Which Circulating Antioxidant Vitamins Are Confounded by Socioeconomic Deprivation? The MIDSPAN Family Study

Background

Antioxidant vitamins are often described as having “independent” associations with risk of cancer, cardiovascular disease (CVD) and mortality. We aimed to compare to what extent a range of antioxidant vitamins and carotenoids are associated with adulthood and childhood markers of socioeconomic deprivation and to adverse lifestyle factors.

Methods and Findings

Socioeconomic and lifestyle measures were available in 1040 men and 1298 women from the MIDSPAN Family Study (30–59 years at baseline) together with circulating levels of vitamins A, C, E, and carotenoids (α-carotene, β-carotene, lutein and lycopene). Markers of socioeconomic deprivation in adulthood were consistently as strongly associated with lower vitamin C and carotenoid levels as markers of adverse lifestyle; the inverse association with overcrowding was particularly consistent (vitamin C and carotenoids range from 19.1% [95% CI 30.3–6.0] to 38.8% [49.9–25.3] lower among those in overcrowded residencies). These associations were consistent after adjusting for month, classical CVD risk factors, body mass index, physical activity, vitamin supplements, dietary fat and fibre intake. Similar, but weaker, associations were seen for childhood markers of deprivation. The association of vitamin A or E were strikingly different; several adult adverse lifestyle factors associated with higher levels of vitamin A and E, including high alcohol intake for vitamin A (9.5% [5.7–13.5]) and waist hip ratio for vitamin E (9.5% [4.8–14.4]), with the latter associations partially explained by classical risk factors, particularly cholesterol levels.

Conclusions

Plasma vitamin C and carotenoids have strong inverse associations with adulthood markers of social deprivation, whereas vitamin A and E appear positively related to specific adverse lifestyle factors. These findings should help researchers better contextualize blood antioxidant vitamin levels by illustrating the potential limitations associated with making causal inferences without consideration of social deprivation.     

代谢工程在维生素生产中的应用及研究进展

维生素是维持人体生命活动必需的一类有机物质,机体本身一般不能合成或合成量不足,因此需经食物或其他强化产品获取。目前,维生素产品已广泛应用于医药、食品添加剂、饲料添加剂、化妆品等领域,而且全球对维生素的需求也是呈逐年增长态势。维生素的生产方法主要包括化学合成法和生物合成法。化学合成法通常安全隐患大、反应条件严苛、废物污染严重,相比之下,代谢工程生产维生素绿色环保安全、能耗低,因此建立微生物细胞工厂具有重大的科学意义和应用需求。文中回顾了近30年来代谢工程在维生素生产领域的研究进展,详细阐述了水溶性维生素(维生素B1、B2、B3、B5、B6、B7、B9、B12和维生素C的前体)和脂溶性维生素(维生素A、维生素D的前体、维生素E和维生素K)的生物合成研究现状,并对其发酵生产的瓶颈进行了探讨,最后对合成生物技术创建维生素生产菌种进行了展望。     

Antioxidant vitamins C, E and beta-carotene reduce DNA damage before as well as after gamma-ray irradiation of human lymphocytes in vitro

The protective effect of Vitamins C, E and beta-carotene against gamma-ray-induced DNA damage in human lymphocytes in vitro was investigated. Cultured lymphocytes were exposed to increasing concentration of these vitamins either before or after irradiation with 2Gy of gamma-rays and DNA damage was estimated using micronucleus assay. A radioprotective effect was observed when antioxidant vitamins were added to cultured cells before as well after irradiation; the strongest effect was observed when they were added no later than 1h after irradiation. The radioprotective effect of vitamins also depended on their concentration; Vitamins C added at low concentration (1 microg/ml) before exposure of the cells to radiation prevented induction of micronuclei. Vitamin E at the concentration above 2 microg/ml decreased the level of radiation-induced micronuclei when compared to the cells irradiated without vitamin treatment. beta-Carotene was effective at all tested concentrations from 1 to 5 microg/ml and reduced the number of micronuclei in irradiated cells. The vitamins had no effect on radiation-induced cytotoxicity as measured by nuclear division index. The radioprotective action of antioxidant Vitamins C, E and beta-carotene was dependent upon their concentration as well as time and sequence of application.     

Plasma antioxidants and longevity: a study on healthy centenarians

A large body of experimental research indicates that oxidative stress contributes to the processes related to aging and to the pathogenesis of several age-related diseases. Vitamins and antioxidant enzymes have a fundamental role in defending the organism from oxidative stress. To better understand the role of antioxidants in human aging, we measured plasma levels of vitamin C (ascorbic acid), uric acid, vitamin E (alpha-tocopherol), vitamin A (retinol), carotenoids, total thiol groups, and the activity of plasma superoxide dismutase (SOD) and glutathione peroxidase (GPX) as well as the activity of red blood cell (RBC) SOD in 32 healthy centenarians-17 elderly subjects aged 80-99 years, 34 elderly subjects aged 60-79 years, and 24 adults aged less than 60 years. Considering the "noncentenarians" only, we observed a consistent behavior in the antioxidant pattern, with a decrease of the nonenzymatic antioxidants and an increase of the enzymatic antioxidant activities relative to age. Remarkably, centenarians were characterized as having the highest levels of vitamins A and E, whereas the activities of both plasma and RBC SOD, which increase with age, decreased in centenarians. From these results, it is evident that healthy centenarians show a particular profile in which high levels of vitamin A and vitamin E seem to be important in guaranteeing their extreme longevity.     

Investigation of antioxidant vitamins (A,E and C) and selenium levels in chickens receiving estrogen or testosterone

In the present study estrogen or testosterone was administered to broiler chickens (6 weeks old) for 5 weeks and levels of antioxidant vitamins (A, E and C) and selenium (Se) were determined. In animals who received estrogen, vitamins A, E, C and Se levels were 0.70 +/- 0.19, 11.0 +/- 2.45, 20.0 +/- 5.17 and 130.0 +/- 25.0 microg l(-1), respectively. Vitamins A, E, C and Se levels in the testosterone-administered group were found to be 0.54 +/- 0.16, 9.9 +/- 1.96, 18.0 +/- 5.18 and 100.0 +/- 18.0 microg l(-1), respectively. Vitamins A, E, C and Se levels were found to be significantly increased in the estrogen-administered group compared to the controls (p < 0.01, p < 0.01, p < 0.05, p < 0.05, respectively). Although all parameters were increased in testosterone-treated animals, only increases in vitamins A and E were found to be statistically significant (p < 0.01, p < 0.01, respectively). Based on the present findings, estrogen and testosterone show direct antioxidant effects by increasing the activities of some enzymes and they also cause an increase in antioxidant vitamin levels and hence indirectly also contribute to antioxidant capacity.     

Homologous metabolic and gene activating routes for vitamins E and K

Vitamins E and K share structurally related side chains and are degraded to similar final products. For vitamin E the mechanism has been elucidated as initial ω-hydroxylation and subsequent β-oxidation. For vitamin K the same mechanism can be suggested analogously. ω-Hydroxylation of vitamin E is catalyzed by cytochrome P450 enzymes, which often are induced by their substrates themselves via the activation of the nuclear receptor PXR. Vitamin E is able to induce CYP3A-forms and to activate a PXR-driven reporter gene. It is shown here that K-type vitamins are also able to activate PXR. A ranking showed that compounds with an unsaturated side chain were most effective, as are tocotrienols and menaquinone-4 (vitamin K₂), which activated the reporter gene 8–10-fold. Vitamers with a saturated side chain, like tocopherols and phylloquinone were less active (2–5-fold activation). From the fact that CYPs commonly responsible for the elimination of xenobiotics are involved in the metabolism of fat-soluble vitamins and the ability of the vitamins to activate PXR it can be concluded that supranutritional amounts of these vitamins might be considered as foreign.     

Stability of vitamins in premixes

The stability of Vitamins A, E, and K₃ in premixes during storage in controlled conditions was studied over a period of one year. Analysis on vitamins content was performed at the beginning of the study and after 3, 6, and 12 months. The effect of the added choline chloride on the vitamin stability was also examined. All vitamins were more stable in a premix containing no choline chloride than in a premix containing choline chloride. During storage for 12 months, the concentrations of Vitamins A, E, and K₃ in the sample without choline chloride decreased to 53%, 59%, and 80% of their initial values, respectively. In the sample containing choline chloride, the concentrations of these vitamins decreased to 39%, 50%, and 9% of their initial values, respectively.     

Processing of vitamin A and E in the human gastrointestinal tract

We aimed to provide basic data on the processing of vitamin A and E in the human gastrointestinal tract and to assess whether the size of emulsion fat globules affects the bioavailability of these vitamins. Eight healthy men received intragastrically two lipid formulas differing in their fat-globule median diameter (0.7 vs. 10. 1 microm. Formulas provided 28 mg vitamin A as retinyl palmitate and 440 mg vitamin E as all-rac alpha-tocopherol. Vitamins were measured in gastric and duodenal aspirates, as well as in chylomicrons, during the postprandial period. The gastric emptying rate of lipids and vitamin A and E was similar. The free retinol/total vitamin A ratio was not significantly modified in the stomach, whereas it was dramatically increased in the duodenum. The proportion of ingested lipid and vitamins was very similar in the duodenal content. The chylomicron response of lipids and vitamins was not significantly different between the two emulsions. Our main conclusions are as follows: 1) there is no significant metabolism of vitamin A and E in the human stomach, 2) the enzyme(s) present in the duodenal lumen is significantly involved in the hydrolysis of retinyl esters, and 3) the size of emulsion fat globules has no major effect on the overall absorption of vitamin A and E.     

Vitamins E and K induce aryl hydrocarbon hydroxylase activity in human cell cultures

Two fat soluble vitamins, Vitamins E and K, when added into culture medium, were found to increase aryl hydrocarbon hydroxylase activity in human cultured cells. The extent of induction in a hepatoma-derived cell line (Hep G2) by these vitamins is of similar magnitude to those cells receiving benz[a]anthracene; whereas in a mammary tumor-derived cell line (MCF-7), benz[a]anthracene is the best inducer for the hydroxylase activity. The increase of the hydroxylase activity is associated with increased levels of a specific mRNA coding for polynuclear aromatic hydrocarbons-induced form of cytochrome P-450 with Vitamins E and K treatment. The size of the induced mRNA is 3.3 kilobase which is the same as that of benz[a]anthracene treatment.     

Effect of vitamins A and E on the structural-functional state of retinal lysosomes

Vitamins A and E (alpha-tocopheryl-acetate and retinol-palmitate) are studied for their effect on structural and functional state of retina lysosomes. These vitamins are shown to exert a pronounced membrane-tropic effect on lysosomes. Vitamin E in chosen concentrations stabilizes membranes of retina lysosomes both in the in vitro and in vivo experiments. Vitamin A acts on them as a labilizing agent. The mentioned effect of vitamins may be corrected by low-energy radiation of the monochromatic coherent light (lambda = 632.8 nm). It is substantiated experimentally that the stabilizing effect of vitamin E may be intensified in case of the action combined with laser radiation on lysosomes. The labilizing effect of vitamin A on membranes of organelles under study may be weakened by application of laser radiation of low intensities.     

Radioprotective effect of vitamins C and E

Albino rats were treated with aqueous vitamin C solution and vitamin E solution dissolved in olive oil at two concentrations, 100 and 300 mg/kg/day, for 6 months. Some of the animals were then subjected to whole-body irradiation. Chromosomal aberrations and mitotic activity in non-irradiated and irradiated groups were recorded. Both vitamins were found to be non-mutagenic. Vitamins C exerted a radioprotective effect but vitamin E was not radioprotective and it suppressed the radioprotection otherwise produced by olive oil.     

Vitamins E and D3 Attenuate Demyelination and Potentiate Remyelination Processes of Hippocampal Formation of Rats Following Local Injection of Ethidium Bromide

Cognitive deficits have been observed in patients with multiple sclerosis (MS) due to hippocampal insults. Antioxidant vitamins D and E are suggested for patients suffering from neurodegenerative diseases like MS, while their mechanisms of action are not well understood. Here, we have tried to study the effects of these vitamins on demyelination, cell death, and remyelination of rat hippocampus following local ethidium bromide (EB) injection. Animals received 100 mg/kg vitamin E or 5 μg/kg of vitamin D3 for 2, 7, or 28 days. The extent of demyelination, myelin staining intensity, and expression of myelin basic protein and caspase-3 were investigated using histological and immunoblotting verification. Administration of EB alone caused demyelination, cell death, and afterward an endogenous repair. Vitamins E and D3 reduced the EB-induced damage and increased the endogenous remyelination of hippocampus. Although the anti-apoptotic effect of these vitamins and protection against demyelination were predictable based on their antioxidant effect, our results indicated the positive effect of vitamins E and D3 on process of remyelination by endogenous progenitor cells and supported their possible therapeutic effects in the context of demyelinating diseases like MS.     

Intracellular Transport of Fat‐Soluble Vitamins A and E

Vitamins are compounds that are essential for the normal growth, reproduction and functioning of the human body. Of the 13 known vitamins, vitamins A, D, E and K are lipophilic compounds and are therefore called fat‐soluble vitamins. Because of their lipophilicity, fat‐soluble vitamins are solubilized and transported by intracellular carrier proteins to exert their actions and to be metabolized properly. Vitamin A and its derivatives, collectively called retinoids, are solubilized by intracellular retinoid‐binding proteins such as cellular retinol‐binding protein (CRBP), cellular retinoic acid‐binding protein (CRABP) and cellular retinal‐binding protein (CRALBP). These proteins act as chaperones that regulate the metabolism, signaling and transport of retinoids. CRALBP‐mediated intracellular retinoid transport is essential for vision in human. α‐Tocopherol, the main form of vitamin E found in the body, is transported by α‐tocopherol transfer protein (α‐TTP) in hepatic cells. Defects of α‐TTP cause vitamin E deficiency and neurological disorders in humans. Recently, it has been shown that the interaction of α‐TTP with phosphoinositides plays a critical role in the intracellular transport of α‐tocopherol and is associated with familial vitamin E deficiency. In this review, we summarize the mechanisms and biological significance of the intracellular transport of vitamins A and E.      

Plant amino acid-derived vitamins: biosynthesis and function

Vitamins are essential organic compounds for humans, having lost the ability to de novo synthesize them. Hence, they represent dietary requirements, which are covered by plants as the main dietary source of most vitamins (through food or livestock’s feed). Most vitamins synthesized by plants present amino acids as precursors (B₁, B₂, B₃, B₅, B₇, B₉ and E) and are therefore linked to plant nitrogen metabolism. Amino acids play different roles in their biosynthesis and metabolism, either incorporated into the backbone of the vitamin or as amino, sulfur or one-carbon group donors. There is a high natural variation in vitamin contents in crops and its exploitation through breeding, metabolic engineering and agronomic practices can enhance their nutritional quality. While the underlying biochemical roles of vitamins as cosubstrates or cofactors are usually common for most eukaryotes, the impact of vitamins B and E in metabolism and physiology can be quite different on plants and animals. Here, we first aim at giving an overview of the biosynthesis of amino acid-derived vitamins in plants, with a particular focus on how this knowledge can be exploited to increase vitamin contents in crops. Second, we will focus on the functions of these vitamins in both plants and animals (and humans in particular), to unravel common and specific roles for vitamins in evolutionary distant organisms, in which these amino acid-derived vitamins play, however, an essential role.     

UVB induced oxidative stress in human keratinocytes and protective effect of antioxidant agents

This study aims at exploring the oxidative stress in keratinocytes induced by UVB irradiation and the protective effect of nutritional antioxidants. Cultured Colo-16 cells were exposed to UVB in vitro followed by measurement of reactive oxygen species (ROS), endogenous antioxidant enzyme activity, as well as cell death in the presence or absence of supplementation with vitamin C, vitamin E, or Ginsenoside Panoxatriol. Intracellular ROS content was found significantly reduced 1 h after exposure, but increased at later time points. After exposure to 150–600 J m⁻² UVB, reduction of ROS content was accompanied by increased activity of catalase and CuZn-superoxide dismutase at early time points. Vitamins C and E, and Ginsenoside Panoxatriol counteracted the increase of ROS in the Colo-16 cells induced by acute UVB irradiation. At the same time, Ginsenoside Panoxatriol protected the activity of CuZn-superoxide dismutase, while vitamin E showed only a moderate protective role. Vitamins C and E, and Ginsenoside Panoxatriol in combination protected the Colo-16 cells from UVB-induced apoptosis, but not necrosis. These findings suggest that vitamins C and E as well as Ginsenoside Panoxatriol are promising protective agents against UVB-induced damage in skin cells.     

Methodological Rigour and Transparency of Clinical Practice Guidelines Developed by Neurology Professional Societies in Croatia

Background

Clinical practice guidelines are systematically created documents that summarize knowledge and assist in delivering high-quality medicine by identifying evidence that supports best clinical care. They are produced not only by international professional groups but also by local professionals to address locally-relevant clinical practice. We evaluated the methodological rigour and transparency of guideline development in neurology formulated by professionals in a local medical community.

Methods

We analyzed clinical guidelines in neurology publicly available at the web-site of the Physicians’ Assembly in Croatia in 2012: 6 guidelines developed by Croatian authors and 1 adapted from the European Federation of Neurological Societies. The quality was assessed by 2 independent evaluators using the AGREE II instrument. We also conducted a search of the Cochrane Library to identify potential changes in recommendation from Cochrane systematic reviews included in guideline preparation.

Results

The methodological quality of the guidelines greatly varied across different domains. „Scope and Purpose” and „Clarity of Presentation“ domains received high scores (100% [95% confidence interval (CI) 98.5–100] and 97% [77.9–100], respectively), the lowest scores were in “Stakeholder Involvement“ (19% [15.5–34.6]) and “Editorial Independence” (0% [0–19.2]). Conclusions of 3 guidelines based on Cochrane systematic reviews were confirmed in updated versions and one update provided new information on the effectiveness of another antidepressant. Two Cochrane reviews used in guidelines were withdrawn and split into new reviews and their findings are now considered to be out of date.

Conclusion

Neurological guidelines used in Croatia differ in structure and their methodological quality. We recommend to national societies and professional groups to develop a more systematic and rigorous approach to the development of the guidelines, timely inclusion of best evidences and an effort to involve target users and patients in the guideline development procedures.     

Proteins involved in uptake, intracellular transport and basolateral secretion of fat-soluble vitamins and carotenoids by mammalian enterocytes

Our understanding of the molecular mechanisms responsible for fat-soluble vitamin uptake and transport at the intestinal level has advanced considerably over the past decade. On one hand, it has long been considered that vitamin D and E as well as β-carotene (the main provitamin A carotenoid in human diet) were absorbed by a passive diffusion process, although this could not explain the broad inter-individual variability in the absorption efficiency of these molecules. On the other hand, it was assumed that preformed vitamin A (retinol) and vitamin K1 (phylloquinone) absorption occurred via energy-dependent processes, but the transporters involved have not yet been identified. The recent discovery of intestinal proteins able to facilitate vitamin E and carotenoid uptake and secretion by the enterocyte has spurred renewed interest in studying the fundamental mechanisms involved in the absorption of these micronutrients. The proteins identified so far are cholesterol transporters such as SR-BI (scavenger receptor class B type I), CD36 (cluster determinant 36), NPC1L1 (Niemann–Pick C1-like 1) or ABCA1 (ATP-Binding Cassette A1) displaying a broad substrate specificity, but it is likely that other membrane proteins are also involved. After overviewing the metabolism of fat-soluble vitamins and carotenoids in the human upper gastrointestinal lumen, we will focus on the putative or identified proteins participating in the intestinal uptake, intracellular transport and basolateral secretion of these fat-soluble vitamins and carotenoids, and outline the uncertainties that need to be explored in the future. Identifying the proteins involved in intestinal uptake and transport of fat-soluble vitamins and carotenoids across the enterocyte is of great importance, especially as some of them are already targets for the development of drugs able to slow cholesterol absorption. Indeed, these drugs may also interfere with lipid vitamin uptake. A better understanding of the molecular mechanisms involved in fat-soluble vitamin and carotenoid absorption is a priority to better optimize their bioavailability.     

Proteins involved in fat-soluble vitamin and carotenoid transport across the intestinal cells: New insights from the past decade

It is now well established that vitamins D, E, and K and carotenoids are not absorbed solely through passive diffusion. Broad-specificity membrane transporters such as SR-BI (scavenger receptor class B type I), CD36 (CD36 molecule), NPC1L1 (Niemann Pick C1-like 1) or ABCA1 (ATP-binding cassette A1) are involved in the uptake of these micronutrients from the lumen to the enterocyte cytosol and in their secretion into the bloodstream. Recently, the existence of efflux pathways from the enterocyte back to the lumen or from the bloodstream to the lumen, involving ABCB1 (P-glycoprotein/MDR1) or the ABCG5/ABCG8 complex, has also been evidenced for vitamins D and K. Surprisingly, no membrane proteins have been involved in dietary vitamin A uptake so far. After an overview of the metabolism of fat-soluble vitamins and carotenoids along the gastrointestinal tract (from the mouth to the colon where interactions with microbiota may occur), a focus is placed on the identified and candidate proteins participating in the apical uptake, intracellular transport, basolateral secretion and efflux back to the lumen of fat-soluble vitamins and carotenoids in enterocytes. This review also highlights the mechanisms that remain to be identified to fully unravel the pathways involved in fat-soluble vitamin and carotenoid intestinal absorption.     

Implementation of the 2015 European Society of Cardiology guidelines for the management of infective endocarditis in the Netherlands

Because the occurrence of infective endocarditis (IE) continues to be associated with high mortality, a working group was created by the Dutch Society of Cardiology to examine how the most recent European Society of Cardiology (ESC) guidelines for IE management could be implemented most effectively in the Netherlands. In order to investigate current Dutch IE practices, the working group conducted a country-wide survey. Based on the results obtained, it was concluded that most ESC recommendations could be endorsed, albeit with some adjustments. For instance, the suggested pre-operative screening and treatment of nasal carriers of Staphylococcus aureus as formulated in the ESC guideline was found to be dissimilar to current Dutch practice, and was therefore made less restrictive. The recently adapted ESC diagnostic criteria for IE were endorsed, while the practical employment of the relevant diagnostic techniques was simplified in an adapted flowchart. In addition, the presence of a multidisciplinary, so-called ‘endocarditis team’ in tertiary centres was proposed as a quality indicator. An adapted flowchart specifically tailored to Dutch practice for microbiological diagnostic purposes was constructed. Lastly, the working group recommended the Stichting Werkgroep Antibioticabeleid (SWAB; Dutch Working Party on Antibiotic Policy) guidelines for IE treatment instead of the antibiotic regimens proposed by the ESC.

     

Basis for the historical stages for studying the biochemistry of vitamins. Noncoenzymatic mechanisms of vitamin B1

Biochemistry of vitamins is one of the leading trends in the fundamental researches of A. V. Palladin Institute of Biochemistry from the moment of its foundation in 1925. The Laboratory of Vitamins Biochemistry was organised in 1994, it was reorganized into the Department of Vitamins Biochemistry in 1966, and later it was renamed as the Department of Coenzymes Biochemistry. Now the investigations at the Coenzymes Biochemistry Department headed (from 1986) by G. V. Donchenko, Corr.-Member of the National Academy of Sciences of Ukraine, are directed to estimation of vitamins A, E, B1 and PP action molecular mechanisms. Investigation of specific protein-acceptors of vitamins and their biologically active derivatives is a contemporary and effective methodological approach to the estimation of some molecular mechanisms of vitamins action on cellular metabolism. Considering the challenging theoretical and practical aspects of the further fundamental investigation development in the molecular vitaminology the following items are currently being worked in the Department last time: 1. Study of some molecular mechanisms of thiamine and vitamin PP neurotropic action. These investigations are oriented to clearing some new aspects of noncoenzymic mechanism of its influence on the nervous cell functioning both in the norm and at some nervous diseases. 2. Study of some molecular mechanisms of regulation by means of fat-soluble vitamins A, E and their specific proteins-acceptors of DNA, RNA and protein biosynthesis in the nuclei and mitochondria of actively proliferous cells. These investigations are aimed to the estimation of molecular mechanisms of fat-soluble vitamins participation in the regulation of DNA-dependent synthesis of RNA, RNA-polymerase activity, mechanism of their anticancerogenous effect, vitamin E participation in the realisation of nuclear genetic information. 3. Study of intracellular protein-receptors, which take part in realisation of vitamins and their biologically active derivatives functions in the human and animals' organism. The investigations, directed to study of a role of retinol-binding proteins in exchange of the vitamin A and in biosynthesis of DNA, RNA and proteins, the role of tocopherol-binding proteins in realisation of biological action of vitamin E in cells and thiamine-binding proteins in realisation of neurotropic action of vitamin B1 are actively developed. 4. Investigation of mechanisms of antioxidizing and antiradical biological action of vitamin D3, ecdisterone and related biologically active compounds. Basing on the fundamental researches some vitamins preparations have been created, such as "Carotin-M", "Cardiovit", "Evit-1", "Soevit", "Metovit", "Caratel'ka" and others. The results of fundamental investigation of noncoenzymic thiamine function led us to elaboration of a new hypothesis about molecular mechanism of vitamin B1 neurotropic action. According to the hypothesis the thiamine high neuroactivity is a result of existence in the nervous ending a specific mobile thiamine pool and connection thiamine metabolism with nervous cell membrane potential and acetylcholine metabolism.