effects on health even if taken on the long term.

The dose of folate/folic acid should be adjusted according to age – take a look at the recommended daily intake amounts, which are listed earlier in the article.

Interactions with Prescription Medications

Check the list to see common medications that interact with folate and folic acid.

Medications for Seizures

Many medications that are used for seizures, epilepsy, migraines, and some psychiatric conditions can reduce the levels of folate in your blood. Likewise, folic acid and folate supplements interfere with the way these medications work and may decrease their effectiveness.

Medications in this group include fosphenytoin (Cerebyx), phenytoin (Dilantin), phenobarbital (Luminal), valproic acid and valproate (Depacon), primidone (Mysoline), and carbamazepine (Carbatrol, Epitol).

Methotrexate

Methotrexate (Rheumatrex, Trexall) is used for treating rheumatoid arthritis, psoriasis and as a chemotherapy drug. It is a folate antagonist, which means that it works by countering the effect of folate and folic acid in the body.

Patients taking methotrexate for cancer should speak with their oncologist before taking folate or folic acid as these supplements can reduce the effectiveness of methotrexate.

On the other hand, if you take methotrexate for psoriasis or rheumatoid arthritis, it is recommended that you also take a folic acid/folate supplement - it may help with some of the side effects that methotrexate has on the gastrointestinal tract (such as nausea, stomach ache, inflammation of the mouth, stomach, etc).

Other Chemotherapy Medications

Folic acid and folate interact with other chemotherapy drugs besides Methotrexate. These supplements may raise the levels of 5-fluorouracil and capecitabine (Xeloda) in your blood to potentially dangerous concentrations.

Consult with your oncologist before taking any supplement when you are undergoing chemotherapy.

Medications for Low Blood Pressure

Folate and folic acid cause a slight decrease in blood pressusre. They may increase the effectiveness of medications for lowering blood pressure. Take folate and folic acid with caution if you are on these medications and monitor your blood pressure.

Medications for Lowering Blood Sugar

Folate and folic acid may lower blood sugar. If you are taking medictaions for low blood sugar alongside these supplements, your blood sugar may drop too low. Monitor your blood sugar levels regularly. You may need to adjust your medications.

Medication for Treating Parasite Infections

Pyrimethamine (Daraprim) is a medication for treating malaria, toxoplasomosis and cystoisosporiasis. It is a folate antagonist, which means that it inhibits the way folate works in the body. Folic acid and folate supplements may decrease the effectiveness of this medication.

Sulfasalazine

Sulfasalazine is used mainly for treating inflammatory bowel disease. It prevents the absorption of folate in the intestine and may cause folate deficiency. If you take sulfasalazine, folate/folic acid supplement would help you maintain healthy blood levels of folate and prevent deficiency.

Tetracycline antibiotics

Folic acid and folate interfere with the absorption of tetracycline antibiotics and reduce their effectiveness. These supplements and all other B group vitamins should not be taken at the same time as tetracycline antibiotics.

Other Medications that Interfere With the Absorption of Folate

Certain medications reduce the absorption of folate. This means that when you take them, you should also take a folate/folic acid supplement to keep up your blood levels of folate.

These medications include:

• Medications for reducing stomach acid (antacids, H2 blockers, proton pump inhibitors)
• Cholesterol lowering medications (from the class of bile acid sequestrants)
• Birth control medications
• NSAIDs (non-steroidal anti-inflammatory medications, such as aspirin, ibuprofen and naproxen)
• Certain diuretics (water pills)

Folic acid and Folate with other Supplements, Herbs and Foods

Vitamins B

Folate/folic acid works synergistically with other B vitamins. This means that these vitamins need each other to be efficient. That is why folate and folic acid are often sold in B complex pills (containing all eight of the B vitamins).

One major problem with folic acid is that it may mask the symptoms of B12 deficiency. Folate, on the other hand, doesn’t do that as it doesn’t prevent the blood symptoms of B12 deficiency (pernicious anemia).  

If you have a family or personal history of B12 deficiency, take folate supplement instead of folic acid supplement.

C vitamin

C vitamin improves the absorption of folate and folic acid and increases their concentration in the blood.

Alcohol

Alcohol decreases the absorption of folate. People who regularly drink alcohol may have low blood folate levels.

Green and Black Tea, Oolong Tea

Drinking green or black tea decreases the bioavailability of folate. If you regularly drink tea, your blood levels of folate might be decreased (9, 10).

Coffee

Coffee has been shown to lower blood folate levels. However, it does that in specific way – it lowers high folate concentrations, while it has negligible effect on low folate concentrations (11).

Other Interactions with Folate and Folic Acid:

Folate and folic acid may also interact with the following:

• Herbs and supplements that lower blood sugar or blood pressure
• Phytoestrogens
• Aged garlic extract
• Herbs and supplements that act as diuretics (promote water loss)
• Iron
• Omega 3 fatty acids
• Probiotics
• Salycylates (willow bark, dropwort, poplar leaf buds)
• Vitamin A
• Zinc

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