Folic acid dosage: how much is too much?

Folate is crucial for fertility and during early pregnancy, where it has been shown to reduce the risk of birth defects. However, like many essential nutrients, humans cannot produce folate, meaning we must get it from our diet.

Because of this, many governments and health authorities recommend folate or folic acid supplementation. Both the European Food Safety Authority (EFSA) and the U.S. Food and Drug Administration (FDA) have set recommendations for folate intake to maintain health at every stage of life.

Does folic acid have side effects ?

Although folic acid is generally regarded as very safe, there are potential side effects from taking very large doses for a long time. This is because the process to become biologically active requires folic acid to go through several transformation steps in the body – each one controlled by a specific enzyme.

Whilst this multi-step bioconversion is not an issue for some, there are many people with a specific genetic trait known as MTHFR polymorphism which means the conversion between folic acid or food folates into 5-MTHF as less efficient and effective.

Because of this polymorphism, there is a big variation in how efficiently folic acid is converted to the bioactive form in different people, meaning that even people who take high doses of folic acid can still be deficient in folate, but have potentially dangerous effects from the high folic acid intake.

A 2016 study reported that excessive intake of folic acid could have adverse health outcomes in elderly by masking vitamin B12 deficiency, which may particularly impact risk of cognitive decline and anaemia as a result of such deficiencies going unnoticed and untreated. People with MTHFR polymorphism may be at increased risk of such issues due to higher levels of circulating folic acid, since the conversion step to 5-MTHF is less effective.

Furthermore, when people take a lot of folic acid the enzymes we convert cannot keep up and so we can end up with higher levels of unmetabolized folic acid (UMFA).

Studies exploring the potential risks and mechanisms behind UMFA have suggested that higher blood levels of UMFA might lower the activity of important immune cells known as natural killer (NK) cells in postmenopausal women. Recent studies have also confirmed that UMFA is associated with a reduction of NK cytotoxicity, which reduces the immune system’s capacity to kill off malignant or pre-malignant cells.

Research in mice and humans has also suggested high folic acid intake may also be linked to an increased risk of asthma and respiratory tract infections and insulin resistance and obesity in children. 

These risks may be important in people who are older or at higher risk of chronic conditions. Indeed, a 2010 report found that one third of elderly participants had detectable levels of UMFA.

How can I ensure I’m safe while taking folate?

When taking a folate supplement it is important to ensure you are maintaining the correct dose and using an effective form. Taking the right dose of an effective form of folate such as 5-MTHF in the form of Quatrefolic^® will ensure the safety and efficacy of supplementation by delivering a bioactive dose of reduced folate directly to the body, without the need for a multi-step conversion process that can result in high levels of UMFA.