Mohamed T. El-Saadony, Zagazig University, Egypt

REVIEWED BY

Ahmed M. Saad, Zagazig University, Egypt Fawze Alnadari, Research and Development Center of Jiangsu Tianmeijian Nature Bioengineering Co. Ltd., China Dina Mostafa Mohammed, National Research Centre, Egypt

*CORRESPONDENCE

Jiao Wu,

[email protected] Yu Wu,

[email protected] Zhongyu Li,

[email protected]

†These authors have contributed equally to this work

RECEIVED 29 March 2025 ACCEPTED 26 May 2025 PUBLISHED 05 June 2025

CITATION

Xu Q, Lian H, Zhou R, Gu Z, Wu J, Wu Y and Li Z

(2025) Curcumin and multiple health outcomes: critical umbrella review of intervention meta-analyses.

Front. Pharmacol. 16:1601204. doi: 10.3389/fphar.2025.1601204

COPYRIGHT

© 2025 Xu, Lian, Zhou, Gu, Wu, Wu and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Qin Xu1†, Hua Lian1†, Rui Zhou1, Zhenzhen Gu1, Jiao Wu2*, Yu Wu1* and Zhongyu Li3*

1. 1Department of Oncology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China,
2. 2Department of Oncology, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China, 3Department of Traditional Chinese Medicine Internal Medicine, Eye Hospital, China Academy of Chinese Medical Sciences, Beijing, China

Objective: This review aimed to determine the therapeutic effects and safety of oral curcumin compared with other comparators for human health and wellbeing outcomes.

Methods: PubMed, Embase, and Cochrane Library were searched from their inception to 18 June 2024. The Assessment of Multiple Systematic Reviews-2 checklist, and Grading of Recommendations, Assessment, Development and Evaluation system were used to assess the methodological and evidence quality for each meta-analysis, respectively. The results are presented in a narrative review.

Results: We included 25 studies. The overall methodological quality was relatively poor, and there is considerable room for improvement. The findings suggest that curcumin has potentially positive effects on lipid profiles, blood pressure, inflammatory markers and oxidative stress, musculoskeletal diseases, emotional and cognitive function, ulcerative colitis, liver and kidney function, primary dysmenorrhea or premenstrual syndrome, rheumatoid arthritis, COVID19, painful statues, and HR-QOL. However, for many diseases, the conclusions remain uncertain.

Conclusion: The available evidence suggests that curcumin is a safe medicinal agent that improves multiple clinical outcomes; however, the scientific quality of published studies needs to be improved.

KEYWORDS

curcumin, metabolic indicators, health outcomes, evidence, meta-analysis, umbrella review

Curcumin, a natural compound derived from the rhizome of the turmeric plant (Curcuma Longa), has garnered significant attention for its health-promoting properties over the years (Ayub et al., 2024). It is particularly popular among residents of India and Southeast Asian countries (Kasprzak-Drozd et al., 2024). The present studies have found that curcumin has various pharmacological effects, including anti-inflammatory (Zhang et al., 2025), antioxidant (Nirgude et al., 2025), and immune response modulation (Gouda et al., 2024). These properties have promoted the exploration of its use as a potential drug

for treating various chronic diseases. For instance, curcumin has demonstrated significant beneficial effects in musculoskeletal diseases (Jamali et al., 2020), gastrointestinal diseases (Ben-Horin et al., 2024), and mood or anxiety disorders (Asadi et al., 2020). Additionally, curcumin targets multitude signaling pathways and exerts cellular-level effects, making it a versatile supplement for various health conditions.

Specifically, curcumin’s antioxidant properties are attributed to scavenging free radicals and enhancing endogenous antioxidant defenses (Wang et al., 2024a). The anti-inflammatory benefits of curcumin are associated with pain reduction (Zhang et al., 2024) and mucosal protective effects in ulcerative colitis (Sadeghi et al., 2020; Wang et al., 2024b). Curcumin has been proven to inhibit cholesterol production and adipogenesis, thereby regulating lipid profiles and aiding in weight management (Shao et al., 2012). Furthermore, curcumin compounds have been shown to have actions similar to antidiabetic agents, reducing insulin resistance (Li et al., 2020), and interacting with the gut microbiota (Gu et al., 2024). Moreover, clinical practice guidelines have acknowledged the therapeutic value of curcumin, particularly in managing osteoarticular pain, making it among the most prescribed supplements for this condition (Liu et al., 2018; Mobasheri et al., 2024).

In recent decades, the popularity of curcumin supplements has surged, driven by widespread promoting in folk media, and the growing use of turmeric dietary supplements. In fact, turmeric has become the best-selling botanical dietary supplement in the United States (Panknin et al., 2023). The medicinal therapeutic value, diverse functionality, and rapid development of curcumin have driven considerable growth in the number of clinical trials worldwide (Yeung et al., 2019; Zhang et al., 2022). However, despite the abundance of clinical studies and mechanistic research supporting the health benefits of curcumin, there is a lack of high-quality integrated studies to determine which health effects are most strongly supported by evidence.

In evidence-based healthcare settings, systematic reviews and meta-analyses are vital for developing clinical practice guidelines and guiding clinical decision-making (Weissgerber, 2021). In particular, umbrella review serves as an effective method to assess the scientific quality of published systematic reviews and to summarize clinical evidence reported in domain-specific meta-analyses (Aromataris et al., 2015). This approach has been successfully applied to other natural products and dietary agents, including berberine (Li et al., 2023), anthocyanins (Sandoval-Ramírez et al., 2022), and tea (Keller and Wallace, 2021). Given the extensive research on curcumin’s health benefits and the need for a comprehensive synthesis of the available evidence, our review aimed to systematically identify and evaluate the therapeutic efficacy and safety of oral curcumin than any comparator for several human health and wellbeing outcomes. We hypothesize that curcumin will demonstrate significant therapeutic benefits across multiple health domains, supported by high-quality evidence from well-conducted systematic reviews and meta-analyses.

The umbrella review is a novel method for deliberately searching, integrating and appraising available evidence on

specific exposures and health outcomes among systematic reviews and/or meta-analyses (Aromataris et al., 2015). To provide a comprehensive evaluation of the therapeutic effect of curcumin, therefore, we only included systematic reviews with meta-analyses.

1. 2.1 Screening and search strategy
2. 2.2 Inclusion and exclusion criteria
3. 2.3 Data extraction
4. 2.4 Quality assessment of included studies

We referred to the relevant literature and used the Assessment of Multiple Systematic Reviews (AMSTAR)-2 checklist, the revised

version of which was officially published by the AMSTAR Working Group in 2017, for methodological quality assessment (Shea et al., 2017). AMSTAR-2 checklist includes 16 items covering selecting topics, design, registration, data extraction, statistical analysis, and discussion of meta-analyses. Specifically, ‘Yes’ (Y), ‘Partial Yes’ (PY), or ‘No’ (N) were used to answer item-related questions. The AMSTAR-2 checklist classified the methodological quality into four levels: high, moderate, low, and critically low levels.

We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework to assess the quality of evidence for each outcome (Guyatt et al., 2011). The GRADE system provides explicit criteria for grading the quality of evidence, including the risk of bias (RoB), inconsistency, indirectness, imprecision, and publication bias. We created an evidence map exhibiting the plausible benefits and the certainty of evidence for each intervention. The certainty of the evidence was assessed using the GRADE methodology (GRADEpro GDT) (https://gdt.gradepro.org/app/) and categorized evidence as high, moderate, low or very low credibility. Finally, the two reviewers (J. W. and Z.Z.G.) cross-checked the quality assessment and reached a consensus. Any disagreements were resolved by a third reviewer (Y.W.).

2.5 Statistical analysis

We extracted the necessary data (for example, estimated effects and 95% confidence interval (CI) for meta-analyses, p-values) directly from meta-analyses for narrative review. I2 statistics were used to assess heterogeneity between studies. Funnel plots, Egger’s

test, and Begg’s test were used to assess publication bias. Statistical significance was set at two-sided p < 0.05.

1. 3.1 Findings of study screening
2. 3.2 Research characteristics

Table 1 summarizes the characteristics of the included metaanalyses. The articles were published between 2016 and 2024. The meta-analyses were from six regions: 16 from Iran, six from China, and the remaining were from Australia, Singapore, and India. Only nine meta-analyses were registered on the PROSPERO platform and reported their registration number, but the remaining reviews failed

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Abbreviations: NA: not available; I: intervention; C: comparator; T2DM, Type 2 diabetes mellitus; HbA1c, hemoglobin A1c; NAFLD, nonalcoholic fatty liver disease; FBG: fasting blood glucose; HOMA-IR: homeostatic model assessment for insulin resistance; QUICKI: quantitative insulin-sensitivity check index; PCOS: polycystic ovarian syndrome; INS: insulin; OGTT: oral glucose tolerance test; SBP: systolic blood pressure; DBP: diastolic blood pressure; VCAM-1: vascular cell adhesion molecule-1; FMD: PWV: pulse wave velocity; TC: total cholesterol; TG: triglyceride; LDL-C: low-density-lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; Apo-A: apolipoproteins A; Apo-B: apolipoproteins B; BMI: body mass index; CRP: C-reactive protein; TNFtumor necrosis factor-alpha; IL-6: interleukin-6; IL-1β: interleukin 1beta; IL-8: interleukin-8; RA: rheumatoid arthritis; TAC: total antioxidant capacity; MDA: malondialdehyde; SOD: superoxide dism neurotrophic factor; WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index; VAS: visual analogue scale; ALT: alanine aminotransferase; AST: aspartate aminotransferase; GGT: gamma-glutamyltransferase; DHEA: dehydroepiandrosteronesulfate; LH: luteinizing hormone; FSH: follicle-stimulating hormone; FAI: free androgen index; PMS: premenstrual syndrome.

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to provide registration details. The number of primary clinical trials in the meta-analyses rangedfrom3 to66, and the numberof participants ranged from 139 to 4,051. The Cochrane RoB assessment tool was the most commonly used to evaluate methodological quality, with one review each in the Jadad score and JBI Critical Appraisal Checklist, and two articles that did not report the tool used to assess methodological quality. Sixteen meta-analyses included only placebo-controlled trials, and the other meta-analyses included placebo, routine care, or medication as comparators. The curcumin dose varied considerably across the original studies, ranging from 50 to 6,000 mg. The treatment duration of curcumin interventions ranged from 1 day to 12 months in the meta-analyses.

methodological quality of each systematic review can be rated as high (no or one non-critical weakness), moderate (more than one non-criticalaw), low (one critical weakness or without a non-critical weakness), or critically low (more than one criticalaw or no non-flfl

Note: AMSTAR-2: Assessment of Multiple Systematic Reviews (AMSTAR)-2; Y: yes; N: no; P: partial yes. AMSTAR-2 consists of 16 items, seven of which (items 2, 4, 7, 9, 11, 13, and 15) are critical domains. Based on the critical and non-critical items, the overall

H YPYNNNYPYNYYYYYNCritically low

Overall

rating

(100%) 19 (76%)13 (52%)20 (80%)17 (68%)24 (96%)

N2%)10 (40%)04 (16%)4 (16%)11 (44%)3 (12%)2 (8%)24 (96%)06 (24%)12 (48%)5 (20%)8 (32%)1 (4%)

P%)011 (44%)0001 (4%)3 (12%)0000000

1. 3
2. 4
3. 5
4. 6
5. 7
6. 8
7. 9
8. 10
9. 11
10. 12
11. 13
12. 14
13. 15
14. 16

1. 3.3 Methodological quality
2. 3.4 Therapeutic efficacy and safety of curcumin

Y0%)15 (60%)14 (56%)21 (84%)21 (84%)14 (56%)21 (84%)20 (80%)1 (4%)25

TABLE 2 (Continued) Quality appraisal results of included systematic reviews using the AMSTAR-2 Tool.

Supplementary Table S2 lists meta-analyses evaluating the effect of curcumin on each human outcome, as reported in the included systematic reviews. These results are more simply presented in Figure 2.

3.4.1 Metabolic indicators

1. 3.4.1.1 Glucose metabolic and insulin secretion Three meta-analyses have evaluated the effects of curcumin on
2. 4.61, −1.06; I2 = 51.3%), homeostatic model assessment for insulin resistance (HOMA-IR) (WMD: 0.52; 95%CI: 0.84, −0.20; I2 = 82.8%), but not including HbA1c (WMD: 0.17; 95%CI: 0.44, 0.11, I2 = 92.4%), insulin levels (WMD: 0.14; 95%CI: 1.03, 0.76; I2 = 83.0%) and quantitative insulin-sensitivity check index (QUICKI) (WMD: 0.01; 95%CI: 0.00, 0.01; I2 = 96.2%) compared with placebo

CItem

critical weakness).

(Ebrahimzadeh et al., 2024). In patients with polycystic ovarian

S

syndrome (PCOS), curcumin reduced FBG (WMD: 3.618; 95%CI:

1. 5.165, −2.071; I2 = 20.4%), and insulin levels (WMD: 1.834; 95%CI:

1. 2.701, −0.968; I2 = 8.4%) (Shen et al., 2022). Moreover, it observed improvement on QUICKI (WMD: 0.011, 95%CI: 0.005, 0.017; I2 = 39.6%) and HOMA-IR (WMD: 0.565; 95%CI: 0.779, −0.351; I2 = 0.0%), but not including blood glucose at 2 h after oral glucose tolerance test (OGTT) (WMD: 0.063, 95%CI: 2.307, 2.181; I2 = 87.4%), insulin at 2 h after OGTT (WMD: 12.445; 95%CI: 44.384, 19.494; I2 = 0.0%) and HbA1c (WMD = −0.042, 95%CI: 0.471, 0.387, I2 = 56.8%) (Shen et al., 2022).
2. 3.4.1.2 Blood pressure and endothelial function Two meta-analyses evaluated the effects of curcumin on blood

pressure and endothelial function (Dehzad et al., 2024; Ebrahimzadeh et al., 2024). For the effect on blood pressure, one meta-analysis demonstrated that curcumin/turmeric supplementation has a beneficial effect on regulating systolic blood pressure (SBP) (WMD: −2.02 mmHg; 95% CI: −2.85, −1.18; I2 = 96.7%), diastolic blood pressure (DBP)

1. (WMD: −0.82 mmHg; 95% CI: −1.46, −0.18; I2 = 93.2%) in adult population when compared to placebo (Dehzad et al., 2024). However, another meta-analysis indicated that curcumin failed to reduce SBP (WMD: −0.93; 95% CI: −2.36, 0.50; I2 = 83.4%) and DBP
2. (WMD: −1.37; 95% CI: −3.09, 0.35; I2 = 90.5%) in patients with NAFLD compared to placebo (Ebrahimzadeh et al., 2024). Regarding endothelial function, curcumin/turmeric

supplementation reduced the levels of vascular cell adhesion molecule-1 (WMD: −39.19 ng/mL; 95% CI: −66.15, −12.23; I2 = 73%), and flow-mediated dilation (WMD: 2.00%; 95% CI: 1.07, 2.94; I2 = 79.5%), but did not significantly change ICAM-1 (WMD: 17.05 ng/mL; 95%CI: 80.79, 46.70; I2 = 94.1%), or pulse wave velocity (WMD: −79.53 cm/s; 95%CI: −210.38, 51.33; I2 = 99.7%) in the adult population compared to placebo (Dehzad et al., 2024).

1. 3.4.1.3 Lipid profiles Three meta-analyses evaluated the effects of curcumin on lipid
2. 4.89 mg/dL; 95% CI: 5.92, −3.87; I2 = 95.6%), and high-density lipoprotein cholesterol (HDL-C) (WMD:1.80 mg/dL; 95%CI:1.43, 2.17; I2 = 95.0%) in adults. However, it has non-significant effects on apolipoproteins-A (WMD:1.58 mg/dL; 95% CI: 3.49, 6.56, I2 = 64.4%) or apolipoproteins B (WMD:1.35 mg/dL; 95% CI: 9.74, 12.44; I2 = 83.4%) (Dehzad et al., 2023a). For patients with T2DM, compared to controls, curcumin significantly reduced TG (WMD: 18.97 mg/dL; 95%CI: 36.47, −1.47; I2 = 80.5%), TC (WMD: 8.91 mg/dL; 95% CI: 14.18, −3.63; I2 = 28.9%), but not including LDL-C (WMD: 4.01 mg/dL; 95% CI: 10.96, 2.95; I2 = 49.7%) and

HDL-C (WMD: 0.32 mg/dL; 95%CI: 0.74, 1.37; I2 = 19.1%) (Tian et al., 2022). For patients with PCOS, curcumin significantly reduced TC (WMD: 15.591; 95% CI: 27.908, −3.273; I2 = 68.9%), but were not identified TG (WMD: 8.889; 95% CI: 27.246, 9.468; I2 = 91.5%), LDL-C (WMD: 6.427; 95%CI: 17.343, 4.489; I2 = 78.8%) and HDL-C (WMD:3.713; 95% CI: 0.786, 8.211; I2 = 81.3%) compared to the control group (Shen et al., 2022).

1. 3.4.2 Anthropometric measurements Three meta-analyses evaluated the effect of curcumin on
2. 3.4.3 Inflammatory and oxidative stress markers Six meta-analyses evaluated the effect of curcumin on

inflammatory and oxidative stress markers (Beba et al., 2022; Emami et al., 2022; Dehzad et al., 2023c; Kou et al., 2023; Shen et al., 2022; Ebrahimzadeh et al., 2024). Compared to placebo, curcumin/turmeric supplementation significantly reduced C-reactive protein (CRP) level (WMD: 0.58 mg/L; 95%CI:

1. 0.74, −0.41; I2 = 98.9%), tumor necrosis factor-alpha (TNF-α) level (WMD: 3.48 pg/mL; 95%CI: 4.38, −2.58; I2 = 99.4%), interleukin-6(IL-6) level (WMD: 1.31 pg/mL; 95%CI: 1.58, 0.67; I2 = 88.2%) but failed to affect interleukin 1beta (IL-1β) level (WMD:

1. 0.46 pg/mL; 95% CI: 1.18, 0.27; I2 = 75.8%) in adults (Dehzad et al., 2023c). In adult with delayed-onset muscle soreness, curcumin supplementation reduced TNF-α levels compared to placebo (WMD: 0.22 pg/mL; 95%CI: 0.33, −0.10; I2 = 93.2%), but did not affect IL-6 (WMD: 0.05 pg/mL; 95% CI: 0.14, 0.04; I2 = 46.9%) and interleukin-8 (IL-8) levels (WMD: 0.33 pg/mL; 95% CI: 1.39, 0.73; I2 = 85.6%) (Beba et al., 2022). For patients with PCOS, curcumin reduced CRP levels (WMD: 0.785; 95%CI: 1.553, −0.017; I2 = 23.9%) compared to placebo (Shen et al., 2022). In patients with rheumatoid arthritis (RA), curcumin significantly reduced the ESR (MD: 29.47; 95%CI: 54.05, −4.88; I2 = 99%) and CRP levels (MD: 0.93; 95%CI:
2. 1.33, −0.53; I2 = 89%) as compared to the control group (Kou et al.,

1. 2023). In chronic kidney disease receiving hemodialysis, when compared with placebo, curcumin had a non-significant effect on

IL-6 (SMD:0.24%; 95% CI: 0.14, 0.62; I2 = 97.1%), TNF-a (SMD:0.11;

1. 95% CI: 0.19, 0.40; I2 = 95.9%) or hs-CRP (SMD: 0.17%; 95%CI: 0.36, 0.03; I2 = 79.6%) (Emami et al., 2022). However, compared with placebo, curcumin supplementation had a non-significant effect on IL-6 (WMD: 1.67; 95%CI: 3.80, 0.47; I2 = 81.3%), TNF-a (WMD:

the musculoskeletal diseases (Wang et al., 2021a; Zeng et al., 2021; Beba et al., 2022). In patients with osteoarthritis, compared with placebo, Curcuma longa extract and curcumin reduced visual analog scale (VAS) (WMD: 11.55; 95%CI: 14.3, −9.06; I2 = 0%) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)

scores-pain (SMD: 0.66, 95% CI: 0.88, −0.43; I2 = 34%), WOMAC scores-function (SMD: 0.79; 95% CI: 1.27, −0.31; I2 = 75%), and WOMAC scores-stiffness (SMD: 0.35; 95%CI: 0.57, −0.12; I2 = 26%) (Zeng et al., 2021). When compared to non-steroidal antiinflammatory drugs (NSAIDs), Curcuma longa extract and curcumin had similar effects on joint pain (WMD: 0.34; 95%CI:

1. 1.25, 0.57; I2 = 0%) (Zeng et al., 2021). In knee osteoarthritis, compared to placebo, turmeric extract also significantly reduced knee pain (SMD: 0.82; 95%CI: 1.17, 0.47; I2 = 86.23%) and improved physical function (SMD: 0.75; 95% CI: 1.18, −0.33; I2 = 90.05%), but had similar effects as NSAIDs (Wang et al., 2021a). Furthermore, one meta-analysis evaluated the effects on adults with delayed-onset muscle soreness, the results found that curcumin supplementation reduced creatine kinase activity level (WMD: 65.98IU/L; 95% CI: 99.53, −32.44; I2 = 86.8%), and muscle soreness (WMD: 0.56; 95%CI: 0.84, −0.27; I2 = 61.2%) compared to the placebo group (Beba et al., 2022). Moreover, curcumin supplementation also significantly improved muscle strength (WMD:3.10 nm; 95% CI:1.45,

1. 4.75; I2 = 0.0%) and affected joint flexibility(WMD: 6.49°, 95% CI: 3.91, 9.07; I2 = 71.7%) (Beba et al., 2022).

1. 3.4.7 Liver and kidney diseases Two studies evaluated the effects of curcumin on liver and
2. 3.4.8 Gynecological disorders Two meta-analyses evaluated the effects of curcumin on

gynecological disorders (Shen et al., 2022; Sharifipour et al.,

1. 2024). Regarding patients with PCOS, curcumin had a nonsignificant effect on improving testosterone (T) level (WMD: 0.128; 95%CI: 0.383, 0.127; I2 = 98.6%), dehydroepiandrosteronesulfate (WMD: 8.239; 95% CI: 30.260, 13.781; I2 = 62.3%), luteinizing hormone (LH) (WMD: 0.003; 95%CI: 0.007, 0.000; I2 = 0.0%) and follicle-stimulating hormone (FSH) (WMD: 0.002; 95%CI: 0.024, 0.029; I2 = 0.0%) compared to placebo (Shen et al., 2022). Compared to the control group, there failed to observed that curcumin improve LH/FSH (WMD: 0.114; 95%CI: 0.311, 0.084; I2 =

1. 0.0%) and ameliorating free androgen index (WMD: 0.245; 95% CI:
2. 1.138, 0.647; I2 = 30.0%) (Shen et al., 2022). As for reproductive-aged women with primary dysmenorrhea or premenstrual syndrome (PMS), curcumin intake significantly reduced the severity of dysmenorrhea (MD: 1.25; 95% CI: 1.52, −0.98; I2 = 31%) and the overall score of PMS (SMD: 1.41; 95% CI: 1.81, −1.02; I2 = 0%) than placebo (Sharifipour et al., 2024). Furthermore, curcumin also significantly reduced behavioral symptoms (MD: 12.90; 95% CI: 17.82, −7.99; I2 = 0%), mood symptoms (MD: 17.61; 95% CI: 22.75, −12.46; I2 = 0%) and physical disorders (MD: 19.65; 95% CI: 25.50, −13.80; I2 = 0%) of PMS patients (Sharifipour et al., 2024).

3.4.9 Other diseases

In patients with COVID-19, curcumin reduced the risk of allcause mortality (RR: 0.37; 95% CI: 0.21, 0.65; I2 = 0%), and patients with no recovery status (RR: 0.55; 95% CI: 0.43, 0.69; I2 = 0%) but did no effect on the incidence of mechanical ventilation (RR: 0.23; 95% CI: 0.05, 1.07; I2 = 0%), hospitalization (RR: 0.17; 95% CI: 0.02, 1.40; I2 = 0%), and the rate of a positive viral polymerase chain reaction test (RR: 0.55; 95% CI: 0.40, 0.77; I2 = 32%) when compared to the control group (Shafiee et al., 2023). For RA, curcumin was beneficial for DAS28 (MD: 1.20; 95% CI: 1.85, −0.55; I2 = 92%), rheumatoid factor (MD: 24.15; 95% CI: 36.47, −11.83; I2 = 97%), VAS pain (MD: 5.32; 95% CI: 9.42, −1.22; I2 = 19%), swollen joint count (MD: 5.33; 95% CI: 9.90, −0.76; I2 = 98%) and tender joint count (MD: 6.33; 95% CI: 10.86, −1.81; I2 = 98%) compared to control group, but not including ACR-20 (MD:0.96; 95% CI:0.39, 1.52; I2 = 0%) (Kou et al., 2023). Moreover, one meta-analysis assessed the therapeutic effect of curcumin on the severity of radiation dermatitis in patients with breast cancer, and the results indicated that curcumin supplementation significantly reduced the radiation dermatitis severity score compared to the placebo group (WMD: 0.50; 95% CI: 0.72, 0.27; I2 = 95.7%) (Mirzaei Dahka et al., 2023). Regarding analgesic effects, one meta-analysis suggested that curcumin significantly reduced the pain severity (SMD: 0.57; 95%CI: 1.1, −0.03; I2 = 86%) in patients with painful statues (Sahebkar and Henrotin, 2016). Furthermore, oral curcumin had a strong positive impact on HR-QOL (SMD: 2.46; 95% CI: 1.30, 3.63; I2 = 97.4%) compared with placebo (Sadeghian et al., 2021).

3.5 Safety

Eight studies reported adverse events (Zhu et al., 2019; Wang et al., 2021a; Wang et al., 2021b; Zeng et al., 2021; Malekmakan et al., 2022; Shen et al., 2022; Yin et al., 2022; Kou et al., 2023), including gastrointestinal symptoms, such as bloating, nausea, abdominal pain, diarrhea and constipation, and other symptoms including headache, dizziness, rash and hot flushes. However, there were no serious adverse events.

To our knowledge, this is the first review to assess the methodological quality and evidence of available meta-analyses on curcumin. Our review included 25 studies that evaluated the therapeutic and preventive effects of curcumin on diverse diseases. The findings suggested that curcumin has potential effects on lipid profiles, blood pressure, inflammatory markers and oxidative stress, musculoskeletal diseases, emotional and cognitive function, ulcerative colitis, liver and kidney function, primary dysmenorrhea or PMS, RA, COVID-19, and painful statues as well as HR-QOL. However, for many of the diseases the conclusions are still uncertain.

The biological activity of curcumin has been well confirmed, and it is expected to increase the clinical applicability of curcumin by revealing its mechanism of action in different diseases. In clinical trials, curcumin as an effective antihyperglycaemic agent, has been found to improve insulin resistance and reduce insulin and blood glucose levels. Numerous studies have revealed that curcumin induces

PPAR-γ activation to regulate glucose metabolism (Jiménez-Flores et al., 2014). Additionally, studies revealed that curcumin could prevent hyperglycemia by promoting insulin secretion, improving β-cell function, and inhibiting β-cell apoptosis (Gu et al., 2024). Curcumin/turmeric can reduce blood pressure by inducing eNOS protein expression, enhancing antioxidant capacity by restoring glutathione, and decreasing the overproduction of reactive oxygen species (Ramaswami et al., 2004; Nakmareong et al., 2011). Curcumin/turmeric can also improve endothelial vasorelaxation response to acetylcholine, increase NO bioavailability, and induce several antioxidant enzyme genes expressions through activation of the Nrf2-antioxidant response element signaling pathways (Aggarwal and Sung, 2009; Rungseesantivanon et al., 2010; Suphim et al., 2010). The exact mechanism by which curcumin/turmeric may affect body measurements has not been fully determined. However, curcumin’s effects on anthropometric aspects have been associated with downregulation of the Janus kinase enzyme and inhibition of adipocyte differentiation (Dehzad et al., 2023d). Curcumin is effectively used in obesity treatment because it is a lipophilic molecule that rapidly penetrates cell membranes and may be associated with lipid metabolism, gut microbiota and antiinflammatory potential (Kasprzak-Drozd et al., 2022).

A recent study found that curcumin exerts beneficial effects on gastrointestinal disorders. This may be related to the regulation of the ‘brain-gut axis’ and restoration of the integrity of the intestinal mucosal barrier (Yu et al., 2015; Wang et al., 2017). Notably, curcumin has been found to modulate neurotransmitters in the brain, particularly serotonin, dopamine and norepinephrine, which may account for its antidepressant effects (Spanoudaki et al., 2024). Curcumin also improves cognitive function. The neuroprotective properties of curcumin act by inducing cAMP response elementbinding protein and, subsequently, BDNF activation (Gomez-Pinilla and Nguyen, 2012). These interactions may contribute to mental and neurological health.

Curcumin has potential therapeutic effects on bone, joint and muscle disorders. This may help modulate inflammatory processes and metabolic pathways, thereby reducing symptoms and potentially slowing disease progression (Maouche et al., 2024). Curcumin, a promising antiviral drug for COVID-19, has been revealed to have high inhibitory activity against this virus (Al-Doori et al., 2021). Meanwhile, computer simulations and molecular docking indicated that the monomer has a good ability to bind to coronavirus and host targets, thus blocking the virus-host binding site (Jena et al., 2021). Therefore, the use of curcumin as an antiviral and anti-inflammatory substance may improve the containment of the damage caused by COVID-19 patients.

Curcumin has potential protective effects on the liver and kidney functions. The mechanism by which curcumin attenuates proteinuria can be explained by referring to recent investigations regarding its anti-inflammatory enhanced autophagy effects (Fan et al., 2020). Given that curcumin is a potent antioxidant, its protective effect on liver function may be related to its free radical scavenging properties. The therapeutic effects of curcumin in radiodermatitis have been associated with anti-inflammatory and antioxidant properties, as well as the ability to stimulate the regeneration of skin epithelial cells and promote wound healing (Kasprzak-Drozd et al., 2024). Curcumin is widely used in most countries globally. Given its multidirectional effects, it is used for

health-promoting purposes. Moreover, further mechanistic studies are needed to explore the effects of curcumin on various signaling cascades in the body.

Although many experts believe that natural remedies may be safer than conventional medicine, patients are still susceptible to adverse reactions to other ingredients. There is a need for certainty when combined with other therapies. Moreover, suitable dosages and contraindications of curcumin need to be explored. There is also a need to study the mechanisms that have revealed the mechanism of action of curcumin on different diseases. There is also a need to explore the mechanism underlying the effects of curcumin on different diseases.

Since the methodological quality assessed using the AMSTAR-2 checklist and the certainty of the outcome effects assessed using the GRADE grading were mostly very low to low, there is a need to improve the quality of future studies. We recommend that researchers maketheir studiespublic inadvance.This could encourage researchers to comply with the protocol and reduce various biases (Sideri et al., 2018). It can also avoid unnecessary duplication and optimize limited resources (Booth et al., 2011). The protocol could be registered and published on platforms such as PROSPERO (https://www.crd.york.ac. uk/prospero/), OSF REGISTRIES (https: //osf.io/registries? viewonly= ). The included primary studies are an important guarantee for the evaluation of evidence, and comprehensive search strategies, as well as reasonable inclusion criteria, an important guarantee for reliability. To improve the accuracy of the meta-analysis results, the following suggestions are made: Choosing multiple search methods and databases, tracing back references, retrieving registry information, consulting with experts in the relevant fields, and searching grey literature to ensure that the relevant literature is not missed.

Furthermore, it is necessary to explain the rationale and reasons for the inclusion of studies, which can provide reviewers and readers with a clearer understanding of whether the processes involved were justified. It is also important to note that authors need to provide a list of excluded literature and reasons, thus avoiding bias in metaanalyses. Furthermore, commercially funded studies are more likely to reach conclusions in favor of the sponsor’s product than independently funded studies (DeAngelis and Fontanarosa, 2008). Therefore, authors must keep detailed records of the funding sources for each study facilitate the judgement of whether funding could lead to a conflict of interest. The investigation and discussion of potential publication bias for the meta-analysis included in this overview needs to be improved. The funnel plot, Egger’s test, Begg’s test, and Macaskill’s can all be used to detect publication bias (Hayashino et al., 2005). Consequently, it is important to strengthen the quality of the systematic reviews to make more confident recommendations. Hence, future reviews should be rigorously reported following the PRISMA guidelines (Page et al., 2021) and use the best practice methods. Finally, given the heterogeneities and the inconsistencies, we suggest that future studies focus on resolving the existing ambiguities concerning the impact of turmeric/curcumin on health outcomes and clinical biomarkers in the high-quality human trials.

4.1 Strengths and limitations

This umbrella review has some strengths and limitations. For instance, our review synthesizes evidence based on clinical practice,

and the findings improve our knowledge of the validityof curcumin in clinical settings. It is worth highlighting that we used a rigorous study design, including use the latest versions of AMSTAR-2 and the GRADE system, to assess methodological quality and quality of evidence. As a result, we synthesized up-to-date comprehensive evidence, which will help guide the integration of adjunctive curcumin use into clinical practice to address general health and wellbeing, as well as therapeutic disease management. For example, healthcare experts may recommend that patients take curcumin as needed to prevent or treat diseases. However, there remains a gap betwwenn evidence and clinical practice, and future research should explore the reasons and mechanisms in different populations. Most of the studies failed to register their protocols, which could impair the transparency and credibility of the evidence. Second, we searched only English databases, which may have limited access to some available evidence. We obtained evidence synthesized by existing reviews, where details of the original trials may have been omitted, and studies included in different reviews may have overlapped. Third, there was significant heterogeneity regarding participants, interventions and assessment of outcomes, which may have affected the stability and accuracy of the findings. Finally, not all included studies were of high quality, which could introduce potential bias.

This umbrella review provides up-to-date evidence for the effect of curcumin on diverse clinical outcomes in humans. Oral curcumin has been found to be safe and therapeutic for human health and wellbeing, with potential benefits for osteoarthritis, blood sugar, lipids, and blood pressure. Curcumin has also been associated with improvements in dysmenorrhea and polycystic ovary syndrome; inflammatory status, including RA, COVID-19, and radiation dermatitis; liver and kidney function; and gastrointestinal and psychological disorders. In summary, while curcumin has demonstrated potential therapeutic benefits across various health domains, its clinical application is still fraught with challenges. In the future, more high-quality studies are needed to determine the effects of curcumin on different populations and to determine the availability of personalized, effective interventions to optimize curcumin use in clinical and healthcare settings.

The authors declare that no Generative AI was used in the creation of this manuscript.