What this is
- This systematic review and meta-analysis assess the effects of supplementation on () indicators.
- The analysis includes 13 randomized controlled trials (RCTs) with 785 participants, focusing on metabolic, inflammatory, and oxidative stress markers.
- Key outcomes include waist circumference, fasting blood sugar, blood pressure, and inflammatory markers, evaluating the efficacy and safety of .
Essence
- supplementation significantly reduces waist circumference, fasting blood sugar, diastolic blood pressure, and inflammatory markers in patients. However, no significant effects were observed on triglycerides or systolic blood pressure.
Key takeaways
- supplementation leads to a reduction in waist circumference by 2.16 cm, indicating potential benefits for abdominal obesity in patients.
- Fasting blood sugar levels decrease by 8.6 mg/dL with , suggesting improved glycemic control among participants.
- Diastolic blood pressure is lowered by 2.8 mmHg in the group, contributing to better cardiovascular health.
Caveats
- The study's findings are limited by high heterogeneity in some outcomes, particularly fasting blood sugar and blood pressure.
- Most included studies were conducted in Asian populations, which may limit the generalizability of the results.
- The risk of bias was noted in several studies, particularly regarding randomization and allocation concealment.
Definitions
- Metabolic Syndrome (MetS): A cluster of conditions including increased waist circumference, high blood pressure, elevated fasting blood sugar, and abnormal cholesterol levels.
- Curcumin: A natural polyphenol derived from turmeric, known for its anti-inflammatory and antioxidant properties.
AI simplified
Introduction
Metabolic syndrome (MetS) is a metabolic disease. The National Cholesterol Education Program Adult Treatment Panel III (NCEP: ATPIII) and the International Diabetes Federation (IDF) are prominent organizations dedicated to addressing issues related to cholesterol and diabetes. At present, the two most extensively adopted definitions are those of the IDF and NCEP: ATP III (1). The criteria of both organizations for assessing MetS include waist circumference (WC), blood pressure (for assessing MetS BP), fasting blood sugar (FBS), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) (2). As a novel non-communicable disease, metabolic syndrome has emerged as a global problem. MetS, although challenging to measure epidemiologically, is estimated to be approximately three times more prevalent than diabetes. Therefore, it is believed to affect around one-fourth of the global population already (3). Moreover, MetS can lead to an increased risk of diabetes and coronary heart disease and is associated with a number of malignancies, including colon, liver, and pancreatic cancers (4, 5).
Abdominal adiposity is highly correlated to increased morbidity and mortality (6). Additionally, it serves as an indicator of “dysfunctional adipose tissue,” which is a key factor in the clinical diagnosis of MetS (7). MetS is a growing global public health concern. To effectively manage the condition, new and efficient treatments with minimal adverse effects are urgently needed.
Curcumin, a natural plant-based dietary polyphenol, is an active ingredient derived from turmeric from the ginger family. Curcumin has anti-inflammatory, anti-oxidant, anti-diabetic, and anti-atherosclerotic properties (8–10), which can improve the metabolic parameters and symptoms of polycystic ovarian syndrome, MetS, non-alcoholic fatty liver, and cardiovascular disease (11). As suggested by a recent study, curcumin is a potential drug for dealing with MetS (12).
In previous research, curcumin supplementation has been reported to improve obesity-related indices, fasting glucose, and lipids in metabolic diseases such as obesity, fatty liver, and MetS (13–18). A previous meta-analysis also revealed that curcumin supplementation improved certain components of MetS, including FBS, TG, diastolic blood pressure (DBP), and HDL-C, but there were no significant changes in systolic blood pressure (SBP) and WC (19). Another study reported similar results (20). However, four (21–24) newly randomized controlled trials on metabolic indices were missed in the aforementioned meta-analysis. Notably, pro-inflammatory state and oxidative stress are significant factors of MetS and play an important role in the development process of MetS (25, 26). In a previous meta-analysis, it was found that curcumin did not have a significant effect in reducing inflammatory markers associated with chronic inflammatory diseases (27). However, a randomized controlled trial demonstrated that curcumin supplementation improved the indicators of inflammation and oxidative stress in patients with critical sepsis (28). Furthermore, in one study, oxidative stress and inflammatory markers in conditions such as obesity, diabetes, and non-alcoholic fatty liver disease (NAFLD) were systematically reviewed (29). However, there has been no systematic review conducted specifically on inflammatory and oxidative stress markers in patients with metabolic syndrome (MetS). As such, the aim of the present study was to perform a meta-analysis of published randomized controlled clinical trials to further evaluate the effects of curcumin on metabolic, inflammatory, and oxidative stress markers in patients with MetS.
Methods
The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) 2020 (30) standards were followed in the execution of the current meta-analysis, which was registered with PROSPERO under ID number CRD42022362553.
Literature search strategy
From the outset through June 2022, six electronic databases—PubMed, SCOPUS, Cochrane Library, EMBASE, Web of Science, and China Biological Medicine (CBM)—were thoroughly searched. The terms used included the following: “curcumin” or “turmeric yellow” or “yellow, turmeric” or “curcumin phytosome” or “curcuminoid” or “curcuma” or “curcuminoid supplement” or “curcumin extract” and “metabolic syndrome” or “metabolic syndromes” or “syndrome, metabolic” or “syndromes, metabolic” or “metabolic syndrome X” or “insulin resistance syndrome X” or “syndrome X, metabolic” or “syndrome X, insulin resistance” or “metabolic X syndrome” or “syndrome, metabolic X” or “X Syndrome, metabolic” or “dysmetabolic syndrome X” or “Reaven syndrome X” or “syndrome X, Reaven” or “metabolic cardiovascular syndrome” or “cardiovascular syndrome, metabolic” or “syndrome, metabolic cardiovascular” or “cardiometabolic syndrome” or “cardiometabolic syndromes” or “syndrome, cardiometabolic” or “insulin resistance syndrome x” or “insulin resistance” or “metabolic diseases” or “plurimetabolic syndrome” or “syndrome x plus”, and “randomized controlled trial” or “randomized” or “placebo” or “RCTs”. In order to include any relevant studies that may not have been captured in the initial database search, a thorough examination of the reference lists of potentially eligible literature was conducted.
Research selection
The studies included in the present analysis met the following inclusion criteria (1): participants of both genders aged 18 years or older, (2) diagnosed with metabolic syndrome according to either NCEP-ATP III or IDF guidelines (31), (3) evaluated the effects of curcumin on at least one metabolic, inflammatory, or oxidative stress marker, and (4) provided data on the baseline and endpoint measurements for both intervention and control groups or reported changes within each group. When there were numerous reports regarding the identical population under study, the most comprehensive dataset was examined. There were no exclusions based on the individuals’ race or sexual orientation (Table 1).
The following exclusion criteria were applied: (1) trials without specific restrictions, (2) studies with a duration of less than 4 weeks, (3) participants taking antihypertensive, antidyslipidemic, or antidiabetic medications, (4) insufficient data reported in the included studies, and (5) participants with malignancies or other systemic or chronic diseases unrelated to diabetes.
| Inclusion criteria | |
|---|---|
| Participants | Patients with a diagnosis MetS |
| Interventions | The intervention group was given curcumin supplementation (unlimited dose, dosage form, or duration) |
| Comparisons | The control group was treated with placebo or blank |
| Outcomes | WC, FBS, SBP, DBP, TG, HDL-C, TNF-a, IL-6, CRP, hsCRP, and MDA |
| Study type | RCTs assessing the effects of curcumin supplementation on MetS |
Data extraction and quality assessment
After removing any duplicate entries, two reviewers individually evaluated the remaining records for qualification using the titles and abstracts. Subsequently, the reviewers individually selected potentially eligible literature in full text for inclusion in the present study. The title of the initial author, the publishing year, the location, the number of participants (in the intervention and placebo arms), the MetS diagnostic criteria, the participants’ ages and genders, the intervention dose, the length of the study, the reported side effects, and the results were all extracted by two reviewers.
Using the method suggested by the Cochrane Handbook V.5.1.0 (32), two writers independently evaluated the included randomized controlled trials’ (RCTs) risk of bias. Seven categories were considered during the evaluation, including the blinding of participants and staff, the blinding of the result evaluation, bad outcome data, selective reporting, and other biases. According to the recommendations in the Cochrane Handbook, each item was awarded a risk-of-bias score that ranged from moderate to high to unclear. In addition, STATA 15.1 software was used to plot funnel plots for determining the presence of publication bias.
Statistical analysis
Review Manager was used for every analysis (RevMan 5.4; Cochrane Collaboration, Copenhagen, Denmark) (33). In comparison to the controls, curcumin’s effects on metabolic indices and inflammatory marker results were expressed as mean differences (MD) and reported with corresponding 95% confidence intervals (CI). For all data, a p-value less than 0.05 was regarded as statistically significant. The heterogeneity was assessed by inconsistency(I2) and chi-square tests. High heterogeneity between studies was considered when the heterogeneity p <0.1 and I2 ≥ 50%. Conversely, low heterogeneity was considered when these criteria were not met. By removing one study at a time and redoing the analysis, a sensitivity analysis was performed. Subgroup analyses were also conducted by sample size and intervention duration based on the features of the included studies.
Results
Selection of trials
The explicit research screening process is shown in Figure 1. The preliminary database retrieval and the additional retrieval yielded a total of 691 records, with 434 articles being excluded for duplicated records. A total of 241 items were eliminated after reading the titles and abstracts in accordance with the inclusion and exclusion criteria. After reading the full texts of 16 studies, two studies were excluded due to non-compliant outcome indicators, and one study had missing data. This resulted in the inclusion of 13 randomized controlled studies with 785 patients (21–24, 34–42).
Flow diagram of the literature screening process and results.
Research characteristics
Table 2 provides an overview of the trials that were taken into consideration. All 13 studies included in the analysis were parallel RCTs conducted between 2014 and 2022. Iran (n = 10) accounted for the majority of the trials, followed by Pakistan (n = 1), China (n = 1), and Italy (n = 1). The total sample size included 785 MetS participants (373/412, male/female). Two cohorts contained exclusively male (34, 36) participants, and two cohorts consisted of only female (24, 35) participants. The trials ranged in length from 4 to 12 weeks, with two lasting 4 weeks (21, 38), three lasting 6 weeks (24, 35, 41), four lasting 8 weeks (34, 36, 39, 40), and four lasting 12 weeks (22, 23, 37, 42).
| Author, year | Location | MetS diagnostic criteria | Age (intervention/control) | No. of participant (intervention/control) | Sex (female/male) | Type of intervention/placebo | Dose of intervention (mg/day) | Duration of study (weeks) | Side effects | Outcome |
|---|---|---|---|---|---|---|---|---|---|---|
| Salimi, 2017 | Iran | NCEP-ATP III | Mean age, 48 | 10/10 | 20/0 | Curcumin/placebo | 20 mg/kg | 8 | None | BMI, weight, WC, FBG, FAT%, BP, HDL-C, TG, TNF-α, |
| Alidadi, 2021 | Iran | IDF | 42.84 ± 6.25/44.43 ± 5.92 | 32/28 | 29/31 | Curcumin/placebo | 500 | 12 | None | BMI, WC, NC, FM, VFA, weight, FPG, TC, TG, HDL-C, LDL-C, SBP, DBP |
| Amin, 2015 | Pakistan | NCEP-ATP III | 42.4 ± 13.7/41.57 ± 12.8 | 56/52 | 108/0 | Supplement of turmeric powder/spaghula husk capsule | 2,400 | 8 | Dyspepsia | BMI, weight, WC, HC, SBP, DBP, FBG, LDL, HDL, TG, CRP |
| Bateni, 2021 | Iran | NCEP-ATP III | 50 ± 9/54 ± 7 | 22/21 | 10/33 | Nana-micelle curcumin/placebo | 80 | 12 | None | BMI, weight, WC, total body fat%, total body muscle%, SBP, DBP, FBS, HbA1c, Insulin, TG, TC, LDL-C, HDL-C |
| Pierro, 2015 | Italy | NCEP-ATP III | 39.10 ± 16.8/41.85 ± 15.91 | 22/22 | 17/27 | Curcumin supplement/phosphatidylserine | 800 | 4 | None | BMI, Weight, WC, HC, FAT% |
| Osali, 2020 | Iran | NCEP-ATP III | Mean age, 62.3 ± 1.23 | 11/11 | 0/22 | Nano-curcumin/placebo | 80 | 6 | None | BMI, Weight, WC, Glucose, SBP, TG, HDL, body fat%, MDA, CRP, IL-6, IL-10 |
| Panahi, 2015 | Iran | NCEP-ATP III | 44.80 ± 8.67/43.46 ± 9.7 | 50/50 | 50/50 | Curcuminoids–piperine/placebo | 1,000 | 8 | None | hsCRP, MDA, SBP, DBP, FBS, HbA1c |
| Saberi-Karimian,2018 | Iran | IDF | 37.52 ± 9.47/38.59 ± 10.28 | 36/36 | 11/61 | Curcumin/placebo | 1,000 | 6 | None | Weight, BMI, WC, FBG, hsCRP, FAT%, SBP, DBP, LDL-C, HDL-C, TC, TG, T-Chol, Apo A, Apo B |
| Yang, 2014 | Iran | NCEP-ATP III | 59.03 ± 10.1/59.61 ± 14.09 | 30/29 | 23/36 | Curcumin extract/placebo | 1,890 | 12 | Stomach pain, mild diarrhea, nausea | Weight, BMI, TG, T-Chol, FPG, HDL-C, LDL-C, T-Chol, VLDL, HbA1c |
| Bateni, 2022 | Iran | NCEP-ATP III | 50 ± 9/54 ± 7 | 22/21 | 10/33 | Nana-micelle curcumin/placebo | 80 | 12 | None | TAC, MDA, hsCRP, NF-kB |
| Panahi, 2016 | Iran | NCEP-ATP III | 44.80 ± 8.67/43.46 ± 9.7 | 50/50 | 50/50 | Curcuminoids–piperine/placebo | 1,000 | 8 | Gastrointestinal | TNF-α, IL-6, TGF-β, MCP-1 |
| Zhang, 2019 | China | NCEP-ATP III | 66.9 ± 14.1/68.1 ± 12.3 | 46/46 | 45/47 | Curcumin/control | 1,500 | 4 | None | TC, TG, FPG, LDL-C, HDL-C |
| Osali, 2018 | Iran | NCEP-ATP III | Mean age, 62.3 ± 1.23 | 11/11 | 0/22 | Nano-curcumin/placebo | 80 | 6 | None | TNF-α |
Risk of bias
Figure 2 demonstrates that three studies were assigned a low risk of bias due to extensive reporting of information on each item, while 10 trials were given an uncertain risk of bias due to insufficient reporting. Among the included studies, 10 RCTs had insufficient information regarding the random sequence generation method (21, 22, 24, 34, 35, 38–42), and 10 RCTs had imperfect allocation concealment information (21, 22, 24, 34, 35, 38–42). The design and blinding implementation of three RCTs were not clear (21, 34, 38).
Risk assessment of the included studies.
Results of the meta-analysis
Waist circumference
Seven trials (22–24, 34, 36, 38, 41) gave waist circumference data without heterogeneity (p = 0.97, I2 = 0%); hence, a fixed-effects model was used. The outcomes demonstrated that, as a consequence of reducing WC, the intervention group surpassed the control group (MD = -2.16, 95% CI: -3.78 to -0.54, p = 0.009) (Figure 3).
Effect of curcumin supplement on waist circumference.
Fasting blood sugar
Nine trials (21–24, 34, 36, 39, 41, 42) showed statistically significant heterogeneity in fasting glucose outcomes (p = 0.0005, I2 = 71%) and therefore used a random-effects model. The findings demonstrated that the experimental group fared better in decreasing the FBS than the placebo group (MD = -8.6, 95% CI: -15.45 to -1.75, p = 0.01) (Figure 4).
Effect of curcumin supplement on fasting blood sugar.
Blood pressure
A fixed-effects model was used to analyze the results, which revealed that the intervention group outperformed the control group in lowering the diastolic blood pressure (MD = -2.8, 95% CI: -4.53 to -1.06, p = 0.002) (Figure 5). A total of five studies (22, 23, 36, 39, 41) reported diastolic blood pressure outcomes without statistically significant homogeneity (p = 0.16, I2 = 40%).
A total of six studies (22–24, 36, 39, 41) reported statistically significant heterogeneity in SBP outcomes (p = 0.0004, I2 = 78%) and therefore used a random-effects model. According to the findings, curcumin had a negligible impact on SBP (MD = -4.82, 95% CI: -9.98 to 0.35, p = 0.07) (Figure 6).
Triglycerides
Eight studies (21–24, 34, 36, 41, 42) showed triglyceride outcomes with no statistically significant heterogeneity (p = 0.21, I2 = 27%). As such, the results of a fixed-effects model demonstrated that curcumin’s influence did not significantly lower the TG (MD = 1.28, 95% CI: -3.75 to 6.30, p = 0.62) (Figure 7).
Effect of curcumin supplement on triglycerides.
High-density lipoprotein cholesterol
Eight trials (21–24, 34, 36, 41, 42) demonstrated significant heterogeneity in the outcomes related to HDL cholesterol (p = 0.001, I2 = 71%). By employing a random-effects model, the data indicated that the intervention group had a more pronounced effect in increasing HDL cholesterol levels compared with the placebo group (MD = 4.98, 95% CI: 2.58 to 7.38, p < 0.0001) (Figure 8).
Effect of curcumin supplement on high-density lipoprotein cholesterol.
Inflammation indicators
Two studies (24, 40) reported statistically significant heterogeneity in the results for interleukin 6 (IL-6) (p = 0.02, I2 = 81%). Thus, the results of a model with random effects showed that curcumin had no discernible impact on IL-6 (MD = -1.5, 95% CI: -3.97 to 0.97, p = 0.23) (Figure 9A).
The tumor necrosis factor-a (TNF-a) results from two trials (35, 40) reported high homogeneity (p = 0.004, I2 = 88%). After employing a model with random effects, the outcomes revealed that the intervention group surpassed the control group in lowering the TNF-a (MD = -12.97, 95% CI: -18.37 to -7.57, p < 0.00001) (Figure 9B).
Based on the results of two studies (24, 36), which did not show statistically significant heterogeneity for C-reactive protein (CRP) outcomes (p = 0.58, I2 = 0%), a fixed-effects model was used. The findings indicated that the intervention group exhibited a greater reduction in CRP levels compared with the control group (MD = -1.24, 95% CI: -1.71 to -0.77, p < 0.00001) (Figure 9C).
Two studies (37, 39) reported statistically significant homogeneity (p < 0.00001, I2 = 98%) in the results for ultrasensitive C-reactive protein (hsCRP). After employing a model with random effects, the findings revealed that the effect of curcumin did not significantly alter the hsCRP (MD = -1.10, 95% CI: -4.35 to 2.16, p = 0.51) (Figure 9D).
Effect of curcumin supplement on inflammation indicators:IL-6,TNF-a,C-reactive protein, andhsCRP. (A) (B) (C) (D)
Oxidative stress marker
Three studies (24, 37, 39) reported statistically significant heterogeneity (p < 0.00001, I2 = 92%) in the results for malondialdehyde (MDA). Using a random-effects model, the results showed that the intervention group was superior to the control group in reducing MDA (MD = -2.35, 95% CI: -4.47 to -0.24, p = 0.03) (Figure 10).
Effect of curcumin supplement on malondialdehyde.
Adverse events
A total of three studies (36, 40, 42) reported mild gastrointestinal and digestive adverse effects, mainly including diarrhea, nausea, and constipation, which could be attributed to the high daily dose of curcumin.
Publication bias
Publication bias was assessed for WC as an outcome indicator using a funnel plot. The Begg’s test yielded a p-value of 0.548, and the Egger’s test yielded a p-value of 0.946. The results suggest that there was no substantial publication bias among the included studies. The funnel plot is shown in Figure 11.
Publication bias.
Sensitivity analysis
Significant heterogeneity was observed in studies reporting FBS, SBP, and HDL-C. As such, sensitivity analyses were performed to identify the potential causes. The sensitivity analysis indicated that the study by Osai et al. (2020) had a notable influence on the heterogeneity of the FBS and SBP outcomes. However, after removing the study from the analysis, the heterogeneity became non-significant (). For the heterogeneous results of HDL-C, no single study interfered with the results when any single study was excluded (). 1 1
Subgroup analysis
The results of the subgroup analyses by sample size or duration did not differ from those of the overall analyses of FBS, SBP, DBP, TG, and HDL-C. (). The only exception was a significant increase in HDL-C in trials with a duration less than or equal to 6 weeks compared with trials with a duration greater than 6 weeks (). The subgroup analyses by duration or sample size showed differences from the overall analysis of WC, which did not change significantly in trials with durations greater than 6 weeks () or in trials with less than 60 patients (). 1 1 1 1
GRADE assessment
The GRADE tool was used to rate the evidence for the 11 outcome indicators (WC, FBS, DBP, SBP, TG, HDL-C, IL-6, TNF-a, CRP, hsCRP, and MDA). The evidence was categorized as “moderate”, “low”, or “very low” based on specific reasons for downgrading, such as a high risk of bias, inconsistency, and imprecision. The detailed ratings and reasons for downgrading can be found in Table 3.
| Outcomes | No. of participants(studies) | Anticipated absolute effects(95% CI) | Relative effect (95% CI) | Certainty of the evidence (GRADE) | |
|---|---|---|---|---|---|
| Risk with CG | Risk difference with EG | ||||
| WC | 369 () [7] | The mean WC ranged from 95.9 to 107.85 | The mean WC in the EG was 2.16 lower (3.78 to 0.54 lower) | – | ⊕⊕○○LOWa,b |
| FBS | 576 () [9] | The mean FBS ranged from 96.28 to 182.1 | The mean FBS in the EG was 8.6 lower (15.46 to 1.74 lower) | – | ⊕⊕○○LOWa,c |
| DBP | 383 () [5] | The mean DBP ranged from 76.18 to 85.1 | The mean DBP in the EG was 2.8 lower (4.53 to 1.06 lower) | – | ⊕⊕○○LOWa,b |
| SBP | 405 () [6] | The mean SBP ranged from 108.11 to 152.7 | The mean SBP in the EG was 4.82 lower (9.98 to 0.35 lower) | – | ⊕⊕○LOWa,c |
| TG | 476 () [8] | The mean TG ranged from 26.28 to 224.09 | The mean TG in the EG was 1.28 higher (3.75 lower to 6.3 higher) | – | ⊕⊕⊕○MODERATE 3 |
| HDL-C | 476 () [8] | The mean HDL-C ranged from 25.74 to 49.42 | The mean HDL-C in the EG was 1.28 higher (2.58 to 7.38 higher) | – | ⊕⊕○○LOWa,c |
| IL-6 | 122 () [2] | The mean IL-6 ranged from 1.81 to 18.68 | The mean IL-6 in the EG was 1.50 lower (3.97 lower to 0.97 higher) | – | ⊕○○○VERY LOWa,b,c |
| TNF-a | 122 () [2] | The mean TNF-a ranged from 36.52 to 78.9 | The mean TNF-a in the EG was 12.97 lower (18.37 to 7.57 lower) | – | ⊕○○○ LOWa,b |
| CRP | 130 () [2] | The mean CRP ranged from 2.31 to 2.8 | The mean CRP in the EG was 1.24 lower (1.71 to 0.77 lower) | – | ⊕⊕○○LOWa,b |
| hsCRP | 143 () [2] | The mean hsCRP ranged from 1.006 to 1.49 | The mean hsCRP in the EG was 1.10 lower (4.35 lower to 2.16 higher) | – | ⊕○○○ VERY LOWa,b,c |
| MDA | 165 () [3] | The mean MDA ranged from 2.81 to 19.78 | The mean MDA in the EG was 2.35 lower (4.47 to 0.24 lower) | – | ⊕○○○ VERY LOWa,b,c |
Discussion
The effects of curcumin supplementation on WC, FBS, BP, TG, and HDL levels and inflammatory markers (IL-6, TNF-a, CRP, and hsCRP) in MetS patients were assessed by analyzing 13 randomized controlled trials. The minimum duration of the studies was 4 weeks, and the maximum duration was 12 weeks. The results of the present study show significant improvements in WC, FBS, DBP, HDL, and inflammatory markers (TNF-a and CRP) levels. However, there were no significant changes observed in SBP, TG levels, IL-6, and hsCRP.
In comparison with a previous systematic evaluation (19), the present results differ in terms of waist circumference, and curcumin supplementation was found to significantly reduce waist circumference. The reason for such findings could be attributed to the inclusion of new studies to increase the sample size. As has been previously demonstrated, the pathophysiological mechanism of MetS involves systemic oxidative stress brought on by central obesity (43–45), and waist circumference is a significant indicator of abdominal obesity and a proxy for visceral adipose tissue (46). Waist circumference plays a crucial role in adult metabolic syndrome early detection and the prediction of insulin resistance (47). Studies have confirmed that WC, similar to body mass index (BMI), is associated with BP, insulin resistance, and blood lipids (48). According to epidemiological research, visceral adiposity is a substantial major risk for insulin resistance, cardiovascular disease, stroke, MetS, and mortality (49). Therefore, a reduction in waist circumference can help improve the metabolic index of metabolic syndrome and reduce mortality. Through inhibiting differentiation medium-induced β-catenin downregulation and downregulating the expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT enhancer binding protein α(C/EBPα), the process may contribute to reducing lipid accumulation in 3T3-L1 adipocytes (50).
Furthermore, the impact of curcumin administration on MetS inflammatory and oxidative stress biomarkers was thoroughly examined. A previous systematic review found that curcumin supplementation improved the inflammation and oxidative stress in obesity, diabetes, and NAFLD (29). However, no studies have been conducted to independently perform a meta-analysis on the co-occurrence of metabolic syndrome, inflammation, and oxidative stress. Notably, curcumin supplementation was found to significantly improve TNF-a, but not hsCRP. The two studies included in the analysis of hsCRP were found to differ in the dose of curcumin used and the duration of the intervention, with Bateni et al. (37) using 80 mg of nanocurcumin per day for 12 weeks and Pahahi et al. (2015) using 1,000 mg of curcumin per day for 8 weeks. One study found that a 10-week intervention with 1,500 mg of curcumin daily in type 2 diabetes significantly improved the hsCRP level (51), and another study showed that a 12-week intervention with nano-curcumin in patients with NAFLD significantly improved the hsCRP level (52). Based on such findings, the present authors believe that metabolic syndrome, as a complex metabolic disorder, may require larger doses of curcumin supplementation to achieve a significant improvement in hsCRP. In the present study, there was a significant improvement in TNF-a and CRP inflammatory indexes with curcumin supplementation. The present study encompasses all available research on the association between curcumin supplementation and inflammation as well as oxidative stress in individuals with MetS. Moreover, a broader range of clinical outcome measures related to curcumin supplementation in patients with metabolic syndrome was evaluated, thereby offering additional evidence-based insights.
Curcumin is significant for the improvement of inflammatory and oxidative stress indicators. While the exact pathophysiology of metabolic syndrome remains unclear, there are widely acknowledged potential pathways that contribute to its development. Such pathways include insulin resistance and the presence of chronic low-grade inflammation, which are commonly associated with central obesity (53, 54). Chronic inflammation also interacts with oxidative stress (55). The majority of MetS patients are asymptomatic, but according to the Framingham Risk Score (56), they have a 16% to 18% chance of experiencing their first coronary event within a 10-year timeframe, which raises their risk of cardiovascular disease by fivefold and their risk of type 2 diabetes by twofold (57). Inflammation can also produce insulin resistance directly or indirectly; therefore, various inflammatory markers are considered as reliable MetS biomarkers. The administration of curcumin, which leads to improvements in inflammatory and oxidative stress markers, not only enhances the overall condition of patients with MetS but also reduces the likelihood of developing cardiovascular disease.
In the obese state, adipocyte hypertrophy and overcrowding lead to the hypoxic necrosis of cells, and necrotic adipocytes attract mononuclear macrophages to cluster, and the number of macrophages in adipose tissue increases from 10%–15% to 40%–50%, leading to the infiltration of macrophages. Such infiltration induces the macrophages to polarize to M1-type pro-inflammatory phenotype and generate and emit inflammatory substances such TNF-a, IL-1, and nitric oxide synthase (NOS2), among others, which, in turn, regulate local and systemic inflammation (58, 59). These inflammatory factors further activate the macrophages and impair insulin signaling in adipocytes, leading to systemic insulin resistance (60). According to epidemiology, patients with diabetes mellitus (DM), hypertension, atherosclerosis, and cardiovascular events had increased levels of IL-6 and TNF-a (45). Thus, an assumption could be made that the possible mechanism of curcumin treatment of MetS involves reducing chronic inflammation and oxidative stress by regulating macrophage polarization.
First, to our knowledge, the present research represents the first meta-analysis of curcumin’s impact on inflammatory and oxidative stress markers in MetS. Second, in the present study, the sample size was expanded by including new studies on the basis of previous meta-analyses. Third, bias was decreased to a certain extent because only randomized controlled clinical trials were included. Fourth, the robustness of the findings was demonstrated through sensitivity analyses in which each study was omitted one at a time, indicating that the conclusions were reliable. Fifth, to evaluate the potential research characteristics of the association between curcumin supplementation and metabolic syndrome, subgroup analyses of intervention duration and the sample size were conducted.
However, the present study also has several limitations. First, although the present study was not restricted to language and region, 12 of the 13 included studies were from Asian countries, including as many as 10 studies from Iran. The generalizability of the results needs to be further verified. Second, despite being the first meta-analysis conducted on the impact of curcumin on inflammatory and oxidative stress markers in individuals with MetS, the credibility of the results was somewhat compromised due to the limited number of publications included in the study. Third, there was a higher risk of bias in the research since two of the included studies had only male participants and two studies had only female participants. Fourth, the use of products that favorably enhance the bioavailability of curcumin (including piperine or alkaloids) was not excluded. Fifth, the limited amount of research available did not allow for a breakdown of the dosage of curcumin utilized in the smaller groups. Sixth, one of the studies included in the analysis used a combination of curcumin and black seed extract. Nigella sativa seed extract had a beneficial effect on MetS, which may have caused a bias in the analysis.
Conclusion
The present meta-analysis demonstrates that curcumin supplementation has a positive impact on MetS patients. Future randomized controlled studies should focus on addressing the limitations identified in the present analysis. Future research should aim to include larger sample sizes that encompass diverse ethnic groups, consider gender differences, and explore various forms of curcumin supplements to ensure high bioavailability. In addition, more thorough research is required to determine how curcumin affects inflammatory and oxidative stress indicators in metabolic syndrome. Further exploration is needed to better understand the mechanisms by which curcumin may be effective in treating metabolic syndrome.
Author contributions
LQ and JZ conceptualized the research question. CG and YR participated in drafting and writing the review. CG, HW, and YR participated in the formulation of retrieval strategies, data acquisition, data analysis, and quality assessment. JL and ML participated in the drawing of tables and figures. XD and WL participated in the critical revision of the manuscript. All authors contributed to the article and approved the submitted version.