Submitted by Biblioteca da Faculdade de Farmácia (bff@ndc.uff.br) on 2018-01-12T16:10:14Z No. of bitstreams: 1 Maria Emília Lopes.pdf: 20093800 bytes, checksum: 9bb89700f8b88159431e067064afe7dd (MD5) / Made available in DSpace on 2018-01-12T16:10:14Z (GMT). No. of bitstreams: 1 Maria Emília Lopes.pdf: 20093800 bytes, checksum: 9bb89700f8b88159431e067064afe7dd (MD5) / Há algumas décadas, dietas cetogênicas como a preconizada pelo Dr. Atkins, composta por 0% a 20% da oferta energética fornecida por carboidratos, 55% a 65% por proteínas e 25% a 35% por lipídeos são usadas visando ao emagrecimento. Mais recentemente, a indicação foi ampliada para algumas doenças neurológicas. A hipótese deste estudo é que, como o fígado recebe diretamente macronutrientes da absorção intestinal, as modificações na composição desses componentes da dieta possam levar à lesão dos hepatócitos. O objetivo geral do estudo é verificar o efeito de uma dieta com teores baixo de carboidratos e elevado de proteínas e lipídeos no fígado de ratas por análise bioquímica plasmática, histologia e citometria de fluxo do fígado. Vinte ratas, divididas em dois grupos, receberam dieta controle e dieta experimental. Os animais controles receberam dieta AIN-93M e os experimentais, dieta baseada na do Dr. Atkins, com carboidrato (8,44%), proteínas (57,19%), lipídeos (34,36%) e água, ad libitum, por oito semanas. As ratas no estro em jejum foram anestesiadas e pesadas, a glicemia capilar foi dosada e a coleta de sangue foi realizada para avaliar transaminases, ureia, creatinina, triacilglicerol, colesterol, lipoproteína de alta densidade, lipoproteína de baixa densidade, β-hidroxibutirato, malondialdeído, glucagon, insulina, interleucina-6 e fator de necrose tumoral. Seis fragmentos do fígado foram retirados e colocados em solução fisiológica a 0,9% para citometria de fluxo, e o restante do órgão colocado em solução de formalina neutra tamponada a 10% para microscopia óptica. O tecido adiposo branco periovariano bilateral foi retirado e pesado. Os resultados foram apresentados, como média e desvio padrão para a comparação, o teste t de Student, não pareado, e o teste ANOVA, seguido do teste de Tukey. Utilizou-se o teste de Pearson para estudos de correlação, sendo p<0,05 com significância. As médias de peso dos dois grupos aumentaram, sem diferença estatística no início e ao final. A média da ingestão de água foi 1,6 vezes maior no experimental. A média do consumo de dieta sempre foi significativamente menor no experimental, exceto na segunda semana. O peso do tecido adiposo foi menor no grupo experimental. Houve diferença estatística nas seguintes dosagens: transaminases, ureia, triacilglicerol, malondialdeído, e β- hidroxibutirato. Com exceção do triacilglicerol, todos foram maiores no grupo experimental. O peso do tecido adiposo periovariano foi menor no grupo de dieta experimental. A média do peso do fígado foi maior no grupo experimental. O aspecto macroscópico do fígado foi normal em ambos os grupos, e o estudo histológico do grupo experimental demonstrou sinusoides hepáticos alargados, hepatócitos de tamanho diminuído e glicogênio hepático diminuído. Não foi identificada autofagia dependende de Blimp-1 no estudo. A citometria de fluxo demonstrou que, o grupo experimental apresentou 30,85 ± 2,20% de células inviáveis; e no controle 13,22 ± 1,43%, com p<0,05. Houve correlação positiva entre o percentual de células inviáveis e malondialdeído plasmático, e negativa com triacilglicerol plasmático, o que pode sugerir serem estes possíveis indicadores plasmáticos de lesão hepática, associados à dieta experimental. Conclui-se que a dieta experimental levou à lesão hepática (apoptose) no estudo. / For many decades, ketogenic diets as Atkins diet, composed of 0% - 20% calories from carbohydrate, 55% - 65% protein and 25% - 35% lipids have been used to weight loss. More recently, the indication was expanded to some neurological diseases. The overall objective of the study is to assess the effect of a lowcarbohydrate, high-protein and lipids diet on the liver of rats by plasma biochemical analysis, histology and cytometric liver flow study.The hypothesis is that as the liver gets directly absorption of macronutrients, low- carbohydrates, high-protein and lipids diets can injure hepatocytes. Twenty female rats were divided into control diet group and experimental diet group. The control group received an AIN-93M diet and the experimental one a diet based on the Atkins's diet with carbohydrates (8.44%), protein (57.19%), lipids (34.36%) and water, ad libitum, for eight weeks. The rats in estrous cycle were anesthetized, weighted, capillary glucose was dosed and blood was collected for measurement of transaminases, urea, creatinine, triglycerides, cholesterol, high-density lipoprotein, low-density lipoprotein, β-hydroxybutyrate, malonaldehyde, glucagon, insulin, interleukin-6 and tumor necrosis factor. Six liver fragments were removed and placed in physiological solution at 0.9% for flow cytometry and the rest of the organ was put in a neutral buffered formalin 10% solution for optical microscopy. The white adipose tissue bilateral periovarian was pulled out and weighted. The results were presented as a mean and standard deviation, and the comparison between the average with Student's t-test unpaired, and ANOVA followed by Tukey test. Pearson's test was used for correlation studies. It was considered a statistically significant difference at p <0.05. The average weight of the two groups increased during the study. At the beginning and in the end of the study, there was no statistical difference in mean weight. The average water intake was 1.6 times higher in the experimental group. The average dietary intake was significantly lower in the experimental group, except in the second week. There was a statistical difference between the groups in only the following dosages: transaminases, urea, triglycerides, malondialdehyde, and β-hydroxybutyrate. Adipose tissue weight was smaller in the experimental group. The mean weight of liver was greater in the experimental. The macroscopic appearance of the liver was normal in both groups and the histological study demonstrated that the experimental group had an extended hepatic sinusoid, decreased the size of hepatocytes and decreased liver glycogen. Autophagy has not been identified. Flow cytometry showed statistical significance, in the experimental group 30.85% ± 2.20% were inviable cells while in the control group 13.22 ± 1.43% were, with p <0.05. There was a positive correlation between the percentage of non-viable cells and plasma malondialdehyde and a negative with plasma triglycerides suggesting that they are possible plasma indicators of hepatic injury associated with the experimental diet. Based on these results, it can be concluded that a low-carbohydrate and high-protein and lipids diet leads to liver damage, and apoptosis is the main cell injury process

Cancer is the second leading cause of death in the United States. Evidence shows that a conventional western diet may contribute to the proliferation of cancer cells, affecting their prognosis. The aim of this review is to examine the efficacy and safety of using the ketogenic diet as an adjuvant to traditional cancer therapy. The systematic literature search was performed in October 2018 on two search engines: EBSCOhost (Medline, CINHAL, Cochrane Central Register of Controlled Trials) and Web of Science using the following key terms: ketogenic diet, high fat & low-carbohydrate diet, Atkins diet, cancer or neoplasms+. The search limitations included clinical studies among adult cancer patients. A total of 544 publications were initially identified. After the first title/abstract screening, 22 articles were eligible for full-text screening; finally, 3 were eligible for data extraction. We synthesized the effects of the ketogenic diet on cancer progression and safety by extracting and summarizing data on 4 items: 1) study characteristics, 2) characteristics of study participants, 3) diet composition and duration, and 4) key findings for efficacy and safety. Although only 3 studies were included, it was observed that more patients who adhered to the ketogenic diet than patients who did not experienced stability of disease and response to treatment. Patients who received the ketogenic diet also experienced a decrease in tumor size, cholesterol, fasting glucose, and triglyceride levels at 90 days. No statistically significant anthropometric changes were experienced; patients weight was maintained. However, more clinical evidence is necessary before applying the ketogenic diet in an oncological setting.

Themitochondrialmalate aspartate shuttle system(MAS)maintains the cytosolicNAD+/NADH redox balance, thereby sustaining cytosolic redox-dependent pathways, such as glycolysis and serine biosynthesis. Human disease has been associated with defects in four MAS-proteins (encoded by MDH1, MDH2, GOT2, SLC25A12) sharing a neurological/epileptic phenotype, as well as citrin deficiency (SLC25A13) with a complex hepatopathic-neuropsychiatric phenotype. Ketogenic diets (KD) are high-fat/low-carbohydrate diets, which decrease glycolysis thus bypassing the mentioned defects. The same holds for mitochondrial pyruvate carrier (MPC) 1 deficiency, which also presents neurological deficits. We here describe 40 (18 previously unreported) subjects with MAS-/MPC1-defects (32 neurological phenotypes, eight citrin deficiency), describe and discuss their phenotypes and genotypes (presenting 12 novel variants), and the efficacy of KD. Of 13 MAS/MPC1- individuals with a neurological phenotype treated with KD, 11 experienced benefits—mainly a striking effect against seizures. Two individuals with citrin deficiency deceased before the correct diagnosis was established, presumably due to high-carbohydrate treatment. Six citrin-deficient individuals received a carbohydrate-restricted/fat-enriched diet and showed normalisation of laboratory values/hepatopathy as well as age-adequate thriving. We conclude that patients with MAS-/MPC1- defects are amenable to dietary intervention and that early (genetic) diagnosis is key for initiation of proper treatment and can even be lifesaving.

BAKGRUND Modifierad Atkins Diet (MAD) och ketogenkost är kostbehandlingar som ordineras till barn med svårbehandlad epilepsi. Andra patientgrupper som behandlas med dessa dieter är patienter med glukostransportprotein typ 1-brist. Kostbehandlingarna är kolhydratfattiga och fettrika. I Sverige finns fyra sjukhus som arbetar med MAD och ketogenkost. I dagsläget saknas studier som beskriver hur behandlingarna upplevs av berörda familjer. SYFTE Syftet med studien var att utforska hur föräldrar till barn som behandlas med MAD eller ketogenkost upplever kostbehandlingen. METOD Kvalitativa intervjuer baserade på en halvstrukturerad frågeguide har genomförts. Fem familjer från olika delar av landet deltog i studien. Intervjuerna spelades in med mp3-spelare för att sedan transkriberas ordagrant. Samtalen analyserades genom kvalitativ innehållsanalys. RESULTAT Föräldrarna berättade om en rädsla och oro inför behandlingsstarten och att introduktionsperioden som familjerna erbjöds inför kostbehandlingen visade sig vara mycket viktig för kommande behandlingsprocess. Föräldrarna upplevde det svårt att tillaga en varierad kost och att det var viktigt med adekvata hjälpmedel och regelbunden vårdkontakt för att kunna tillämpa kostbehandlingen i vardagslivet. Deras behov av stöd förändrades under behandlingsprocessen. Genomgående var att informanterna upplevde att de sociala aktiviteterna anpassades efter kostbehandlingen. Föräldrarna upplevde det som viktigt att ha kontakt med andra familjer i liknade situation. Trots att föräldrarna upplevde flera olika praktiska och sociala problem ansåg de ändå att det positiva, som var kopplat till behandlingens resultat övervägde. En förälder uttryckte sig med orden ”Vi fick tillbaka vårt barn”- vilket återspeglar många föräldrars åsikt om behandlingen. SLUTSATS MAD och ketogenkost kräver mycket tid och kunskap för berörda familjer och påverkar deras vardag både praktiska och socialt. Med stöd från vård, barnomsorg, familj och vänner upplevde föräldrarna att det var lättare att upprätthålla behandlingen. Det finns också ett behov av att få prata med andra föräldrar och familjer som är liknande situationer. / BACKGROUND Modified Atkins Diet (MAD) and Ketogenic Diet are treatments prescribed to children suffering from refractory epilepsy. Patients with glucose transporter protein type 1 deficiency are also commonly treated with these diets, which are low in carbohydrates and high in fat. In Sweden, there are four hospitals implementing these treatments, but there is currently not sufficient information on how they are affecting the families. OBJECTIVE The purpose of this study was to explore how parents of children treated with MAD or Ketogenic Diet experience the treatment. METHOD Qualitative interviews based on a semi-structured topic guide was conducted. Five families from different parts of Sweden participated in this study. The interviews were recorded with an mp3 device and transcribed verbatim. Qualitative content analysis was used for data analysis. RESULT The parents disclosed anxiety before the start of the treatment and they acknowledged that the first week of introduction, which they, were offered before the start, proved to be essential for the rest of the treatment process. The families found it difficult to cook a balanced meal according to the dietary requriements, and also that it was important to have adequate resources and routine contact with health services to be able to apply the treatment to daily life. Their need for support changed during the treatment process. The informants believed their social activities were accommodated due to treatment. The parents felt the need to be in contact with other families in a similar situation. One parent expressed him-/herself with the words “We got our child back”, which reflects many parents view, regarding the treatment. CONCLUSION MAD and Ketogenic Diet require a lot of time and knowledge and affect practical and social aspects in daily living. With the support of health care, child care, family and friends, the parents felt it was easier to maintain treatment. The informants also shed light on the necessity of being in contact with other parents and families in similar situations.