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Folate

Folate (Folic Acid)

Folate is one of the B vitamins. Also known as vitamin B9, folate is essential for the production of red and white blood cells, and the conversion of food into useable energy. Folate also plays an integral role in producing DNA and RNA. Adequate amounts of folate are necessary especially during pregnancy. Folate is found in most foods such as broccoli, brussels sprouts, cabbage, kale, spinach, and breakfast cereals. When taken as supplements, it is available as folic acid which is the manmade version of folate.

Overall Health Benefits

  • Maintains Healthy Pregnancy [1-7]
  • Prevents Cardiovascular Disease [8-13]
  • Lowers Risk of Stroke [14-18]
  • Treats Depression and Improves Mood [19-22]
  • Prevents Vision Loss [23-24]
  • Prevents Cognitive Decline [25-29]
  • Treats Anemia [30-40]

Proven Health Benefits

Maintains Healthy Pregnancy

A convincing number of studies suggest that folate and folic acid are essential for a healthy pregnancy:

  1. Studies showed that early supplementation of folate on reproductive-aged women is essential to prevent complications for both the mother and the fetus during pregnancy.[1]
  2. Clinical studies showed that folate supplementation during pregnancy was effective in preventing birth defects. [2-4]
  3. In infertile Swedish women, folate supplementation resulted in higher pregnancy rate. [5]
  4. Studies showed that folate supplementation in infertile women increased the chance of being pregnant. [6]
  5. Studies showed that folate supplementation was associated with a reduced risk of infertility and pregnancy loss. [7]

Prevents Cardiovascular Disease

The cardioprotective effects of folate and folic acid are also backed by a number of studies:

  1. A study showed that folate supplementation dramatically decreased the risk of death in patients with cardiovascular disease (CVD). [8]
  2. A study also showed that folate supplementation was associated with a decreased risk of CVD. [9]
  3. Folic acid was found to be effective in lowering homocysteine concentrations; high levels of homocysteine were associated with an early development of cardiovascular disease. [10-13]

Lowers Risk of Stroke

Evidence suggests that folate and folic acid can also protect against stroke:

  1. A study suggested that folate supplementation has beneficial effects on stroke prevention. [14]
  2. Clinical trials showed that folate supplementation can help lower stroke risk. [15]
  3. In patients with CVD, folic acid administration resulted in lower risk of stroke. [16]
  4. In male patients, folate supplementation lowered stroke risk. [17]
  5. Long-term supplementation with folic acid reduced the risk of stroke by 10%, which may be due to folic acid’s role in lowering homocysteine concentrations. [18]

Treats Depression and Improves Mood

A good deal of evidence shows that folate and folic acid have mood-enhancing effects:

  1. A study found that high concentrations of folate can relieve symptoms of depression. [19]
  2. In depressed patients, a combination of folate administration and standard therapy produced positive effects on symptom of depression. [20]
  3. Studies showed that folic acid deficiency were associated with a higher risk of depression. [21-22]

Prevents Vision Loss

Studies also found that folate and folic acid can help improve eye function and prevent vision problems:

  1. In a study conducted among the smoker and alcoholic patients who had poor vision, oral intake of folic acid significantly improved their vision.  [23]
  2. In animal models, regular supplementation with folate resulted in fast recovery of eye function. [24]

Prevents Cognitive Decline

Folate and folic acid have also been shown to boost cognitive function and prevent age-related cognitive decline:

  1. A study reported that folic acid can help improve brain function by reducing the levels of homocysteine. [25]
  2. A study showed that folate administration improved cognitive function in patients with mild cognitive impairment. [26]
  3. In elderly Chinese with mild cognitive impairment, oral administration of folate resulted in great improvement in brain performance. [27]
  4. In patients with mild cognitive impairment, folic acid supplementation boosted their brain function. [28]
  5. In older individuals, high folate concentrations were associated with a reduced risk of brain disease. [29]

Treats Anemia

Studies show that folate and folic acid can help protect against different types of anemia (low red blood cells):

  1. Studies showed that folate deficiency was associated with a higher risk of anemia. [30-38]
  2. When combined with iron, folate can significantly reduce the risk of pregnancy-associated anemia. [39]
  3. In older adults, folic acid supplementation reduced the prevalence of folate-deficiency anemia. [40]

References:

  1. Greenberg JA, Bell SJ, Guan Y, Yu YH. Folic Acid supplementation and pregnancy: more than just neural tube defect prevention. Rev Obstet Gynecol. 2011;4(2):52-59.
  2. Available at https://jbiomedsci.biomedcentral.com/articles/10.1186/s12929-014-0077-z.
  3. Honein M. et al. Impact of folic acid fortification of the US food supply on the occurrence of neural tube defects. JAMA; 285(23) 2981-2986.
  4. Berry R. et al. 1999. Prevention of Neural-Tube Defects with Folic Acid in China. New England Journal of Medicine; 341, 1485-1490.
  5. Murto T, Yngve A, Skoog Svanberg A, et al. Compliance to the recommended use of folic acid supplements for women in Sweden is higher among those under treatment for infertility than among fertile controls and is also related to socioeconomic status and lifestyle. Food Nutr Res. 2017;61(1):1334483. Published 2017 Jun 9. doi:10.1080/16546628.2017.1334483.
  6. Schaefer E, Nock D. The Impact of Preconceptional Multiple-Micronutrient Supplementation on Female Fertility. Clin Med Insights Womens Health. 2019;12:1179562X19843868. Published 2019 Apr 23. doi:10.1177/1179562X19843868.
  7. Gaskins AJ, Chavarro JE. Diet and fertility: a review. Am J Obstet Gynecol. 2018;218(4):379-389. doi:10.1016/j.ajog.2017.08.010.
  8. Lonn E. et al. 2006. Homocysteine lowering with folic acid and B vitamins in vascular disease. The New England Journal of Medicine; 354 (15) 1567-1577.
  9. Malinow M. et al. 1998. Reduction of Plasma Homocyst(e)ine Levels by Breakfast Cereal Fortified with Folic Acid in Patients with Coronary Heart Disease. New England Journal of Medicine; 338, 1009-1015
  10. Collaboration HLT. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. BMJ : British Medical Journal. 1998;316(7135):894-898.
  11. Wang Y, Jin Y, Wang Y, Li L, Liao Y, Zhang Y, Yu D. The effect of folic acid in patients with cardiovascular disease: A systematic review and meta-analysis. Medicine (Baltimore). 2019 Sep;98(37):e17095. doi: 10.1097/MD.0000000000017095. PMID: 31517834; PMCID: PMC6750242.
  12. Li Y, Huang T, Zheng Y, Muka T, Troup J, Hu FB. Folic Acid Supplementation and the Risk of Cardiovascular Diseases: A Meta-Analysis of Randomized Controlled Trials. J Am Heart Assoc. 2016 Aug 15;5(8):e003768. doi: 10.1161/JAHA.116.003768. PMID: 27528407; PMCID: PMC5015297.
  13. Yang HT, Lee M, Hong KS, Ovbiagele B, Saver JL. Efficacy of folic acid supplementation in cardiovascular disease prevention: an updated meta-analysis of randomized controlled trials. Eur J Intern Med. 2012 Dec;23(8):745-54. doi: 10.1016/j.ejim.2012.07.004. Epub 2012 Aug 11. PMID: 22884409.
  14. Hsu CY, Chiu SW, Hong KS, et al. Folic Acid in Stroke Prevention in Countries without Mandatory Folic Acid Food Fortification: A Meta-Analysis of Randomized Controlled Trials. J Stroke. 2018;20(1):99-109. doi:10.5853/jos.2017.01522.
  15. Tian T, Yang KQ, Cui JG, Zhou LL, Zhou XL. Folic Acid Supplementation for Stroke Prevention in Patients With Cardiovascular Disease. Am J Med Sci. 2017 Oct;354(4):379-387. doi: 10.1016/j.amjms.2017.05.020. PMID: 29078842.
  16. Available at https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.109.573410.
  17. Available at https://www.nursingcenter.com/journalarticle?Article_ID=842587&Journal_ID=515680&Issue_ID=842562.
  18. Li Y, Huang T, Zheng Y, Muka T, Troup J, Hu FB (2016). “Folic Acid Supplementation and the Risk of Cardiovascular Diseases: A Meta-Analysis of Randomized Controlled Trials”. J Am Heart Assoc. 5 (8).
  19. Available at https://core.ac.uk/download/pdf/143840127.pdf.
  20. Coppen A, Bolander-Gouaille C (January 2005). “Treatment of depression: time to consider folic acid and vitamin B12”. J. Psychopharmacol. (Oxford). 19 (1): 59–65.
  21. Gilbody S, Lewis S, Lightfoot T (January 2007). “Methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms and psychiatric disorders: a HuGE review”. Am. J. Epidemiol. 165 (1): 1–13.
  22. García-Miss Mdel R, Pérez-Mutul J, López-Canul B, et al. (May 2010). “Folate, homocysteine, interleukin-6, and tumor necrosis factor alfa levels, but not the methylenetetrahydrofolate reductase C677T polymorphism, are risk factors for schizophrenia”. J Psychiatr Res. 44 (7): 441–6.
  23. Golnik KC, Schaible ER. Folate-responsive optic neuropathy. J Neuroophthalmol. 1994 Sep;14(3):163-9. PMID: 7804421.
  24. Elisa Santandrea, Ilaria Sani, Gianpaolo Morbioli, Domenico Multari, Giorgio Marchini, Leonardo Chelazzi; Optic Nerve Degeneration and Reduced Contrast Sensitivity Due to Folic Acid Deficiency: A Behavioral and Electrophysiological Study in Rhesus Monkeys. Invest. Ophthalmol. Vis. Sci. 2018;59(15):6045-6056. doi: https://doi.org/10.1167/iovs.18-24822.
  25. Vijayakumar A, Kim EK, Kim H, Choi YJ, Huh KB, Chang N. Effects of folic acid supplementation on serum homocysteine levels, lipid profiles, and vascular parameters in post-menopausal Korean women with type 2 diabetes mellitus. Nutr Res Pract. 2017;11(4):327-333. doi:10.4162/nrp.2017.11.4.327.
  26. Enderami A, Zarghami M, Darvishi-Khezri H. The effects and potential mechanisms of folic acid on cognitive function: a comprehensive review. Neurol Sci. 2018 Oct;39(10):1667-1675. doi: 10.1007/s10072-018-3473-4. Epub 2018 Jun 23. PMID: 29936555.
  27. Ma F, Wu T, Zhao J, et al. Folic acid supplementation improves cognitive function by reducing the levels of peripheral inflammatory cytokines in elderly Chinese subjects with MCI. Sci Rep. 2016;6:37486. Published 2016 Nov 23. doi:10.1038/srep37486.
  28. Ma F, Li Q, Zhou X, Zhao J, Song A, Li W, Liu H, Xu W, Huang G. Effects of folic acid supplementation on cognitive function and Aβ-related biomarkers in mild cognitive impairment: a randomized controlled trial. Eur J Nutr. 2019 Feb;58(1):345-356. doi: 10.1007/s00394-017-1598-5. Epub 2017 Dec 18. PMID: 29255930.
  29. Araújo JR, Martel F, Borges N, Araújo JM, Keating E. Folates and aging: Role in mild cognitive impairment, dementia and depression. Ageing Res Rev. 2015 Jul;22:9-19. doi: 10.1016/j.arr.2015.04.005. Epub 2015 May 2. PMID: 25939915.
  30. Available at https://clinicalnutritionespen.com/article/S2212-8263(13)00104-8/fulltext.
  31. Hariz A, Bhattacharya PT. Megaloblastic Anemia. [Updated 2020 Oct 23]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537254/.
  32. Khan KM, Jialal I. Folic Acid Deficiency. [Updated 2020 Jun 30]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK535377/.
  33. 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. Am J Clin Nutr. 2007;85(1):193-200. doi:10.1093/ajcn/85.1.193.
  34. Dugdale AE. Predicting iron and folate deficiency anaemias from standard blood testing: the mechanism and implications for clinical medicine and public health in developing countries. Theor Biol Med Model. 2006;3:34. Published 2006 Oct 9. doi:10.1186/1742-4682-3-34.
  35. Haidar J. Prevalence of anaemia, deficiencies of iron and folic acid and their determinants in Ethiopian women. J Health Popul Nutr. 2010;28(4):359-368. doi:10.3329/jhpn.v28i4.6042.
  36. Aslinia F, Mazza JJ, Yale SH. Megaloblastic anemia and other causes of macrocytosis [published correction appears in Clin Med Res. 2006 Dec;4(4):342]. Clin Med Res. 2006;4(3):236-241. doi:10.3121/cmr.4.3.236.
  37. Hoffbrand AV. Pathology of folate deficiency. Proc R Soc Med. 1977;70(2):82-84.
  38. Swain RA, St Clair L. The role of folic acid in deficiency states and prevention of disease. J Fam Pract. 1997 Feb;44(2):138-44. PMID: 9040515.
  39. Yakoob MY, Bhutta ZA. Effect of routine iron supplementation with or without folic acid on anemia during pregnancy. BMC Public Health. 2011;11 Suppl 3(Suppl 3):S21. Published 2011 Apr 13. doi:10.1186/1471-2458-11-S3-S21.
  40. Odewole OA, Williamson RS, Zakai NA, et al. Near-elimination of folate-deficiency anemia by mandatory folic acid fortification in older US adults: Reasons for Geographic and Racial Differences in Stroke study 2003-2007. Am J Clin Nutr. 2013;98(4):1042-1047. doi:10.3945/ajcn.113.059683.

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