Introdução - A dieta cetogênica (DC) é um tratamento não farmacológico prescrito especialmente para crianças e adolescentes com epilepsia refratária. Objetivo - Avaliar o impacto da dieta cetogênica clássica nas características oxidativas, físicas e lipídicas das lipoproteínas de crianças e adolescentes com epilepsia refratária. Métodos - Ensaio clínico não controlado de séries temporais com recrutamento de crianças e adolescentes com epilepsia refratária de 1 a 19 anos de ambos os sexos do Instituto da Criança do Hospital das Clínicas da FMUSP. Parâmetros bioquímicos foram analisados: perfil lipídico, concentração de ácidos graxos não esterificados (AGNEs), LDL eletronegativa [LDL(-)], Anticorpo anti- LDL(-), substâncias reativas ao ácido tiobarbitúrico (TBARs), subfrações da lipoproteína de alta densidade (HDL) e lipoproteína de baixa densidade (LDL). Além das análises bioquímicas foram avaliadas medidas antropométricas para classificação do estado nutricional, medidas de composição corporal por bioimpedância elétrica e consumo alimentar por registro alimentar de 3 dias. Todas essas medidas foram coletadas antes da DC (T=0), 3 meses após a DC (T1) e 6 meses após a DC (T2). Resultados - A concentração de colesterol total (CT), triacilgliceróis (TG), LDL, HDL, apolipoproteínas (APO A-I e APOB) e não-HDL aumentaram significativamente nos momentos T1 e T2. As razões CT/HDL, LDL/HDL e APOB/APOA-I também apresentaram aumento significativo indicando aumento superior das lipoproteínas e apolipoproteínas mais aterogênicas. Apesar desses aumentos, nenhuma dessas relações ou concentração de lipoproteínas e apolipoproteínas apresentaram aumento progressivo comparando-se T1 versus T2. De modo contrário, observamos aumento progressivo ao longo do tempo na concentração de AGNEs, partículas pequenas de LDL e redução no tamanho médio da LDL de 27,3 nm no T0 versus 26,7 nm no T2. A concentração de TBARs aumentou enquanto a LDL(-) reduziu. A classificação do estado nutricional bem como o % de massa magra e % de massa gorda não mudaram ao longo do tempo. Conclusões - A DC apresentou impacto negativo no metabolismo lipídico contribuindo com o aumento de partículas pequenas de LDL e um fenótipo mais aterogênico. / Introduction - The ketogenic diet (KD) is a non-pharmacological treatment prescribed for children and adolescents with refractory epilepsy. Objective To assess the impact of the classic ketogenic diet in the oxidative, physical and lipid lipoprotein characteristics of children and adolescents with refractory epilepsy. Methods - Single arm, times series trial with recruitment of children and adolescents 1-19 years of both sexes of the Instituto da Criança do Hospital das Clínicas da FMUSP, after doctor indication for treatment with KD. Biochemical parameters were analyzed: lipid profile, level of non esterified fatty acids (NEFAS), LDL electronegative [LDL (-)], anti-LDL (-), thiobarbituric acid reactive substances (TBARS), subfractions of high density lipoprotein (HDL), subfractions of low density lipoprotein (LDL) and LDL size. In addition, anthropometric measurements for classification of nutritional status, body composition by bioimpedance electrical and dietary intake through food records evaluated in 3 days. All these measures were collected before the KD (T = 0), three months after the KD (T1) and 6 months after KD (T2). Results - The level of total cholesterol (TC), triglycerides (TG), LDL, HDL, apolipoproteins (Apo A-I and Apo B) and non-HDL increased significantly in T1 and T2. The rations TC/HDL, LDL/HDL and APOB/APO A-I also showed a significant increase indicating higher increase in lipoproteins and apolipoproteins atherogenic. Despite these increases, any such rations or levels of lipoproteins and apolipoproteins progressive increase comparing T1 versus T2. Conversely, we observed a progressive increase along time in the levels of NEFAS, small LDL and reduction of LDL size of 27.3 nm (T0) to 26.7 nm (T2). The levels of TBARS increased while LDL (-) reduced. The classification of nutritional status as well as the % of lean mass and % of fat mass didn´t change along time. Conclusions - The KD showed a negative impact on lipid metabolism contributing to increased small LDL particles and a more atherogenic phenotype.

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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.

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Studiens syfte var att undersöka psykisk hälsa och välbefinnande i en grupp som äter LCHF (Low Carb High Fat). I studien deltog 246 personer, rekryterade från intressegrupper om LCHF på Facebook. Deltagarna delades in i två grupper efter hur strikt och hur länge de ätit LCHF. Studien genomfördes som en enkätundersökning. Psykiskt välbefinnande och nedsatt psykiskt välbefinnande undersöktes med GHQ-12. Psykiskt hälsotillstånd undersöktes med en självskattad retrospektiv före- och eftermätning. Resultaten av nedsatt psykiskt välbefinnande jämfördes med Folkhälsomyndighetens nationella populationsvärde. Resultaten visade att båda LCHF-grupperna skattade sitt psykiska hälsotillstånd signifikant bättre efter LCHF diet än före. Hela LCHF gruppen skattade nedsatt psykiskt välbefinnande signifikant bättre än den svenska populationen. Resultaten tyder på att LCHF diet har en positiv inverkan på den psykiska hälsan och välbefinnandet. / The purpose of the study was to investigate mental health and mental well-being in a group eating LCHF (Low Carb High Fat). In the study, 246 people recruited from interest groups about LCHF on Facebook participated. The participants were divided into two groups by how strictly and how long they had eaten LCHF. The study was conducted as a questionnaire survey. Mental well-being and impaired mental well-being were investigated with GHQ-12. Mental health status was investigated with self-assessed retrospective pre- and post-measurement. The results of impaired mental well-being were compared with the The Public Health Agency of Swedens national population value. The results showed that both LCHF groups estimated their mental health status significantly better after LCHF diet than before. The entire LCHF group estimated its impaired mental well-being significantly better than the Swedish population. The results indicate that LCHF diet has a positive impact on mental health and well-being.

The main importance of temporal lobe epilepsy due to its high prevalence and high proportion of patients with refractory epilepsy to treatment, making it necessary in this case, the use of alternative therapies, such as the ketogenic diet. This diet is rich in fat, low in carbohydrates and proteins, and since 1921 has been used for patients unresponsive to medical therapy. This dissertation deals with the investigation of the effects of the ketogenic diet based on triheptanoin in epileptic seizures in rats and was developed in the form of two articles. The first article, The role of the ketogenic diet on oxidative stress occurring in epilepsy, presents a review of the relationship between oxidative stress and epilepsy, highlighting the possible beneficial effect of ketogenic diet in this context. Several results show that, in fact, this dietary method reduces oxidative stress markers. The second article, entitled Effects of ketogenic diet based on triheptanoin in seizures of rats with epilepsy induced by pilocarpine, describes the experimental study conducted in Wistar rats were divided into three groups, named according to the diet received, in control (standard diet AIN-93G), CetoTAGC7 (ketogenic based in triheptanoin; AIN-93G diet modified to contain 4% soybean oil, 25.79% of triheptanoin and 40% margarine) and CetoTAGsoja (ketogenic based in soybean; AIN-93G diet modified to contain 29.79% of soybean oil margarine and 40%). The ratio lipid: carbohydrate + protein ketogenic diets was 3.5:1 (control diet, 1:11,8) and experimental period lasted 19 days. It was found that the energy value of the share of feed intake and weight gain made by the three groups during the experimental period were not different (P> 0.05). There was no significant difference among the three groups regarding the ratio of feed efficiency (P> 0.05). The behavioral analysis showed no difference for the variable frequency of spontaneous recurrent seizures, however the duration of the attacks of animals belonging to the group triheptanoin was lower in the last experimental day. Future additional research are encouraged, therefore, the results of this study indicate, however modestly, to a potential beneficial effect of triheptanoin to control seizures, which could be investigated under different conditions, like a period longer than is tested by this protocol. / A principal importância da epilepsia do lobo temporal decorre de sua alta prevalência e elevada proporção de pacientes com crises epilépticas refratárias ao tratamento medicamentoso, fazendo-se necessário, neste caso, o uso de terapias alternativas, como a dieta cetogênica. Esta dieta é rica em lipídeos, pobre em carboidratos e proteínas e desde 1921 tem sido utilizada para pacientes não responsivos à terapia medicamentosa. A presente dissertação trata da investigação dos efeitos da dieta cetogênica à base de trienantina nos episódios convulsivos de ratos epilépticos e foi desenvolvida na forma de dois artigos. O primeiro artigo, O papel da dieta cetogênica no estresse oxidativo presente na epilepsia, apresenta uma revisão sobre a relação existente entre o estresse oxidativo e a epilepsia, destacando o possível efeito benéfico da dieta cetogênica neste contexto. Vários resultados atestam que, de fato, esta modalidade dietética diminui os marcadores de estresse oxidativo.O segundo artigo, intitulado Efeitos da dieta cetogênica à base de trienantina nos episódios convulsivos de ratos portadores de epilepsia induzida por pilocarpina, descreve o estudo experimental, realizado em ratos Wistar, subdivididos em três grupos, denominados, segundo a dieta recebida, em Controle (dieta padrão AIN-93G), CetoTAGC7 (cetogênico à base de trienantina; AIN-93G modificada para conter 4% de óleo de soja, 25,79% de trienantina e 40% de margarina) e CetoTAGsoja (cetogênico à base de soja; AIN-93G modificada para conter 29,79% de óleo de soja e 40% de margarina). A proporção lipídeos:carboidratos+proteína das dietas cetogênicas foi de 3,5:1 (dieta controle, 1:11,8) e o período experimental totalizou 19 dias. Verificou-se que o valor energético da cota de ração ingerida e o ganho de peso apresentado pelos três grupos, no período experimental, não foram diferentes (P>0,05). Não houve diferença significativa entre os três grupos, quanto ao coeficiente de eficiência alimentar (P>0,05). As análises comportamentais demonstraram que não houve diferença para a variável frequência de crises recorrentes espontâneas, entretanto a duração das crises dos animais pertencentes ao grupo da trienantina foi menor no último dia experimental. Pesquisas adicionais futuras são encorajadas, pois, os resultados do presente estudo apontam, ainda que modestamente, para um potencial efeito benéfico da trienantina no controle de crises epilépticas, que poderia ser investigado em condições diferentes, a exemplo de um período de tempo superior ao testado pelo presente protocolo de pesquisa.

Type 2 diabetes mellitus (T2D) is a highly prevalent metabolic disorder linked with the development of specific complications and comorbidities that negatively affect life quality and greatly increase the risk of an early death. The main goal of T2D treatment, which in common clinical practice comprises lifestyle changes and pharmacotherapy, is to delay onset of these complications. Evidence from many recent studies shows the ability of some interventional methods to induce remission of T2D, meaning a major improvement or complete disappearance of T2D symptoms. Besides bariatric surgery procedures, some dietary regimens such as low-energy diet, low-carbohydrate diet and intermittent fasting, can also lead to T2D remission. Attributes of these dietary regimens, especially their effect in T2D treatment, is summarized in the theoretical part of this theses. The aim of the practical part of this thesis was to assess the effect of the dietary regimens mentioned above on morphometric and biochemical parameters associated with T2D by clinical and survey research. In most of the subjects with T2D, the individual dietary regimens, more precisely low-energy diet and low-carbohydrate diet, decreased body weight, where the weight loss induced by low-carbohydrate diet was caused by major decrease in the amount...

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Résumé : Les personnes atteintes de la maladie d’Alzheimer présentent une diminution de la capture cérébrale du glucose, qui semble être impliquée dans le développement des problèmes cognitifs associés à la maladie. Toutefois, il n’y a encore aucun consensus quant à savoir si la capture cérébrale du glucose est diminuée chez les personnes âgées cognitivement saines. En condition de déficit de glucose, les cétones sont le substrat énergétique alternatif pour le cerveau. La diète cétogène, induisant une cétose légère, améliore les fonctions cognitives chez les modèles animaux et chez l’homme. Notre premier objectif était d’évaluer l’effet du vieillissement sain et de la diète cétogène sur la capture cérébrale du glucose et des cétones chez le rat. Pour cela, la capture cérébrale de radiotraceurs analogues au glucose et aux cétones a été mesurée par tomographie par émission de positons. Nos résultats montrent que la capture des deux principaux substrats énergétiques du cerveau est globalement similaire chez des rats sains jeunes et âgés, mais est plus élevée suite à la diète cétogène. L’induction d’une cétose légère pourrait corriger la diminution de capture cérébrale du glucose subvenant au cours de la maladie d’Alzheimer. Le second objectif était de déterminer l’effet d’une diète cétogène sur le métabolisme cérébral du glucose et des cétones chez le rat. Pour cela, les différents intermédiaires des voies métaboliques du glucose et des cétones ont été mesurés par spectroscopie par résonance magnétique nucléaire. Les résultats démontrent que le métabolisme du glucose et des cétones dans les cellules du cerveau est plus élevé suite à la diète cétogène. Le contenu en acide [gamma]-aminobutyrique, le principal neurotransmetteur inhibiteur, est aussi plus élevé suite à la diète cétogène, ce qui pourrait contribuer à l’effet antiépileptique de la diète cétogène. Le troisième objectif était d’évaluer l’impact d’une restriction calorique à long terme, pouvant induire une cétose légère, sur le métabolisme cérébral chez des rats âgés sains. Nos résultats montrent que, couplée à une diète à haute teneur en sucrose et faible en acides gras oméga-3, la restriction calorique à long terme chez les rats âgés ne modifie pas le profil des métabolites et des acides gras du cerveau. La déficience en acides gras oméga-3 et la surcharge de sucrose pourraient empêcher une grande partie des effets bénéfiques de la restriction calorique au cerveau.//Abstract : Alzheimer’s disease is associated with a reduction of brain glucose uptake, which may be involved in the development of the cognitive problems associated with the disease. It is however unclear whether brain glucose uptake is decreased in the cognitively healthy elderly. Under conditions of glucose deficit, ketones are the alternative brain energy substrate. A mild ketosis, induced by the ketogenic diet, improves cognitive functions in animal models and humans. Our first objective was to evaluate the effect of healthy aging and of a ketogenic diet on brain glucose and ketone uptake in the rat. Brain uptake of radiotracers analogous to glucose and ketones was measured by positron emission tomography. Our results show that the uptake of the brains two main energy substrates is generally similar in healthy young and aged rats, but is higher under the ketogenic diet. The induction of a mild ketosis may compensate the reduction of brain glucose uptake occurring in Alzheimer’s disease. The second objective was to assess the effect of a ketogenic diet on brain glucose and ketone metabolism in the rat. Metabolic pathway intermediates of glucose and ketones were measured by nuclear magnetic resonance spectroscopy. Results show that glucose and ketone metabolism in brain cells is higher under the ketogenic diet. Content of [gamma]-aminobutyric acid, the main inhibitory neurotransmitter, is also higher under the ketogenic diet, which could contribute to the antiepileptic effect of the ketogenic diet. The third objective was to evaluate the effect of a long-term calorie restriction, which may induce a mild ketosis, on brain metabolism in healthy aged rats. Our results show that, in conjunction with a diet enriched in sucrose and low in omega-3 fatty acids, long-term calorie restriction in aged rats does not change brain metabolite and fatty acid profiles. Omega-3 fatty acid deficiency and an overload of sucrose may prevent the beneficial effects associated with calorie restriction in the brain.