Bioavailability Of Riboflavin Research Articles

Enhanced physicochemical properties and riboflavin delivery ability of soy isolate protein/sugar beet pectin composite freeze-dried gels prepared by double crosslinking strategy

Improving the mechanical strength of protein freeze-dried gels materials has become a research priority in the field of nutrient delivery system development in recent years. In this study, double crosslinking freeze-dried gels were prepared by integrating laccase catalyzed sugar beet pectin (SBP) as a highly active filler molecule into the soybean isolate protein (SPI) thermally induced gel network, followed by freeze-drying. The double crosslinking freeze-dried gels were a porous material and the addition of SBP resulted in the formation of amorphous forms of freeze-dried gels with lower binding energy. The freeze-dried gels with 2.0 % SBP addition had the densest microstructure with the highest density (19.00 mg/cm3) and mechanical strength (180.43 ± 15.27 KPa), and hydrogen bonding, NH, CN, and CO bands were the most important factors to maintain the freeze-dried gels structure. As the concentration of sugar beet pectin increased, the release mechanism of riboflavin underwent a shift from a Fickian to a non-Fickian diffusion mechanism. In addition, the highest bioavailability of riboflavin was found in the freeze-dried gels spiked with 2.0 % SBP. These results will contribute to the development of double crosslinking freeze-dried gels carriers for targeted slow release of hydrophilic bioactive.

Oxygen-supplemented transepithelial-accelerated corneal crosslinking with pulsed irradiation for progressive keratoconus: 1 year outcomes.

To investigate the effects of combining oxygen supplementation with enhanced UV-A light and increased riboflavin permeability in improving the efficacy of epithelium-on crosslinking (epi-on CXL). Private eye clinic in Brisbane, Queensland, Australia. Retrospective single-center nonrandomized uncontrolled longitudinal cohort case series. Transepithelial CXL was performed on keratoconic eyes. Applications of an oxygen goggle and pulsed UV-A irradiation (1 second on, 1 second off) were used to enhance oxygen kinetics during epi-on CXL. Additional procedural modifications included the use of benzalkonium chloride and high UV-A irradiance level (30 mW/cm 2 ) to improve the stromal bioavailability of riboflavin and UV-A. The main efficacy outcomes were the changes in mean corrected distance visual acuity (CDVA) and safety over 12 months. Additional refractive and keratometry (K) outcomes were also observed. 53 eyes (38 patients) were included in this study. 12 months postoperatively, mean CDVA improved from a mean of 0.18 ± 0.2 at baseline to 0.07 ± 0.1 logMAR ( P < .0001). No statistically significant change was observed in maximum K (Kmax) and mean K, which were respectively 51.7 ± 5.8 diopters (D) and 46.4 ± 3.85 D at baseline and 51.2 ± 5.7 D ( P = .152) and 46.0 ± 3.84 D ( P = .06) 12 months postoperatively. Only 3 eyes experienced an increase of more than 2 D in Kmax; however, none of these eyes experienced a CDVA loss. There were no reported infections, corneal scarring, or other severe adverse effects. Performing supplemental oxygen epi-on CXL with accelerated, pulsed UV-A irradiation in conjunction with riboflavin permeability enhancers resulted in improved CDVA ( P < .0001) and stable keratometry up to 12 months postoperatively with a good safety profile.

Riboflavin Bioavailability Varies with Milk Type and Is Altered in Self-Reported Dairy Intolerance States (P24-012-19)

ObjectivesRiboflavin, the most abundant and bioavailable B-vitamin present in milk, is highly sensitive to degradation; thus, riboflavin content may vary depending on processing or the type of milk. Milk is one of the richest dietary source of riboflavin, making sufficient intake more challenging for those with dietary restrictions, such as lactose and dairy intolerant populations. Additionally, these individuals experience altered digestive function following dairy intake which may alter the bioavailability of ingested nutrients. Therefore, this study investigated whether B-vitamin bioavailability from milk is altered by milk type or processing, and whether this bioavailability is diminished in individuals with lactose and dairy intolerance. MethodsThe study recruited self-reported milk tolerant and intolerant young women (n = 40). All participants underwent a lactose challenge (50 g) for classification as dairy tolerant (DT, n = 10), lactose intolerant (LI, n = 10) or non-lactose dairy intolerant (NLDI, n = 20; self-reported dairy intolerance, but lactose tolerant). All participants ingested 750 mL of conventional milk (CM), lactose-free conventional milk (LF-CM) and a2 MilkTM (A2M) in a double-blind randomized crossover controlled trial. Plasma samples collected at fasting and hourly until 3 hours were analyzed for B-vitamins using high performance liquid chromatography coupled with mass spectrometry. ResultsOnly plasma riboflavin concentrations increased following all types of milk ingestion in all groups. Riboflavin concentrations were higher post CM (P < 0.05) at all postprandial time points than LF-CM and A2M (time x treatment interaction, P = 0.010) in all groups; however, the incremental area under the curve (iAUC) following CM was only higher than A2M (P = 0.001) but not LF-CM. NLDI subjects had lower postprandial riboflavin concentrations and iAUC (group x treatment interaction, P = 0.040; iAUC P = 0.049) than LI individuals. ConclusionsRiboflavin from CM is more bioavailable than LF-CM or A2M indicating that riboflavin content depends on the milk type or processing. However, regardless of milk type, decreased bioavailability may put NLDI individuals at increased risk of riboflavin inadequacy compared to LI people. Funding SourcesAgResearch, The a2 Milk Company, High Value Nutrition, Riddet Institute.

Effects of Different Processing Methods on the Micronutrient and Phytochemical Contents of Maize: From A to Z.

Maize is a staple human food eaten by more than a billion people around the world in a variety of whole and processed products. Different processing methods result in changes to the nutritional profile of maize products, which can greatly affect the micronutrient intake of populations dependent on this crop for a large proportion of their caloric needs. This review summarizes the effects of different processing methods on the resulting micronutrient and phytochemical contents of maize. The majority of B vitamins are lost during storage and milling; further loss occurs with soaking and cooking, but fermentation and nixtamalization (soaking in alkaline solution) can increase bioavailability of riboflavin and niacin. Carotenoids, found mainly in the kernel endosperm, increase in concentration after degermination, while other vitamins and minerals, found mainly in the germ, are reduced. Mineral bioavailability can be improved by processing methods that reduce phytic acid, such as soaking, fermenting, cooking, and nixtamalization. Losses of micronutrients during processing can be mitigated by changes in methods of processing, in addition to encouraging consumption of whole-grain maize products over degermed, refined products. In some cases, such as niacin, processing is actually necessary for nutrient bioavailability. Due to the high variability in the baseline nutrient contents among maize varieties, combined with additional variability in processing effects, the most accurate data on nutrient content will be obtained through analysis of specific maize products and consideration of in vivo bioavailability.

Self-assembled liquid crystalline nanoparticles as an ophthalmic drug delivery system. Part II: optimization of formulation variables using experimental design

In the field of keratoconus treatment, a lipid-based liquid crystal nanoparticles system has been developed to improve the preocular retention and ocular bioavailability of riboflavin, a water-soluble drug. The formulation of this ophthalmic drug delivery system was optimized by a simplex lattice experimental design. The delivery system is composed of three main components that are mono acyl glycerol (monoolein), poloxamer 407 and water and two secondary components that are riboflavin and glycerol (added to adjust the osmotic pressure). The amounts of these three main components were selected as the factors to systematically optimize the dependent variables that are the encapsulation efficiency and the particle size. In this way, 12 formulas describing experimental domain of interest were prepared. Results obtained using small angle X-rays scattering (SAXS) and cryo-transmission electron microscopy (cryo-TEM) evidenced the presence of nano-objects with either sponge or hexagonal inverted structure. In the zone of interest, the percentage of each component was determined to obtain both high encapsulation efficiency and small size of particles. Two optimized formulations were found: F7 and F1. They are very close in the ternary phase diagram as they contain 6.83% of poloxamer 407; 44.18% and 42.03% of monoolein; 46.29% and 48.44% of water for F7 and F11, respectively. These formulations displayed a good compromise between inputs and outputs investigated.

Modified-release capsules containing sodium riboflavin 5′-phosphate

Introduction: The focus of this work was to produce delayed-release capsules containing riboflavin (vitamin B2, as API) layered pellets. Riboflavin therapy is indicated in patients with a riboflavin deficiency, which usually occurs in conjunction with malabsorption, alcoholism or a protein-calorie deficiency and rarely as the sole vitamin deficiency. Riboflavin is readily absorbed from the upper gastrointestinal tract by a specific transport mechanism. The dissolution rate of coated capsules was controlled through the coating of the capsules and the thickness of the coating layer.Methods: The core pellets (Cellet 300) were loaded with a 10% aqueous solution of sodium riboflavin 5′-phosphate by a layering technique in a coating pan. Hard capsules were filled with riboflavin layered pellets and coated with Eudragit NE polymer with different coating layer thicknesses. The dissolution was tested in gastric and intestinal fluids with the half-change method. The dissolution profiles were analyzed with the use of different mathematical models and an attempt was made to predict the optimum coating film thickness that ensures the required degree and rate of dissolution.Results: A new solid dosage form was developed which can enhance the bioavailability of riboflavin. RRSBW distribution and the Chapman–Richards growth function were used to fit the dissolution profiles. Statistical analysis indicated that the best products were described by the Chapman–Richards equation. The results were utilized to create a theoretical model suitable for prediction of the optimum film thickness that ensures the required release of riboflavin.

Development and evaluation of dual controlled release microballoons containing riboflavin and citric acid: in vitro and in vivo evaluation

The objective of this work was to optimize the incorporation of citric acid (CA) in the gastroretentive microballoons containing riboflavin (RF) in order to achieve dual controlled release system and consequently enhance the bioavailability of RF. Microballoons of 739 ± 1.9 µm containing RF–CA were prepared by modified emulsion solvent diffusion method and were evaluated both for in vitro and in vivo performance. RF–CA microballoons with 22.8% RF and 37.2% CA entrapped in the shell matrix composed of Eudragit® S 100 and HPMCK4M and in vitro buoyancy of 86.0 ± 0.88% (RCM3) was selected for further studies. RCM3 exhibited biphasic, pH-dependent in vitro dual controlled release of RF (0.9933–0.9962) and CA (0.996–0.9984) beyond 1 h in both simulated fasted and fed state conditions. RCM3 was able to achieve higher mean plasma concentrations than reference formulation RM2 (RF microballoon) both in fed and fasted states in rabbits. The mean AUC0–24 estimate of RCM3 was 55% higher in fasted state (p < 0.01) and about 51% higher in fed state (p < 0.05) relative to mean AUC0–24 from RM2 formulation. Conclusively, enhancement in RF in the presence of CA along the entire plasma level curve suggests a possibility of reduction in dosing frequency. This controlled release drug delivery system of RF, where CA is incorporated in the microballoons can be easily encapsulated in capsule dosage form negating the need of CA solution as vehicle for administration of RF microballoons.

Inability to assess the safety of riboflavin‐enriched yeast added for nutritional purposes as a source of riboflavin in food supplements and the bioavailability of riboflavin from this source, based on the supporting dossier

Inability to assess the safety of riboflavin‐enriched yeast added for nutritional purposes as a source of riboflavin in food supplements and the bioavailability of riboflavin from this source, based on the supporting dossier

Quantification of the bioavailability of riboflavin from foods by use of stable-isotope labels and kinetic modeling

Background:Discrepancies have been reported between estimates of the prevalence of riboflavin deficiency based on intakes of riboflavin and estimates based on measures of riboflavin status. One reason for this may be an overestimate of the bioavailability of riboflavin from foods, about which relatively little is known.Objective:We aimed to quantify the bioavailability of riboflavin from milk and spinach by using stable-isotope labels and a urinary monitoring technique and by a plasma appearance method based on kinetic modeling.Design:Twenty healthy women aged 18–65 y were recruited for a randomized crossover study performed with extrinsically labeled (13C) milk and intrinsically labeled (15N) spinach as sources of riboflavin. An intravenous bolus of labeled riboflavin was administered with each test meal to assess the apparent volume of distribution of riboflavin in plasma.Results:No significant differences were noted in riboflavin absorption from the spinach meal and from the milk meal according to either the urinary monitoring technique (60 ± 8.0% and 67 ± 5.4%, respectively; P= 0.549) or the plasma appearance method (20 ± 2.8% and 23 ± 5.3%, respectively; P= 0.670).Conclusions:A large fraction of newly absorbed riboflavin is removed by the liver on “first pass.” The plasma appearance method therefore underestimates riboflavin bioavailability and should not be used to estimate riboflavin bioavailability from foodstuffs. Urinary monitoring suggests that riboflavin from spinach is as bioavailable as is riboflavin from milk.

Bioavailability of riboflavin from a gastric retention formulation

A gastric retention formulation (GRF) made of naturally occurring carbohydrate polymers and containing riboflavin was tested in vitro for swelling and dissolution characteristics as well as in fasting dogs for gastric retention. The bioavailability of riboflavin, a drug with a limited absorption site in the upper small intestine, from the GRF was studied in fasted healthy humans and compared to an immediate release formulation. It was found that when the GRF is dried and immersed in gastric juice it swells rapidly and releases its drug content in a zero-order fashion for a period of 24 h. In vivo studies in dogs showed that a rectangular shaped GRF stayed in the stomach of fasted dogs for more than 9 h, then disintegrated and reached the colon in 24 h. Endoscopic studies in dogs showed that the GRF hydrates and swells back to about 75% of its original size in 30 min. These in vivo results correlated with in vitro results. Pharmacokinetic parameters determined from urinary excretion data from six human subjects under fasting conditions showed that bioavailability depended on the size of the GRF. The biostudy indicated that bioavailability of riboflavin from a large size GRF was more than triple that measured after administration of an immediate release formulation. Deconvolved input functions from biostudy data suggest that the large size GRF stayed in the stomach for about 15 h.

Gastroretentive Accordion Pill: Enhancement of riboflavin bioavailability in humans

The purpose of this study was to evaluate the ability of the Accordion Pill™ (AP), a novel controlled release gastroretentive unfolding dosage form (DF), to increase the bioavailability of riboflavin (RF) in humans. Three formulations containing 75 mg of RF and differing in release rate (immediate release (IR) capsule, AP#1, and AP#2) were administered with a low-calorie meal. Gastric residence time (GRT) of the AP was assessed by magnetic resonance imaging. Serial blood and urine samples were taken and assayed for RF. The AP demonstrated prolonged (up to 10.5 h) GRT in humans. Significant elevation in RF bioavailability (209 ± 37%, mean ± S.E.) was achieved by the AP#1 in comparison to the IR capsule. A correlation was established between the in-vitro release rates from DF and bioavailability of RF in humans, and it was modeled taking into account the saturable nature of RF absorption transport and its narrow absorption window (NAW) in the upper gastro-intestinal tract. It is anticipated that the AP will provide a valuable pharmaceutical solution to enhance therapy with NAW drugs.

Citric acid prolongs the gastro-retention of a floating dosage form and increases bioavailability of riboflavin in the fasted state

A floating dosage form based on calcium alginate beads has been developed. Riboflavin, was selected as the model drug and successfully incorporated into calcium alginate beads. The aims of the current study were to: (a) assess the influence of prolonged gastro-retention on the bioavailability of riboflavin from freeze dried calcium alginate beads administered under varying conditions of food intake and (b) to investigate the potential of citric acid to delay the gastric emptying of the calcium alginate beads. Gamma scintigraphy was selected as the method to monitor the movement of the calcium alginate beads in vivo. Riboflavin concentrations in the urine were analysed by HPLC. Prolonged gastro-retention can be achieved, in the fasted state, when citric acid solution is used as an administering vehicle. However, prolonged gastro-retention is not achieved to the same extent when the gastric emptying times are compared to those obtained in the fed state. The bioavailability of riboflavin improved when calcium alginate beads were administered in the fasted state with citric acid solution, compared to the bioavailability obtained when the calcium alginate beads were administered in the absence of citric acid.

Relative bioavailability of riboflavin in cows' milk and fermented milk using rat bioassay

Abstract Bioavailability of riboflavin from cows' milk and fermented milk was assessed using riboflavin-depleted rats. The fermented milk was prepared using Lactococcus lactis subsp. lactis, and cremoris and Propionibacterium shermanii as starter cultures. Rats were depleted of riboflavin by feeding a riboflavin-free diet for 30 days. At this stage, hepatic riboflavin and erythrocyte glutathione reductase (EGR) activity decreased significantly (P Relative bioavailability (RBV), relative to pure vitamin, of riboflavin from milk and fermented milk was determined by slope ratio statistics using multiple linear regression with hepatic riboflavin, EGR activity and AC on FAD addition as response criteria. RBV for milk and fermented milk were 144 and 161% with hepatic riboflavin as a response criterion, 135 and 154% with EGR activity as a criterion and 116 and 125% with AC as a criterion. RBVs were significantly greater for milk and fermented milk than for the pure vitamin.

Riboflavin Requirement of Chicks Fed Purified Amino Acid and Conventional Corn-Soybean Meal Diets

Three experiments were conducted to determine the riboflavin requirement for maximal growth of young chicks. Graded levels of crystalline riboflavin were added to either riboflavin-free, purified amino acid diets or corn-soybean meal diets. Chick growth responses were obtained upon adding riboflavin to both diets. Chicks fed the purified diet required 1.8 mg of riboflavin per kg of diet, but those fed the corn-soybean meal diet required 2.63 mg of riboflavin per kg of diet. Retarded growth and leg paralysis, rather man curled-toe paralysis, were the predominant signs of riboflavin deficiency. Calculations suggested that riboflavin bioavailability in the corn-soybean meal diet was 59.1%.

Bioavailability of riboflavin from fortified palm juice.

The bioavailability of riboflavin from fortified palm juice was assessed in young adult men, Riboflavin status was assessed from urinary riboflavin excretion and erythrocyte glutathione reductase activity coefficient (EGR-AC) while iron status was assessed from haemoglobin and serum ferritin concentrations. Although the consumption of unfortified palm juice made significant contribution to the meager riboflavin intake, it conferred no metabolic advantage. The consumption of fortified palm juice produced a marked reduction in EGR-AC values and a significant increase in urinary riboflavin excretion. Since iron release from storage sites may be flavin dependent, riboflavin deficiency may affect iron utilization. Fortification may prove effective in alleviating nutrient deficiencies, but the carrier vehicle must be acceptable to all age groups.

Dosage form and formulation effects on the bioavailability of vitamin E, riboflavin, and vitamin B-6 from multivitamin preparations

The effects of formulation factors and pharmaceutical dosage form on the bioavailability of RRR-alpha-tocopherol (d-alpha-tocopherol), riboflavin, and pyridoxine hydrochloride were studied after administration of two capsule formulations and a tablet to 12 normal humans. Absorption of RRR-alpha-tocopherol was increased from the Aquabiosorb soft elastic gelatin (SEG) capsule formulation compared with the modified standard-SEG capsule and the commercial tablet. There were no significant differences in bioavailability of riboflavin and pyridoxine hydrochloride between the SEG formulation and the tablet albeit a trend toward consistent absorption was seen from the SEG formulation. The modified-SEG formulation exhibited significantly lower bioavailability for these water-soluble vitamins. The enhanced bioavailability of vitamin E and the trend towards faster and more consistent absorption of riboflavin and vitamin B-6 from the SEG formulation may be related to the surfactant vehicle employed and the attendant wetting properties. The results also suggest ethnic differences in vitamin bioavailability.

Mechanisms underlying the differential effects of ethanol on the bioavailability of riboflavin and flavin adenine dinucleotide.

Chronic alcoholism is associated with a high prevalence of riboflavin deficiency. Experiments were designed in an animal model to determine whether ethanol alters selectively the absorption of riboflavin and flavin adenine dinucleotide (FAD), the predominant dietary form of the vitamin. Rats received by gavage a liver homogenate to which either [14C]riboflavin or [14C]FAD was added with either ethanol or isocaloric sucrose solutions. Ethanol markedly diminished the bioavailability of [14C]FAD to a greater degree than that of [14C]riboflavin. Corroboration of an ethanol-impaired intraluminal hydrolysis of FAD was provided by using everted jejunal segments and measuring mucosal uptake of [14C]riboflavin together with nonradiolabeled FAD. In subsequent studies with mucosal cell extracts, ethanol markedly inhibited activities of FAD pyrophosphatase and flavin mononucleotide (FMN) phosphatase. These findings suggest that dietary sources of riboflavin (FMN and FAD) are not absorbed as well in the presence of ethanol than are vitamin preparations containing riboflavin, which is utilized more readily.

Effect of Carbonated Beverages and of an Antiemetic Containing Carbohydrate and Phosphoric Acid on Riboflavin Bioavailability and Salicylamide Biotransformation in Humans

Two carbohydrate‐phosphoric acid solutions, one a widely used beverage (Solution C) and the other a pharmaceutical product used as an antiemetic (Solution E), administered together with riboflavin‐5′‐phosphate or salicylamide to healthy human adults, significantly increased the bioavailability of riboflavin and appreciably altered the metabolic fate of salicylamide (increased conversion to the sulfate and decreased formation of the glucuronide). A beverage containing phosphoric acid but no carbohydrates (Solution T) also increased the bioavailability of riboflavin but not as much as Solution C. These effects are attributed to a decrease of the gastric emptying rate caused by carbohydrates and phosphoric acid, consistent with the empirical use of Solution C syrup and Solution E as antinauseants and antiemetics. The results demonstrate also that the choice of beverage to be taken with medication can affect the bioavailability and/or metabolic fate of medicinals with saturable absorption and/or biotransformation characteristics.