Folic acid is probably the supplement most people associate with pregnancy, and for good reason. It’s one of the few supplements where the evidence is genuinely strong enough that public health agencies worldwide recommend universal supplementation for women who might become pregnant.

But folic acid does more than prevent birth defects. It’s involved in DNA synthesis, cell division, and amino acid metabolism throughout the body. The question is: how much of the broader health claims hold up under scrutiny?

What is folic acid?

Folic acid belongs to the vitamin B complex family. The name comes from the Latin word “folium” meaning leaf, since leafy greens are one of the richest natural sources.

Here’s where terminology gets confusing. “Folate” refers to the natural form found in foods like spinach, lentils, asparagus, and liver. “Folic acid” is the synthetic form used in supplements and fortified foods. Your body needs to convert both forms into 5-methyltetrahydrofolate (5-MTHF) to actually use them.

This conversion requires an enzyme called MTHFR. About 10-15% of the population has genetic variations that make this enzyme work less efficiently 1. For these individuals, unconverted folic acid can accumulate in the bloodstream, which some researchers have raised concerns about, though the clinical significance remains debated.

Folate deficiency typically results from poor diet, alcohol abuse, malabsorption disorders, or increased needs during pregnancy and breastfeeding. Symptoms can include fatigue, mouth sores, grey hair, and a specific type of anaemia called megaloblastic anaemia where red blood cells become abnormally large.

The difference between folate and folic acid

Dietary folate is heat-sensitive and easily destroyed by cooking. You’ll find it naturally in:

Dark leafy greens (spinach, kale, rocket)
Legumes (lentils, chickpeas, black beans)
Asparagus and Brussels sprouts
Citrus fruits
Liver and eggs

Folic acid, the synthetic version, is actually more stable and better absorbed than food folate. The bioavailability of folic acid from supplements is about 85% on an empty stomach, compared to roughly 50% for food folate 2.

Many countries now mandate folic acid fortification of flour and cereals. In the UK, mandatory fortification of non-wholemeal wheat flour was approved in 2021, following decades of debate. The US, Canada, and Australia already fortify their flour supply.

A note on methylfolate supplements

Some people prefer supplements containing 5-MTHF (methylfolate) rather than folic acid. The thinking goes: if your body might struggle to convert folic acid, why not take the pre-converted form?

The evidence on whether this matters clinically is mixed. For most people, standard folic acid works fine. But if you know you have MTHFR variants and want to be cautious, methylfolate supplements are an option. They tend to cost more, and I wouldn’t say they’re necessary for everyone, but they’re not unreasonable either.

What does the evidence actually show?

Let me walk through the main areas where folic acid has been studied. I’ll be honest about where the evidence is strong versus where it’s more preliminary.

1. Preventing neural tube defects

This is the gold standard for folic acid supplementation, and it’s one of the clearest examples in nutrition science where supplementation genuinely prevents serious disease.

Neural tube defects like spina bifida and anencephaly occur when the neural tube fails to close properly in the first 21-28 days of pregnancy. Often, this happens before a woman even knows she’s pregnant.

A Cochrane review of 4 studies involving 6,425 women found that folic acid supplementation from preconception through early pregnancy reduced neural tube defects by 72% 3. The NHS recommends 400 micrograms daily from before conception until the 12th week of pregnancy 4.

My honest assessment: This is rock-solid evidence. If there’s one thing folic acid definitely does, it’s this.

2. Reducing autism risk

A meta-analysis of 10 observational studies suggested that folic acid supplementation in early pregnancy was associated with reduced autism risk in offspring 5. The protective effect appeared most consistent when supplementation started before conception and continued through the first trimester.

However, these are observational studies, not randomised trials. Women who take prenatal vitamins may differ from those who don’t in ways that independently affect autism risk (better healthcare access, different lifestyle factors, etc.).

The catch: Promising but not definitive. It’s another reason to take folic acid during pregnancy, but I wouldn’t overstate the autism-prevention claim specifically.

3. Reducing preterm birth risk

A meta-analysis of 27 studies found that higher blood folate levels and folate supplementation were inversely associated with preterm birth 6. The association held for dietary folate intake as well.

Reality check: Again, observational data with all its limitations. But combined with the neural tube evidence, it reinforces the general principle that adequate folate during pregnancy matters.

4. Preventing congenital heart defects

A meta-analysis of 20 case-control studies found that folic acid supplementation during pregnancy reduced the risk of congenital heart defects by approximately 40% in Chinese and European populations 7. Interestingly, no association was found in US populations, possibly due to widespread flour fortification creating a higher baseline folate status.

Worth noting: The inconsistency across populations is actually informative. It suggests the benefit may be greatest in populations with lower baseline folate intake.

5. Reducing cleft lip and palate

A meta-analysis of 37 studies found that maternal folic acid supplementation reduced the risk of oral clefts. Specifically, folic acid alone reduced non-syndromic cleft palate risk by 27%, while multivitamins containing folic acid showed a 35% reduction 8.

The most protective timing was from before pregnancy through the first trimester.

My take: Consistent with the other pregnancy outcomes. Folic acid isn’t magic, but adequate intake during early pregnancy genuinely seems to support normal fetal development across multiple systems.

6. Blood sugar regulation

Moving beyond pregnancy, the evidence becomes less compelling.

A meta-analysis of 24 randomised controlled trials found that folic acid supplementation reduced fasting blood glucose, fasting insulin, and insulin resistance compared with controls 9. Higher doses (5mg or more daily) showed more pronounced effects.

However, there was no significant change in HbA1c, which is the more clinically relevant marker for long-term blood sugar control.

In practice: The improvements were statistically significant but relatively small. I wouldn’t recommend folic acid specifically for diabetes management. If you’re taking it anyway and happen to have blood sugar concerns, there might be a modest benefit, but it’s not a treatment.

7. Cholesterol and triglycerides

A meta-analysis of 38 trials found that folic acid supplementation reduced triglycerides and total cholesterol, but had no effect on LDL (“bad”) or HDL (“good”) cholesterol 10.

A word of caution: The triglyceride reduction sounds good on paper, but the lack of effect on LDL and HDL makes the clinical relevance questionable. For cholesterol management, established approaches like fish oil or red yeast rice have better evidence.

8. Stroke prevention

A meta-analysis of 12 randomised controlled trials involving 47,523 patients with cardiovascular disease found that folic acid treatment significantly reduced stroke risk, particularly at doses under 2mg daily with follow-up of 40 months or more 11.

Notably, there was no effect on all-cause mortality, cardiovascular mortality, or coronary heart disease.

The honest truth: Folic acid may lower homocysteine (an amino acid linked to cardiovascular risk), but the clinical translation to actual heart disease prevention has been disappointing. The stroke finding is interesting but hasn’t changed clinical practice.

A meta-analysis of 14 studies found that folic acid supplementation combined with multivitamins reduced preeclampsia risk, though folic acid alone didn’t show the same benefit 12.

My assessment: This suggests it’s the overall nutritional adequacy during pregnancy that matters, not folic acid specifically. Taking a prenatal multivitamin rather than folic acid alone makes sense.

10. Gastric precancerous lesions

One area where higher-dose folic acid has shown promise is in gastric precancerous conditions. A meta-analysis of 11 trials found that folic acid at 20-30mg daily for 3-6 months improved markers of chronic atrophic gastritis and intestinal metaplasia 13.

Worth considering: These are very high doses requiring medical supervision. This isn’t something to try on your own, but it’s an interesting therapeutic use in gastroenterology.

How much folic acid do you need?

For most adults, the recommended daily intake is 400 micrograms. During pregnancy and breastfeeding, this increases to 400-600 micrograms daily according to the NHS 4.

Higher doses (4-5mg daily) are recommended for women with:

Previous pregnancy affected by neural tube defect
Family history of neural tube defects
Diabetes
Epilepsy treated with certain medications
Obesity (BMI over 30)
Sickle cell disease
Coeliac disease or other malabsorption conditions

These higher doses require a prescription in the UK and should be taken under medical guidance.

Side effects of folic acid

At normal supplemental doses (up to 1000 micrograms daily), folic acid is generally well-tolerated. You can’t really overdose on dietary folate from food.

Potential side effects at higher doses include:

Nausea and loss of appetite
Bloating and flatulence
Bitter taste in the mouth
Sleep disturbances
Irritability or confusion
Skin reactions (rarely)

The main concern with high-dose folic acid isn’t direct toxicity but rather masking vitamin B12 deficiency. Both deficiencies cause a similar type of anaemia, and high folic acid can correct the blood abnormalities while allowing B12 deficiency to progress silently, potentially causing irreversible nerve damage. This is particularly relevant for older adults and vegans.

Who should be careful with folic acid?

1. People with a history of allergic reactions

Though rare, allergic reactions to folic acid can occur. Symptoms include rash, itching, swelling, and difficulty breathing.

2. Those with seizure disorders

Folic acid may increase seizure frequency in some people with epilepsy, particularly at higher doses.

3. People who have had coronary stents

Some earlier research suggested that combined folic acid, vitamin B6, and B12 supplementation might increase the risk of stent restenosis. The evidence here is mixed, but if you’ve had a coronary stent, discuss supplementation with your cardiologist.

4. Those with undiagnosed B12 deficiency

As mentioned, high folic acid can mask B12 deficiency symptoms. If you’re taking high-dose folic acid, your B12 status should be monitored.

5. Those with a history of colorectal adenomas

Some observational studies have raised concerns about high folic acid intake and colorectal cancer in people with pre-existing adenomas. The relationship is complex, with folate potentially protective early in cancer development but possibly promoting existing precancerous lesions 14.

6. Men with concerns about prostate cancer

Elevated serum folate has been associated with increased prostate cancer risk in some studies. Whether this applies to supplemental folic acid specifically remains unclear.

Drug interactions

Folic acid can interact with several medications:

Anticonvulsants: Phenytoin, fosphenytoin, and primidone levels can be reduced by folic acid, potentially worsening seizure control. These drugs also increase folate requirements, creating a tricky balance.

Methotrexate: This drug works partly by interfering with folate metabolism. High folic acid intake can reduce methotrexate’s effectiveness for conditions like rheumatoid arthritis or psoriasis. Low-dose folic acid is sometimes prescribed alongside methotrexate to reduce side effects, but the dosing requires careful medical management.

Pyrimethamine: This antimalarial drug is a folate antagonist, and folic acid can reduce its effectiveness.

Barbiturates: These sedatives may have reduced effectiveness with concurrent folic acid use.

Practical recommendations

For women planning pregnancy or of childbearing age: 400 micrograms of folic acid daily is well-supported by evidence. Start before conception if possible.

For the general population: If you eat a varied diet including leafy greens and fortified foods, you probably get enough folate. A standard multivitamin providing 400 micrograms is reasonable but not essential.

For specific health conditions: Talk to your doctor. The evidence for folic acid treating diabetes, heart disease, or other conditions is generally too weak to recommend supplementation specifically for those purposes.

References

Genetics of the MTHFR gene. Hum Mol Genet. 2016
Bioavailability of food folate vs folic acid. Am J Clin Nutr. 2004
Cochrane review on folic acid for neural tube defects. Cochrane Database Syst Rev. 2001
NHS guidance on pregnancy vitamins and supplements
Meta-analysis on folic acid and autism risk. Nutrients. 2021
Folate and preterm birth meta-analysis. J Matern Fetal Neonatal Med. 2019
Folic acid and congenital heart defects. Sci Rep. 2016
Folic acid and oral clefts meta-analysis. Sci Rep. 2018
Folic acid and glycaemic control meta-analysis. Nutrients. 2021
Folic acid and lipid profile meta-analysis. Nutr Metab Cardiovasc Dis. 2021
Folic acid and stroke prevention meta-analysis. BMC Cardiovasc Disord. 2019
Folic acid and pregnancy hypertension meta-analysis. Pregnancy Hypertens. 2018
Folic acid and gastric precancerous lesions. Front Pharmacol. 2022
Folate and colorectal cancer concerns. Am J Clin Nutr. 2008