Dr. Nuria Roda / Alberto Tejero
Concern for health and nutrition is a current topic of interest. The optimization of vitamin intake is sought, especially in vulnerable population groups. In this context, Vitamin B9 is in the spotlight due to its importance in health and in processes as critical as emotional well-being, the synthesis of DNA and red blood cells, or defects in the closure of the spinal cord during embryonic development.
Concern for health and nutrition is a current topic of interest. The optimization of vitamin intake is sought, especially in population groups with increased needs, such as pregnant women, the elderly, or those with certain variations in their diet (vegans and vegetarians). In this context, vitamin B9 (known as folate in its natural form and folic acid in its synthetic form) is in the spotlight, not only for its essential role in DNA production and the prevention of neural tube defects, but also due to the growing interest in cognitive health and emotional well-being.
An important factor when choosing this vitamin is looking for its active form. The problem arises because not all forms of vitamin B9 are absorbed or utilized in the same way by the body. Synthetic folic acid, although widely used in supplements and fortified foods, requires a series of complex metabolic steps (mediated by enzymes such as MTHFR) to be converted into its biologically active form, 5-methyltetrahydrofolate (5-MTHF). A significant portion of the population may have a reduced capacity to perform this conversion efficiently. This is where innovation comes into play, as compounds such as Quatrefolic® (a glucosamine salt of 5-MTHF) represent the active and pre-metabolized form of folate. This version offers higher bioavailability by completely bypassing the conversion process, ensuring that the body can use B9 immediately and effectively. Below are the health benefits it provides:
1. Prevention of Neural Tube Defects
This is the most well-known benefit and is especially important during pregnancy. Adequate consumption of folic acid before and during the first weeks of gestation significantly reduces the risk of serious birth defects in the fetus’s brain and spine, such as spina bifida and anencephaly—two defects caused by the improper closure of the neural tube. This embryonic structure eventually becomes the baby’s brain and spinal cord, and its closure occurs very early, generally between days 21 and 28 after conception, which is often before a woman knows she is pregnant.1
2. Blood Cell Formation and Anemia Prevention
Vitamin B9 deficiency leads to a type of anemia known as megaloblastic anemia. This is caused by a failure in the maturation of red blood cells because, when there is a folate shortage, DNA synthesis slows down. Red blood cell precursor cells in the bone marrow cannot divide normally and complete their maturation. Consequently, these immature cells (megaloblasts) grow abnormally and become overly large, making them fragile and ineffective at transporting oxygen. Thus, they are prematurely destroyed by the spleen, resulting in an even lower number of functional red blood cells in circulation, which causes the symptoms of anemia (fatigue, weakness, and paleness). It is important to highlight that folate works closely with vitamin B12 (cobalamin) in DNA synthesis. B12 deficiency also causes megaloblastic anemia.2
3. Cardiovascular Health and Homocysteine Regulation
B9, together with vitamins B6 and B12, plays a vital role in homocysteine metabolism. High levels of homocysteine in the blood are considered a risk factor for the development of heart and blood vessel diseases, although less significant compared to high cholesterol or hypertension. High homocysteine can damage the arterial endothelium, which promotes the hardening of the arteries (atherosclerosis) and the formation of blood clots. Folate, in its active form (5-MTHF), acts as a crucial methyl group donor. This process allows homocysteine to be converted back into methionine (non-toxic) or degraded into other compounds. By facilitating this conversion, adequate intake of folic acid (and B12) significantly reduces homocysteine levels in the blood.3
A vitamin B12 deficiency can cause a misdiagnosis of B9 deficiency. 5-MTHF cannot be utilized because the enzyme methionine synthase, which requires B12, stops or works very inefficiently. As a result, folate becomes “trapped” because it cannot donate its methyl group to complete the homocysteine conversion reaction. In this way, it can be determined whether a person suffers from a B12 deficiency if the pathology persists once active folate is administered.4
4. Cognitive Function
Vitamin B9 is essential for the proper functioning of the central nervous system and has implications for mental health and brain function throughout life. It is associated with better cognitive performance and memory in older adults. Folate’s influence on cognitive function is due to its role in the synthesis of neurotransmitters and brain antioxidants (glutathione). As previously mentioned, folate is key in the metabolic pathway of homocysteine, which is closely linked to the methionine cycle. This cycle is essential for the production of the universal methyl donor, S-adenosylmethionine (SAMe). This compound is crucial for the methylation of DNA, RNA, proteins, and, most importantly, for the synthesis of neurotransmitters such as serotonin, dopamine, and norepinephrine, which regulate mood and memory. Furthermore, hyperhomocysteinemia is associated with a higher risk of cerebral vascular damage, which can lead to blood flow issues and, consequently, impaired cognitive function (known as vascular dementia).5
Several studies have found an association between low folate levels and an increased risk of cognitive decline, dementia, and Alzheimer’s disease in old age. It has also been observed that patients with depression often have lower folate levels in blood serum, which is linked to a deficiency in the production of SAMe-dependent neurotransmitters.6
In conclusion, vitamin B9 or folate is an essential micronutrient, especially for women of childbearing age, pregnant women, and the elderly, due to its functions in neurotransmitter synthesis, red blood cell production, and the prevention of neural tube closure defects. Its strong relationship with vitamin B12 is crucial, as a B12 deficiency can mask the cause of anemia and affects the elimination pathway of homocysteine, which is toxic to the body.
Bibliographic References
- Mironenko, A., & Eliseeva, T. (2019). Vitamin B9–description, benefits, effects on the body and best sources. Journal of Healthy Nutrition and Dietetics, 4(10), 88-100.
- Tobar, K., & Tite, S. (2023). Effects of vitamin B9 and B12 deficiency on the genesis of megaloblastic anemia. Medisur, 21(6), 1331-1337.
- Bajic, Z., Sobot, T., Skrbic, R., Stojiljkovic, M. P., Ponorac, N., Matavulj, A., & Djuric, D. M. (2022). Homocysteine, vitamins B6 and folic acid in experimental models of myocardial infarction and heart failure—how strong is that link?. Biomolecules, 12(4), 536.
- Bailey LB, Gregory JF, 3rd. Folate metabolism and requirements. J Nutr. 1999;129(4):779-782
- Smith, A. D., & Refsum, H. (2016). Homocysteine, B Vitamins, and Cognitive Impairment. Annual review of nutrition, 36, 211–239. https://doi.org/10.1146/annurev-nutr-071715-050947
- Khalilullah, K., Saragih, J., Al-Gunaid, S. T., Gurky, N. K., & Al-Gunaid, L. T. (2025). Effect of folic acid on cognitive function in older adults: A systematic review and meta-analysis. Narra Review, 1(1).