Citation: Albu, C.-C.; Bencze, M.-A.; Dragomirescu, A.-O.; Suciu, I.; T˘ anase, M.; Albu, ¸ S.-D.; Russu, E.-A.; Ionescu, E. Folic Acid and Its Role in Oral Health: A Narrative Review. Processes 2023, 11, 1994. https:// doi.org/10.3390/pr11071994 Academic Editor: Angela Scala Received: 25 May 2023 Revised: 22 June 2023 Accepted: 30 June 2023 Published: 2 July 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). processes Review Folic Acid and Its Role in Oral Health: A Narrative Review Cristina-Crengut , a Albu 1 , Maria-Angelica Bencze 2, * , Anca-Oana Dragomirescu 2, *, Ioana Suciu 3 , Mihaela Tănase 4 ,¸ Stefan-Dimitrie Albu 5 , Emily-Alice Russu 6 and Ecaterina Ionescu 2 1 Department of Genetics, Faculty of Dentistry, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; cristina.albu@umfcd.ro 2 Department of Orthodontics and Dentofacial Orthopaedics, Faculty of Dentistry, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; ecaterina.ionescu@umfcd.ro 3 Department of Endodontics, Faculty of Dentistry, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; ioana.suciu@umfcd.ro 4 Department of Pedodontics, Faculty of Dentistry, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; mihaela.tanase@umfcd.ro 5 Department of Periodontology, Faculty of Dentistry, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; stefan-dimitrie.albu@drd.umfcd.ro 6 Department of Dermatology, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; emily-alice.russu@rez.umfcd.ro * Correspondence: maria.bencze@umfcd.ro (M.-A.B.); anca.dragomirescu@umfcd.ro (A.-O.D.) Abstract: Vitamins, exogenous organic compounds that play a vital role in metabolic reactions, and fundamental powerful antioxidants with a crucial role in the genetic transcription process, are considered essential nutritional factors. Folic acid (FA), also known as folate, or Vitamin B9, plays an indispensable role in various intracellular reactions, being the main pawn, with a strong impact on medical and dental science. The aim of this paper mainly focuses on presenting the latest and most advanced aspects related to the following topics: (1) the resonance that FA, and more specifically FA deficiency, has at the level of the oral cavity; (2) the elements involved in the molecular landscape, which reflect the interaction and the possible mechanisms of action, through which FA influences oral health; and (3) the particular processes by which FA deficiency causes certain clinical conditions. Moreover, we aim to draw the attention and trigger the curiosity of health professionals on the need to know the specific host–environment interactions, particularly the linkage between individual genotype and phenotypic variability, which in the future could represent the basis of novel and effective treatment methods. From this perspective, we begin by providing an overview of the general radar echo of the human body induced by FA deficiency, before focusing on the genetic strategic substrate and biochemical processes involved in the molecular mechanisms through which FA acts at the cellular level. Finally, we reflect on the resulting conclusions: (1) the complex interrelationships between different types of cytokines (CKs) and abnormal folate metabolism are involved in the occurrence of neural tube defects (NTDs) and orofacial clefts (OFCs); (2) increased oxidative stress, endothelial dysfunction, and genomic instability, induced by folate deficiency, have a major impact on periodontal health; and (3) glutamate carboxypeptidase II, GCP2 1561C>T allelic variant, constitutes the main pawn, which specifically influences the bioavailability of natural folates and FA, as the main actors, with essential roles in oral health. Keywords: folic acid; oral health; MTHFR C677T mutation; cytokines; orofacial clefts; periodon- tal disease 1. Introduction Vitamins are essential organic compounds for the proper functioning of the body, playing an important role in metabolic reactions, in which they act as catalysts and function as electron donors. Also, they are powerful antioxidants, active in the cellular transcription process [1]. Processes 2023, 11, 1994. https://doi.org/10.3390/pr11071994 https://www.mdpi.com/journal/processes