Is vitamin B9 safe?

Upper limit

Folate from food has not been reported to cause harm, so there is no upper limit for it.^[1] The limits apply to folic acid from supplements and fortified foods. In the US they are:^[1]

• 300 µg a day for children aged 1 to 3^[1]
• 400 µg for ages 4 to 8^[1]
• 600 µg for ages 9 to 13^[1]
• 800 µg for ages 14 to 18^[1]
• 1,000 µg for adults, also in pregnancy and while breastfeeding^[1]

In 2023, EFSA kept 1,000 µg a day for adults, including pregnant and breastfeeding women, and set 200 µg a day for infants aged 4 to 11 months. The EU limit covers folic acid and the 5-MTHF forms together.^[2] The limits do not apply to people who take high doses under medical care.^[1]

Vitamin B12 deficiency

Large amounts of folate can correct the anemia of a vitamin B12 deficiency, but not its nerve damage. Experts were worried that folic acid could hide a B12 deficiency until the nerve damage became permanent. The concern now is also that large amounts of folate may make the anemia and thinking problems of a B12 deficiency worse.^[1] EFSA based its upper limit on this risk: nerve symptoms that get worse in people who lack B12.^[2] See vitamin B12.

Cancer

A 2013 analysis of 13 trials with 49,621 people found no effect of folic acid on cancer over about 5 years. There were 1,904 cancers in the folic acid groups and 1,809 in the placebo groups, a difference that was not significant.^[3] Some trials found more cancers with folic acid, and the effect in people who already had colorectal polyps or cancer is unclear.^[1] See Does folic acid raise the risk of cancer?

Pregnancy

The 2015 Cochrane review found no clear difference in miscarriages with folic acid (risk ratio 1.10).^[4] A 2017 review for the US Preventive Services Task Force found no significant rise in twins and no consistent rise in asthma or allergy.^[5] Studies have linked 1,000 µg or more of folic acid a day around conception with lower scores on some tests of development in children at 4 to 5 years. The comparison was with mothers who took 400 to 999 µg. A link like this does not prove that folic acid was the cause.^[1]

Children and unmetabolized folic acid

In the US, 30% to 66% of children aged 1 to 13 who take supplements with folic acid get more than the upper limit from fortified food and supplements together. Little is known about the long-term effects.^[1] When the body gets more folic acid than it can change into active forms, unchanged folic acid stays in the blood. A single dose of 300 or 400 µg leaves measurable amounts, and 100 or 200 µg do not. Its effects, for example on immune cells, are not well understood.^[1]

Medicines

Folate interacts with some medicines:^[1]

• Methotrexate for cancer: folate could interfere with the drug, so ask the oncologist first. For rheumatoid arthritis, folic acid lowers its side effects.^[1][6]
• Medicines for epilepsy (phenytoin, carbamazepine, valproate): they lower folate, and folate may lower the level of the medicine.^[1]
• Sulfasalazine for ulcerative colitis: it lowers the absorption of folate.^[1]

Ask a doctor or pharmacist before taking folic acid if you take one of these medicines. Ask too if you may be low in vitamin B12 or plan a dose above the upper limit.^[1]