Vitamins and minerals with antioxidant properties and cardiometabolic risk: controversies and perspectives

No processo celular de obtenção de energia, são gerados compostos chamados espécies reativas de oxigênio (ERO) que, em excesso, podem causar danos celulares. Estresse oxidativo resulta do desequilíbrio no estado de óxido-redução a favor da oxidação. Dos mecanismos de defesa antioxidante, participam enzimas endógenas e algumas vitaminas e minerais. A vitamina E encontra-se no plasma e na partícula de LDL, protegendo lipídeos da oxidação. Estudos observacionais relataram associação inversa entre ingestão de vitamina E e risco cardiometabólico (RCM). Entretanto, ensaios clínicos não comprovaram a eficácia de sua suplementação nos desfechos cardiometabólicos. A vitamina C participa do sistema de regeneração da vitamina E, mantendo o potencial antioxidante plasmático. Dados sobre os benefícios de sua suplementação na redução do risco cardiometabólico são inconclusivos. A atividade antioxidante dos carotenoides é responsável, em parte, por seu papel protetor contra doenças cardiovasculares e cânceres. A suplementação desse nutriente também não trouxe resultados consistentes no que se refere à redução do RCM. A participação do zinco e do selênio na defesa antioxidante vem sendo estudada mais recentemente, mas a sua suplementação em indivíduos com níveis séricos normais e ingestão adequada na dieta desses minerais não parece ser necessária. De um modo geral, há muita controvérsia sobre o papel desses micronutrientes no RCM. Estudos epidemiológicos sugerem que o consumo de substâncias antioxidantes provenientes da dieta ou dietas ricas em frutas e hortaliças diminui o RCM. Mais estudos são necessários antes de se recomendar o uso de antioxidantes isolados na forma de suplementos para tal finalidade.Oxygen reactive species (ROS) are generated during cellular processes. In excess, they may cause damages to the cell. Oxidative stress is an imbalance in the redox state that favors oxidation. Endogenous enzymes and some vitamins and minerals participate in the plasma antioxidant defense. Vitamin E is found in the plasma and in the LDL particle, avoiding lipid peroxidation. Observational studies reported an inverse association between vitamin E consumption and cardiometabolic (CM) risk. However, clinical trials were not able to prove the efficacy of its supplementation on CM endpoints. Vitamin C participates in the vitamin E regeneration system, keeping the plasma's antioxidant potential. Data about beneficial effects of its supplementation in CM risk reduction are inconclusive. The antioxidant activity of carotenoids is partially responsible for its protective role against cardiovascular diseases and cancer. Supplementation of this nutrient did not provide consistent findings in terms of CM risk reduction. Recently, zinc and selenium's participation in the antioxidant defense has been studied, yet its supplementation in individuals with normal levels and adequate ingestion of these nutrients does not seem necessary. In summary, the role of these micronutrients for CM risk is still very controversial. Epidemiological studies suggest that diets rich in antioxidants, or simply in fruit and vegetables intake, can reduce CM risk. Further studies are needed before recommending antioxidant supplements for this purpose

Benefits on quality of life concomitant to metabolic improvement in intervention program for prevention of diabetes mellitus

To evaluate whether an interdisciplinary intervention program on lifestyle results in better quality of life (QoL) and lower frequencies of depression and binge eating disorder (BED) in individuals at risk for type 2 diabetes mellitus. A total of 177 individuals (32.2% men, age 55.4 +/- A 12.5 years) at risk for diabetes were allocated to a 9-month traditional (TI) or intensive interdisciplinary intervention (II) on dietary habits and physical activity including psychoeducative groups. They were submitted to questionnaires and clinical and laboratory examinations. Predictors of non-adherence were analyzed by logistic regression. Only individuals submitted to II had blood pressure and plasma glucose levels reduced. Frequencies of depression reduced in both interventions but of BED only in II (28.0-4.0%, P < 0.001). Increments in the scores of SF-36 domains (physical functioning: 11.1 +/- A 14.0 vs. 5.3 +/- A 13.0, role-emotional: 20.4 +/- A 40.2 vs. 6.2 +/- A 43.8, P = 0.05) were greater in the II than in TI, respectively. Changes in SF-36 correlated with decreases in anthropometry, blood pressure and glucose levels, depression and BED scores. Male gender was independently associated with non-adherence to the II. In addition to metabolic benefits, an interdisciplinary approach may induce desirable extrametabolic effects, favoring the control of psychiatric disorders and improving the QoL of individuals at risk for diabetes

Cardiometabolic risk reduction through lifestyle intervention programs in the Brazilian public health system

Public health strategies to reduce cardiovascular morbidity and mortality should focus on global cardiometabolic risk reduction. The efficacy of lifestyle changes to prevent type 2 diabetes have been demonstrated, but low-cost interventions to reduce cardiometabolic risk in Latin-America have been rarely reported. Our group developed 2 programs to promote health of high-risk individuals attending a primary care center in Brazil. This study compared the effects of two 9-month lifestyle interventions, one based on medical consultations (traditional) and another with 13 multi-professional group sessions in addition to the medical consultations (intensive) on cardiometabolic parameters. Adults were eligible if they had pre-diabetes (according to the American Diabetes Association) and/or metabolic syndrome (International Diabetes Federation criteria for Latin-America). Data were expressed as means and standard deviations or percentages and compared between groups or testing visits. A p-value < 0.05 was considered significant. Results: 180 individuals agreed to participate (35.0% men, mean age 54.7 ± 12.3 years, 86.1% overweight or obese). 83 were allocated to the traditional and 97 to the intensive program. Both interventions reduced body mass index, waist circumference and tumor necrosis factor-α. Only intensive program reduced 2-hour plasma glucose and blood pressure and increased adiponectin values, but HDL-cholesterol increased only in the traditional. Also, responses to programs were better in intensive compared to traditional program in terms of blood pressure and adiponectin improvements. No new case of diabetes in intensive but 3 cases and one myocardial infarction in traditional program were detected. Both programs induced metabolic improvement in the short-term, but if better results in the intensive are due to higher awareness about risk and self-motivation deserves further investigation. In conclusion, these low-cost interventions are able to minimize cardiometabolic risk factors involved in the progression to type 2 diabetes and/or cardiovascular disease.FAPESP - Fundação de Apoio à Pesquisa do Estado de São PauloFAPESP Fundação de Apoio à Pesquisa do Estado de São Paul

Associations of the TNF-alpha-308 G/A, IL6-174 G/C and AdipoQ 45 T/G polymorphisms with inflammatory and metabolic responses to lifestyle intervention in Brazilians at high cardiometabolic risk

Background: Cytokines secreted by the adipose tissue influence inflammation and insulin sensitivity, and lead to metabolic disturbances. How certain single-nucleotide polymorphisms (SNPs) interfere on lifestyle interventions is unclear. We assessed associations of selected SNPs with changes induced by a lifestyle intervention. Methods: This 9-month intervention on diet and physical activity included 180 Brazilians at high cardiometabolic risk, genotyped for the TNF-alpha -308 G/A, IL-6 -174 G/C and AdipoQ 45 T/G SNPs. Changes in metabolic and inflammatory variables were analyzed according to these SNPs. Individuals with at least one variant allele were grouped and compared with those with the reference genotype. Results: In the entire sample (66.7% women; mean age 56.5 +/- 11.6 years), intervention resulted in lower energy intake, higher physical activity, and improvement in anthropometry, plasma glucose, HOMA-IR, lipid profile and inflammatory markers, except for IL-6 concentrations. After intervention, only variant allele carriers of the TNF-alpha -308 G/A decreased plasma glucose, after adjusting for age and gender (OR 2.96, p = 0.025). Regarding the IL-6 -174 G/C SNP, carriers of the variant allele had a better response of lipid profile and adiponectin concentration, but only the reference genotype group decreased plasma glucose. In contrast to individuals with the reference genotype, carriers of variant allele of AdipoQ 45 T/G SNP did not change plasma glucose, apolipoprotein B, HDL-c and adiponectin concentrations in response to intervention. Conclusion: The TNF alpha -308 G/A SNP may predispose a better response of glucose metabolism to lifestyle intervention. The IL-6 -174 G/C SNP may confer a beneficial effect on lipid but not on glucose metabolism. Our findings reinforce unfavorable effects of the AdipoQ 45 T/G SNP in lipid profile and glucose metabolism after intervention in Brazilians at cardiometabolic risk. Further studies are needed to direct lifestyle intervention to subsets of individuals at cardiometabolic risk.State of Sao PauloState of Sao Paul

Associations of the TNF-alpha -308 G/A, IL6 -174 G/C and AdipoQ 45 T/G polymorphisms with inflammatory and metabolic responses to lifestyle intervention in Brazilians at high cardiometabolic risk

Abstract\ud \ud \ud \ud Background\ud \ud Cytokines secreted by the adipose tissue influence inflammation and insulin sensitivity, and lead to metabolic disturbances. How certain single-nucleotide polymorphisms (SNPs) interfere on lifestyle interventions is unclear. We assessed associations of selected SNPs with changes induced by a lifestyle intervention.\ud \ud \ud \ud Methods\ud \ud This 9-month intervention on diet and physical activity included 180 Brazilians at high cardiometabolic risk, genotyped for the TNF-α -308 G/A, IL-6 -174 G/C and AdipoQ 45 T/G SNPs. Changes in metabolic and inflammatory variables were analyzed according to these SNPs. Individuals with at least one variant allele were grouped and compared with those with the reference genotype.\ud \ud \ud \ud Results\ud \ud In the entire sample (66.7% women; mean age 56.5 ± 11.6 years), intervention resulted in lower energy intake, higher physical activity, and improvement in anthropometry, plasma glucose, HOMA-IR, lipid profile and inflammatory markers, except for IL-6 concentrations. After intervention, only variant allele carriers of the TNF-α -308 G/A decreased plasma glucose, after adjusting for age and gender (OR 2.96, p = 0.025). Regarding the IL6 -174 G/C SNP, carriers of the variant allele had a better response of lipid profile and adiponectin concentration, but only the reference genotype group decreased plasma glucose. In contrast to individuals with the reference genotype, carriers of variant allele of AdipoQ 45 T/G SNP did not change plasma glucose, apolipoprotein B, HDL-c and adiponectin concentrations in response to intervention.\ud \ud \ud \ud Conclusion\ud \ud The TNFα -308 G/A SNP may predispose a better response of glucose metabolism to lifestyle intervention. The IL-6 -174 G/C SNP may confer a beneficial effect on lipid but not on glucose metabolism. Our findings reinforce unfavorable effects of the AdipoQ 45 T/G SNP in lipid profile and glucose metabolism after intervention in Brazilians at cardiometabolic risk. Further studies are needed to direct lifestyle intervention to subsets of individuals at cardiometabolic risk.Foundation for Research Support of the State of São Paulo

Realistic changes in monounsaturated fatty acids and soluble fibers are able to improve glucose metabolism

Abstract\ud \ud Background/objectives\ud Cardioprotective effects of Mediterranean-style diet have been shown. Instead of excluding foods, replacement or addition may facilitate compliance with impact on glucose metabolism of individuals at cardiometabolic risk. This study investigated the effect of changing selected nutrients intake on glucose metabolism during a lifestyle intervention tailored to living conditions of prediabetic Brazilians.\ud \ud \ud Subjects/methods\ud 183 prediabetic adults treated under the Brazilian public health system underwent an 18-month intervention on diet and physical activity. Dietary counseling focused on reducing saturated fat replaced by unsaturated fatty acids. Data were collected at baseline and after follow-up. ANOVA and multiple linear regression were used to test association of changes in nutrients intake with changes in plasma glucose.\ud \ud \ud Results\ud Changes in fasting and 2-h plasma glucose but not in weight, HOMA-IR or C-reactive protein decreased after intervention across tertiles of MUFA changes (p-trend 0.017 and 0.024, respectively). Regression models showed that increase in MUFA intake was independently associated with reduction in fasting (β -1.475, p = 0.008) and 2-h plasma glucose (β -3.321, p = 0.007). Moreover, increase in soluble fibers intake was associated with decrease in fasting plasma glucose (β -1.579, p = 0.038). Adjustment for anthropometric measurements did not change the results but did after including change in insulin in the models.\ud \ud \ud Conclusions\ud Increases of MUFA and soluble fibers intakes promote benefits on glucose metabolism, independently of adiposity, during a realistic lifestyle intervention in at-risk individuals. Mechanisms mediating these processes may include mainly insulin sensitivity improvement.Research supported by FAPESP (# 07/55120-0)

Effects of total fat intake on body fatness in adults

Background: The ideal proportion of energy from fat in our food and its relation to body weight is not clear. In order to prevent overweight and obesity in the general population, we need to understand the relationship between the proportion of energy from fat and resulting weight and body fatness in the general population. Objectives: To assess the effects of proportion of energy intake from fat on measures of body fatness (including body weight, waist circumference, percentage body fat and body mass index) in people not aiming to lose weight, using all appropriate randomised controlled trials (RCTs) of at least six months duration. Search methods: We searched CENTRAL, MEDLINE, Embase, Clinicaltrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) to October 2019. We did not limit the search by language. Selection criteria: Trials fulfilled the following criteria: 1) randomised intervention trial, 2) included adults aged at least 18 years, 3) randomised to a lower fat versus higher fat diet, without the intention to reduce weight in any participants, 4) not multifactorial and 5) assessed a measure of weight or body fatness after at least six months. We duplicated inclusion decisions and resolved disagreement by discussion or referral to a third party. Data collection and analysis: We extracted data on the population, intervention, control and outcome measures in duplicate. We extracted measures of body fatness (body weight, BMI, percentage body fat and waist circumference) independently in duplicate at all available time points. We performed random-effects meta-analyses, meta-regression, subgrouping, sensitivity, funnel plot analyses and GRADE assessment. Main results: We included 37 RCTs (57,079 participants). There is consistent high-quality evidence from RCTs that reducing total fat intake results in small reductions in body fatness; this was seen in almost all included studies and was highly resistant to sensitivity analyses (GRADE high-consistency evidence, not downgraded). The effect of eating less fat (compared with higher fat intake) is a mean body weight reduction of 1.4 kg (95% confidence interval (CI) -1.7 to -1.1 kg, in 53,875 participants from 26 RCTs, I2 = 75%). The heterogeneity was explained in subgrouping and meta-regression. These suggested that greater weight loss results from greater fat reductions in people with lower fat intake at baseline, and people with higher body mass index (BMI) at baseline. The size of the effect on weight does not alter over time and is mirrored by reductions in BMI (MD -0.5 kg/m2, 95% CI -0.6 to -0.3, 46,539 participants in 14 trials, I2 = 21%), waist circumference (MD -0.5 cm, 95% CI -0.7 to -0.2, 16,620 participants in 3 trials; I2 = 21%), and percentage body fat (MD -0.3% body fat, 95% CI -0.6 to 0.00, P = 0.05, in 2350 participants in 2 trials; I2 = 0%). There was no suggestion of harms associated with low fat diets that might mitigate any benefits on body fatness. The reduction in body weight was reflected in small reductions in LDL (-0.13 mmol/L, 95% CI -0.21 to -0.05), and total cholesterol (-0.23 mmol/L, 95% CI -0.32 to -0.14), with little or no effect on HDL cholesterol (-0.02 mmol/L, 95% CI -0.03 to 0.00), triglycerides (0.01 mmol/L, 95% CI -0.05 to 0.07), systolic (-0.75 mmHg, 95% CI -1.42 to -0.07) or diastolic blood pressure(-0.52 mmHg, 95% CI -0.95 to -0.09), all GRADE high-consistency evidence or quality of life (0.04, 95% CI 0.01 to 0.07, on a scale of 0 to 10, GRADE low-consistency evidence). Authors' conclusions: Trials where participants were randomised to a lower fat intake versus a higher fat intake, but with no intention to reduce weight, showed a consistent, stable but small effect of low fat intake on body fatness: slightly lower weight, BMI, waist circumference and percentage body fat compared with higher fat arms. Greater fat reduction, lower baseline fat intake and higher baseline BMI were all associated with greater reductions in weight. There was no evidence of harm to serum lipids, blood pressure or quality of life, but rather of small benefits or no effect

Trans fatty acid intake is associated with insulin sensitivity but independently of inflammation

High saturated and trans fatty acid intake, the typical dietary pattern of Western populations, favors a proinflammatory status that contributes to generating insulin resistance (IR). We examined whether the consumption of these fatty acids was associated with IR and inflammatory markers. In this cross-sectional study, 127 non-diabetic individuals were allocated to a group without IR and 56 to another with IR, defined as homeostasis model assessment-IR (HOMA-IR) >2.71. Diet was assessed using 24-h food recalls. Multiple linear regression was employed to test independent associations with HOMA-IR. The IR group presented worse anthropometric, biochemical and inflammatory profiles. Energy intake was correlated with abdominal circumference and inversely with adiponectin concentrations (r = -0.227, P = 0.002), while saturated fat intake correlated with inflammatory markers and trans fat with HOMA-IR (r = 0.160, P = 0.030). Abdominal circumference was associated with HOMA-IR (r = 0.430, P < 0.001). In multiple analysis, HOMA-IR remained associated with trans fat intake (&#946; = 1.416, P = 0.039) and body mass index (&#946; = 0.390, P < 0.001), and was also inversely associated with adiponectin (&#946; = -1.637, P = 0.004). Inclusion of other nutrients (saturated fat and added sugar) or other inflammatory markers (IL-6 and CRP) into the models did not modify these associations. Our study supports that trans fat intake impairs insulin sensitivity. The hypothesis that its effect could depend on transcription factors, resulting in expression of proinflammatory genes, was not corroborated. We speculate that trans fat interferes predominantly with insulin signaling via intracellular kinases, which alter insulin receptor substrates

Associations of the TNF-alpha -308 G/A, IL6 -174 G/C and AdipoQ 45 T/G polymorphisms with inflammatory and metabolic responses to lifestyle intervention in Brazilians at high cardiometabolic risk

Abstract Background Cytokines secreted by the adipose tissue influence inflammation and insulin sensitivity, and lead to metabolic disturbances. How certain single-nucleotide polymorphisms (SNPs) interfere on lifestyle interventions is unclear. We assessed associations of selected SNPs with changes induced by a lifestyle intervention. Methods This 9-month intervention on diet and physical activity included 180 Brazilians at high cardiometabolic risk, genotyped for the TNF-α -308 G/A, IL-6 -174 G/C and AdipoQ 45 T/G SNPs. Changes in metabolic and inflammatory variables were analyzed according to these SNPs. Individuals with at least one variant allele were grouped and compared with those with the reference genotype. Results In the entire sample (66.7% women; mean age 56.5 ± 11.6 years), intervention resulted in lower energy intake, higher physical activity, and improvement in anthropometry, plasma glucose, HOMA-IR, lipid profile and inflammatory markers, except for IL-6 concentrations. After intervention, only variant allele carriers of the TNF-α -308 G/A decreased plasma glucose, after adjusting for age and gender (OR 2.96, p = 0.025). Regarding the IL6 -174 G/C SNP, carriers of the variant allele had a better response of lipid profile and adiponectin concentration, but only the reference genotype group decreased plasma glucose. In contrast to individuals with the reference genotype, carriers of variant allele of AdipoQ 45 T/G SNP did not change plasma glucose, apolipoprotein B, HDL-c and adiponectin concentrations in response to intervention. Conclusion The TNFα -308 G/A SNP may predispose a better response of glucose metabolism to lifestyle intervention. The IL-6 -174 G/C SNP may confer a beneficial effect on lipid but not on glucose metabolism. Our findings reinforce unfavorable effects of the AdipoQ 45 T/G SNP in lipid profile and glucose metabolism after intervention in Brazilians at cardiometabolic risk. Further studies are needed to direct lifestyle intervention to subsets of individuals at cardiometabolic risk.</p