Reduction of the Metabolic Syndrome in Navarra-Spain (RESMENA-S)

Reduction of the Metabolic Syndrome in Navarra-Spain (RESMENA-S) Through an Innovative Multidisciplinary Strategy Based on the Crononutrition and Dietary Training Concepts, in Addition to Both Dietary and Psychological Control

The purpose of this study is to determine whether a dietary pattern based on crononutrition and dietary training, together with dietary and psychological control, can reduce the body weight, improve the oxidative and inflammatory state in subjects with diagnosed metabolic syndrome features and can reduce the prevalence of the Metabolic syndrome in the population.

The dietary pattern that characterizes the present nutritional intervention study is based on personalized diet, by elaborating tailoring-diets for each subject regarding his energetic needs and assuring a high adherence to the Mediterranean Diet. Moreover, the diet to be performed will be a hyperproteic diet to guarantee a satiety effect and a lower recovery of the lost weight, in accordance with the results derived from the main European study about nutrition (DIOGENES). The glycemic index/load will be also controlled in the study diet. The increase of the antioxidant capacity of the diet will be increased by the intake of fruits, walnuts and virgin olive oil among other antioxidant containing foods. The present initiative, based on the traditional diet, aims to integrate the main results obtained from diverse observational epidemiological studies and interventional studies in the dietary pattern of the present study. At the same time, the study will apply the concept of crononutrition by selecting and distributing the foods thorough the day according the physiological needs of each individual. In addition to the quantitative and qualitative composition of the diet, the study will take into account other important factors such as the behavior habits regarding the food, the frequency of consumption, the size of the eating portions, the distribution of the portions along the day, the feeling of fullness, the eating speed and so on. The aforementioned factors have recently been shown to be related to the gain of weight. Other non dietary factors, such as smoking habits, sedentary life, socio-economic level, will be also controlled in the present study. Moreover, the project will integrate the dietary support together with psychological support due to the fact that the state of mind has been shown to be associated with the MS in some scientific publications.

Metabolic syndrome, Oxidative stress, Proinflammatory state, Insulin resistance, Hypertension, Dyslipidemia, Mediterranean diet, Glycemic index, Hypocaloric diet, Hyperproteic diet, Macronutrient distribution, Antioxidant capacity of the diet, Crononutrition, Dietary and psychological support, Waist circumference

Dietary pattern: Personalized diet Caloric restriction (-30% Total energy intake) High adherence to the Mediterranean Diet Macronutrient distribution (30% Protein, 40% Carbohydrates and 30% Fat) Low glycemic index/load Increased antioxidant capacity of the diet

Dietary pattern: Personalized diet Caloric diet (-30% Total energy intake) Macronutrients distribution according to the American Heart Association (AHA) guidelines

After the recruitment and selection of the study participants, the study will consists of a 2-month nutritional intervention (Crononutrition versus AHA) followed by second 6-month period ("autonomy phase") in which the subjects of the study will continue with their ruled dietary patterns, but without any dietary or psychological support.

After the recruitment and selection of the study participants, the study will consists of a 2-month nutritional intervention (Crononutrition versus AHA) followed by second 6-month period ("autonomy phase") in which the subjects of the study will continue with their ruled dietary patterns, but without any dietary or psychological support.

Through this specific nutritional intervention program we will try to reduce the metabolic syndrome features such as waist circumference, body weight and adiposity. To evaluate the body composition, bioimpedance, DEXA and anthropometry methodology will be used at the beginning and after two months of intervention.

To evaluate lipid improvements the following measurements will be taking into account: Free fatty acids Total cholesterol HDL-cholesterol LDL-cholesterol

To evaluate glucose improvements the following measurements will be taking into account: Glucose Insulin HOMA

As secondary outcome some inflammatory markers will be analyzed: CRP IL-6 TNF-alpha IL-18 PAI-1 Homocystein

As secondary outcome some oxidative stress markers will be analyzed: MDA LDL-OX Total antioxidant capacity (TAC)

Beck Depression Inventory Stai Trait Anxiety Inventory Mood thermometer visual analogue scale Anxiety thermometer visual analogue scale NEO personality inventory-revised test

Measurements in fatty liver biomarkers: Serum transaminases (AST & ALT (U/L)), GGT (U/L) and CK18 (U/L) concentrations will be measured in a fasting state at the beginning, at 2 months and at the end of the intervention. - A specificif Fatty Liver Index was calculated at the begining, at 2 months and at the end of the intervention.

Inclusion Criteria: 35-70 years old Both sexes: Male and Female Metabolic Syndrome according to the IDF(2005)criteria: Waist circumference cutoffs (male ≥94 cm or female ≥80 cm) plus any two of the following four factors: Fasting glucose ≥5.55 mmol/L or use of antidiabetic medication Systolic BP ≥130 mm Hg, diastolic BP ≥85 mm Hg, or use of antihypertensive medication Fasting triglycerides ≥1.7 mm/L; and HDL-C <1.0 mm/L in men and <1.3 mm/L in women or specific treatment for this lipid abnormality Exclusion Criteria: Recent follow-up of diets designed for weight loss Unstable weight in the past 3 months Alcoholic and drug dependence Hormonal treatment No stable pharmacological treatment Eating-disordered behaviors Severe physical or mental disability Pregnancy Terminal disease Institutionalization

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Puchau B, Zulet MA, de Echavarri AG, Hermsdorff HH, Martinez JA. Dietary total antioxidant capacity is negatively associated with some metabolic syndrome features in healthy young adults. Nutrition. 2010 May;26(5):534-41. doi: 10.1016/j.nut.2009.06.017. Epub 2009 Sep 26.

Perez-Matute P, Zulet MA, Martinez JA. Reactive species and diabetes: counteracting oxidative stress to improve health. Curr Opin Pharmacol. 2009 Dec;9(6):771-9. doi: 10.1016/j.coph.2009.08.005. Epub 2009 Sep 18.

Toledo E, de A Carmona-Torre F, Alonso A, Puchau B, Zulet MA, Martinez JA, Martinez-Gonzalez MA. Hypothesis-oriented food patterns and incidence of hypertension: 6-year follow-up of the SUN (Seguimiento Universidad de Navarra) prospective cohort. Public Health Nutr. 2010 Mar;13(3):338-49. doi: 10.1017/S1368980009991066. Epub 2009 Aug 6.

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Puchau B, Zulet MA, Gonzalez de Echavarri A, Navarro-Blasco I, Martinez JA. Selenium intake reduces serum C3, an early marker of metabolic syndrome manifestations, in healthy young adults. Eur J Clin Nutr. 2009 Jul;63(7):858-64. doi: 10.1038/ejcn.2008.48. Epub 2008 Nov 5.

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Cantero I, Abete I, Del Bas JM, Caimari A, Arola L, Zulet MA, Martinez JA. Changes in lysophospholipids and liver status after weight loss: the RESMENA study. Nutr Metab (Lond). 2018 Jul 17;15:51. doi: 10.1186/s12986-018-0288-5. eCollection 2018.

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Bondia-Pons I, Martinez JA, de la Iglesia R, Lopez-Legarrea P, Poutanen K, Hanhineva K, Zulet Mde L. Effects of short- and long-term Mediterranean-based dietary treatment on plasma LC-QTOF/MS metabolic profiling of subjects with metabolic syndrome features: The Metabolic Syndrome Reduction in Navarra (RESMENA) randomized controlled trial. Mol Nutr Food Res. 2015 Apr;59(4):711-28. doi: 10.1002/mnfr.201400309. Epub 2015 Feb 5.

Perez-Cornago A, de la Iglesia R, Lopez-Legarrea P, Abete I, Navas-Carretero S, Lacunza CI, Lahortiga F, Martinez-Gonzalez MA, Martinez JA, Zulet MA. A decline in inflammation is associated with less depressive symptoms after a dietary intervention in metabolic syndrome patients: a longitudinal study. Nutr J. 2014 Apr 24;13:36. doi: 10.1186/1475-2891-13-36.

Lopez-Legarrea P, de la Iglesia R, Crujeiras AB, Pardo M, Casanueva FF, Zulet MA, Martinez JA. Higher baseline irisin concentrations are associated with greater reductions in glycemia and insulinemia after weight loss in obese subjects. Nutr Diabetes. 2014 Feb 24;4(2):e110. doi: 10.1038/nutd.2014.7.

de la Iglesia R, Mansego ML, Sanchez-Muniz FJ, Zulet MA, Martinez JA. Arylesterase activity is associated with antioxidant intake and paraoxonase-1 (PON1) gene methylation in metabolic syndrome patients following an energy restricted diet. EXCLI J. 2014 Apr 9;13:416-26. eCollection 2014.

Perez-Cornago A, Lopez-Legarrea P, de la Iglesia R, Lahortiga F, Martinez JA, Zulet MA. Longitudinal relationship of diet and oxidative stress with depressive symptoms in patients with metabolic syndrome after following a weight loss treatment: the RESMENA project. Clin Nutr. 2014 Dec;33(6):1061-7. doi: 10.1016/j.clnu.2013.11.011. Epub 2013 Nov 22.

Lopez-Legarrea P, Mansego ML, Zulet MA, Martinez JA. SERPINE1, PAI-1 protein coding gene, methylation levels and epigenetic relationships with adiposity changes in obese subjects with metabolic syndrome features under dietary restriction. J Clin Biochem Nutr. 2013 Nov;53(3):139-44. doi: 10.3164/jcbn.13-54. Epub 2013 Oct 31.

Lopez-Legarrea P, de la Iglesia R, Abete I, Bondia-Pons I, Navas-Carretero S, Forga L, Martinez JA, Zulet MA. Short-term role of the dietary total antioxidant capacity in two hypocaloric regimes on obese with metabolic syndrome symptoms: the RESMENA randomized controlled trial. Nutr Metab (Lond). 2013 Feb 13;10(1):22. doi: 10.1186/1743-7075-10-22.

Zulet MA, Bondia-Pons I, Abete I, de la Iglesia R, Lopez-Legarrea P, Forga L, Navas-Carretero S, Martinez JA. The reduction of the metabolyc syndrome in Navarra-Spain (RESMENA-S) study: a multidisciplinary strategy based on chrononutrition and nutritional education, together with dietetic and psychological control. Nutr Hosp. 2011 Jan-Feb;26(1):16-26.