Folic Acid is the synthetic form of Vitamin B9 or Folate. Folate is essential for the Central Nervous system (CNS), red blood cell formation, division and cell growth. It also helps in repairing the hereditary material or the DNA. Doctors recommend folic acid to pregnant women to prevent prenatal neural tube defects (NTDs) related to the brain and spine, particularly anencephaly and spina bifida.
The primary task of red blood cells is to carry oxygen in the body. A low number of red blood cells can lead to folate deficiency anaemia with symptoms such as paleness and fatigue. Dementia, seizures, heart palpitations, depression, shortness of breath, mouth sores and developmental delays are other related health issues (1).
Folic acid is not broken by heat or UV rays and remains stable under these conditions. So, it is added to many fortified grains, vitamin capsules/tonics, and dietary supplements due to the extensive benefits it provides. It is also widely used to treat symptoms of Rheumatoid Arthritis.
Despite possessing several health benefits, there have been concerns and studies on the adverse effects of excessive folic acid in the body.
Ideal Recommendation of Folic Acid
The ideal amount of folic acid varies with age. An important point to note here is the difference between folate and folic acid requirements in the body. The body absorbs folic acid more readily than dietary folate, so it needs less folic acid than folate to meet the recommended dosage.
Babies up to the age of six months require around 39 mcg of folic acid, while teens and adults need around 240 mcg of folic acid daily (2).
Women in their reproductive age should consume around 400 mcg of folic acid every day, as per CDC (3). This requirement can shoot up to 4,000 mcg if there is a family history of neural tube defects.
Foods Rich in Folate
Following foods are rich in natural folate and are the sources of your dietary folate;
- Nuts and Peanuts
- Green Leafy Vegetables- Spinach, Mustard Greens, Brussels Sprouts, and Asparagus
- Fruits and Juices (Orange, Tomato)
- Pulses such as black-eyed peas, kidney beans
- Synthetic folate or Folic acid might be present in the following foods;
- Flours- Wheat and Corn
- Rice
- Bread and Pasta
- Fortified breakfast cereals
- Fortified corn masa doughs- used for making tamales, tortillas, etc
- Edible Oils
You can check the nutrient labels for the composition of these food products to ascertain the amount of folic acid you are consuming and take additional supplements accordingly to prevent an excess of folic acid.
The mandatory crop fortification in the US and a few other parts of the world is being questioned. It might lead to more than the required amount of folates in the body as people generally aren’t aware of the amount of dietary folate they consume. The Scientific Advisory Committee on Nutrition, London, recommended reducing the consumption of folic acid supplements with fortified food items.
Potential Side Effects of Excessive Folic Acid
1. Interact with Other Medications
Folic acid can interact with certain medications and cause extremely harmful effects;
- Using sulfasalazine (Azulfidine®) for treating ulcerative colitis can reduce the body’s ability to absorb folic acid. Thus, consuming excessive Folic acid supplements can lead to Unmetabolized folic acid (UMFA), which accounts for many health issues.
- Methotrexate (Rheumatrex®, Trexall®) prescribed to treat cancer, and other auto-immune diseases can make the drug less effective when combined with folic acid supplements. As a result, the patients might need to be administered higher doses.
- Anti-seizure medications such as phenytoin (Dilantin®), phenobarbital, valproate (Depacon®), and carbamazepine (Carbatrol®, Tegretol®, Equetro®, Epitol®) have contradictory effects as their consumption can reduce folate levels in the body and folic acid consumption can lessen their expected benefits.
2. Causes Vitamin B12 Deficiency and Slow Metabolism
Folate is in a polyglutamate form which is hydrolysed to form monoglutamates in the mucosa of the intestines and transported around the body. Whereas folic acid is absorbed with a two-step process by reducing to dihydrofolate reductase (DHFR) and then to tetrahydrofolate (THF) in the liver. Thus absorbing excess folic acid lowers the metabolism.
Vitamin B9 or Folate helps in Vitamin B12 absorption. The excessive unmetabolised folic acid in the body and the accumulation of cellular folate masks vitamin B12 deficiency. The body shows similar symptoms with either of these vitamin deficiencies. The delayed treatment for low vitamin B12 levels can lead to irreversible neurological damage and megaloblastic anaemia.
If there are symptoms of weakness and breathing issues while consuming folic acid, patients can have a probable case of Vitamin B12 deficiency.
Also, high levels of folic acid can be hepatotoxic for people with low levels of the methylene-tetrahydrofolate reductase protein.
3. Accelerate Age-related Mental Decline
Certain studies have indicated high folate levels and low B12 levels, above 60 years of age experience increased mental decline (4). It is because it severely affects cognitive abilities in the elderly population. In some other studies, the imbalance of these vitamins leads to a complete loss of brain function.
4. Affecting Carcinogenesis
Carcinogenesis is the process by which normal cells convert themselves to Cancer cells. A few studies in Europe have linked consumption of folic acid to causing colorectal cancer (5).
Some other studies have seen cancer progression with folic acid administration. Consuming folic acid in the presence of pre-neoplastic cells leads to excessive cell proliferation and growth. A higher rate of nucleotide synthesis leads to more DNA replication. Also, cancer cells cause folate receptors to absorb more folate in the cells, multiplying them further.
Folates are also linked to reducing natural killer cell cytotoxicity. It is a natural body mechanism to fight any infected cells in the body- viral or cancer cells. A study indicated up to 23% reduced cytotoxicity in post-menopausal women with detectable folic acid levels (6). It naturally leads to a weakened immune response against cancer.
5. Health Effects in Children
A few studies have also indicated high folate levels in the mother’s body during pregnancy pose an increased risk of extreme obesity or adiposity and insulin resistance in the children (7). The decreased adiponectin concentrations have also led to type 2 diabetes mellitus in certain cases.
Another striking observation on women with DHFR19del gene taking folic acid supplements indicated low memory and cognitive scores of the offspring. Also, because folic acid masks the deficiency of vitamin B12, a high folic acid to vitamin B12 ratio increases the risk of the baby being smaller than the gestation age at birth- a condition called small for gestational age (SGA). It can lead to coronary heart disease, hypertension, and type 2 diabetes mellitus.
These results come as a surprise as folic acid is recommended to pregnant women since the pre-pregnancy phase to decrease the possibilities of neural tube defects.
Before We Go
The hypertoxicity of folic acid should be given its due diligence, particularly because folic acid supplements are not very expensive, and there is no medical prescription required to buy. Also, consumption and requirement can vary with genetic, dietary, and cultural factors, and benefits to a particular group of people can cause dis-benefits to others.
Moderate consumption of folates and its supplements under the prescribed levels is fine, but more research and observations are still required to prove these potential side effects.