Lipid-modifying effects of adjunctive therapy with curcuminoids–piperine combination in patients with metabolic syndrome: Results of a randomized controlled trial
Introduction
The metabolic syndrome (MS) is a cluster of several inter-related cardiometabolic risk factors including abdominal obesity, hyperglycemia/impaired glucose tolerance, hypertension and atherogenic dyslipidemia.1 Constellation of these risk factors puts the affected patient at an increased risk of type 2 diabetes and atherosclerotic cardiovascular disease (ACVD).2 MS has been the focus of increasing attention over the past few years owing to its rapidly increasing prevalence that is nearing epidemic proportions in Western societies.3 The cornerstone in the management of MS is controlling the individual risk factors. Dyslipidemia is a key yet modifiable risk factor of MS. The predominant type of dyslipidemia in patients with MS is atherogenic dyslipidemia, which is characterized by elevated plasma triglyceride and low high-density lipoprotein cholesterol (HDL-C) levels.4 Moreover, MS is most often associated with a preponderance of small dense low-density lipoprotein (sdLDL) particles, a subfraction of LDL that is more susceptible to oxidation, and triggering foam cell formation and atherogenesis.5 Based on the recent guidelines, the primary goal in the management of dyslipidemia in MS is to achieve an optimal, yet strict, plasma LDL-cholesterol (LDL-C) levels of <70 mg/dL.6 This is due to the strong and unequivocal association of LDL-C with ACVD outcomes in large trials, and the established efficacy of LDL-C reduction in both primary and secondary prevention of ACVD. Secondary lipid goals in MS patients include reducing plasma non-HDL-C and triglycerides, and elevation of HDL-C.7
The efficacy of statins, as the first-choice and the most potent class of LDL-lowering agents, in achieving LDL-C targets and modulation of features associated with atherogenic dyslipidemia is limited. Therefore, a considerable proportion of statin-treated MS patients require combination therapy with fibrates or niacin. However, such combinations would introduce additional problems owing to the potential interactions, and more importantly, adverse events such as flushing (with niacin) and risk of myopathies, and hepatic and renal dysfunction (with statin–fibrate combination therapy).8 These limitations necessitate further research to find effective lipid-modifying treatments that could be used as adjunctive to statin therapy in MS and associated comorbidities.9, 10, 11, 12, 13, 14, 15, 16
Curcuminoids are polyphenolic phytochemicals and active ingredients of the famous dietary spice turmeric. Curcuminoids have been extensively studied in relation to their therapeutic efficacy in different disease models.17, 18 To date, numerous pharmacological activities have been identified for curcuminoids in preclinical and clinical models, nominating these phytochemicals as a multifunctional supplement for several diseases.17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 The versatility of medicinal properties of curcuminoids is due to their potential to interact with a wide spectrum of molecular targets such as enzymes, receptors, transcription factors, growth factors, hormones, cytokines, adipokines and adhesion molecules.31 Notably, curcuminoids have been shown to modulate several features of MS by improving insulin sensitivity,32, 33 suppressing adipogenesis,34 reducing elevated blood pressure35 and mitigating inflammation22, 36 and oxidative stress.37, 38 Moreover, there is evidence indicating that curcuminoids modulate the expression of genes and activity of enzymes involved in lipoprotein metabolism, and through which reduce plasma triglycerides and cholesterol,39, 40, 41 and elevate HDL-C concentrations.42 In spite of such a strong mechanistic rationale,43 the efficacy of curcuminoids has not yet been tested in a clinical trial in MS patients. The objective of the present study was to investigate the clinical efficacy of a unique curcuminoid formulation as adjunctive to standard of care in patients with MS.
Section snippets
Subjects
Participants were selected from those referring to the Cardiology or Endocrinology Clinics of the Baqiyatallah Hospital (Tehran, Iran) from May 2013 to January 2013. Inclusion criteria were subjects from both genders aged 25–75 years, who fulfilled diagnostic criteria for MS based on the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) guidelines a follows: ≥3 of the following conditions: waist circumference ≥102 cm (male) or ≥88 cm (female), blood pressure ≥130/85
Results
One hundred and seventeen subjects met the inclusion and were assigned to either curcuminoids–piperine combination (n = 59) or placebo (n = 58). Seventeen subjects dropped out of the trial, 9 from the curcuminoids–piperine and 8 from the placebo group (Fig. 1). The number of drop-outs did not differ between the study groups. The main reason for drop-outs was loss to follow-up, followed by gastrointestinal side effects, both being comparable between the groups. Therefore, 50 subjects in each group
Discussion
The results of the present trial supported the effectiveness of adjunctive therapy with curcuminoids in improving serum lipid concentrations in patients with MS. To the best of authors’ knowledge, the present study has been the first trial investigating the efficacy of curcuminoids in patients with MS. The robust design and the use of a bioavailability-optimized preparation of curcuminoids in this study provide a strong evidence for the use of curcuminoids in the management of MS. Nevertheless,
Conclusion
The present study provided the first clinical evidence on the efficacy and safety of adjunctive therapy with curcuminoids–piperine combination in modulating serum lipid concentrations of patients with MS receiving standard treatment. These findings encourage the use of bioavailability-enhanced curcuminoid preparations as part of treatment regimen in MS patients, who are at a high risk of ACVD. However, further evidence from larger-scale randomized controlled trials is still required to verify
Conflict of interest
The authors have no competing interests to declare.
References (68)
- et al.
New LDL-cholesterol lowering therapies: pharmacology, clinical trials, and relevance to acute coronary syndromes
Clin Ther
(2013) Citrus auraptene: a potential multifunctional therapeutic agent for nonalcoholic fatty liver disease
Ann Hepatol
(2011)Molecular mechanisms for curcumin benefits against ischemic injury
Fertil Steril
(2010)- et al.
Cancer chemopreventive activity of diversin from Ferula diversivittata in vitro and in vivo
Phytomedicine
(2010) - et al.
Antioxidant effects of bioavailability-enhanced curcuminoids in patients with solid tumors: a randomized double-blind placebo-controlled trial
J Funct Foods
(2014) - et al.
Antioxidant and radical scavenging properties of curcumin
Chem Biol Interact
(2008) - et al.
Curcumin effects on blood lipid profile in a 6-month human study
Pharmacol Res: Off J Ital Pharmacol Soc
(2007) - et al.
An hydroalcoholic extract of Curcuma longa lowers the apo B/apo A ratio. Implications for atherogenesis prevention
Mech Ageing Dev
(2000) - et al.
The protective role of curcumin in cardiovascular diseases
Int J Cardiol
(2009) - et al.
Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases
Int J Biochem Cell Biol
(2009)