Article

Correcting a marginal riboflavin deficiency improves hematologic status in young women in the United Kingdom (RIBOFEM)

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Abstract

Moderate riboflavin deficiency is prevalent in certain population groups in affluent countries, but the functional significance of this deficiency is not clear. Studies have indicated a role for riboflavin in the absorption and use of iron. We investigated the effect of riboflavin supplementation on hematologic status in a group of moderately riboflavin-deficient women aged 19-25 y in the United Kingdom. One hundred twenty-three women with biochemical evidence of riboflavin deficiency [erythrocyte glutathione reductase activation coefficient (EGRAC) >1.40] were randomly assigned to receive 2 or 4 mg riboflavin or a placebo for 8 wk. Measurements of hematologic status were made pre- and postsupplementation, and dietary intakes were also assessed; iron absorption was measured in a subgroup of women. One hundred nineteen women completed the intervention. The use of a riboflavin supplement for 8 wk elicited a significant improvement in riboflavin status with a dose response (P < 0.0001). For women who received supplemental riboflavin, an increase in hemoglobin status correlated with improved riboflavin status (P < 0.02). Women in the lowest tertile of riboflavin status at baseline (EGRAC >1.65) showed a significantly greater increase in hemoglobin status in response to the supplement than did women in the first and second tertiles (P < 0.01). Dietary iron intake and iron absorption did not change during the study. Moderately poor riboflavin status can affect iron status: the lower the riboflavin status, the greater the hematologic benefits of improving status. The results also suggest that consideration should be given to raising the currently accepted EGRAC threshold for deficiency. This trial was registered at controlled-trials.com as ISRCTN35811298.

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... Dietary data from the National Health and Nutrition Examination Surveys (NHANES) in the USA also show that adolescents are at higher risk of nutritional deficiencies than other age groups in the population [2] . Some of these deficiencies may be of particular functional importance to adolescent females given that they are of childbearing age and that low micronutrient intakes in this group influence risk of anaemia, peak bone mass attainment and adverse effects in the offspring [3][4][5][6][7]. ...
... Participants had to be female, aged between 16 and 19 years at the time of recruitment, who self-reported missing breakfast at least 4 times a week. They had to have no diagnosed illness and have low measures of riboflavin status and haemoglobin, as these have previously been found to track well with self-reported breakfast skipping [3]. ...
... Samples with a low riboflavin status have a higher EGRAC value. An EGRAC value of >1.30 is conventionally used to indicate poor riboflavin status [3]. In this study, girls with an EGRAC value >1.40 and a hemoglobin of <137 g/L were eligible for the main study. ...
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Background Poor micronutrient status is reported among adolescents across Europe and USA. This may be related to the well-documented decline in the regular consumption of breakfast by this group. The regular consumption of a breakfast cereal offers a possible means to improve micronutrient status; fortified cereal is likely to have enhanced benefit. A study was conducted to determine the efficacy of the regular consumption of a fortified cereal with milk, compared with unfortified cereal, consumed either as a breakfast or a supper, in improving micronutrient intake and micronutrient status of adolescent girls. Methods A randomised, double-blind, placebo-controlled intervention trial was conducted in girls recruited at ages 16–19 years, from schools and colleges in Sheffield, UK. Girls were randomised to receive 50 g fortified or unfortified cereal, with 150 ml semi-skimmed milk, daily, for 12 weeks, as a breakfast or as a supper. Dietary intake was estimated using a 4-d food diary and blood collected for the assessment of nutritional status. Within-group changes were tested using a paired sample t test; two-way ANOVA was used to analyse effects of the intervention, with cereal type and time of consumption as factors, correcting for baseline values. The analysis was conducted on 71 girls who completed the study. Results Consumption of unfortified cereal elicited an increase in the intake of vitamins B1, B2 and B6; consumption of fortified cereal elicited increases in vitamins B1, B2, B6, B12, folate and iron (P < 0.001) and of vitamin D (P = 0.007), all increases were significantly greater than for unfortified cereal. Consumption of the fortified cereal also led to a significant improvement in biomarkers of status for vitamins B2, B12, folate and of iron, compared with girls receiving the unfortified cereal, and maintained vitamin D status, in contrast with the girls receiving the unfortified cereal (P < 0.001). Conclusions The daily consumption of cereal with milk for 12 weeks by adolescent girls, increased intakes of micronutrients. The consumption of fortified cereal elicited greater increases than for unfortified cereal and improved biomarkers of micronutrient status. The findings justify strategies to encourage the consumption of fortified cereal with milk by adolescents, either as a breakfast or a supper. Trial registration Registered with Current Controlled Trials (Registration: ISRCTN55141306)
... As an example, they are crucial for the synthesis, conversion and recycling of niacin, folate and vitamin B 6 , and for the synthesis of all heme proteins, including hemeglobin, nitric oxide synthases, P450 enzymes, and proteins involved in electron transfer and oxygen transport and storage [11]. The flavoproteins are also co-factors in the metabolism of essential fatty acids in brain lipids [12], the absorption and utilisation of iron [43], and the regulation of thyroid hormones [11]. Dysregulation of any of these processes by riboflavin deficiency would be associated with its own broad negative consequences for brain function. ...
... With regards to riboflavin, the highest of two doses (4 mg/day, i.e., 3ˆRDA) administered for eight weeks to young females had the greatest effects both on riboflavin status and benefits to haematological parameters [43]. It is also notable that, whilst riboflavin has no demonstrable toxicity, the maximum daily intestinal absorption is approximately 20 times the RDA of 1.3 mg. ...
... Some supportive evidence does exist that shows that several of this group can modulate peripheral cardiovascular and gluco-regulatory function-and it is certainly the case that modulation of these parameters should have an impact on brain function. For instance, administration of 1.6 mg/day of riboflavin attenuated the hypertensive effect of the MTHFR 677TT genotype [140] and up to 4 mg/day led to dose-related increases in the number of circulating red blood cells and the concentration of haemoglobin [43]. Additionally, large doses (60+ˆRDA) of biotin, with [141,142] or without additional chromium [143,144] have been shown to improve glycaemic control and/or insulin sensitivity in sufferers from diabetes. ...
Article
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The B-vitamins comprise a group of eight water soluble vitamins that perform essential, closely inter-related roles in cellular functioning, acting as co-enzymes in a vast array of catabolic and anabolic enzymatic reactions. Their collective effects are particularly prevalent to numerous aspects of brain function, including energy production, DNA/RNA synthesis/repair, genomic and non-genomic methylation, and the synthesis of numerous neurochemicals and signaling molecules. However, human epidemiological and controlled trial investigations, and the resultant scientific commentary, have focused almost exclusively on the small sub-set of vitamins (B₉/B12/B₆) that are the most prominent (but not the exclusive) B-vitamins involved in homocysteine metabolism. Scant regard has been paid to the other B vitamins. This review describes the closely inter-related functions of the eight B-vitamins and marshals evidence suggesting that adequate levels of all members of this group of micronutrients are essential for optimal physiological and neurological functioning. Furthermore, evidence from human research clearly shows both that a significant proportion of the populations of developed countries suffer from deficiencies or insufficiencies in one or more of this group of vitamins, and that, in the absence of an optimal diet, administration of the entire B-vitamin group, rather than a small sub-set, at doses greatly in excess of the current governmental recommendations, would be a rational approach for preserving brain health.
... Sadowski set an upper limit for adequate riboflavin status of 1.34 based on the mean EGRac + 2 SD of a group of healthy older adult men and women (aged ≥ 60 y; n = 927) from the Boston Nutritional Status Survey (48). Accordingly, many have considered EGRac > 1.40 (2,14,49) and ≥1.40 (13,20,29,35,42) as a cutoff for deficiency, but even higher cutoffs have been used (12,50). ...
... MCV, mean corpuscular volume; RBP, retinol-binding protein; sTfR, soluble transferrin receptor. 2 Values are means ± SDs. 3 Values are n (%). 4 Values are medians (IQRs). 5 Ferritin and RBP were adjusted for subclinical inflammation with use of AGP and CRP biomarkers (33,34). ...
... A study conducted in the United Kingdom in n = 123 women (aged 19-25 y), all of whom had baseline EGRac > 1.40, reported a negative correlation between hemoglobin and EGRac (n = 117; r = −0.22, P = 0.016) (2). The study also showed a significant improvement in riboflavin status (decreased EGRac values) after 8 wk of riboflavin supplementation (2 or 4 mg/d) with a dose-dependent response. ...
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Background: Riboflavin is required for several redox reactions. Clinical riboflavin deficiency occurs mainly in low-income countries, where it is associated with anemia. The functional significance of suboptimal riboflavin status in different populations and its role in anemia is not well understood. Objectives: We assessed the biomarker status of riboflavin and its association with hemoglobin concentration and anemia in women living in Vancouver, Canada, and Kuala Lumpur, Malaysia. Methods: Healthy nonpregnant, nonbreastfeeding women (19-45 y) were recruited from Canada ( n = 206) and Malaysia (n = 210) via convenience sampling. Fasting blood was collected to assess riboflavin status [erythrocyte glutathione reductase activity coefficient (EGRac)], hematological indicators, soluble transferrin receptor (sTfR), ferritin, vitamin A, folate, and vitamin B-12 concentrations. Linear and logistic regression models were used to assess the association of riboflavin status with hemoglobin concentration and anemia. Results: EGRac (mean ± SD) values were higher, indicating poorer riboflavin status, in Malaysian compared with Canadian women (1.49 ± 0.17 compared with 1.38 ± 0.11). Likewise, riboflavin biomarker deficiency (EGRac ≥1.40) was significantly more prevalent among Malaysians than Canadians (71% compared with 40%). More Malaysian than Canadian women were anemic (hemoglobin <120 g/L; 18% compared with 7%). With use of linear regression (pooled sample; n = 416), EGRac values were negatively associated with hemoglobin concentration (r = -0.18; P < 0.001). This relation remained significant (P = 0.029) after adjusting for age, parity, ethnicity, vitamin B-12, folate, sTfR, ferritin, and vitamin A. Women with riboflavin deficiency (EGRac ≥1.40) were twice as likely to present with anemia (adjusted OR: 2.38; 95% CI: 1.08, 5.27) compared with women with EGRac <1.40. Conclusions: Biochemical riboflavin deficiency was observed in Canadian and Malaysian women, with higher rates of deficiency among Malaysian women. Deficient biomarker status of riboflavin was a weak but significant predictor of hemoglobin and anemia, suggesting that the correction of riboflavin deficiency may potentially play a small protective role in anemia, but this requires further investigation.
... Flavin-dependent enzymes that can mobilize iron from ferritin have been shown to be sensitive to riboflavin depletion in animal models [84]. And repleting vitamin B6 caused an increase in ferritin [85]. ...
... Supplementing with the vitamin may decrease the frequency and severity of asthma attacks [94]. As we mentioned above that Flavin-dependent enzymes that can mobilize iron from ferritin have been shown to be sensitive to riboflavin depletion in animal models [84]. ...
... Deficiencies and dietary inadequacies in vitamins and minerals have been found in other well-nourished populations. For example, a low riboflavin status was found in 57% of young UK women [67], intakes were below the estimated average requirement for thiamine (26%), zinc (39%), vitamins B6 (25%), and vitamin B12 (27%) in young Canadian women with mood disorders [68], 17% of New Zealand women in Dunedin had a zinc status indicative of mild deficiency [69], and magnesium status in 18% of Canadian women of South-Asian background was low [70]. Regarding international surveys, intakes of iodine, magnesium, iron, and vitamin D were considered to be a concern in a review of several European countries [71], and over 30% of community-dwelling older adults had intakes of vitamin D, thiamin, riboflavin, calcium, magnesium, and selenium lower than the EAR [72]. ...
... Nutrient-nutrient interactions can also mean that biochemical deficiency results from the low intake of a nutrient not captured by the NHANES dataset. For example, biochemical riboflavin status, which was not measured within NHANES 2003-2006, can affect iron homeostasis and anemia prevalence [67]. ...
Article
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Certain population sub-groups in the United States are vulnerable to micronutrient malnutrition. Nationally representative data from the National Health and Nutrition Examination Survey (NHANES) describing the biochemical status of vitamins A, B6, B12, C, D, E, folate, and anemia, were aggregated to determine the overall risk of multiple concurrent deficiencies in U.S. children and adults (n = 15,030) aged >9 years. The prevalence of deficiency risk according to socio-demographic, life-stage, dietary supplement use, and dietary adequacy categories was investigated. Thirty-one percent of the U.S. population was at risk of at least one vitamin deficiency or anemia, with 23%, 6.3%, and 1.7% of the U.S. population at risk of deficiency in 1, 2, or 3–5 vitamins or anemia, respectively. A significantly higher deficiency risk was seen in women (37%), non-Hispanic blacks (55%), individuals from low income households (40%), or without a high school diploma (42%), and underweight (42%) or obese individuals (39%). A deficiency risk was most common in women 19–50 years (41%), and pregnant or breastfeeding women (47%). Dietary supplement non-users had the highest risk of any deficiency (40%), compared to users of full-spectrum multivitamin-multimineral supplements (14%) and other dietary supplement users (28%). Individuals consuming an adequate diet based on the Estimated Average Requirement had a lower risk of any deficiency (16%) than those with an inadequate diet (57%). Nearly one-third of the U.S. population is at risk of deficiency in at least one vitamin, or has anemia.
... However, studies with regard to the effects of riboflavin (vitamin B2) on the course of the immune response in deficiency states or low-dose supplementation are limited. Riboflavin deficiency is a common problem concerns not only developing countries, where a high prevalence of B2 deficiency may occur as a result of poor diet, but also affluent countries such as the USA or the UK (2). The importance and commonness of this aspect was emphasized by Powers et al. (2) who reported that riboflavin deficiency was identified in 41% of elderly people and 95% of adolescent girls in the UK. ...
... Riboflavin deficiency is a common problem concerns not only developing countries, where a high prevalence of B2 deficiency may occur as a result of poor diet, but also affluent countries such as the USA or the UK (2). The importance and commonness of this aspect was emphasized by Powers et al. (2) who reported that riboflavin deficiency was identified in 41% of elderly people and 95% of adolescent girls in the UK. Furthermore, Subramanian et al. (3) reported that vitamin B2 deficiency ranged from 15% to 50% among alcohol abusers. ...
Article
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Ariboflavinosis, that is, vitamin B2 deficiency, is a common problem affecting the populations of both developing and affluent countries. Teenagers, elderly people, pregnant women, and alcohol abusers represent groups that are particularly susceptible to this condition. This study was aimed to determine the effect of different riboflavin concentrations (deficiency and supplementation) on macrophages response induced by bacteria or yeast-derived factors i.e. lipopolysaccharide (LPS) and zymosan, respectively. Mouse macrophage RAW 264.7 cells were cultured for 5 days in a medium with a riboflavin concentration corresponding to moderate riboflavin deficiency (3.1 nM), physiological state (10.4 nM), or vitamin pill supplementation (300 nM). On the third or fourth day of deprivation, the medium in some groups was supplemented with riboflavin (300 nM). Macrophages activation were assessed after LPS or zymosan stimulation. Short-term (5 days) riboflavin deprivation resulted in the pathological macrophages activation, manifested especially in a reduction of cell viability and excess release of tumor necrosis factor-α (TNF-α) and high-mobility group box 1 (HMGB1) protein. Moreover, the levels of inducible nitric oxide synthase (iNOS), nitric oxide (NO), heat shock protein (Hsp72), interleukin 1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and interleukin 10 (IL-10) decreased after riboflavin deprivation, but medium enrichment with riboflavin (300 nM) on the third or fourth day reversed this effect. In the riboflavin-supplemented group, LPS-stimulated macrophages showed lower mortality accompanied by higher Hsp72 expression, reduction of Toll-like receptor 4 (TLR4) and TNF-α, and elevation of NO, IL-6, and IL-10. Moreover, the TLR6, NO, iNOS, IL-1β, MCP-1, and the keratinocyte chemoattractant (KC) levels significantly decreased in the zymosan-stimulated groups maintained in riboflavin-enriched medium. We conclude that short-term riboflavin deficiency significantly impairs the ability of macrophages to induce proper immune response, while riboflavin enrichment decreases the proinflammatory activation of macrophages.
... Early animal studies have linked riboflavin deficiency with impaired iron absorption, increased intestinal loss of iron, and/or impaired iron utilisation for the synthesis of Hb (10) . More recently, supplementation with riboflavin has been shown to enhance circulating Hb levels in human subjects (11) furthermore, correcting riboflavin deficiency in individuals who were both riboflavin and iron deficient improved the response of iron deficiency anaemia to iron therapy (12) . Irrefutable evidence has shown the metabolism of other B-vitamins is dependent on riboflavin coenzymes. ...
... EGRac is calculated as a ratio of FAD stimulated to unstimulated enzyme activity, with higher values reflective of lower riboflavin status. However currently there is no consensus as to the appropriate EGRac cut-off values to indicate low/high status, with studies reporting deficiency ranges from >1·2, >1·3 or >1·4 (11,45,46) . Recent changes made to the assay methodology resulted in the acceptance of a cutoff ≥1·3 although others have suggested that this cut-off value should be further increased (46) . ...
Article
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Clinical deficiency of the B-vitamin riboflavin (vitamin B 2 ) is largely confined to developing countries; however accumulating evidence indicates that suboptimal riboflavin status is a widespread problem across the developed world. Few international data are available on riboflavin status as measured by the functional biomarker, erythrocyte glutathione reductase activation coefficient, considered to be the gold standard index. One important role of riboflavin in the form of flavin dinucleotide is as a co-factor for the folate-metabolising enzyme methylenetetrahydrofolate reductase (MTHFR). Homozygosity for the common C677T polymorphism in MTHFR, affecting over 10 % of the UK and Irish populations and up to 32 % of other populations worldwide, has been associated with an increased risk of CVD, and more recently with hypertension. This review will explore available studies reporting riboflavin status worldwide, the interaction of riboflavin with the MTHFR C677T polymorphism and the potential role of riboflavin in personalised nutrition. Evidence is accumulating for a novel role of riboflavin as an important modulator of blood pressure (BP) specifically in individuals with the MTHFR 677TT genotype, with results from a number of recent randomised controlled trials demonstrating that riboflavin supplementation can significantly reduce systolic BP by 5–13 mmHg in these genetically at risk adults. Studies are however required to investigate the BP-lowering effect of riboflavin in different populations and in response to doses higher than 1·6 mg/d. Furthermore, work focusing on the translation of this research to health professionals and patients is also required.
... Intake of dietary protein, or specific amino acids, which may be low in vegetarian diets (17), may also have a role in supporting the immune system, including production or activation of white blood cells (18,19). Other nutrients, such as zinc, vitamin A, and riboflavin, which are less bioavailable in plant-based diets (5,20), have also been linked to blood cell or hemoglobin production (21)(22)(23)(24)(25). ...
... In addition, zinc is a catalyst in iron metabolism (21) and is less bioavailable in vegetarian diets (5), and low serum zinc levels have been associated with anemia (21,22). Vegetarians or vegans also tend to have lower intakes of other micronutrients, such as vitamin A or riboflavin (20), which might also have roles in blood cell or hemoglobin production (24,25). ...
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Background: There may be differences in hematological parameters between meat-eaters and vegetarians. Objective: The aim of this study was to perform cross-sectional analyses of hematological parameters by diet group in a large cohort in the United Kingdom. Methods: A complete blood count was carried out in all UK Biobank participants at recruitment (2006-2010). We examined hemoglobin, red and white blood cell counts, and platelet counts and volume in regular meat eaters (>3 times/wk of red/processed meat consumption, n = 212,831), low meat eaters (n = 213,092), poultry eaters (n = 4815), fish eaters (n = 10,042), vegetarians (n = 6548), and vegans (n = 398) of white ethnicity and meat eaters (n = 3875) and vegetarians (n = 1362) of British Indian ethnicity. Results: In both white and British Indian populations, compared with regular meat eaters (or meat eaters in Indians), the other diet groups had up to 3.7% lower age-adjusted hemoglobin concentrations (difference not significant in white vegan women) and were generally more likely to have anemia (e.g., 8.7% of regular meat eaters compared with 12.8% of vegetarians in white premenopausal women; P < 0.05 after Bonferroni correction). In the white population, compared with regular meat eaters, all other diet groups had lower age- and sex-adjusted total white cells, neutrophils, lymphocytes, monocytes, and eosinophils (P-heterogeneity < 0.001 for all), but basophil counts were similar across diet groups; in British Indians, there was no significant difference in any of the white blood cell counts by diet group. Compared with white regular meat eaters, the low meat eaters, poultry eaters, fish eaters, and vegans had significantly lower platelet counts and higher platelet volume, whereas vegetarians had higher counts and lower volume. Compared with British Indian meat eaters, vegetarians had higher platelet count and lower volume. Conclusions: In the UK Biobank, people with low or no red meat intake generally had lower hemoglobin concentrations and were slightly more likely to be anemic. The lower white blood cell counts observed in low and non-meat eaters, and differences in mean platelet counts and volume between diet groups, warrant further investigation. This observational study was registered at http://www.isrctn.com/ as ISRCTN10125697.
... Clinical symptoms of riboflavin deficiency appear only after several months of insufficient riboflavin intake, and vary from milder symptoms as sore throat, loss of hair, and skin inflammation, to severe symptoms as swollen tongue, anemia and impaired nerve functions. Although these symptoms are rarely seen in non-developing countries and well-nourished societies, dietary insufficiency and subclinical riboflavin deficiency is detected in remarkably large groups in the population [26][27][28][29]. Several population studies of vitamin status report on riboflavin insufficiency in children and young adults, especially in young women [30]. ...
... The increase of riboflavin insufficiency in both boys and girls is comparable to a declined consumption of milk, from 25% of the daily riboflavin intake in the 4-6-year-olds to only 10% of the daily riboflavin intake in the 15-18-year-olds. The implications for this riboflavin insufficiency, especially in young girls, are not fully known, but it has been shown that subclinical riboflavin deficiency could influence iron handling and that a daily supplement with riboflavin (2 or 4 mg) for 8 weeks significantly improves the hematologic status, with an increase in circulating red blood cells and hemoglobin concentrations in young women, even without an additional iron supplementation [28]. ...
Article
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As an essential vitamin, the role of riboflavin in human diet and health is increasingly being highlighted. Insufficient dietary intake of riboflavin is often reported in nutritional surveys and population studies, even in non-developing countries with abundant sources of riboflavin-rich dietary products. A latent subclinical riboflavin deficiency can result in a significant clinical phenotype when combined with inborn genetic disturbances or environmental and physiological factors like infections, exercise, diet, aging and pregnancy. Riboflavin, and more importantly its derivatives, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), play a crucial role in essential cellular processes including mitochondrial energy metabolism, stress responses, vitamin and cofactor biogenesis, where they function as cofactors to ensure the catalytic activity and folding/stability of flavoenzymes. Numerous inborn errors of flavin metabolism and flavoenzyme function have been described, and supplementation with riboflavin has in many cases been shown to be lifesaving or to mitigate symptoms. This review discusses the environmental, physiological and genetic factors that affect cellular riboflavin status. We describe the crucial role of riboflavin for general human health, and the clear benefits of riboflavin treatment in patients with inborn errors of metabolism.
... RF is also a water-soluble and heat-stable essential vitamin, as well as an often-neglected antioxidant (2). Studies have shown that higher dietary RF intake showed beneficial anti-aging (3) and anti-cancer effects (4,5), while insufficient RF intake was associated with increased risks of various diseases, including anemia (6) and cardiovascular diseases (7). ...
... To normalize between-run variability, each assay plate contained 8 control DNA. The inter-assay coefficient of variation was 6 ...
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Background Dietary habits and dietary intake affect telomere length, a reliable marker of biological aging and a predictor of chronic disease. Riboflavin (RF) is known as a water-soluble antioxidant vitamin, but its role in telomere length maintenance has yet to be elucidated. Objective The purpose of this study was to examine the relationship between dietary RF intake and telomere length in a nationally representative sample of adults. Methods Using the NHANES (1999–2002), telomere data of 4,298 participants aged ≥45 years were analyzed in a cross-sectional manner. Leukocyte telomere length was measured using the quantitative real-time polymerase chain reaction (qPCR). Dietary RF intake was assessed by a trained interviewer using 24-h dietary recall method. Generalized linear regressions were performed to evaluate the association between dietary RF intake and telomere length. Subgroup analyses were performed to further explore this relationship in sex and body mass index (BMI) subgroups. Results Among the 3,788 participants included, the average telomere length was longer in females ( P = 0.014), while they had a lower average RF intake compared to males ( P < 0.001). There was a weak positive correlation between RF intake and telomere length both when unadjusted (β = 0.011; P = 0.037) and adjusted for age, sex, and ethnicity (β = 0.013; P = 0.033). Subgroup analyses showed a positive association between RF intake and the telomere length in female after adjusting for confounding factors (β = 0.029; P = 0.046). In the female subgroup, there were significant positive relationships between telomere length and RF intake in the obese group (β = 0.086, P = 0.022). Conclusion Increased dietary RF intake was significantly associated with longer telomere length in middle-aged and older American females, especially in low RF intake obese female.
... • Improved hematological response 190 • Prevention of migraine 191 • Improved refractory infectious keratitis and non-healing ulcers when combined with ultraviolet A therapy 192,193 • Improved neonatal jaundice 194 • Pellagra (photosensitive pigmented dermatitis, diarrhea, and dementia; may progress to death) 195 • Neurologic symptoms including insomnia, anxiety, disorientation, delusions, dementia, and encephalopathy 196 • Pronounced watery diarrhea and colitis 196 • Cheilosis, angular fissures, atrophy of the tongue, hypertrophy of the fungiform papillae and painful inflammation of the mouth 195 Benefits from Supplementation A) In Vitro/In Vivo • Antioxidant effects 197 • Anti-inflammatory effects 198 • Anti-thrombotic effects 199 ...
Article
Over‐nutrition and its late consequences are a dominant theme in medicine today. In addition to the health hazards brought on by over‐nutrition, the medical community has recently accumulated a roster of health benefits with obesity, grouped under “obesity paradox”. Throughout the world and throughout history until the 20th century, under‐nutrition was a dominant evolutionary force. Under‐nutrition brings with it a mix of benefits and detriments that are opposite to and continuous with those of over‐nutrition. This continuum yields J‐shaped or U‐shaped curves relating body mass index to mortality. The overweight have an elevated risk of dying in middle age of degenerative diseases while the underweight are at increased risk of premature death from infectious conditions. Micronutrient deficiencies, major concerns of nutritional science in the 20th century, are being neglected. This “hidden hunger” is now surprisingly prevalent in all weight groups, even among the overweight. Because micronutrient replacement is safe, inexpensive, and predictably effective, it is now an exceptionally attractive target for therapy across the spectrum of weight and age. Nutrition‐related conditions worthy of special attention from caregivers include excess vitamin A, excess vitamin D and deficiency of magnesium.
... There is a further potential confounder in determining which patients might eventually develop clinical cobalamin deficiency, which relates to unrecognized deficiency of riboflavin. When riboflavin status is examined with the use of the functional marker, erythrocyte glutathione reductase activation coefficient (EGRAC), many young women have been identified as deficient, and the lower the riboflavin status, the greater the effect on hemoglobin concentrations with riboflavin supplementation (12). In addition, riboflavin status affects serum Hcy values in patients with the methylenetetrahydrofolate reductase polymorphism 677C→T, and the methionine synthase polymorphism 66A→G, and the cobalamin status affects Hcy concentrations in the latter polymorphism as well (13). ...
... Suboptimal riboflavin status occurs in children, elderly and women worldwide, particularly in regions with low intakes of dairy products and meat (1)(2)(3)(4)(5)(6) . Riboflavin is an essential precursor for the biosynthesis of FMN and FAD. ...
Article
Suboptimal vitamin B 2 status is encountered globally. Riboflavin deficiency depresses growth and results in a fatty liver. The underlying mechanisms remain to be established and an overview of molecular alterations is lacking. We investigated hepatic proteome changes induced by riboflavin deficiency to explain its effects on growth and hepatic lipid metabolism. In all, 360 1-d-old Pekin ducks were divided into three groups of 120 birds each, with twelve replicates and ten birds per replicate. For 21 d, the ducks were fed ad libitum a control diet (CAL), a riboflavin-deficient diet (RD) or were pair-fed with the control diet to the mean daily intake of the RD group (CPF). When comparing RD with CAL and CPF, growth depression, liver enlargement, liver lipid accumulation and enhanced liver SFA (C6 : 0, C12 : 0, C16 : 0, C18 : 0) were observed. In RD, thirty-two proteins were enhanced and thirty-one diminished (>1·5-fold) compared with CAL and CPF. Selected proteins were confirmed by Western blotting. The diminished proteins are mainly involved in fatty acid β -oxidation and the mitochondrial electron transport chain (ETC), whereas the enhanced proteins are mainly involved in TAG and cholesterol biosynthesis. RD causes liver lipid accumulation and growth depression probably by impairing fatty acid β -oxidation and ETC. These findings contribute to our understanding of the mechanisms of liver lipid metabolic disorders due to RD.
... Vitamin B 2 is present in a wide variety of animal and plant foods, such as liver, dairy products, and leafy vegetables. Low intake of dairy products, excessive alcohol consumption, and certain diseases may contribute to vitamin B 2 deficiency, characterized by anemia, angular cheilitis, cataracts, seborrheic dermatitis, and growth retardation (Kennedy, 2016;MacMillan et al., 2017;Mazur-Bialy & Pocheć, 2017;Mazur-Bialy, Pochec, & Plytycz, 2015;Powers et al., 2011;Qi, Kniazeva, & Han, 2017;Thomas & Mirowski, 2010). Therefore, vitamin B 2 supplementation is particularly important for individuals with vitamin B 2 deficiency. ...
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Vitamin B2 (riboflavin) is a water-soluble vitamin that has important roles in human health. In this study, we developed a sensitive and specific monoclonal antibody-based indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) and lateral-flow immunochromatographic assay (ICA) strip for the rapid detection of vitamin B2. Following routine fusion and selection, the optimum monoclonal antibody against vitamin B2 was obtained. The 50% inhibitory concentration and limit of detection of ic-ELISA were 8.18 and 1.80 ng/mL, respectively. The cut-off value of the lateral-flow ICA strip was 50 ng/mL. The results revealed that our developed methods are suitable for the on-site detection and mass screening of vitamin B2 in food and pharmaceutical products.
... In order to understand the importance of adequate ingestion of riboflavin, numerous animals studies have been performed to study the consequences of its absence in diets (6)(7)(8)(9) . Extreme riboflavin deficiency, called ariboflavinosis, can cause many disorders such as reduced growth rates, oral lesions including cracked and red lips, glossitis, angular cheilitis, atrophy of taste buds, ulcers and sore throat (10,11) , and hyperhomocysteinaemia (12) , among others. ...
Article
Inflammatory bowel diseases (IBD) are idiopathic diseases of the gastrointestinal tract characterised by recurrent inflammation that require lifelong treatments. It has been shown that certain strains of lactic acid bacteria (LAB) can produce specific health-promoting compounds in foods or in the gastrointestinal tract that can in turn prevent and/or treat IBD. This study was designed to evaluate the possible therapeutic potential of soymilk fermented by the riboflavin-producing strain Lactobacillus plantarum CRL 2130 in a trinitrobenzene sulfonic induced colitis mouse model. Mice that received soymilk fermented by L. plantarum CRL 2130 showed a decrease in weight loss, lower damage scores in their large intestines, lower microbial translocation to liver and decreased cytokines levels in their intestinal fluids compared to animals that received unfermented soymilk or soymilk fermented by a nonriboflavin- producing L. plantarum strain. This is the first report that demonstrates that a riboflavin-producing LAB was able to prevent experimental colitis in a murine model.
... As regards association between EGRAC and some other health parameters, in a randomised controlled trial (RCT) in 123 women with EGRAC > 1.4, supplementation with 2 or 4 mg/day riboflavin for 8 weeks, compared with placebo, in addition to a mean intake of 1.1-1.3 mg/day according to groups, did not lead to any significant change in any of the haematologic markers investigated (Powers et al., 2011). However, in this study, a significant positive relationship (p < 0.02) was observed between baseline EGRAC and the change in haemoglobin concentration in the 4 mg/day group or both supplemented groups combined (but not in the 2 mg/day group). ...
Technical Report
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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.
... In the present study, it is noted that the expression of ferritin (FTH1), a protein functioning in maintaining iron homeostasis, was significantly decreased at the protein level, indicating that riboflavin deficiency can impact significantly on iron absorption and utilization 48,49 . Powers et al. 5 also demonstrated that riboflavin alone without iron supplementation was effective in improving hematologic status in young women in the United Kingdom. Therefore, riboflavin is one of the determinants in the prevention of anemia. ...
Article
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Riboflavin deficiency is widespread in many regions over the world, especially in underdeveloped countries. In this study, we investigated the effects of riboflavin deficiency on protein expression profiles in HepG2 cells in order to provide molecular information for the abnormalities induced by riboflavin deficiency. HepG2 cells were cultured in media containing different concentrations of riboflavin. Changes of cell viability and apoptosis were assessed. A comparative proteomic analysis was performed using a label-free shotgun method with LC–MS/MS to investigate the global changes of proteomic profiles in response to riboflavin deficiency. Immunoblotting test was used to validate the results of proteomic approach. The cell viability and apoptosis tests showed that riboflavin was vital in maintaining the cytoactivity of HepG2 cells. The label-free proteomic analysis revealed that a total of 37 proteins showing differential expression (±2 fold, p < 0.05) were identified after riboflavin deficiency. Bioinformatics analysis indicated that the riboflavin deficiency caused an up-regulation of Parkinson’s disease pathway, steroid catabolism, endoplasmic reticulum stress and apoptotic process, while the fatty acid metabolism, tricarboxylic citrate cycle, oxidative phosphorylation and iron metabolism were down-regulated. These findings provide a molecular basis for the elucidation of the effects caused by riboflavin deficiency.
... As an example, they are crucial for the synthesis, conversion and recycling of niacin, folate and vitamin B6, and for the synthesis of all hemo proteins, including hemeglobin, nitric oxide synthases, P450 enzymes, and proteins involved in electron transfer and oxygen transport and storage (Rivlin, 2007). The flavoproteins are also cofactors in the metabolism of essential fatty acids in brain lipids (SinigagliaCoimbra, 2011) the absorption and utilisation of iron (Mushtaq, 2011) and the regulation of thyroid hormones (Rivlin, 2007). Dysregulation of any of these processes by riboflavin deficiency would be associated with its own broad negative consequences for brain function. ...
Article
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The aim of this review is to refer a possibility of using natural substances for treating or reducing the symptoms of tinnitus. Tinnitus is a sensation of sound without an external source. It often manifests as a ringing in the ears, but it may also sound like a buzzing, hissing, whistling or even roaring in the head. Tinnitus is a symptom of an underlying condition. It can be linked to hearing loss, stress, ear damage, blood pressure, tumours and atherosclerosis. Exposure to loud noise is one major cause of tinnitus, since it wears down the delicate hair cells in inner ear that translate sounds into nerve impulses. Potential therapy of tinnitus is a pharmacological treatments. Fortunately, there are many effective natural alternatives to drugs that can bring considerable relief and help cope. The potential form of treatment is vitamins and natural flavonoids therapy. Low levels of melatonin and vitamin B12 in body have a significant correlation with the development of tinnitus. It was reported that melatonin is useful in the treatment of tinnitus, even in cases associated with sleep disturbance. There are relationship between vitamin B12 deficiency and dysfunction of the auditory pathway. Antioxidants are another substances which have a promising effect in the treatments of tinnitus. The constituents of G. biloba are potent scavengers of free radicals and has been prescribed their positive effect on treat of central nervous system disorders and cognitive deficits. Positive antioxidant effects have vitamin C, hesparidin and diosmin also.
... In order to understand the importance of adequate ingestion of riboflavin, numerous animals studies have been performed to study the consequences of its absence in diets (6)(7)(8)(9) . Extreme riboflavin deficiency, called ariboflavinosis, can cause many disorders such as reduced growth rates, oral lesions including cracked and red lips, glossitis, angular cheilitis, atrophy of taste buds, ulcers and sore throat (10,11) , and hyperhomocysteinaemia (12) , among others. ...
Article
Full-text available
It has been previously shown that Lactobacillus plantarum CRL 2130 is able to produce riboflavin in soyamilk. The aim of the present study was to evaluate the efficiency of this riboflavin-bio-enriched soyamilk to revert and/or prevent the nutritional deficiency of riboflavin using different animal models. When used to supplement the diets of previously depleted animals, it was shown that the growth, riboflavin status and morphology of the small intestines reverted to normal parameters and were similar to animals supplemented with commercial riboflavin. In the prevention model, the same tendency was observed, where animals that received soyamilk fermented with L. plantarum CRL 2130 did not show signs of riboflavin deficiency. This new bio-fortified soya-based product could be used as part of normal diets to provide a more natural alternative to mandatory fortification with riboflavin for the prevention of its deficiency.
... These findings are in keeping with the known biological role of riboflavin in enhancing iron absorption and utilization. When riboflavin intake is high the ability to mobilise iron from ferritin to and utilize it for the synthesis of hemoglobin will be high (36). ...
Article
Full-text available
Aiming to evaluate the effectiveness of functional cereal-fermented milk beverage against anemia in rats. The experiment was carried out by dividing rats into three groups. Negative control (normal) was fed on standard diet, positive control group was fed on standard diet + tannic acid (15 gm/kg diet) and the third group was fed on standard diet + tannic acid (15 gm/kg diet) + 20% of tested functional beverage. Our results revealed that the probiotic containing beverage ameliorated blood hemoglobin, serum iron, total iron binding capacity, ferritin, lipid peroxidation and total antioxidant capacity. Histopathological examination of the anemic rats showed disturbed splenic pulps with congested blood vessels and lymphocytic infiltration around the central vein. These changes were markedly restored by the tested functional beverage. It was concluded that foods containing folic acid and riboflavin - producing encapsulated probiotic bacteria enhanced iron absorption and utilization. Hence it protects against iron deficiency anemia.
... The average iron intake is 24 mg/day [24] in China, which is much higher than in Western countries [28]. Thus, taking VB2 supplementation, rather than taking iron supplementation may have greater benefit in preventing anaemia in the older Chinese population by enhancing the ability to mobilise iron from ferritin to allow haemoglobin synthesis [24,26,29]. ...
Article
Summary Background & aims Epidemiological data of dietary patterns and anaemia among older Chinese remains extremely scarce. We examined the association between dietary patterns and anaemia in older Chinese, and to assess whether biomarkers of serum magnesium, C-reactive protein (CRP) and serum ferritin can mediate these associations. Methods We analysed the 2009 China Health and Nutrition Survey data (2401 individuals aged ≥60 years for whom both dietary and biomarker data are available). Dietary data was obtained using 24 h-recall over three consecutive days. Fasting blood samples and anthropometry measurement were also collected. Factor analysis was used to identify dietary patterns. Factor scores representing dietary patterns were used in Poisson regression models to explore the association between each dietary pattern and anaemia. Results Of the 2401 participants, 18.9% had anaemia, 1.9% had anaemia related to inflammation (AI), and 1.3% had iron-deficiency anaemia (IDA). A traditional dietary pattern (high intake of rice, pork and vegetables) was positively associated with anaemia; a modern dietary pattern (high intake of fruit and fast food) was inversely associated with anaemia. Progressively lower magnesium and BMI levels were associated with increasing traditional dietary quartiles; while a progressively higher magnesium and BMI levels were associated with increasing modern dietary quartiles (p < 0.001). There were no significant differences (p > 0.05) in CRP and serum ferritin across quartiles for either dietary pattern. In the fully adjusted model, the prevalence ratio (PR) of anaemia, comparing the fourth quartile to the first quartile, was 1.75 (95% CI: 1.33; 2.29) for a traditional dietary pattern, and 0.89 (95% CI: 0.68; 1.16) for a modern dietary pattern. The association between dietary patterns and anaemia is mediated by serum magnesium.
... Although we chose to define riboflavin deficiency as EGRac $ 1.4, we acknowledge this as a limitation because there is currently no consensus on the EGRac cutoffs that should be used to define riboflavin status. A wide range of values was used previously: riboflavin deficiency as EGRac > 1.2 (46), EGRac > 1.3 (30,47), and EGRac > 1.4 (48); low riboflavin as EGRac > 1.7 (49), suboptimal status as EGRac $ 1.3 (31)(32)(33), and graduated levels of deficiency, with high risk of deficiency or severe deficiency classified as EGRac > 1.29 (50), >1.4 (12,51), and >1.6 (52). Further research into these cutoffs is warranted to ensure women are not misclassified as riboflavin deficient. ...
... Ruston et al. noted that EGRac is highly sensitive to even small levels of glutathione reductase desaturation (Ruston et al. 2004), potentially because compared with other enzymes involved with energy metabolism, glutathione reductase loses FAD at an early stage of riboflavin deficiency (Ross and Hansen 1992). Others have noted that EGRac values above the cut-off of 1.3 are not well aligned with physiological or functional changes (Powers et al. 2011). However, there is potential for adverse functional outcomes even with subclinical riboflavin deficiency (McAuley et al. 2016), so the 40% prevalence of suboptimal or deficient status (EGRac ≥ 1.3) we report here may warrant continued investigation of riboflavin status of Canadians. ...
Article
Older adults have potential increased risk of nutrient deficiencies due to age-related decreased dietary intake and malabsorption; it is important to ensure nutrient needs are met to avoid adverse health outcomes. B vitamins are of particular interest: vitamin B12 deficiency can cause irreversible neurodegeneration; there is mandatory folic acid fortification in Canada; and suboptimal riboflavin status has been reported among older adults in the United Kingdom. In this exploratory secondary analysis study we assessed vitamin B12 and riboflavin biochemical status (via microparticle enzyme immunoassay and erythrocyte glutathione reductase activity coefficient (EGRac), respectively), and the vitamin B12, riboflavin, and folate content of menus served to a convenience sample of older adults (≥65 years) from five residential care facilities within the Lower Mainland of British Columbia, Canada. Diet was assessed from customized 28-day cycle meal plans. Participants (n=207, 53 men and 154 women) were 86 ± 7 years, largely of European descent (92%), and non-smokers (95%). The menus served had a low prevalence of inadequacy for vitamin B12 and riboflavin (only 4% and 1% of menus contained less than the estimated average requirement [EAR], respectively), but 93% contained less than the EAR for folate. Mean ± SD serum total vitamin B12 concentration was 422 ± 209 pmol/L, and EGRac was 1.30 ± 0.19. The majority of older adults in residential care were provided with adequate vitamin B12 and riboflavin menu amounts, and only 5% were vitamin B12 deficient (<148 pmol/L). However, 26% were riboflavin deficient (EGRac ≥1.4), which may warrant further investigation.
... A recent trial in China showed that retinol and riboflavin supplements decreased the prevalence of anemia in pregnant women who were also taking iron and folic acid supplements [27] . In United Kingdom, it has been found that riboflavin supplementation improves hematologic status among women aged 1925 years with moderate riboflavin deficiency [28] . ...
Article
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Historically, Eastern China has the highest prevalence of anemia among adults in China. It is commonly believed that iron deficiency is the main cause of anemia in China. Iron fortified soysauce is used to prevent anemia. Findings from Jiangsu Nutrition Study suggest that diet is related to anemia in this region. However, iron deficiency is not the main cause. Micronutrients other than iron (e.g. , riboflavin) need to be considered in the prevention of anemia in the region.
... Deficiencies of vitamins A, 106-108 B6, 109,110 B12, 111,112 and C, 113,114 copper, [115][116][117] folate, 111 riboflavin, 75,118,119 and zinc 120 have been associated with anemia in various populations and contexts. Assessment of micronutrient status often requires a venous blood sample and specialized equipment and/or methods. ...
Article
Anemia affects over 800 million women and children globally. Defined as a limited or insufficient functional red blood cell supply in peripheral blood, anemia causes a reduced oxygen supply to tissues and can have serious health consequences for women and children. Hemoglobin (Hb) concentration is most commonly measured for anemia diagnosis. Methods to measure Hb are usually invasive (requiring a blood sample); however, advances in diagnostic and clinical chemistry over the past decade have led to the development of new noninvasive methods. Accurate diagnosis at the individual level is important to identify individuals who require treatment. At the population level, anemia prevalence estimates are often the impetus for national nutrition policies or programs. Thus, it is essential that methods for Hb measurement are sensitive, specific, accurate, and reproducible. The objective of our narrative review is to describe the basic principles, advantages, limitations, and quality control issues related to methods of Hb measurement in clinical and field settings. We also discuss other biomarkers and tests that can help to determine the severity and underlying causes of anemia. In conclusion, there are many established and emerging methods to measure Hb concentration, each with their own advantages, limitations, and factors to consider before use. The objective of our narrative review is to describe the basic principles, advantages and limitations, and quality control issues related to methods of hemoglobin measurement in clinical and field settings. We also discuss other biomarkers and tests that can help to determine the severity and underlying causes of anemia.
... Riboflavin has 2 cofactor forms, FMN and FAD, which are essential for numerous oxidation-reduction reactions and thus required in the metabolism of energy, certain drugs, and toxins and in supporting cellular antioxidant potential (63). Of note, riboflavin-dependent metabolism involves interaction with a number of other nutrients including iron (64). Of particular relevance to one-carbon metabolism is the close metabolic interaction of riboflavin with vitamin B-6 (65), where riboflavin is required (as FMN) for the generation in tissues of the active vitamin B-6 coenzyme form pyridoxal 5' phosphate (PLP) from pyridoxine phosphate by pyridoxine-phosphate oxidase (PPO). ...
Article
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Hypertension in adulthood is recognized as the leading risk factor contributing to mortality worldwide, primarily from cardiovascular disease, whereas hypertension in pregnancy leads to serious adverse fetal and maternal outcomes. This article explores the under-recognized role of one-carbon metabolism in blood pressure (BP) and the potential for folate-related B vitamins to protect against hypertension. Genome-wide association studies and clinical studies provide evidence linking the 677C→T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) with BP and increased risk of hypertension and hypertension in pregnancy. A novel role for riboflavin (the MTHFR cofactor) has recently emerged, however, with evidence from randomized trials that supplemental riboflavin can lower BP specifically in adults with the variant MTHFR 677TT genotype. Further studies are required to elucidate the biological mechanisms linking one-carbon metabolism with BP and explore the effect of riboflavin in modulating the genetic risk of hypertension in early and later life.
... Our findings suggest that vitamin B2 status was suboptimal (EGRAC > 1.3) in almost all females (15 out of 16 low-fit and 13 out of 15 high-fit females). The risks of vitamin B2 deficiency have been observed in other exercise studies [14][15][16][18][19][20]44,45], but also in other study populations, including adolescents, young women, adults, and the elderly from developed countries such as the United Kingdom, Spain, and France [31,[46][47][48][49]. In The Netherlands, vitamin B2 status studies are scarce; one cross-sectional study from 1989 showed that the mean EGRAC in adult (18-64 y) females was 1.11 [50], and the first Dutch food consumption survey from 1987-1988 showed that the average vitamin B2 intake among females aged 22-49 y was 1.49 mg/d [51]. ...
Article
Full-text available
High-fitness individuals have been suggested to be at risk of a poor vitamin B2 (riboflavin) status due to a potentially higher vitamin B2 demand, as measured by the erythrocyte glutathione reductase (EGR) activation coefficient (EGRAC). Longer-term exercise interventions have been shown to result in a lower vitamin B2 status, but studies are contradictory. Short-term exercise effects potentially contribute to discrepancies between studies but have only been tested in limited study populations. This study investigated if vitamin B2 status, measured by EGRAC, is affected by a single exercise bout in females who differ in fitness levels, and that represents long-term physical activity. At baseline and overnight after a 60-min cycling bout at 70% V·O2peak, EGR activity and EGRAC were measured in 31 young female adults, divided into a high-fit (V·O2peak ≥ 47 mL/kg/min, N = 15) and low-fit (V·O2peak ≤ 37 mL/kg/min, N = 16) group. A single exercise bout significantly increased EGR activity in high-fit and low-fit females (Ptime = 0.006). This response was not affected by fitness level (Ptime*group = 0.256). The effect of exercise on EGRAC was not significant (Ptime = 0.079) and not influenced by EGR activity. The exercise response of EGRAC was not significantly different between high-fit and low-fit females (Ptime*group = 0.141). Thus, a single exercise bout increased EGR activity, but did not affect EGRAC, indicating that vitamin B2 status was not affected. The exercise response on EGRAC and EGR did not differ between high-fit and low-fit females.
... TrxR is also a flavoprotein [27], presumably vulnerable to riboflavin deficiency in a similar way as glutathione reductase (GR) [37,38]. The physiological role of TrxR is the transfer of reducing equivalents from NADPH to Trx recovering its reduced state ( Fig. 1) [18,39]. ...
Article
Thioredoxin reductases (TrxRs) belong to the pyridine nucleotide disulfide oxidoreductase family enzymes that reduce thioredoxin (Trx). The couple TrxR and Trx is one of the major antioxidant systems that control the redox homeostasis in cells. The thioredoxin system, comprised of TrxR Trx and NADPH, exerts its activities via a disulfide-dithiol exchange reaction. Inhibition of TrxR is an important clinical goal in all conditions in which the redox state is perturbed. The present review focuses on the most critical aspects of the cellular functions of TrxRs and their inhibition mechanisms by metal ions or chemicals, through direct targeting of TrxRs or their substrates or protein interactors. To update the involvement of overactivation/dysfunction of TrxRs in various pathological conditions, human diseases associated with TrxRs genes were critically summarized by publicly available genome-wide association study (GWAS) catalogs and literature. The pieces of evidence presented here justify why TrxR is recognized as one of the most critical clinical targets and the growing current interest in developing molecules capable of interfering with the functions of TrxR enzymes.
... To prevent riboflavin deficiency, many countries, including the United States, have included this vitamin in essential fortification programs in mass consumption foods. However, vegetarians or people who rarely consume dairy products are still exposed to riboflavin deficiency [12][13][14]. Therefore, some of the beneficial microorganisms, including lactic acid bacteria (LAB), have been proposed as alternative means to increase the concentration of group B vitamins in foods based on their de novo biosynthetic ability [15,16]. ...
Article
Full-text available
Vitamin B2, also known as riboflavin, is essential for maintaining human health. The purpose of this study was to isolate novel lactic acid bacteria that overproduce vitamin B2 and to validate their potential as probiotics. In this study, Lactobacillus plantarum HY7715 (HY7715) was selected among lactic acid bacteria isolated from Kimchi. HY7715 showed a very high riboflavin-producing ability compared to the control strain due to the high expression of ribA, ribB, ribC, ribH, and ribG genes. HY7715 produced 34.5 ± 2.41 mg/L of riboflavin for 24 h without consuming riboflavin in the medium under optimal growth conditions. It was able to produce riboflavin in an in vitro model of the intestinal environment. In addition, when riboflavin deficiency was induced in mice through nutritional restriction, higher levels of riboflavin were detected in plasma and urine in the HY7715 administration group than in the control group. HY7715 showed high survival rate in simulated gastrointestinal conditions and had antibiotic resistance below the cutoff MIC value suggested by the European Food Safety Authority; moreover, it did not cause hemolysis. In conclusion, HY7715 could be considered a beneficial probiotic strain for human and animal applications, suggesting that it could be a new alternative to address riboflavin deficiency.
... Severe riboflavin deficiency is associated with dermatological and visual abnormalities (1,2). Milder forms of riboflavin deficiency, based on riboflavin biomarkers, have been associated with anemia and hypertension in women as well as pre-eclampsia in pregnancy (3)(4)(5)(6)(7)(8)(9). Riboflavin status has generally been assumed to be sufficient in Canadian women. ...
Article
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Background Nutrition surveys suggest that less than 10% of Canadian adults have inadequate riboflavin intakes. However, biochemical riboflavin deficiency (erythrocyte glutathione reductase activity coefficient, EGRac ≥ 1.40) has been reported in 41% of young adult women living in Metro Vancouver. Canadian Chinese ethnicity comprise > 25% of Vancouver's population and are postulated to have poorer riboflavin status than those of European ethnicity, as they may be less likely to consume dairy products and fortified wheat. Objectives The objectives of this study were to determine dietary riboflavin intake and food sources, and to assess the association between riboflavin intake and status among young women of European (n = 107) and Chinese (n = 91) ethnicities living in Metro Vancouver, Canada. Methods This was a cross-sectional study conducted on women (19 - 45 years). Women were healthy, not pregnant or breastfeeding, of European or Chinese ethnicities, and not taking riboflavin-containing supplements for the past 4 months. Dietary riboflavin intake was assessed using the past-year Diet History Questionnaire II and ໿riboflavin status (EGRac) was measured in fasting venous blood samples. Results Only 7% of participants had dietary riboflavin intakes below the EAR (0.9 mg/d), but 40% of women had biochemical riboflavin deficiency (EGRac ≥ 1.40). Although more Canadian women of European ethnicity than Chinese ethnicity had biochemical riboflavin deficiency (46% and 34%; P < 0.001), median dietary riboflavin intake did not differ (1.73 and 1.82 mg/d; P = 0.587). Dairy products and vegetables contributed the most to riboflavin intake. Energy-adjusted dietary riboflavin intake was inversely associated with EGRac (B = -0.04, 95% CI: -0.07, -0.01). However, after further adjustment the relationship was not significant. Conclusions Overall, women of reproductive age living in Metro Vancouver, Canada, had a low prevalence of inadequate dietary riboflavin intake despite the high prevalence of apparent biochemical riboflavin deficiency.
... However, according to the recommended dosage of the American Food and Nutrition Board (1.3 mg/day), a large proportion of the population does not meet the daily nutritional requirement of this vitamin [2]. Riboflavin deficiency is prevalent in many regions over the world, particularly in developing countries with a low intake of dairy products and meats [3,4]. Riboflavin deficiency also occurs frequently in pregnant women, lactating women, infants, schoolchildren, and the elderly [1,5,6]. ...
Article
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PurposeRiboflavin deficiency causes ariboflavinosis, a common nutritional deficiency disease. The purpose of this study is to investigate the effects of riboflavin deficiency on the important internal organs and its potential mechanisms.Methods Experiment 1, male F344 rats were randomly assigned to R6 (normal riboflavin, 6 mg/kg) and R0 (riboflavin-deficient, 0 mg/kg) groups. Experiment 2 rats were assigned to R6, R0.6 (0.6 mg/kg) and R0.06 (0.06 mg/kg) groups. Experiment 3 rats were assigned to R6 and R0 → R6 (riboflavin replenishment) groups. Bacterial communities were analyzed based on 16S rRNA gene sequencing.ResultsRiboflavin deficiency induced ariboflavinosis (R0.06 46.7%; R0 72%) and esophageal epithelial atrophy (R0.06 40%; R0 44%) in rats, while the R6 group did not display symptoms (P < 0.001, respectively). Esophageal epithelial atrophy occurred simultaneously (R0.06 66.7%; R0 63.6%) with ariboflavinosis or appeared alone (R0.06 33.3%; R0 36.4%). Esophagus is the most vulnerable internal organ. Riboflavin deficiency followed by replenishment (R0 → R6) was effective in treating ariboflavinosis (83.3% vs. 0%, P < 0.001) and esophageal epithelial atrophy (66.7% vs. 20%, P = 0.17). Riboflavin deficiency modulated gut microbiota composition. The several key genera (Romboutsia, Turicibacter and Clostridium sensu stricto 1) were strongly correlated with ariboflavinosis and esophageal epithelial atrophy (P < 0.01 or P < 0.05). The potential mechanism is that gut microbiota affects body's xenobiotic biodegradation and metabolism, and genomic instability.Conclusions Riboflavin deficiency induces ariboflavinosis and esophageal epithelial atrophy by modulating the gut microbiota, and offers new Queryinsight into riboflavin deficiency and esophageal lesions.
... Dietary riboflavin is essential, as the human body is unable to synthesize this vitamin [2]. Riboflavin deficiency is prevalent in underdeveloped countries with a low intake of dairy products and meat [3,4]. During periods of physiological and pathological stress, humans are vulnerable to developing riboflavin deficiency [1,[5][6][7]. ...
Article
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Riboflavin deficiency confers a predisposition for esophageal cancer. The role of plasma riboflavin levels in development and prognosis of individuals with digestive tract inflammation and ulcer (DTIU), digestive tract polyps (DTPs), and ESCC is not well understood. We performed a cross-sectional study, including 177 DTIU, 80 DTP, and 324 ESCC cases, to measure the plasma riboflavin levels among the three populations. Correlation between plasma riboflavin levels (categorized as ≥31.8, 6.5–31.8 and ≤6.5 nmol/L groups) and clinical characteristics, as well as survival of ESCC patients (556 cases) was analyzed. There was no difference in plasma riboflavin levels between DTIU, DTP, and ESCC cases (P > 0.05). Plasma riboflavin levels were inversely correlated with invasive depth (correlation coefficient = −0.09, P = 0.026) and lymph node metastasis (correlation coefficient = −0.11, P = 0.010) of ESCC, and ESCC patients with low riboflavin levels had poor recurrence-free survival (P = 0.035) and overall survival (P = 0.003). Decreased riboflavin was a prognostic factor for poor overall survival (HR = 1.91, 95% CI = 1.19–3.07, P = 0.007). Plasma riboflavin levels in DTIU, DTP, and ESCC patients are similar. Plasma riboflavin levels are associated with the development and prognosis of ESCC.
... Furthermore, a significant association between RF and iron intake in correspondence to the risk of anemia was detected. There have been cross-sectional studies to illustrate the link between RF intake and anemia, while prospective population studies are limited [91]. ...
Article
Full-text available
Riboflavin (RF) is a water-soluble member of the B-vitamin family. Sufficient dietary and supplemental RF intake appears to have a protective effect on various medical conditions such as sepsis, ischemia etc., while it also contributes to the reduction in the risk of some forms of cancer in humans. These biological effects of RF have been widely studied for their anti-oxidant, anti-aging, anti-inflammatory, anti-nociceptive and anti-cancer properties. Moreover, the combination of RF and other compounds or drugs can have a wide variety of effects and protective properties, and diminish the toxic effect of drugs in several treatments. Research has been done in order to review the latest findings about the link between RF and different clinical aberrations. Since further studies have been published in this field, it is appropriate to consider a re-evaluation of the importance of RF in terms of its beneficial properties.
... We have applied cutoffs for EGRac in this study that have been widely used to determine riboflavin inadequacy, but there is a large degree of variation in applicable cutoffs. Previous studies have used EGRac cutoffs that range from 1.20 to 1.70 to determine low riboflavin or riboflavin deficiency (47)(48)(49)(50)(51). The EFSA panel considers that, on the basis of urinary excretion studies in adults, an EGRac of <1. 30 can be applied to define riboflavin adequacy (44), which is in keeping with the cutoffs for marginal status and deficiency we have applied in this study. ...
Article
Background: Riboflavin is required for erythropoiesis, which is increased in people with hemoglobinopathies due to increased hemolysis and erythrocyte turnover. Dietary intake and status of riboflavin is poor in Cambodia, where hemoglobinopathies are common. Objective: We assessed the association between genetic hemoglobin disorders and riboflavin status in women of reproductive age in Cambodia. Methods: Venous blood samples from 515 Cambodian women of reproductive age, 18-45 y, were analyzed for biomarker status of riboflavin [erythrocyte glutathione reductase activation coefficient (EGRac)], genetic hemoglobin (Hb) disorders, and hematological indices. Linear regression analysis was used to estimate the association between EGRac with Hb, ferritin, and Hb genotypes. EGRac was log transformed in the analyses, and the regression coefficients represent the geometric mean differences. Results: Genetic Hb disorders were present in 57% of the population, with the homozygous hemoglobin E variant (Hb EE) occurring in ∼10% of women (n = 53). Deficient (EGRac ≥1.40) or marginal riboflavin status (EGRac ≥1.30 and <1.40) was observed in 92% (n = 475) of women. The variant Hb EE genotype was associated with 18% (95% CI: 9%, 28%) higher geometric mean EGRac values than the normal Hb AA genotype (P < 0.001). Conclusions: Although riboflavin biomarker deficiency or marginal status is widely prevalent in Cambodian women, lower riboflavin status was observed more frequently in women with the Hb EE genotype than in women with normal Hb AA. The relation between genetic Hb disorders and riboflavin warrants further investigation. This trial was registered at clinicaltrials.gov as NCT01593423 and NCT02481375.
... The latter increased from 0.56 nmol/L to 13.86 and 29.49 nmol/L respectively, after 2 and 4 mg vitamin B2 daily [119]. A recent original study has addressed symptoms that can be connected to physical fatigue, due to muscle pain and soreness after a physical exercise. ...
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Vitamins and minerals are essential to humans as they play essential roles in a variety of basic metabolic pathways that support fundamental cellular functions. In particular, their involvement in energy-yielding metabolism, DNA synthesis, oxygen transport, and neuronal functions makes them critical for brain and muscular function. These, in turn, translate into effects on cognitive and psychological processes, including mental and physical fatigue. This review is focused on B vitamins (B1, B2, B3, B5, B6, B8, B9 and B12), vitamin C, iron, magnesium and zinc, which have recognized roles in these outcomes. It summarizes the biochemical bases and actions of these micronutrients at both the molecular and cellular levels and connects them with cognitive and psychological symptoms, as well as manifestations of fatigue that may occur when status or supplies of these micronutrients are not adequate.
... However, acute examples are limited, and exhaustive B-vitamin and vitamer dynamics are unavailable. Health outcome benefits have been demonstrated with greater long term intake in compromised populations; for instance, greater riboflavin and thiamine intake have been shown to improve circulating riboflavin [55,60,61], thiamine status [62], glucose tolerance [63], general health and wellbeing [62,64], and cognitive function [65]. ...
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B-vitamin deficiency is common in ageing populations either due to altered dietary habits or altered digestive and metabolic functions. There is limited data on the acute circulating concentrations of B-vitamins and their various forms (vitamers), following ingestion of realistic meals. This study compared the acute circulating B-vitamin and vitamer responses to either an energy-dense (ED) or a nutrient-dense (ND) breakfast meal, consumed in a randomized cross-over sequence, in older and younger adults (n = 15 and 15, aged 67.3 ± 1.5 and 22.7 ± 0.5 years (mean ± SEM), respectively). Eleven differing B-vitamins and vitamers were determined in plasma samples by ultra-high-performance liquid chromatography-tandem mass spectrometry, in the fasting and postprandial state (hourly for 5 h). While postprandial thiamine concentration increased following both meals, riboflavin increased only following a ND meal in both age groups. Many vitamins including nicotinic acid, pantothenic acid, pyridoxal, pyridoxamine, pyridoxal-5'phosphate, and 4-pyridoxic acid remained unaltered, and flavin mononucleotide (FMN), nicotinamide and nicotinuric acid concentrations reduced following both meals. Biological age and food composition had minimal impact on postprandial B-vitamin concentrations, yet the differences between the ED and ND meals for riboflavin highlight the importance of riboflavin intake to achieve adequacy.
... Riboflavin-dependent metabolism involves interaction with a number of other nutrients. Riboflavin deficiency in animals is associated with impaired iron absorption, whilst riboflavin supplementation in human subjects was shown to enhance circulating Hb concentrations and improve the response of iron deficiency anaemia to iron therapy (121) . In addition, riboflavin involves close metabolic interaction with vitamin B 6 , in that it is required (as FMN) for the generation of pyridoxal 5′ phosphate (PLP; the active vitamin B 6 coenzyme form) in tissues from pyridoxine phosphate by pyridoxine-phosphate oxidase. ...
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The functional effects of folate within C 1 metabolism involve interrelationships with vitamin B 12 , vitamin B 6 and riboflavin, and related gene–nutrient interactions. These B vitamins have important roles throughout life, from pregnancy, through childhood, to middle and older age. Achieving optimal nutritional status for preventing folate-related disease is challenging, however, primarily as a result of the poor stability and incomplete bioavailability of folate from natural food sources when compared with the synthetic vitamin form, folic acid. Thus, in European countries, measures to prevent neural tube defects (NTD) have been largely ineffective because of the generally poor compliance of women with folic acid supplementation as recommended before and in early pregnancy. In contrast, countries worldwide with mandatory folic acid fortification policies have experienced marked reductions in NTD. Low vitamin B 12 status is associated with increased risk of cognitive dysfunction, CVD and osteoporosis. Achieving optimal B 12 status can be problematic for older people, however, primarily owing to food-bound B 12 malabsorption which leads to sub-clinical deficiency even with high dietary B 12 intakes. Optimising B-vitamin intake may be particularly important for sub-populations with impaired folate metabolism owing to genetic characteristics, most notably the 677C→T variant in the gene encoding the enzyme methylenetetrahydrofolate reductase (MTHFR). This common folate polymorphism is linked with several adverse health outcomes, including stroke, however, recent evidence has identified its novel interaction with riboflavin (the MTHFR cofactor) in relation to blood pressure and risk of developing hypertension. This review addresses why and how the optimal status of folate-related B vitamins should be achieved through the lifecycle.
... There are two flavoprotein coenzymes derived from riboflavin, flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) working as limiting factors in most cellular enzymatic processes. They are involved in the synthesis, conversion and recycling of niacin, folate and vitamin B 6 , in the synthesis of all heme proteins, including hemoglobin, in NO synthesis, P450 enzymes, and proteins involved in electron transfer and oxygen transport and storage (Rivlin, 2007) and in the uptake and use of iron (Powers et al., 2011). The flavoproteins are also involved in the metabolism of essential fatty acids in brain lipids (Sinigaglia-Coimbra et al., 2011) and in the regulation of thyroid hormones (Rivlin, 2007). ...
... The entire farm-to-fork food production process affects micronutrient composition and bioavailability (28)(29)(30). Moreover, humans consume complex diets and the combination of food sources (plant compared with animal) within a meal affects micronutrient bioavailability and absorption (31)(32)(33)(34)(35). Nutritional status is further complicated by human genetic variants that affect the expression of genes involved in the uptake, conversion, metabolism, and transport of micronutrients, and thus contribute to interindividual differences in micronutrient profiles (36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46). The genetic component is further affected by physiological and pathological conditions [e.g., increased adiposity (47)] that also contribute to impair or alter nutritional status. ...
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Diet and lifestyle are vital to population health, but their true contribution is difficult to quantify using traditional methods. Nutrient–health relations are typically based on epidemiological associations that are assessed at the population level, traditionally using self-reported dietary and lifestyle data. Unfortunately, such measures are inherently inaccurate. New technologies such as metabolomics can measure nutritional and micronutrient profiles in body fluids, providing objective evaluation of nutritional status. A critical step toward accurate health prediction models would be the building of integrated repositories of nutritional measures combining subjective methods of reporting with objective metabolomics profiles and precise phenotypic data. Here we outline a roadmap to achieve this goal and discuss both the advantages and risks of this approach. We also highlight the uncertain associations between the complexity of high-dimensional data generated in ‘omics research (along with the public confusion this may engender) and the rapid adoption of ‘omics approaches by nutrition and health companies to develop nutritional products and services.
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This publication is linked to the following EFSA Journal article: http://onlinelibrary.wiley.com/doi/10.2903/j.efsa.2017.4919/full
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Lipid metabolism is dependent on riboflavin status. Apolipoprotein B100 plays an important role in lipids transportation. This study was aimed to investigate the effect of riboflavin status on lipid metabolism and explore its association with apolipoprotein B100 synthesis in vivo. Riboflavin deficiency was developed in rats by feeding riboflavin-deficient diets. Compared to the control rats, the mRNA and protein expressions of apolipoprotein B100 were significantly reduced in riboflavin-deficient rats. Endoplasmic reticulum oxidoreductin 1 (ERO1) and protein disulfide isomerase (PDI), two enzymes involved in the oxidative folding of apolipoprotein B100, were also lowered remarkably in expression at protein level. Meanwhile, total cholesterol and triglyceride levels were decreased in the plasma and increased in the liver of riboflavin-deficient rats. The plasma very low-density lipoprotein cholesterol (VLDL-c) and low-density lipoprotein cholesterol (LDL-c) were also reduced in riboflavin-deficient rats. Our findings demonstrate that riboflavin deficiency affects lipid metabolism partly by reducing apolipoprotein B100 synthesis.
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Mammalian thioredoxin reductase (TrxR) is a selenoprotein with three existing isoenzymes (TrxR1, TrxR2, and TrxR3), which is found primarily intracellularly but also in extracellular fluids. The main substrate thioredoxin (Trx) is similarly found (as Trx1 and Trx2) in various intracellular compartments, in blood plasma, and is the cell’s major disulfide reductase. Thioredoxin reductase is necessary as a NADPH-dependent reducing agent in biochemical reactions involving Trx. Genetic and environmental factors like selenium status influence the activity of TrxR. Research shows that the Trx/TrxR system plays a significant role in the physiology of the adipose tissue, in carbohydrate metabolism, insulin production and sensitivity, blood pressure regulation, inflammation, chemotactic activity of macrophages, and atherogenesis. Based on recent research, it has been reported that the modulation of the Trx/TrxR system may be considered as a new target in the management of the metabolic syndrome, insulin resistance, and type 2 diabetes, as well as in the treatment of hypertension and atherosclerosis. In this review evidence about a possible role of this system as a marker of the metabolic syndrome is reported.
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Scope: Epidemiologic evidence suggests that riboflavin (RBF) deficiency is a specific nutritional predisposition for esophageal cancer. The aim of this study is to investigate the potential roles of gut microbiota in esophageal tumorigenesis caused by the RBF deficiency. Methods: Male F344 rats were subcutaneously injected with the chemical carcinogen N-nitrosomethylbenzylamine (NMBA, 0.35 mg kg-1). Rats were assigned to 4 groups, denoted as R6 (normal RBF, 6 mg kg-1), R6N (normal RBF combined with NMBA), R6N → R0N (normal RBF conversion to RBF-deficiency), and R0N → R6N (RBF-deficiency conversion to normal RBF). Bacterial communities were analyzed based on high-throughput 16S rRNA gene sequencing. Oxidative DNA damage and double-strand break markers were studied by immunohistochemistry. Results: The R6N → R0N diet enhanced the incidence of esophageal intraepithelial neoplasia (EIN, 40 weeks 66.7% vs. 25 weeks 16.7%, P < 0.05). RBF deficiency and replenishment modulated the gut microbiota composition. The gut microbiota (e.g. Caulobacteraceae, Sphingomonas and Bradyrhizobium) affected xenobiotic biodegradation and the genomic instability of the host. Furthermore, the RBF deficiency aggravated oxidative DNA damage and DNA double-strand breaks (immunohistochemistry) in the esophageal epithelium, whereas the RBF replenishment had the opposite effect (P < 0.05, respectively). Conclusions: RBF deficiency promotes NMBA-induced esophageal tumorigenesis, which is associated with gut microbiota-associated genomic instability, and offers new insights into the role of RBF deficiency in esophageal carcinogenesis.
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Having been awarded the 2019 British Nutrition Foundation Annual Prize I had looked forward to delivering a lecture to assembled guests at the BNF Annual Day at the Royal College of Physicians in London, in 2020. Unfortunately, this was not to be; the COVID‐19 global pandemic prevented a face‐to‐face meeting, and my talk was delivered remotely. In the paper, I shall summarise some of the research that I have carried out during my career as a nutrition scientist. I shall not dwell in much detail on any single aspect of my work but rather I shall attempt to show how my research interests developed over the decades, how one thing led to another, so to speak. The elements of my work that I have selected, in order to make this short walk together, commence with vitamin B2, riboflavin and a consideration of two particular aspects of function. I then move on to folate in the context of homocysteine metabolism and cardiovascular disease and finally consider the role of this vitamin and other methyl donors in cancer risk and outcome.
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Recent studies elucidated how riboflavin transporters and FAD forming enzymes work in humans and create a coordinated flavin network ensuring the maintenance of cellular flavoproteome. Alteration of this network may be causative of severe metabolic disorders such as multiple acyl-CoA dehydrogenase deficiency (MADD) or Brown-Vialetto-van Laere syndrome. A crucial step in the maintenance of FAD homeostasis is riboflavin uptake by plasma and mitochondrial membranes. Therefore, studies on recently identified human plasma membrane riboflavin transporters are presented, together with those in which still unidentified mitochondrial riboflavin transporter(s) have been described. A main goal of future research is to fill the gaps still existing as for some transcriptional, functional and structural details of human FAD synthases (FADS) encoded by FLAD1 gene, a novel “redox sensing” enzyme. In the frame of the hypothesis that FADS, acting as a “FAD chaperone”, could play a crucial role in the biogenesis of mitochondrial flavo-proteome, several basic functional aspects of flavin cofactor delivery to cognate apo-flavoenzyme are also briefly dealt with. The establishment of model organisms performing altered FAD homeostasis will improve the molecular description of human pathologies. The molecular and functional studies of transporters and enzymes herereported, provide guidelines for improving therapies which may have beneficial effects on the altered metabolism.
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has lately been a renewed interest in Riboflavin owing to insight into its recognition as an essential component of cellular biochemistry. The knowledge of the mechanisms and regulation of intestinal absorption of riboflavin and its health implications has significantly been expanded in recent years. The purpose of this review is to provide an overview of the importance of riboflavin, its absorption and metabolism in health and diseased conditions, its deficiency and its association with various health diseases and metabolic disorders. Efforts have been made to review the available information in literature on the relationship between riboflavin and various clinical abnormalities. The role of riboflavin has also been dealt in the prevention of a wide array of health diseases like migraine, anemia, cancer, hyperglycemia, hypertension, diabetes mellitus and oxidative stress directly or indirectly. The riboflavin deficiency has profound effect on iron absorption, metabolism of tryptophan, mitochondrial dysfunction, gastrointestinal tract, brain dysfunction and metabolism of other vitamins as well as is associated with skin disorders. Toxicological and photosensitizing properties of riboflavin make it suitable for biological use such as virus inactivation, excellent photosensitizer and promising adjuvant in chemo radiotherapy in cancer treatment. A number of recent studies have indicated and highlighted the cellular processes and biological effects associated with riboflavin supplementation in metabolic diseases. Overall, a deeper understanding of these emerging roles of riboflavin intake is essential to design better therapies for future.
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Согласно определению Всемирной организации здравоохранения, состояние здоровья человека определяется 4 группами факторов: генетическими, средовыми, поведенческими, а также доступностью надлежащей медико-профилактической помощи. Сказанное в полной мере относится к состоянию здоровья беременной женщины, плода, новорожденного и, следовательно, к перинатальному исходу. Состояние здоровья беременной, плода, новорожденного, а также перинатальные исходы во многом зависят от характера питания и адекватного потребления беременной ключевых нутриентов. Более того, в настоящее время вполне сформировалась концепция фетального (или внутриутробного) программирования, в соответствии с которой характер питания беременной является определяющим фактором, влияющим на будущее психофизическое развитие, показатели здоровья и заболеваемости новорожденного ребенка в течение многих последующих лет и даже десятилетий. Это позволяет говорить о том, что оптимальный подход к питанию беременных и грамотное консультирование по данному вопросу со стороны врача – акушера-гинеколога играют важную роль не только для улучшения показателей материнского здоровья, но и для формирования здоровой нации. According to the definition of the World Health Organization, the state of human health is determined by 4 groups of factors: genetic, environmental, behavioral, as well as the availability of appropriate medical and preventive care. The foregoing fully applies to the state of health of a pregnant women, fetus, newborn and, therefore, to the perinatal outcome. The health status of a pregnant woman, fetus, newborn, as well as perinatal outcomes largely depends on the nature of the diet and adequate consumption of key nutrients by the pregnant woman [1]. Moreover, at present, the concept of fetal (or intrauterine) programming has fully formed, according to which the nature of a pregnant woman’s diet is a determining factor affecting the future psychophysical development, health indicators and morbidity of the newborn for many subsequent years and even decades [2]. This allows us to say that the optimal approach to the nutrition of pregnant women and competent counseling on this issue from the obstetrician-gynecologist play an important role not only for improving maternal health indicators, but also for the formation of a healthy nation.
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In today’s world there is more than one point of view and different debates about how to determine and what constitutes the concept of nuclear security. A narrow attitude, which we can not agree with, is that it is an area that deals with issues of the model of physical security of nuclear materials. A broader interpretation of nuclear safety advocates a more comprehensive view of the activities that support the more ‘aims and content of nuclear safety’. This multidisciplinary approach is necessary for effective and sustainable nuclear security framework, both at the national and supranational levels. Generally speaking, nuclear safety can be defined as a set of measures to ensure the conditions for the operation of the nuclear facility to prevent nuclear accidents or mitigate their consequences and reduce the radiation risk to the prescribed level. It is well known that nuclear safety cannot be treated outside of the context of responsibility for carrying out nuclear activities and nuclear damage caused by a nuclear accident, and thus the insurance to cover liability for nuclear damage.
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The bioavailability of iron glycine added to a vegetable infant weaning food was compared with ferrous sulfate. Stable, isotopically labeled compounds (57Fe or 58Fe) were mixed into the midday meal (1.4 mg added Fe/serving) and fed to 9-mo-old infants on alternate days for 8 d. Bioavailability, expressed as a percentage of the dose consumed, was measured from isotopic enrichment of hemoglobin 14 d after the last test meal. There was no difference between iron glycine and ferrous sulfate (x+/-SEM): 9.0+/-0.7% and 9.9+/-0.8%, respectively. The effect of chelation was examined by measuring iron bioavailability of iron glycine and ferrous sulfate added to a high-phytate (310 mg/100 g) whole-grain cereal weaning food and comparing it with a lower-phytate (147 mg/100 g) vegetable food, as used in the first study. Both iron compounds had lower bioavailability from the high-phytate food, 5.2+/-0.5% for iron glycine and 3.8+/-0.9% for ferrous sulfate, than the lower-phytate food, 9.8+/-1.5% for iron glycine and 9.1+/-1.3% for ferrous sulfate. The results showed no significant difference in bioavailability between the two forms of iron when added to infant weaning foods, suggesting that the glycine complex was fully or partially dissociated in the gastrointestinal tract. It is concluded that chelation does not improve the bioavailability of iron in the presence of dietary inhibitors.
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Iron absorption from 3.38 mg 58Fe was measured in riboflavin-deficient Gambian men with haemoglobin (Hb) less than 11.5 g/dl before and after oral riboflavin therapy, and the results compared with a group not receiving riboflavin. Riboflavin status (as determined by erythrocyte glutathione reductase activation coefficient) and Hb increased in teh riboflavin-supplemented but not placebo group. Plasma ferritin levels were low and did not change in either group. There was very wide variation in percentage iron absorption between individuals and also within single individuals on two separate occasions but no measurable change with riboflavin supplementation. The results of the study indicate that the efficiency of iron utilization is impaired in riboflavin deficiency, but that iron absorption is unaffected.
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Iron absorption and daily loss of Fe were measured in riboflavin-deficient (B2-) Norwegian hooded rats and controls (B2+). Animals were fed on a test meal extrinsically labelled with 59Fe and whole-body radioactivity measured for 15 d. Riboflavin deficiency led to a reduction in the percentage of the 59Fe dose absorbed and an increased rate of 59Fe loss. All post-absorption 59Fe loss could be accounted for by faecal 59Fe, confirming that the loss was gastrointestinal. Fe concentrations and 59Fe as a percentage of retained whole-body 59Fe were higher in the small intestine of riboflavin-deficient animals than their controls, 14 d after the test meal. A separate experiment demonstrated that riboflavin deficiency was associated with a significant proliferative response of the duodenal crypts of the small intestine. These observations may explain the enhanced Fe loss in riboflavin deficiency.
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1. Riboflavin may play a part in the transport of iron across the gastrointestinal mucosa. Fe absorption was measured in the rat by monitoring whole-body retention of a dose of ⁵⁹ Fe using a small-animal γ-counter. 2. Female Norwegian Hooded rats were fed on a diet deficient in riboflavin (B 2 −) from 5 weeks of age. Control animals, fed on a complete diet (B 2 +), were weight-matched to rats fed on the B 2 − diet. After 7 weeks all rats were fed on a test meal extrinsically labelled with ⁵⁹ Fe and whole-body radioactivity measured for 15 d. 3. Riboflavin deficiency was associated with a reduction in the percentage of the dose absorbed and an increase in the rate of loss of Fe post absorption. 4. A smaller percentage of the absorbed dose was present in the livers of the riboflavin-deficient animals.
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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.
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Plasma total homocysteine (tHcy) is a risk factor for cardiovascular disease. tHcy concentrations are partly determined by folate, cobalamin, and vitamin B(6) status, and methylenetetrahydrofolate reductase (MTHFR) and other flavoenzymes are important for the biotransformation of these vitamins. This motivates the investigation of the possible relationship between riboflavin status and tHcy. The study had a cross-sectional design and included 423 healthy blood donors, ages 19-69 years. We determined plasma tHcy, serum folate, serum cobalamin, serum creatinine, and MTHFR C677T genotype. In addition, we measured riboflavin and its two coenzyme forms, flavin mononucleotide and flavin adenine dinucleotide, in EDTA plasma by capillary electrophoresis and laser-induced fluorescence detection. Riboflavin determined tHcy independently in a multiple linear regression model with adjustment for sex, age, folate, cobalamin, creatinine, and MTHFR genotype (P = 0.008). tHcy was 1.4 micromol/L higher in the lowest compared with the highest riboflavin quartile. The riboflavin-tHcy relationship was modified by genotype (P = 0.004) and was essentially confined to subjects with the C677T transition of the MTHFR gene. Plasma riboflavin is an independent determinant of plasma tHcy. Studies on deficient populations are needed to evaluate the utility of riboflavin supplementation in hyperhomocysteinemia.
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Established determinants of fasting total homocysteine (tHcy) concentration include folate and vitamin B-12 status, serum creatinine concentration, and renal function. Our objective was to examine the relation between known and suspected determinants of fasting plasma tHcy in a population-based cohort. We examined the relations between fasting plasma tHcy concentrations and nutritional and other health factors in 1960 men and women, aged 28-82 y, from the fifth examination cycle of the Framingham Offspring Study between 1991 and 1994, before the implementation of folic acid fortification. Geometric mean tHcy was 11% higher in men than in women and 23% higher in persons aged > or = 65 y than in persons aged < 45 y (P < 0.001). tHcy was associated with plasma folate, vitamin B-12, and pyridoxal phosphate (P for trend < 0.001). Dietary folate, vitamin B-6, and riboflavin were associated with tHcy among non-supplement users (P for trend < 0.01). The tHcy concentrations of persons who used vitamin B supplements were 18% lower than those of persons who did not (P < 0.001). tHcy was positively associated with alcohol intake (P for trend = 0.004), caffeine intake (P for trend < 0.001), serum creatinine (P for trend < 0.001), number of cigarettes smoked (P for trend < 0.001), and antihypertensive medication use (P < 0.001). Our study confirmed, in a population-based setting, the importance of the known determinants of fasting tHcy and suggested that other dietary and lifestyle factors, including vitamin B-6, riboflavin, alcohol, and caffeine intakes as well as smoking and hypertension, influence circulating tHcy concentrations.
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The suggestion that carriers of the HFE C282Y mutation absorb nonheme iron more efficiently than do carriers of the wild type has public health implications for countries where the C282Y mutation is common and foods are fortified with iron. We investigated the effect of C282Y heterozygosity on nonheme-iron absorption from a diet high in bioavailable iron and from iron-fortified cereals. The subjects were recruited from a parallel study investigating the relation between HFE mutations, habitual diet, and iron status. Iron absorption was measured in 15 wild-type carriers and 15 C282Y heterozygotes aged >/=40 y. Each subject consumed 3 meals of high iron bioavailability (labeled with Fe-57) for 2 d and 2 meals with fortified cereal products (labeled with Fe-54) for the next 3 d. Iron absorption was measured from isotope incorporation into red blood cells 14 d after the last labeled meal and was corrected for utilization of absorbed iron by means of an intravenous infusion of Fe-58. Absorption of Fe-57 with the high-iron-bioavailability diet was 6.8 +/- 6.8% (0.6 +/- 0.6 mg/d) in the wild-type carriers and 7.6 +/- 3.2% (0.7 +/- 0.3 mg/d) in the C282Y heterozygotes. Absorption of Fe-54 with cereal products was 4.9 +/- 2.0% (0.7 +/- 0.3 mg/d) in the wild-type carriers and 5.3 +/- 1.3% (0.8 +/- 0.2 mg/d) in the C282Y heterozygotes. There was no overall significant difference between C282Y heterozygotes and wild-type men in iron absorption from either dietary nonheme iron or fortified cereal products.
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Background: Established determinants of fasting total homocysteine (tHcy) concentration include folate and vitamin B-12 status, serum creatinine concentration, and renal function. Objective: Our objective was to examine the relation between known and suspected determinants of fasting plasma tHcy in a population-based cohort. Design: We examined the relations between fasting plasma tHcy concentrations and nutritional and other health factors in 1960 men and women, aged 28–82 y, from the fifth examination cycle of the Framingham Offspring Study between 1991 and 1994, before the implementation of folic acid fortification. Results: Geometric mean tHcy was 11% higher in men than in women and 23% higher in persons aged ≥65 y than in persons aged <45 y (P < 0.001). tHcy was associated with plasma folate, vitamin B-12, and pyridoxal phosphate (P for trend < 0.001). Dietary folate, vitamin B-6, and riboflavin were associated with tHcy among non–supplement users (P for trend < 0.01). The tHcy concentrations of persons who used vitamin B supplements were 18% lower than those of persons who did not (P < 0.001). tHcy was positively associated with alcohol intake (P for trend = 0.004), caffeine intake (P for trend < 0.001), serum creatinine (P for trend < 0.001), number of cigarettes smoked (P for trend < 0.001), and antihypertensive medication use (P < 0.001). Conclusions: Our study confirmed, in a population-based setting, the importance of the known determinants of fasting tHcy and suggested that other dietary and lifestyle factors, including vitamin B-6, riboflavin, alcohol, and caffeine intakes as well as smoking and hypertension, influence circulating tHcy concentrations.
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The findings of a survey of the diet and nutrition of young people aged 4–18 years living in private households in the UK, carried out between January 1997 and January 1998. The National Diet and Nutrition Survey (NDNS) of young people aged 4–18 years forms part of the NDNS programme, which aims to provide a comprehensive, cross-sectional picture of the dietary habits, nutrient intakes and nutritional status of the British population by studying representative samples of defined age groups. The survey components included a detailed interview covering dietary habits, lifestyle and socio-demographic characteristics; a 7-day weighed dietary record; a 7-day physical activity diary; measurements of height, weight, mid-upper arm, waist and hip circumferences, and blood pressure; a blood sample for analysis of a range of nutritional status indices; a single urine sample; and an oral health interview and dental examination. A total of 1701 young people provided 7-day dietary records, representing a response rate of 64%. Results have been published in two volumes covering the diet and nutrition survey and the oral health survey. The reports present results for boys and girls separately in four age groups: 4–6 years; 7–10 years; 11–14 years and 15–18 years. Results are also presented by region and by socio-economic characteristics. This review summarises some of the main findings of the diet and nutrition survey, including: the proportion of young people who ate selected foods; energy and nutrient intakes compared with UK Dietary Reference Values; nutritional status; physical measurements; and physical activity.
Article
Dietary intakes of several minerals and vitamins were assessed in two US sub-populations of older men and women between 60 and 80 years as part of the Lipid Research Clinics Program Prevalence Study conducted in the mid-1980s prior to widespread fortification. Dietary intakes were analyzed from 24-hour recalls using the Minnesota Nutrition Coding Center. Descriptive statistics on the two diverse sub-populations were generated for the elderly subjects at the two clinic sites, southern California and Oklahoma. Regression analyses of specific micronutrients were performed while controlling for several variables, namely, age, sex, clinic (region), education, Body Mass Index (BMI), alcohol consumption, and smoking status. Compared to current (1999–2004) Estimated Average Requirements (EARs) and Adequate Intakes (AIs) for three micronutrients without EARs for the US and Canada, several micronutrients were consumed at or close to their EAR values. Exceptions include intakes of vitamin A, vitamin E, folic acid, potassium and calcium which were very low; intakes of thiamin, riboflavin, niacin, and vitamin C were low but closer to the published EAR or AI values. High intakes approaching cut-offs for practically all subjects were found for both groups of elders at the two clinic sites for iron, phosphorus, and sodium. In general, California elderly had somewhat better consumption patterns for the vitamins, but the Oklahomans, males at least, had higher overall mineral intakes. The micronutrient deficits found in this small study suggest that most elderly US citizens were likely to be deficient in five micronutrients and marginally insufficient in four others in the mid-1980s and, despite even greater fortification currently, elderly intakes seem not to have improved substantially since the 1980s, except for subjects who are regular multi-supplement users.
Article
The Commission's Subcommittee for the Isotopic Composition of the Elements (SIAM) has carried out its biennial review of isotopic compositions, as determined by mass spectrometry and other relevant methods. This involves a critical evaluation of the published literature, element by element, and forms the basis of the Table of Isotopic Compositions of the Elements as Determined by Mass Spectrometry presented here. New guidelines have been used to arrive at the uncertainties on the isotopic abundances and there are numerous changes to the Table since it was last published in 1991. Atomic Weights calculated from this table are consistent with (A) under bar(r)(E) values listed in the Table of Standard Atomic Weights 1997.
Article
The purpose of the present study was to test the hypothesis that the already well-established mitochondria1 lesion in fatty acid oxidation in riboflavin-deficient experimental animals, might be accompanied by an alteration in vivo in the kinetics of oxidation of labelled adipic acid. This dicarboxylic acid was chosen for testing as a metabolic probe because a block in its oxidation was already apparent from urine analysis of riboflavin-deficient animals, whereas the oxidation of medium- or long-chain monocarboxylic acids seemed to be little affected by deficiency in vivo. Female adult Norwegian hooded rats fed on purified diets containing either 15 mg riboflavin/kg diet (controls) or about 0.4 mg/kg (riboflavin-deficient) received an intragastric dose of either [l,6-I4C] adipic acid or [l-'4C] octanoic acid. Expired carbon dioxide was then collected in an alkaline trap over 3 h, for determination of radioactivity.This test was repeated at intervals for up to 2 weeks following riboflavin repletion of the deficient animals, and in riboflavin-dosed controls. Whereas the rate and extent of ['4C]octanoic acid oxidation was not significantly affected by the deficiency or repletion, the extent of [I4C]adipic acid oxidation was markedly and significantly increased during repletion of the deficient animals. The time-course indicated a temporary overshoot, followed by a slow return to the control values over 1–2 weeks. Adipate oxidation was also much less affected by a preceding period of overnight starvation, than was octanoate oxidation. Thus, adipic acid (or a related metabolic probe) may have appropriate properties for the design of a functional test of fatty acid oxidation efficiency, during riboflavin deficiency or allied metabolic conditions in human subjects.
Article
The Commission's Subcommittee for the Isotopic Composition of the Elements (SIAM) has carried out its biennial review of isotopic compositions, as determined by mass spectrometry and other relevant methods. This involves a critical evaluation of the published literature, element by element, and forms the basis of the Table of Isotopic Compositions of the Elements as Determined by Mass Spectrometry presented here. New guidelines have been used to arrive at the uncertainties on the isotopic abundances and there are numerous changes to the Table since it was last published in 1991. Atomic Weights calculated from this table are consistent with (A) under bar(r)(E) values listed in the Table of Standard Atomic Weights 1997.
Article
Commissioned by the Ministry of Agriculture, Fisheries and Food, the Department of Health and carried out by Social and Community Planning Research and MRC Dunn Nutrition Unit, the dental hospitals of the Universities of Newcastle and Birmingham and the Department of Epidemiology of the University of London, this research forms part of the National Diet and Nutrition Survey. Set up in 1992 the surveys cover representative groups of the population and examine the diet of the over-65s in terms of actual dietary intake, habits, energy and nutrient intakes, physical measurements. Regional and socio-economic comparisons are made.
Article
Fractional iron absorption from a breakfast meal was determined in Peruvian children employing stable iron isotopes as labels. Iron isotopic analysis was performed by the recently developed negative thermal ionization technique for high-precision iron isotope ratio measurements using FeF4 – ions. By increasing the ascorbic acid content of the standard breakfast meal as served within the Peruvian school-breakfast program from 27 mg to 70 mg, it was possible to increase the geometric mean fractional iron absorption significantly from 5.1% (range 1.6–13.5%) to 8.2% (range 3.1–25.8%). Fractional iron absorption was calculated according to isotope dilution principles and by considering the non-monoisotopic character of the used spikes.
Article
In rural China, many pregnant women in their third trimester suffer from anemia (48%) and iron deficiency (ID; 42%), often with coexisting deficiencies of retinol and riboflavin. We investigated the effect of retinol and riboflavin supplementation in addition to iron plus folic acid on anemia and subjective well-being in pregnant women. The study was a 2-mo, double-blind, randomized trial. Subjects (n = 366) with anemia [hemoglobin (Hb) 105 g/L] were randomly assigned to 4 groups, all receiving 60 mg/d iron and 400 µg/d folic acid. The iron+folic acid (IF) group (n = 93) served as reference, the iron+folic acid+retinol group (IFA) (n = 91) was treated with 2000 µg retinol, the iron+folic acid+riboflavin group (IFB) (n = 91) with 1.0 mg riboflavin, and the iron+folic acid+retinol+riboflavin group (IFAB) (n = 91) with retinol and riboflavin. After the 2-mo intervention, the Hb concentration increased in all 4 groups (P < 0.001). The increase in the IFAB group was 5.4 ± 1.1 g/L greater than in the IF group (P < 0.001). The reduced prevalence of anemia (Hb < 110g/L) and ID anemia were significantly greater in the groups supplemented with retinol and /or riboflavin than in the IF group. Moreover, gastrointestinal symptoms were less prevalent in the IFA group than in the IF group (P < 0.05) and improved well-being was more prevalent in the groups receiving additional retinol and/or riboflavin than in the IF group (P < 0.05). Thus, a combination of iron, folic acid, retinol, and riboflavin was more effective than iron plus folic acid alone. Multimicronutrient supplementation may be worthwhile for pregnant women in rural China.
Article
Dietary intakes of several minerals and vitamins were assessed in two US sub-populations of older men and women between 60 and 80 years as part of the Lipid Research Clinics Program Prevalence Study conducted in the mid-1980s prior to widespread fortification. Dietary intakes were analyzed from 24-hour recalls using the Minnesota Nutrition Coding Center. Descriptive statistics on the two diverse sub-populations were generated for the elderly subjects at the two clinic sites, southern California and Oklahoma. Regression analyses of specific micronutrients were performed while controlling for several variables, namely, age, sex, clinic (region), education, Body Mass Index (BMI), alcohol consumption, and smoking status. Compared to current (1999-2004) Estimated Average Requirements (EARs) and Adequate Intakes (AIs) for three micronutrients without EARs for the US and Canada, several micronutrients were consumed at or close to their EAR values. Exceptions include intakes of vitamin A, vitamin E, folic acid, potassium and calcium which were very low; intakes of thiamin, riboflavin, niacin, and vitamin C were low but closer to the published EAR or AI values. High intakes approaching cut-offs for practically all subjects were found for both groups of elders at the two clinic sites for iron, phosphorus, and sodium. In general, California elderly had somewhat better consumption patterns for the vitamins, but the Oklahomans, males at least, had higher overall mineral intakes. The micronutrient deficits found in this small study suggest that most elderly US citizens were likely to be deficient in five micronutrients and marginally insufficient in four others in the mid-1980s and, despite even greater fortification currently, elderly intakes seem not to have improved substantially since the 1980s, except for subjects who are regular multi-supplement users.
Article
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.
Article
The purpose of the present study was to test the hypothesis that the already well-established mitochondrial lesion in fatty acid oxidation in riboflavin-deficient experimental animals, might be accompanied by an alteration in vivo in the kinetics of oxidation of labelled adipic acid. This dicarboxylic acid was chosen for testing as a metabolic probe because a block in its oxidation was already apparent from urine analysis of riboflavin-deficient animals, whereas the oxidation of medium- or long-chain monocarboxylic acids seemed to be little affected by deficiency in vivo. Female adult Norwegian hooded rats fed on purified diets containing either 15 mg riboflavin/kg diet (controls) or about 0.4 mg/kg (riboflavin-deficient) received an intragastric dose of either [1,6-14C]adipic acid or [1-14C]octanoic acid. Expired carbon dioxide was then collected in an alkaline trap over 3 h, for determination of radioactivity. This test was repeated at intervals for up to 2 weeks following riboflavin repletion of the deficient animals, and in riboflavin-dosed controls. Whereas the rate and extent of [14C]octanoic acid oxidation was not significantly affected by the deficiency or repletion, the extent of [14C]adipic acid oxidation was markedly and significantly increased during repletion of the deficient animals. The time-course indicated a temporary overshoot, followed by a slow return to the control values over 1-2 weeks. Adipate oxidation was also much less affected by a preceding period of overnight starvation, than was octanoate oxidation. Thus, adipic acid (or a related metabolic probe) may have appropriate properties for the design of a functional test of fatty acid oxidation efficiency, during riboflavin deficiency or allied metabolic conditions in human subjects.
Article
The effect of supplementing a regular diet with riboflavin or a combination of riboflavin and ascorbic acid on haematological indices was studied in 27 young Nigerian adults. Vitamin supplementation produced a significant increase (p less than 0.001) in haemoglobin concentration, haematocrit level and erythrocyte count. Both males and females responded similarly to the supplementation. The effect of riboflavin was similar to the combined effect of riboflavin and ascorbic acid. A significant association suggestive of enhanced erythropoiesis existed between Hb concentration and erythrocyte count in vitamin-supplemented subjects (r = 0.9722, p less than 0.002). The withdrawal of vitamin(s) supplements significantly diminished Hb concentration, haematocrit level and erythrocyte count to values similar to placebo. The data further showed that, even in malarial infection, Hb concentration, Hct level and erythrocyte count were maintained if high vitamin status was established through supplementation.
Article
Eighty-one pregnant or lactating women living in a village in The Gambia were allocated to treatment groups to receive a daily placebo, riboflavin, ferrous sulphate or ferrous sulphate plus riboflavin. At the beginning of the study and at 3 and 6 weeks thereafter women were examined clinically and blood samples collected for haematological and biochemical measurements. Pregnant women showed a wide range of response to supplement but among the lactating women an interesting pattern emerged: whereas the haematological status of the placebo group declined over 6 weeks, in the group receiving iron supplements this deterioration was reduced although not significantly. Riboflavin given in addition to iron resulted in a significant increase in circulating plasma iron and in iron stores, relative to the placebo.
Article
This chapter describes the erythroid aplasia of marasmus and kwashiorkor and similar ones produced experimentally in baboons on a synthetic riboflavin-deficient diet. Hematological, biochemical, and histological findings in both marasmus and kwashiorkor and baboons are considered and compared in the chapter. It is noted that the erythroid aplasia of marasmus and kwashiorkor develops during the recovery period while the patients are on a high-protein diet and when the clinical symptoms have disappeared. The erythroid aplasias in both marasmus and kwashiorkor and in the baboons respond to either riboflavin or prednisone. The relation between riboflavin deficiency and adrenal function is discussed in the chapter, and it is suggested that the erythroid aplasia both in marasmus and kwashiorkor and in the baboon is associated with the riboflavin deficiency interfering with adrenal cortical function.
Article
Using female Norwegian hooded rats on controlled dietary intakes we have looked at the effects of pregnancy, and of riboflavin status, on levels of circulating iron, hepatic ferritin, iron stores and iron mobilisation in vitro from ferritin. Results suggest that pregnancy, and rapid growth, increase the demand for iron turnover, and deplete ferritin stores, and that riboflavin deficiency may impair iron mobilisation for these purposes.
Article
Adult males and children between 4 and 12 years in a subsistence farming community in The Gambia were screened for haematological status. 80 men and 80 children with initially poor status were identified and allocated to three treatment groups comprising: a placebo, ferrous sulphate, and ferrous sulphate with riboflavin. Over a period of 6 weeks of supplementation there was a general improvement in haematological status in the two supplemented groups. The inclusion of riboflavin in the supplement enhanced recovery, particularly in those individuals with strikingly low levels of haemoglobin at the outset.
Article
Female Norwegian Hooded rats were given a diet low in riboflavin prior to pregnancy and during gestation and lactation. Each animal had a pair-fed control receiving a diet adequate in riboflavin. The ability of liver mitochondrial preparations to mobilise iron from ferritin was measured in the dams and their pups. The rate of mobilisation was reduced in the deficient animals relative to their controls and significantly so for the pups. The data support the hypothesis that riboflavin is an important factor in controlling iron utilisation.
A supplementation trial was carried out in 101 children, 6-12 years of age, in 3 primary schools in a rural area. Their hemoglobin level and PCV (mean +/- SD) were 11.64 +/- 1.21 g/dl and 0.356 +/- 0.028 respectively, 74% of them were anemic and the hemoglobin level were correlated with the MCHC (P < .01) . Fifty-one per cent of them had hookworm infection and all those with hemoglobin levels below 10 g/dl had hookworm infection, but there was no difference in mean hemoglobin level between those with hookworm infection and those without. The children were divided into 3 groups: Group I comprising 39 children who received placebo tablest; Group II of 33, who received ferrous sulphate (60 mg elemental iron); Group III of 29, who received ferrous sulphate (60 mg elemental iron) with riboflavin (6mg). Each child received one tablet after lunch on schooldays and evaluation was carried out after receiving 80 to 90 tablets. The mean hemoglobin change of Group II was 0.60 g/dl larger than that of Group I (P < .005) with 52% of them responding to iron. The mean hemoglobin change of Group III was 0.38 g/dl larger than that of Group II (P < .005) with 86% of them responding to iron and riboflavin. Thus additional riboflavin is beneficial in iron supplementation.
Article
In a population of schoolchildren aged 12-15 years in which biochemical deficiencies of vitamin C, riboflavin and pyridoxine affected 30.0, 33.9 and 17.2 per cent of subjects respectively, a small but statistically significant correlation was found between VO2max and vitamin C, riboflavin, vitamin A, and parameters of iron nutrition status. The administration of tablets containing 70.0 mg ascorbic acid, 2.0 mg riboflavin and 2.0 mg pyridoxine resulted in a statistically significant reduction in prevalence of vitamin deficiency, and in a small but statistically significant increase in VO2max. No such changes were observed in the untreated control groups. When data from both the experimental and control groups were pooled and analysed together, the results showed that the increase in VO2max was associated with an increase in plasma vitamin C level, in erythrocyte riboflavin content and in blood haemoglobin level. On the basis of presented data, it is not possible to conclude whether the increase in VO2max was the result of correction of vitamin deficiency per se or was due to its effect on resorption and utilization of dietary iron.
Article
Mild elevation of plasma homocysteine is an independent risk factor for vascular disease. We studied the role of 5-methyltetrahydrofolate (5-MTHF), the folate form directly involved in homocysteine metabolism, in contrast to previous studies, which used total folate measurements, in 70 coronary artery disease (CAD) patients and control subjects. We also measured S-adenosylmethionine (SAM), which controls the activity of critical enzymes of homocysteine metabolism. Fasting plasma total homocysteine was elevated (> 12.4 mumol/L for women, > 13.3 mumol/L for men) in 17% of patients, in accordance with earlier studies. These patients showed lower 5-MTHF (12.4 +/- 1.0 mumol/L, mean +/- SD) than control subjects (24.2 +/- 15.0, P < .001), and there was a clear correlation (multiple linear regression analysis: P = .002) of this relevant form of folate with homocysteine. However, 37% of the normohomocysteinemic patients also revealed similarly low 5-MTHF levels, suggesting that a decrease of 5-MTHF does not necessarily cause hyperhomocysteinemia. SAM was significantly decreased in patients (1.4 +/- 0.4 mumol/L) compared with control subjects (1.8 +/- 0.3, P < .001) but was not correlated to homocysteine or 5-MTHF. The correlation between homocysteine and 5-MTHF that was found in CAD patients but not in control subjects confirms the direct relationship between these compounds in vivo. The new finding of low SAM in patients demands further studies, since it might indicate that low levels pose risk and that SAM might be a protective factor against the development of CAD.