Water-soluble B-vitamin Research Articles

Biotin Homeostasis and Human Disorders: Recent Findings and Perspectives.

Biotin (vitamin B7, or vitamin H) is a water-soluble B-vitamin that functions as a cofactor for carboxylases, i.e., enzymes involved in the cellular metabolism of fatty acids and amino acids and in gluconeogenesis; moreover, as reported, biotin may be involved in gene regulation. Biotin is not synthesized by human cells, but it is found in food and is also produced by intestinal bacteria. Biotin status/homeostasis in human individuals depends on several factors, including efficiency/deficiency of the enzymes involved in biotin recycling within the human organism (biotinidase, holocarboxylase synthetase), and/or effectiveness of intestinal uptake, which is mainly accomplished through the sodium-dependent multivitamin transporter. In the last years, administration of biotin at high/"pharmacological" doses has been proposed to treat specific defects/deficiencies and human disorders, exhibiting mainly neurological and/or dermatological symptoms and including biotinidase deficiency, holocarboxylase synthetase deficiency, and biotin-thiamine-responsive basal ganglia disease. On the other hand, according to warnings of the Food and Drug Administration, USA, high biotin levels can affect clinical biotin-(strept)avidin assays and thus lead to false results during quantification of critical biomarkers. In this review article, recent findings/advancements that may offer new insight in the abovementioned research fields concerning biotin will be presented and briefly discussed.

Biotin: a scoping review for Nordic Nutrition Recommendations 2023.

Biotin is a water-soluble B-vitamin with key roles in metabolism and are found in most foods at low concentrations. Symptomatic biotin deficiency is rare, and few studies have investigated biotin requirements in relation to health outcomes. Data to support the setting of dietary reference values for biotin are limited.

Modulation of DNA methylation by one-carbon metabolism: a milestone for healthy aging.

Healthy aging can be defined as an extended lifespan and health span. Nutrition has been regarded as an important factor in healthy aging, because nutrients, bioactive food components, and diets have demonstrated beneficial effects on aging hallmarks such as oxidative stress, mitochondrial function, apoptosis and autophagy, genomic stability, and immune function. Nutrition also plays a role in epigenetic regulation of gene expression, and DNA methylation is the most extensively investigated epigenetic phenomenon in aging. Interestingly, age-associated DNA methylation can be modulated by one-carbon metabolism or inhibition of DNA methyltransferases. One-carbon metabolism ultimately controls the balance between the universal methyl donor S-adenosylmethionine and the methyltransferase inhibitor S-adenosylhomocysteine. Water-soluble B-vitamins such as folate, vitamin B6, and vitamin B12 serve as coenzymes for multiple steps in one-carbon metabolism, whereas methionine, choline, betaine, and serine act as methyl donors. Thus, these one-carbon nutrients can modify age-associated DNA methylation and subsequently alter the age-associated physiologic and pathologic processes. We cannot elude aging per se but we may at least change age-associated DNA methylation, which could mitigate age-associated diseases and disorders.

Folic acid ameliorates synaptic impairment following cerebral ischemia/reperfusion injury via inhibiting excessive activation of NMDA receptors

Folic acid, a water-soluble B-vitamin, has been demonstrated to decrease the risk of first stroke and improve its poor prognosis. However, the molecular mechanisms responsible for the beneficial effect of folic acid on recovery from ischemic insult remain largely unknown. Excessive activation of the N-methyl-d-aspartate receptors (NMDARs) has been shown to trigger synaptic dysfunction and excitotoxic neuronal death in ischemic brains. Here, we hypothesized that the effects of folic acid on cognitive impairment may involve the changes in synapse loss and NMDAR expression and function following cerebral ischemia/reperfusion injury. The ischemic stroke models were established by middle cerebral artery occlusion/reperfusion (MCAO/R) and by oxygen-glucose deprivation and reperfusion (OGD/R)-treated primary neurons. The results showed that folic acid supplemented diets (8.0 mg/kg for 28 days) improved cognitive performances of rats after MCAO/R. Folic acid also caused a reduction in the number of neuronal death, an increase in the number of synapses and the expressions of synapse-related proteins including SNAP25, Syn, GAP-43 and PSD95, and a decrease in p-CAMKII expression in ischemic brains. Similar changes in synaptic functions were observed in folic acid (32 µM)-treated OGD/R neurons. Furthermore, NMDA treatment reduced folic acid-induced upregulations of synapse-associated proteins and Ca2+ influx, whereas downregulations of NMDARs by NR1 or both NR2A and NR2B siRNA further enhanced the expressions of synapse-related proteins raised by folic acid in OGD/R neurons. Our findings suggest that folic acid improves cognitive dysfunctions and ameliorates ischemic brain injury by strengthening synaptic functions via the NMDARs.

Reduced Methionine Synthase (Mtr) Expression, a Model of Vitamin B12 Deficiency, Leads to Uracil Accumulation in Mitochondrial and Nuclear DNA

ObjectivesIntegrity of both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) is affected by nutritional and environmental factors. Folate and B12 are water-soluble B-vitamins that act as cofactors in folate-mediated one-carbon metabolism (FOCM), a series of one-carbon transfer reactions that support several essential cell processes including nucleotide biosynthesis. Impairments in FOCM, such as folate or vitamin B12 deficiency, can disturb thymidylate (dTMP, the “T” base in DNA) synthesis and lead to uracil misincorporation to DNA. Both folate and B12 deficiency as well as genetic polymorphisms affecting FOCM function are associated with increased uracil accumulation and DNA damage in nDNA. However, dTMP synthesis occurs in multiple cellular compartments (cytosol, nucleus, and mitochondria), and it is not well defined how FOCM impairments affects mtDNA integrity and nucleotide pool balance between compartments. MethodsCurrently, we are using in vivo and in vitro experiments to assess nucleotide synthesis and uracil accumulation in a functional model of vitamin B-12 deficiency with decreased expression of methionine synthase (Mtr), one of two B12-requiring enzymes. Tissues from Mtr+/+,+/– mice and Mtr+/+,+/- mouse-derived cells were exposed to either folate-replete or folate-deplete conditions to explore the combined effects of folate and B12 deficiency on nucleotide synthesis capacity and integrity of both nDNA and mtDNA. ResultsWe have developed and validated a novel real-time PCR-based assay to quantify uracil misincorporation into mtDNA. In mouse liver, we observed a significant increase of uracil in mtDNA with decreased Mtr expression as well as an interaction between Mtr genotype and folate status. Mouse embryonic fibroblasts (MEFs) demonstrated perturbed dTMP synthesis and increased uracil accumulation in nDNA with decreased Mtr expression. ConclusionsThese data suggest that functional B12 deficiency, as modeled by decreased Mtr expression, disrupts nucleotide synthesis in more than one cellular compartment and increases uracil accumulation not only in nDNA, but also in mtDNA. Reduced Mtr expression may cause a redistribution of folates in the cytoplasm which impacts mitochondrial folate levels, and subsequently mitochondrial dTMP synthesis. Funding SourcesN/A.

P668 Does biotin deficiency play a role in the pathogenesis of Inflammatory Bowel Disease? Preliminary results of a cross-sectional study

Abstract Background Biotin, a water-soluble B-vitamin, has been shown to have anti-inflammatory properties. A biotin-deficient diet was recently shown to induce a colitis-like phenotype in mice, alleviated by biotin substitution. Mice with DSS colitis showed biotin deficiency and significantly reduced levels of SDMT, a protein involved in biotin absorption. Oral biotin substitution reversed DSS colitis and induced remission by inhibiting NF-κB, a transcription factor that hinders inflammatory cytokine expression and plays a role in intestinal barrier integrity and IBD. We investigated for the first time a possible clinical role of biotin status in IBD. Methods In a comparative, cross-sectional study, serum samples of IBD patients were compared with samples of 80 healthy blood donors (40f;18-65y). CBC, albumin and hsCRP were determined by standard tests and samples assessed for presence/absence of inflammation (serum hsCRP, cutoff <5mg/L). Since its known that serum biotin levels does not accurately reflect biotin status, serum 3-hydroxyisovaleryl carnitine (3HIAc) levels were determined by LC-MS/MS. Results 138 IBD patients (67f;72 CD/66 UC;42.5±14.3y) were enrolled. Of these, 83/138 had inflammation (39f;43CD/40UC;42.5±14.6y) and 55/138 no inflammation (28f;29CD/26UC;42.5±13.9y). In IBD patients, mean serum 3HIAc levels were significantly higher vs. controls but similar with vs. without inflammation (Table 1). The reference serum 3HIAc level was calculated as 11.0–27.3 nmol/L from controls; biotin deficiency was defined as >27.3 nmol/L 3HIAc (90thPC), since no validated cut-off exists. Biotin deficiency in IBD patients was significantly greater than in controls (Table 1). Conclusion High serum 3HIAc levels were associated with IBD. In line with preclinical studies, biotin deficiency was more pronounced in IBD patients than controls. No relation was found with inflammatory activity or disease type. Our findings suggest that biotin may have a bigger role than thought in IBD; whether as a cause or effect in IBD pathogenesis warrants investigation. Routine assessment and correction of biotin status may ameliorate IBD and help maintain intestinal integrity. Table 1: 3-hydroxyisovaleryl carnitine levels and biotin deficiency

Metabolic engineering provides insight into the regulation of thiamin biosynthesis in plants.

Thiamin (or thiamine) is a water-soluble B-vitamin (B1), which is required, in the form of thiamin pyrophosphate, as an essential cofactor in crucial carbon metabolism reactions in all forms of life. To ensure adequate metabolic functioning, humans rely on a sufficient dietary supply of thiamin. Increasing thiamin levels in plants via metabolic engineering is a powerful strategy to alleviate vitamin B1 malnutrition and thus improve global human health. These engineering strategies rely on comprehensive knowledge of plant thiamin metabolism and its regulation. Here, multiple metabolic engineering strategies were examined in the model plant Arabidopsis thaliana. This was achieved by constitutive overexpression of the three biosynthesis genes responsible for B1 synthesis, HMP-P synthase (THIC), HET-P synthase (THI1), and HMP-P kinase/TMP pyrophosphorylase (TH1), either separate or in combination. By monitoring the levels of thiamin, its phosphorylated entities, and its biosynthetic intermediates, we gained insight into the effect of either strategy on thiamin biosynthesis. Moreover, expression analysis of thiamin biosynthesis genes showed the plant's intriguing ability to respond to alterations in the pathway. Overall, we revealed the necessity to balance the pyrimidine and thiazole branches of thiamin biosynthesis and assessed its biosynthetic intermediates. Furthermore, the accumulation of nonphosphorylated intermediates demonstrated the inefficiency of endogenous thiamin salvage mechanisms. These results serve as guidelines in the development of novel thiamin metabolic engineering strategies.

Strategies for mitigating risk posed by biotin interference on clinical immunoassays

Recently, biotin use as an oral supplement has increased significantly among the general population. Biotin is a water soluble B-vitamin and is marketed to improve the cosmetic appearance of hair, skin, and nails. In addition, high-dose biotin (>5 mg/day) is prescribed to treat inborn errors of metabolism and multiple sclerosis. Many commercial immunoassays employ the high affinity interaction between biotin and streptavidin, a protein purified from bacteria, as part of the analyte capture mechanism. As such, these immunoassays are subject to this interference. The list of affected immunoassays is vendor specific but includes tests for troponin, serum and urine Beta hCG, thyroid function, and tumor markers. The interference can be positive or negative in nature depending on the immunoassay. To address this issue, patients are recommended to abstain from taking biotin supplements for 48 h, and laboratorians and clinicians must be familiar with the potential for biotin interference in performed lab tests. Here we describe strategies to treat high biotin specimens and make them suitable for testing; and detail a number of approaches used successfully by our laboratory to educate patients, doctors, and other healthcare professionals about this interference and to mitigate the posed patient safety risk.

Genome-wide identification and transcriptional analysis of folate metabolism-related genes in maize kernels.

BackgroundMaize is a major staple food crop globally and contains various concentrations of vitamins. Folates are essential water-soluble B-vitamins that play an important role as one-carbon (C1) donors and acceptors in organisms. To gain an understanding of folate metabolism in maize, we performed an intensive in silico analysis to screen for genes involved in folate metabolism using publicly available databases, followed by examination of the transcript expression patterns and profiling of the folate derivatives in the kernels of two maize inbred lines.ResultsA total of 36 candidate genes corresponding to 16 folate metabolism-related enzymes were identified. The maize genome contains all the enzymes required for folate and C1 metabolism, characterized by highly conserved functional domains across all the other species investigated. Phylogenetic analysis revealed that these enzymes in maize are conserved throughout evolution and have a high level of similarity with those in sorghum and millet. The LC-MS analyses of two maize inbred lines demonstrated that 5-methyltetrahydrofolate was the major form of folate derivative in young seeds, while 5-formyltetrahydrofolate in mature seeds. Most of the genes involved in folate and C1 metabolism exhibited similar transcriptional expression patterns between these two maize lines, with the highest transcript abundance detected on day after pollination (DAP) 6 and the decreased transcript abundance on DAP 12 and 18. Compared with the seeds on DAP 30, 5-methyltetrahydrofolate was decreased and 5-formyltetrahydrofolate was increased sharply in the mature dry seeds.ConclusionsThe enzymes involved in folate and C1 metabolism are conserved between maize and other plant species. Folate and C1 metabolism is active in young developing maize seeds at transcriptional levels.

Race‐Ethnic Differences in B‐Vitamin Biomarkers and Intake Among US Adults in NHANES 2003–2006

The water‐soluble B‐vitamins folate, B‐6, and B‐12 are cofactors in 1‐carbon and amino acid metabolism. Low biomarker levels are associated with an increased risk for certain birth defects and/or chronic diseases. Serum folate (S‐FOL) and red blood cell folate (RBC‐FOL), serum pyridoxal‐5′‐phosphate (PLP) and pyridoxic acid (4PA), serum vitamin B‐12 (B‐12), and nutrient‐specific total vitamin intake (from diet based on one 24‐h recall and from supplements) were assessed as part of NHANES 2003–2006. We investigated race‐ethnic differences in these outcome variables in US adults (蠅20 y) stratified by nutrient‐specific supplement use. Spearman correlation coefficients between B‐vitamin biomarkers and total intake were mostly weak (r <0.4); correlations were slightly higher in supplement users (SUP+; 0.23 蠄 r 蠄 0.46) compared to nonusers (SUP‐; 0.17 蠄 r 蠄 0.35). In SUP+, non‐Hispanic whites (NHW) had higher S‐FOL, RBC‐FOL, and 4PA, while non‐Hispanic blacks (NHB) had higher B‐12 geometric mean levels compared to NHW and Mexican Americans (MA). In SUP+, total median folate intake was higher in NHW compared to NHB, but there were no race‐ethnic differences for vitamins B‐6 and B‐12. In SUP‐, NHB had lower S‐FOL, RBC‐FOL, PLP, and 4PA geometric mean levels compared to MA and NHW; NHW had lower B‐12 concentrations compared to MA and NHB. In SUP‐, total median intakes for folate, B‐6, and B‐12 were lowest in NHB and similar in NHW and MA. These preliminary data show that race‐ethnic intake patterns in B‐vitamins do not always match biomarker patterns.

Ion-transfer voltammetric determination of folic acid at meso-liquid-liquid interface arrays.

Voltammetric studies on the simple ion transfer (IT) behaviors of an important water-soluble B-vitamin, folic acid (FA), at the liquid-liquid (L-L) interface were firstly performed and then applied as a novel detection method for FA under physiological conditions. Meso-water-1,6-dichlorohexane (W-DCH) and meso-water-organogel interface arrays were built by using a hybrid mesoporous silica membrane (HMSM) with a unique structure of pores-in-pores and employed as the new platforms for the IT voltammetric study. In view of the unique structure of the HMSM, the impact of the ionic surfactant cetyltrimethylammonium bromide (CTAB), self-assembled within the silica nanochannels of the HMSM, was investigated. In particular, its effect on the IT voltammetric behavior and detection of FA at meso-L-L interface arrays was systematically examined by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and differential pulse stripping voltammetry (DPSV). It was found that all the voltammetric responses of CV, DPV, and DPSV and the corresponding detection limit of FA at such meso-L-L interface arrays are closely related to the CTAB in the HMSM. Significantly, the calculated detection limit of FA could be improved to 80 nM after the combination of the DPSV technique with the additional preconcentration of FA in the silica-CTAB nanochannels, achieved through an anion-exchange process between FA(-) and the bromide of CTAB in HMSM. This provides a new and attractive strategy for the detection of those biological anions.

Folate and breast cancer: what about high-risk women?

Folate is a water-soluble B-vitamin and is an important cofactor in one-carbon metabolism. This vitamin plays an important role in the pathogenesis of several chronic diseases. In recent years, there has been much interest in the relationship between folate status and breast cancer risk, particularly given the dramatic increase in dietary intake and blood serum folate levels in North America as a result of mandatory folic acid fortification and the widespread use of folic acid supplementation. The well-described dual effects of folate on carcinogenesis underscore the need to clarify the role of folate in the development and progression of breast cancer. This is of particular importance among those at high risk of developing breast cancer because of benign breast disease, a strong family history of breast cancer or an inherited mutation in BRCA1 or BRCA2. BRCA mutation carriers face a high lifetime risk of developing breast cancer, estimated at 80% compared with 11% in the general population. Predictive genetic testing permits the identification of these high-risk women prior to diagnosis; however, prevention is limited to surgery and chemoprevention, and the importance of modifiable risk factors such as diet and lifestyle has not been elucidated. Our goal is to develop practical and safe interventions for high-risk women leading to a decrease in the number of breast cases and deaths attributed to breast cancer.

Nephrotoxic effects of water-soluble B-vitamin therapy in diabetic nephropathy?--How true can this be?

We read with amazement and astonishment, the recent report by House et al .1 in the Journal of the American Medical Association (JAMA) suggesting that water-soluble B-vitamin supplementation with folic acid (2.5 mg/day), vitamin B(6) (25 mg/day) and vitamin B(12) (1 mg/day), versus matching placebo, accelerated diabetic nephropathy. Interestingly, it took the authors, recruiting from five different medical centers, as many as 6 long years to recruit only 238 participants, raising concerns about consistency of follow-up of the various participants scattered out among the five recruiting centers. Second, it is unclear whether a particular center contributed a preponderance of the participants thereby raising concerns about a single-center effect.2 Such details are now preferred to be available in reports of parallel-group randomized …

Hyperhomocysteinemia is a Biomarker of Sulfur-Deficiency in Human Morbidities~!2009-10-03~!2009-11-18~!2009-12-22~!

Methionine (Met) is crucially involved in the synthesis of S-compounds endowed with molecular, structural and functional properties of survival value. Dietary Met may undergo transmethylation processes to release homocysteine (Hcy) which may either be regenerated to Met following remethylation (RM) pathways or catabolized along the transsul- furation (TS) cascade. The activity of enzymes governing RM and TS pathways is depending on pyridoxine, folate and cobalamin bioavailability. Dietary restriction in any of these watersoluble B-vitamins may lead to hyperhomocysteinemia (HHcy) causing a panoply of cardiovascular disorders. Taken together, the vitamin triad only affords partial account of Hcy variance, prompting the search for additional causal factor(s). Body composition studies demonstrate that nitrogen (N) and sulfur (S) maintain tightly correlated concentrations in tissues of both healthy subjects and diseased patients. Any morbid condition characterized by insufficient N intake or assimilation, as seen in protein malnutrition or intestinal malabsorption, reduces body S accretion rates. Excessive urinary N-losses, as reported in acute or chronic inflammatory disorders, entail proportionate obligatory S-losses. As a result, lean body mass (LBM) undergoes downsizing and con- comitant depletion of N and S body stores which depresses the activity of cystathionine-� -synthase, thereby promoting upstream accumulation of Hcy and overstimulation of RM processes. HHcy thus appears as the dark side of efforts devel- oped by S-deprived patients to safeguard Met homeostasis. Irrespective of vitamin-B status, Hcy values are negatively correlated with LBM shrinkage well identified by the serial measurement of plasma transthyretin (TTR). The S- deprivation theory fulfills the gap and allows full causal coverage of the metabolic anomaly, hence providing together with vitamin-deficiencies an unifying overview of the main nutritional determinants implicated in HHcy epidemiology.

Evidence for the involvement of the opioid system in the antidepressant-like effect of folic acid in the mouse forced swimming test

The opioid system has been implicated in major depression and in the mechanism of action of antidepressants. This study investigated the involvement of the opioid system in the antidepressant-like effect of the water-soluble B-vitamin folic acid in the forced swimming test (FST). The effect of folic acid (10 nmol/site, i.c.v.) was prevented by the pretreatment of mice with naloxone (1 mg/kg, i.p., a nonselective opioid receptor antagonist), naltrindole (3 mg/kg, i.p., a selective δ-opioid receptor antagonist), naloxonazine (10 mg/kg, i.p., a selective μ 1-opioid receptor antagonist, 24 h before), but not with naloxone methiodide (1 mg/kg, s.c., a peripherally acting opioid receptor antagonist). In addition, a sub-effective dose of folic acid (1 nmol/site, i.c.v.) produced a synergistic antidepressant-like effect in the FST with a sub-effective dose of morphine (1 mg/kg, s.c.). A further approach was designed to investigate the possible relationship between the opioid system and NMDA receptors in the mechanism of action of folic acid in the FST. Pretreatment of the animals with naloxone (1 mg/kg, i.p.) prevented the synergistic antidepressant-like effect of folic acid (1 nmol/site, i.c.v.) and MK-801 (0.001 mg/kg, i.p., a non-competitive NMDA receptor antagonist). Together the results firstly indicate that the anti-immobility effect of folic acid in the FST is mediated by an interaction with the opioid system (μ 1 and δ), likely dependent on the inhibition of NMDA receptors elicited by folic acid.

Polymorphisms in folate metabolizing enzymes and transport proteins and the risk of breast cancer

An accumulating body of evidence suggests that there is an inverse relationship between the intake of folate (a water-soluble B-vitamin) and the risk of developing breast cancer. Individual variation in the genes involved in the transport of folate, or its metabolism, may affect risk, or may modify the association between folate and breast cancer risk. We performed a case-control study to evaluate the association between common polymorphisms in six folate-related genes and the risk of breast cancer in 1,009 breast cancer patients and 907 healthy controls. Study subjects were genotyped for eight single nucleotide polymorphisms (SNPs) in these six genes. We observed no association between the MTHFR, RFC, MS and MTRR genotypes and the risk of breast cancer. These data do not support the hypothesis that genetic variation in genes involved in the metabolism of folate are implicated in the etiology of breast cancer.

P.2.130 Efficacy of ziprasidone in dysphoric mania

The opioid system has been implicated in major depression and in the mechanism of action of antidepressants. This study investigated the involvement of the opioid system in the antidepressant-like effect of the water-soluble B-vitamin folic acid in the forced swimming test (FST). The effect of folic acid (10 nmol/site, i.c.v.) was prevented by the pretreatment of mice with naloxone (1 mg/kg, i.p., a nonselective opioid receptor antagonist), naltrindole (3 mg/kg, i.p., a selective δ-opioid receptor antagonist), naloxonazine (10 mg/kg, i.p., a selective μ1-opioid receptor antagonist, 24 h before), but not with naloxone methiodide (1 mg/kg, s.c., a peripherally acting opioid receptor antagonist). In addition, a sub-effective dose of folic acid (1 nmol/site, i.c.v.) produced a synergistic antidepressant-like effect in the FST with a sub-effective dose of morphine (1 mg/kg, s.c.). A further approach was designed to investigate the possible relationship between the opioid system and NMDA receptors in the mechanism of action of folic acid in the FST. Pretreatment of the animals with naloxone (1 mg/kg, i.p.) prevented the synergistic antidepressant-like effect of folic acid (1 nmol/site, i.c.v.) and MK-801 (0.001 mg/kg, i.p., a non-competitive NMDA receptor antagonist). Together the results firstly indicate that the anti-immobility effect of folic acid in the FST is mediated by an interaction with the opioid system (μ1 and δ), likely dependent on the inhibition of NMDA receptors elicited by folic acid.

Physiology of folate and vitamin B12 in health and disease.

Folate is a water-soluble B-vitamin and enzymatic cofactor that is necessary for the synthesis of purine and thymidine nucleotides and for the synthesis of methionine from homocysteine. Impairment of folate-mediated one-carbon metabolic pathways can result from B-vitamin deficiencies and/or single nucleotide polymorphisms, and increases risk for pathologies, including cancer and cardiovascular disease, and developmental anomalies including neural tube defects. Although several well validated metabolic and genomic biomarkers for folate deficiency exist, our understanding of the biochemical and genetic mechanisms whereby impaired folate metabolism increases risk for developmental anomalies and disease is limited, as are the mechanisms whereby elevated folate intake protects against these pathologies. Therefore, current initiatives to increase folate intakes in human populations to ameliorate developmental anomalies and prevent disease, while effective, lack predictive value with respect to unintended adverse outcomes.

Vitamins and sport.

In a double blind test on 40 men and women high performance fencers the influence of a multivitamin-electrolyte-preparation on reaction time, hit-frequency and neuromuscular irritability was determined. Evidence of B1, B2 and B6-deficiencies up to 70% were found. After application of the preparation an increase of performance of 3% could be observed. The tests were carried out by means of coenzymatic activation of the respective vitamins in the haemolysate of erythrocytes. The results are explained by the role of the vitamins in the human organism and by the special conditions under which endurance athletes have to perform: high turn-over rate of the energy metabolism, an increase of the body core temperature and thus increased sweat loss, factors leading to deficiencies of the water soluble B-vitamins.

Intestinal Absorption of Riboflavin by Rat and Hamster

A number of techniques in vivo and in vitro have provided quantitative data concerning passage of carbohydrates, lipids, and amino acids across the intestinal wall. The water-soluble B-vitamins, aside from B!2 have not been extensively studied by these techniques. We present data here on the absorption in vivo and in vitro of riboflavin by the intestinal tract of rat and hamster, and a correlation of this information with available knowledge of riboflavin metabolism by the intestine.