Folate Absorption Research Articles

Managing Normal Tension Glaucoma with Dietary Folate

Normal-Tension Glaucoma (NTG) is the most prevalent form of glaucoma among individuals in Asian countries. While lowering intraocular pressure (IOP) remains the standard of care, this approach is insufficient for most NTG patients. Recent evidence documents the role of ischemia and oxidative stress as critical factors affecting the optic nerve in NTG. Consequently, addressing these factors has been recommended as a neuroprotective strategy. While conventional treatment strategies primarily target the reduction of IOP, this yields limited efficacy and eventual blindness in many NTG cases. Recent studies document another crucial parameter: Retinal Venous Pressure (RVP). Elevated RVP impedes retinal perfusion, resulting in oxidative stress and localized ischemia, and exacerbating optic nerve damage in NTG. Elevated RVP also appears to be a contributing factor in small vessel ischemia associated with diabetic retinopathy and macular degeneration. The underlying cause of elevated RVP is small vessel endotheliopathy, which may result from alterations in methylation and B-vitamin metabolism, leading to changed microcirculation. This metabolic disruption can arise from dietary inadequacies, malabsorption, or genetic polymorphisms affecting the methylation pathways. Restoring plasma levels of folate and B-12 can be achieved through supplementation with natural forms of these vitamins, specifically L-methylfolate, and methylcobalamin. Unlike oxidized folate (folic acid), which must be enzymatically converted to methylfolate to penetrate the blood-retinal barrier, L-methylfolate can be directly utilized. Excess unmetabolized folic acid can impede methyl folate absorption into the retina, underscoring the necessity of using methyl folate for effective supplementation. We propose integrating RVP screening into NTG risk assessments and consider a targeted vitamin supplement, such as Ocufolin®, as a viable adjunct approach to manage elevated RVP and potentially mitigate NTG progression.

Role of Folate in Liver Diseases.

Folate is a water-soluble B vitamin involved in the synthesis of purines and pyrimidines and is one of the essential vitamins for human growth and reproduction. Folate deficiency due to low dietary intake, poor absorption of folate, and alterations in folate metabolism due to genetic defects or drug interactions significantly increases the risk of diseases such as neural tube defects, cardiovascular disease, cancer, and cognitive dysfunction. Recent studies have shown that folate deficiency can cause hyperhomocysteinemia, which increases the risk of hypertension and cardiovascular disease, and that high homocysteine levels are an independent risk factor for liver fibrosis and cirrhosis. In addition, folate deficiency results in increased secretion of pro-inflammatory factors and impaired lipid metabolism in the liver, leading to lipid accumulation in hepatocytes and fibrosis. There is substantial evidence that folate deficiency contributes to the development and progression of a variety of liver diseases, including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcoholic liver disease (ALD), viral hepatitis, hepatic fibrosis, and liver cancer. Here we review key studies on the role of folate in the pathophysiology of liver diseases, summarize the current status of studies on folate in the treatment of liver diseases, and speculate that folate may be a potential therapeutic target for liver diseases.

Impact of Drug-Mediated Inhibition of Intestinal Transporters on Nutrient and Endogenous Substrate Disposition…an Afterthought?

A large percentage (~60%) of prescription drugs and new molecular entities are designed for oral delivery, which requires passage through a semi-impervious membrane bilayer in the gastrointestinal wall. Passage through this bilayer can be dependent on membrane transporters that regulate the absorption of nutrients or endogenous substrates. Several investigations have provided links between nutrient, endogenous substrate, or drug absorption and the activity of certain membrane transporters. This knowledge has been key in the development of new therapeutics that can alleviate various symptoms of select diseases, such as cholestasis and diabetes. Despite this progress, recent studies revealed potential clinical dangers of unintended altered nutrient or endogenous substrate disposition due to the drug-mediated disruption of intestinal transport activity. This review outlines reports of glucose, folate, thiamine, lactate, and bile acid (re)absorption changes and consequent adverse events as examples. Finally, the need to comprehensively expand research on intestinal transporter-mediated drug interactions to avoid the unwanted disruption of homeostasis and diminish therapeutic adverse events is highlighted.

Parallel Metabolomics and Lipidomics of a PSMA/GCPII Deficient Mouse Model Reveal Alteration of NAAG Levels and Brain Lipid Composition.

Glutamate carboxypeptidase II (GCPII, also known as PSMA or FOLH1) is responsible for the cleavage of N-acetyl-aspartyl-glutamate (NAAG) to N-acetyl-aspartate and glutamate in the central nervous system and facilitates the intestinal absorption of folate by processing dietary folyl-poly-γ-glutamate in the small intestine. The physiological function of GCPII in other organs like kidneys is still not known. GCPII inhibitors are neuroprotective in various conditions (e.g., ischemic brain injury) in vivo; however, their utilization as potential drug candidates has not been investigated in regard to not yet known GCPII activities. To explore the GCPII role and possible side effects of GCPII inhibitors, we performed parallel metabolomic and lipidomic analysis of the cerebrospinal fluid (CSF), urine, plasma, and brain tissue of mice with varying degrees of GCPII deficiency (fully deficient in Folh1, -/-; one allele deficient in Folh1, +/-; and wild type, +/+). Multivariate analysis of metabolites showed no significant differences between wild-type and GCPII-deficient mice (except for NAAG), although changes were observed between the sex and age. NAAG levels were statistically significantly increased in the CSF, urine, and plasma of GCPII-deficient mice. However, no difference in NAAG concentrations was found in the whole brain lysate likely because GCPII, as an extracellular enzyme, can affect only extracellular and not intracellular NAAG concentrations. Regarding the lipidome, the most pronounced genotype-linked changes were found in the brain tissue. In brains of GCPII-deficient mice, we observed statistically significant enrichment in phosphatidylcholine-based lipids and reduction of sphingolipids and phosphatidylethanolamine plasmalogens. We hypothesize that the alteration of the NAA-NAAG axis by absent GCPII activity affected myelin composition. In summary, the absence of GCPII and thus similarly its inhibition do not have detrimental effects on metabolism, with just minor changes in the brain lipidome.

Low-dose daily folic acid (400 μg) supplementation does not affect regulation of folate transporters found present throughout the terminal ileum and colon of humans: a randomized clinical trial

BackgroundFolic acid supplementation during the periconceptional period reduces the risk of neural tube defects in infants, but concern over chronic folic acid exposure remains. An improved understanding of folate absorption may clarify potential risks. Folate transporters have been characterized in the small intestine, but less so in the colon of healthy, free-living humans. The impact of folic acid fortification or supplementation on regulation of these transporters along the intestinal tract is unknown. ObjectiveThe objective was to characterize expression of folate transporters/receptor (FT/R) and folate hydrolase, glutamate carboxypeptidase II (GCPII), from the terminal ileum and throughout the colon of adults and assess the impact of supplemental folic acid. MethodsIn this 16-wk open-labeled randomized clinical trial, adults consumed a low folic acid-containing diet, a folate-free multivitamin, and either a 400 μg folic acid supplement or no folic acid supplement. Dietary intakes and blood were assessed at baseline, 8 wk, and 16 wk (time of colonoscopy). Messenger RNA (mRNA) expression and protein expression of FT/R and GCPII were assessed in the terminal ileum, cecum, and ascending and descending colon. ResultsAmong 24 randomly assigned subjects, no differences in dietary folate intake or blood folate were observed at baseline. Mean ± SD red blood cell folate at 16 wk was 1765 ± 426 and 911 ± 242 nmol/L in the 400 and 0 μg folic acid group, respectively (P < 0.0001). Reduced folate carrier, proton-coupled folate transporter, and folate-receptor alpha expression were detected in the terminal ileum and colon, as were efflux transporters of breast cancer resistance protein and multidrug resistance protein-3. Other than a higher mRNA expression of FR-alpha and GCPII in the 400 μg supplement group in the ascending colon, no treatment differences were observed (P < 0.02). ConclusionsFolate transporters are present throughout the terminal ileum and colon; there is little evidence that a low dose of folic acid supplementation affects colonic absorption.This trial was registered at clinicaltrials.gov as NCT03421483.

Orodispersible Film Based on Maltodextrin: A Convenient and Suitable Method for Iron Supplementation.

Orodispersible film (ODF) is an innovative dosage form used to administer drugs and nutrients, designed to disintegrate or dissolve in the oral cavity without needing water. One of the advantages of ODF is that it is suitable for administration in older people and children who have difficulty swallowing because of psychological or physiological deficiencies. This article describes the development of an ODF based on maltodextrin, which is easy to administer, has a pleasant taste, and is suitable for iron supplementation. An ODF containing 30 mg of iron as pyrophosphate and 400 µg of folic acid (iron ODF) was developed and manufactured on an industrial scale. The kinetic profile for serum iron and folic acid upon consumption of ODF compared with a Sucrosomial® iron capsule (known for its high bioavailability) was evaluated in a crossover clinical trial. The study was conducted in nine healthy women, and the serum iron profile (AUC0-8, Tmax, and Cmax) of both formulations was defined. Results showed that the rate and extent of elemental iron absorption with iron ODF was comparable to that obtained using the Sucrosomial® iron capsule. These data represent the first evidence of iron and folic acid absorption concerning the newly developed ODF. Iron ODF was proven to be a suitable product for oral iron supplementation.

Folate administration ameliorates neurobehavioral effects of prenatal ethanol exposure

ABSTRACT Background: Prenatal ethanol exposure (PEE) induces heightened ethanol intake at adolescence in preclinical studies. Ethanol intake alters the absorption of folate, a methyl-group donor critical for numerous cellular functions. The prenatal administration of folate is, therefore, a promising approach to reduce the effects of PEE. Objectives: Experiment 1 determined if prenatal folate modulated the effects of PEE on ethanol intake, anxiety-like response, and exploratory behaviors (Experiment 1) in Wistar rats. Experiment 2 assessed, in rats not given PEE, if postnatal folate reversed effects of ethanol exposure at postnatal days 28–42. Experiment 3 assessed if folate altered blood ethanol levels (BELs). Methods: Experiment 1 involved 242 (125 male) adolescent Wistar rats derived from dams given folate (20 mg/kg, gestational days – GD- 13-20) + ethanol (2.0 g/kg, GD 17–20), ethanol, or vehicle only at pregnancy. Experiment 2 involved 29 male adolescents administered vehicle or ethanol doses co-administered or not with folate. In Experiment 3 twelve adult females were tested for BELs after folate administration. These tests were applied: intake tests, light dark box (LDB), elevated plus maze, open field and concentric square field. Results: PEE heightened ethanol intake (η2 ps = 0.06–07) and induced hyperactivity and a reduced latency to exit the white area of the LDB (η2 ps = 0.12–17). These effects were partially inhibited by folate (p > .05). Rats exposed to ethanol exposure at adolescence exhibited reduced motor activity (η2 p = .17), regardless of folate treatment. Folate did not affect BELs. Conclusion: Folate administration should be considered as a preventive or acute treatment to attenuate the neurobehavioral effects of PEE.

Oat β-glucan supplementation pre- and during pregnancy alleviates fetal intestinal immunity development damaged by gestational diabetes in rats.

Oat β-glucan (OG) has been shown to improve intestinal microecology in gestational diabetes mellitus (GDM), but the effect on fetal intestine health is unknown. Herein, we aimed to investigate the effects of OG supplementation during gestation in GDM dams on fetal intestinal immune development. OG was supplemented one week before mating until the end of the experiment. GDM rats were made with a high-fat diet (HFD) with a minimal streptozotocin (STZ) dose. The fetal intestines were sampled at gestation day (GD) 19.5, and the intestinal morphology, chemical barrier molecules, intraepithelial immune cell makers, and levels of inflammatory cytokines were investigated. The results showed that OG supplementation alleviated the decrease of the depth of fetal intestinal villi and crypts, the number of goblet cells (GCs), protein expression of mucin-1 (Muc1) and Muc2, the mRNA levels of Gpr41, Gpr43, and T cell markers, and increased the number of paneth cells (PCs), the mRNA levels of defensin-6 (defa6), and macrophage (Mø) marker and the expression of cytokines induced by GDM. In addition, OG supplementation alleviated the function of immune cell self-proliferation, chemotaxis and assembly capabilities, protein, fat, folic acid, and zinc absorption damaged by GDM. As indicated by these findings, OG supplementation before and during pregnancy improved the fetal intestinal chemical barriers, immune cells, cytokines, and the metabolism of nutrients to protect the fetal intestinal immunity.

Inflammatory Bowel Disease and Pregnancy

Inflammatory Bowel Disease and Pregnancy

Women Taking a Folic Acid Supplement in Countries with Mandatory Food Fortification Programs May Be Exceeding the Upper Tolerable Limit of Folic Acid: A Systematic Review.

Background: In preconception and pregnancy, women are encouraged to take folic acid-based supplements over and above food intake. The upper tolerable limit of folic acid is 1000 mcg per day; however, this level was determined to avoid masking a vitamin B12 deficiency and not based on folic acid bioavailability and metabolism. This review’s aim is to assess the total all-source intake of folate in women of childbearing age and in pregnancy in high-income countries with folate food fortification programs. Methods: A systematic search was conducted in five databases to find studies published since 1998 that reported folate and folic acid intake in countries with a mandatory fortification policy. Results: Women of childbearing age do not receive sufficient folate intake from food sources alone even when consuming fortified food products; however, almost all women taking a folic acid-based supplement exceed the upper tolerable limit of folic acid intake. Conclusions: Folic acid supplement recommendations and the upper tolerable limit of 1000 mcg set by policy makers warrant careful review in light of potential adverse effects of exceeding the upper tolerable limit on folic acid absorption and metabolism, and subsequent impacts on women’s health during their childbearing years.

Repurposing benzbromarone as antifolate to develop novel antifungal therapy for Candida albicans.

Fungal infections in humans are responsible for mild to severe infections resulting in systemic effects that cause a large amount of mortality. Invasive fungal infections are having similar symptomatic effects to those of COVID-19. The COVID-19 patients are immunocompromised in nature and have a high probability of developing severe fungal infections, resulting in the development of further complications. The existing antifungal therapy has associated problems related to the development of drug resistance, being sub-potent in nature, and the presence of undesirable toxic effects. The fungal dihydrofolate reductase is an essential enzyme involved in the absorption of dietary folic acid and its conversion into tetrahydrofolate, which is a coenzyme required for the biosynthesis of the fungal nucleotides. Thus, in the current study, an attempt has been made to identify potential folate inhibitors of Candida albicans by a computational drug repurposing approach. Based upon the molecular docking simulation-based virtual screening followed by the molecular dynamic simulation of the macromolecular complex, benzbromarone has been identified as a potential anti-folate agent for the development of a novel therapy for the treatment of candidiasis.Supplementary informationThe online version contains supplementary material available at 10.1007/s00894-022-05185-w.

Absorption and Tissue Distribution of Folate Forms in Rats: Indications for Specific Folate Form Supplementation during Pregnancy.

Food fortification and folic acid supplementation during pregnancy have been implemented as strategies to prevent fetal malformations during pregnancy. However, with the emergence of conditions where folate metabolism and transport are disrupted, such as folate receptor alpha autoantibody (FRαAb)-induced folate deficiency, it is critical to find a folate form that is effective and safe for pharmacologic dosing for prolonged periods. Therefore, in this study, we explored the absorption and tissue distribution of folic acid (PGA), 5-methyl-tetrahydrofolate (MTHF), l-folinic acid (levofolinate), and d,l-folinic acid (Leucovorin) in adult rats. During absorption, all forms are converted to MTHF while some unconverted folate form is transported into the blood, especially PGA. The study confirms the rapid distribution of absorbed folate to the placenta and fetus. FRαAb administered, also accumulates rapidly in the placenta and blocks folate transport to the fetus and high folate concentrations are needed to circumvent or overcome the blocking of FRα. In the presence of FRαAb, both Leucovorin and levofolinate are absorbed and distributed to tissues better than the other forms. However, only 50% of the leucovorin is metabolically active whereas levofolinate is fully active and generates higher tetrahydrofolate (THF). Because levofolinate can readily incorporate into the folate cycle without needing methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) in the first pass and is relatively stable, it should be the folate form of choice during pregnancy, other disorders where large daily doses of folate are needed, and food fortification.

Folic acid supplementation and malaria susceptibility and severity among people taking antifolate antimalarial drugs in endemic areas.

Folic acid supplementation and malaria susceptibility and severity among people taking antifolate antimalarial drugs in endemic areas.

The evolving biology of the proton-coupled folate transporter: New insights into regulation, structure, and mechanism.

The human proton‐coupled folate transporter (PCFT; SLC46A1) or hPCFT was identified in 2006 as the principal folate transporter involved in the intestinal absorption of dietary folates. A rare autosomal recessive hereditary folate malabsorption syndrome is attributable to human SLC46A1 variants. The recognition that hPCFT was highly expressed in many tumors stimulated substantial interest in its potential for cytotoxic drug targeting, taking advantage of its high‐level transport activity under acidic pH conditions that characterize many tumors and its modest expression in most normal tissues. To better understand the basis for variations in hPCFT levels between tissues including human tumors, studies have examined the transcriptional regulation of hPCFT including the roles of CpG hypermethylation and critical transcription factors and cis elements. Additional focus involved identifying key structural and functional determinants of hPCFT transport that, combined with homology models based on structural homologies to the bacterial transporters GlpT and LacY, have enabled new structural and mechanistic insights. Recently, cryo‐electron microscopy structures of chicken PCFT in a substrate‐free state and in complex with the antifolate pemetrexed were reported, providing further structural insights into determinants of (anti)folate recognition and the mechanism of pH‐regulated (anti)folate transport by PCFT. Like many major facilitator proteins, hPCFT exists as a homo‐oligomer, and evidence suggests that homo‐oligomerization of hPCFT monomeric proteins may be important for its intracellular trafficking and/or transport function. Better understanding of the structure, function and regulation of hPCFT should facilitate the rational development of new therapeutic strategies for conditions associated with folate deficiency, as well as cancer.

Impact of nanodisc lipid composition on cell-free expression of proton-coupled folate transporter.

The Proton-Coupled Folate Transporter (PCFT) is a transmembrane transport protein that controls the absorption of dietary folates in the small intestine. PCFT also mediates uptake of chemotherapeutically used antifolates into tumor cells. PCFT has been identified within lipid rafts observed in phospholipid bilayers of plasma membranes, a micro environment that is altered in tumor cells. The present study aimed at investigating the impact of different lipids within Lipid-protein nanodiscs (LPNs), discoidal lipid structures stabilized by membrane scaffold proteins, to yield soluble PCFT expression in an E. coli lysate-based cell-free transcription/translation system. In the absence of detergents or lipids, we observed PCFT quantitatively as precipitate in this system. We then explored the ability of LPNs to support solubilized PCFT expression when present during in-vitro translation. LPNs consisted of either dimyristoyl phosphatidylcholine (DMPC), palmitoyl-oleoyl phosphatidylcholine (POPC), or dimyristoyl phosphatidylglycerol (DMPG). While POPC did not lead to soluble PCFT expression, both DMPG and DMPC supported PCFT translation directly into LPNs, the latter in a concentration dependent manner. The results obtained through this study provide insights into the lipid preferences of PCFT. Membrane-embedded or solubilized PCFT will enable further studies with diverse biophysical approaches to enhance the understanding of the structure and molecular mechanism of folate transport through PCFT.

Folic Acid Absorption Characteristics and Effect on Cecal Microbiota of Laying Hens.

This experiment was conducted to investigate the characteristics of folic acid (FA) absorption in laying hens and the effect of FA supplementation on cecal microbiota. A total of 432 healthy hens (30-week-old) were randomly assigned to four diets supplemented with FA: 0, 1, 6, and 24 mg/kg of feed for 8 w. Blood, duodenum, jejunum, ileum, cecum, and cecal chyme samples (six samples per treatment) were collected from the hens at the end of the feeding trial. Expression profiles of folate transport and transformation genes in intestine and cecal microbiota were detected. Results showed that serum folate level significantly increased (P < 0.01) with an increase in dietary FA supplementation, reaching a plateau at 6 mg/kg FA supplementation. The expression of FA transport and transformation genes was not affected in the cecum (P > 0.05) by dietary FA supplementation; however, it was affected in the duodenum, jejunum, and ileum and mostly showed a downward trend in treatment groups (P < 0.05). The genes affected include duodenal folate receptor (Folr) and dihydrofolate reductase (Dhfr), jejunal proton-coupled folate transporter (Pcft) and reduced folate carrier (Rfc), and ileal ATP binding cassette subfamily C member (Abcc2), Abcc3, Rfc, Folr, and Dhfr. Furthermore, according to the operational taxonomic unit classification and taxonomic position identification, the cecal microbiota population of the hens was not affected by dietary FA supplementation at the phylum, class, order, family, genus, and species levels (P > 0.05). However, the relative abundance of some microbiota was affected by dietary FA supplementation (P < 0.05). In conclusion, FA transport from the intestinal lumen into enterocytes, and then into the bloodstream, is strictly regulated, which may be associated with the regulation of the expression profiles of genes involved in FA absorption. Pathogenic bacteria decreased in the cecum, especially at 24 mg/kg supplementation, but the beneficial bacteria (Bifidobacteriaceae) decreased at this level, too. Overall, FA supplementation at 6 mg/kg, which was selected for folate-enriched egg production, did not affect the health and metabolism of laying hens negatively.

Potential for elimination of folate and vitamin B12 deficiency in India using vitamin-fortified tea: a preliminary study

IntroductionThe majority of Indian women have a poor dietary folate and vitamin B12 intake resulting in their chronically low vitamin status, which contributes to anaemia and the high incidence of...

Folate Transporters Are Found Throughout the Colon of Humans and Their mRNA Expression Appears to Be Unaffected by Low Dose Folic Acid Supplementation

ObjectivesA large depot of folate resides in the colon and can exceed dietary intake. Little is known about the capacity of the colon to absorb folate. We aimed to determine the expression of key folate transporters, reduced folate carrier (RFC) and proton-coupled folate transporter (PCFT), throughout the colon of healthy adults and the impact of low dose folic acid (FA) supplementation. MethodsIn this 16 wk open-labelled randomized control trial, healthy adults (n = 25) from a colonoscopy waiting list were randomized to receive daily a multivitamin plus a 400 μg FA (400FA, n = 12) or no FA supplement (0FA, n = 13). Subjects were provided with low FA bread and pasta and instructions how to follow a low FA containing diet. Six 24-hr diet recalls were administered throughout the study and blood samples were collected at baseline, 8 and 16 wk. At colonoscopy (16 wk), 4 tissue biopsies were collected from the terminal ileum, cecum, ascending and descending colon. Blood folates were determined by microbial assay; mRNA levels of folate transporters were assessed using qPCR. ResultsOne subject was removed from analysis due to missing data (0FA). No group differences in age, sex, BMI, dietary intake, vitamin B12, red blood cell (RBC) and plasma folate levels at baseline were observed. Mean ± SD FA supplement adherence was 92 ± 12% and 96 ± 9% at 8 and 16 wk, respectively. Subjects in the 400FA group had higher total folate intake (P < 0.05) and higher RBC and plasma folate levels (P < 0.01) at 8 and 16 wk compared to 0FA subjects. RBC values at 16 wk were 1764 ± 636 and 865 ± 190 nmol/L in the 400FA and 0FA group, respectively. RFC and PCFT were detected in terminal ileum and colon biopsies (n = 96) and their mRNA levels in each section did not differ between groups. However, expression of RFC was markedly higher than PCFT across all biopsy sections (P < 0.05) and highest in the terminal ileum, compared to the cecum, ascending and descending colon in both groups (P < 0.05). ConclusionsWe demonstrated expression of folate transporters, RFC and PCFT, throughout the human colon suggesting their potential contribution to overall folate absorption. mRNA expressions were not affected by a low dose FA supplement. A deeper understanding of how FA and folate status affect colonic transporter regulation may inform future revisions of folate intake recommendations. Funding SourcesNatural Sciences and Engineering Research Council.

Bioequivalence Study of Two Multivitamin Formulations Containing Vitamin E and Folate in Healthy Adults

ObjectivesBioequivalence of vitamin E and folate in a single oral dose multivitamin (MVI) gummy or tablet. MethodsThis crossover clinical trial involved healthy adults randomized to either gummy or tablet MVI containing vitamin E (VE – 279 IU gummy; 239 IU tablet) and folate (1860 μg gummy; 1877 μg tablet) as a single dose in Phase 1 with blood samples collected at pre-dose and 0.5-, 1-, 2-, 4-, 6-, 8-, 9-, 10-, 24-, and 48-hours after dosing, followed by a 2-week washout period. In Phase 2, participants crossed over to receive MVI in the form not previously given, with blood draws at the same timepoints. Maximum Concentration (Cmax), Time of Maximum Concentration (Tmax), and Area Under the Curve (AUC) were calculated for each subject for both vitamin forms. Bioequivalence for AUC, Tmax, and Cmax was defined as a 90% confidence interval (CI) for the gummy to tablet comparator ratio of the geometric mean between 80% and 125%. ResultsNineteen participants completed the study. Both gummy and tablet demonstrated absorption for both vitamins. The ratio of geometric means demonstrated bioequivalence between gummy and tablet for both VE and folate with both AUC and Cmax. While bioequivalence was also demonstrated for VE with Tmax, folate absorption peaked earlier in the gummy group (Tmax 1.89 hrs) than the tablet group (Tmax 4.00 hrs), shifting Cmax values in the gummy group to earlier timepoints than in the tablet group without affecting total absorption AUC. These results were consistent with a previous pilot study. ConclusionsOverall, under the conditions of this study, both gummy and tablet showed similar absorption of vitamin E and folate. Funding SourcesChurch & Dwight Co., Inc.

Iatrogenic deficits of micronutrients

Long-term use of certain drugs causes subclinical and clinically significant micronutrient deficiencies, which can affect the course of the disease, its prognosis, quality of life, and patient compliance with therapy. The aim of the study was to single out groups of drugs, which long-term use leads to micronutrient deficiency, and to determine vitamins, minerals and trace elements, which supply can be reduced as a result of pharmacotherapy, basing on the analysis of data published in the scientific literature. Material and methods. This review analyzes articles on medical sciences from MEDLINE and PubMed-NCBI bibliographic databases. Results. Combined oral contraceptives reduce woman's supply with B vitamins (B6, B12, B9), can cause hypomagnesemia, affect the calcium/magnesium blood ratio, reduce the amount of vitamin E circulating in blood. Proton pump inhibitors reduce the absorption of vitamin B12, calcium, magnesium, iron, zinc. Aspirin increases ascorbic acid metabolism. Loop diuretics increase urinary excretion of calcium, magnesium, thiamine, thiazide ones elevate zinc and vitamin B9 excretion. Loss of taste when taking captopril is associated with a decrease in zinc supply. The use of calcium channel blockers interfere with the absorption of folic acid by gingival fibroblasts. Conclusion. Given the growing prevalence of long-term drug use, it is necessary to be able to predict and prevent potential consequences of interactions with micronutrients. It is advisable, along with a varied and healthy diet, to provide patients with supplementation in order to prevent micronutrient deficiencies. Optimization of vitamin status of the population in terms of its significance for public health is comparable to drug therapy and is one of the technologies for reducing losses from chronic diseases.