What are the side effects of folic acid?

Folic acid, folates, and vitamin B9

Folic acid is a synthetic form of vitamin B9. Vitamin B9 refers to a group of molecules that includes folic acid, as well as its negatively charged form and its derivatives: folates. Once absorbed by the body, folic acid and folates are converted into tetrahydrofolate (FH₄), a coenzyme essential to numerous biological reactions. Folic acid is more stable than folates and is better absorbed by the human body.

Good to know: From a nutritional standpoint, the term “folate” is commonly used to refer to the forms of vitamin B9 found naturally in food, while the term “folic acid” refers to the synthetic form used in certain dietary supplements. In biology, folates refer to all forms of vitamin B9. The definition is therefore not the same for biologists and nutritionists!

How does vitamin B9 work?

Once converted into tetrahydrofolate, vitamin B9 plays a role in the synthesis of DNA and certain amino acids that make up proteins (methionine, histidine, and serine). It is therefore essential for cell renewal and the growth and development of many tissues. Cells and tissues that renew rapidly are therefore the first to be affected by a vitamin B9 deficiency in the body: this is the case, for example, with blood cells, hair follicles, skin cells, and the intestinal lining. Vitamin B9 is also involved in the synthesis of substances that influence brain activity. During fetal development, an adequate intake of vitamin B9 is important to support the proper formation of the neural tube, the embryonic brain, and the spinal cord.

Discover the health benefits of folic acid as well as its benefits for skin and hair health.

What are the dietary sources of folic acid and folates?

Humans, like all animals, are unable to synthesize folic acid or folates and must therefore obtain them through their diet. Liver and legumes are particularly rich in folates: chicken liver contains 1,440 µg/100g, while red beans contain an average of 394 µg/100g and chickpeas 369 µg/100g. It is also found, to a lesser extent, in cabbage, spinach, broccoli, asparagus, green beans, melons, and aged cheeses. But the clear winner in folate content is brewer’s yeast: over 2,000 µg per 100g!

Be careful, however, as folate is sensitive to heat and can be degraded by cooking. Therefore, opt for gentle cooking methods such as steaming.

Folic acid requirements vary by age and population (ANSES):

• Infants under 6 months: 65 µg/day in folate equivalents (or 39 µg/day of folic acid)

• Infants 6 months to 1 year old: 80 µg/day in folate equivalents (or 48 µg/day of folic acid)

• Children 1 to 3 years old: 120 µg/day of folate equivalents (or 72 µg/day of folic acid)

• Children aged 4 to 6 years: 140 µg/day of folate equivalents (or 84 µg/day of folic acid)

• Children aged 7 to 10: 200 µg/day of folate equivalents (or 120 µg/day of folic acid)

• Children aged 11 to 14: 270 µg/day of folate equivalents (or 162 µg/day of folic acid)

• Ages 14 and older: 330 µg/day of folate equivalents (or 198 µg/day of folic acid) for both men and women

• Pregnant women or women planning to conceive: 600 µg/day of folate equivalents (or 360 µg/day of folic acid)

• Breastfeeding women: 500 µg/day of folate equivalents (or 300 µg/day of folic acid)

Folic acid excess and adverse effects

The safety limit for vitamin B9 in adults is 1,000 µg/day in folate equivalents, or 600 µg/day of folic acid. Side effects have been reported with excessive intake, such as gastrointestinal issues (including nausea, bloating, gas, heartburn, diarrhoea, or constipation) and sleep disturbances. 

The risk of side effects from excessive vitamin B9 intake through diet is very low, as vitamin B9 is water-soluble and is excreted in the urine in cases of mild overdose. However, when taking a dietary supplement, it is important to adhere to the recommended doses to avoid side effects caused by folic acid.

Folic acid and vitamin B12 deficiency

Folic acid supplementation causes side effects in cases of a pre-existing deficiency in vitamin B12: It can exacerbate the effects of the deficiency. This is because folic acid redirects the small amount of vitamin B12 remaining in the body toward blood cell regeneration. The problems with nerve tissue regeneration observed during a vitamin B12 deficiency are then exacerbated and can lead to neurological disorders. 

The symptoms of mild to moderate vitamin B12 deficiency are as follows: Fatigue, anaemia, tingling sensations, and/or pain in the tongue. If in doubt, do not hesitate to consult your doctor.

Folic acid and interactions with other compounds

Folic acid universally promotes cell growth: this is also true for bacteria and cancer cells. Certain antibiotics work by interfering with folic acid metabolism, as do some antimalarial and anticancer drugs. Folic acid supplementation therefore has the side effect of reducing their effectiveness. Folates and folic acid may also interact with antiepileptic drugs.

If in doubt, consult your doctor before taking a dietary supplement rich in folic acid to avoid side effects.

Even though folic acid is an essential vitamin, there are situations where taking it as a supplement is not recommended without medical advice, or may even be contraindicated:

• Known allergy to folic acid or any component of a supplement: any previous allergic reaction (skin rash, itching, swelling) is a contraindication.

• Untreated vitamin B12 deficiency: Folic acid can mask anaemia caused by a B12 deficiency while allowing nerve damage to progress if the deficiency is not corrected.

• Folate-dependent cancer or tumour without a confirmed deficiency: In this context, supplementation is generally not recommended unless a deficiency is clearly diagnosed and treated.

• Renal dialysis (hemodialysis): People on hemodialysis should avoid any folic acid supplementation without medical advice, as their needs and intake must be precisely adjusted.

• Presence of a cardiac stent: If a cardiac stent has recently been implanted, folic acid supplementation should be discussed with a healthcare professional.

• Significant drug interactions: Certain medications (anticonvulsants, methotrexate, specific antibiotics, etc.) alter the effect or absorption of folic acid and require medical supervision.

Other natural extracts contain vitamin B9, although in smaller amounts than in brewer’s yeast:

• Spirulina: Spirulina powder contains an average of 94 µg/100g of folate equivalent

• Nettle: Fresh nettle leaves contain an average of 212 µg/100g of folate equivalent.

Follow the recommended dosages. Do not use if you have a pre-existing vitamin B12 deficiency.

If you are planning to become pregnant or are breastfeeding, consult a doctor to ensure your vitamin B9 intake is appropriate.

Morgane , who completed her PhD in 2022, is a researcher specialising in phytochemistry. Passionate about natural substances, she devotes her research to studying the composition and properties of plant extracts.