Why folic acid ain’t no good (but folate rocks)

A set of pantry items, not super exciting, one jar says folic acid, the other says lemons.

Folic acid is the synthetic form of folate, and is used in fortified foods and some supplements. But, it’s no good for a body and has no natural place, biologically speaking.

But we do need folate (B9) – it’s a pretty important nutrient. Here’s where you learn the difference between the different forms of folate, and how to navigate a life without folic acid.

  • Folic acid is a manmade, synthetic vitamin that does not exist in nature
  • Folate is found in folate-rich foods
  • Activated folate is found in supplements and your cells

We can uptake up to 200mcg of folic acid in our gut receptors per day, but often we are taking in more than this in ‘fortified’ foods like bread, flour, cereals and so on.

Check your labels – if it says folic acid or even just folate, without specifying the type, avoid it. It’s all folic acid.

How did we end up with folic acid?

In the North America, Costa Rica, Chile, South Africa, Australia, and other countries, fortifying cereals and grains (flour, bread, breakfast cereals, drinks) with folic acid was a mandated intervention​1,2​ like fluoride in water and iodine in salt to try to stop neural tube defects in babies, caused by low folate in the mother.

Which it largely did – but it can also have some very serious implications for those with genetic variations/mutations like MTHFR (nearly half the population) and anyone with a folic-acid-heavy diet.

There is also mounting evidence that the excess unabsorbed folic acid simply roams around the bloodstream, causing trouble.

One of the things you’ll find once you start looking is that even many researchers have absolutely no idea what form of folate they are talking about, and the terms folic acid and folate are used interchangeably.

Why folic acid is used in processed foods – and not folate

Folic acid is synthetic because other forms of folate are not stable and can’t be used in processed foods. Some natural foods contain folate that is useful for us, like leafy greens, but if folic acid is blocking the receptor, it can’t be absorbed no matter how much spinach you eat.

Folic acid needs to be converted to its active form – requiring B12 – so it can be used by the body. Folic acid can leave you more deficient in folate than ever.  

Folic acid, MTHFR and activated folate

Many older generation prenatal supplements contain folic acid, which can be a problem if this folic acid is over 200mcg or if you’re eating folic acid-fortified foods as well. But, if you’re trying to conceive or are currently pregnant, you need folate for DNA replication for conception as well as growing a baby. It’s essential.

If you have MTHFR genetic mutations, your body isn’t very efficient at converting folic acid to activated forms of folate. Better forms of folate come in ‘activated’ or ‘methylated’ supplements, but these can be tricky – not everyone is ready for activated B vitamins and they might make you feel unwell.

It’s useful to try a good prenatal supplement with active forms of folate, but if they make you feel bad, it means you’ve got bigger issues that you may need some specialised practitioner support with.

Seek out an experienced practitioner who can work with you to support your other pathways before you’ll be able to tolerate activated forms of folate. 

Types of folate​3​

  • L-Methylfolate (methylated folate, like L-5-MTHF, also known as methylfolate)
  • L-5-Methyltetrahydrofolate (L-5-MTHF) (does not require DHFR conversion to active folate, best form of L-methylfolate found in supplements, well absorbed and used by the body, also known as 5-Methyltetrahydrofolate (5-MTHF))
  • Tetrahydrofolate and Dihydrofolate (natural folates found in fresh foods, used for DNA and RNA synthesis, easily converted into the active form of L-methylfolate, but must be converted prior to absorption in the intestine)
  • Folinic acid (does not require DHFR conversion to active folate, natural, reduced form of folate, an alternative to L-methylfolate in cases of sensitivity to methylated supplements, don’t confuse with folic acid!)
  • Folic acid (oxidised folate, synthetic and not identical to any folate used by the body, used in fortified foods and some dietary supplements, no biological activity unless converted to folate)

What happens to folic acid in your body

Folic acid requires conversion to other forms of folate before it can be used by the body. The most basic conversion is to tetrahydrofolate (THF), via the dihydrofolate reductase (DHFR) enzyme.

Further enzymatic steps include the conversion to 5-methyltetrahydrofolate (5-MTHF), the most common form of folate in the blood, using the MTHFR enzyme.

5-MTHF is biologically active (‘active folate’), used for methylation – an important process vital for cognition, sleep, breastfeeding, pregnancy, fertility, foetal development, mood, and much more​4​.

To convert folic acid into proper folate requires over seven enzymes (run by genes), specific nutrient co-factors, and the absence of excessive loads of heavy metals, reactive oxygen species, toxins, bacterial infections, etc.

If you have genetic mutations in DHFR, SLC, MTHFD1 or MTHFR genes, your enzymes can be a little slower than is optimal, making it difficult for your body to convert as much folic acid into folate as it needs.

When folic acid isn’t converted into folate, it roams around the bloodstream where it doesn’t belong and doesn’t fit, potentially causing problems​3​.

Measuring folate in a blood test

Serum folate blood tests look for the whole folate pool in the body, including unmetabolised folic acid, folinic acid, 5-MTHF, dihydrofolate and tetrahydrofolate.

This is only so useful, particularly if there is a low level of all forms of folate. But, if you’re eating lots of fortified foods and taking supplements containing folic acid, this can elevate your numbers, making your folate levels look good, when it’s a little red herring.

Remember, folic acid has no biological use and has no home in our bodies until it is converted to another form of folate using DHFR enzymes. Structurally, it is different to the other forms of folate, and as a result, taking folic acid may not replenish folate levels​5​.

In fact, even without a folate-related genetic mutation, the presence of folic acid can still slow down the folate pathway by blocking gut folate receptors and impeding folate transport​3,6–8​.

When My Vagina practitioners request folate blood tests, they’re most likely to request RBC folate, or red cell folate. The difference in folate tests is that serum folate levels measure folic acid intake in the short-term, while RBC folate increases only with higher additional doses of folic acid supplementation, even in those with MTHFR genetic mutations​9​.

Folic acid easily binds to folate receptors, which is a problem, as it then blocks the passageway of better forms of folate from food. Unfortunately, the ready binding of folic acid versus its use to us is not equivalent​3,7,8​.

When the folic acid blocks the receptors, leaving you normal or even high on a serum folate test, but in reality, deficient in folate, this is known as a functional folate deficiency​3,10,11​.

Issues with folic acid consumption

  • Falsely elevated serum folate blood test results
  • Functional folate deficiency
  • Blocked folate receptors
  • Cognitive and immune related issues
  • Slows MTHFR enzyme function
  • Slowed DHFR enzyme function, causing bioterpin deficiency
  • May hide a B12 deficiency by skipping a step in nucleic acid production and allowing cell division to occur without enough methyl groups​3,12,13​
  • Anaemia and cognitive impairment with high folic acid and B12 deficiency​14​

Choosing good forms of folate

Avoid all forms of folic acid where possible, and choose bioavailable forms of folate such as L-methylfolate and folinic acid, and work on ensuring plenty of folate from fresh foods.

If you’re not sure, before you supplement, please see a folate-wise healthcare practitioner for advice. Using L-5-MTHF is an excellent form of folate, and can reverse folate deficiency better than folic acid.

A B complex vitamin supplement is a useful way to get all your B vitamins, and active folate, but check the label and avoid any supplements that say ‘folic acid’ or simply ‘folate’ on the label.

Good forms of folate in supplements include:

  • L-5-MTHF
  • L-Methylfolate
  • Dihydrofolate
  • Tetrahydrofolate
  • Folinic acid (calcium folinate)
  • L-Methylfolate (L-5-Methyltetrahydrofolate
  • 6(S)-L-Methyltetrahydrofolate)

If you don’t respond well to B complex vitamin supplements, talk to a healthcare provider, as you may need to start to build up your pathway supports in another way, or choose folinic-based B complexes and see if that helps.

You also don’t need to take supplements every day – if you feel like you need it, take it, but if you feel good, you don’t need it so don’t take it.


How to get plenty of good forms of folate from food

Stop eating or taking anything with folic acid in it, and instead eat get your folate from food high in folate – the real deal. 

  • Dark green leafy vegetables (turnip greens, spinach, romaine lettuce, asparagus, Brussels sprouts, broccoli)
  • Beans
  • Peanuts
  • Sunflower seeds
  • Fresh fruits, fruit juices
  • Whole grains
  • Liver
  • Seafood
  • Eggs
Foodmcg folate per serve
Beef liver, braised, 3 oz/85 g215
Spinach, boiled, ½ cup131
Black-eyed peas (cowpeas), boiled, ½ cup105
Asparagus, boiled, 4 spears89
Brussels sprouts, frozen, boiled, ½ cup78
Lettuce, romaine, shredded, 1 cup64
Avocado, raw, sliced, ½ cup59
Spinach, raw, 1 cup58
Broccoli, chopped, frozen, cooked, ½ cup52
Mustard greens, chopped, frozen, boiled, ½ cup52
Green peas, frozen, boiled, ½ cup47
Kidney beans, canned, ½ cup46
Wheat germ, 2 tablespoons40
Crab, Dungeness, 3 oz/85 g36
Tomato juice, canned, ¾ cup36
Orange juice, ¾ cup35
Turnip greens, frozen, boiled, ½ cup32
Orange, fresh, 1 small29
Papaya, raw, cubed, ½ cup27
Peanuts, dry roasted, 1 oz/28g27
Banana, 1 medium24
Yeast, baker’s, ¼ teaspoon23
Egg, whole, hard boiled, 1 large22
Yeast Extract Spread20.46
Cantaloupe, raw, cubed, ½ cup17
Vegetarian baked beans, canned, ½ cup15
Fish, halibut, cooked, 3 oz/85 g12
Milk, 1% fat, 1 cup12
Raw Spinach8.43
Endive8.35
Cos or Romaine Lettuce8
Chrysanthemum Leaves7.38
Mustard Spinach (Tendergreen)7.23
Ground beef, 85% lean, cooked, 3 oz/85 g7
Asparagus6.77
Epazote6.72
Turnip Greens6.06
Butterhead Lettuce5.62
Goose Liver5.55
Duck Liver5.43
Turkey Liver5.29
Arrowroot5.2
Escarole5.2
Chinese Cabbage (Pak-Choi)5.08
Malabar Spinach4.96
Chinese Cabbage (Pe-Tsai)4.94
Chicken Liver4.94
Okra4.93
Chayote Fruit4.89
Chicory Greens4.78
Chinese Broccoli4.5
Wakame Seaweed4.36
Balsam-Pear Leafy Tips (Bitter Gourd)4.27
Balsam-Pear Pods (Bitter Gourd)4.24
Parsley4.22
Kelp Seaweed4.19
Laver Seaweed4.17
Collards4.03
Cardoon4
Pumpkin Flowers3.93
Arugula3.88
Sesbania Flower3.78
Broccoli Raab3.77
Irishmoss Seaweed3.71
Amaranth Leaves3.7
Jute3.62
Napa Cabbage3.58
Chives3.5
Cowpea Leafy Tips3.48
Kimchi Cabbage3.47
Artichokes3.32
Agar Seaweed3.27
Capon Chicken3.03
Chicken breast, roasted, 3 oz/85 g3
Taro Leaves3
Water Convolvulus3
Savoy Cabbage2.96
Edamame2.78
Red Leaf Lettuce2.77

References

  1. 1.
    Crider KS, Bailey LB, Berry RJ. Folic Acid Food Fortification—Its History, Effect, Concerns, and Future Directions. Nutrients. Published online March 15, 2011:370-384. doi:10.3390/nu3030370
  2. 2.
    Centers for Disease Control and Prevention (CDC). CDC Grand Rounds: additional opportunities to prevent neural tube defects with folic acid fortification. MMWR Morb Mortal Wkly Rep. 2010;59(31):980-984. https://www.ncbi.nlm.nih.gov/pubmed/20703205
  3. 3.
    Smith AD, Kim YI, Refsum H. Is folic acid good for everyone? The American Journal of Clinical Nutrition. Published online March 2008:517-533. doi:10.1093/ajcn/87.3.517
  4. 4.
    Costello JF. Methylation matters. Journal of Medical Genetics. Published online May 1, 2001:285-303. doi:10.1136/jmg.38.5.285
  5. 5.
    Bailey SW, Ayling JE. The extremely slow and variable activity of dihydrofolate reductase in human liver and its implications for high folic acid intake. Proc Natl Acad Sci USA. Published online September 8, 2009:15424-15429. doi:10.1073/pnas.0902072106
  6. 6.
    Chita DS, Tudor A, Christodorescu R, et al. MTHFR Gene Polymorphisms Prevalence and Cardiovascular Risk Factors Involved in Cardioembolic Stroke Type and Severity. Brain Sciences. Published online July 24, 2020:476. doi:10.3390/brainsci10080476
  7. 7.
    Ashokkumar B, Mohammed ZM, Vaziri ND, Said HM. Effect of folate oversupplementation on folate uptake by human intestinal and renal epithelial cells. The American Journal of Clinical Nutrition. Published online July 2007:159-166. doi:10.1093/ajcn/86.1.159
  8. 8.
    Qiu A, Jansen M, Sakaris A, et al. Identification of an Intestinal Folate Transporter and the Molecular Basis for Hereditary Folate Malabsorption. Cell. Published online December 2006:917-928. doi:10.1016/j.cell.2006.09.041
  9. 9.
    Anderson CAM, Beresford SAA, McLerran D, et al. Response of serum and red blood cell folate concentrations to folic acid supplementation depends on methylenetetrahydrofolate reductase <scp>C</scp>677<scp>T</scp> genotype: Results from a crossover trial. Molecular Nutrition Food Res. Published online March 4, 2013:637-644. doi:10.1002/mnfr.201200108
  10. 10.
    Kalmbach RD, Choumenkovitch SF, Troen AP, Jacques PF, D’Agostino R, Selhub J. A 19-Base Pair Deletion Polymorphism in Dihydrofolate Reductase Is Associated with Increased Unmetabolized Folic Acid in Plasma and Decreased Red Blood Cell Folate. The Journal of Nutrition. Published online December 2008:2323-2327. doi:10.3945/jn.108.096404
  11. 11.
    Cosar A, Ipcioglu OM. Detection of functional vitamin B12 and folate deficiencies, while serum levels are normal. Blood Transfusion. Published online 2014. doi:10.2450/2013.0040-13
  12. 12.
    Reynolds E. Vitamin B12, folic acid, and the nervous system. The Lancet Neurology. Published online November 2006:949-960. doi:10.1016/s1474-4422(06)70598-1
  13. 13.
    Smith AD. Folic acid fortification: the good, the bad, and the puzzle of vitamin B-12. The American Journal of Clinical Nutrition. Published online January 2007:3-5. doi:10.1093/ajcn/85.1.3
  14. 14.
    Morris MS, Jacques PF, Rosenberg IH, Selhub J. Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification. The American Journal of Clinical Nutrition. Published online January 2007:193-200. doi:10.1093/ajcn/85.1.193


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Jessica Lloyd - Vulvovaginal Specialist Naturopathic Practitioner, BHSc(N)

Jessica is a degree-qualified naturopath (BHSc) specialising in vulvovaginal health and disease, based in Melbourne, Australia.

Jessica is the owner and lead naturopath of My Vagina, and is a member of the:

  • International Society for the Study of Vulvovaginal Disease (ISSVD)
  • International Society for the Study of Women's Sexual Health (ISSWSH)
  • National Vulvodynia Association (NVA) Australia
  • New Zealand Vulvovaginal Society (ANZVS)
  • Australian Traditional Medicine Society (ATMS)
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