By Carrie Decker, ND
Founder and Medical Director,
Dr. Decker reports no financial relationships relevant to this field of study.
- The study investigated the effect of curcuminoid (and piperine) supplementation on inflammation and oxidative stress parameters in individuals with metabolic syndrome.
- A significant reduction from baseline was observed in C-reactive protein (CRP), malondialdehyde (MDA), fasting blood glucose, and hemoglobin A1C in individuals supplemented with curcuminoids, and a significant increase in superoxide dismutase (SOD) activity was seen.
- Serum CRP and MDA concentrations were significantly decreased while SOD activity was significantly improved in the curcuminoid group compared to the control.
- Meta-analysis of eight additional randomized placebo-controlled trials found a significant reduction in serum CRP concentration after supplementation with curcuminoids.
SYNOPSIS: Bioavailable cucuminoids were found to reduce oxidative stress and inflammation in individuals diagnosed with metabolic syndrome. Superoxide dismutase activity, malondialdehyde, and C-reactive protein (CRP) concentration were each significantly improved after short-term (8 weeks) of supplementation with curcuminoids. Meta-analysis of eight other studies investigating the impact of curcuminoids on various health parameters, including serum CRP concentration, also found a significant reduction of CRP with curcuminoid supplementation.
SOURCE: Panahi Y, 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. Clin Nutr 2015; Jan 7 [Epub ahead of print].
Curcuminoids, the bioactive constituents of Curcuma longa (commonly known as turmeric), have been researched extensively for the treatment of a variety of conditions including autoimmune disease, cancer prevention, liver disease, atherosclerosis, and diabetes.1 Multiple anti-oxidative and anti-inflammatory actions of curcuminoids have been demonstrated, including the inhibition and scavenging of free radicals,2 as well as the reduction of pro-inflammatory cytokines such as interleukin-6 and tumor necrosis factor-α.3
In this Phase 3, randomized, double-blind, placebo-controlled trial, 117 individuals diagnosed with metabolic syndrome and not receiving lipid-lowering therapy were randomized to receive a bioavailable curcuminoid preparation or a placebo daily for a period of 8 weeks. A bioavailable curcuminoid preparation containing 500 mg of mixed curcuminoids (curcumin, demethoxycurcumin, and bisdemethoxycurcumin) with 5 mg of piperine was administered twice daily. Bioavailability of curcumin is known to be enhanced when taken in combination with piperine.4 Diagnosis of metabolic syndrome was made according to the criteria of the National Cholesterol Education Program Adult Treatment Panel III. Individuals were excluded from the study if they were pregnant or breastfeeding, had a known malignancy, had a known sensitivity to turmeric, or were not compliant with protocols for at least 1week.
Parameters assessed in this study included:
- serum highly-specific C-reactive protein (hs-CRP) concentration
- serum malondialdehyde (MDA) concentration (a marker of lipid peroxidation)
- serum superoxide dismutase (SOD) activity
- fasting blood glucose (FBG)
- hemoglobin A1c (HbA1c)
At baseline, the intervention group was found to have significantly higher BMI, FBG, and HbA1c levels and a lower SOD activity. Results were subsequently assessed for the possible effect of the different baseline body mass index (BMI) and FBG using a univariate analysis of covariance assessment.
Upon completion of the 8-week intervention period, significant reduction from baseline was observed in CRP (P < 0.001), MDA (P < 0.001), FBG (P < 0.001), and HbA1c (P = 0.048) in the individuals supplemented with curcuminoids, and a significant increase in SOD activity (P < 0.001) was seen. The placebo group experienced a significant increase in serum SOD activity (P = 0.001) and FBG (P = 0.011) and no significant change in CRP, MDA, or HbA1C levels. In comparison to the placebo group, a significant reduction in serum CRP (P < 0.001) and MDA (P < 0.001) concentrations and increased SOD (P < 0.001) activity were seen in the curcuminoid group. No significant adverse effects were reported, and dropouts were comparable between the two groups (nine and eight subjects from the curcuminoid group and placebo group, respectively).
Although multiple parameters (BMI, FBG, HbA1c, and SOD) were significantly different in the intervention group from the control at baseline, when the effect of confounders was assessed, the impact of curcuminoid supplementation on SOD, MDA, and CRP remained statistically significant (P < 0.001).
Additionally, a meta-analysis was performed by the authors of this study to investigate the impact of curcumin supplementation on serum CRP. Eight studies met the inclusion criteria for this meta-analysis, and all but one were a placebo-controlled, double-blind studies. Curcumin dosage ranged from 80 mg to 6 g per day, and the intervention period ranged from 2-12 weeks. Curcuminoid supplementation was found to be associated with a significant reduction in serum CRP of -2.20 mg/L (P = 0.01; 95% confidence interval [CI] -3.96 to -0.44). Meta-regression did not find an association between administered dose of curcuminoids and change in CRP; however, in two of the studies utilizing higher doses of curcumin, the form was not optimized for bioavailability.
Turmeric is a popular supplement for conditions involving inflammation and oxidative damage. Non-medically educated consumers often self-select products that include curcumin as well as other popular botanicals such as ginger (Zingiber officinale) and Boswellia serrata (also known as Indian frankincense) for inflammation.5 Clinical studies have been performed investigating the use of curcuminoids for the treatment of more than 35 common and less common medical conditions as diverse as renal transplant, ß-Thalassemia, peptic ulcer, and Helicobacter pylori, to the more common issues of autoimmunity, diabetes, Alzheimer’s disease, and cancer therapies.1 Curcumin has been found to reduce inflammation in a multitude of other conditions and pathology associated with an inflammatory state.6 A multitude of mechanisms by which curcuminoids may act therapeutically has been shown. These often relate back to oxidative stress and inflammation, but they also encompass other antimicrobial7 and anticancer8 actions.
Metabolic syndrome is associated with multiple negative health effects, including increased cardiovascular, diabetes, and cancer risk. Inflammation9 and oxidative stress10 are associated with the development of further pathology, and both tend to be increased in individuals with metabolic syndrome. Means by which to address this syndrome with nutritional and botanical agents is of interest, as the primary agents that are used for treatment of this condition only include hypoglycemic and lipid-altering agents.
One of the primary drawbacks of this study was that there were significant differences between the intervention and control groups at baseline. Although the results were assessed for the possible impact of a higher baseline BMI and FBG, the baseline difference of HbA1c and SOD activity was not accounted for. One might anticipate that if SOD activity is lower at baseline, it would be easier to improve upon this parameter. It also may be that there were some individuals who had baseline data significantly outside of a standard deviation of the remainder of the group. A significant deviation from the mean possibly should have been exclusion criteria for the study, as it may indicate other physiologic or unknown disease processes that may have an effect on the study outcomes. Finally, an intention-to-treat analysis was not performed, as the individuals who dropped out were lost to follow-up.
There are many reasons to consider the selection of curcumin as an agent for the treatment of metabolic syndrome. Curcuminoids have been shown to improve lipid profiles, reducing serum triglycerides, total cholesterol, non-high density lipoprotein cholesterol, and lipoprotein(a) levels. Curcumin also has been shown to have anti-hyperglycemic and insulin sensitizer effects.12 CRP levels are commonly elevated in individuals with abdominal adiposity characteristic of metabolic syndrome,13 and they are associated with the development of cardiovascular pathology.14 Therefore, findings that curcuminoids also serve to improve this parameter (including the meta-analysis data) further support the use of curcuminoids to support the overall health of individuals with metabolic syndrome.
The bioavailability of curcumin, as addressed by this study and mentioned pertaining to the meta-analysis as well, is something that must not be neglected. Studies have shown that curcumin and its metabolites are not detectable in serum or plasma at doses of curcuminoids < 3.6-4.0 grams per day when taken without special preparation for improved bioavailability.16,17 Selection of curcumin preparations with piperine4 or in a phospholipid-complexed form have been shown to have increased bioavailability over curcumin taken without these agents. Additional formulations may be available with improved bioavailability, but until this has been verified with clinical studies, curcumin in a preparation with piperine or phospholipids should be selected.
Turmeric, from which curcuminoids are extracted, contains between 2-9% curcumin.18 Since 1 teaspoon of turmeric is approximately 1.5 grams (a maximum of 0.135 g of curcuminoids), to achieve a dosage of 4 grams of curcuminoids a person would have to consume a minimum of 30 teaspoons. It is likely that the dietary consumption of turmeric may not impact physiological parameters in a demonstrable manner, as this is a dosage far greater than most individuals would ever consume. Since curcuminoids are fat-soluble, in theory, there may be improved absorption when turmeric is taken with other fats or black pepper (source of piperine); however, there have not been studies to support this hypothesis.
Given the wide array of data supporting the use of curcumin for the reduction of an inflammatory state, supplementation with curcumin should be considered for individuals with metabolic syndrome particularly if there are other concomitant inflammation-mediated conditions such as autoimmune disease.
- Gupta SC, et al. Therapeutic roles of curcumin: Lessons learned from clinical trials. AAPS J 2013;15:195-218.
- Calabrese V, et al. Curcumin and the cellular stress response in free radical-related diseases. Mol Nutr Food Res 2008;52:1062-1073.
- Das L, Vinayak M. Long-term effect of curcumin down-regulates expression of tumor necrosis factor-α and interleukin-6 via modulation of E26 transformation-specific protein and nuclear factor-αß transcription factors in livers of lymphoma bearing mice. Leuk Lymphoma 2014;55:2627-2636.
- Shoba G, et al. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med 1998;64:353-356.
- Di Lorenzo C, et al. Plant food supplements with anti-inflammatory properties: A systematic review (II). Crit Rev Food Sci Nutr 2013;53:507-516.
- Jurenka JS. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: A review of preclinical and clinical research. Altern Med Rev 2009;14:141-153.
- Moghadamtousi SZ, et al. A review on antibacterial, antiviral, and antifungal activity of curcumin. Biomed Res Int 2014;2014:186864.
- Tuorkey MJ. Curcumin a potent cancer preventive agent: Mechanisms of cancer cell killing. Interv Med Appl Sci 2014;6:139-146.
Rohla M, Weiss TW. Metabolic syndrome, inflammation and atherothrombosis. Hamostaseologie 2013;33:
- Hopps E, et al. A novel component of the metabolic syndrome: The oxidative stress. Nutr Metab Cardiovasc Dis 2010;20:72-77.
Panahi Y, et al. Lipid-modifying effects of adjunctive therapy with curcuminoids-piperine combination in patients with metabolic syndrome: Results of a randomized controlled trial. Complement Ther Med 2014;22:
- Ghorbani Z, et al. Anti-hyperglycemic and insulin sensitizer effects of turmeric and its principle constituent curcumin. Int J Endocrinol Metab 2014;12:e18081.
- Brooks GC, et al. Relation of C-reactive protein to abdominal adiposity. Am J Cardiol 2010;106:56-61.
- Tsimikas S, et al. C-reactive protein and other emerging blood biomarkers to optimize risk stratification of vulnerable patients. J Am Coll Cardiol 2006;47:C19-31.
Gupta NK, Dixit VK. Bioavailability enhancement of curcumin by complexation with phosphatidyl choline.
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- Sharma RA, et al. Phase I clinical trial of oral curcumin: Biomarkers of systemic activity and compliance. Clin Cancer Res 2004;10:6847-6854.
- Lechtenberg M, et al. Quantitative determination of curcuminoids in Curcuma rhizomes and rapid differentiation of Curcuma domestica Val. and Curcuma xanthorrhiza Roxb. by capillary electrophoresis. Phytochem Anal 2004;15:152-158.