Introduktion: Ur ett globalt perspektiv är depression en stor sjukdomsbörda som berör omkring 280 miljoner människor. Tillgängliga behandlingsalternativ innefattar antidepressiva läkemedel och olika former av psykologiska behandlingar. Tidigare forskning indikerar att det finns ett samband mellan kost och psykisk ohälsa och en koppling mellan intag av ultraprocessad kost och depressiva symptom har påvisats. Det anses därmed relevant att undersöka effekten av en hälsosam kosthållning på depression och depressiva symptom. Syfte: Studiens syfte var att undersöka om kost har en positiv effekt vid behandling av depression eller depressiva symptom bland vuxna individer mellan 18 - 65 år. Metod: En strukturerad litteraturstudie som baserades på 20 randomiserade kontrollerade studier som hämtades från databaserna PubMed och Scopus och sedan analyserades med hjälp av en tematisk analys. Resultat: Sex teman identifierades efter att de inkluderade studierna hade analyserats; En oprocessad och näringsrik kostintervention är grundläggande; Kostfiber är en central komponent som gynnar tarmfloran; Omättade fettsyror kopplar till minskade depressiva symptom; Medelhavskosten är en effektiv kostintervention vid depression; Viktnedgång minskar inflammation och depressiva symptom samt Kost i kombination med en annan intervention är mer effektiv. Slutsats: Resultatet av denna litteraturstudie visar att olika kostinterventioner kan minska klinisk depression eller depressiva symptom inom olika riskgrupper. Det saknas dock tillräcklig och även enhetlig evidens för att kunna dra några säkra slutsatser kring kosten som en alternativ behandlingsmetod. / Introduction: Depression is a major disease burden from a global perspective that is affecting approximately 280 million people. Treatment options available today include various forms of psychological treatments and antidepressants. Previous research indicates that there is a connection between diet and mental illness and a link between the intake of ultra-processed food and depressive symptoms has been demonstrated. It is therefore considered relevant to investigate the effect of a healthy diet on depression and depressive symptoms. Aim: The aim of this study was to investigate whether diet has a positive effect in the treatment of depression or depressive symptoms among adult individuals between 18 - 65 years of age. Methods: A structured literature review was chosen as study design and 20 randomized controlled trial studies were retrieved from the databases PubMed and Scopus and then analyzed using a thematic analysis. Results: After the studies selected were analyzed six themes were identified; An unprocessed and nutritious dietary intervention is fundamental; Dietary fiber is a central component that benefits the intestinal flora; Unsaturated fatty acids are linked to reduced depressive symptoms; The Mediterranean diet is an effective dietary intervention for depression; Weight loss reduces inflammation and depressive symptoms and Diet combined with another intervention is more effective. Conclusion: The results of this literature study show that different dietary interventions can reduce clinical depression or depressive symptoms within different risk groups. However, there is a lack of sufficient and even uniform evidence to draw any certain conclusions about diet as an alternative treatment.

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Accumulation of cervical and chin subcutaneous adipose tissues (SAT) represent known phenotypes of obesity. We aimed to evaluate the sensitivity of these fat storages to long-term weight-loss directed lifestyle-intervention and to assess their relations to bodily-adiposity, insulin-resistance, and cardiometabolic risk; We randomly assigned 278 participants with abdominal-obesity/dyslipidemia to low-fat or Mediterranean/low-carbohydrate diets +/− physical-activity. All participants underwent an 18 month whole-body magnetic resonance imaging follow-up, from which we assessed cervical and chin SAT-areas; Participants (age = 48 years; 90% men; body-mass-index = 30.9 kg/m2) had an 18-month adherence-rate of 86%. Cervical-SAT and chin-SAT decreased after 6-months (−13.1% and −5.3%, respectively, p < 0.001). After 18-months only cervical-SAT remained decreased compared to baseline (−5%, p < 0.001). Cervical and chin-SAT 18-month changes were associated with changes in weight (r = 0.70, r = 0.66 respectively; <0.001 for both) and visceral-adipose-tissue (VAT; r = 0.35, r = 0.42 respectively; <0.001 for both). After adjustment to VAT, waist-circumference, or weight-changes, chin-SAT 18-month reduction was associated with favorable changes in fasting-glucose (β = 0.10; p = 0.05), HbA1c (β = 0.12; p = 0.03), and homeostasis-model-assessment-of-insulin-resistance (β = 0.12; p = 0.03). Cervical-SAT 18-month reduction was associated with decreased triglycerides (β = 0.16; p = 0.02) and leptin (β = 0.19; p = 0.01) independent of VAT; Cervical and chin-SATs are dynamic fat depots that correspond with weight-loss and are associated with changes in cardiometabolic profile. In long-term, chin-SAT displays a larger rebound compared with cervical-SAT. Chin-SAT accumulation is associated with in insulin-resistance, independent of central obesity. (ClinicalTrials identifier NCT01530724)

Introdução: Mudanças na alimentação e atividade física das populações elevaram a incidência de doenças crônicas não-transmissíveis associadas à adiposidade corporal. Este quadro contribui para mortalidade cardiovascular, motivando iniciativas em saúde pública visando à prevenção. Há evidências de que populações que consomem a dieta mediterrânea apresentam menor mortalidade por todas as causas, inclusive cardiovasculares. Os benefícios desta dieta, rica em fibras, gorduras insaturadas e polifenóis, parecem decorrer da atenuação da inflamação, envolvida na gênese de doenças cardiometabólicas. Objetivo: Este estudo investigou os efeitos da modificação de uma refeição diária, o desjejum, de forma a incluir alimentos mediterrâneos, sobre o metabolismo lipídico, glicídico, inflamação subclínica e expressão de genes inflamatórios. Métodos: Foi um ensaio clínico cruzado com duração total de 10 semanas, incluindo 80 adultos com excesso de peso, não-diabéticos. Os participantes passaram por 2 intervenções de 4 semanas no desjejum, com wash-out de 2 semanas entre elas. Os desjejuns, brasileiro e modificado, foram isocalóricos, diferindo quanto ao conteúdo de fibras e tipos de ácidos graxos. Antes e após cada intervenção foi realizado teste de sobrecarga de gorduras (FTT) com refeição rica em gorduras (saturadas e insaturadas MUFA e PUFA, dependendo da intervenção) e coletas sanguíneas seriadas até 240 minutos para determinação de glicose, insulina, lípides e marcadores inflamatórios. Foram também analisadas as expressões de genes inflamatórios, antes e após cada intervenção. Para comparar as respostas às intervenções foram usados teste t de Student ou os correspondentes não-paramétricos e ANOVA para medidas repetidas. Para as expressões dos genes foi utilizado o método delta ct e a expressão relativa calculada tendo como base valores de jejum e pré-intervenção. Valor de p <0,05 foi considerado significante. Resultados: No Artigo 1 (Modification in a single meal is sufficient to provoke benefits in inflammatory responses of individuals at low-tomoderate cardiometabolic risk), o FTT com desjejum brasileiro comparada ao modificado provocou maiores concentrações de IL-6 e IL-8, e esta resposta se acentuou após intervenção. As concentrações de selectina E, TNF-, IFN-, IL-10 e IL-17 se elevaram apenas após intervenção brasileira. No Artigo 2 (Inflammatory and metabolic response to dietary intervention differs among individuals at distinct cardiometabolic risk levels), a intervenção com desjejum modificado reduziu (p<0.05) a circunferência da cintura e pressão arterial e aumentou as concentrações de HDL. Indivíduos com síndrome metabólica melhoraram fatores clássicos (pressão arterial e glicemia, além de apolipoproteína B) após desjejum modificado, enquanto aqueles sem a síndrome melhoraram marcadores inflamatórios. O Artigo 3 (Comparison of inflammatory genes expression and their circulating products after short-term fatty acids interventions in humans) mostrou que o FTT com desjejum rico em gordura saturada induziu maior expressão pós-prandial de IL-1 quando comparado ao rico em insaturadas, antes e após as intervenções. Houve tendência à maior expressão de IFN- e IL-6 após intervenção com desjejum brasileiro. Na metanálise do Artigo 4 (Impact of the content of fatty acids of oral fat tolerance tests on postprandial triglyceridemia: systematic review and meta-analysis) foram incluídos 18 estudos buscando comparar as respostas dos triglicérides a ácidos graxos saturados e insaturados. Verificou-se que após 8 horas de refeição rica em MUFA há menor trigliceridemia. As menores concentrações observadas após ingestão de PUFA em relação à de saturados não atingiu significância. Conclusões: Pequenas modificações na dieta podem, em período relativamente curto, promover benefícios ao perfil de risco cardiometabólico. Tais benefícios foram evidentes em parâmetros clínicos habituais e reforçados pelos efeitos na expressão de genes inflamatórios e em marcadores circulantes. Vislumbra-se potencial de aceitação da introdução de componentes da dieta mediterrânea em população não-mediterrânea como a brasileira, o que poderia melhorar o perfil de risco cardiometabólico no longo prazo. / Introduction: Changes in dietary pattern and physical activity of populations have elevated the incidence of chronic non-communicable diseases associated with increased adiposity. Evidence has shown that populations consuming Mediterranean diets have lower mortality from all causes, including cardiovascular diseases. The benefits of this diet rich in fiber and unsaturated fats, derived in part on the effects of these nutrients on inflammatory condition that triggers cardiometabolic diseases. Objective: This study investigated the effects of changing a meal of Brazilian menu, the breakfast, in order to approximate it to the Mediterranean pattern on lipid and glucose metabolism, subclinical inflammation and also on the expression of inflammatory genes. Methods: This study was a crossover trial lasting a total of 10 weeks, including 80 overweight adults, nondiabetic without drug treatment for dyslipidemia. Participants who met the inclusion criteria underwent two 4-week interventions in breakfast, with wash-out of two weeks between them. The breakfasts (Brazilian and modified) were isocaloric, differing according to fiber and types of fatty acids contents. Before and after each intervention, fat tolerance tests with meals rich in fat (saturated and unsaturated depending on the intervention) were perfomed, with blood sample collections for glucose, insulin, lipids and inflammatory markers up to 240 minutes. Also, expression of inflammatory genes before and after each intervention was analyzed. To compare the acute and sub-acute responses to interventions were used Student t test or the corresponding nonparametric test and ANOVA for repeated measures. For expression of the genes, delta CT method was used and the relative expression calculated based on fasting and pre-intervention values. P value <0.05 was considered significant. Results: In Article 1 (Modification in a single meal is sufficient to provoke benefits in inflammatory responses of Individuals at low-to-moderate cardiometabolic risk), we observed higher IL-6 and IL- 8 concentrations after ingestion of the Brazilian FTT compared with the modified one, whose elevations were even more pronounced after the intervention period. Higher concentrations of E-selectin, TNF-, IFN-, IL-10 and IL-17 were found at fasting and in postprandial state only after the Brazilian intervention. In Article 2 (Inflammatory and metabolic response to dietary intervention Differs Among Individuals at distinct cardiometabolic risk levels), the intervention with the modified breakfast decreased waist circumference and blood pressure and increased the concentrations HDL (p <0.05). Participants with metabolic syndrome showed improvements in traditional risk factors (blood pressure and plasma glucose and apolipoprotein B) whit the modified breakfast, while those without the syndrome improved inflammatory markers. Article 3 (Comparison of inflammatory gene expression and their circulating products after short-term interventions fatty acids in humans) showed that the Brazilian FTT induced higher expression of IL-1 compared to the modified one, before and after the interventions. A tendency for higher postprandial expression of IFN- and increased IL-6 expression after intervention with Brazilian breakfast were also detected. In the meta-analysis of Article 4 (Impact of the content of fatty acids in oral fat tolerance tests on postprandial triglyceridemia: systematic review and metaanalysis) a total of 18 studies were included. When comparing the triglycerides responses to saturated and unsaturated fatty acids, lower areas under the curve with the meals rich in MUFA were observed. Postprandial triglyceridemia after PUFA was lower, but not significantly different from meals rich in saturated fat. Conclusions: Small changes in diet are able to induce benefits in cardiometabolic risk profile in a relatively short period. Such benefits are seen in routine clinical parameters, which are compatible with the favorable effects on the expression of inflammatory genes and circulating biomarkers. There is a potential acceptance of introducing components of the Mediterranean diet in non-Mediterranean populations like Brazil, which could improve the cardiometabolic risk profile in the long term.

<p>The development of the metabolic syndrome (MetS) and cardiovascular diseases have been suggested to be influenced more by the quality than the amount of dietary fat. The FA composition of serum lipids may be used as biomarkers of dietary fat quality. FAs can, however, also be endogenously synthesized by lipogenic enzymes such as elongases and desaturases. Three desaturases are important in humans: Stearoyl-CoA-desaturase (SCD), ∆6-desaturase (D6D) and ∆5-desaturase (D5D) and surrogate measures of desaturase activities can be estimated as product-to-precursor FA ratios.</p><p>In this thesis, we demonstrated that high SCD, D6D and low D5D estimated activities predicted MetS 20 years later, as well as cardiovascular and total mortality during a maximum of 33.7 years. The relation between D5D and MetS was independent of lifestyle and BMI, while the relation between SCD, D6D and MetS was confounded by BMI. Serum proportions of palmitic (16:0), palmitoleic (16:1) and dihomo-γ-linoleic acids were higher and the serum proportion of linoleic acid (LA) lower at baseline in those individuals who developed MetS. Further, LA was inversely related to mortality, while palmitic, palmitoleic and dihomo-γ-linoleic acids were directly associated with mortality. We also demonstrated that a diet rich in saturated fat “induced” a similar serum FA pattern (including estimated desaturase activities) that was associated with MetS, cardiovascular disease and mortality. We also propose that the SCD ratio [16:1/16:0] might be a novel and useful marker of dietary saturated fat, at least in Western high-fat diets. Finally, genetic variations in the human SCD1 gene were linked to obesity and insulin sensitivity, results that agree with data in SCD1 deficient mice.</p><p>This thesis suggests that dietary fat quality and endogenous desaturation may play a role in the development of metabolic and cardiovascular diseases and the results support current dietary guidelines.</p>

The development of the metabolic syndrome (MetS) and cardiovascular diseases have been suggested to be influenced more by the quality than the amount of dietary fat. The FA composition of serum lipids may be used as biomarkers of dietary fat quality. FAs can, however, also be endogenously synthesized by lipogenic enzymes such as elongases and desaturases. Three desaturases are important in humans: Stearoyl-CoA-desaturase (SCD), ∆6-desaturase (D6D) and ∆5-desaturase (D5D) and surrogate measures of desaturase activities can be estimated as product-to-precursor FA ratios. In this thesis, we demonstrated that high SCD, D6D and low D5D estimated activities predicted MetS 20 years later, as well as cardiovascular and total mortality during a maximum of 33.7 years. The relation between D5D and MetS was independent of lifestyle and BMI, while the relation between SCD, D6D and MetS was confounded by BMI. Serum proportions of palmitic (16:0), palmitoleic (16:1) and dihomo-γ-linoleic acids were higher and the serum proportion of linoleic acid (LA) lower at baseline in those individuals who developed MetS. Further, LA was inversely related to mortality, while palmitic, palmitoleic and dihomo-γ-linoleic acids were directly associated with mortality. We also demonstrated that a diet rich in saturated fat “induced” a similar serum FA pattern (including estimated desaturase activities) that was associated with MetS, cardiovascular disease and mortality. We also propose that the SCD ratio [16:1/16:0] might be a novel and useful marker of dietary saturated fat, at least in Western high-fat diets. Finally, genetic variations in the human SCD1 gene were linked to obesity and insulin sensitivity, results that agree with data in SCD1 deficient mice. This thesis suggests that dietary fat quality and endogenous desaturation may play a role in the development of metabolic and cardiovascular diseases and the results support current dietary guidelines.

Dietary fat quality influences the risk of type 2 diabetes and cardiovascular disease. A low-grade inflammation is suggested to contribute to the disease development, often accompanied by obesity. Whereas n-3 polyunsaturated fatty acids (PUFA) have been considered anti-inflammatory, n-6 PUFA have been proposed to act pro-inflammatory. Saturated fatty acids (SFA) act pro-inflammatory in vitro. This thesis aimed to investigate effects of different fatty acids on low-grade inflammation in observational and interventional studies. In Paper I and II, fatty acid composition in serum cholesterol esters was used as objective marker of dietary fat quality and related to serum C-reactive protein (CRP) and other circulating inflammatory markers in two population-based cohorts, conducted in middle-aged men and elderly men and women, respectively. In Paper III and IV, the impact of diets differing in fat quality on inflammation and oxidative stress was investigated in randomised controlled studies, in subjects with metabolic syndrome and abdominal obesity. In Paper I and II, a low proportion of linoleic acid (18:2 n-6) in serum was associated with higher CRP concentrations, indicating that a low intake of vegetable fats may be related to low-grade inflammation. High CRP concentrations were also associated with high proportions of palmitoleic (16:1) and oleic (18:1) acids and high stearoyl coenzymeA desaturase index, possibly reflecting altered fat metabolism and/or high SFA intake in this population. When comparing two high-fat diets rich in either saturated or monounsaturated fat, and two low-fat diets with or without long-chain n-3 PUFA supplementation during 12 weeks (Paper III), no differences in inflammation or oxidative stress markers were observed. Moreover, a 10-week intervention (Paper IV) with high linoleic acid intake showed no adverse effects on inflammation or oxidative stress. Instead, interleukin-1 receptor antagonist and tumor necrosis factor receptor-2 decreased after linoleic acid intake compared with a diet high in SFA. The results in this thesis indicate that dietary n-6 PUFA found in vegetable fats is associated with lower inflammation marker levels, and to some extent reduces systemic inflammation when compared with SFA. Supplementation of n-3 PUFA did not exert any systemic anti-inflammatory effects, maybe due to a relatively low dose.