Acta Portuguesa de Nutrição

O MICROMUNDO

APORTE E ADEQUAÇÃO NUTRICIONAL ANTES E DURANTE A GESTAÇÃO: ESTUDO DE ACOMPANHAMENTO NA ILHA DO FAIAL

RESUMO A nutrição afeta a saúde materna e das futuras gerações. São vários os estudos que reportam um inadequado aporte nutricional antes da conceção e durante a gestação. Pretendeu-se avaliar o aporte nutricional de mulheres da ilha do Faial (Açores) antes e durante a gravidez e analisar a sua adequação. Neste estudo prospetivo foram analisados dados de 34 mulheres. Para avaliar a ingestão alimentar foi aplicado um questionário de frequência de consumo alimentar semi-quantitativo, em dois momentos: na primeira consulta pré-natal (primeiro trimestre de gestação) e na última consulta pré-natal (final do terceiro trimestre de gestação). Para analisar a adequação do aporte nutricional foram utilizadas, sempre que possível, as recomendações da European Food Safety Authority, 2017. Os nutrientes com maior inadequação antes da conceção foram: vitamina D (100%), iodo (76,5%), lípidos (73,5%), hidratos de carbono (55,9%) e fibra (44,1%). Na gestação, para além dos quatro nutrientes mencionados anteriormente, os folatos também apresentaram uma elevada prevalência de inadequação (58,8%). Neste período, verificou-se que os folatos e o iodo foram os nutrientes com maior aumento na inadequação (44,1 e 20,6 pontos percentuais, respetivamente). Os resultados deste estudo reforçam a importância da adesão à suplementação, avaliação da adequação do aporte nutricional e da individualização da terapêutica nutricional.

ABSTRACT Nutrition affects both maternal and future generations’ health. There are several studies reporting an inadequate nutritional supply before conception and during pregnancy. It was intended to assess the nutritional intake of women from the island of Faial (Azores) before and during pregnancy and to analyze its adequacy. In this prospective study, data from 34 women were analyzed. To assess food intake, a semi-quantitative food frequency questionnaire was applied in two moments: first pre-birth appointment (first trimester of gestation) and last pre-birth appointment (end of the third trimester of gestation). To analyze the adequacy of nutritional support, the recommendations of the European Food Safety Authority, 2017 were used, whenever possible. The nutrients with higher inadequacy before conception were: vitamin D (100%), iodine (76.5%), lipids (73.5%), carbohydrates (55.9%) and fiber (44.1%). During pregnancy, in addition to the four mentioned above, folates also had a high prevalence of inadequacy (58.8%). In this period, we found that folates and iodine were the nutrients with the greatest increase in inadequacy (44.1 and 20.6 percentage points, respectively). The results of this study reinforce the importance of promoting the adherence to supplementation, the assessment of the adequacy of nutritional intake and the individualization of nutrition therapy.

HÁBITOS ALIMENTARES, ESTADO NUTRICIONAL E ESTILOS DE VIDA DE UMA AMOSTRA DE TIMORENSES RESIDENTES EM PORTUGAL

RESUMO INTRODUÇÃO: A presença de um número considerável de timorenses a residir em Portugal, justifica a necessidade de investigar acerca dos seus hábitos alimentares, uma vez que até à data, existe uma lacuna de informação relativamente a este tema. OBJETIVOS: Avaliar e conhecer os hábitos alimentares, o estado nutricional e os estilos de vida de uma amostra de timorenses a residir em Portugal. METODOLOGIA: Trata-se de um estudo epidemiológico descritivo observacional, de desenho transversal que abrange uma amostra da população timorense residente em Portugal, de idade igual ou superior a 18 anos. Integraram a amostra 88 indivíduos. Foi elaborado um questionário estruturado de aplicação direta, com questões relativas às características sociodemográficas, estilos de vida e estado de saúde, caraterísticas antropométricas, hábitos alimentares e suas alterações após a emigração. A recolha de dados aconteceu entre fevereiro e março de 2020. RESULTADOS: Foram analisadas 82 respostas dos participantes com idade média de 29,7±12,5 anos. A maioria apresentava um Índice de Massa Corporal normal (64,1%) e 21,9% eram pré-obesos ou obesos. 26,5% dos inquiridos realizaram as refeições, de forma completa e saudável. 62,2% da amostra relatou melhorias no seu estado de saúde após a vinda para Portugal e 69,5% considerou que a alimentação teve influência nessa mudança. Relativamente às alterações dos hábitos alimentares, 70,7% dos inquiridos mencionaram terem alterado o número de refeições, as quantidades de alimentos consumidos (78%) e 58,5% o local habitual onde realizavam as suas refeições. CONCLUSÕES: Dos timorenses que vieram para Portugal, só ¼ da amostra realizaram refeições completas e saudáveis, mas só cerca de metade ingeria frutas e hortícolas. Com a vinda para Portugal, reportaram consumir um maior número de refeições, maiores quantidades de alimentos e faziam as suas refeições mais vezes fora de casa. Reduziram a prática de atividade física e ¼ da amostra fumava e bebia álcool semanalmente. Mais de metade da amostra era normoponderal, apresentando pré-obesidade e obesidade ¼ dos inquiridos.

ABSTRACT INTRODUCTION: A considerable number of Timorese living in Portugal justifies the need to investigate their eating habits, since to date there is a lack of information on this topic. OBJETIVES: To evaluate the eating habits, nutritional status and lifestyles from a sample of the Timorese population living in Portugal. METHODOLOGY: This is a cross-sectional design, covering a sample of the Timorese population living in Portugal, aged 18 years or above. The sample comprised 88 individuals. A structured questionnaire for direct application was prepared, with questions related to sociodemographic characteristics, lifestyles and health status, anthropometric characteristics, eating habits and their changes after emigration. Data collection took place between February and March 2020. RESULTS: The sample include 82 responses from Timorese participants (mean age of 30 years, SD = 12). Most of them had a Body Mass Index corresponding to normality (64.1%) and 21.9% were pre-obese or obese. 26.5% of the participants ate their meals in a complete and healthy way. 62.2% of the sample reported improvements in their health status after coming to Portugal and 69.5%, considered that diet had an influence on this change. Regarding changes in EA, 70.7% of the respondents mentioned having changed the number of meals, 78.0% the quantities of food consumed and 58.5% the place where they usually ate. CONCLUSIONS: Among this sample of Timorese who came to Portugal, only one quarter of the sample had complete and healthy meals, and only half of them ate fruits and vegetables. Upon coming to Portugal, they reported an increasing of the number of meals, greater amounts of food and eating out more often. They reduced the practice of physical activity and one quarter of the sample smoked and drank alcohol weekly, with the number of hours of sleep within the recommended range. More than half of the sample had normal weight, with pre-obesity or obesity being present in about one quarter.

FÓRMULAS INFANTIS: INDICAÇÃO, FUNÇÃO E CONSTITUIÇÃO

RESUMO Os primeiros meses de vida das crianças são determinantes para o seu desenvolvimento físico e cognitivo e podem ter repercussões na sua saúde. O leite materno é considerado como o único alimento capaz de suprir todas as necessidades nutricionais do lactente, de forma exclusiva, no primeiro semestre de vida. No entanto, quando a mãe não tem a possibilidade de amamentar, ou opta por não o fazer, existem fórmulas infantis concebidas para substituir o leite materno. As fórmulas infantis têm sido continuamente aperfeiçoadas com o intuito de se assemelharem, tanto quanto possível, ao leite materno, permitindo a ingestão de nutrientes nas quantidades preconizadas para cada estado de maturação fisiológico e neurológico do lactente, contribuindo para o seu crescimento saudável. Este trabalho aborda alguns conceitos-chave acerca da alimentação e nutrição do lactente, evidenciando a diversidade de fórmulas infantis existentes no mercado português, especificando as diferenças entre os produtos e algumas orientações para a sua correta utilização.

ABSTRACT The first months of a child’s life are determinant for their physical and cognitive development and may have repercussions on their health. Breast milk supplies all the infant’s nutritional needs during the first semester of life. However, when the mother cannot breastfeed, or chooses not to do so, there are infant formulas that can replace breast milk. infant formulas have been continuously improved to resemble breast milk, allowing the recommended nutrient intake for each state of physiological and neurological maturation of the infant, contributing to a healthy growth. This paper addresses some key concepts of infant feeding and nutrition, evidencing the diversity of infant formulas in the Portuguese market, specifying the differences between products and some guidelines for their correct use.

ALIMENTOS PARA DESPORTISTAS: DEFINIÇÃO E ATUALIDADE

RESUMO No contexto desportivo, é muito frequente o uso de alimentos para desportistas. No entanto, estes devem ser encarados como uma estratégia complementar, como forma de auxílio nos seus objetivos enquanto atleta, aquando da necessidade de uma combinação específica de nutrientes essenciais. Neste artigo de revisão é analisada a regulamentação vigente e recomendações dos alimentos para desportistas. Além disso, ainda é demonstrado o papel crucial do Nutricionista no aconselhamento dos alimentos para desportistas, bem como no esclarecimento das diferenças entre estes últimos e suplementos alimentares.

ABSTRACT In the sports context, the use of food for athletes is very common. However, these should be seen as a complementary strategy, as a way of reaching the athlete’s goals, when they need a specific combination of essential nutrients. In this review article, the current regulations and food recommendations for athletes are analyzed. In addition, the crucial role of the Nutritionist is demonstrated in advising on foods for athletes, as well as in clarifying the differences between the latter and food supplements.

EFEITOS DO JEJUM INTERMITENTE NA COMPOSIÇÃO CORPORAL E NO RENDIMENTO FÍSICO

RESUMO A comunidade científica manifesta atualmente um elevado nível de interesse no jejum intermitente - períodos de abstinência voluntária da ingestão de energia, variando de várias horas a dias. O jejum intermitente é clinicamente relevante e pode representar uma estratégia não-farmacológica eficaz para melhorar o desempenho físico e a composição corporal. Tem sido estudado principalmente em atletas durante o período religioso do Ramadão e em pessoas predispostas a diminuir a adiposidade corporal sem perda paralela de massa isenta de gordura. O objetivo desta revisão é fornecer uma visão geral do impacto do jejum intermitente durante o Ramadão vs. jejum intermitente não-Ramadão ao nível do rendimento físico e da composição corporal. A literatura evidencia algumas inconsistências ao nível da interação entre o jejum intermitente e o rendimento físico. Contudo, verifica-se que o jejum intermitente não-Ramadão é eficaz para melhorar a potência aeróbia máxima. Não obstante, esta intervenção reduz o desempenho durante sprints repetidos ao longo dos primeiros dias de intervenção. Por outro lado, o jejum intermitente durante o Ramadão diminui a potência aeróbia máxima e isto é mais expressivo durante a segunda metade deste período religioso. Ao contrário, ambas as intervenções são manifestamente inócuas ao nível da força muscular e da capacidade anaeróbia. No que se refere à composição corporal, existe maior consensualidade. De acordo com os dados disponíveis, ambas as intervenções estimulam adaptações benéficas a este nível. Ainda assim, as perdas de massa gorda são mais pronunciadas com o jejum intermitente não-Ramadão.

ABSTRACT The scientific community currently expresses a high level of interest in intermittent fasting - periods of voluntary abstinence from energy intake, ranging from several hours to days. Intermittent fasting is clinically relevant and may represent an effective non- pharmacological strategy to improve physical performance and body composition. It has been studied mainly in athletes during the religious period of Ramadan and in people predisposed to decrease body fat without loss of fat-free mass parallel. The purpose of this review is to provide an overview of the impact of intermittent fasting during Ramadan vs. non-Ramadan intermittent fasting in terms of physical performance and body composition. The literature shows some inconsistencies in terms of the interaction between intermittent fasting and physical performance. However, non-Ramadan intermittent fasting is found to be effective in improving maximal aerobic power. Nevertheless, this intervention reduces performance during the repeated sprints over the first few days of intervention. On the other hand, intermittent fasting during Ramadan being the maximum aerobic power and this is more expressive during the second half of this religious period. However, both interventions are manifestly innocuous in terms of muscle strength and anaerobic capacity. With regard to body composition, there is greater consensus. According to available data, both interventions encourage beneficial adaptations at this level. Still, fat loss is more pronounced with intermittent non-Ramadan fasting.

O CONSUMO DE HIDRATOS DE CARBONO EM FUTEBOLISTAS MASCULINOS: REVISÃO SISTEMÁTICA E META-ANÁLISE

RESUMO INTRODUÇÃO: As diretrizes relativas ao consumo de hidratos de carbono têm sido extensivamente discutidas. Apesar deste macronutriente ser reconhecidamente determinante no rendimento desportivo, escassas revisões sistemáticas e meta-análises foram conduzidas para avaliar a ingestão de hidratos de carbono em futebolistas masculinos. OBJETIVOS: O objetivo desta revisão sistemática, com meta-análise, foi avaliar a ingestão de hidratos de carbono em diferentes períodos da época competitiva. Adicionalmente, foi examinado o consumo de hidratos de carbono por grupo posicional. METODOLOGIA: As bases de dados utilizadas foram PubMed, SPORTDiscus e Web of Science Core Collection. Os estudos incluídos consideraram os seguintes critérios de elegibilidade: jogadores de futebol masculino, idade superior a 18 anos e consumo de hidratos de carbono expresso em g.kg-1.dia-1. RESULTADOS: Inicialmente, foram identificados 1992 artigos. Destes, 11 foram considerados elegíveis para a revisão sistemática e 10 foram incluídos na meta-análise. Os resultados demonstraram que os futebolistas masculinos, consomem em média, 4,3 g.kg-1. dia-1 e 5,0 g.kg-1.dia-1 nos períodos competitivos e preparatórios (pré-época), respetivamente. Não foi encontrado qualquer estudo que reportasse o consumo de hidratos de carbono durante a off-season. Apenas três estudos examinaram a variação do consumo de hidratos de carbono por grupo posicional. Embora as amostras sejam limitadas, os guarda-redes parecem ingerir uma menor quantidade de hidratos de carbono comparativamente a atletas de outras posições em campo. CONCLUSÕES: Considerando as limitações associadas às metodologias utilizadas para aferir o consumo de hidratos de carbono em atletas, a presente revisão sistemática realça a necessidade de desenvolver estratégias nutricionais para o cumprimento das diretrizes deste macronutriente.

ABSTRACT INTRODUCTION: Guidelines for carbohydrate (CHO) intake have been systematically updated. Although CHO are determinant to soccer performance, few systematic reviews or meta-analyses described the CHO ingestion among male soccer players. OBJECTIVES: This systematic-review, with meta-analyses, examined the CHO intake in male soccer players according to the competitive schedule (preparatory season, season and off-season). Additionally, the variability of CHO intake considering playing position was described. METHODOLOGY: Three databases were consulted: PubMed, SPORTDiscus and Web of Science Core Collection. Studies were included according to the following eligibility criteria: (i) male soccer players, (ii) age ≥ 18.0 years, (iii) CHO intake expressed in g.kg-1.day-1. RESULTS: Initially, 1992 manuscripts were identified. Of those, 11 manuscripts were considered eligible for the systematic review and 10 manuscripts were included in the meta-analyses. The results of the current meta-analysis showed that male soccer players consumed, on average, 4.3 g.kg-1.day-1 and 5.0 g.kg-1.day-1 of CHO during the season and in the preparatory period, respectively. Surprisingly, no studies reported CHO intake during off-season. Only three studies examined CHO ingestion by playing position. Although samples were limited, goalkeepers seemed to ingest less CHO than outfielders. CONCLUSIONS: Considering the limitations associated with CHO intake reporting, nutritional strategies to confirm that athletes meet the intake of this macronutrient are needed.

A INFLUÊNCIA DO GLUCOMANANO NO CONTROLO DE PESO

RESUMO INTRODUÇÃO: O excesso de peso e a obesidade são considerados uma problemática de saúde, podendo ter repercussões na mortalidade e qualidade de vida dos indivíduos. O glucomanano é um componente significante do cormo de konjac, proveniente da planta designada por Amorphophallus konjac. É considerado uma fibra dietética fermentável solúvel, que forma géis, e o seu papel como suplemento alimentar tem sido estudado nos últimos anos de modo a avaliar potenciais benefícios, nomeadamente no controlo ponderal. OBJETIVOS: Analisar a evidência científica existente sobre a suplementação de glucomanano no controlo de peso, bem como entender os riscos para a saúde inerentes ao seu consumo. METODOLOGIA: A pesquisa bibliográfica foi realizada nas bases de dados PubMed e ScienceDirect, recorrendo-se às palavras chave “glucomannan” e “weight”. Os resultados obtidos incluíram artigos, preferencialmente, dos últimos 10 anos, sendo que inicialmente foram selecionados pelo título, em seguida pelo resumo e por fim pela leitura completa dos mesmos. RESULTADOS: O glucomanano promove sensação de saciedade devido à sua capacidade de absorção de água, potenciando a motilidade intestinal. A maioria das revisões analisadas verificou uma perda de peso significativa a curto prazo, em adultos com excesso de peso ou obesidade, no entanto um outro estudo com maior número de participantes, não verificou resultados positivos neste aspeto. Em crianças e adolescentes, os estudos são escassos não mostrando efeitos significativos na redução de peso. A dose recomendada com potenciais efeitos benéficos em adultos é de 3g/dia. CONCLUSÕES: Os ensaios futuros devem ter melhor qualidade metodológica. Assim sendo, apesar da recomendação de glucomanano para perda de peso parecer segura, esta não deve ser a primeira abordagem nem uma prioridade.

ABSTRACT INTRODUCTION: Overweight and obesity are considered major health problems that increase mortality and quality of life. Glucomannan is the significant component of konjac corm, which comes from the plant Amorphophallus konjac. Glucomannan is a soluble, fermentable dietary and natural gel-forming fiber and in the last few years, its role as a dietary supplement has been evaluated to access its potential health benefits, namely weight control. OBJECTIVES: Evaluate the evidence for or against the efficacy of glucomannan supplement in body weight control and if there’s any health risk related to its intake. METHODOLOGY: Data collection was carried out through scientific databases Pubmed and ScienceDirect, using as research expressions: “glucomannan” AND “weight”. The results, preferably from the last ten years, were first analysed by title, then abstract and finally full-text reading. RESULTS: Glucomannan promotes a “feeling full” effect due to the water-absorbing capacity of the fiber. It also helps intestinal motility. In the short term, most of the reviews found a significant weight loss in overweight and obese adults, although another study with a greater number of participants found no significant weight loss. In children and adolescents, the studies are scarce. However, they show no effect on bodyweight reduction. The recommended dose for potential beneficial effects in adults is 3g/day. CONCLUSIONS: Future trials should have better methodological quality. Until then, glucomannan recommendation for weight loss, although it seems safe in most cases, should not be a first approach nor a priority.

A TERAPIA COMPORTAMENTAL E COGNITIVA COMO ESTRATÉGIA NA REDUÇÃO E MANUTENÇÃO DO PESO CORPORAL: UMA REVISÃO SISTEMÁTICA

RESUMO INTRODUÇÃO: Intervenções nutricionais para redução de peso podem falhar e entender as causas dessas falhas pode auxiliar nutricionistas no acompanhamento e tratamento de pacientes. A terapia comportamental e cognitiva é um procedimento psicopedagógico focado no problema atual do paciente, no seu comportamento e na sua cognição de autocontrole. OBJETIVOS: Esta revisão sistemática teve como objetivo geral avaliar a terapia comportamental e cognitiva como coadjuvante da terapêutica nutricional no processo de emagrecimento. METODOLOGIA: Dezasseis estudos foram incluídos e selecionados nas bases de dados PubMed e SciElo, usando os descritores perda de peso, emagrecimento e terapia comportamental e cognitiva. RESULTADOS: Existem evidências de que a terapia comportamental e cognitiva contribui para o processo de perda de peso, especialmente em estudos de longa duração, através de melhor adesão às mudanças no estilo de vida, controle emocional e comportamental. CONCLUSÕES: Embora não se possa afirmar que a abordagem comportamental é superior à abordagem focada na restrição calórica, a terapia comportamental e cognitiva como estratégia auxiliar parece promissora e mais estudos são necessários para identificar as especificidades que apoiem melhorias duradouras na cognição e comportamento alimentar. Assim, é indicada a identificação de crenças disfuncionais em pacientes quanto à possibilidade de perda e de manutenção do peso, seguida de intervenção para transformá-las ou substituí-las por crenças funcionais para reduzir as falhas no processo de perda de peso.

ABSTRACT INTRODUCTION: Nutritional interventions for weight loss can fail sometimes, and understanding the causes of these failures can assist nutritionists in monitoring and treating patients. Cognitive-behavioural therapy is a psycho-pedagogical therapy focused on the patient's current problem, behaviour, and knowledge of self-control. OBJECTIVES: This systematic review aimed to evaluate cognitive-behavioural therapy as an auxiliary strategy to nutritional therapy in the weight loss process. METHODOLOGY: Sixteen studies were included and selected in the PubMed and SciElo databases, using weight loss, weight loss, and cognitive-behavioural therapy descriptors. RESULTS: There is evidence that cognitive-behavioural therapy contributes to the weight loss process, especially in long-term studies, through better adherence to changes in lifestyle, emotional and behavioural control. CONCLUSIONS: Although the behavioural approach cannot be superior to the calorie-restricted approach, cognitive-behavioural therapy as an adjunct strategy appears promising. More studies are needed to identify specifics that support lasting improvements in cognition and eating behaviour. Thus, identifying dysfunctional beliefs in patients regarding the possibility of losing weight and weight maintenance is indicated, followed by intervention to transform or replace them with practical ideas to reduce failures in the weight loss process.

SAÚDE MENTAL EM PERSPETIVA - O PAPEL DA NUTRIÇÃO E DA MICROBIOTA INTESTINAL

RESUMO As perturbações mentais representam um dos mais importantes desafios da atualidade. No entanto, as opções terapêuticas disponíveis são nalguns casos pouco eficazes ou apresentam efeitos adversos importantes. As intervenções no âmbito do estilo de vida, onde se incluem intervenções nutricionais e alimentares, têm vindo a ser exploradas na área da doença psiquiátrica e já demonstraram exercer um efeito benéfico na sua otimização. Adicionalmente, existe uma conhecida associação entre a doença psiquiátrica e os distúrbios gastrointestinais. A evidência sugere que indivíduos com depressão apresentam uma composição da microbiota intestinal alterada, em comparação com indivíduos saudáveis. Neste sentido, também a microbiota intestinal poderá constituir um alvo terapêutico atrativo. Várias estratégias para a sua modificação já foram descritas, incluindo a manipulação da dieta, a utilização de suplementos probióticos e/ou prebióticos e o transplante de microbiota fecal. Pretende-se com este trabalho abordar importância da nutrição e alimentação no foro da psiquiatria, assim como a modulação da microbiota intestinal e utilização de psicobióticos, reconhecidos como uma potencial coadjuvante para o tratamento destas patologias. Conclui-se que, embora a informação atualmente disponível nesta matéria seja promissora, são necessários mais estudos para que seja possível formular recomendações específicas e cientificamente sustentadas.

ABSTRACT Psychiatric disorders are some of the most serious challenges of our time. However, the currently available therapeutic options are often ineffective or carry severe side effects. Lifestyle interventions, which include dietary interventions, are being explored in the field of mental illness and have already been shown to exert beneficial effects. Additionally, there is a known association between psychiatric illness and gastrointestinal disorders, and patients with depression were reported to display an altered gut microbiota composition, when compared to healthy controls. In line with this, the gut microbiota may also be an attractive therapeutic target. Several approaches for its manipulation have already been described, such as dietary interventions, the use of probiotics and/or prebiotics and fecal microbiota transplantation. Thus, this review aims to summarize the importance of food and nutrition in the field of psychiatry, as well as the modulation of the gut microbiota and the use of psychobiotics, which have been recognized as a possible adjuvant therapy for these disorders. Finally, although current evidence in this matter is promising, further investigation is needed in order to translate this knowledge into clinical practice and make scientifically supported recommendations.

DIETA CETOGÉNICA E EPILEPSIA: UMA REVISÃO NARRATIVA DA LITERATURA

ABSTRACT Several studies have already explored the role of ketone bodies on the physiological processes involved in the onset of seizures and ketogenic diet is a common treatment option in drug-resistant epilepsy either in children, adolescents or adults. This narrative review aims to summarize the available evidence on the possible mechanisms of action, and on the efficacy of the ketogenic diet and its variants on the treatment of epilepsy from infants to adults. Even though there is a robust biologic plausibility and either mechanistic studies and randomized controlled trials supporting ketogenic diet as a valid approach to reduce seizures in drug-resistant childhood epilepsy, the level of evidence is not as strong for the treatment of drug-resistant epilepsy in adults.

INTRODUCTION Epilepsy is a neurological disorder characterized by seizures, which affect about 70 million people worldwide (1). Almost one-third of patients with epilepsy continue to have disabling seizures despite the treatment with anti-seizures drugs (2). The International League Against Epilepsy defines drug resistant epilepsy as a failure of adequate trials of two tolerated and appropriately chosen and dosed epileptic drugs (whether as monotherapies or in combination) to achieve sustained seizure freedom (3). Resective epilepsy surgery is a possibility for patients with drug resistant epilepsy, but, in a proportion of drug resistant epilepsy patients, resective surgery might not be an option (2), and Ketogenic diet (KD) therapies are used as an established non-pharmacologic alternative (3). Following a KD requests careful dietary planning with balanced macronutrient proportion in order to achieve ketosis (4). Supported in the alterations of metabolic processes due to the increase of ketone bodies, multiple papers are now available on the effect of the KD on seizures in epileptic patients. Therefore, this review aims to summarize the mechanisms which supports the role of KD on epilepsy management and to condense the available evidence on the effectiveness of KD on seizures prevention on epileptic human subjects. METHODOLOGY The entire review was conducted on the basis of a PubMed search with no date restrictions and aiming mainly to identify mechanistic studies and randomized controlled trials, using the keywords ‘ketone bodies’, ’ketogenic diet’ and ’epilepsy’. After analysing the title and sometimes the abstract of the 322 articles identified, 35 were integrated in this review. History and Origins Fasting and other diets have been used to treat epilepsy since 500 BC (5), but only in 1921, Woodyatt observed that in healthy subjects, starvation or a diet containing a low proportion of carbohydrates and a high proportion of fat, increased acetone and beta‐ hydroxybutyric levels in the blood. Wilder proposed that a KD should be tested in patients with epilepsy. He suggested that the KD could be as effective as fasting, but likely to be maintained long-term. Wilder subsequently coined the term KD to the ketone‐producing diet (5). In 1925 Peterman proposed a macronutrients ratio for the KD, still accepted nowadays: 1 g of protein per kilogram of body weight in children, 10-15 g of carbohydrates per day, and the remainder of the calories in fat (5). In 1972 Livingston, at Johns Hopkins Hospital, based on the results obtained using KD in over a thousand children with epilepsy, showed that 52% achieved seizures freedom 27% had improved seizures (5). In 1938, Merritt and Putnam discovered diphenylhydantoin, and the KD popularity, as a therapeutic diet for pediatric epilepsy ceased with the introduction of antiepileptic drugs (5). Historically, the classic KD is a very low-carbohydrate with moderate- protein and high-fat diet, composed of a 4:1 ratio (4 g of fat to every 1 g of protein and carbohydrate) (2). Although KD is currently used in clinical practice, its application requires detailed calculation, education, and training, precise food weighing, and careful food preparation (6). Therefore, with the aim of improving compliance to KD, the modified Atkins diet is often used as a modification of the classic KD, always with defined protocols (6). The modified Atkins diet is typically composed of a net 10-20 g/day carbohydrate limit, equivalent to a ratio 1-2:1 of fat to protein and carbohydrates (2). A hybrid between the classic KD and the modified Atkins diet is called the modified KD, where carbohydrates provides around 5% of the total energy intake (approximately 20-30 g/day) and fat provides about 75%. This strategy offers the dietary control offered by the classic KD and the flexibility of modified Atkins diet (6). This variants aim to increase the variability, the palatability, and the tolerability of the diet, improving the compliance, an important factor for a successful dietary treatment (7). It seems that, after a few days with such drastically reduced carbohydrate consumption, glucose reserves become insufficient, both for normal fat oxidation through the supply of oxaloacetate in the Krebs cycle and for the supply of glucose to the central nervous system. The central nervous system cannot use fatty acids as a nutritional source. Hence, after 3-4 days of carbohydrate restriction, the central nervous system is forced to find an alternative energy source: ketone bodies (8). Biochemistry of Ketone Bodies Ketogenesis, starting either from fatty acid oxidation or oxidation of ketogenic amino acids, leads to the formation of ketone bodies, three distinct molecules known as β-hydroxybutyrate, acetoacetate, and acetone. They represent circulating energy molecules during fasting or prolonged exercise. Most of the biosynthetic process occurs in the mitochondria of the hepatocytes, even though a small production may be found in other tissues, like kidney epithelia, astrocytes, and enterocytes (9). In the initial phase of fasting, tissues rely primarily on glucose metabolism, and glycogen stored in muscle and liver is depleted first. After a prolonged fast, fatty acids are mobilized from the adipose tissue to the liver, and they undergo β-oxidation to produce acetyl-CoA that enters the tricarboxylic acid cycle (Krebs cycle). Under normal conditions, acetyl-CoA from fatty acid β-oxidation is further oxidized via the tricarboxylic acid cycle, and then, the reduced coenzymes NADH and FADH2 allow the production of energy by the electron transport chain in the mitochondria coupled to ATP synthesis (oxidative phosphorylation, OXPHOS). However, the tricarboxylic acid cycle cannot handle the large amount of acetyl-CoA derived from fatty acid β-oxidation due to low levels of insulin, the increase of the fatty acids release and of the enzymes required for ketone body synthesis and utilization. Simultaneously, the diversion of oxaloacetate to feed gluconeogenesis in the liver leads to low activity of TCA cycle due to reduced amounts of metabolic intermediates, which increases acetyl-CoA levels that increases its usage as a substrate for ketone body synthesis (10). Acetyl-CoA derived from fatty acid β-oxidation is the substrate for the first step of ketogenesis: acetoacetyl-CoA thiolase (ACAT1) catalyzes the condensation of two molecules of acetyl-CoA to form acetoacetyl-CoA. Mitochondrial hydroxymethyl glutaryl-CoA synthase (HMGCS2), the rate-limiting enzyme of the pathway, promotes the addition of a third acetyl-CoA molecule to form 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). The first ketone body, acetoacetate, is then produced by HMG-CoA lyase (HMGCL). ACA is the common precursor of the other two ketone bodies: it is mainly reduced to βOHB by NADH-dependent β-hydroxybutyrate dehydrogenase (BDH). The third ketone body derives from the spontaneous decarboxylation of ACA in a volatile product, acetone, which is excreted mainly through the lungs (11). Regulators of Ketogenesis Higher levels of insulin strongly inhibit ketogenesis, even when catabolic hormones are also secreted. Insulin acts in two complementary manners: first, it blocks lipolysis in adipocytes; and, it promotes glucose uptake and oxidation by tissues, which results in elevated succinyl-CoA and malonyl- CoA levels. These intermediates are potent inhibitors of fatty acid oxidation and ketone body formation in the liver and other ketogenic tissues. When insulin levels are low, the catabolic hormones, namely glucagon (secreted by the pancreas), cortisol, catecholamines, epinephrine, norepinephrine, and thyroid hormones, come into prominence (12, 13). Ketogenic Diet Mechanisms in Seizure Managment In a diet rich in carbohydrates, glucose is the ‘preferred’ substrate by the brain to obtain energy, in the KD the situation changes. The ingested fatty acids are metabolised in liver mitochondria into ketone bodies which are then released into the blood stream and are taken up by multiple organs including the brain. In the mitochondria of neurons and glial cells ketone bodies are catabolised to acetyl-CoA, which can then enter the TCA cycle for energy generation (producing NADH and ultimately ATP), or it can be used in lipogenesis to produce fatty acids. A consequence of the increased dependence on mitochondria for energy generation with the KD is that the numbers of that organelle increase in neurons and glia (12). ATP and energy metabolism are intimately connected to another process through which the KD is involved in neuroprotective mechanisms, proposed to increase the seizure threshold and to reduce the damage to the brain that is generated by seizures. (14) As mentioned above, KD leads to mitochondrial biogenensis (13) probably because of the importance of the mitochondria for energy generation from fat, increasing ATP production capacity which is used to full Na/K-ATPase and other pumps, which serve to stabilize neuronal membrane potential (13). Reactive oxygen species (ROS) formation occurs when unpaired electrons escape the electron transport chain and react with molecular oxygen; ROS increase causes cell damage and death (15). An increase of ROS is observed at onset of KD, followed by a decrease when the diet is prolonged at least one week, thanks to the involvement of the Nrf2 pathway and to stimulation of glutathione production (14). The above improves neuronal homeostasis and reduces the impacts of the high energy drain during seizures (15). The increase in the biosynthesis of different fat products in patients on a KD provide other neuroprotective mechanisms. Hypomyelination is a feature of some epilepsies and a KD increases brain levels of acetyl-CoA (from ketone bodies) and aspartate (from TCA-cycle intermediates) which both contribute to the synthesis of myelin (16). Another product of fat metabolism with probable anti-seizure effects is poly-unsaturated fatty acids which can be higher in the brain of patients on a KD and they are thought to protect neurons through simulating mitochondrial uncoupling proteins which reduce reactive oxygen species production, and poly- unsaturated fatty acids can also directly modulate different types of ion pumps and channels thereby reducing neuronal hyperexcitability (17). There is also evidence that the decrease in glycolysis in patients on a KD contributes to the improved seizure control, in fact, there is a rapid resumption of seizures when patients on a KD resume ingesting carbohydrates or glucose (18), these effects may be linked to reductions in lactate (which is produced by glycolysis) which can alter neuronal membrane polarity through ATP-dependent potassium channels (19). Ketone bodies may also alter the behaviour of vesicular glutamate transporters (VGLUTs). Cl− acts as an allosteric activator of VGLUT and triggers glutamate uptake upon binding. Ketone bodies compete for the putative Cl− binding site(s) and turn VGLUT activity off upon binding, causing a reduction in glutamatergic neurotransmission in vivo (20, 21). Evidence in Children and Adolescents KD has been successfully used in drug-resistant epilepsy, and research has shown that this diet is more successful at younger age in achieving seizure freedom (22). Many studies have shown that children and adolescents following a KD have a 50% reduction in seizure frequency, which is considered as clinically relevant (23). Based on the current guidelines for infancy and the high capacity of achieving ketosis in infancy, a fat/non-fat ratio of 3:1 is recommended (22). In 2016 Kim and colleagues compare the efficacy, safety, and tolerability of a modified Atkins diet with the classic KD for the treatment of drug- resistant childhood epilepsy, and showed that the modified Atkins diet might be considered a good treatment, but the classic KD is more suitable in patients under two years of age (24). The treatment with KD and modified Atkins diet was effective in children with refractory epilepsy of genetic etiology with responder rates at 1, 3, 6, 12, and 24 months being 63%, 61%, 54%, 53%, and 41% respectively (3). A recent cohort study evaluated the efficacy and safety of KD for children with refractory epilepsy and despite the low compliance with the recommended distribution of macronutrients and the reported lack of palatability of the diet, the antiepileptic effect of the treatment was confirmed. There were 139 patients included in this study and at 1 month’ follow-up, 39 of 139 (28.0%) subjects were responders: 9 (6.5%) were seizure-free, 12 (8.6%) had a seizure reduction of >75%, and 18 (12.8%) had a seizure reduction of 50-75%. At 3 months’ follow-up, 71 of 129 (55%) subjects were responders: 17 (13.2%) were seizure-free, 23 (17.8%) had a seizure reduction of >75%, and 31 (24.0%) had a seizure reduction of 50-75%. At 6 months’ follow-up, 70 of 103 (67.9%) subjects were responders: 24 (23.3%) were seizure-free, 16 (15.5%) had a seizure reduction of >75%, and 30 (29.0%) had a seizure reduction of 50-75% (25). In fact, a recent meta-analysis (26) which aimed to assess whether spasm remission during the period of 3 months KD can be a prediction index for the therapeutic effect of 6 months treatment, showed that a period of 3 months KD can be a prediction index of 6 months duration in term of spasm remission. Baby and colleagues reported the efficacy and tolerability of KD in a series of 74 South Indian children with refractory epilepsy during 5 years. The results were that 44 children reported a seizure reduction higher than 50%. Among these, 19 children reported seizure reduction between 50 and 90%, 25 children more than 90% of seizure reduction and 6 children (8.1%) achieved seizure freedom during the maintenance phase (27). Ketogenic treatment in children is safe, without significant adverse reactions, but can lead to micronutritional deficits as selenium (23). In recent meta-analysis (1) regarding the efficacy and tolerability of the KD and modified Atkins diet in children and adolescents with refractory epilepsy, KD and its variations were considered as a promising treatment option in epilepsy, thanks to the beneficial clinical results regarding efficacy and safety. Evidence in Adults The benefits of the KD in the treatment of epilepsy in adults have not been clarified yet (28). Martin-McGil et al. identified 13 studies with 932 participants; 711 children and 221 adults and concluded that the evidence suggests that KD demonstrate eIectiveness in children with drug-resistant epilepsy but that the evidence for its use in adults remains uncertain (29). In a randomized control trial, the authors found a significant seizure reduction in the diet group compared to the controls, but only for moderate benefits (25-50% of seizure reduction) (28). Husari et al. evaluated data from recent clinical trials showing that some adults with epilepsy achieve significant benefits with KD treatment stating that it is clear that some adults with epilepsy achieve significant benefits by the treatment with KD, but that future studies are needed to explore the effectiveness of this treatment in specific epilepsy syndrome (e.g. focal, generalized) (2). Roehl et al. evaluated the efficacy of the modified KD on seizure frequency, severity and quality of life in adults with drug-resistant epilepsy; and observed a ≥ 50% seizure frequency improvement, 42 (76%) reported improvement in seizure severity, and 48 (87%) reported improvement in quality of life after 3 months of diet therapy (30). Recent evidence suggests that KD treatments improve seizure control and improve other neurologic conditions, including nonmotor Parkinson’s disease symptoms; specific themes that emerged from clinical trials in adults may impact and guide future studies (31). A recent systematic review reports current evidence regarding the use of KD in adults, the results show that this therapy can be a good option, but the dates need to be interpreted with caution due to inherent bias and the small sample size of the studies included (32). Another recent study in the United Kingdom investigated the effectiveness, retention, and safety profile of modified KD in adults with epilepsy and showed that modified KD can be effective in adults, although, even with regular dietetic support, retention rates remain low, and periods of worsening seizure frequency are common, nevertheless 60% of the patients improved seizure frequency, 38% experiencing > 50% of seizure reduction and 13% experiencing a seizure freedom (33). CRITICAL ANALYSIS We analyzed the beneficial effects of KD in epilepsy, but other aspects need to be considered before it can be called a ‘miraculous diet’ (8). The most recurrent reported adverse effects related to KD treatment are gastrointestinal effects, weight loss, alteration in lipid profile (2), stress, constipation (30), vomiting (3), and all those often represent a reason to drop out the treatment. However, these side effects can generally be managed with extra dietary advice (e.g. increasing dietary fiber and fluid intake) (7). Another important concern should be the diet compliance since several studies in adults shows compliances between 38 and 62.9%. Regarding compliance the modified Atkins diet seems a better option (2). Mc Donald et al. evaluated whether the use of a ketogenic formula (KetoCal®) during the first month of modified Atkins diet can improve diet compliance in adults, and the results have shown that even though the supplementation does not increase the likelihood of reducing seizure it significantly increases the compliance with the treatment (34). KD, especially the more restrictive variants, are characterized by low variability, palatability, and tolerability; in recent years, to improve the quality of life in patients following the KD treatment, food companies have started to develop and commercialize, several food products for these patients like non caloric sweeteners, the use of ‘ketogenic powders’ and ketogenic liquid formulas’, products rich in medium- or long-chain triglycerides. Other types of products that are growing on the market are ready-to- eat ketogenic products like biscuits, bread, focaccia, and desserts that improve the palatability and tolerability of the diet. Nowadays is possible to find ‘ketogenic’ ’foods as pasta, bread biscuits, and desserts with high protein content and low carbohydrates content (7). A recent review (35) highlights other controversial questions which need to be discussed and researched in what regards to KD therapies; for example, maybe in the future KD may be used as a first-line treatment, or ketogenic treatment may be replicated in a pill or patients may be able to start the KD on their own without supervision. In addition, more research is needed about the potential adverse effects of KD therapy (e.g. bone health and menstrual cycle). CONCLUSIONS In conclusion, although there is a robust biologic plausibility and either mechanistic studies and randomized controlled trials supporting KD as a valid approach to reduce seizures in drug-resistant childhood epilepsy, the level of evidence is not as strong for the treatment of drug-resistant epilepsy in adults and many questions remain open due to study limitations, as low sample size, short-term follow-ups, the low compliance with the diet, and therefore, future studies are needed to clarify certain aspects of the relationship between KD and epilepsy management.

RESUMO Vários estudos têm explorado o papel dos corpos cetónicos nos processos fisiológicos envolvidos no despontar de convulsões sendo a dieta cetogénica uma opção de tratamento usual na epilepsia fármaco-resistente, quer em crianças, adolescentes ou adultos. A presente revisão narrativa procura resumir a evidência disponível sobre os possíveis mecanismos de ação e eficácia da dieta cetogénica e suas variantes no tratamento da epilepsia de crianças a adultos. Apesar da forte plausibilidade biológica e da existência de estudos mecanicistas e ensaios clínicos controlados e aleatorizados que suportam a dieta cetogénica como uma abordagem válida para reduzir a probabilidade de convulsões na epilepsia fármaco-resistente em crianças, o nível de evidência não é tão forte para a sua utilização no tratamento de adultos.

ECOTROPHELIA PORTUGAL (2017-2020): CONTENT ANALYSIS OF A COMPETITION TO PROMOTE ACADEMIC ENTREPRENEURSHIP AND FOOD INNOVATION

ABSTRACT INTRODUCTION: The food sector is considered worldwide as one of the main business sectors, being constantly changing and facing multiple challenges. OBJECTIVES: This paper aims to describe the finalist teams and products in the competition for the Ecotrophelia Portugal (2017- 2020) as sources of innovation for the food sector. METHODOLOGY: A content analysis approach was adopted. The analyzed contents were collected through the official website of Ecotrophelia Portugal. Information from the 41 finalist teams in the competition between 2017 and 2020 was analyzed. RESULTS: In general, most of the finalists were female (2017 edition), belonging to the North region (57.4%), followed by the Centro region (27.9%) and Lisbon (13.1%), with the Universidade do Porto (26.2%), Universidade Católica Portuguesa (Porto: 16.4%) and the Instituto Politécnico de Coimbra (13.1%) being the main institutions from which the finalists came. The main categories to which the finalist products belonged were: snacks (34.1%), desserts (17.1%), ready-to-eat meals (12.2%), drinks (9.8%). The characteristics most mentioned in the description of these products were that they are: rich in bioactive compounds (34.2%), gluten / lactose free or low in sugar / fat (19.0%), healthy (11.4%) and vegetarian / vegan (11.4%). CONCLUSIONS: This study provides useful information for future competitors to new editions of this competition, as well as a source of inspiration for the development of new food products by entrepreneurs.

RESUMO INTRODUÇÃO: O setor alimentar é considerado a nível mundial como um dos principais setores de negócios, estando em constante mudança e enfrentando múltiplos desafios. OBJETIVOS: Este artigo tem como objetivo descrever as equipas e produtos finalistas da competição Ecotrophelia Portugal (2017- 2020) como fontes de inovação para o setor alimentar. METODOLOGIA: Foi adotada uma metodologia de análise de conteúdo. Os conteúdos analisados foram recolhidos através do site oficial da Ecotrophelia Portugal. Foram analisadas informações sobre as 41 equipas finalistas da competição entre 2017 e 2020. RESULTADOS: De um modo geral, os finalistas foram maioritariamente mulheres (edição 2017), pertencentes à região Norte (57,4%), seguida da região Centro (27,9%) e Lisboa (13,1%), com a Universidade do Porto (26,2%), a Universidade Católica Portuguesa (Porto: 16,4%) e o Instituto Politécnico de Coimbra (13,1%) a serem as principais instituições de proveniência dos finalistas. As principais categorias dos produtos finalistas foram: snacks (34,1%), sobremesas (17,1%), refeições prontas a consumir (12,2%), bebidas (9,8%). As características mais mencionadas na descrição desses produtos foram: rico em compostos bioativos (34,2%), sem glúten / sem lactose ou com baixo teor de açúcar / gordura (19,0%), saudável (11,4%) e vegetariano / vegano (11,4 %). CONCLUSÕES: Este estudo proporciona informação útil para os participantes nas futuras edições desta competição, assim como uma fonte de inspiração para empreendedores desenvolvam novos produtos alimentares.