The coronavirus disease 2019 (COVID-19) pandemic is provoking a global public health crisis. Even though the academic world is intensively pursuing new therapies, there is still no “game changer” in the management of COVID 19. The Mammalian Target of Rapamycin (mTOR) is an ancient signaling system that has been proposed as a molecular tool used by coronaviruses and other RNA and DNA viruses in order to replicate and persist in the host cell. In recent years, Intermittent Fasting (IF), a practice consisting on a strict calorie restriction during a prolonged period of time during the day, has gained popularity due to its potential benefits in multiple health systems and in regulating inflammation. IF inhibits the mTOR pathway which is similar to the effects of Rapamycin in some animal models. mTOR inhibition and promotion of autophagy could potentially be the link between the possible direct benefits of IF in COVID-19 due to the interruption of the viral cycle (protein synthesis). Besides, IF has shown to be a strong anti-inflammatory in multiple prior studies, and may play a role in attenuating COVID -19 severity. This review hypothesizes the possible intersection between viral, immunological, and metabolic pathways related to mTOR and the potential mechanisms through which IF may improve clinical outcomes. Future prospective randomized controlled clinical trials to evaluate intermittent fasting (IF) regimens in order to prevent and treat moderate to severe forms of COVID-19 in humans are needed. / Revisión por pares

As dietas intermitentes (IF) compreendem ciclos alternados de 24 horas de jejum e alimentação. Como os efeitos de IF sobre o balanço redox não são bem conhecidos, esse trabalho teve por objetivo avaliar os efeitos desta dieta sobre o estado redox de diferentes tecidos de ratos. Após um mês de tratamento, os fígados dos ratos em IF apresentaram um aumento de capacidade respiratória mitocondrial juntamente com níveis elevados de proteínas carboniladas. Verificou-se ainda um aumento em danos oxidativos no cérebro destes animais. IF promoveu significativa proteção contra danos oxidativos no coração, enquanto que não houve alterações no estado redox do músculo esquelético. Os efeitos metabólicos de IF também foram investigados com o intuito de compreender os mecanismos envolvidos com o menor peso e a hiperfagia promovidos por esta intervenção. Observou-se que o menor peso dos ratos submetidos à IF é consequência de um aumento em taxas metabólicas em dias de alimentação somado à oxidação lipídica aumentada durante o jejum. A hiperfagia, por sua vez, é consequencia de elevação nos níveis de neurotransmissores orexigênicos hipotalâmicos, mesmo quando estes animais estão alimentados. Os níveis do neutransmissor TRH também foram modulados por esta dieta, o que pode estar relacionado com as alterações de taxas metabólicas observadas no modelo. Concluímos, portanto, que as dietas intermitentes promovem modificações funcionais no hipotálamo que estão associadas com diferenças no peso corpóreo e no apetite. Além disso, IF afeta o balanço redox de forma tecido específica, levando a um desbalanço oxidativo no fígado e no cérebro e à proteção contra danos oxidativos no coração. / Intermittent fasting (IF) is a dietary intervention that comprises 24 hour cycles alternating ad libitum feeding and fasting. We address here the effects of IF on redox state in different tissues, which are still poorly understood. After one month on the diet, IF rats livers presented increased mitochondrial respiratory capacity along with increased levels of protein carbonyls. Surprisingly, IF animals also presented an increase in oxidative damage in the brain. Conversely, IF promoted a substantial protection against oxidative damage in the heart. No difference in redox homeostasis was observed in the skeletal muscle. We also assessed metabolic effects of IF to uncover the mechanisms involved in the lower body mass and loss of feeding control in IF rats. As measured calorimetrically, IF animals presented high metabolic rates during feeding days and increased lipid oxidation on fasting days, which explains the lower body weight. IF-induced overeating was a consequence of increased expression of hypothalamic orexigenic neurotransmitters, even on feeding days. THR levels also were changed, in parallel with the feeding-dependent alterations on metabolic rates. Overall, we find that intermittent fasting promotes functional hypothalamic alterations associated with differences in body weight and appetite. In addition, IF affects redox balance in a tissue-specific manner, leading to redox imbalance in the liver and brain, as well as protection against oxidative damage in the heart

As dietas intermitentes (IF) compreendem ciclos alternados de 24 horas de jejum e alimentação. Como os efeitos de IF sobre o balanço redox não são bem conhecidos, esse trabalho teve por objetivo avaliar os efeitos desta dieta sobre o estado redox de diferentes tecidos de ratos. Após um mês de tratamento, os fígados dos ratos em IF apresentaram um aumento de capacidade respiratória mitocondrial juntamente com níveis elevados de proteínas carboniladas. Verificou-se ainda um aumento em danos oxidativos no cérebro destes animais. IF promoveu significativa proteção contra danos oxidativos no coração, enquanto que não houve alterações no estado redox do músculo esquelético. Os efeitos metabólicos de IF também foram investigados com o intuito de compreender os mecanismos envolvidos com o menor peso e a hiperfagia promovidos por esta intervenção. Observou-se que o menor peso dos ratos submetidos à IF é consequência de um aumento em taxas metabólicas em dias de alimentação somado à oxidação lipídica aumentada durante o jejum. A hiperfagia, por sua vez, é consequencia de elevação nos níveis de neurotransmissores orexigênicos hipotalâmicos, mesmo quando estes animais estão alimentados. Os níveis do neutransmissor TRH também foram modulados por esta dieta, o que pode estar relacionado com as alterações de taxas metabólicas observadas no modelo. Concluímos, portanto, que as dietas intermitentes promovem modificações funcionais no hipotálamo que estão associadas com diferenças no peso corpóreo e no apetite. Além disso, IF afeta o balanço redox de forma tecido específica, levando a um desbalanço oxidativo no fígado e no cérebro e à proteção contra danos oxidativos no coração. / Intermittent fasting (IF) is a dietary intervention that comprises 24 hour cycles alternating ad libitum feeding and fasting. We address here the effects of IF on redox state in different tissues, which are still poorly understood. After one month on the diet, IF rats livers presented increased mitochondrial respiratory capacity along with increased levels of protein carbonyls. Surprisingly, IF animals also presented an increase in oxidative damage in the brain. Conversely, IF promoted a substantial protection against oxidative damage in the heart. No difference in redox homeostasis was observed in the skeletal muscle. We also assessed metabolic effects of IF to uncover the mechanisms involved in the lower body mass and loss of feeding control in IF rats. As measured calorimetrically, IF animals presented high metabolic rates during feeding days and increased lipid oxidation on fasting days, which explains the lower body weight. IF-induced overeating was a consequence of increased expression of hypothalamic orexigenic neurotransmitters, even on feeding days. THR levels also were changed, in parallel with the feeding-dependent alterations on metabolic rates. Overall, we find that intermittent fasting promotes functional hypothalamic alterations associated with differences in body weight and appetite. In addition, IF affects redox balance in a tissue-specific manner, leading to redox imbalance in the liver and brain, as well as protection against oxidative damage in the heart

Purpose: Fasting has been promoted as a method of preventing disease and aging for thousands of years. With heart disease being a leading cause of death in the U.S., researchers have explored the effects of fasting on variables that influence cardiovascular disease (CVD), like LDL cholesterol. Therefore, the purpose of this study was to assess the effects of weekly water-only fasting on LDL cholesterol (LDL-C) in men and women with metabolic risk factors for CVD. Methods: This study was a randomized control trial in adult men and women. Participants were randomized to fasting (treatment) or normal diet (control). The fasting protocol consisted of four weeks of two 24-hour water-only fasts, followed by 22 weeks of once-weekly water-only 24-hour fasts. Measurements such as height, weight, waist circumference and LDL-C were assessed at baseline, 4 weeks, 13 weeks, and 26 weeks. Results: Intermittent fasting (n = 50) and control (n = 53) participants were 49.3 ± 12.0 and 47.0 ± 9.8 years, respectively, predominantly females (66.0% and 67.9%), overweight (103 ± 24 and 100 ± 21 kg), and with mild LDL-C elevation (124 ± 19 and 128 ± 20 mg/dL). Change in weight was −1.70 ± 4.69 (kg) in the fasting group and 0.20 ± 3.45 (kg) in the control group and not different between conditions (p = 0.06). There was no condition-by-period interaction for LDL-C (p = 0.06). Similarly, the change in LDL-C from baseline to follow-up was not different between conditions (t = −0.538, p = 0.59; Cohens D = 0.12) Conclusions: A once-per-week intermittent fasting regimen did not reduce weight or LDL-C. Further research of such fasting regimens is needed to evaluate their potential impact on cardiometabolic health.

No description available.

Alzheimer's disease is the most common dementia disease and the main cause of death. The hallmark is neurofibrillary tangles (abnormal aggregates of tau protein) and beta-amyloid (Aβ) neuritic plaques that leads to impaired cognitive function such as memory loss and learning difficulties. Researchers have discovered that intermittent fasting improves these cognitive abilities, even though eating regularly is recommended for good cognition. This systematic review aims to investigate further if intermittent fasting improves cognitive function in Alzheimer’s disease and if levels of Aβ and tau pathology explain these changes in cognitive function. The research question is: does intermittent fasting improve cognitive abilities in Alzheimer’s disease and does the levels of Aβ and tau pathology explain these cognitive changes? A literature search for articles was performed on three electronic databases: Pubmed, Web of Science, and WorldCat which gave n=744 articles. The cognitive tests showed a trend toward improved memory, learning, and exploratory behavior in Alzheimer’s disease from intermittent fasting. However, the effects on the levels of Aβ and tau pathology were inconsistent, which invites the possibility of a more prominent, underlying issue of Alzheimer's disease.

A dieta intermitente (DI) estimula mecanismos de defesa do organismo, tornando-o mais resistente a estímulos tóxicos. A DI parece atuar em vias associadas à resposta inflamatória, autofagia, sobrevivência celular e aumenta a resistência contra estresse oxidativo. No entanto, pouco se sabe sobre o papel dos receptores TLR4 e TLR2 nos efeitos da DI. Este trabalho avaliou a influência do TLR4 e TLR2 nos efeitos da DI sobre a memória e a sinalização associada aos fatores de transcrição NF-κB, NRF2 e FOXO em camundongos nocaute para TLR4 ou TLR2. Os resultados sugerem que o TLR4 e TLR2 participam da modulação pela DI dos níveis de estresse oxidativo, biomarcadores periféricos e do NF-κB, CREB, AP1, NRF2, além das proteínas moduladas por esses fatores de transcrição como o BDNF, HO1, enzimas antioxidantes, chaperonas e citocinas. Esses resultados permitem um maior entendimento dos processos fisiológicos que visam o desenvolvimento de novas intervenções farmacológicas para a promoção da longevidade, envelhecimento saudável e o tratamento de distúrbios neurodegenerativos. / Intermittent fasting (IF) stimulates the body\'s defense mechanisms, making it more resistant to toxic stimuli. IF seems to act by mechanisms associated with cell survival, autophagy, inflammation and enhancing oxidative stress resistance, thereby involving the modulation of transcription factors. However, little is known about the involvement of TLR4 and TLR2 on IF effects. The present work investigated the influence of TLR2 and TLR4 on IF effects on memory and on signaling mechanisms associated with the transcription factors NF-κB, NRF2 and FOXO in TLR2 KO or TLR4 KO mice. The results suggest that TLR4 and TLR2 participate in the effects of IF on oxidative stress levels, peripheral biomarkers, and on NF-κB, CREB, AP1 and NRF2, as well as proteins modulated by these transcription factors such as BDNF, HO1, antioxidant enzymes, chaperones and cytokines. These results allow a better understanding of physiological processes that aim at developing new pharmacological interventions to promote longevity, healthy aging, and the treatment of neurodegenerative disorders.

A crescente incidência de disfunções metabólicas, como resistência à insulina e diabetes mellitus tipo 2 (T2DM), está correlacionada com a elevação da ocorrência de obesidade e sobrepeso. Em busca da melhora da saúde e de um corpo ideal segundo os padrões estéticos propagados atualmente, um número cada vez maior de indivíduos adere às dietas da moda que prometem rápida redução do peso corporal, ao invés de adotar uma alimentação balanceada e a prática regular de exercícios físicos. Uma dieta bastante divulgada e até recomendada por profissionais da saúde é o jejum intermitente (JI), que consiste em alternar períodos de jejum de até 24 horas com períodos de ingestão alimentar. Diversos estudos experimentais têm relatado alterações metabólicas em consequência do JI, como modificações da glicemia e da tolerância à glicose, porém, os resultados encontrados na literatura são conflitantes e, além disso, o impacto do jejum intermitente, em longo prazo, sobre as ilhotas pancreáticas ainda não foi devidamente elucidado. Desta forma, o presente estudo teve como objetivo caracterizar os impactos de doze semanas de JI em ratas Wistar. Para tal, ratas Wistar com 30 dias de idade foram distribuídas aleatoriamente em dois grupos: controle, com livre acesso à ração balanceada; e jejum intermitente, submetido a 24 horas de jejum intercalado com 24 horas de livre acesso à ração balanceada. Foi observado que os animais submetidos ao JI, apresentaram menor ganho de peso corporal, redução do comprimento da tíbia e da distância naso-anal, e alteração da composição corporal, incluindo diminuição da massa muscular e aumento do tecido adiposo. Em média, o consumo de ração do grupo JI foi menor, porém, no dia que era disponibilizado alimento, os animais apresentaram hiperfagia o que resultou em grande aumento das dimensões do estômago. O jejum intermitente reduziu os valores plasmáticos do colesterol total, triglicérides, LDL, HDL e glicemia, e aumentou a concentração basal da insulina plasmática, bem como a secreção da insulina após o estímulo com glicose. Foi observada redução significativa da massa de ilhotas pancreáticas e aumento da porcentagem de células dispersas de ilhotas em apoptose. Ainda nas células dispersas de ilhotas pancreáticas, houve aumento do conteúdo de espécies reativas de oxigênio mitocondrial e total, e do peróxido de hidrogênio (H2O2), além de aumento da expressão do sistema antioxidante. Assim, nossos dados sugerem que esse protocolo estudado de 24 horas de jejum intercalados com 24 horas de alimentação à vontade não seja saudável em longo prazo. Mais estudos em longo prazo são necessários para investigar qual seria o melhor protocolo de jejum intermitente de forma a reduzir os efeitos colaterais e melhorar a saúde, para então o JI ser considerado uma boa alternativa para perda e manutenção do peso. / The increasing incidence of metabolic dysfunctions, such as insulin resistance and type 2 diabetes mellitus (T2DM), is correlated with increased occurrence of obesity and overweight. In pursuit of improved health and an ideal body according to today\'s aesthetic standards, an increasing number of individuals adhere to fad diets that promise a rapid reduction of body weight, instead of adopting a balanced diet and regular practice of physical exercises. A well-publicized diet and even recommended by health professionals is intermittent fasting (IF), which consists of alternating fasting periods of up to 24 hours with periods of food intake. Several experimental studies have reported metabolic changes as a consequence of IF, such as changes in glucose and glucose tolerance, but the results found in the literature are conflicting and, in addition, the impact of intermittent fasting in the long term on pancreatic islets has not yet been properly elucidated. Thus, the present study aimed to characterize the effects of twelve-week IF on Wistar rats. For this, 30-day-old Wistar rats were randomly assigned to two groups: control, with free access to balanced chow; and intermittent fasting, subjected to 24-hour fast intercalated with 24 hours of free access to the balanced chow. It was observed that the animals submitted to IF presented lower body weight gain, reduced tibia length and naso-anal distance, and altered body composition, including decreased muscle mass and increased adipose tissue. On average, the dietary intake of the IF group was lower, but on the day that food was available, the animals presented hyperphagia which resulted in a large increase in the stomach size. Intermittent fasting reduced plasma levels of total cholesterol, triglycerides, LDL, HDL, and glycaemia, and increased basal plasmatic insulin level, as well as insulin secretion after stimulation with glucose. We observed significant reduction in pancreatic islet mass and increase in percentage of islet-dispersed cells in apoptosis. Still in islet-dispersed cells, there was an increase in mitochondrial and total reactive oxygen species content, and of hydrogen peroxide (H2O2), in addition to an increase in expression of antioxidant system. Thus, our data suggest that this protocol of 24-hour fasting intercalated with 24-hour feed at will is not healthy in the long run. More long-term studies are needed to investigate the best intermittent fasting protocol in order to reduce side effects and improve health, so IF be considered a good alternative for weight loss and maintenance.

A dieta intermitente (DI) estimula mecanismos de defesa do organismo, tornando-o mais resistente a estímulos tóxicos. A DI parece atuar em vias associadas à resposta inflamatória, autofagia, sobrevivência celular e aumenta a resistência contra estresse oxidativo. No entanto, pouco se sabe sobre o papel dos receptores TLR4 e TLR2 nos efeitos da DI. Este trabalho avaliou a influência do TLR4 e TLR2 nos efeitos da DI sobre a memória e a sinalização associada aos fatores de transcrição NF-κB, NRF2 e FOXO em camundongos nocaute para TLR4 ou TLR2. Os resultados sugerem que o TLR4 e TLR2 participam da modulação pela DI dos níveis de estresse oxidativo, biomarcadores periféricos e do NF-κB, CREB, AP1, NRF2, além das proteínas moduladas por esses fatores de transcrição como o BDNF, HO1, enzimas antioxidantes, chaperonas e citocinas. Esses resultados permitem um maior entendimento dos processos fisiológicos que visam o desenvolvimento de novas intervenções farmacológicas para a promoção da longevidade, envelhecimento saudável e o tratamento de distúrbios neurodegenerativos. / Intermittent fasting (IF) stimulates the body\'s defense mechanisms, making it more resistant to toxic stimuli. IF seems to act by mechanisms associated with cell survival, autophagy, inflammation and enhancing oxidative stress resistance, thereby involving the modulation of transcription factors. However, little is known about the involvement of TLR4 and TLR2 on IF effects. The present work investigated the influence of TLR2 and TLR4 on IF effects on memory and on signaling mechanisms associated with the transcription factors NF-κB, NRF2 and FOXO in TLR2 KO or TLR4 KO mice. The results suggest that TLR4 and TLR2 participate in the effects of IF on oxidative stress levels, peripheral biomarkers, and on NF-κB, CREB, AP1 and NRF2, as well as proteins modulated by these transcription factors such as BDNF, HO1, antioxidant enzymes, chaperones and cytokines. These results allow a better understanding of physiological processes that aim at developing new pharmacological interventions to promote longevity, healthy aging, and the treatment of neurodegenerative disorders.

abstract: ABSTRACT Background. College students’ modifiable health behaviors, including unhealthful eating patterns, predispose them to risk for future cardiometabolic conditions. Purpose. This novel 8-week randomized control parallel-arm study compared the effects of a daily 18-hour Time-Restricted Feeding protocol vs. an 8-hour fast on diet quality in college students. Secondary outcomes were resting morning blood pressure, biomarkers of glucose regulation, biomarkers of lipid metabolism, and anthropometric measures. Methods. Eighteen healthy college students (age = 23 ± 4 years; BMI = 23.2 ± 2.3 kg/m2; MET = 58.8 ± 32.9 min/wk) completed this study. Participants were randomized to a daily 18-hour fasting protocol (Intervention; n = 8) or a daily 8-hour fasting protocol (Control; n = 10) for eight weeks. One ‘cheat’ day was permitted each week. Outcomes were measured at weeks 0 (baseline), 4, and 8. A non-parametric Mann Whitney U test was used to compare the week 4 change from baseline between groups. Statistical significance was set at p≤0.05. Results. Diet quality (p = 0.030) and body weight (p = 0.016) improved from baseline to week 4 for the INV group in comparison to the CON group. The data suggest these improvements may be related to reductions in snacking frequency and increased breakfast consumption. Fasting blood glucose and hip circumference tended to improve for the INV group in comparison to the CON group (p = 0.091 and p = 0.100). However, saturated fat intake tended to increase in the INV group in comparison to the CON group (p = 0.064). Finally, there were no treatment differences between groups (p>0.05) for the 4-week change in total calories, dietary vitamin C, added sugars, resting systolic blood pressure, resting diastolic blood pressure, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), low-density lipoprotein (LDL) cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, waist circumference, or MET. Conclusion. These data, although preliminary, suggest that the 18-hour fasting protocol was effective for improving diet quality and reducing weight in comparison to the 8-hour fasting protocol in healthy college students. Future intervention trials will need to confirm these findings and determine the long-term relevance of these improvements for health outcomes. / Dissertation/Thesis / Doctoral Dissertation Nutrition 2020