Curcuminoids modify lipid profile in type 2 diabetes mellitus: A randomized controlled trial.

BACKGROUND Type 2 diabetes (T2D) is an established risk factor for cardiovascular disease (CVD) and is associated with disturbed metabolism of lipids and lipoproteins. Curcuminoids are natural products with anti-diabetic and lipid-modifying actions but their efficacy in improving dyslipidemia in diabetic individuals has not been sufficiently studied. OBJECTIVE To investigate the efficacy of supplementation with curcuminoids, plus piperine as an absorption enhancer, in improving serum lipids in patients with T2D. METHODS In this 12-week randomized double-blind placebo-controlled trial, subjects with T2D (n=118) were assigned to curcuminoids (1000mg/day plus piperine 10mg/day) or placebo plus standard of care for T2D. Serum concentrations of lipids including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), lipoprotein(a) [Lp(a)], and non-HDL-C were determined at baseline and at the end of trial. RESULTS Between-group comparison of change in the study parameters revealed significant reductions in serum levels of TC (-21.86±25.78 versus -17.06±41.51, respectively; p=0.023), non-HDL-C (-23.42±25.13 versus -16.84±41.42, respectively; p=0.014) and Lp(a) (-1.50±1.61 versus -0.34±1.73, respectively; p=0.001) and elevations in serum HDL-C levels (1.56±4.25 versus -0.22±4.62, respectively; p=0.048) in the curcuminoids group as compared with the placebo group (p<0.05). Serum TG and LDL-C changes did not show any significant difference between the study groups (p>0.05). CONCLUSION Curcuminoids supplementation can reduce serum levels of atherogenic lipid indices including non-HDL-C and Lp(a). Therefore, curcuminoids supplementation could contribute to a reduced risk of cardiovascular events in dyslipidemic patients with T2D.

[1]  Y. Panahi,et al.  Investigation of the Efficacy of Adjunctive Therapy with Bioavailability‐Boosted Curcuminoids in Major Depressive Disorder , 2015, Phytotherapy research : PTR.

[2]  A. Sahebkar,et al.  Comparison of the effects of fibrates versus statins on plasma lipoprotein(a) concentrations: a systematic review and meta-analysis of head-to-head randomized controlled trials , 2017, BMC Medicine.

[3]  R. DiSilvestro,et al.  Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people , 2012, Nutrition Journal.

[4]  M. Banach,et al.  Raloxifene Lowers Plasma Lipoprotein(a) Concentrations: a Systematic Review and Meta-analysis of Randomized Placebo-Controlled Trials , 2017, Cardiovascular Drugs and Therapy.

[5]  M. Majeed,et al.  Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. , 1998, Planta medica.

[6]  A. Sahebkar,et al.  Curcumin as a natural regulator of monocyte chemoattractant protein-1. , 2017, Cytokine & growth factor reviews.

[7]  Biao Xu,et al.  Safety and efficacy of anti-PCSK9 antibodies: a meta-analysis of 25 randomized, controlled trials , 2015, BMC Medicine.

[8]  A. Sahebkar,et al.  Preventing cardiovascular heart disease: Promising nutraceutical and non-nutraceutical treatments for cholesterol management. , 2017, Pharmacological research.

[9]  A. Sahebkar,et al.  Curcumin and Endothelial Function: Evidence and Mechanisms of Protective Effects. , 2017, Current pharmaceutical design.

[10]  Y. Panahi,et al.  Curcumin as a potential candidate for treating hyperlipidemia: A review of cellular and metabolic mechanisms , 2018, Journal of cellular physiology.

[11]  A. Sahebkar,et al.  Lipid-modifying effects of nutraceuticals: An evidence-based approach. , 2016, Nutrition.

[12]  J. Zamorano,et al.  A review of the evidence on reducing macrovascular risk in patients with atherogenic dyslipidaemia: A report from an expert consensus meeting on the role of fenofibrate-statin combination therapy. , 2015, Atherosclerosis. Supplements.

[13]  A. Sahebkar,et al.  Supplementation with coenzyme Q10 reduces plasma lipoprotein(a) concentrations but not other lipid indices: A systematic review and meta-analysis. , 2016, Pharmacological research.

[14]  A. Kontush,et al.  HDL particle subpopulations: Focus on biological function , 2015, BioFactors.

[15]  A. Sahebkar Are Curcuminoids Effective C‐Reactive Protein‐Lowering Agents in Clinical Practice? Evidence from a Meta‐Analysis , 2014, Phytotherapy research : PTR.

[16]  Y. Panahi,et al.  Lipid-modifying effects of adjunctive therapy with curcuminoids-piperine combination in patients with metabolic syndrome: results of a randomized controlled trial. , 2014, Complementary therapies in medicine.

[17]  A. Sahebkar,et al.  Curcumin: A new candidate for melanoma therapy? , 2016, International journal of cancer.

[18]  Y. Panahi,et al.  Curcumin Lowers Serum Lipids and Uric Acid in Subjects With Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial , 2016, Journal of cardiovascular pharmacology.

[19]  A. Sahebkar,et al.  Curcumin downregulates human tumor necrosis factor-α levels: A systematic review and meta-analysis ofrandomized controlled trials. , 2016, Pharmacological research.

[20]  A. Sahebkar,et al.  Curcumin: An Effective Inhibitor of Interleukin-6. , 2017, Current pharmaceutical design.

[21]  S. Asgary,et al.  Treatment of Non‐alcoholic Fatty Liver Disease with Curcumin: A Randomized Placebo‐controlled Trial , 2016, Phytotherapy research : PTR.

[22]  J. Borén,et al.  Lipoprotein(a) as a cardiovascular risk factor: current status , 2010, European heart journal.

[23]  Jennifer G. Robinson,et al.  Lipid-lowering efficacy of the PCSK9 inhibitor evolocumab (AMG 145) in patients with type 2 diabetes: a meta-analysis of individual patient data. , 2016, The lancet. Diabetes & endocrinology.

[24]  G. Ferns,et al.  Effects of Supplementation with Curcuminoids on Dyslipidemia in Obese Patients: A Randomized Crossover Trial , 2013, Phytotherapy research : PTR.

[25]  S. Bo,et al.  Effect of curcumin on circulating interleukin-6 concentrations: A systematic review and meta-analysis of randomized controlled trials. , 2016, Pharmacological research.

[26]  Ž. Reiner Managing the residual cardiovascular disease risk associated with HDL-cholesterol and triglycerides in statin-treated patients: a clinical update. , 2013, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[27]  Sarah Parish,et al.  Effects of extended-release niacin with laropiprant in high-risk patients. , 2014, The New England journal of medicine.

[28]  S. Jirawatnotai,et al.  Curcumin Extract for Prevention of Type 2 Diabetes , 2012, Diabetes Care.

[29]  A. Sahebkar Curcuminoids for the management of hypertriglyceridaemia , 2014, Nature Reviews Cardiology.

[30]  G. Ferns,et al.  Investigation of the Effects of Curcumin on Serum Cytokines in Obese Individuals: A Randomized Controlled Trial , 2014, TheScientificWorldJournal.

[31]  M. Amiri,et al.  Improvement of sulphur mustard-induced chronic pruritus, quality of life and antioxidant status by curcumin: results of a randomised, double-blind, placebo-controlled trial , 2011, British Journal of Nutrition.

[32]  Y. Panahi,et al.  Mitigation of Systemic Oxidative Stress by Curcuminoids in Osteoarthritis: Results of a Randomized Controlled Trial , 2016, Journal of dietary supplements.

[33]  M. Ghanei,et al.  Effects of Curcuminoids-Piperine Combination on Systemic Oxidative Stress, Clinical Symptoms and Quality of Life in Subjects with Chronic Pulmonary Complications Due to Sulfur Mustard: A Randomized Controlled Trial , 2016, Journal of dietary supplements.

[34]  A. Sahebkar,et al.  Impact of L-carnitine on plasma lipoprotein(a) concentrations: A systematic review and meta-analysis of randomized controlled trials , 2016, Scientific Reports.

[35]  A. Sahebkar,et al.  Analgesic Efficacy and Safety of Curcuminoids in Clinical Practice: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. , 2015, Pain medicine.

[36]  A. Sahebkar,et al.  Is There a Role for Curcumin Supplementation in the Treatment of Non-Alcoholic Fatty Liver Disease? The Data Suggest Yes. , 2017, Current pharmaceutical design.

[37]  A. Sahebkar Why it is necessary to translate curcumin into clinical practice for the prevention and treatment of metabolic syndrome? , 2013, BioFactors.

[38]  Y. Panahi,et al.  Antioxidant and anti-inflammatory effects of curcuminoid-piperine combination in subjects with metabolic syndrome: A randomized controlled trial and an updated meta-analysis. , 2015, Clinical nutrition.

[39]  A. Colletti,et al.  Role of phytochemicals in the management of metabolic syndrome. , 2016, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[40]  A. Sahebkar,et al.  Lipoprotein(a) and inflammation: A dangerous duet leading to endothelial loss of integrity , 2017, Pharmacological research.

[41]  I. Pećin,et al.  Alirocumab: targeting PCSK9 to treat hypercholesterolemia. , 2015, Drugs of Today.

[42]  A. Sahebkar,et al.  Tibolone decreases Lipoprotein(a) levels in postmenopausal women: A systematic review and meta-analysis of 12 studies with 1009 patients. , 2015, Atherosclerosis.

[43]  T. Santoso,et al.  The effect of curcumin on lipid level in patients with acute coronary syndrome. , 2008, Acta medica Indonesiana.

[44]  A. Sahebkar,et al.  Curcuminoids Modulate Pro‐Oxidant–Antioxidant Balance but not the Immune Response to Heat Shock Protein 27 and Oxidized LDL in Obese Individuals , 2013, Phytotherapy research : PTR.

[45]  Y. Li,et al.  Curcuminoids exert glucose-lowering effect in type 2 diabetes by decreasing serum free fatty acids: a double-blind, placebo-controlled trial. , 2013, Molecular nutrition & food research.

[46]  A. Sahebkar A systematic review and meta-analysis of randomized controlled trials investigating the effects of curcumin on blood lipid levels. , 2014, Clinical nutrition.

[47]  P. Kolh,et al.  ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). , 2011, European heart journal.

[48]  M. Banach,et al.  Effects of curcumin on HDL functionality , 2017, Pharmacological research.

[49]  Y. Panahi,et al.  A randomized controlled trial on the anti-inflammatory effects of curcumin in patients with chronic sulphur mustard-induced cutaneous complications , 2012, Annals of clinical biochemistry.

[50]  A. Hoes,et al.  2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. , 2016, European heart journal.

[51]  B. Aggarwal,et al.  Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature. , 2008, Biochemical pharmacology.

[52]  Ž. Reiner,et al.  Effect of extended-release niacin on plasma lipoprotein(a) levels: A systematic review and meta-analysis of randomized placebo-controlled trials. , 2016, Metabolism: clinical and experimental.