The Benefits of Folic Acid

The Benefits of Folic Acid

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Katie Stone - Naturopath

Written By:

Katie Stone - Naturopath
Kari Asadorian - BSN, RN

Medical Reviewer:

Kari Asadorian - BSN, RN
Jamie Hope - Methyl-Life® Founder

Edited By:

Jamie Hope - Methyl-Life® Founder
Last updated:

The Benefits of Folic Acid

What is folic acid?

Folic acid (also known as vitamin B9) is the synthetically derived form of dietary folate. The umbrella term ‘folate’ actually refers to a group of water-soluble compounds (called folates) that play an essential role in synthezising deoxyribonucleic acid (DNA).1


Folic acid is not naturally occurring and is not biologically active in the body until it undergoes a multi-step conversion process. Natural folate is a nutrient present in leafy green vegetables, legumes, egg yolk, liver, and citrus fruits. Folic acid is a synthetic dietary supplement that is added into artificially fortified foods such as breads and cereals and pharmaceutical vitamins.


Folic acid is more stable than natural folate, and if added to food, it is not destroyed in cooking or heating as is the case with natural folate.


Folic acid is approved by the FDA for treating folate deficiency and anemia, and is often prescribed to women who are pregnant or planning to conceive.


Folic acid is often added to foods such as grain-based products (breads, flour, cereal, and pasta).


However, unlike the natural form of folate, folic acid must undergo several steps involving the DHFR and MTHFR enzymes to be converted into its active form, methylfolate. Methylfolate is then used for many essential downstream processes in the body.


Supplementing with methylfolate will of course bypass this entire process, as methylfolate is directly absorbed into the bloodstream and can be immediately used by the body. (link?)


Folate is required for numerous biological processes, including the recycling of homocysteine (a potentially harmful amino acid) into methionine. Folate works alongside B6 and B12 to convert methionine into SAM-e (S-adenosylmethionine), the body's universal methyl donor. SAM-e then provides methyl groups for creating and repairing DNA/RNA, neurotransmitter production (including serotonin and dopamine), myelin formation (the insulation around nerve fibers), and cell membrane health.2 SAMe may reduce inflammatory chemicals in the body which can then reduce pain.3

List of benefits of folic acid

The benefits of folic acid for women during pregnancy

Demands for folate increase significantly during pregnancy because it is required for the proper growth and development of the fetus. Folate deficiency has been linked to health conditions and abnormalities in babies, including neural tube defects such as spina bifida and anencephaly.4 Mothers may also be affected by anemia and peripheral neuropathy.

After folic acid was added to foods in the US in 1998, there was a significant decrease in the prevalence of children born with NTDs.5 The US National Institutes of Health (NIH) recommends that pregnant women take 600 µg of folic acid per day during pregnancy, and 500 µg during lactation.

Prescription of folic acid to women in the preconception period and during pregnancy is a standard practice.

However, recent research has highlighted concerns for the safety of folic acid supplementation, and methylfolate is often recommended as an alternative as it does not require conversion in the body. Methylfolate is also more effective than folic acid for pregnant women with MTHFR.6

The benefits of folic acid for women (not during pregnancy)

All women of reproductive age are encouraged to take folic acid or folate, even if they are not pregnant or planning to conceive. However, it should be noted that methylfolate is more effective than folic acid - especially during pregnancy - as it is immediately absorbed and can bypass the MTHFR genetic mutation.


 

  • Red blood cell production
    Women are at higher risk of iron deficiency anemia due to regular iron losses during reproductive years, as well as demands during pregnancy.7
    Folate is required for the formation and maturation of red blood cells (RBCs).8Deficiency of folate and/or vitamin B12 inhibits DNA production, which can cause developing red blood cells to die before they mature, resulting in anemia (low red blood cell count).


  • Mood and cognitive function
    The prevalence of depression among women is 50% higher than among men.9 Folate is required for the synthesis of neurotransmitters, including serotonin, dopamine, and norepinephrine, which are involved in many aspects of mental health, including mood, appetite, and cognition.10
    Methylfolate has been shown in numerous studies to improve response to antidepressants, including in those with treatment-resistant depression. Methylfolate increases neurotransmitter production, which then increases the effectiveness of antidepressant medication. Several clinical trials have found that taking 15mg L-methylfolate per day with an SSRI is more effective than taking SSRIs alone in people with depression.11


  • Preconception/fertility
    Folate deficiency is significantly associated with poor fertility, recurrent miscarriage and stillbirth, especially among women with MTHFR variants.12
    However, research has shown that folic acid does not benefit women with the homozygous 677TT genetic mutation as they lack the MTHFR enzyme required for proper conversion to methylfolate.13 Methylfolate is recommended instead as it bypasses the conversion process and is immediately available for use in the body.14


  • Cardiovascular health
    Folate is required for regulating homocysteine, an amino acid that can increase the risk of heart disease if in excess. One study found that folic acid supplementation reduced the risk of stroke by 10% and the overall risk of cardiovascular disease by 4%.15
    However, a 2024 study found that methylfolate supplementation in people with MTHFR reduced major biomarkers of heart disease including elevated homocysteine by 30% and high cholesterol by 7.5% within six months.16

The benefits of folic acid for men

  • Cardiovascular disease
    Men generally develop CVD at a younger age and are more likely to develop coronary heart disease (CHD) than women. Stroke and CHD mortality rates in middle-aged men are typically higher than in middle-aged women.17
    Folate supplementation is one of the major interventions to reduce homocysteine levels and the most recent meta‐analyses of randomized control trials have concluded that homocysteine‐lowering interventions were associated with 10% reduced risk of first‐ever stroke.18


  • Fertility
    Low folate is significantly associated with low sperm concentration in men, and folate deficiency significantly reduces the expression of genes critical to spermatogenesis.19 One study found that high-dose folic acid supplementation in men requiring Intracytoplasmic Sperm Injection for male infertility helped reproductive outcomes, but further research is pending.20 However, it has been noted that methylfolate is recommended over folic acid as the most bioavailable form of folate.


  • Mood
    While women are more likely to experience depression and anxiety, men are more prone to substance use disorders and antisocial behaviors, and are more likely to die by suicide.21
    A meta-analysis found that folic acid supplementation was associated with a 44% reduction in suicide events.22 However, as those with treatment-resistant depression (TRD) are more likely to have the MTHFR genetic mutation, methylfolate is recommended as an adjunct to antidepressant medication.23

Folic acid and weight loss

Folic acid is unlikely to help with weight loss. A 2023 meta-analysis found that folic acid supplementation did not change BMI or body weight, although it showed a small decrease in BMI in people with elevated homocysteine levels (≥15 μmol/L) and women with polycystic ovarian syndrome. However, further long-term studies on both sexes are required to confirm this finding.24


Folate deficiency may increase the risk of weight gain and adiposity. Several studies have indicated a link between low folate intake or low folate levels and greater body mass, BMI, overall fat accumulation, and higher waist circumference.25

The benefits of folic acid for skin conditions

Elevated homocysteine levels have been linked to chronic autoimmune disorders, including rheumatoid arthritis, systemic lupus erythematosus, chronic plaque psoriasis, and psoriatic arthritis. Folic acid supplementation appears to alleviate symptoms of chronic inflammatory skin diseases, such as moderate to severe psoriasis, especially in those who also have high homocysteine, low folate and cardiovascular health issues.26

The benefits of folic acid for Bodybuilding

A study examining red blood cell folate and skeletal muscle mass found that increased folic acid intake led to increased muscle mass, but only up to a certain point. When folate levels peaked, muscle mass started to decrease. Excessive folic acid was found to impair blood flow to muscles (associated with arteriosclerosis), disrupt cellular metabolism, and interfere with other nutrients.27

The benefits of folic acid for the liver

Folate deficiency disrupts liver function by triggering inflammatory pathways and impairing lipid metabolism. This may lead to hepatic fat accumulation and fibrosis. Research demonstrates that inadequate folate levels contribute to the development and progression of non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, alcoholic liver disease, viral hepatitis, hepatic fibrosis, and liver cancer.28


Excess folic acid can reduce MTHFR activity, which lowers the body’s ability to methylate properly and may also interfere with fat metabolism in the liver. However, adding methyl donors (such as methylfolate, active B6 and B12) to high-fat diets may help to reverse signs of fatty liver disease in both males and females, as these nutrients are required for lowering homocysteine levels and supporting methylation, lipid metabolism, and liver detoxification.29

The benefits of folic acid for seniors

Older adults are at higher risk of folate deficiency, often due to poor dietary intake and reduced absorption due to digestive issues and/or interactions with medications.30
This also increases the risk of many other health conditions, including megaloblastic anemia and depression.


Folate plays a critical role in cognitive function, especially in older people, and folate deficiency can increase the risk of neurodegenerative diseases such as Alzheimer’s and Parkison’s disease.31 A 2024 systematic review found that folic acid supplementation seemed to have a positive impact on cognitive function in older adults with mild cognitive impairment, but further research is pending.32
However, a ‘therapeutic cocktail’ involving supplementation with 5-methyltetrahydrofolate, methyl B12, betaine, and N-acetylcysteine (NAC) has been shown to target multiple pathways in reducing the risk of dementia.33

The benefits of folic acid for women over 50 and during menopause

Some research has suggested that folate may have actions similar to hormone replacement therapy (HRT), as it may influence neurotransmitters norepinephrine and serotonin.34 Some studies found that folic acid helped reduce hot flash frequency and duration after 3-4 weeks of supplementation.35


Low folate and high homocysteine are also common in women over 50, and has been linked to a higher risk of heart disease and depression. Folic acid may help to support normal mood and healthy cardiovascular function in older women by restoring folate levels.36 However, methylfolate is recommended over folic acid as it is the most bioavailable form of folate and immediately available for use in the body.37

The benefits of folic acid in combination with other supplements

  • B vitamins
    Vitamins B12, B6 and folic acid are cofactors in the metabolism of homocysteine, and many studies show that supplementation with combinations of these B vitamins is effective in lowering homocysteine levels.
    Deficiencies in both B12 and folate are associated with increased risk and incidence of depression. Several studies have shown that a higher intake of all B vitamins is associated with a lower prevalence of depression, anxiety, and stress symptoms.


  • Iron
    Both iron and folic acid are recommended for women who are pregnant or planning pregnancy, as both support healthy red blood cell production and development of the fetus.


  • Vitamin D3
    Vitamin D deficiency is a risk factor for Alzheimer’s disease and mild cognitive impairment, as it helps to protect against biological processes linked to dementia and cognitive decline, including amyloid deposition and inflammation in the brain.
    Recent studies have shown that vitamin D3 combined with folate supplementation is more effective on overall cognitive function than folate alone.


  • Vitamin E
    Vitamin E is a potent antioxidant, and combined supplementation of folic acid and vitamin E in pregnancy has been shown to reduce complications linked to diabetes.  This appeared to be due to vitamin E reducing abnormal proteins.


  • Zinc
    Folate is important for healthy female reproductive function, especially oocyte production and maturation, as well as fetal growth and organ development. Zinc is also involved in testicular development, sperm maturation and testosterone synthesis. Both folate and zinc have antioxidant properties that counteract reactive oxygen species (ROS), and both may help to support healthy fertility.

Folic acid dosage

When supplementing with folic acid, it is important to avoid exceeding recommended dosages, especially if:

  1. You have an MTHFR genetic mutation, and/or;
  2. You have low B12 levels, and/or;
  3. You already eat a lot of fortified foods that contain added folic acid
  4. Taking certain medications, e.g., anticonvulsants and methotrexate


Increased folic acid intake from fortified foods and supplements has raised safety concerns, especially in older adults with low vitamin B12 levels.45 

Folic acid can ‘mask’ low B12, and high folic acid intake and low B12 is linked to anemia, cognitive impairment, and elevated methylmalonic acid (MMA) and homocysteine.46

High folic acid intake has been linked to:

  • Insulin resistance and/or increased risk of retinoblastoma in children (if taken during pregnancy)47
  • Increased risk of gestational diabetes48
  • Reduced natural killer cell activity in elderly women49
  • Unmetabolized folic acid syndrome (UMFA)
  • Increased risk of colon cancer50 and prostate cancer51

Methylfolate vs folic acid

Methylfolate is the most active and bioavailable form of folic acid. Unlike folic acid, methylfolate doesn’t need to go through a conversion process. It can be absorbed and utilized by the body upon ingestion.


Methylfolate does not mask vitamin B12 deficiency and is less likely to interact with certain drugs. Most importantly, methylfolate is able to bypass the MTHFR mutation that prevents proper breakdown of folic acid in the body.52

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Katie Stone - Naturopath

About the Author

Katie is a qualified Naturopath (BNatMed) and freelance writer from New Zealand. She specializes in all things health and wellness, particularly dietary supplements and nutrition. Katie is also a dedicated runner and has completed more half-marathons than she can count!

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