7 Signs & Symptoms of Folate (Vitamin B9) Deficiency & Treatment – Research Studies

What is Folate (B9)?

Vitamin B9, commonly known as folate, is a water-soluble vitamin that is approved by the Food and Drug Administration (FDA) for the treatment of anemias associated with the deficiency of folate. This vitamin plays an integral role in the production of deoxyribonucleic acid (DNA). The synthetic form of folate is known as folic acid. In the human body, folate is converted into tetrahydrofolic acid, which is subjected to various methylation reactions for the production of nitrogenous basis that form the constituents of ribonucleic acid (RNA) and DNA, which in turn is important for red blood cells (RBCs) maturation. The deficiency of folic acid manifests as macrocytic megaloblastic anemia. While there are reserve pools of vitamin B9 in the kidney and liver, deficiency of vitamin B9 can be caused by increased demand during pregnancy, chronic alcoholism, or hemolytic anemia. [1]

Why Folate is Important?

The key indications of folate include central nervous system (CNS) development, particularly during pregnancy. Folic acid supplements are recommended for women who are planning to conceive in order to reduce the development of neural tube defects in the fetus. The role of folate in reducing the risk of neural tube defects is to reduce the levels of homocysteine. This vitamin is also important for reducing the risk of preterm delivery of the fetus. The clinical significance of folate includes the role of this vitamin in restoring hematopoiesis in cases of macrocytic anemia, preventing the occurrence of cervical dysplasia, protecting against neoplastic changes in ulcerative colitis, and reducing inflammation. [1]

The signs and symptoms of vitamin B9 deficiency are described as follows. 

1. Depression

Depression is common in individuals suffering from folate deficiency. Various studies have demonstrated the correlation between the high incidence of deficiency of folate and the development of mental symptoms. These may include cognitive decline and depression in neurological, psychiatric, and epileptic patients. Depression associated with severe folate deficiency can be reversed with vitamin supplementation. [2]

2. Dementia 

Folic acid is integral to the development of CNS at different stages of life. In older patients, folic acid deficiency plays an essential role in aging brain processes, which increases the risk of the development of vascular dementia and Alzheimer’s disease. Critically severe folic acid deficiency can also lead to the development of reversible dementia. Studies have also demonstrated that the severity of dementia as measured by mental assessment score has a significant association with concentrations of folate in the body. [2] 

3. Infertility 

One of the most frequent factors contributing to male infertility is an injury to the sperm’s DNA. The deficiency of folic acid is associated with an increase in the level of methylation of genes involved in the repair pathway of DNA double-strand break (DSB). Supplementation with folic acid is related to relatively lower levels of methylation. Clinical supplementation of folic acid is helpful for male patients to reduce damage to the DNA of the sperm. [3]

4. Increased Cancer Risk

Lower levels of folate in the body are associated with an elevated risk of the development of different forms of cancers. Folic deficiency impairs the pathways of repair and synthesis of DNA. However, excessive intake of folic acid is also a clinical concern. Higher serum levels of folic acid increase the risk of the development of prostate cancer. [4]

5. Increased Cardiovascular Disease Risk 

Lower levels of folic acid in the body are associated with an increased risk for the development of cardiovascular diseases. This can be explained by higher homocysteine levels, which contribute to increased thrombogenicity, damage to the endothelium, and oxidative stress. Supplementation with folic acid significantly decreases the risk of the development of stroke in patients suffering from cardiovascular disorders. [5]

6. Canker Sores 

Recurrent aphthous stomatitis or canker sores are among the most frequent oral mucosal disease present in humans. Canker sores are associated with nutritional deficiencies, one of which includes the deficiency of folic acid. It shall also be noted that individuals suffering from canker sores are prone to reduced dietary intake of folic acid compared to healthy individuals. Supplementation with vitamin B9 is useful for the prevention of recurrent episodes of canker sores. [6]

7. Peripheral Neuropathy 

A deficiency of vitamin B9 is also implicated in an increased risk for the development of peripheral neuropathy, particularly in patients less than 40 years of age. The characteristic features of peripheral neuropathy include numbness in extremities, pain, and paresthesia. The neurological symptoms of folate deficiency tend to improve following supplementation with the vitamin. Physicians may also consider the combined administration of vitamin B9 and vitamin B12 or B6 so as to achieve better treatment outcomes in patients. [7]

Folate (B9) Deficiency Treatment 

According to the World Health Organization (WHO), the recommended daily intake of folic acid is 400-800 mcg for the prevention of neural tube defects in a fetus. The administration of folic acid can occur via oral, subcutaneous, or intravenous routes. The potential contraindication to the administration of folic acid is the development of hypersensitivity to the vitamin or its pharmaceutical formulation. [1]

Take advantage of free consultation with one of our Health Coach through the chat icon on the website to determine of vitamin B9 deficiency along with the identification of appropriate dosages. ASTR program recommends taking all types of vitamins together because they depend on each other for absorption. Too much of one vitamin may cause a deficiency of another, which is why it is recommended that all vitamin Bs are taken together in a single capsule.


  1. Merrell BJ, McMurry JP. Folic Acid. [Updated 2022 Dec 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554487/
  2. Reynolds E. H. (2002). Folic acid, ageing, depression, and dementia. BMJ (Clinical research ed.)324(7352), 1512–1515. https://doi.org/10.1136/bmj.324.7352.1512
  3. Wang, W., Peng, M., Yuan, H., Liu, C., Zhang, Y., Fang, Y., Su, Y., Zhang, X., Zhang, H., Tang, Y., & Zhao, K. (2022). Studying the mechanism of sperm DNA damage caused by folate deficiency. Journal of cellular and molecular medicine26(3), 776–788. https://doi.org/10.1111/jcmm.17119
  4. Pieroth, R., Paver, S., Day, S., & Lammersfeld, C. (2018). Folate and Its Impact on Cancer Risk. Current nutrition reports7(3), 70–84. https://doi.org/10.1007/s13668-018-0237-y
  5. Wang, Y., Jin, Y., Wang, Y., Li, L., Liao, Y., Zhang, Y., & Yu, D. (2019). The effect of folic acid in patients with cardiovascular disease: A systematic review and meta-analysis. Medicine98(37), e17095. https://doi.org/10.1097/MD.0000000000017095
  6. Kozlak, S. T., Walsh, S. J., & Lalla, R. V. (2010). Reduced dietary intake of vitamin B12 and folate in patients with recurrent aphthous stomatitis. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology39(5), 420–423. https://doi.org/10.1111/j.1600-0714.2009.00867.x
  7. Taverner, T., Crowe, F. L., Thomas, G. N., Gokhale, K., Thayakaran, R., Nirantharakumar, K., & Rajabally, Y. A. (2019). Circulating Folate Concentrations and Risk of Peripheral Neuropathy and Mortality: A Retrospective Cohort Study in the U.K. Nutrients11(10), 2443. https://doi.org/10.3390/nu11102443