Compendium of the most significant studies with reference to properties, intake, effects.

Mikkelsen K, Prakash MD, Kuol N, Nurgali K, Stojanovska L, Apostolopoulos V. Anti-Tumor Effects of Vitamin B2, B6 and B9 in Promonocytic Lymphoma Cells. Int J Mol Sci. 2019 Aug 1;20(15):3763. doi: 10.3390/ijms20153763. 

Abstract. Chronic inflammation can lead to tumour initiation and progression. Vitamin B complex has the ability to regulate the immune response and, therefore, inflammation but many of the mechanistic and molecular processes involved in this regulation are still not fully understood. This study sought to determine some of these processes by studying the effects of vitamin B2 (riboflavin) B6 (pyridoxine) and B9 (folic acid) on un-differentiated pro-monocytic lymphoma cells in regard to their ability to alter the proliferation, migration, apoptosis, cytokines and expression levels of programmed death ligand 1. We show that vitamin B2, B6 and B9, on pro-monocytic lymphoma cells exerted an anti-tumorigenic effect. This data could form the basis for future studies in using vitamin B supplementation to reduce cancer cell growth in vivo.

Coelho SC, Rocha F, Estevinho BN. Electrospinning of Microstructures Incorporated with Vitamin B9 for Food Application: Characteristics and Bioactivities. Polymers (Basel). 2022 Oct 15;14(20):4337. doi: 10.3390/polym14204337. 

Abstract. The food industry has been expanding, and new vectors to entrap vitamins have been constantly investigated, aiming at versatile systems with good physico-chemical characteristics, low-cost production, high stability and the efficient release of active ingredients. The vitamin B9 (folic acid or folate) is essential for the healthy functioning of a variety of physiological processes in humans and is beneficial in preventing a range of disorders. In this study, two approaches were developed to encapsulate vitamin B9. Zein and the combination of modified starch with two plasticizers were the selected encapsulating agents to produce microstructures via the electrospinning technique. The objective was to improve the stability and the B9 antioxidant capacity in the final formulations. The work strategy was to avoid limitations such as low bioavailability, stability and thermosensitivity. The microstructures were fabricated and the morphology and shape were assessed by scanning electron microscopy. The B9 release profiles of modified starch and zein microstructures were analyzed in simulated gastric fluid at 37 °C, and in deionized water and ethanol at room temperature. The B9 encapsulation efficiency and the stability of the systems were also studied. The ABTS assay was assessed and the antioxidant activity of the produced microstructures was evaluated. The physico-chemical characterization of loaded B9 in the microstructures was achieved. High encapsulation efficiency values were achieved for the 1% B9 loaded in 12% w/w modified starch film; 5% B9 vitamin encapsulated by the 15% w/w modified starch with 4% w/w tween 80; and 4% w/w glycerol film with heterogeneous microstructures, 5% w/w zein compact film and 10% w/w zein film. In conclusion, the combinations of 7 wt.% of modified starch with 4 wt.% tween 80 and 4 wt.% glycerol; 15 wt.% of modified starch with 4 wt.% tween 80 and 4 wt.% glycerol; and 12 wt.% modified starch and 5 wt.% zein can be used as delivery structures in order to enhance the vitamin B9 antioxidant activity in the food and nutraceutical fields.

Ratajczak AE, Szymczak-Tomczak A, Rychter AM, Zawada A, Dobrowolska A, Krela-Kaźmierczak I. Does Folic Acid Protect Patients with Inflammatory Bowel Disease from Complications? Nutrients. 2021 Nov 12;13(11):4036. doi: 10.3390/nu13114036.

Abstract. Folic acid, referred to as vitamin B9, is a water-soluble substance, which participates in the synthesis of nucleic acids, amino acids, and proteins. Similarly to B12 and B6, vitamin B9 is involved in the metabolism of homocysteine, which is associated with the MTHFR gene. The human body is not able to synthesize folic acid; thus, it must be supplemented with diet. The most common consequence of folic acid deficiency is anemia; however, some studies have also demonstrated the correlation between low bone mineral density, hyperhomocysteinemia, and folic acid deficiency. Patients with inflammatory bowel disease (IBD) frequently suffer from malabsorption and avoid certain products, such as fresh fruits and vegetables, which constitute the main sources of vitamin B9. Additionally, the use of sulfasalazine by patients may result in folic acid deficiency. Therefore, IBD patients present a higher risk of folic acid deficiency and require particular supervision with regard to anemia and osteoporosis prevention, which are common consequences of IBD.

Kalter H. Folic acid and human malformations: a summary and evaluation. Reprod Toxicol. 2000 Sep-Oct;14(5):463-76. doi: 10.1016/s0890-6238(00)00093-9. 

Abstract. A large body of evidence gathered over the past 30 or more years has led to the firmly established belief that deficiency of the vitamin folic acid is a cause of congenital malformations of neural tube closure. Beginning with studies showing folic acid levels of mothers of children with such defects to be low, this belief has been solidified by epidemiologic studies revealing that this consequence is prevented by maternal supplements of the vitamin from early pregnancy. The present article reviews this evidence for the purpose of examining the claims of the efficacy of folic acid in this respect. This seems to be an advantageous moment to do so, because no clear impact of folic acid supplementation and fortification on the prevalence of neural tube defects has as yet been documented; and furthermore a pause seems to have been reached in such studies. It is felt that a historical, i.e. a chronologic approach will best describe the findings, and therefore they will be considered as they unfolded.

Björklund NK, Evans JA, Greenberg CR. Folic acid supplementation: more work is needed. CMAJ. 2000 Oct 31;163(9):1129-30. 

Abstract. James House and colleagues recently reported that 25% of Newfoundland women had low or indeterminate red blood cell folate levels (< 420 nmol/L) at their first prenatal visit.1 Booth and colleagues reported that the reference values in use today were defined on the basis of absence of biochemical signs of folate deficiency.2 These values do not reflect recommendations for folic acid intake to prevent neural tube defects.3 Booth and colleagues found that for women of child-bearing age attempting to reach a folate intake of 400 μg/day, deficiency is best defined as a serum homocysteine value above 10 μmol/L or a red blood cell folate value below 615 nmol/L.....

Kim J, Yon M, Kim CI, Lee Y, Moon GI, Hong J, Hyun T. Preconceptional use of folic acid and knowledge about folic acid among low-income pregnant women in Korea. Nutr Res Pract. 2017 Jun;11(3):240-246. doi: 10.4162/nrp.2017.11.3.240. 

Abstract. Background/objectives: Folic acid supplementation before pregnancy is known to significantly reduce the risk of having a baby with neural tube defects (NTDs). Therefore, it is important for women to be aware of the effects of folic acid supplementation before pregnancy. The purpose of this study was to investigate the awareness and preconceptional use of folic acid and to assess the current knowledge about folic acid among low-income pregnant women in Korea.....Conclusions: Our results suggest that public health strategies are needed to increase the preconceptional use of folic acid among Korean women.

Kelly GS. Folates: supplemental forms and therapeutic applications. Altern Med Rev. 1998 Jun;3(3):208-20. 

Abstract. Folates function as a single carbon donor in the synthesis of serine from glycine, in the synthesis of nucleotides form purine precursors, indirectly in the synthesis of transfer RNA, and as a methyl donor to create methylcobalamin, which is used in the re-methylation of homocysteine to methionine. Oral folates are generally available in two supplemental forms, folic and folinic acid. Administration of folinic acid bypasses the deconjugation and reduction steps required for folic acid. Folinic acid also appears to be a more metabolically active form of folate, capable of boosting levels of the coenzyme forms of the vitamin in circumstances where folic acid has little to no effect. Therapeutically, folic acid can reduce homocysteine levels and the occurrence of neural tube defects, might play a role in preventing cervical dysplasia and protecting against neoplasia in ulcerative colitis, appears to be a rational aspect of a nutritional protocol to treat vitiligo, and can increase the resistance of the gingiva to local irritants, leading to a reduction in inflammation. Reports also indicate that neuropsychiatric diseases secondary to folate deficiency might include dementia, schizophrenia-like syndromes, insomnia, irritability, forgetfulness, endogenous depression, organic psychosis, peripheral neuropathy, myelopathy, and restless legs syndrome.

Meshkin B, Blum K. Folate nutrigenetics: a convergence of dietary folate metabolism, folic acid supplementation, and folate antagonist pharmacogenetics. Drug Metab Lett. 2007 Jan;1(1):55-60. doi: 10.2174/187231207779814319. 

Abstract. Folate (Vitamin B9, Folic acid, folinic acid, folacin, pteroyglutamic acid) is essential for life-sustaining processes of DNA synthesis, replication, and repair which are naturally present in common foods such as peas, oranges, broccoli, and whole-wheat products. Folate levels have been associated with birth defects, cardiovascular disease, and many other important healthcare issues, which has resulted in government-mandated food fortification to deliver minimum levels of intake. Despite this one-size-fits-all recommendation by governmental regulatory bodies, studies suggest that a genetic predisposition may exist within as much as 67% (combining both the CT and TT alleles) of the population that causes a metabolic folate deficiency. Thus, genetic factors may play an important role in folate levels and metabolism. A substantial body of scientific evidence supports the importance of folate, genes associated with folate, genes associated with anti-folate therapeutics, and thereby a convergence in nutritional genetics or nutrigenetics. This review will comment on the substantial body of scientific evidence demonstrating the relevance for nutrigenetic measurements to guide dietary folate intake and nutritional supplementation with folic acid.