Integrated Nursing, Nutritional, and Health Information Perspectives on Folic Acid Deficiency: An Updated Review
Abstract
Background: Folic acid (Vitamin B9) is a water-soluble micronutrient essential for DNA synthesis, erythropoiesis, and one-carbon metabolism. Deficiency disrupts these processes, leading to clinical consequences such as megaloblastic anemia, elevated homocysteine levels, and, critically, neural tube defects (NTDs) in developing fetuses. Despite public health measures like food fortification, deficiency remains a significant global health concern, particularly in vulnerable populations.
Aim: This review aims to provide an integrated, multidisciplinary perspective on folic acid deficiency, synthesizing its etiology, pathophysiology, clinical manifestations, and management strategies from nursing, nutritional, and medical viewpoints to guide comprehensive patient care and public health initiatives.
Methods: The approach is a comprehensive literature review and clinical synthesis. It details the diagnostic evaluation, including clinical assessment, complete blood count analysis, and biochemical testing (serum/red blood cell folate, homocysteine, and methylmalonic acid levels). Management strategies, from oral and parenteral supplementation to dietary modification and public health fortification, are examined.
Results: Folic acid deficiency has a multifactorial etiology, including inadequate dietary intake, malabsorption syndromes, medications, and increased physiological demand. Diagnosis is confirmed through characteristic macrocytic anemia and low folate levels. Treatment with oral folic acid (1-5 mg/day) is highly effective, leading to hematological recovery within weeks. Public health fortification programs have successfully reduced the prevalence of deficiency and NTDs in many countries.
Conclusion: A collaborative, interprofessional approach is fundamental to the effective prevention, diagnosis, and management of folic acid deficiency. Integrating medical treatment, nursing care, nutritional counseling, and public health strategies is essential to mitigate its hematological, neurological, and developmental consequences.
Full text article
References
US Preventive Services Task Force. Barry MJ, Nicholson WK, Silverstein M, Chelmow D, Coker TR, Davis EM, Donahue KE, Jaén CR, Li L, Ogedegbe G, Rao G, Ruiz JM, Stevermer J, Tsevat J, Underwood SM, Wong JB. Folic Acid Supplementation to Prevent Neural Tube Defects: US Preventive Services Task Force Reaffirmation Recommendation Statement. JAMA. 2023 Aug 01;330(5):454-459.
Green R, Datta Mitra A. Megaloblastic Anemias: Nutritional and Other Causes. Med Clin North Am. 2017 Mar;101(2):297-317.
Attia AAA, Amer MAEM, Hassan M, Din SFG. Low serum folic acid can be a potential independent risk factor for erectile dysfunction: a prospective case-control study. Int Urol Nephrol. 2019 Feb;51(2):223-229.
Verhaar MC, Stroes E, Rabelink TJ. Folates and cardiovascular disease. Arterioscler Thromb Vasc Biol. 2002 Jan;22(1):6-13.
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.
Metayer C, Milne E, Dockerty JD, Clavel J, Pombo-de-Oliveira MS, Wesseling C, Spector LG, Schüz J, Petridou E, Ezzat S, Armstrong BK, Rudant J, Koifman S, Kaatsch P, Moschovi M, Rashed WM, Selvin S, McCauley K, Hung RJ, Kang AY, Infante-Rivard C. Maternal supplementation with folic acid and other vitamins and risk of leukemia in offspring: a Childhood Leukemia International Consortium study. Epidemiology. 2014 Nov;25(6):811-22.
Shulpekova Y, Nechaev V, Kardasheva S, Sedova A, Kurbatova A, Bueverova E, Kopylov A, Malsagova K, Dlamini JC, Ivashkin V. The Concept of Folic Acid in Health and Disease. Molecules. 2021 Jun 18;26(12)
Allen LH. Causes of vitamin B12 and folate deficiency. Food Nutr Bull. 2008 Jun;29(2 Suppl):S20-34; discussion S35-7.
Ganji V, Kafai MR. Trends in serum folate, RBC folate, and circulating total homocysteine concentrations in the United States: analysis of data from National Health and Nutrition Examination Surveys, 1988-1994, 1999-2000, and 2001-2002. J Nutr. 2006 Jan;136(1):153-8.
Odewole OA, Williamson RS, Zakai NA, Berry RJ, Judd SE, Qi YP, Adedinsewo DA, Oakley GP. 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 Oct;98(4):1042-7.
Rogers LM, Cordero AM, Pfeiffer CM, Hausman DB, Tsang BL, De-Regil LM, Rosenthal J, Razzaghi H, Wong EC, Weakland AP, Bailey LB. Global folate status in women of reproductive age: a systematic review with emphasis on methodological issues. Ann N Y Acad Sci. 2018 Nov;1431(1):35-57.
Tinker SC, Hamner HC, Qi YP, Crider KS. U.S. women of childbearing age who are at possible increased risk of a neural tube defect-affected pregnancy due to suboptimal red blood cell folate concentrations, National Health and Nutrition Examination Survey 2007 to 2012. Birth Defects Res A Clin Mol Teratol. 2015 Jun;103(6):517-26.
Choi R, Oh Y, Park MJ, Lee SG, Lee EH. Prevalence of Folate Deficiency in Korean Women of Reproductive Age Using a Serum Folate Assay Traceable to the WHO International Standard. Clin Lab. 2021 Sep 01;67(9)
Slagman A, Harriss L, Campbell S, Muller R, McDermott R. Low proportions of folic acid deficiency after introduction of mandatory folic acid fortification in remote areas of northern Queensland, Australia: a secondary health data analysis. Biomarkers. 2019 Nov;24(7):684-691.
Crider KS, Bailey LB, Berry RJ. Folic acid food fortification-its history, effect, concerns, and future directions. Nutrients. 2011 Mar;3(3):370-84.
Koury MJ, Ponka P. New insights into erythropoiesis: the roles of folate, vitamin B12, and iron. Annu Rev Nutr. 2004;24:105-31.
Scaglione F, Panzavolta G. Folate, folic acid and 5-methyltetrahydrofolate are not the same thing. Xenobiotica. 2014 May;44(5):480-8.
Wani NA, Thakur S, Kaur J. Mechanism of intestinal folate transport during folate deficiency in rodent model. Indian J Med Res. 2012 Nov;136(5):758-65.
Milman N. Intestinal absorption of folic acid - new physiologic & molecular aspects. Indian J Med Res. 2012 Nov;136(5):725-8.
Chang S, Lu X, Wang S, Wang Z, Huo J, Huang J, Shangguan S, Li S, Zou J, Bao Y, Guo J, Wang F, Niu B, Zhang T, Qiu Z, Wu J, Wang L. The effect of folic acid deficiency on FGF pathway via Brachyury regulation in neural tube defects. FASEB J. 2019 Apr;33(4):4688-4702.
Akchiche N, Bossenmeyer-Pourié C, Kerek R, Martin N, Pourié G, Koziel V, Helle D, Alberto JM, Ortiou S, Camadro JM, Léger T, Guéant JL, Daval JL. Homocysteinylation of neuronal proteins contributes to folate deficiency-associated alterations of differentiation, vesicular transport, and plasticity in hippocampal neuronal cells. FASEB J. 2012 Oct;26(10):3980-92.
Thakur S, Rahat B, Hamid A, Najar RA, Kaur J. Identification of regulatory mechanisms of intestinal folate transport in condition of folate deficiency. J Nutr Biochem. 2015 Oct;26(10):1084-94.
Neggers Y. The Relationship between Folic Acid and Risk of Autism Spectrum Disorders. Healthcare (Basel). 2014 Oct 23;2(4):429-44.
Waxman S, Schreiber C. Measurement of serum folate levels and serum folic acid-binding protein by 3H-PGA radioassay. Blood. 1973 Aug;42(2):281-90.
WATERS AH, MOLLIN DL. Studies on the folic acid activity of human serum. J Clin Pathol. 1961 Jul;14(4):335-44
Pfeiffer CM, Sternberg MR, Hamner HC, Crider KS, Lacher DA, Rogers LM, Bailey RL, Yetley EA. Applying inappropriate cutoffs leads to misinterpretation of folate status in the US population. Am J Clin Nutr. 2016 Dec;104(6):1607-1615.
Stabler SP, Marcell PD, Podell ER, Allen RH, Savage DG, Lindenbaum J. Elevation of total homocysteine in the serum of patients with cobalamin or folate deficiency detected by capillary gas chromatography-mass spectrometry. J Clin Invest. 1988 Feb;81(2):466-74.
Devalia V, Hamilton MS, Molloy AM., British Committee for Standards in Haematology. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol. 2014 Aug;166(4):496-513.
HERBERT V. The diagnosis and treatment of folic acid deficiency. Med Clin North Am. 1962 Sep;46:1365-78.
Moussa HN, Hosseini Nasab S, Haidar ZA, Blackwell SC, Sibai BM. Folic acid supplementation: what is new? Fetal, obstetric, long-term benefits and risks. Future Sci OA. 2016 Jun;2(2):FSO116.
Mierzecki A, Kłoda K, Bukowska H, Chełstowski K, Makarewicz-Wujec M, Kozłowska-Wojciechowska M. Association between low-dose folic acid supplementation and blood lipids concentrations in male and female subjects with atherosclerosis risk factors. Med Sci Monit. 2013 Sep 04;19:733-9.
Lever EG, Elwes RD, Williams A, Reynolds EH. Subacute combined degeneration of the cord due to folate deficiency: response to methyl folate treatment. J Neurol Neurosurg Psychiatry. 1986 Oct;49(10):1203-7.
Green R, Miller JW. Folate deficiency beyond megaloblastic anemia: hyperhomocysteinemia and other manifestations of dysfunctional folate status. Semin Hematol. 1999 Jan;36(1):47-64.
Okada A, Koike H, Nakamura T, Watanabe H, Sobue G. Slowly progressive folate-deficiency myelopathy: report of a case. J Neurol Sci. 2014 Jan 15;336(1-2):273-5.
Reynolds EH. The neurology of folic acid deficiency. Handb Clin Neurol. 2014;120:927-43.
Dey M, Dhume P, Sharma SK, Goel S, Chawla S, Shah A, Madhumidha G, Rawal R. Folic acid: The key to a healthy pregnancy - A prospective study on fetomaternal outcome. Tzu Chi Med J. 2024 Jan-Mar;36(1):98-102.
Mason JB, Tang SY. Folate status and colorectal cancer risk: A 2016 update. Mol Aspects Med. 2017 Feb;53:73-79.
Wilson RD, Genetics Committee. Wilson RD, Audibert F, Brock JA, Carroll J, Cartier L, Gagnon A, Johnson JA, Langlois S, Murphy-Kaulbeck L, Okun N, Pastuck M, Special Contributors. Deb-Rinker P, Dodds L, Leon JA, Lowel HL, Luo W, MacFarlane A, McMillan R, Moore A, Mundle W, O'Connor D, Ray J, Van den Hof M. Pre-conception Folic Acid and Multivitamin Supplementation for the Primary and Secondary Prevention of Neural Tube Defects and Other Folic Acid-Sensitive Congenital Anomalies. J Obstet Gynaecol Can. 2015 Jun;37(6):534-52.
Watson J, Lee M, Garcia-Casal MN. Consequences of Inadequate Intakes of Vitamin A, Vitamin B12, Vitamin D, Calcium, Iron, and Folate in Older Persons. Curr Geriatr Rep. 2018;7(2):103-113.
Baddam, S., Khan, K.M. and Jialal, I., 2025. Folic acid deficiency. In StatPearls [internet]. StatPearls Publishing.
Authors
Copyright (c) 2025 Zahra Mohammed Marwaie Khobrani, Khalid Muaybid Mohammed Alharbi, Abrar Mohammed Alanzi, Mutaib Abdulrahman Mukhlid Alotaibi, Saad Hazzaa Gazi Aljsh, Mohammed Ali Aldahmali, Jamilah Shutayt M Alharbi, Mohammad Ayed H Alenizi, Ibrahim Ataya Ali ALzubudie , Abdulrhman Mohmmed Al Sahli, Abdullah Nuwaysh Saud Alotaibi, Abdullah Ghanem Almutairi, Abdulrahman Saud Mohammad Al Sulaiman
This work is licensed under a Creative Commons Attribution 4.0 International License.