Magistro baigiamajame darbe bus išanalizuota ir įvertinta maisto papildų reklamos atitikimas teisės aktų reikalavimams, iškeltos maisto papildų ženklinimo, tvirtinimo vartoti, vartojimo kėblumai visuomenėje bei pateikti siūlymai, kaip šias problemas spręsti. Pirmojoje darbo dalyje bus nagrinėjami maisto papildų reklamos bei kiti teisinei aktai. Antrojoje dalyje bus vykdomi tyrimai norint išsiaiškint realia maisto papildų reklamos situaciją Lietuvoje, bei to poveikio įtaką visuomenei. Trečiojoje dalyje bus nagrinėjamas atliktas tyrimas, kuriuo norima išsiaiškinti ar maisto papildų reklama atitinka visus Lietuvos Respublikos teisinius aktus. / Master's thesis will be analyzed and evaluated food supplements advertising compliance with legislative requirements, bringing food supplement labeling approval for use, consumption in the complexities of society and to provide suggestions on how to address these issues. The first part will be considered food supplements advertising and other legal acts. The second part will be carried out tests in order to check on the actual food supplements advertising situation in Lithuania, as well as the impact of societal impact. The third part will be examined in the study, which is necessary to clarify or supplements advertising complies with all the legal acts of the Republic of Lithuania.

Lactic acid bacteria are natural habitants of human gastrointectinal tract. Among the most important are bacteria of genus Lactobacillus and genus Bifidobacterium that contain a lot of probiotic species. Probiotic species are used as food supplements. This work was focused on DNA separation from crude cell lysates of 4 food supplements using magnetic carrier P(HEMA-co-GMA) covered by carboxyl groups. DNA was reversible adsorbed to the carriers in the presence of PEG 6000 (16%) and NaCl (2 M) (final concentrations) and eluted into TE buffer. Lysis of cells from food supplements was performed by lysozyme, SDS and proteinase K. The amount of lysozyme was optimalized. Concentration of separated DNA was measured by spectrophotometric method. The amount of isolated DNA was suitable for PCR. Isolated DNA was used for PCR with universal primers, PCR specific for genus Lactobacillus and genus Bifidobacterium and for 9 different species-specific PCRs: Lactobacillus rhamnosus, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus fermentum, Lactobacillus casei/paracasei, Streptococcus thermophilus, Bifidobacterium longum, Bifidobacterium bifidum and Bifidobacterium infantis. Amplicons were detected by agarose gel electrophoresis (1,8%). It was shown that DNA amplification methods are quick and precise for identification of studied species. The results of bacteria identification were compared with data provided by the manufacturer. In all food supplements, bacteria of genus Lactobacillus and Bifidobacterium were detected. However, only some species provided by manufacturer were identified by PCR in each tablet.

Name of the work: The content of the anthocyanidines and other pigments in commercial drugs and food supplements Author: Hana Karanská This thesis is focused on the determination of anthocyanins and anthocyanidins in food supplements, fruits and juices. The substances were extracted with methanol using an ultrasonic bath or boiling water bath. Analysis was performed by HPLC. The results of this work show that the content of anthocyanins and anthocyanidins are in the determined samples represented in varying degrees. All the analysed samples showed the content of these substances. Based on information from the manufacturer we can say that the product Ostrovidky plus contained the declared amount of anthocyanins. Manufacturers of remaining specimens does not provide sufficient information about the composition for unambiguous determination of the result, but we can say that the products approximately satisfy the content of substances declared by the manufacturer. The amount of anthocyanins in the fruit meets the values reported in literature. Juices did not indicate the exact amount of anthocyanins.

This work deals with the regulation of advertising of drugs and food supplements. The goal is to assess whether the rules are complied with and whether the current decision-making practice of supervisory authorities in the markets for medicinal and nutritional supplements sufficient.

Η παρούσα εργασία αποσκοπεί στο να διερευνήσει τις αντιλήψεις των φαρμακοποιών ως επιστημόνων υγείας απέναντι στα συμπληρώματα διατροφής, αλλά και τις πρακτικές επιλογής και προώθησης των σκευασμάτων αυτών στο φαρμακείο. Τα δεδομένα συλλέχθηκαν με τη βοήθεια ειδικά διαμορφωμένου ερωτηματολογίου που απευθυνόταν σε επαγγελματίες φαρμακοποιούς. Συγκεντρώθηκαν 100 ερωτηματολόγια από διάφορους νομούς της βόρειας Ελλάδας κυρίως, με προσωπική συνέντευξη, τηλεφωνική επικοινωνία καθώς και αποστολή στο χώρο εργασίας για τα πιο απομακρυσμένα φαρμακεία. Οι φαρμακοποιοί του δείγματος εμφανίστηκαν συγκρατημένοι όσον αφορά την ικανοποίηση απ’ τις πωλήσεις των συμπληρωμάτων διατροφής στα φαρμακεία τους. Εξίσου επιφυλακτικοί παρουσιάστηκαν και ως προς την τάση να συστήνουν κάποιο σκεύασμα με δική τους πρωτοβουλία σε περιπτώσεις που πιθανώς να αφορούν κάποιο πρόβλημα υγείας. Στοιχεία Μάρκετινγκ των συμπληρωμάτων διατροφής όπως η ισχύς της εμπορικής ονομασίας και η φήμη της παραγωγού εταιρίας φάνηκαν να επηρεάζουν καθοριστικά τόσο τις επιλογές των πελατών, κατά τη γνώμη των φαρμακοποιών, όσο και τις δικές τους επιλογές ως προς τα σκευάσματα που θα επιλέξουν να διαθέτουν στο φαρμακείο τους. Ως βασικότερος παράγοντας σύστασης κάποιου συγκεκριμένου σκευάσματος από τους φαρμακοποιούς αναδείχθηκε η πίστη στην αποτελεσματικότητά του. Γενικά το δείγμα εμφανίστηκε θετικό ως προς την αναγκαιότητα των συμπληρωμάτων διατροφής εξαιτίας των συνθηκών που επιβάλλει ο σύγχρονος τρόπος ζωής και συγκρατημένο ως προς την ανεπιφύλακτη σύσταση και προώθησή τους στο φαρμακείο. Επιπρόσθετα, σημείωσε ότι η συντριπτική πλειοψηφία των πελατών που έρχονται στο φαρμακείο αναζητώντας κάποιο συμπλήρωμα ζητούν τη συμβουλή του φαρμακοποιού ως προς την επιλογή τους, ενισχύοντας το συμβουλευτικό ρόλο του φαρμακοποιού στη διάθεσή τους. Τέλος, οι ερωτηθέντες δήλωσαν λιγότερο ενημερωμένοι σχετικά με τα συμπληρώματα διατροφής, απ’ ότι σίγουροι για τις σχετικές συμβουλές/ συστάσεις τους προς το κοινό. Αν και στη θεωρία τάχθηκαν υπέρ της αναγκαιότητας των συμπληρωμάτων διατροφής σε μια πληθώρα ανθρώπων λόγω του σύγχρονου τρόπου ζωής, εντούτοις οι φαρμακοποιοί του δείγματος εμφανίστηκαν πιο συντηρητικοί στην πράξη όσον αφορά την σύσταση και προώθηση τους. Όσο αντιλαμβάνονται να επηρεάζουν τα προϊόντικα στοιχεία των διαφόρων συμπληρωμάτων διατροφής τις επιλογές του αγοραστικού κοινού, άλλο τόσο φάνηκε να καθορίζουν τις επιλογές των φαρμακοποιών σχετικά με τα σκευάσματα που επιλέγουν να διαθέτουν στο φαρμακείο τους. Σημαντικό ρόλο στις επιλογές τους διαδραματίζει και η σχέση του φαρμακοποιού με την παραγωγό εταιρία (εμπιστοσύνη στο κύρος της εταιρίας και την αποτελεσματικότητα των σκευασμάτων της, ευελιξία της εταιρίας στη συνεργασία με τον φαρμακοποιό). Γενικά όσο πιο ικανοποιημένοι δήλωσαν οι φαρμακοποιοί απ’ τις πωλήσεις των συμπληρωμάτων διατροφής στο φαρμακείο, τόσο πιο ενημερωμένοι σχετικά εμφανίστηκαν. Η αυτοπεποίθηση των φαρμακοποιών για τις συμβουλές/ συστάσεις τους επηρεάζεται τόσο από την σχετική ενημέρωση τους όσο και από την επαγγελματική τους εμπειρία. / To explore the beliefs of pharmacists as health care professionals towards food supplements and their practices of choosing, recommending and promoting such products. Data was collected by administering a specially designed questionnaire to be completed by community pharmacists. 100 questionnaires were gathered coming from various areas, mostly in the north of Greece using personal interviews, phone interviews as well as by mailing the questionnaires to professionals based at distant areas. The pharmacists of the sample appeared merely satisfied from the sales of food supplements in their pharmacies. They also appeared reserved towards taking sole responsibility of suggesting a supplement, in cases that could involve some health problem. Certain Marketing elements such as the brand name and the prestige of the company seemed to play a key role in the buying decision of the customers from the pharmacists’ view, as well as in their own decisions over which supplements they will include for sale in the pharmacy. The belief in the effectiveness of the product was regarded as the most important reason for suggesting a certain supplement. Generally, the sample appeared more likely to believe in the necessity of food supplements as a result of the current way of living, though reserved as far as uninhibitedly suggesting and promoting their use. It was also noted that the majority of customers seeking to purchase a food supplement, ask for the pharmacist’s opinion and suggestion instead of picking one on their own, which reinforces the counseling role of the pharmacist in the buy. Finally, the pharmacists stated to be more confident over their advice/ suggestions, rather than well-informed as far as food supplements are concerned. The pharmacists included in the research seemed skeptical about the wide use and promotion of food supplements, though in theory they appeared to agree with the fact that they are necessary to various people due to the current way of living. The more they believe that certain marketing elements of these products affect the customers’ buying decisions, the more likely they are to be affected by these elements in deciding which supplements to include for sale in their pharmacies. As far as these decisions are concerned, the relationship with the producing company plays an important role (trust in the company’s credibility and its products’ effectiveness, flexibility of the company in terms of pharmacist’s needs). Generally, the more satisfied the pharmacist was from the sales of food supplements in the pharmacy, the more informed about them he/she stated to be. The confidence of the pharmacists as far as their suggestions are concerned is affected by how well-informed they are and by their experience behind the counter.

Les compléments alimentaires à visée oculaire qui envahissent le marché, contiennent dans la majorité des cas des oméga 3, des vitamines, des oligoéléments auxquels sont associés d’autres molécules connues pour leurs propriétés anti-inflammatoires et/ou anti-oxydantes. Néanmoins, à notre connaissance il n’existait pas d’étude portant sur les formes finalisées complexes de ces compléments. Notre projet a donc pour objectif d’évaluer et de caractériser in-vivo et in-vitro l’effet protecteur sur les cellules rétiniennes d’une supplémentation alimentaire à visée oculaire commercialisée en France et en Tunisie. Ce supplément contient des oméga 3, des caroténoïdes, des vitamines, des oligoéléments et du résvératrol. In-vivo, nous avons utilisé un modèle de dégénérescence rétinienne progressive induite par la lumière et in-vitro un modèle de mort des cellules d’épithélium pigmentaire rétinien (ARPE-19) induite par le peroxyde d’hydrogène (H2O2 ).Dans une première étape nous avons mis en évidence que le complément alimentaire protège la fonction (électrorétinographie, ERG) et la structure (histologie et comptage de cellules apoptotiques) de la rétine contre les lésions induites par la lumière et protège lescellules ARPE-19 contre le stress oxydant induit par le H2O2 (MTT). Dans une deuxième étape, nous avons montré qu’une semaine de supplémentation entraîne une modification du contenu en acides gras dans le plasma et les rétines in-vivo, et dans les cellules ARPE919 in-vitro, caractérisée par une augmentation des taux d’EPA et DPA, deux précurseurs de DHA(HPLC). In-vivo, ni la quantité (spectromètre) ni la vitesse de régénération de la rhodopsine (ERG) ne sont affectées. Au cours de l’exposition à la lumière, l’expression des cytokines (milliplex) est orientée vers un profil anti-inflammatoire et l’expression génique (qPCR) d’iPLA2, PPAR-α, Caspase-12 est maintenue élevée tout au long de l’exposition à la lumière cyclique intense chez les animaux supplémentés. En conclusion, nous avons émis l’hypothèse que l’accumulation préférentielle des acides gras polyinsaturés à longue chaine (EPA et DPA) participe à l’effet protecteur du complément alimentaire en permettant 1/ un renouvellement facilité du DHA rétinien et 2/ ainsi le maintien de l’activité d’iPLA 2. Le DHA libéré des membranes activerait les voies de signalisation anti-inflammatoire et anti-oxydante par l’intermédiaire du récepteur nucléaire PPAR-α. / Dietary supplement for ocular purpose have exploded on the market. In most cases, they contain omega 3, vitamins and trace elements associated with molecules known for their anti-inflammatory and/or anti-oxidant proprieties. However, to our knowledge no studies had evaluated dietary supplements on their finalized complex formulation. In this context, the aim of our project was to evaluate and characterize in-vivo and in-vitro the protective effect on retinal cells of a dietary supplement for ocular purpose marketed in France and Tunisia. This dietary supplement contains omega 3, vitamins, trace elements, carotenoids and resveratrol. Therefore, we have used,an in-vivo experimental model of progressive light-induced retinal damage and an in-vitro model of hydrogen peroxide(H2O2 )-induced retinal pigment cells (ARPE-19) death. First, we have demonstrated that the dietary supplement prevented retinal function (electroretinography, ERG) and structure (histology and detection of apoptotic nuclei) from light-induced retinal damage and protects ARPE-19 cells (MTT) from H2O2 induced oxidative stress. Second, we have shown that one-week supplementation induced modifications in retinal (in-vivo), plasma (in-vivo) and ARPE-19 cells (in-vitro) fatty acids contents, characterized by an increase in EPA and DPA contents, the two synthetic precursors of DHA (HPLC). In addition, in-vivo neither rhodopsin content (spectrometer) nor response recovery (ERG) were affected. Furthermore, during light-exposure cytokines expression (milliplex) were oriented towards an anti-inflammatory profile and gene expression (qPCR) of iPLA2, PPAR-α, Caspase-12 was kept high throughout exposure to intense cyclic light in retina of supplemented animals. In conclusion, we hypothesized that preferential accumulation of long-chain polyunsaturated fatty acids (EPA and DPA ) is involved in the protective effect of dietary supplement allowing : 1 / facilitated renewal of retinal DHA and 2 / maintaining of iPLA 2 activity. DHA released from membranes activate the anti- inflammatory and antioxidant signaling pathways via the nuclear receptor PPAR- α.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / For the proper functioning of the human body are essential various nutrients, among these are the macro and micro. The minerals are important in the physiological and biochemical functions of the human body. Insufficient intake can cause deficiencies, on the other hand excessive intake may be toxic. For the recommended doses of each mineral we need to consume fruits, vegetables, grains and vegetables. The food supplement is useful when selecting foods in a diet has some nutrient deficiencies. However, not all nutrient contained in a food supplement can be made available to be absorbed by the body, ie bioaccessible. Thus, the study of mineral bioaccessibility in this array is necessary. Thus, the aim of this study was to evaluate the in vitro bioaccessibility of macro and micro minerals in samples of amaranth, and quinoa multimixture, used as a food supplement. To determine the total content of minerals, samples were digested in oven with microwave cavity and the content of mineral measured by ICP OES. To evaluate the bioaccessibility, the samples were subjected to in vitro gastrointestinal digestion. The bioaccessible fraction was digested in the digester block prior to analysis by ICP OES. The three studied food supplements, as the total contents, are rich in Cu, Fe, Mg, Mn and P, and only multimixture is a source of Ca and Zn, with respective contributions of 19.1% and 20.1%, considering : source (15-29% of RDA) and rich (at least 30% of RDA). However, the amount of Cu and Mn amaranth and quinoa multimixture exceeded the UL (upper tolerable limit intake). After in vitro digestion, there was a marked reduction in the contribution to the RDA of all the three minerals and food supplements. The bioaccessibility study results show that the amaranth is a source of Fe, Mg and Mn-rich P and Cu; multimixture is the source of Fe, Mn and high in P and quinoa source of Mn and high in P and Cu. The application of PCA (principal component analysis) showed that multimixture has higher content of K, Cu, Mg, Zn, Fe and Ca and amaranth Mg and P (total contents) and the bioaccessibility, amaranth was more bioaccessible of Ca, Fe and Mg; multimixture K and Zn; and amaranth and quinoa, similarly, Cu, Mn and P. Regarding the content of phytic acid in the samples was observed that the greater the anti-nutritional content of such lower bioaccessibility of Ca, Cu, Fe and Mn. This work shows that the study of bioaccessibility and anti-nutritional factors performed to amaranth, and quinoa multimixture were relevant, since they can be inserted more precise information on the absorption of minerals in nutritional composition tables of these foods / Para o bom funcionamento do corpo humano sÃo essenciais vÃrios nutrientes, dentre estes estÃo os macro e microminerais. Os minerais sÃo importantes nas funÃÃes fisiolÃgicas e bioquÃmicas do corpo humano. A ingestÃo insuficiente pode causar deficiÃncias, por outro lado a ingestÃo excessiva pode ser tÃxica. Para obter as doses recomendadas de cada mineral à preciso consumir frutas, verduras, cereais e hortaliÃas. A complementaÃÃo alimentar à Ãtil quando a seleÃÃo de alimentos em uma dieta possui carÃncias de algum nutriente. Contudo, nem todo nutriente contido em um complemento alimentar pode estar disponÃvel para ser absorvido pelo organismo, ou seja, bioacessÃvel. Logo, o estudo da bioacessibilidade de minerais nessa matriz faz-se necessÃrio. Desse modo, o objetivo deste trabalho foi avaliar a bioacessibilidade in vitro de macro e microminerais em amostras de amaranto, multimistura e quinoa, usadas como complemento alimentar. Para a determinaÃÃo dos teores totais dos minerais, as amostras foram digeridas em forno de micro-ondas com cavidade e o teor dos minerais medidos por ICP OES. Para avaliaÃÃo da bioacessibilidade, as amostras foram submetidas à digestÃo gastrointestinal in vitro. A fraÃÃo bioacessÃvel foi digerida em bloco digestor antes das anÃlises por ICP OES. Os trÃs complementos alimentares estudados, quanto aos teores totais, sÃo ricos em Cu, Fe, Mg, Mn e P, e apenas a multimistura à fonte de Ca e Zn, com respectivas contribuiÃÃes de 19,1% e 20,1%, considerando: fonte (15-29% da RDA) e rico (no mÃnimo 30% da RDA). No entanto, a quantidade de Cu e Mn no amaranto, multimistura e quinoa excedeu a UL (Limite superior tolerÃvel de ingestÃo). ApÃs digestÃo in vitro, houve uma reduÃÃo acentuada na contribuiÃÃo para a RDA de todos os minerais e nos trÃs complementos alimentares. Os resultados do estudo de bioacessibilidade mostram que o amaranto à fonte de Fe, Mg e Mn e rico em P e Cu; a multimistura à fonte de Fe, Mn e rica em P e a quinoa fonte de Mn e rica em P e Cu. A aplicaÃÃo da PCA (anÃlise de componentes principais) mostrou que a multimistura possui maior teor de K, Cu, Mg, Zn, Fe e Ca e o amaranto de Mg e P (teores totais) e com a bioacessibilidade, o amaranto foi mais bioacessÃvel em Ca, Fe e Mg; a multimistura em K e Zn; e o amaranto e a quinoa, de forma similar, em Cu, Mn e P. Quanto aos teores de Ãcido fÃtico nas amostras observou-se que quanto maior à o teor desse antinutricional menor a bioacessibilidade de Ca, Cu, Fe e Mn. Este trabalho mostra que o estudo de bioacessibilidade e dos fatores antinutricionais realizados para amaranto, multimistura e quinoa foram pertinentes, uma vez que podem ser inseridas informaÃÃes mais precisas quanto à absorÃÃo de minerais em tabelas de composiÃÃo nutricionais desses alimentos.

Inledning: Den svenska träningstrenden fortsätter enligt stadiums årliga undersökning om svenskarnas träningsvanor. Enligt Livsmedelsverket är kosttillskott ett komplement som ska konsumeras utöver den vanliga kosten, och motiveringen till att idrottare använder kosttillskott är exempelvis för att skydda hälsa och prestation. Proteintillskott konsumeras för att öka proteinsyntesen och påverkar muskelfunktioner och träning positivt. Studier har tidigare undersökt atleters inställning till kosttillskott, men få studier har undersökt inställningen till proteintillskott hos människor som har styrketräning som ett fritidsintresse.       Syfte: Studien avser att undersöka inställningen till användandet av kosttillskott i form av protein (proteinpulver, bars). Studien ska också undersöka proteinintaget hos användare och icke-användare av proteintillskott.   Material och metod: Studien utgjordes av en webbaserad enkät och en kostregistrering. Inklusionskriterierna för att delta i studien var att träna minst tre gånger i veckan, vara man och minst 18 år gammal. Rekryteringen genomfördes via en Facebook grupp som riktar sig mot dom som har ett intresse för träning och hälsa.    Resultat: Totalt deltog tio personer i kostregistreringen. Det förekom underrapportering av energiintaget i samtliga kostregistreringar, vilket påverkar resultatets trovärdighet. Det fanns en viss skillnad i proteinintaget mellan användare och icke-användare av proteintillskott, och icke-användare av proteintillskott konsumerade mer animalieprodukter än användare. Det var 26 personer som besvarade enkäten, och var mellan 18–50 år gamla och tränade minst tre gånger i veckan på gym. Svarsfrekvensen på frågorna varierade eftersom det var öppna frågor. Anledningen för att använda proteintillskott är att få i sig extra protein, och anledningen för att inte använda proteintillskott är för att de får i sig tillräckligt med protein från den vardagliga kosten.   Slutsats: Trots osäkerheten i rapporterade data av energiintaget visar kostregistreringarna att användare av proteintillskott till stor del förlitar sig på att proteintillskott täcker proteinbehovet, och konsumtions skillnaden av olika typer av livsmedelsgrupper var framförallt animalieprodukter. Anledningen till att avstå från proteintillskott är huvudsakligen på grund av kostnaden och dess effekt. / Introduction: The Swedish training trend continues according to Stadiums annual survey of Swedes' training habits. Dietary supplements are a supplement that should be consumed in addition to the usual diet, and the motivation for athletes to use dietary supplements is, for example, to protect health and performance. Protein supplements are consumed to increase protein synthesis and positively affect muscle function and exercise. Studies have previously examined athletes' attitudes towards dietary supplements, but few studies have examined the attitude towards protein supplements in people who have weight training as a hobby.     Aim: The study aims to investigate the attitude to the use of dietary supplements in the form of protein (protein powder, bars). The study will also examine the protein intake of users and non-users of protein supplements.   Material and method: The study consisted of a web-based questionnaire and a diet registration. The recruitment was carried out via a Facebook group that focuses on exercise and health.   Results: A total of ten people participated in the diet registration. There was underreporting of energy intake in all diet registrations, which affects the credibility of the results. There was some difference in protein intake between users and non-users of protein supplements, and non-users of protein supplements consumed more animal products than users. A total of 26 people answered the web formula questionnaire from 18 years up to 50 years old and trained at least three times per week, the response rate varied as there were open ended questions. Intake of protein supplements is largely due to the fact that you need to get extra protein and for those who choose to abstain, it was more about they got enough from their everyday diet.     Conclusion: Despite the uncertainty in reported data on energy intake, dietary records show that users of protein supplements largely rely on protein supplements to cover protein requirements, and the difference in consumption of different types of food groups was primarily animal products. The reason for refraining from protein supplements is because of the cost and its effect.

A busca por um padrão estético globalizado e o aumento da obesidade fazem crescer o uso de suplementos alimentares e compostos emagrecedores à base de extratos vegetais. Produtos contendo a associação de p-sinefrina, efedrina, salicina e cafeína são amplamente consumidos e não apresentam efetividade e segurança bem esclarecidas. Portanto, o objetivo deste trabalho foi avaliar a toxicidade subcrônica de p-sinefrina, efedrina, cafeína e salicina, isoladas e em associação, em ratos Wistar machos. Doses de salicina 6 mg/kg, efedrina 4 mg/kg, p-sinefrina 10 mg/kg, cafeína 80 mg/kg e a associação de salicina, efedrina, p-sinefrina e cafeína 100 mg/kg (6:4:10:80, respectivamente) foram testadas via oral por 28 dias consecutivos. A massa corporal foi verificada semanalmente e o teste da atividade locomotora foi realizado no 28º dia. O sangue foi coletado para análise bioquímica e órgãos vitais como fígado e rins foram utilizados para avaliação histológica. Os resultados mostraram uma redução significativa (p<0,05) na massa corporal nos dias 21 e 28 do grupo tratado com cafeína comparado ao grupo controle. Nos dias 14, 21 e 28 ocorreu um aumento significativo (p<0,05) da massa corporal no grupo tratado com p-sinefrina comparado com os grupos efedrina, salicina, cafeína e associação. No teste da atividade locomotora houve um aumento significativo (p<0,05) no grupo tratado com a associação comparado ao grupo controle. Não foram encontradas alterações nos marcadores bioquímicos de fígado, rim e coração, bem como nas avaliações macroscópicas dos órgãos vitais. Entretanto, na análise histológica do fígado, verificou-se em todos os grupos a presença de vacuolização e tumefação celular, congestão vascular e alargamento dos sinusóides, e apenas os grupos p-sinefrina, efedrina e salicina apresentaram degeneração hidrópica. Na histologia dos rins todos os grupos demonstraram vacuolização celular e aumento do espaço da cápsula de Bowman e o grupo p-sinefrina mostrou a presença de infiltrado inflamatório. Esses resultados sugerem que o uso dessas substâncias, tanto na forma isolada como em associação, apresenta um perfil toxicológico considerável. / The search for a globalized aesthetic standard and the increasing obesity are enhancing the use of food supplements and weight loss compounds from plant base extracts. Products containing the combination of p-synephrine, ephedrine, caffeine and salicin are widely consumed and the effectiveness and safety are not well understood. Therefore, the aim of this study was to evaluate the subchronic toxicity of p-synephrine, ephedrine, caffeine and salicin, isolated and in combination, in male Wistar rats. Doses of salicin 6 mg/kg, ephedrine 4 mg/kg, p-synephrine 10 mg/kg, caffeine 80 mg/kg and the association of salicin, ephedrine, p-synephrine and caffeine (100 mg/kg; 6:4:10:80, respectively) were administered orally for 28 consecutive days. Body weight was recorded weekly and a locomotor activity test was performed on the 28th day. Blood was collected for biochemical analysis and vital organs such as liver and kidneys were used for histologic evaluation. The results showed a significant reduction (p <0.05) in body mass on days 21 and 28 in the caffeine-treated group compared to control group. Besides that, on days 14, 21 and 28 a significant increase (p <0.05) in body weight was observed in the group treated with p-synephrine compared to the ephedrine, salicin, caffeine and association-treated groups. In the test of locomotor activity, a significant increase (p <0.05) was observed in the association-treated group treated compared to the control group. No changes were found in biochemical markers associated with liver, kidney and heart conditions or in macroscopic evaluations of vital organs. However, the histological analysis of the liver in all groups shown presence of cellular vacuolization and swelling, vascular congestion and enlargement of the sinusoids, whereas the p-synephrine, ephedrine and salicin groups exhibited hydropic degeneration. In the histology of kidneys, all groups showed cellular vacuolation and increased of the Bowman's capsule space and the p-synephrine group showed the presence of inflammatory infiltrate. These results suggest that the use of these substances either in isolation or in combination showed a considerable toxicological profile.

Ce projet de thèse avait pour objet d’étudier la régulation de la biodisponibilité du monoxyde d’azote (NO) à travers la supplémentation en nitrate (NO3-) chez l’homme, et la perfusion d’ADMA chez l’animal. Nous avons essayé de déterminer les répercussions de la modulation de la biodisponibilité du NO sur la perfusion musculaire à l’exercice, et l’effet de l’aptitude aérobie sur cette modulation. Dans notre méta-analyse, nous avons rapporté une diminution de la consommation d’oxygène (V̇O2) lors d’exercices d’intensité modérée à élevée, avec une amélioration de la tolérance à l’exercice sans réduction du V̇O2 chez les sujets présentant une pathologie. Dans une seconde étude, aucune amélioration de la tolérance à l’effort n’a été observée chez des athlètes [consommation maximale d’oxygène (V̇O2max) > 65 mL.min-1.kg-1] au cours d’un exercice intermittent d’intensité supramaximale après une supplémentation en NO3- et sans modification au niveau du V̇O2 et de la perfusion musculaire. Une troisième étude montre que l’aptitude aérobie et l’apport en O2 aux muscles, dépendante de la perfusion musculaire, ne sont pas associés à la concentration plasmatique d’ADMA chez des sujets jeunes et sains. Enfin, notre quatrième étude ne rapporte pas d’effet de la perfusion de l’ADMA sur la perfusion musculaire au cours d’un exercice de course chez des rats. En conclusion, la supplémentation en NO3- peut contribuer à une amélioration de la performance à travers une réduction du coût en O2 pour des exercices sous-maximaux. Cependant, les sujets entraînés en endurance avec une aptitude aérobie élevée ne présentent ni d’effet ergogénique, ni d’amélioration de la perfusion musculaire à la suite d’une supplémentation en NO3- lors d’exercices intermittents supramaximaux, contrairement aux sujets modérément entraînés. En outre, l’ADMA, en tant inhibiteur de la synthèse du NO, ne semble pas jouer un rôle dans la régulation du débit sanguin et de l’apport en O2 aux muscles actifs, en l’absence de conditions pathologiques. / We aimed to determine whether dietary nitrate (NO3-) supplementation and ADMA modulate NO bioavailability and muscle blood flow during exercise. The second purpose was to establish whether aerobic fitness alters the effects of dietary NO3- supplementation and ADMA on muscle blood flow during exercise. In our meta-analysis, we found that dietary NO3- supplementation decreases V̇O2 during exercise performed in the moderate and heavy intensity domains in healthy subjects, and enhances exercise tolerance in subjects with chronic diseases, but no change in V̇O2. Our second study showed that dietary NO3- supplementation did not increase the number of repetitions completed during supramaximal intensity intermittent exercise in endurance athletes with high aerobic fitness (V̇O2max > 65 mL.kg-1.min-1), and did not increase muscle blood volume. In the third study, aerobic fitness is not related to muscle O2 delivery and plasma ADMA concentrations in young male subjects with a wide range of aerobic fitness level. In the fourth study, increased plasma ADMA levels did not decrease muscle blood flow during low-treadmill running exercise in healthy rats. In conclusion, dietary NO3- supplementation could contribute to an improved tolerance to exercise by reducing O2 cost during exercises at submaximal intensities. However, endurance-trained athletes with high V̇O2max level do not benefit from the effects of dietary NO3- supplementation on exercise performance and muscle blood flow as reported in moderately trained subjects. Moreover, ADMA did not regulate muscle blood flow and O2 delivery during exercise in conditions free from cardiovascular and metabolic diseases in humans and in the rat with pharmacological-induced increase in plasma ADMA levels.