Abstract
Background
Radiation-induced injury (RII) is a common condition among patients receiving radiation therapy which affects the quality of life and clinical outcomes in cancer patients. Curcumin has shown promising therapeutic potential in the ameliorating RII through its radioprotective, anti-inflammatory and antioxidant properties. However, the findings across studies remain inconsistent.
Methods
A comprehensive systematic search of PubMed, Web of Science, Embase, Cochrane Library, CNKI, Wanfang, and VIP was conducted from inception to 2 July 2025. Risk of bias was assessed using the Cochrane RoB 2.0 tool, and certainty of evidence was evaluated using GRADE approach.
Results
Based on finding, curcumin significantly reduced the incidence of severe RII (RR: 0.58, 95% CI: 0.46, 0.74; P < 0.001), the score of radiation injury severity (SMD: -0.90, 95% CI: -1.25, -0.55; P < 0.001), score of pain using NRS (SMD: -7.56, 95% CI: -9.47, -5.65; P < 0.001) and VAS (SMD: -1.53, 95% CI: -2.52, -0.54; P = 0.002) and weight (SMD: -0.69, 95% CI: -1.25, -0.13; P = 0.015). However, curcumin was not associated with the incidence of overall RII (RR: 0.98, 95% CI: 0.95, 1.01; P = 0.259).
Conclusion
The present systematic review and meta-analysis indicated that curcumin may exert promising effects in mitigating RII. It has been shown that patients with RII may benefit from curcumin treatment through reduced incidence of severe RII and score of severity and adverse events. Nevertheless, well-designed studies across multiple populations with rigorous methodologies and optimized dose regimens are warranted to establish firm conclusions.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12885-026-15985-5.
Keywords: Curcumin, Radiation-induced injury, Radiotherapy, Radiochemotherapy systematic review, Meta-analysis
Introduction
Radiotherapy has been known as an effective treatment modality in patients with cancer [1]. However, it has short-term and long-term consequences classified as radiation-induced injury (RII) [2]. The RII is a spectrum of normal-tissue toxicities organ-specific differences and exposure to ionizing radiation make patients susceptible for several manifestations [3]. Radiation induces DNA damage and excessive generation of reactive oxygen species (ROS) subsequently, leading to inflammation and oxidative stress [4]. These effects are associated with RII which affects multiple organ function and impair quality of life [5]. However, the development of RII is associated with decreased compliance of patients with radiotherapy. Likewise, it is suggested to alleviate the RII at early stages. In this regard, turmeric has shown more beneficial and biological effects.
Curcumin (Curcuma longa L.) as a hydrophobic polyphenol extracted from Curcuma longa has gained attention of scientific society due to its broad spectrum of biological activities [6]. It has several anti-inflammatories, antioxidant, anticancer, antiproliferative properties [7–9]. Curcumin has been shown to scavenge free radicals induced by radiation and promote antioxidant defense system [10]. These modulatory effects of curcumin are mediated through several mechanisms including nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathway pathways [11, 12].
Overall, curcumin share promising radioprotective effects for RII. However, limited clinical data warrant further investigation to reveal its therapeutic effectiveness in patients with RII. Accordingly, curcumin as low-cost, high efficacy compound could have more potential effects on the patients with RII. Therefore, the present systematic review and meta-analysis aimed to evaluate the effect of curcumin on RR to address research gaps.
Materials and methods
Search strategy
The present study is conducted using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines [13] (Supplementary Table 1). The study protocol was registered in the International Prospective Registry of Systematic Reviews (PROSPERO) with ID; CRD420251272770.
Search strategy
A comprehensive search was conducted in PubMed, Web of Science (WOS), Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Database, China Science and Technology Journal Database (VIP) and the China Biomedical Medicine database (CBM), from their inception until 2 July 2025 without any language limitation. The search strategy using MESH terms and keywords has been outlined in the Supplementary Table 2.
Eligibility criteria
Studies meeting our eligibility criteria were included in this study. Inclusion criteria were based on the prespecified PICO. P; Participants: adult patients with cancer aged 18 to 80 years undergoing radiotherapy or radiochemotherapy. I; Intervention: oral or topical curcumin. C; Comparator: Placebo or other standardized interventions. O; Outcome: incidence of radiation injury, incidence of severe radiation injury (score ≧ 3), score of radiation injury severity, pain score, and weight loss. Radiation injury evaluated using various grading systems including Radiation Therapy Oncology Group (RTOG), World Health Organization (WHO), Radiation Dermatitis Severity (RDS), National Cancer Institute Common Terminology Criteria (NCI-CTC V.2), and National Cancer Institute Common Terminology Criteria for Adverse Events (AEs) (NCI CTCAE V.4). We have harmonized these grading systems to enable comparability across included studies [13, 14].We defined grades 3–4 as severe radiation injury. Across all scales, grades 3–4 indicate clinically severe condition. This harmonization allows data synthesis of severe radiation injury outcomes. Multicentre RCTs were included and analysed as separate two-arm comparative trials with appropriate adjustment for pooled control groups in accordance with the Cochrane Handbook on Systemic Reviews of Interventions.
In contrast, animal studies, in vitro, gray literatures, reviews, studies which have evaluated the effect of curcumin in combination to other compounds were excluded.
Data extraction
Two independent researchers completed screening process. The authors resolved any discrepancies with third investigator. The extracted items included first author name, publication year, age, gender, sample size, type of cancer, treatment (radiotherapy or radiochemotherapy), curcumin intervention, study duration and grading system.
Risk of bias and quality assessment
Two researchers completed quality assessments independently. RCTs were evaluated using the Cochrane risk of bias tool (ROB-2) which is consisted of the following domains: randomization procedures, intervention allocation, incomplete outcome data, measurement of outcomes, and selective outcome reporting [15]. The certainty of evidence for each outcome was evaluated using the GRADE approach, considering risk of bias, inconsistency, indirectness, imprecision, and publication bias across the meta-analysis.
Statistical analysis
The data synthesis was done using the STATA 15.0. The data were reported using risk ratio (RR) and standard mean difference (SMD) with 95% confidence intervals (CI). Continuous outcomes measured on different scales were pooled using SMD with 95% CI. All meta-analyses were conducted using a random-effects model, with the DerSimonian and Laird estimator for between-study variance (τ²) [16]. Heterogeneity was quantified using I² and τ², and 95% prediction intervals were reported for key outcomes [17]. Subgroup analyses were performed to explore potential sources of heterogeneity. Subgroups included cancer type, treatment modality, curcumin formulation, and route of administration. Sensitivity analysis was done using to evaluate the robustness of the findings and assess the single study effects. Publication bias was explored using Begg’s test. Publication bias was assessed for outcomes including ≥ 10 studies using funnel plots, Egger’s test, and the trim-and-fill method [18]. For meta-analyses involving studies with zero events in one or both arms, a continuity correction of 0.5 was applied. In accordance with Cochrane guidelines, the single multi-arm trial was incorporated by splitting the shared comparator group to create two independent pairwise comparisons, thereby avoiding double-counting of participants in the control group.
Results
Study selection and study characteristics
The flow diagram of study selection process is presented in the Fig. 1. The search process identified a total of 312 publications. Twenty-five studies were detected as duplicates using Endnote. Based on primary screening process 259 irrelevant studies were excluded. The 28 remained studies were evaluated using full-texts. Finally, 17 RCTs met predefined inclusion criteria and were included in our study.
Fig. 1.
PRISMA flow diagram of study selection
Our meta-analysis included seventeen RCTs published between 2013 and 2023 involving 1,307 patients with RII [19–35]. One three-arm RCT was analyzed as two independent comparisons [36]. The treatment duration varied across studies from 2 to 8 weeks. The basic characteristics of the included studies are provided in Table 1.
Table 1.
Basic characteristics of the included studies
| Study (Year) | Participants (Int/Con) | Type of cancer therapy | Gender (Male) | Age (Int/Con) | Cancer type | Intervention group | Control group | Duration |
|---|---|---|---|---|---|---|---|---|
| Alsalim et al., 2023 [20] |
16 15 |
Radiotherapy | 54 | NR | Head and neck | Curcumin | Standard mouthwash | 3 weeks |
| Ramezani et al., 2023 [19] |
15 15 15 |
Radiotherapy | 23 |
51.8 55.7 52.5 |
Head and neck | Curcumin / capsule | Placebo | 3 weeks |
| Soni et al., 2022 [21] |
20 20 20 |
Radiochemotherapy | 55 |
40.0 46.2 45.1 |
Head and neck | Bio‑enhanced turmeric capsules | Placebo | 6 weeks |
| Talakesh et al., 2022 [30] | 42 | Radiotherapy | 20 | 49.7 | Breast | Curcumin capsule | Placebo | 7 weeks |
| Kia et al., 2021 [22] |
7 6 |
Radiochemotherapy | 5 | NR | Head and neck | Curcumin capsule | Placebo | 7 weeks |
| Shah et al., 2020 [23] |
35 33 |
Radiochemotherapy | 54 |
55.0 53.8 |
Head and neck | Curcumin | Benzydamine mouthwash | 6 weeks |
| Arun et al., 2020 [25] |
30 31 |
Radiochemotherapy | 28 |
55.0 53.8 |
Head and neck | Curcumin capsule | Placebo | 4 weeks |
| Jyothi et al., 2020 [24] |
25 25 |
Radiotherapy | 25 | NR | Head and neck | Curcumin | Placebo | 2 weeks |
| Ryan‑Wolf et al., 2020 [31] |
59 52 |
Radiotherapy | 171 |
59.0 60.7 |
Breast | Curcumin gel | HPR / Placebo | 8 weeks |
| Delavarian et al., 2019 [37] |
16 16 |
Radiotherapy | 13 |
62.2 55.9 |
Head and neck | Curcumin capsule | Placebo | 6 weeks |
| David et al., 2019 [26] |
25 25 |
Radiotherapy | 21 | Head and neck | Curcumin | Sodium bicarbonate mouthwash | 2 weeks | |
| Saadipoor et al., 2019 [35] |
33 31 |
Radiotherapy | 37 | NR | Prostate | Curcumin capsule | Placebo | 7 weeks |
| Ryan‑Wolf et al., 2018 [32] |
349 342 |
Radiotherapy | 686 | 57.6 | Breast | Curcumin capsule | Placebo | 6 weeks |
| Rao et al., 2017 [33] |
20 20 |
Radiotherapy | 40 |
49.1 50.9 |
Breast | Turmeric cream | Baby oil | 5 weeks |
| Mansouri et al., 2015 [28] |
18 19 |
Radiotherapy | 31 | NR | Head and neck | Curcumin gel | Placebo | 8 weeks |
| Rao et al., 2014 [29] |
64 16 |
Radiochemotherapy | 40 |
55.1 56.8 |
Head and neck | Curcumin | Povidone‑iodine mouthwash | 7 weeks |
| Ryan et al., 2013 [34] |
14 16 |
Radiotherapy | 30 | NR | Breast | Curcumin capsule | Placebo | 7 weeks |
Curcumin on incidence of RII
Eleven RCTs [21, 23, 25, 26, 28, 29, 33, 35, 37, 38] involving 513 participants evaluated the effect of curcumin on the incidence of RII. Accordingly, it has been shown that curcumin is not associated with RII significantly (RR: 0.98, 95% CI: 0.95, 1.01; P = 0.259; I2 = 31.3%, P = 0.149) (Fig. 2).
Fig. 2.
Effect of curcumin on the incidence of radiation-induced injury (RII)
Curcumin on incidence of severe RII
Ten RCTs [19, 21, 23, 25, 26, 28–30, 32, 33, 37] evaluated the effect of curcumin on incidence of severe RII in patients who has grade ≥ 3 radiation injury. The pooled analysis demonstrated that curcumin is significantly effective reducing incidence of severe RII (RR: 0.58, 95% CI: 0.46, 0.74; P < 0.001) (Fig. 3). Between-study heterogeneity was low (I² = 17.8%), with a between-study variance of τ² = 0.02. The 95% prediction interval ranged from 0.36 to 0.81, indicating that the protective effect of curcumin is likely to be observed in future studies, though the magnitude may vary. Heterogeneity was observed mainly in the route of administration and subgroups of nano-curcumin, whereas no heterogeneity was observed in the treatment mode. Moreover, subgroup analyses indicated that curcumin was associated with a reduced incidence of RII across different cancer types, treatment modalities, and curcumin formulations (Table 2). Among all subgroups, patients undergoing radiochemotherapy and those receiving curcumin by the oral route had the greatest protective effect of curcumin against severe RII (Table 2).
Fig. 3.
Effect of curcumin on the incidence of severe radiation-induced injury
Table 2.
Subgroup analysis across included studies
| Number | RR (95% CI) | I2 (%) | τ² | 95% Prediction Interval | |
|---|---|---|---|---|---|
| Incidence severe radiation | |||||
| Overall | 10 | 0.58 (0.46, 0.74) | 17.8 | 0.15 | 0.28–1.04 |
| Treatment type | |||||
| Radiotherapy | 5 | 0.69 (0.53, 0.85) | 0.0 | 0.00 | 0.53–0.85 |
| Radiochemotherapy | 5 | 0.38 (0.21, 0.55) | 0.0 | 0.00 | 0.21–0.55 |
| Cancer types | |||||
| Head and neck | 8 | 0.53 (0.36, 0.70) | 22.2 | 0.01 | 0.33–0.85 |
| Breast | 2 | 0.58 (0.33, 0.83) | 0.0 | 0.00 | 0.33–0.83 |
| Type of curcumin | |||||
| Curcumin | 6 | 0.55 (0.38, 0.72) | 0.0 | 0.00 | 0.38–0.72 |
| Nano-curcumin | 4 | 0.56 (0.32, 0.79) | 28.7 | 0.02 | 0.30–1.04 |
| Route of Administration | |||||
| Oral | 4 | 0.46 (0.14, 0.79) | 37.3 | 0.03 | 0.16–1.10 |
| Mouthwash | 4 | 0.56 (0.32, 0.79) | 61.5 | 0.04 | 0.21–1.50 |
| Topical | 2 | 0.58 (0.33, 0.83) | 0.0 | 0.00 | 0.33–0.83 |
| Number | SMD (95% CI) | I2 (%) | τ² | 95% Prediction Interval | |
|---|---|---|---|---|---|
| Radiation injury sever score | |||||
| Overall | 18 | -0.90 (-1.25, -0.55) | 85.3 | 0.18 | -2.20 to 0.40 |
| Treatment type | |||||
| Radiotherapy | 11 | -0.81 (-1.24, -0.38) | 86.9 | 0.20 | -2.10 to 0.48 |
| Radiochemotherapy | 6 | -1.04 (-1.33, -0.76) | 0.0 | 0.00 | -1.33 to -0.76 |
| Cancer types | |||||
| Head and neck | 12 | -1.11 (-1.32, -0.90) | 5.8 | 0.01 | -1.35 to -0.87 |
| Breast | 5 | -0.26 (-0.64, 0.13) | 73.7 | 0.12 | -1.20 to 0.68 |
| Type of curcumin | |||||
| Curcumin | 10 | -0.76 (-1.21, -0.30) | 86.2 | 0.19 | -2.25 to 0.73 |
| Nano-curcumin | 7 | -1.03 (-1.29, -0.77) | 9.6 | 0.02 | -1.35 to -0.71 |
| Route of Administration | |||||
| Oral | 8 | -0.97 (-1.60, -0.34) | 89.0 | 0.22 | -3.10 to 1.16 |
| Mouthwash | 6 | -0.94 (-1.19, -0.68) | 0.0 | 0.00 | -1.19 to -0.68 |
| Topical | 3 | -0.59 (-1.55, 0.36) | 88.0 | 0.21 | -2.90 to 1.72 |
Curcumin on radiation injury severity score
Seventeen RCTs [19–26, 28, 29, 31–34, 37, 38] involving 1262 participants (638 treatment group and 624 control group) reported the radiation injury severity score and data synthesis illustrated that curcumin treated group were benefited more in term of reduced radiation injury severity score compared to control group (SMD: -0.90, 95% CI: -1.25, -0.55, P < 0.001) (Fig. 4). Heterogeneity across studies was high (I² = 85.3%), with a between-study variance of τ² = 0.18. The 95% prediction interval ranged from − 2.20 to 0.40, indicating that while the pooled effect favors curcumin, individual study effects may vary. These results show that there was a significant heterogeneity in the oral and topical dosing, standard curcumin formulations and breast cancer subgroups, while there was a low degree of heterogeneity in the subgroups of mouthwash, nano-curcumin, head and neck cancer and radiochemotherapy. Subgroup analyses showed that patients with head and neck cancer, patients receiving radiochemical therapy with nano-curcumin, or patients receiving curcumin by mouth had the highest reduction in radiation injury severity scores (Table 2).
Fig. 4.
Effect of curcumin on radiation injury severity scores
Curcumin on pain management
Two studies have evaluated the efficacy of the curcumin in the management of pain using Numeric rating scale (NRS) [19, 22] and two studies using Visual analogue scale (VAS) [20, 28]. Accordingly, it has been shown that curcumin was associated with decreased NRS score (SMD: -7.56, 95% CI: -9.47, -5.65, P < 0.001; I2 = 0.0%, P = 0.515) and VAS score (SMD: -1.53, 95% CI: -2.52, -0.54, P = 0.002; I2 = 69.0%, P = 0.072) in patients with RII (Fig. 5).
Fig. 5.
Effect of curcumin on pain intensity assessed by NRS and VAS
Curcumin on weight loss
Three RCTs [21, 29, 37] reported weight changes in patients with RII, and the meta-analysis demonstrated that the curcumin was potent enough to attenuate weight loss process in patients with RII significantly (SMD: -0.69, 95% CI: -1.25, -0.13, P = 0.015; I2 = 59.6%, P = 0.084) (Fig. 6).
Fig. 6.
Effect of curcumin on weight loss in patients with radiation-induced injury
Curcumin on adverse events (AEs)
The meta-analysis indicated no difference in the incidence of AEs between the curcumin and control groups (RR: 0.49; 95% CI: 0.07, 3.69; P = 0.489; I2= 0.0%, P = 0.480) (Fig. 7).
Fig. 7.
Effect of curcumin on adverse events
Sensitivity analysis and publication bias assessment
Also, sensitivity analysis was conducted to promote the robustness of the results. Accordingly, leave-one-out approach did not alter the overall results in incidence of RII, incidence of severe RII, and RII severity score (Supplementary Fig. 1.A, B, C). In contrast, excluding Soni and Delavaran’s study was able to change the overall effect of curcumin on weight to non-significant mode (Supplementary Fig. 1.D.).
The publication bias using Egger’s test and visual inspection of the funnel plots indicated no evidence of publication bias for included outcomes (Begg’s test for severe RII: 0.283, severity score: 0.913, pain: 0.308, and weight loss: 0.296) (Supplementary Fig. 2.A, B, C). While, incidence of RII in cancer patients showed an asymmetric distribution (Begg’s and Egger’s test: 0.001 and 0.001) (Supplementary Fig. 2.D.).
Quality assessment and GRADE approach
Quality assessment was done for all seventeen included RCTs using ROB 2.0 (Supplementary Table 3). The results showed that the overall quality of included studies is moderate; two RCT [24] were scored as lower risk of bias, two RCTs [20, 23] were judged to be at a higher risk of bias, and thirteen RCTs [20–23, 26, 28, 29, 31–35, 37, 38] were rated as unclear risk of bias. In the domain of randomization process twelve RCTs [19, 21–23, 25, 28, 29, 31–33, 35, 37] got lower risk of bias. Three RCTs [23, 31, 38] were triple-blinded, seven [21, 22, 28, 32, 34, 35, 37] were double-blinded, four [19, 25, 29, 33] were single-blinded, and three [20, 24, 26] were unspecified. For allocation concealment, 13 RCTs did not specify their allocation method.
GRADE assessment was done for all outcomes to reveal the certainty of evidence (Table 3). Likewise, severity score and pain score were graded as low certainty of evidence. While, incidence of RII, incidence of severe RII and weight measurement scored as moderate.
Table 3.
Summary of findings and quality of evidence assessment using the GRADE approach
| No of patients (meta-analysis) | ES (95% CI) | Risk of biasa | Inconsistencyb | Indirectnessc | Imprecisiond | Publication biase | Quality of evidencef | |
|---|---|---|---|---|---|---|---|---|
| Incidence of RII | 556 (11) | 0.98 (0.95, 1.01) | Not serious | Not serious | Not serious | Serious | Not serious | Moderate |
| Incidence of severe RII | 1149 (10) | 0.58 (0.46, 0.74) | Not serious | Not serious | Not serious | Not serious | Not serious | High |
| Radiation injury severity score | 1262 (17) | -0.90 (-1.25, -0.55) | Not serious | Serious | Not serious | Not serious | Not serious | Moderate |
| Pain management (NRS) | 38 (2) | -7.56 (-9.47, -5.65) | Not serious | Not serious | Not serious | Not serious | Not serious | High |
| Pain management (VAS) | 68 (2) | -1.53 (-2.52, -0.54) | Not serious | Serious | Not serious | Not serious | Not serious | Moderate |
| Weight loss | 149 (3) | -0.69 (-1.25, -0.13) | Not serious | Serious | Not serious | Not serious | Not serious | Moderate |
| Adverse events (AEs) | 107(2) | 0.49 (0.07, 3.69) | Not serious | Not serious | Not serious | Serious | Not serious | Moderate |
a Risk of bias based on the Cochrane risk of bias tool 2
b Downgraded if there was a substantial unexplained heterogeneity (I2 > 50%, P < 0.10) that was not explained by subgroup analyses
c Downgraded if there were factors present relating to the participants, interventions, or outcomes which restrict the overall generalizability of the results
d Downgraded if the 95% confidence interval (95% CI) crossed the minimally important difference (MID)
e Downgraded if there was an evidence of publication bias using funnel plot
f Since all included studies were randomized controlled trials, the certainty of the evidence was graded as high for all outcomes by default and then downgraded based on prespecified criteria
Discussion
This comprehensive systematic review and meta-analysis share beneficial effects of curcumin in cancer patients undergoing radiotherapy with RII. It has been shown that it is potent enough to reduce the incidence of the severe RII, RII severity score, pain, and weight in cancer patients. Subgroup analyses revealed that curcumin was more effective in reducing the incidence of severe radiation injury in patients undergoing chemoradiotherapy compared to those receiving radiotherapy. Regarding cancer types, the head and neck cancer subgroup demonstrated a significant reduction in the radiation injury severity score, whereas breast cancer subgroups initially displayed high heterogeneity (I² = 85%). Sensitivity analysis, excluding two RCTs, resolved heterogeneity (I² = 0%) and revealed significant improvements in severity scores, aligning with prior systematic evidence [39]. Regarding dosage form, standard curcumin was more effective in reducing the incidence of severe radiation injury, whereas nano-curcumin demonstrated greater efficacy in reducing the radiation injury severity score. Concerning the route of administration, topical ointment had a weak impact on radiation injury, while mouthwash and oral capsules showed significant efficacy in mitigating radiation injury.
Curcumin effectively reduces both the incidence and severity of radiation-induced injury, with the greatest protective effects observed in head and neck cancer, radiochemotherapy settings, nano-curcumin formulations, and oral administration. Differences in tissue sensitivity, formulation bioavailability, administration route, and baseline toxicity explain the observed heterogeneity. High heterogeneity across key outcomes, including overall incidence and severity scores, indicates substantial variability between studies. Prediction intervals were wide, reflecting uncertainty in the magnitude of benefit in individual settings. Subgroup and sensitivity analyses suggest that route of administration, curcumin formulation, and cancer type are major contributors to heterogeneity, limiting the certainty and generalizability of the pooled estimates. It is important to note that these subgroup findings are exploratory and should be interpreted with caution due to the potential for multiplicity and the observational nature of these analyses within the trial data.
The observed reduction in the incidence of severe RII and severity score values following curcumin treatment points to protective effect of curcumin against radiation. This finding highlights the antioxidant and anti-inflammatory effects of curcumin compound, which is involved in the biological reactions to mitigate the injury [40]. It has been shown that radiation ions induce oxidative stress, generate reactive oxygen species (ROS), and activate inflammatory cascades [41, 42]. While, curcumin contribute to alleviate the radiation induced inflammation and scavenge free radicals [43]. Also, it is involved in upregulating antioxidant capacity of the body including: SOD, CAT, and GPx [44–47]. All these features are highlighted in the severe condition.
Furthermore, this study indicates that curcumin possesses radioprotective effects and is associated with reduced pain in patients. This issue points that curcumin may improve tissue damage and reduce pain subsequently [48, 49]. Evidence suggests that inflammation and tissue damage driven by oxidative stress and inflammatory signaling cascades play a key role in pain initiation. While, curcumin seems to downregulate inflammatory factors such as NF-κB, TNF-α, and IL-6, and modulate oxidative stress pathways properly [49, 50]. On the other hand, curcumin has analgesic properties and modulate nociceptive signaling pathways [51, 52]. Therefore, it is logical to observe reduced pain following curcumin treatment, consistent with the reduction in severity scores associated with curcumin therapy. However, based on established thresholds, the pooled effects for pain reduction was significant that warrants caution to interpret this finding.
In addition, curcumin was able to attenuate the wight loss process in these patients what is common consequence in patients undergoing radiotherapy due to reduced appetite. Also, the MCID thresholds for weight loss outcome are less defined in various populations which limits to translate this clinical effect.
This study had some limitations too. First, small sample size within each subgroup limits the generalizability of the findings. Second, there was high heterogeneity due to variability in the grading systems, and differences in curcumin formulation and administration route which contributed to high heterogeneity in the overall outcome of score of radiation injury severity, which necessitating cautious interpretation of the results. Third, based on the ROB2 tool, the methodological rigor of some studies was lower and the results is better to be interpreted with caution.
Conclusion
The synthesized evidence suggests that curcumin may have beneficial effects in reducing the incidence of severe radiation induced injury. In addition, it seems that it could be beneficial at reducing radiation injury severity score, pain score, and weight. Also, both patients undergoing radiotherapy and radiochemotherapy were benefited from curcumin treatment. However, large-scale, well-designed prospective studies are warranted to confirm these findings.
Supplementary Information
Acknowledgements
none.
Author contributions
Litong Zhan, Man Qia, Yin Cha, Xiaofeng Gao: Design, conception, performing statistical analysis, interpreting data, drafting and revising manuscript, extracting data, evaluating quality, performing statistical analysis, interpreting data, interpreting data. Litong Zhan, Xiaofeng Gao: drafting and revising manuscript.
Funding
None.
Data availability
The data underlying this article are available in the article and its online supplementary materials.
Declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
- 1.Webster M, et al. New approaches in radiotherapy. Cancers. 2025;17(12):1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Wang Y, et al. Prevention and treatment for radiation-induced skin injury during radiotherapy. Radiation Med Prot. 2020;1(02):60–8. [Google Scholar]
- 3.Kutanzi KR, et al. Pediatric exposures to ionizing radiation: carcinogenic considerations. Int J Environ Res Public Health. 2016;13(11):1057. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Kawamura K, Qi F, Kobayashi J. Potential relationship between the biological effects of low-dose irradiation and mitochondrial ROS production. J Radiat Res. 2018;59(suppl2):ii91–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.McKelvey KJ, et al. Radiation, inflammation and the immune response in cancer. Mamm Genome. 2018;29(11):843–65. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Kiamahalleh MV, et al. High performance curcumin subcritical water extraction from turmeric (Curcuma longa L). J Chromatogr B. 2016;1022:191–8. [DOI] [PubMed] [Google Scholar]
- 7.Zhang P, et al. Role of Curcuma longae Rhizoma in medical applications: research challenges and opportunities. Front Pharmacol. 2024;15:1430284. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Fuller BB. Antioxidants and Anti-inflammatories. Cosmet Dermatol: Prod Proc. 2022:366–87.
- 9.Sharifi-Rad J, et al. Turmeric and its major compound curcumin on health: bioactive effects and safety profiles for food, pharmaceutical, biotechnological and medicinal applications. Front Pharmacol. 2020;11:550909. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Liang W-F, et al. Curcumin activates ROS signaling to promote pyroptosis in hepatocellular carcinoma HepG2 cells. vivo. 2021;35(1):249–57. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Wang Y, et al. Curcumin as a therapeutic agent for blocking NF-κB activation in ulcerative colitis. Immunopharmacol Immunotoxicol. 2018;40(6):476–82. [DOI] [PubMed] [Google Scholar]
- 12.Shamsnia HS, et al. Impact of curcumin on p38 MAPK: therapeutic implications. 2023;31(5):2201–2212. [DOI] [PubMed]
- 13.Page MJ, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Dharman S, et al. A Systematic Review and Meta-Analysis on the Efficacy of Curcumin/Turmeric for the Prevention and Amelioration of Radiotherapy/Radiochemotherapy Induced Oral Mucositis in Head and Neck Cancer Patients. Asian Pac J Cancer Prev. 2021;22(6):1671–84. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Higgins JP, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Veroniki AA, et al. Methods to estimate the between-study variance and its uncertainty in meta-analysis. Res Synth Methods. 2016;7(1):55–79. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Melsen WG, et al. The effects of clinical and statistical heterogeneity on the predictive values of results from meta-analyses. Clin Microbiol Infect. 2014;20(2):123–9. [DOI] [PubMed] [Google Scholar]
- 18.Peters JL, et al. Performance of the trim and fill method in the presence of publication bias and between-study heterogeneity. Stat Med. 2007;26(25):4544–62. [DOI] [PubMed] [Google Scholar]
- 19.Ramezani V, et al. Efficacy of curcumin for amelioration of radiotherapy-induced oral mucositis: a preliminary randomized controlled clinical trial. BMC Cancer. 2023;23(1):354. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Alsalim SA. The effect of curcumin oral gel on radiation-induced oral mucositis in relation to salivary epidermal growth factor. J Emerg Med. 2024;(2):4.
- 21.Soni TP, Randomized A, et al. Placebo-Controlled Study to Evaluate the Effect of Bio-Enhanced Turmeric Formulation on Radiation-Induced Oral Mucositis. Orl-Journal Oto-Rhino-Laryngology Head Neck Surg. 2022;84(2):103–13. [DOI] [PubMed] [Google Scholar]
- 22.Kia SJ, et al. Effects of nanomicelle curcumin capsules on prevention and treatment of oral mucosits in patients under chemotherapy with or without head and neck radiotherapy: a randomized clinical trial. BMC Complement Med Ther. 2021;21(1):232. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Shah S, et al. Effectiveness of curcumin mouthwash on radiation-induced oral mucositis among head and neck cancer patients: A triple-blind, pilot randomised controlled trial. Indian J Dent Res. 2020;31(5):718–27. [DOI] [PubMed] [Google Scholar]
- 24.Jyothi NM, Randomized Clinical A. Trial to assess the effectiveness of turmeric mouth wash on radiation induced oral mucositis among patient with head and neck cancer admitted at oncology units of selected hospitals of Bagalkot. Int J Sci Res. 2020:2319–7064.
- 25.Arun P et al. Role of turmeric extract in minimising mucositis in patients receiving radiotherapy for head and neck squamous cell cancer: a randomised, placebo-controlled trial. J Laryngol Otol. 2020:1–6. [DOI] [PubMed]
- 26.David R. Effectiveness of Turmeric Mouthwash and Sodium Bicarbonate Mouthwash to Reduce Oral Mucositis among Patient Undergoing Radiation Therapy. Scholars Int J Tradit Complement Med. 2019:2616–8634.
- 27.Charantimath S. Use of curcumin in radiochemotherapy induced oral mucositis patients: a control trial study. Eng Technol Int J Med Health Sci. 2016;10(3):147–52.
- 28.Mansourian A, et al. The effect of Curcuma Longa topical gel on radiation-induced oral mucositis in patients with head and neck cancer. 2015;13(3):269.
- 29.Rao S, et al. The Indian Spice Turmeric Delays and Mitigates Radiation-Induced Oral Mucositis in Patients Undergoing Treatment for Head and Neck Cancer: An Investigational Study. Integr Cancer Ther. 2014;13(3):201–10. [DOI] [PubMed] [Google Scholar]
- 30.Talakesh T, et al. Effect of Nano-Curcumin on Radiotherapy-Induced Skin Reaction in Breast Cancer Patients: A Randomized, Triple-Blind, Placebo-Controlled Trial. Curr Radiopharm. 2022;15(4):332–40. [DOI] [PubMed] [Google Scholar]
- 31.Ryan Wolf J, et al. Utility of topical agents for radiation dermatitis and pain: a randomized clinical trial. Support Care Cancer. 2020;28(7):3303–11. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Ryan Wolf J, et al. Oral curcumin for radiation dermatitis: a URCC NCORP study of 686 breast cancer patients. Support Care Cancer. 2018;26(5):1543–52. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Rao S et al. Sandalwood oil and turmeric-based cream prevents ionizing radiation-induced dermatitis in breast cancer patients: clinical study. Med (Basel). 2017;4(3). [DOI] [PMC free article] [PubMed]
- 34.Ryan JL, et al. Curcumin for radiation dermatitis: a randomized, double-blind, placebo-controlled clinical trial of thirty breast cancer patients. Radiat Res. 2013;180(1):34–43. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Saadipoor A, et al. Randomized, double-blind, placebo-controlled phase II trial of nanocurcumin in prostate cancer patients undergoing radiotherapy. Phytother Res. 2019;33(2):370–8. [DOI] [PubMed] [Google Scholar]
- 36.Soni TP, Randomized A, et al. Placebo-Controlled Study to Evaluate the Effect of Bio-Enhanced Turmeric Formulation on Radiation-Induced Oral Mucositis. ORL J Otorhinolaryngol Relat Spec. 2022;84(2):103–13. [DOI] [PubMed] [Google Scholar]
- 37.Delavarian Z, et al. Oral administration of nanomicelle curcumin in the prevention of radiotherapy-induced mucositis in head and neck cancers. Spec Care Dentist. 2019;39(2):166–72. [DOI] [PubMed] [Google Scholar]
- 38.Talakesh T. Effect of nano-curcumin on radiotherapy-induced skin reaction in breast cancer patients: a randomized, triple-blind, placebo-controlled trial. Curr Radiopharmaceut. 2022;15(4):332–340. [DOI] [PubMed]
- 39.Mirzaei Dahka S, et al. Impact of Curcumin Supplementation on Radiation Dermatitis Severity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Asian Pac J Cancer Prev. 2023;24(3):783–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40.Dehzad MJ, et al. Antioxidant and anti-inflammatory effects of curcumin/turmeric supplementation in adults: A GRADE-assessed systematic review and dose–response meta-analysis of randomized controlled trials. Cytokine. 2023;164:156144. [DOI] [PubMed] [Google Scholar]
- 41.Boroumand N, Samarghandian S, Hashemy SI. Immunomodulatory, anti-inflammatory, and antioxidant effects of curcumin. J Herbmed Pharmacol. 2018;7(4):211–9. [Google Scholar]
- 42.Memarzia A, et al. Experimental and clinical reports on anti-inflammatory, antioxidant, and immunomodulatory effects of Curcuma longa and curcumin, an updated and comprehensive review. BioFactors. 2021;47(3):311–50. [DOI] [PubMed] [Google Scholar]
- 43.Asouri M, et al. Antioxidant and free radical scavenging activities of curcumin. Asian J Chem. 2013;25(13):7593. [Google Scholar]
- 44.Verma V. Relationship and interactions of curcumin with radiation therapy. World J Clin Oncol. 2016;7(3):275–83. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 45.Xie Y, et al. Curcumin ameliorates cognitive deficits heavy ion irradiation-induced learning and memory deficits through enhancing of Nrf2 antioxidant signaling pathways. Pharmacol Biochem Behav. 2014;126:181–6. [DOI] [PubMed] [Google Scholar]
- 46.Gupta SC, et al. Multitargeting by curcumin as revealed by molecular interaction studies. Nat Prod Rep. 2011;28(12):1937–55. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 47.Balogun E, et al. Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element. Biochem J. 2003;371(Pt 3):887–95. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 48.Ahangari N, et al. Curcumin in tissue engineering: A traditional remedy for modern medicine. BioFactors. 2019;45(2):135–51. [DOI] [PubMed] [Google Scholar]
- 49.Jagetia GC, Rajanikant G. Role of curcumin, a naturally occurring phenolic compound of turmeric in accelerating the repair of excision wound, in mice whole-body exposed to various doses of γ-radiation. J Surg Res. 2004;120(1):127–38. [DOI] [PubMed] [Google Scholar]
- 50.Gulcubuk A, et al. Effects of curcumin on proinflammatory cytokines and tissue injury in the early and late phases of experimental acute pancreatitis. Pancreatology. 2013;13(4):347–54. [DOI] [PubMed] [Google Scholar]
- 51.Eke-Okoro U, et al. Curcumin in turmeric: Basic and clinical evidence for a potential role in analgesia. J Clin Pharm Ther. 2018;43(4):460–6. [DOI] [PubMed] [Google Scholar]
- 52.Hajimirzaei P, et al. The analgesic effect of curcumin and nano-curcumin in clinical and preclinical studies: a systematic review and meta-analysis. Naunyn Schmiedebergs Arch Pharmacol. 2025;398(1):393–416. [DOI] [PubMed] [Google Scholar]
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