Folate

Overview

Folate is a water-soluble B vitamin essential for one-carbon metabolism, including nucleotide synthesis, amino acid interconversion, and methylation reactions. In biology and medicine, the term can refer broadly to naturally occurring folate compounds as well as the folic acid form used in supplementation and drug-conjugation strategies. Adequate folate status is important for hematopoiesis, cellular proliferation, and normal neurologic function, while deficiency is classically associated with megaloblastic anemia and elevated homocysteine.

In biomedical research, folate is also widely used as a targeting ligand because folate receptors are overexpressed in some activated immune cells and cancer cells. This has made folic acid useful in nanomedicine and drug delivery systems, where it can be attached to carriers to improve selective uptake. Recent studies have also examined folate status in relation to bariatric surgery outcomes, kidney stone risk, cognitive function, and cardiometabolic or inflammatory disease mechanisms, reflecting its broad relevance across nutrition, metabolism, and targeted therapeutics.

Focus of Latest Publications

Recent publications have used folate in two main ways: as a clinical biomarker of nutritional status and as a molecular targeting component in engineered delivery systems.

In a prospective cohort study of patients undergoing bariatric surgery, investigators measured serum ferritin, folate, and vitamin B12 levels to assess whether these markers were associated with postoperative weight loss. The study context indicates that folate was evaluated as part of the nutritional profile surrounding bariatric surgery, alongside ferritin and vitamin B12, rather than as a direct intervention. This reflects the clinical importance of monitoring folate status in patients undergoing major weight-loss procedures, where micronutrient deficiencies can be relevant to recovery and long-term outcomes.

A separate cross-sectional NHANES analysis examined dietary and circulating folate markers in relation to kidney stones in American adults. The study framed folate status as biologically relevant to stone formation because folate participates in one-carbon metabolism, a pathway linked to metabolic processes implicated in kidney stone disease. The publication context suggests an observational association study rather than a causal intervention, with folate treated as a nutritional exposure and biomarker.

In neurocognitive research, a cohort study from the Hubei Memory and Aging Cohort examined serum homocysteine, hemoglobin, and Alzheimer’s biomarkers in the relationship between folate, vitamin B12, and cognitive function. The study context emphasizes that folate and vitamin B12 deficiency are significant risk factors for cognitive impairment, with homocysteine likely serving as a mechanistic intermediary. Related entities mentioned in the same research context included Beta amyloid and Serum glial fibrillary acidic protein, indicating that the investigators were considering folate status alongside biomarkers of neurodegeneration.

Folate also appeared in cardiovascular and hematologic contexts. In a case report of erythrovirus-B19-induced pure red cell aplasia revealing untreated HIV infection, folic acid supplementation was given together with antiretroviral therapy using dolutegravir and lamivudine, plus trimethoprim-sulfamethoxazole prophylaxis. Here, folic acid functioned as supportive therapy rather than a primary treatment. In another multi-omics study of dilated cardiomyopathy, drug-gene interaction mapping and molecular docking identified folic acid as a potential therapeutic candidate, suggesting interest in repurposing or mechanistic association rather than established clinical use.

Several studies used folic acid as a targeting ligand in drug delivery systems. One report described a folic acid-functionalized exopolysaccharide integrated into a coordination polymer for targeted and controlled drug release. The chemistry involved amide bond formation between the primary amine group of folic acid and the carboxyl group of the exopolysaccharide, producing an FA-functionalized material. Another study developed amino-functionalized Zn(II)-based trilinker metal-organic frameworks conjugated with folic acid to enable selective delivery of doxorubicin to MCF-7 breast cancer cells. In this setting, folic acid served as a receptor-targeting moiety to improve tumor selectivity for an antineoplastic payload.

Folic acid was also used in immune and inflammatory disease nanomedicine. A mitochondria-targeted salvianic acid A delivery system for rheumatoid arthritis incorporated folic acid to support folate receptor-mediated targeting of M-like macrophages, alongside triphenylphosphine for mitochondrial localization. Similarly, a nanoinformatics-guided study designed folic acid-functionalized fullerene therapies for lupus nephritis, selecting folic acid because of its affinity for folate receptors expressed on activated macrophages. These studies highlight folate receptor targeting as a strategy for directing therapeutics to inflammatory cells.

In oncology and microbiome-related research, folate appeared as part of multi-omics signatures and mechanistic hypotheses. A precision-microbiome analysis in microsatellite-stable colorectal cancer linked biosynthetic genes for inosine, riboflavin, and folate to durable clinical benefit, suggesting that folate-related microbial metabolism may contribute to treatment response. The same broader research area referenced organisms such as Fusobacterium nucleatum and Enterococcus faecium, underscoring the microbiome context in which folate biosynthesis was considered. Although these findings do not establish folate as a standalone therapy, they position folate metabolism as a potentially informative biomarker or pathway in cancer immunotherapy response.

Key Publications

• Jun Folic acid-targeted PLGA nanoparticles co-delivering doxorubicin and MnTPP enable ultrasound-triggered synergy and apoptosis in nasopharyngeal carcinoma. (Biomaterials science, 2026, PMID 42093547): "In this study, we prepared folic acid (FA)-functionalized poly(lactic-co-glycolic acid) (PLGA) nanoparticles (FPMD NPs) co-loaded with doxorubicin (Dox) and the sonosensitizer manganese(III) meso-tetrakis(4-carboxyphenyl)porphyrin (MnTPP) via a double-emulsion solvent evaporation method."
• Jun Effects of betaine-containing nutrients on homocysteine levels and glucose-lipid metabolism in overweight and obese patients with hyperhomocysteinemia. (Nutricion hospitalaria, 2026, PMID 41960847): "or a control group (n = 50, routinely administered with vitamin B6, vitamin B12 and folic acid) using a random number table."
• Jun Folic acid functionalized exopolysaccharide integrated into a coordination polymer for targeted and controlled drug release. (Carbohydrate polymers, 2026, PMID 41943355): "This reaction facilitated the formation of an amide linkage between the primary amine group of FA and the carboxyl group of the EPS."
• May Association between dietary and circulating folate markers and kidney stones in American adults: A cross-sectional NHANES analysis. (Medicine, 2026, PMID 42216366): "The relationship between folate status and kidney stone disease (KSD) is poorly understood, despite folate's essential role in one-carbon metabolism, which is related to pathways of stone formation."
• May The Effect of Ferritin on Weight Loss in Patients Undergoing Bariatric Surgery: A Prospective Cohort Study. (Journal of investigative surgery : the official journal of the Academy of Surgical Research, 2026, PMID 42179354): "This study aimed to assess serum ferritin, folate, and vitamin B12 levels and examine their roles in weight loss after bariatric surgery (BS)."
• May Amino-Functionalized Zn(II)-Based Trilinker Metal-Organic Frameworks Conjugated with Folic Acid for Targeted Delivery of Doxorubicin on the MCF-7 Cell Line of Human Breast Cancer. (Inorganic chemistry, 2026, PMID 42133888): "...and conjugated with folic acid (FA), to enable selective delivery of doxorubicin (DOX) as a model anticancer drug."
• May Erythrovirus-B19-Induced Pure Red Cell Aplasia Revealing Untreated HIV Infection. (The American journal of case reports, 2026, PMID 42154736): "Antiretroviral therapy with tenofovir, lamivudine, and dolutegravir was initiated, along with prophylaxis comprising trimethoprim-sulfamethoxazole and folic acid supplementation."
• May A mitochondria-targeted salvianic acid a delivery system for anti-inflammatory treatment of rheumatoid arthritis. (International journal of pharmaceutics, 2026, PMID 41985598): "SAHM-FA/TPP encapsulates SA within metal-phenolic networks (MPNs)-coated silica nanoparticles, which was surface-functionalized with Folic Acid (FA) for folate receptor-mediated M-like macrophage Targeting and Triphenylphosphine (TPP) for mitochondrial localization."
• May Identification of diagnostic and therapeutic roles of programmed cell death-related proteins in dilated cardiomyopathy: a multi-omics and experimental validation study. (Scientific reports, 2026, PMID 42151293): "Drug-gene interaction mapping and molecular docking highlighted decitabine and folic acid as potential therapeutic candidates."
• May Nanoinformatics-guided design and molecular dynamic evaluation of folic acid-functionalized fullerene therapies for lupus nephritis in women. (Journal of molecular modeling, 2026, PMID 42118345): "Folic acid was selected as a targeting ligand due to its affinity for folate receptors expressed on activated macrophages, while hydroxylated fullerenes provide a stable nanocarrier capable of strong hydrophobic interactions."