Urinary Excretion Of Riboflavin Research Articles

Influence of chronic immobilization stress on vitamin status in rats fed different diets

The influence of a stress factor, widespread in modern conditions, on the vitamin status has not been studied enough. At the same time, the negative stress impact can be aggravated against the background of unhealthy nutrition, which in turn affects the vitamin status of the organism. In this regard, the goal of the research was to evaluate the effect of chronic restrict stress on the vitamin supply in rats fed a diet with adequate and increased content of fat, sugar and cholesterol. Material and methods. The experiment was carried out on 37 growing male Wistar rats (initial body weight of 45±5 g) divided into 4 groups. Animals of the 1st (control) and the 2nd groups received a complete semi-synthetic diet (CSSD) (20% protein, 10% fat, 58% carbohydrates in the form of starch, 384 kcal/100 g) for 92 days. The levels of all vitamins and mineral elements in the rats' diets were adequate for growing rats. Rats of the 3rd and the 4th groups were fed a high-calorie, high-fat high-carbohydrate diet (HFHCD) (20% protein, 28% fat, 2% cholesterol, 18% carbohydrates in the form of starch, 20% sucrose, 511 kcal/100 g). Animals of groups 2 and 4 were subjected to daily 90-minute immobilization. The concentration of vitamins A (retinol and retinol palmitate) and E (α-tocopherol) in the blood serum and liver were determined by high-performance liquid chromatography, vitamins B1 and B2 in the liver and urine, as well as riboflavin in the blood serum and 4-pyridoxic acid (4-PA) in urine were determined by fluorimetric methods. Biochemical parameters of blood serum were determined on a biochemical analyzer; the total content of fat, triglycerides (TG) and cholesterol (CH) was determined in the liver. Results. Replacing CSSD with HFHCD, both under restraint stress and without, was accompanied by an increase in liver weight by 1.8-2.0 fold, in its fat content by 2.6-3.3 fold, cholesterol by 32.6-35.3 fold and TG - by 33.0-57.6 fold (p=<0.001). An increase in alanine aminotransferase (ALT) activity by 1.7-2.0 fold (p=<0.01), in low-density lipoprotein (LDL) cholesterol level by 5.4 fold (p=<0.05) and the atherogenic coefficient by 2.5 fold (p<0.01) as well as a decrease in creatinine and urea level (p=<0.05) in blood serum were revealed. Immobilization was accompanied by a decrease in body weight, liver and liver fat in rats fed both CSSD and HFHCD (p<0.05), but didn't affect the blood serum biochemical parameters, with the exception of an increase in ALT activity. If the activity of alkaline phosphatase (ALP) did not change during immobilization of rats fed the CSSD, then in animals fed the high-calorie diet it decreased by 37.5% (p=<0.05 from the control) under its increase against the background of restrict stress by 78.7% (p=<0.01) compared to the indicator of rats of the 3rd group. Immobilization of rats treated with CSSD was accompanied by an increase in both absolute serum α-tocopherol level and concentration correlated with the level of cholesterol and triglycerides by 26.0-57.5% (p<0.05), with a simultaneous decrease in its content in the liver per 1 g of wet tissue by 22.1% (p=0.041) relative to the indicators of intact animals. Immobilization reduced the level of retinol palmitate in the liver by 2.3 times (p<0.01), but did not affect retinol level in the blood serum. At the same time, indicators of B vitamin status (the content of vitamins B1 and B2 in the liver per 1 g of wet tissue and per organ, blood serum riboflavin level, urinary excretion of riboflavin and 4-PA) did not change, with the exception of thiamine urinary excretion, which reduced compared to the control by 38.8%. In rats fed HFHCD, immobilization had no additional effect on the supply with vitamins A and E. The content of vitamins B1 and B2 in the liver in terms of the whole organ was reduced by 14.0-26.7% relative to the indicator in animals of the 3rd group, not subjected to chronic stress, only due to differences in liver weight in animals of these groups. Conclusion. The data obtained indicate that chronic stress has a negative effect on the vitamin status of the body, worsening the supply with vitamins A, E and B1, and substantiate the feasibility of studying the mechanisms of this effect in order to develop effective vitamin complexes for the treatment and prevention of diseases caused by long-term stress.

Influence of the rat diet enrichment with oat β-gucans on the assimilation of B group vitamins, mineral elements and lipid metabolism

Despite the widespread use of oat β-glucans as ingredient of foods and dietary supplements, there is insufficient data on their effect on the metabolism of vitamins and minerals. The purpose of the study was to evaluate the effect of including oat bran with a high content of β-glucans (β-glucan) in the diet on the absorption of micronutrients and lipid metabolism in growing rats deficient in vitamins D, group B and trace elements (iron, copper, zinc). Material and methods. After the development of micronutrient deficiency (for 23 days), in order to assess the effect of oat bran (5%) with a high content of β-glucans on the correction of the micronutrient status of growing male Wistar rats (with initial body weight of 70.7±0.7 g), the missing micronutrients were introduced in the semi-synthetic diet deficient in vitamins D, group B, iron, copper and zinc within 7 days either along with β-glucan (1.47%) or without its addition. Indicators of micronutrient sufficiency (riboflavin serum concentration, daily urinary excretion of thiamine, riboflavin and 4-pyridoxic acid, measured by fluorometric methods; serum concentration and urinary excretion of calcium, magnesium, iron, zinc, copper, phosphorus, measured by the atomic absorption method or using standard methods on a biochemical analyzer) and the biochemical parameters of blood serum were compared with the parameters of rats adequately provided with all micronutrients throughout the experiment. Results. Replenishment of missing micronutrients in the diet of rats with deficiency in vitamins D and group B, iron, copper and zinc for 7 days led to the elimination of deficiency of vitamins B1, B2 and B6, regardless of the presence of β-glucans in the diet. At the same time, against the background of the presence of β-glucans in the feed, an increase in the absorption of iron was observed, as evidenced by an increase by 1.73 times in iron blood plasma level (р<0.05) and a tendency towards its urinary excretion decrease by 1.60 fold (р<0.10) compared to animals from the control group. Adding oat bran with β-glucans to the feed did not lead to a decrease in blood plasma level of total cholesterol and low-density lipoproteins cholesterol. The levels of high-density lipoprotein cholesterol and triglycerides in rats of all three groups did not have statistically significant differences. Conclusion. The presence of β-glucans in the diet had virtually no effect on the absorption of B vitamins and improved the absorption of iron.

ВЛИЯНИЕ АЛИМЕНТАРНОЙ НЕДОСТАТОЧНОСТИ КАЛЬЦИЯ, МАГНИЯ И ЙОДА НА ВИТАМИННЫЙ СТАТУС КРЫС

The diet of the majority of the population of Russia is characterized by an insufficient content of a number of micronutrients, including macro- and micronutrients. The aim of the study is to characterize in a rat model experiment the effect of combined nutritional deficiency of calcium, magnesium and iodine on the availability of other mineral substances, vitamin metabolism and biochemical parameters blood plasma. The lack of minerals in growing Wistar male rats with an initial body weight (51.4 ± 0.5) g was created for 23 days by halving of a calcium, magnesium and iodine in the salt mixture. Alimentary deficiency of calcium, magnesium and iodine in growing rats significantly and multidirectionally affected the metabolism of other minerals and vitamins, as well as a number of diagnostically significant indicators of blood and urine. In rats of the experimental group, the liver concentration of α-tocopherol, vitamin B1 and retinol palmitate decreased, the concentration of iron and zinc increased, the copper content in the whole brain decreased significantly. The molar ratio of γ- and α-tocopherols in blood plasma was increased, the concentration of the circulating form of vitamin D decreased. The ratio of AlAT / AsAT (de Ritis coefficient) markedly decreased due to increased activity of AlAT. Phosphate reabsorption decreased slightly. Increased urinary excretion of riboflavin was accompanied by a decrease in its concentration in blood plasma. The conclusion that insufficient intake of calcium, magnesium and iodine may disturb vitamin-mineral status of organism has been made.

Effect of B-vitamin deficiency on biochemical, immunologic markers and trace element status of rats and mice of various lines

Biochemical, vitamin, trace element and immunological changes were searched for the combined nutritional deficiency of vitamins B1, B2, B6 on in vivo models in rats and mice. Female rats of Wistar (W) strain and hybrids of the 1st generation of Dark Aguti and Wistar (DA x W) strains, female mice of BALB/c strain and DBCB tetrahybrids were used in experiment. Animals received for 35 days a balanced diet (control) according to AIN-93 or a similar diet with the exception of vitamins B1, B2, B6 (experimental groups). The content of vitamins B1, B2 in liver, riboflavin blood plasma level and urinary excretion of thiamine, riboflavin and 4-pyridoxic acid were determined, as well as in rats: blood and liver content of α-tocopherol and retinol, blood biochemical indices of lipid and nitrogen metabolism, activity of cytochrome P isoforms-450 (CYP) in liver; in mice: the circulating levels of pro- and anti-inflammatory cytokines of blood plasma, in animals of both species - the content of essential and toxic elements in the kidneys. DAxW rats compared to W and DBCB mice compared to BALB/c were more sensitive to the development of B-vitamin deficiency judging by the B-vitamin status indicators. In the rats of the experimental groups, there were signs of a deterioration in blood and liver levels of vitamin E, multidirectional shifts in vitamin A sufficiency, increased activity of the CYP3A isoform (6β-TG), a decrease in triglycerides, total protein and albumin fraction levels with an increase in urea level. Manifestation degree of these effects depended on the choice of the animal's line. In mice, the B-vitamin deficiency was characterized by an increase in the levels of proinflammatory cytokines TNF-α, IL-10, IL-Ιβ, IL-6 and a decrease in IFN-γ and IL-17A. The content of magnesium, copper, zinc, chromium and silver was lowered, of cesium - was increased in the kidneys of the rats of the experimental groups. In mice, B-vitamin deficiency resulted in diminishment of magnesium, copper, zinc, chromium, selenium, cadmium and lead content, excess accumulation of cobalt and cesium. Some of these biomarkers are supposed to be used in pre-clinical evaluation of the effectiveness of new vitamin complexes, specialized foods and dietary supplements, as well as studies of interactions of various vitamins.

Dietary Reference Values for riboflavin.

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) derives dietary reference values (DRVs) for riboflavin. The Panel considers that the inflection point in the urinary riboflavin excretion curve in relation to riboflavin intake reflects body saturation and can be used as a biomarker of adequate riboflavin status. The Panel also considers that erythrocyte glutathione reductase activation coefficient is a useful biomarker, but has limitations. For adults, the Panel considers that average requirements (ARs) and population reference intakes (PRIs) can be determined from the weighted mean of riboflavin intake associated with the inflection point in the urinary riboflavin excretion curve reported in four intervention studies. PRIs are derived for adults and children assuming a coefficient of variation of 10%, in the absence of information on the variability in the requirement and to account for the potential effect of physical activity and the methylenetetrahydrofolate reductase 677TT genotype. For adults, the AR and PRI are set at 1.3 and 1.6 mg/day. For infants aged 7–11 months, an adequate intake of 0.4 mg/day is set by upward extrapolation from the riboflavin intake of exclusively breastfed infants aged 0–6 months. For children, ARs are derived by downward extrapolation from the adult AR, applying allometric scaling and growth factors and considering differences in reference body weight. For children of both sexes aged 1–17 years, ARs range between 0.5 and 1.4 mg/day, and PRIs between 0.6 and 1.6 mg/day. For pregnant or lactating women, additional requirements are considered, to account for fetal uptake and riboflavin accretion in the placenta during pregnancy or the losses through breast milk, and PRIs of 1.9 and 2.0 mg/day, respectively, are derived.

Assessment of vitamin supply in preschoolers

Objective : to assess the vitamin status of preschoolers according to the results of one-hour urinary vitamin excretion and the data of actual nutrition. Subjects and methods . A survey was conducted in winter 2016, covering 33 children (19 boys and 14 girls) aged from 2 to 7 years who went to a Yekaterinburg preschool educational institution. The amount of essential nutrients was calculated according to the data of actual nutrition during 5 days. The vitamin status was evaluated from the urinary excretion of thiamine, riboflavin, and 4-piridoxyl acid, by testing a morning fasting urine portion. Results. Determination of urinary excretion revealed deficiency of vitamin B2 in 24.2% of the examinees, and that of vitamins B1 and B6 in significantly more children (in 66.7–69.7%). According to the actual nutrition data, inadequate intakes of vitamins B2, A, and C were detected in 27.3–30.3% of the examinees, those of niacin and vitamin B1 in 54.5 and 69.7%, respectively. The proportion of the coincidental data obtained by two methods for assessing the vitamin status was 63.6% for vitamin B1 and 69.7% for vitamin B2. Conclusion . The findings suggest that the two methods to assess the supply of vitamins B1 and B2 are interchangeable and the children need additional vitamin intakes.

Plasma riboflavin is a useful marker for studying riboflavin requirement in Chinese male adults

Urinary riboflavin excretion and erythrocyte glutathione reductase activation coefficient are frequently applied in determining riboflavin requirement. Previously, we found that plasma riboflavin is a sensitive marker in the assessment of riboflavin status in rat models. Here, we hypothesize that plasma riboflavin is a useful maker in studying riboflavin requirement. This study examines the changes of fasting plasma riboflavin and urinary riboflavin excretion in response to different riboflavin intake levels in Chinese male adults. The estimated average requirement (EAR) of riboflavin was extrapolated. Seventy-eight participants were randomly divided into the control and 5 riboflavin-supplemented groups. A 6-week riboflavin supplementation was performed at the doses of 0, 0.2, 0.4, 0.6, 0.8, or 1.0 mg daily. The energy expenditure was 15.4 ± 1.9 MJ/d, as estimated by the 24-hour physical activity recording method. Dietary riboflavin intake was 1.0 ± 0.2 mg/d, based on chemical analysis. The fasting plasma riboflavin was increased significantly in a dose-dependent manner when the supplemented riboflavin exceeded 0.4 mg/d and the EAR of riboflavin was suggested to be between 1.3 and 1.5 mg/d. In addition, we found a significant increase in fasting urinary riboflavin excretion when the supplemented riboflavin exceeded 0.6 mg/d. The critical point was calculated as 1.4 mg/d, based on the intersecting point of the 2 regression lines at lower and higher riboflavin intakes. These findings demonstrate that plasma riboflavin is a sensitive marker for riboflavin status, and the EAR of riboflavin for Chinese male adults is 1.4 mg.

Regular moderate exercise training can alter the urinary excretion of thiamin and riboflavin.

BACKGROUND/OBJECTIVESPhysical exercise promotes energy producing pathways requiring thiamin and riboflavin as a coenzyme. Therefore, this study investigated the effects of regular exercise training on urinary excretion of thiamin and riboflavin.MATERIALS/METHODSFifty rats were randomly assigned to one of two groups: non-exercise training (NT, n = 25) and regular exercise training (ET, n = 25) for 5 weeks. The rats performed moderate exercise on a treadmill (0.5-0.8 km/hour) for 30 min/day, 5 days/week. Twenty-four hour urine samples were collected at the end of the 0 week, 3rd week, and 5th week of training and thiamin and riboflavin were analyzed.RESULTSNo significant differences in thiamin and riboflavin intakes for each week were observed between the NT and ET groups. Urinary thiamin excretion of each group was the highest at the 5th week compared to the levels at 0 and 3rd week. Urinary thiamin at the 5th week was significantly lower in the ET group than in the NT group. Urinary riboflavin excretion was increased by training duration, however, no difference was observed between NT and ET for each week. At 0 and 3rd week, no significant relationships were observed between dietary intake and urinary excretion of thiamin and riboflavin, however, at the 5th week, urinary excretion was significantly increased by dietary intake only in the NT group (P < 0.05). Thiamin excretion of both NT and ET groups was significantly increased with riboflavin excretion at the 5th week (P < 0.01).CONCLUSIONRegular moderate exercise training increased urinary excretion of thiamin. Dietary intakes and urinary excretions of thiamin and riboflavin showed positive correlation in both the exercise training and non-exercise training groups as the exercise training period went by, while the correlations in the exercise training group were weaker than those in the non-exercise training group. Therefore, regular exercise training can alter the urinary excretion of thiamin and riboflavin in rats.

Evaluation of riboflavin intakes and status of 20-64-year-old adults in South Korea.

A recent Korea National Health and Nutrition Survey indicated inadequate riboflavin intake in Koreans, but there is limited research regarding riboflavin status in South Korea. The purpose of this study was to determine riboflavin intake and status of Korean adults. Three consecutive 24-h food recalls were collected from 412 (145 men and 267 women) healthy adults, aged 20–64 years, living in South Korea and urine samples were collected from 149 subjects of all subjects. The dietary and total (dietary plus supplemental) riboflavin intake was 1.33 ± 0.34 and 2.87 ± 6.29 mg/day, respectively. Approximately 28% of the subjects consumed total riboflavin less than the Estimated Average Requirement. Urinary riboflavin excretion was 205.1 ± 190.1 μg/g creatinine. Total riboflavin intake was significantly positively correlated to the urinary riboflavin excretion. (r = 0.17171, p = 0.0363). About 11% of the Korean adults had urinary riboflavin <27 μg/g creatinine indicating a riboflavin deficiency and 21% had low status of riboflavin (27 μg/g creatinine ≤ urinary riboflavin < 80 μg/g creatinine). Thus, one-third of Korean adults in this study had inadequate riboflavin status. In some adults in Korea, consumption of riboflavin-rich food sources should be encouraged.

Excess Vitamin Intake before Starvation does not Affect Body Mass, Organ Mass, or Blood Variables but Affects Urinary Excretion of Riboflavin in Starving Rats

B-vitamins are important for producing energy from amino acids, fatty acids, and glucose. The aim of this study was to elucidate the effects of excess vitamin intake before starvation on body mass, organ mass, blood, and biological variables as well as on urinary excretion of riboflavin in rats. Adult rats were fed two types of diets, one with a low vitamin content (minimum vitamin diet for optimum growth) and one with a sufficient amount of vitamins (excess vitamin diet). Body mass, organ mass, and blood variables were not affected by excess vitamin intake before starvation. Interestingly, urinary riboflavin excretion showed a different pattern. Urine riboflavin in the excess vitamin intake group declined gradually during starvation, whereas it increased in the low vitamin intake group. Excess vitamin intake before starvation does not affect body mass, organ mass, or blood variables but does affect the urinary excretion of riboflavin in starving rats.

Riboflavin as an Oral Tracer for Monitoring Compliance in Clinical Research

We studied urinary riboflavin as an objective biomarker of compliance in clinical research using a simplified method amenable to high throughput analysis. Six healthy women not taking vitamin supplements ingested a study pill containing riboflavin (32 mg) as an inactive tracer and the soy isoflavones daidzin (0.243 mmole) and genistin (0.222 mmole) as active ingredients once daily for four days. Riboflavin and metabolites of the isoflavones were measured in urine samples obtained before and after each pill. Urinary excretion of riboflavin and metabolites of both isoflavones peaked within 8 hrs and remained higher than baseline for 24 hrs. Urinary excretion of riboflavin was also measured in 152 additional women with unrestricted dietary supplement intakes. Mean and median urinary riboflavin concentrations in these women were 0.42 and 0.31 μg/mL, respectively, compared to 0.2 μg/mL during a riboflavin-restricted diet. Receiver operating characteristics (ROC) curves indicated that urinary riboflavin within 24 hrs after a 32 mg dose would perform well as a measure of compliance (all areas under the ROC curves ≥0.84. Samples collected during the initial 8 hrs after pill ingestion performed better as a compliance measure than later collections. In summary, compliance in a clinical study can be monitored in real time by incorporating 32 mg of riboflavin into study pills, with compliance indicated by urinary riboflavin levels increasing over individual baselines or to ≥1.0 μg/mL, with a false positive rate of being classified as compliant at <5%.

A novel riboflavin gastro-mucoadhesive delivery system based on ion-exchange fiber

A novel gastro-mucoadhesive delivery system based on ion-exchange fiber has been developed. Rriboflavin-5′-phosphate sodium salt (RF5P), which is site-specifically absorbed from the upper gastrointestinal tract, was used as model drug. A modified dissolution system, which can also be called ‘flow through diffusion cell’ (FTDC), was used to study the drug release from the drug fibers. Gastrointestinal transit studies of the RF5P fiber complexes in rats and gamma imaging study in volunteer was carried out to evaluate the gastro-retentive behavior of the fiber. The pharmacokinetic profile and parameters of riboflavin via analysis of urinary excretion of riboflavin on man were measured. Study on rat and man provide evidence for the validity of the hypothesis that the drug fiber provided good mucoadhesive properties in vivo and should therefore be of considerable interest for the development of future mucoadhesive oral drug delivery dosage forms.

Influence of Probiotic and Conventional Yoghurt on the Status of Vitamins B1, B2 and B6 in Young Healthy Women

Background: In vitro studies indicate that yoghurt bacteria are able to generate several water-soluble vitamins and therefore yoghurt could be a good source of these micronutrients. However, whether lactobacilli or other viable bacteria release the synthesized vitamins or utilize vitamins from their surroundings is a matter of debate. This study was carried out to investigate whether probiotic and traditional yoghurt bacteria are able to influence the status of different B vitamins (B₁, B₂, B₆) in young healthy women. Methods: In this investigation, female volunteers consumed 100 g/day of probiotic (n = 17) or conventional yoghurt (n = 16) for 2 weeks (T1–T2) and 200 g/day for another 2 weeks (T2–T3). A wash-out phase lasting 2 weeks followed. Plasma and urine concentrations of thiamine (vitamin B₁), riboflavin (B₂) and pyridoxine (B₆) were analyzed using HPLC. The functional parameters, i.e. the erythrocyte transketolase (α-ETK) expressed as TPP (thiamine pyrophosphate) effect, erythrocyte glutathione reductase (α-EGR) and glutamic oxaloacetic transaminase (α-EGOT) were determined photometrically. Results: The plasma levels of vitamin B₁ increased significantly in both the probiotic (p < 0.001) and the control group (p < 0.01) when consuming 200 g yoghurt/day (T2–T3) and decreased to the baseline levels after the wash-out phase (T3–T4). Urinary excretion of thiamine and the TPP effect did not significantly change in either the probiotic or the control group during the period of daily yoghurt consumption (T1–T3). The plasma concentration of flavin adenine dinucleotide (FAD) decreased significantly (p < 0.001) after consuming 100 g yoghurt/day (T1–T2) while plasma concentrations of flavin mononucleotide (FMN) (probiotic: p < 0.01, control: p < 0.001) and free riboflavin increased significantly (probiotic: p < 0.01, control: p < 0.001). Afterwards, the levels of these parameters remained unchanged to the end of the study in both tested groups. The urinary excretion of riboflavin and α-EGR remained unaffected throughout the study in both the probiotic and the control group. The average status of vitamin B₆, evaluated by its plasma level, urinary excretion and α-EGOT was unaffected by daily intake of 100 g (T1–T2) and 200 g yoghurt (T2–T3), respectively, for 4 weeks (T1–T3). Conclusion: The results of the present study indicate that daily consumption of 200 g of both, probiotic and conventional yoghurt for 2 weeks can contribute to the total intake of vitamin B₁ and B₂ reflected by increased levels of plasma thiamine and free riboflavin in healthy women. The diminished plasma FAD and increased FMN concentrations, observed during the period of daily yoghurt consumption in both groups, may be the result of enhanced immune function and an oxidant/antioxidant imbalance, caused by the daily intake of lactic acid bacteria. Since the long term status parameters of all three investigated vitamins (B₁, B₂, B₆) remained unaffected during the investigation the changes in plasma concentrations seem more likely the result of regular yoghurt consumption as a fermented dairy product, rather than of the specific intake of probiotic bacteria.

In vitro and in vivo evaluation of floating riboflavin pellets developed using the melt pelletization process

Floating pellets were prepared using the melt pelletization process in a Mi-Pro ® high shear mixer (Pro-C-epT, Belgium). Formulations were based on a mixture of Compritol ® and Precirol ® as meltable binders and on the use of sodium bicarbonate and tartaric acid as gas-generating agents. Good floating abilities were obtained by using the gas-generating agents in both the inner matrix and the outer coating layer of the pellets. In vitro evaluation of floating capability was performed both by using the resultant weight apparatus and by counting floating pellets at the surface of beakers containing 0.1N HCl solution, in vivo evaluation of floating pellets capabilities was also performed. Riboflavin-containing floating pellets (FRF) were administered orally to nine healthy volunteers versus non-floating pellets (NFRF). Volunteers were divided in two groups, fasted group ( n = 4) 729 kcal and fed group ( n = 5) 1634 kcal as the total calorie intake on the testing day. An increase of urinary excretion of riboflavin was observed when the volunteers were dosed with the floating pellets, especially after feeding. As riboflavin has a narrow window of absorption in the upper part of small intestine, this phenomenon could be attributable to the gastric retention of floating pellets.

Effect of B Vitamins-fortified Foods on Primary School Children in Beijing

The objective of this study is to investigate the effect of B vitamins-fortified foods on primary school children. A controlled trial was conducted in 101 normal primary school children aged 9-11 years. They were randomly assigned to supplemental control group (S-control, n=36), riboflavin supplementation group (+riboflavin 0.625 mg/day, n=32), and B vitamin compound supplementation group (+riboflavin 0.625 mg/day, +thiamin 0.512 mg/day, +nicotinic acid 0.365 mg/day, +folic acid 0.13 mg/day, n=33) based on school classes. Urinary riboflavin excretion and erythrocyte glutathione reductase activity coefficient (EGRAC) along with erythrocyte transketolase activity (ETKA) were used to evaluate B vitamin levels in the children. AYP index, an index reflecting the brain performance ability, was chosen to assess the children's study abilities. Health education was carried out to help children and their parents adopt scientific dietary concepts. The urinary riboflavin excretion was higher in two supplementation groups (435.24 +/- 153.3 microg/g creatinine, 374.6 +/- 144.6 microg/g creatinine) than in S-control group (235.1 +/- 86.2 microg/g creatinine). Average values of EGRAC were lower in two supplementation groups (0.90 +/- 0.11, 0.80 +/- 0.10) than in S-control group (1.08 +/- 0.25). At the same time, the percentage of thiamine pyrophosphate (TPP%) decreased from 63.69 +/- 28.04 to 42.16 +/- 16.31 in B vitamin compound supplementation group. Meanwhile, AYP index increased at the end of the supplementation in two supplementation groups. B vitamins supplementation can significantly increase B vitamin level in children. Biochemical activities of riboflavin and thiamin can improve with the intake of fortified foods. The effect of B vitamin compound supplementation is better than that of single riboflavin supplementation when the effect of riboflavin's biofunction is considered. In addition, micronutrient supplementation appears to assist children's study abilities.

In vitro and in vivo evaluation of riboflavin-containing microballoons for a floating controlled drug delivery system in healthy humans

Microballoons (MB) possessing a spherical cavity enclosed within a hard polymer shell have been developed as a dosage form characterized by excellent buoyancy in the stomach. MB were prepared by the emulsion solvent diffusion method using enteric acrylic polymers dissolved in a mixture of dichloromethane and ethanol. Riboflavin-containing MB were administered orally to each of three healthy volunteers. The pharmacokinetics of riboflavin was investigated by analysis of the urinary excretion. Prolongation of the urinary excretion of riboflavin could be obtained by ingestion of water as well as “fed” conditions. This phenomenon was attributable to the buoyancy properties of MB in the stomach and an increase in the gastric residence time (GRT). The excretion half-life time ( t 1/2) following administration of MB (particle size: 500–1000 μm) exhibiting high buoyancy was longer than that of MB (particle size: <500 μm) displaying low buoyancy. Therefore, the intragastric floating properties of MB are potentially beneficial as far as a sustained pharmacological action is concerned. MB prepared by mixing it with hydroxypropylmethylcellulose (HPMC) in different ratio, results in improved riboflavin-release properties. These MB were evaluated in vivo by analysis of the urinary excretion of riboflavin. As a result, strong correlations were observed between the buoyancy and excretion half-life ( t 1/2) and between the riboflavin release from the MB and total urinary excretion.

In vivo evaluation of riboflavin-containing microballoons for floating controlled drug delivery system in healthy human volunteers

Hollow microspheres (microballoons) floatable in JPXIII no. 1 solution were developed as a floating controlled drug delivery system. Microballoons (MB) were prepared by the emulsion solvent diffusion method utilizing enteric acrylic polymers dissolved in a mixture of dichloromethane and ethanol. To assess the usefulness of the intragastric floating properties of MB in sustained pharmacological action, nonfloating microspheres (NF) possessing riboflavin release profiles equivalent to those of MB were prepared. Riboflavin powder, riboflavin-containing MB, and riboflavin-containing NF were administrated orally to each of three healthy volunteers. Riboflavin pharmacokinetics was investigated via analysis of urinary excretion of riboflavin. As a result, although urinary excretion of riboflavin following administration of MB was not sustained in the fasted state, urinary excretion of MB was significantly sustained in comparison to riboflavin powder and NF in the fed condition. Additionally, the excretion half-life time ( t 1/2) of MB was prolonged significantly by feeding. Furthermore, MB provided significantly high total urinary excretion (%) of riboflavin compared to NF in the fasted and the fed conditions. In view of the finding regarding similar riboflavin release profiles of MB and NF in JP XIII no. 1 solution (pH 1.2) and no. 2 solution (pH 6.8), the intragastric floating properties of MB appeared to be beneficial with respect to sustained pharmacological action.

Pharmacokinetics of orally and intravenously administered riboflavin in healthy humans

The pharmacokinetics and utilization (flavocoenzyme synthesis) of orally and intravenously administered riboflavin in healthy humans were assessed. After the determination of circadian rhythms of riboflavin concentrations in blood plasma and urine of four males and five females (control period), each of these subjects received three different oral riboflavin doses (20, 40, and 60 mg) and one intravenous bolus injection of riboflavin (11.6 mg). Vitamins were administered in a randomized, cross-over design with 2 wk between each administration. Blood plasma and urine specimens were collected repeatedly over a period of 48 h after each administration. Concentrations of flavocoenzymes and riboflavin were analyzed in blood plasma; riboflavin was assayed in urine. During the control period, a small circadian variation was observed: plasma concentrations and urinary excretion of riboflavin were low during the afternoon (P < 0.05). Pharmacokinetics were calculated using a two-compartment open model. The maximal amount of riboflavin that can be absorbed from a single dose was 27 mg per adult. Half-life of absorption was 1.1 h. First-order rate constants describing distribution and elimination of riboflavin were significantly higher after intravenous than after oral administration (P < 0.01). Release of flavocoenzymes into plasma was low compared with the increase of riboflavin concentrations. 7 alpha-Hydroxyriboflavin was identified in plasma. Clearance data indicated that urinary excretion of riboflavin contributes to one-half of the overall removal of riboflavin from plasma. No sex differences were observed for any of the pharmacokinetic variables (P > 0.05).

Riboflavin Requirement of Healthy Elderly Humans and Its Relationship to Macronutrient Composition of the Diet ,

The riboflavin requirements of two groups of riboflavin-deficient, but otherwise healthy, Guatemalan elderly persons over the age of 60 y were studied by varying the fat:carbohydrate ratio in two diets. The first group consumed a diet similar in macronutrient content to a Western-type diet with low carbohydrate and high fat; the second group consumed a typical Guatemalan diet with high carbohydrate and low fat. Energy and protein intakes of both groups were similar. Riboflavin status was monitored by weekly measurements of erythrocyte glutathione reductase activity coefficient (EGRAC) and urinary riboflavin excretion. Increasing increments of riboflavin were added to the subjects' diets until their status was normalized, as indicated by EGRAC of < 1.34 and a sharp increase in urinary riboflavin excretion. Using the EGRAC method, the mean value of riboflavin intake at which the subjects' EGRAC reached the limit of normality was 1.37 +/- 0.03 mg/d in the first phase and 1.29 +/- 0.03 mg/d in the second phase. The sharp increase in urinary excretion occurred at riboflavin intakes of 1.13 and 1.03 mg/d for Groups 1 and 2, respectively. Thus, the differences between the two groups suggest that diets with a lower fat:carbohydrate ratio can decrease the dietary need for riboflavin. The dietary requirement of riboflavin, as estimated by the more reliable urinary excretion method, was 1.1-1.3 mg/d for those consuming the Western-type diet, which is similar to values found over 40 y ago in young adults. We conclude that the dietary requirements of riboflavin in the elderly do not differ from those of young adults.

The effect of exercise on the riboflavin status of adult men.

Six sedentary to moderately active men with biochemical signs of riboflavin deficiency were studied under metabolic ward conditions to examine the effects of physical activity on riboflavin status. All participants were subjected to additional exercise (EXER) for an 18 d period between two maintenance (M1 and M2) periods (16 and 13 d respectively) of habitual physical activity. Energy balance and riboflavin intake were maintained throughout the study. Riboflavin status, as judged by a significant reduction in erythrocyte glutathione reductase (EC 1.6.4.2) activation coefficient (EGR-AC), improved on changing from home (1.53 (SD 0.14)) to period M1 (1.36 (SD 0.21)) diets. The exercise period, however, resulted in a significant deterioration in riboflavin status (1.57 (SD 0.31)) which persisted in the subsequent period M2 (1.54 (SD 0.15)). There was a concomitant fall in the urinary excretion of riboflavin only in the EXER period, when results were expressed as a percentage of the dietary intake of riboflavin. These results suggest an increased demand for the vitamin for selective biochemical functions during exercise. However, the energy cost of walking (treadmill 4 km/h), 50 W and 100 W work-loads (bicycle ergometer) as well as delta mechanical efficiency (DME) did not change during the three metabolic periods. The urinary excretion of riboflavin was inversely related to DME (r -0.49; P < 0.05) and directly correlated with haemoglobin levels (r 0.63; P < 0.005). The present study suggests that riboflavin status further deteriorates during a short period of increased physical activity in individuals whose riboflavin status is marginal.