Turmeric supplementation with piperine is more effective than turmeric alone in attenuating oxidative stress and inflammation in hemodialysis patients: A randomized, double-blind clinical trial.

PURPOSE: Turmeric has renop rotective effects that can act to reduce oxidative stress and inflammation in hemodialysis (HD) patients. Piperine has been indicated as a bioavailability enhancer of turmeric and consequently of its biological effects. However, data on the efficacy of the turmeric/piperine combination in HD patients are limited. We aimed to verify whether turmeric supplementation in combination with piperine has a superior effect to turmeric alone in increasing antioxidant capacity and reducing oxidative stress and inflammation in HD patients. METHODS: This randomized, double-blind clinical trial was conducted in HD patients (age 20-75 years). Patients were supplemented with turmeric (3 g/day) or turmeric/piperine (3 g turmeric + 2 mg piperine/day) for 12 weeks. Malondialdehyde (MDA), antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), high-sensitivity C-reactive protein (hs-CRP), and ferritin were evaluated at baseline and the end of the study. RESULTS: There was a reduction in the MDA and ferritin levels in the turmeric/piperine group and in the comparison between groups at the end of the study [MDA: -0.08(-0.14/0.01) nmol/mL versus -0.003(-0.10/0.26) nmol/mL, p = 0.003; ferritin: -193.80 ±â€¯157.29 mg/mL versus 51.99 ±â€¯293.25 mg/mL, p = 0.018]. In addition, GPx activity reduced in the turmeric group (p = 0.029). No changes were observed for CAT, GR, and hs-CRP. CONCLUSION: Turmeric plus piperine was superior to turmeric alone in decreasing MDA and ferritin levels. The use of a combination of turmeric and piperine as a dietary intervention may be beneficial for modulating the status oxidative and inflammation in HD patients. BRAZILIAN REGISTRY OF CLINICAL TRIALS NUMBER: RBR-2t5zpd; Registration Date: May 2, 2018.

Antioxidant and anti-inflammatory response to curcumin supplementation in hemodialysis patients: A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND AND OBJECTIVES: Hemodialysis (HD) patients are vulnerable to malnutrition and cardiovascular complications due to many factors, including oxidative stress and inflammation. Curcumin supplementation is associated with attenuation of proinflammatory cytokines and increased activity of antioxidant enzymes, but its effects in HD patients are unknown. This study aimed to evaluate the effect of curcumin supplementation on oxidative stress and inflammation in HD patients. METHODS: This randomized, double-blind, placebo-controlled trial enrolled 43 HD patients and divided them into two groups: supplemented with curcumin (1 g/day) or placebo (corn starch) for 12 weeks. Demographic information and blood samples were taken at the start and the end of the study to determine serum malondialdehyde (MDA) concentrations, antioxidant enzyme activity, and high-sensitivity C-reactive protein (hs-CRP). RESULTS: The curcumin group showed a significant increase in catalase activity [Δ = 1.13 ± 2.87 versus Δ = -1.08 ± 2.68; p = 0.048] and preserved glutathione peroxidase activity [Δ = -4.23 ± 11.50 versus Δ = -14.44 ± 13.96; p < 0.01] compared with the placebo group. However, no significant changes were found in MDA concentrations, glutathione reductase activity, and hs-CRP concentrations after the intervention. CONCLUSION: Curcumin supplementation for 12 weeks had potential effects on antioxidant response, but it was not enough to reduce oxidative stress markers and inflammation in HD patients. This trial was registered at EnsaiosClínicos.gov.br under registration number RBR-2t5zpd.

Insights Into Thiamine Supplementation in Patients With Septic Shock.

Septic shock is associated with unacceptably high mortality rates, mainly in developing countries. New adjunctive therapies have been explored to reduce global mortality related to sepsis. Considering that metabolic changes, mitochondrial dysfunction and increased oxidative stress are specific disorders within the path of septic shock, several micronutrients that could act in cellular homeostasis have been studied in recent decades. Thiamine, also known as vitamin B1, plays critical roles in several biological processes, including the metabolism of glucose, synthesis of nucleic acids and reduction of oxidative stress. Thiamine deficiency could affect up to 70% of critically ill patients, and thiamine supplementation appears to increase lactate clearance and decrease the vasopressor dose. However, there is no evident improvement in the survival of septic patients. Other micronutrients such as vitamin C and D, selenium and zinc have been tested in the same context but have not been shown to improve the outcomes of these patients. Some problems related to the neutrality of these clinical trials are the study design, doses, route, timing, length of intervention and the choice of endpoints. Recently, the concept that multi-micronutrient administration may be better than single-micronutrient administration has gained strength. In general, clinical trials consider the administration of a single micronutrient as a drug. However, the antioxidant defense is a complex system of endogenous agents in which micronutrients act as cofactors, and the physiological interactions between micronutrients are little discussed. In this context, the association of thiamine, vitamin C and corticoids was tested as an adjunctive therapy in septic shock resulting in a significant decrease in mortality. However, after these initial results, no other study conducted with this combination could reproduce those benefits. In addition, the use of low-dose corticosteroids is recommended in patients with septic shock who do not respond to vasopressors, which can affect the action of thiamine. Therefore, given the excellent safety profile, good biologic rationale and promising clinical studies, this review aims to discuss the mechanisms behind and the evidence for single or combined thiamine supplementation improving the prognosis of patients with septic shock.

Erythrocyte selenium concentration predicts intensive care unit and hospital mortality in patients with septic shock: a prospective observational study.

INTRODUCTION: Selenoenzymes can modulate the extent of oxidative stress, which is recognized as a key feature of septic shock. The pathophysiologic role of erythrocyte selenium concentration in patients with septic shock remains unknown. Therefore, the objective of this study was to evaluate the association of erythrocyte selenium concentration with glutathione peroxidase (GPx1) activity, GPx1 polymorphisms and with ICU and hospital mortality in septic shock patients. METHODS: This prospective study included all patients older than 18 years with septic shock on admission or during their ICU stay, admitted to one of the three ICUs of our institution, from January to August 2012. At the time of the patients' enrollment, demographic information was recorded. Blood samples were taken within the first 72 hours of the patients' admission or within 72 hours of the septic shock diagnosis for determination of selenium status, protein carbonyl concentration, GPx1 activity and GPx1 Pro198Leu polymorphism (rs 1050450) genotyping. RESULTS: A total of 110 consecutive patients were evaluated. The mean age was 57.6 ± 15.9 years, 63.6% were male. Regarding selenium status, only erythrocyte selenium concentration was lower in patients who died in the ICU. The frequencies for GPx1 Pro198Leu polymorphism were 55%, 38% and 7% for Pro/Pro, Pro/Leu and Leu/Leu, respectively. In the logistic regression models, erythrocyte selenium concentration was associated with ICU and hospital mortality in patients with septic shock even after adjustment for protein carbonyl concentration and acute physiology and chronic health evaluation II score (APACHE II) or sequential organ failure assessment (SOFA). CONCLUSIONS: Erythrocyte selenium concentration was a predictor of ICU and hospital mortality in patients with septic shock. However, this effect was not due to GPx1 activity or Pro198Leu polymorphism.