The discovery and characterization of riboflavin.

The first observation of a pigment in milk with yellow-green fluorescence can be traced to the English chemist Alexander Wynter Blyth in 1872, but it was not until the early 1930s that the substance was characterized as riboflavin. Interest in accessory food factors began in the latter half of the 19th century with the discovery of the first vitamin, thiamin. Thiamin was water soluble and given the name vitamin B(1). However, researchers realized that there were one or more additional water-soluble factors and these were called the vitamin B-2 complex. The search to identify these accessory food factors in milk, whole wheat, yeast, and liver began in the early 1900s. As there is no classical nutritional disease attributable to riboflavin deficiency, it was the growth-stimulating properties of the food extracts given to young rats that provided the tool with which to investigate and eventually extract riboflavin. Riboflavin was the second vitamin to be isolated and the first from the vitamin B-2 complex; the essential nature of the vitamin as a food constituent for man was shown in 1939.

Riboflavin supplementation does not attenuate hyperoxic lung injury in transgenic (spc-mt)hGR mice.

The aims of this study were to test the hypothesis that mice expressing mitochondrially targeted human glutathione reductase (GR) driven by a surfactant protein C promoter ((spc-mt)hGR) are functionally riboflavin deficient and that this deficiency exacerbates hyperoxic lung injury. The authors further hypothesized that dietary supplementation with riboflavin (FADH) will improve the bioactivity of GR, thus enhancing resistance to hyperoxic lung injury. Transgenic (mt-spc)hGR mice and their nontransgenic littermates were fed control or riboflavin-supplemented diets upon weaning. At 6 weeks of age the mice were exposed to either room air (RA) or >95% O(2) for up to 84 hours. GR activities (with and without exogenous FADH) and GR protein levels were measured in lung tissue homogenates. Glutathione (GSH) and glutathione disulfide (GSSG) concentrations were assayed to identify changes in GR activity in vivo. Lung injury was assessed by right lung to body weight ratios and bronchoalveolar lavage protein concentrations. The data showed that enhanced GR activity in the mitochondria of lung type II cells does not protect adult mice from hyperoxic lung injury. Furthermore, the addition of riboflavin to the diets of (spc-mt)hGR mice neither enhances GR activities nor offers protection from hyperoxic lung injury. The results indicated that modulation of mitochondrial GR activity in lung type II cells is not an effective therapy to minimize hyperoxic lung injury.

Long-term intermittent multiple micronutrient supplementation enhances hemoglobin and micronutrient status more than iron + folic acid supplementation in Bangladeshi rural adolescent girls with nutritional anemia.

Previous short-term supplementation studies showed no additional hematologic benefit of multiple micronutrients (MMN) compared with iron + folic acid (IFA) in adolescent girls. This study examines whether long-term once- or twice-weekly supplementation of MMN can improve hemoglobin (Hb) and micronutrient status more than twice-weekly IFA supplementation in anemic adolescent girls in Bangladesh. Anemic girls (n = 324) aged 11-17 y attending rural schools were given once- or twice-weekly MMN or twice-weekly IFA, containing 60 mg iron/dose in both supplements, for 52 wk in a randomized double-blind trial. Blood samples were collected at baseline and 26 and 52 wk. Intent to treat analysis showed no significant difference in the Hb concentration between treatments at either 26 or 52 wk. However, after excluding girls with hemoglobinopathy and adjustment for baseline Hb, a greater increase in Hb was observed with twice-weekly MMN at 26 wk (P = 0.045). Although all 3 treatments effectively reduced iron deficiency, once-weekly MMN produced significantly lower serum ferritin concentrations than the other treatments at both 26 and 52 wk. Both once- and twice-weekly MMN significantly improved riboflavin, vitamin A, and vitamin C status compared with IFA. Overall, once-weekly MMN was less efficacious than twice-weekly MMN in improving iron, riboflavin, RBC folic acid, and vitamin A levels. Micronutrient supplementation beyond 26 wk was likely important in sustaining improved micronutrient status. These findings highlight the potential usefulness of MMN intervention in this population and have implications for programming.

Riboflavin status in acutely ill patients and response to dietary supplements.

BACKGROUND: Although a number of studies have reported riboflavin deficiency in free-living older people, no data are available on riboflavin intake and status in older people during acute illness. METHODS: To determine the riboflavin response to dietary supplements during acute illness, 297 hospitalized, acutely ill older patients are randomly assigned to receive a daily oral nutritional supplement containing 1.3 mg of riboflavin or a placebo for 6 weeks. Outcome measures are riboflavin intake and riboflavin biochemical status at baseline, 6 weeks, and 6 months using the erythrocyte glutathione reductase activation coefficient (EGRAC), a measure of riboflavin tissue saturation. EGRAC values are inversely proportional to riboflavin status. RESULTS: Fifty-six percent of patients (167/297) have suboptimal riboflavin status (EGRAC > 1.30). No significant correlation is found between EGRAC and either total energy or riboflavin intakes. Significant correlations are found between total energy intake and riboflavin intakes both in hospital and at home (r = 0.67, P < .0001 and r = 0.57, P < .0001, respectively). Smokers and patients with chronic obstructive pulmonary disease (COPD) have lower riboflavin status (high EGRAC values) compared with nonsmokers and those without COPD. Riboflavin status improves significantly in the supplement group at 6 weeks compared with the placebo group, but status declines between 6 weeks and 6 months, after patients stop taking the supplements. CONCLUSIONS: A high proportion of acutely ill patients have suboptimal riboflavin status. Supplementation with a physiological amount of riboflavin in a mixed-nutrient supplement significantly improves riboflavin status, but the effect is transient and status deteriorates again after patients stop taking the supplements.

Supplementation with iron and riboflavin enhances dark adaptation response to vitamin A-fortified rice in iron-deficient, pregnant, nightblind Nepali women.

BACKGROUND: Nightblindness affects 16-52% of pregnant women in areas of Nepal and in some cases persists after vitamin A treatment. Iron and riboflavin affect vitamin A utilization and photoreceptor function, respectively, and pilot data in the study population showed a high prevalence of iron and riboflavin deficiencies. OBJECTIVE: The objective was to assess the effect of supplemental iron and riboflavin on pupillary threshold (PT) and plasma retinol in nightblind, pregnant Nepali women given vitamin A-fortified rice. DESIGN: Nightblind pregnant women were randomly assigned to receive, 6 d/wk under supervision for 6 wk, a vitamin A-fortified rice curry dish providing 850 microg retinal activity equivalents/d with either a 30-mg Fe and 6-mg riboflavin (FeR + VA) capsule or a placebo control (VA only) capsule. Hemoglobin, erythrocyte riboflavin, and plasma ferritin and retinol were measured before and after the intervention. Dark adaptation was assessed by PT score. RESULTS: Women who were iron deficient at baseline (n=38) had significantly greater improvement in PT score with iron and riboflavin supplementation than without (P=0.05). Iron and riboflavin supplements significantly reduced the prevalences of riboflavin deficiency (from 60% to 6%; P<0.0001), iron deficiency anemia (from 35% to 15%; P<0.007), and abnormal PT (from 87% to 30%; P<0.05) from baseline. Mean increases in erythrocyte riboflavin (P<0.0001) and plasma ferritin (P=0.01) were greater in the FeR + VA group than in the VA only group. CONCLUSIONS: Iron deficiency may limit the efficacy of vitamin A to normalize dark adaptation in pregnant Nepali women. Further studies are needed to assess the effect of simultaneous delivery of iron and vitamin A for the treatment of nightblindness.

Biochemical indices and neuromuscular function tests in rural Gambian schoolchildren given a riboflavin, or multivitamin plus iron, supplement.

Ninety preselected children, aged between 8 and 14 years, living in two rural West African (Gambian) villages, were randomly divided into three groups, matched for age and sex. One group received a placebo (lactose) tablet, one received riboflavin (5 mg) on 5 d every week, which was sufficient to correct an endemic riboflavin deficiency, and one received a multivitamin supplement (Protovit; Hoffmann La Roche), on 5 d every week, together with FeSO4 (200 mg) once weekly, and the supplements were given for 1 year. Neuromuscular tests, including arm tremor and manipulative skills, were performed on three occasions: once just before the introduction of the supplements; again 6 weeks after commencing the supplements; and again 1 year later. Venous blood samples were collected at the same time as the first two sets of neuromuscular tests. These samples were used for haematology and nutrient status indices: plasma ferritin, ascorbic acid, cyanocobalamin and pyridoxal phosphate, and erythrocyte tests for folate status, for riboflavin status (erythrocyte glutathione reductase activation coefficient) and thiamine status (erythrocyte transketolase activation coefficient). The riboflavin in both supplements achieved a clear-cut response in biochemical status, which was dose-dependent. The pyridoxine, ascorbic acid and Fe components of the multivitamin also affected the associated biochemical indices. Although overall the arm tremor and related neuromuscular function tests did not respond significantly to the supplements, significant improvement was seen in the boys for the arm-tremor test in both the supplemented groups.

Riboflavin requirement of Filipino women.

The level of riboflavin intake that will correct riboflavin deficiency in seven non-pregnant and in twelve pregnant Filipino women was determined in order to reassess the adequacy of the current Recommended Dietary Allowance (RDA) for riboflavin in Filipinos. Increasing levels of riboflavin were given to the subjects who were rated as riboflavin-deficient based on an initial erythrocyte glutathione reductase activation coefficient (EGR-AC) of greater than or equal to 1.3 in screening. The minimum riboflavin requirement, defined as the intake of riboflavin required to achieve an EGR-AC of less than 1.3, was estimated from the regression of EGR-AC on riboflavin intake (mg/1000 kcal). The estimates of minimum riboflavin requirement from the non-pregnant women ranged from 0.16 to 0.42 with a mean of 0.35 +/- 0.09 (SD) mg/1000 kcal. For the pregnant subjects, the estimates of minimum riboflavin requirement ranged from 0.36 to 0.81 with a mean of 0.58 +/- 0.18 (SD) mg/1000 kcal. Adding 30% to the mean, to cover the upper limits of 97.5% of the population, the estimated RDA for non-pregnant women is 0.46/1000 kcal. This value is approximately equal to the 1976 Philippine RDA of 0.5 mg riboflavin/1000 kcal. For pregnant women, adding 30% to the mean minimum requirement of 0.58 mg/1000 kcal, the estimated RDA is 0.75 mg/1000 kcal or 1.75 mg/day computed at the energy allowance of 2350 kcal during pregnancy. This value is 25% higher than the current Philippine RDA of 1.4 mg/day for pregnant women.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of a multivitamin and iron supplement on running performance in Gambian children.

Forty boys and girls between 11 and 14.5 years with evidence of subclinical vitamin deficiencies were allocated to two groups to receive, twice weekly, either a placebo or a multivitamin and iron supplement. Prior to supplementation and on two subsequent occasions about 5 weeks apart, the children performed an exercise regimen on a treadmill during which expired air was collected and heart rate monitored. The supplement resulted in marked improvements in riboflavin and vitamin C status and checked the decline in iron stores seen in the unsupplemented children. During the study the running performance of unsupplemented children deteriorated, and markedly so in a subgroup with initially poor nutrient status. The vitamin and iron supplement prevented this deterioration so as to produce a significant reduction in the energy cost of treadmill running in the more malnourished subgroup, relative to the changes seen in children receiving no supplement.

Protective effect of riboflavin on suppression of growth caused by oxidized oil.

When oxidized corn oil (100 nmol in terms of malondialdehyde/day/rat) was administered to a riboflavin-deficient rat, the body weight gain was markedly suppressed. However, when 20 microgram of riboflavin/day/rat was administered with the oxidized corn oil, reasonable growth and normal flavin levels in the liver, kidney and heart could be attained, though they were somewhat less than those of the animals fed on the normal diet containing non-oxidized corn oil. It was noted that the elevation of lipid peroxide level in blood plasma of animals administered with the oxidized oil was effectively prevented by riboflavin. These results indicate the protective effect of riboflavin on suppression of growth caused by the oxidized oil.

The effects of riboflavin administration on iron metabolism parameters in a school-going population.

The effect of riboflavin administration on iron metabolism was studied in a group of riboflavin-deficient children with Erythrocyte Glutathione Reductase (EC 1.6.4.2) reactivation above 1.20. The results have shown that the administration of riboflavin has resulted in a decrease of serum iron as well as in transferrin saturation which was accompanied by an increase in blood hemoglobin in subjects with initially lower hemoglobin values (less than or equal to 13.5 g/100 ml). There was, however, no change in blood hemoglobin in the group with initially higher hemoglobin values (greater than or equal to 14.0 g/100 ml). The results suggest that inadequate riboflavin intake may affect the iron utilization. The possible mechanism of riboflavin action on iron utilization is discussed.

NADH-FMN oxidoreductase activity and iron content of organs from riboflavin and iron-deficient rats.

NADH-FMN oxidoreductase has been proposed as an enzyme involved in the release of iron from ferritin. The effects of riboflavin and/or iron deficiencies and of dietary allopurinol on the activities of this enzyme and on the iron contents of liver, kidney and duodenum were investigated. Allopurinol, a xanthine oxidase inhibitor, did not affect organ enzyme activities nor iron contents. Riboflavin-deficient rats and iron-deficient rats both had significantly lower organ enzyme activities and iron contrnts than controls. Organ enzyme activities and iron contents of rats fed a diet deficient in both iron and riboflavin were significantly lower than those of controls. After dietary iron and/or riboflavin repletion, organ enzyme activities and iron contents increased. Rats fed an irons-overload diet had enzyme activities similar to that of controls, but organ iron contents were significantly increased over those of controls. Effects of riboflavin and/or deficiencies in rats on NADH-FMN oxidoreductase activities and iron contents of liver, kidney and duodenum appeared to be reversible by riboflavin and/or iron supplementation. The data support the view that NADH-FMN oxidoreductase may be a controlling enxyme in iron release from ferritin.

Controlled trial of combinations of hydroxocobalamin-cystine and riboflavine-cystine, in Nigerian ataxic neuropathy.

Chronic cyanide intoxication of dietary origin and riboflavine deficiency are believed to be major aetiological factors in Nigerian tropical ataxic neuropathy. The results are presented of a double-blind controlled therapeutic trial of combinations of large doses of hydroxocobalamin and cystine as cyanide binding agents together with riboflavine or placebos in Nigerian patients suffering from the tropical ataxic neuropathy. No clinical benefit was demonstrable with any of the treatments.