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BACKGROUND: Curcumin and turmeric are widely studied for their potential renoprotective effects, but evidence regarding their impact on kidney function in individuals with diabetes remains inconsistent. OBJECTIVE: To systematically evaluate the effects of curcumin/turmeric supplementation on kidney function parameters in subjects with diabetes. METHODS: PubMed, Web of Science and Scopus were searched from inception until August 2025. Randomised controlled trials (RCTs) assessing the effects of curcumin/turmeric on serum creatinine, blood urea nitrogen (BUN), uric acid, urea and albumin in diabetic populations were included. Data were pooled using random-effects models and reported as weighted mean differences (WMDs) with 95% confidence intervals (CIs). Subgroup, sensitivity, and meta-regression analyses were conducted. Risk of bias was assessed using the Cochrane RoB 2 tool, and evidence certainty was evaluated via GRADE. RESULTS: Twelve RCTs (n = 1303 participants) were included. Curcumin/turmeric supplementation did not significantly affect creatinine (WMD: -0.01 mg/dL, 95% CI: -0.03 to 0.01, p = 0.519) or BUN (WMD: -0.41 mg/dL, 95% CI: -3.15 to 2.33, p = 0.769). A trend toward reduction in uric acid was observed (WMD: -1.46 mg/dL, 95% CI: -2.93 to 0.02, p = 0.053). However, urea levels were significantly reduced (WMD: -2.53 mg/dL, 95% CI: -4.09 to -0.96, p = 0.002). No significant change was found in albumin (WMD: 0.07 g/dL, 95% CI: -0.02 to 0.17, p = 0.133). Subgroup analyses showed no significant moderating effects. Publication bias was detected for creatinine (Egger's p = 0.028). The certainty of evidence was moderate for creatinine, urea, and albumin, and low for BUN and uric acid. CONCLUSION: Curcumin/turmeric supplementation significantly reduces urea levels but does not significantly affect creatinine, BUN, uric acid or albumin in individuals with diabetes. Further high-quality, long-term RCTs are needed to clarify its renoprotective potential and optimal dosing. © 2026 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.

Curcuminoids are dietary polyphenols that can improve health indices through various mechanisms, such as anti-inflammatory, antioxidant, and other clinical properties. Due to the lack of evidence on the efficacy of curcuminoids in critically ill patients, this meta-analysis was conducted. The aim of this study was to assess and quantify the influence of curcumin supplementation on markers of inflammation, liver function, and clinical outcomes in critically ill patients. In this study, relevant randomized clinical trials were identified via electronic database searches, including MEDLINE, Scopus, and Web of Science, up until January 2025. The Cochrane risk-of-bias tool was utilized to assess the quality of the studies. Standardized mean differences (SMDs) and risk ratio (RR) in changes between intervention and placebo groups were calculated. Both random-effects and fixed-effects models were applied, and pre-specified stratified analyses were performed to explore potential sources of heterogeneity. Out of a total of 691 studies screened, seven trials met the inclusion criteria, encompassing data from 571 participants. The pooled analysis demonstrated that curcumin supplementation significantly lowered alanine transaminase (ALT) levels (SMD: -0.4, 95% CI: -0.8 to -0.001, p = 0.03), total bilirubin levels (SMD: -0.4, 95% CI: -0.9 to -0.07, p = 0.01), Sequential Organ Failure Assessment (SOFA) scores (SMD: -0.8, 95% CI: -1.2 to -0.4, p < 0.001), the duration of intensive care unit (ICU) stays (SMD: -0.3 days, 95% CI: -0.6 to -0.1, p = 0.01), compared to placebo. Furthermore, curcumin supplementation was associated with significant increases in albumin (SMD: 0.3, 95% CI: 0.001 to 0.6, p = 0.004) and alkaline phosphatase levels (SMD: 0.4, 95% CI: 0.02 to 0.8, p = 0.01). This meta-analysis demonstrates that curcumin supplementation improves liver function, albumin levels, SOFA scores, and ICU stay duration in critically ill patients, suggesting its potential role in mitigating organ dysfunction in this population. © 2026 John Wiley & Sons Ltd.

INTRODUCTION: Hypertension is a major cardiovascular risk factor in individuals with prediabetes and type 2 diabetes (T2D). Curcumin, with its anti-inflammatory and antioxidant properties, has emerged as a potential adjunct therapy, but its effect on blood pressure in this population remains unclear. AIMS: This meta-analysis aimed to evaluate the effects of curcumin or turmeric supplementation on systolic (SBP) and diastolic (DBP) blood pressure in adults with prediabetes or T2D. METHODS: A systematic search of PubMed, Scopus, and Web of Science was conducted until August 2025. Randomised controlled trials (RCTs) investigating curcumin/turmeric supplementation on blood pressure in adults with prediabetes or T2D were included. A meta-analysis was performed using a random-effects model. RESULTS: Fifteen RCTs comprising 16 treatment arms (n = 855 participants) were included. Pooled results indicated that curcumin/turmeric supplementation significantly reduced SBP (WMD: -2.69 mmHg; 95% CI: -3.84 to -1.55; p < 0.001; I2 = 30.1%) compared to control groups. A more substantial reduction in SBP (-3.41 mmHg) was observed in the subgroup of participants with baseline hypertension (SBP ≥ 130 mmHg). However, no significant effect was found on DBP (WMD: -1.20 mmHg; 95% CI: -2.84 to 0.44; p = 0.15; I2 = 84.3%). Subgroup analyses showed significant reductions in SBP in individuals with T2D or prediabetes, in those who were overweight, and with interventions using nano-curcumin, turmeric, or curcumin with piperine at doses > 1 g/day. In addition, subgroup analysis showed that curcumin/turmeric supplementation led to a significant reduction in DBP in individuals with T2D. CONCLUSIONS: Curcumin/turmeric supplementation demonstrates a modest, yet significant reduction in SBP in individuals with prediabetes and diabetes, with a more pronounced effect in those with baseline hypertension. Further high-quality RCTs are needed to confirm these findings and establish optimal dosing. © 2025 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.

BACKGROUND: Curcumin has been proposed as a potential adjunctive anti-inflammatory therapeutic option in rheumatoid arthritis (RA); however, the evidence regarding its clinical efficacy remains inconsistent. This meta-analysis aimed to evaluate whether curcumin supplementation improves disease activity and systemic inflammatory parameters in patients with RA. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria, PubMed, Cochrane Library, Web of Science, and Embase were searched from inception to August 26, 2025. Eligible randomized controlled trials included adult RA patients diagnosed according to American College of Rheumatology or European League Against Rheumatism criteria and compared curcumin in any formulation with placebo or standard care. Two independent reviewers conducted study selection, data extraction, and methodological quality assessment using the Cochrane Risk of Bias 2.0 tool. Pooled analyses were conducted using Review Manager, version 5.4 and Stata, version 18, with fixed-effect or random-effects models based on heterogeneity. RESULTS: Seven randomized controlled trials were included. Curcumin significantly reduced Disease Activity Score in 28 joints (weighted mean difference [WMD] -1.47; 95% confidence interval [CI] -1.68 to -1.26), rheumatoid factor (WMD -24.15; 95% CI -36.47 to -11.83), erythrocyte sedimentation rate (WMD -31.26; 95% CI -58.59 to -3.93), and C-reactive protein (WMD -0.93; 95% CI -1.33 to -0.53). Substantial heterogeneity was observed; nevertheless, leave-one-out sensitivity analyses confirmed stability of pooled estimates, and Egger tests revealed no significant publication bias. CONCLUSION: Curcumin supplementation was associated with statistically and clinically relevant improvements in disease activity and systemic inflammatory markers in RA. These findings support curcumin as a promising adjunctive therapeutic strategy, though larger, exposure-verified trials with extended follow-up remain required to validate long-term treatment effects and inform clinical implementation.

BACKGROUND: Curcumin, the primary bioactive compound in turmeric (Curcuma longa Linn.), has demonstrated potential benefits in managing type 2 diabetes mellitus (T2DM) and hyperglycemia. This systematic meta-review aimed to evaluate the effectiveness of turmeric in improving glycemic control, lipid profiles, and other metabolic markers in the patients with T2DM or hyperglycemia. METHODS: A comprehensive literature search was conducted across seven electronic databases to identify relevant studies published up to December 2023. Inclusion criteria focused on randomized controlled trials included in systematic reviews or meta-analyses assessing curcumin's effects on metabolic markers. Data were extracted systematically, and the methodological quality of included reviews was assessed using AMSTAR-2. Meta-analyses were performed using STATA 17 to synthesize outcomes for fasting blood glucose (FBG), glycated hemoglobin (HbA1c), lipid profiles, and other markers, employing random-effects models to account for heterogeneity. RESULTS: Thirteen systematic reviews and meta-analyses of 63 unique randomized controlled trials involving 3706 human participants met the inclusion criteria. The pooled analysis revealed that curcumin significantly reduced FBG (mean difference [MD] = - 6.30 mg/dL; 95% CI: - 9.33, - 3.27), HbA1c (MD = - 0.31%; 95% CI: - 0.57, - 0.05), low - density lipoprotein (LDL) cholesterol (MD = - 5.95 mg/dL; 95% CI: - 9.43, - 2.47), and triglycerides (TG) (MD = -12.88 mg/dL; 95% CI: - 20.09, - 5.67) while increasing high-density lipoprotein (HDL) cholesterol (MD = 1.46 mg/dL; 95% CI: 0.37, 2.56). No significant effects were observed on total cholesterol, blood pressure, body mass index, blood urea nitrogen, or creatinine levels. Heterogeneity across studies was high but consistent with meta-analytical expectations for diverse populations and interventions. CONCLUSIONS: Curcumin supplementation shows statistically significant improvements in glycemic control and lipid profiles in individuals with T2DM or hyperglycemia, supporting its potential as an adjunct therapy. However, its effects on renal markers, blood pressure, and body weight remain inconclusive. More

Dyslipidemia is a known risk factor for cardiovascular diseases (CVD). Research indicates that curcuminoids plus piperine co-supplementation (Curc + Pipe) can alter serum lipids. However, the findings from various studies are inconsistent. This meta-analysis aims to evaluate the efficacy of Curc + Pipe in serum lipid parameters in adults. A systematic search was conducted in databases until August 2025 to identify eligible randomized controlled trials (RCTs). To estimate the pooled effect size, weighted mean differences (WMDs) with corresponding 95% confidence intervals (CIs) were calculated, applying a random-effects model to account for potential variability between studies. A pooled analysis of 16 RCTs, encompassing a total of 1038 participants (Intervention: 522, Control: 516) revealed that Curc + Pipe significantly reduced triglycerides (TG) (WMD: -18.64 mg/mL, 95% CI: -29.94, -7.34, p < 0.001) and total cholesterol (TC) (WMD: -6.58 mg/mL, 95% CI: -12.60, -0.55, p = 0.032) and increased high-density lipoprotein cholesterol (HDL-C) (WMD: 1.51 mg/mL, 95% CI: 0.29, 2.72, p = 0.015). However, the reduction in low-density lipoprotein cholesterol (LDL-C) was not statistically significant (WMD: -2.20 mg/mL, 95% CI: -7.22, 2.80, p = 0.387). Curc + Pipe has clinically meaningful lipid-modulating effects, particularly in reducing TG and TC and modestly increasing HDL-C levels. These benefits were most pronounced in more prolonged supplementation in individuals with dyslipidemia, metabolic disorders, and overweight. Clinically, Curc + Pipe may serve as a valuable complementary therapy for dyslipidemia management to decrease the risk of CVD. © 2025 AOCS.

The effective management of diabetes, a prevalent metabolic condition globally, relies on paying close attention to anthropometric measurements, while recent years have seen a growing interest in researching the potential anti-obesity properties of turmeric/curcumin. In this systematic review and dose-response meta-analysis of randomized controlled trials, the impact of turmeric/curcumin supplementation on anthropometric indices in individuals with prediabetes and type 2 diabetes mellitus (T2DM) was assessed. PubMed, Cochrane Library, Web of Science, Scopus, and Google Scholar were searched to identify relevant records published from 1 January 1990 to 1 June 2024. Random-effects meta-analysis was performed to evaluate the weighted mean difference (WMD) and 95% confidence interval (CI), with a p-value ≤ 0.05 indicating statistical significance. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess the certainty of evidence. Twenty randomized controlled trials (RCTs) were included in the meta-analysis. Pooled analysis displayed that supplementation with turmeric/curcumin significantly decreased body weight (WMD: -1.9 kg; 95% CI: -2.9 to -0.9; P ≤ 0.001; GRADE = low), waist circumference (WMD: -1.9 cm; 95% CI: -3.5 to -0.2; P = 0.024; GRADE = low), fat mass% (WMD: -2.9%; 95% CI: -5.6 to -0.1, P = 0.041; GRADE = very low), and hip circumference (WMD: -1.0 cm; 95% CI: -1.2 to -0.8; P ≤ 0.001; GRADE = moderate) but no effects on body mass index and waist-to-hip ratio in people with T2DM. In individuals with prediabetes, body weight (WMD: -2.5 kg; 95% CI: -4.8 to -0.2; P = 0.037; GRADE = moderate) and waist circumference (WMD: -2.9 cm; 95% CI: -5.3 to -0.6; P = 0.015; GRADE = moderate) were significantly lower in the turmeric/curcumin supplement-treated group than their untreated counterparts. The study found that turmeric/curcumin has a beneficial effect on some obesity indicators, which could contribute to weight management in individuals with prediabetes and T2DM. Systematic Review Registration: This study was registered at PROSPERO as CRD42023440612. © 2025. The Author(s).

Background: Knee osteoarthritis (KOA) is a prevalent degenerative joint disease that can greatly affect quality of life in middle-aged and elderly individuals. Nutritional supplements are increasingly used for KOA due to their low risk, but direct comparative evidence on their efficacy and safety remains scarce. This study aimed to systematically compare the effectiveness and safety of seven common nutritional supplements for KOA. Methods: A systematic review and network meta-analysis were conducted following PRISMA guidelines. Embase, PubMed, and the Cochrane Library were searched through December 2024 for randomized controlled trials (RCTs) evaluating use of eggshell membrane, vitamin D, Boswellia, curcumin, ginger, krill oil, or collagen, versus placebo, in adults with KOA. Primary outcomes included changes in scores for WOMAC pain, stiffness and function, and pain visual analog scale (VAS). Adverse events were also assessed. Bayesian network meta-analyses estimated ranking probabilities for each intervention. Results: In total, 39 RCTs (42 studies; 4599 patients) were included. Compared with placebo, Boswellia showed significant improvements in WOMAC pain (mean difference [MD] = 10.58, 95% CI: 6.45 to 14.78, p < 0.05), stiffness (MD = 9.47, 95% CI: 6.39 254 to 12.74, p < 0.05), function (MD = 14.00, 95% CI: 7.74 to 20.21, p < 0.05), and VAS pain (MD = 17.26, 95% CI: 8.06 to 26.52, p < 0.05). Curcumin, collagen, ginger, and krill oil also demonstrated benefits in some outcomes. No supplement was associated with increased adverse events compared to placebo. Bayesian rankings indicated Boswellia had the highest probability of being most effective for pain and stiffness, with krill oil and curcumin showing potential for function improvement. Conclusions: Nutritional supplements, particularly Boswellia, appear to be effective and well-tolerated for improving KOA symptoms and function. These results suggest that certain supplements may be useful as part of non-pharmacological KOA management. However, further large-scale, well-designed randomized controlled trials (RCTs) are needed to confirm these findings, particularly those that include more standardized dosages

BACKGROUND: Cognitive aging is a growing public health concern, and curcumin, a bioactive compound derived from turmeric, has been proposed as a potential intervention to support cognitive function due to its anti-inflammatory and antioxidant properties. OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the effects of curcumin on cognitive outcomes related to aging. METHODS: A comprehensive search of PubMed, Embase, Cochrane Library, Web of Science, and Scopus was conducted to identify studies published up to June 18, 2024, including both in vivo preclinical animal studies and randomized controlled trials (RCTs) assessing curcumin's effects on cognitive function. In vivo animal studies using Alzheimer's disease (AD) models and RCTs in human participants were included. Data were extracted and analyzed using meta-analytic techniques. RESULTS: In preclinical in vivo murine studies (n = 25; total animals = 572), curcumin consistently improved both acquisition memory (SMD = -1.78, 95 % CI: -2.12 to -1.43) and retention memory (SMD = 2.36, 95 % CI: 1.72 to 3.00) in rodent models of AD. Ten human studies include 531 participants. Overall, curcumin showed no significant effect on global cognitive outcomes compared to placebo (SMD = 0.14, 95 % CI: -0.78 to 1.07). Subgroup analyses revealed significant improvements in working memory (SMD = 1.01, 95 % CI: 0.15 to 1.87) and processing speed (SMD = 0.37, 95 % CI: 0.07 to 0.67). The incidence of adverse events was higher in the curcumin group than in the control group. CONCLUSIONS: Preclinical in vivo evidence suggests curcumin enhances cognitive function in AD models. However, human studies show inconsistent findings with benefits limited to specific cognitive domains. Larger, well-designed randomized controlled trials are needed to establish curcumin's efficacy and safety in cognitive aging.

Curcumin is a bioactive compound derived from the rhizome of Curcuma longa (turmeric) that has garnered increasing attention for its potential health benefits. However, its use in clinical practice is limited due to its generally poor bioavailability. This issue can be overcome using novel delivery systems that enhance curcumin's solubility, extend its residence time in plasma, improve its pharmacokinetic profile, and increase its cellular uptake. Novel curcumin formulations with improved bioavailability have been suggested to elevate plasma concentrations of lipoprotein(a) (Lp(a)), but there is no definitive evidence of a causal relationship. To address this, a systematic literature search was conducted in multiple electronic databases to identify relevant randomized placebo-controlled clinical studies published without a time limit. A meta-analysis of data suggested that dietary supplementation with highly bioavailable forms of curcumin significantly reduces Lp(a) levels [Standardized Mean Difference (SMD)= -0.96 (95 % Confidence Interval (CI): -1.82, -0.11)]. The effect size was robust in the leave-one-out sensitivity analysis and was not primarily driven by any single study. Of course, the clinical significance of this observation should be more thoroughly evaluated in longer-term trials, where the combined metabolic and anti-inflammatory effects of curcumin have vascular protective effects.

Post-burn pruritus (PBP) is a common and refractory condition that can significantly impair quality of life (QoL). Curcumin, a bioactive compound with anti-inflammatory and neuroprotective properties, has been proposed as a therapeutic option for chronic pruritus. This study evaluated the efficacy of a nano-micelle formulation of curcumin in patients with refractory PBP. In this randomized controlled trial, 100 adults with PBP were assigned to receive standard treatment alone or with curcumin nano-micelle capsules (40 mg, twice daily) for 12 weeks. Outcomes included pruritus severity, frequency, distribution, sleep condition, sleep disturbance, total pruritus intensity, and QoL (ItchyQoL), assessed at baseline, week 6, and week 12. Analyses were performed using mixed-effects models with group, time, and group×time as factors. Both groups demonstrated significant within-group improvements in some pruritus domains. However, in the mixed-effects model, curcumin produced a significant between-group reduction in total pruritus intensity (adjusted mean difference -2.83; 95 % CI -5.54 to -0.11; p = 0.041). No significant between-group effects were observed for individual domains. Sleep condition improved with curcumin (adjusted mean difference -0.50; 95 % CI -1.04-0.03) but did not reach statistical significance. QoL improved significantly over time (time effect p = 0.045) in both groups, with a non-significant trend favoring curcumin (adjusted mean difference 2.85; 95 % CI -2.13-7.83). Adjunctive curcumin nano-micelle therapy significantly reduced overall pruritus intensity in patients with refractory PBP. Sleep and QoL outcomes improved in both groups, with trends favoring curcumin. Larger, longer trials with optimized dosing are warranted to confirm these findings.

OBJECTIVES: Considering the proven anti-inflammatory effects of curcumin, we aimed to investigate the effect of curcumin supplementation on fatigue and musculoskeletal health (primary outcomes) and depression and its side effects (secondary outcomes) in postmenopausal women. DESIGN: This was a parallel-group, double-blind, randomised placebo-controlled superiority trial. SETTING: The trial was conducted at two general clinics in Tabriz, Iran, in 2023. PARTICIPANTS: A total of 74 postmenopausal women were enrolled. The participants were women aged between 40 years and 60 years with normal menopause and at least 1 year after amenorrhoea. INTERVENTION: They were randomly assigned (1:1 allocation ratio) using a block randomisation method to receive either 500 mg curcumin capsules (intervention group, n=37) or identical placebo capsules (control group, n=37) twice daily for 8 weeks. Both participants and researchers were blinded to the group assignments. PRIMARY AND SECONDARY OUTCOME MEASURES: Data were collected using the questionnaires of demographic characteristics, short form of the perimenopausal fatigue scale, musculoskeletal health, Beck Depression Inventory (BDI-13) and the side effects checklist. Independent t, ANCOVA and Mann-Whitney U tests were used to compare the results between the two groups. RESULTS: A total of 74 women were randomised, with 33 in the curcumin group and 31 in the placebo group completing the study and being included in the final analysis. After the 8-week intervention, ANCOVA adjusting for baseline values revealed that the curcumin group showed a statistically significant improvement in musculoskeletal health (mean difference (MD): 5.3; 95% CI: 3.3 to 7.4; p<0.001); the observed mean difference falls just short of the MCID (the minimum clinically important difference), yet it is remarkably close. A statistically significant decrease in fatigue scale (MD: -2.6; 95% CI: -3.8 to -1.4; p<0.001) was observed compared with the placebo group; there is no MCID validated for this scale. No significant difference was observed between the groups in terms of depression (p=0.245); there is no universally accepted MCID specifically validated for th

The potential of the phytoconstituent, curcumin, as an adjuvant to chemoradiotherapy has been investigated because of its ameliorating effects, including the sensitization of cancer and cancer stem cells. Curcumin, a strong antioxidant with pharmacologically non-toxic effects, can be used as an adjuvant with enhanced bioavailability and administered along with chemotherapy to achieve better treatment outcomes. The present study was carried out with a total of 120 women with locally advanced/metastatic breast cancer, who were randomized to receive standard chemotherapy alone or chemotherapy with oral curcumin, a 500 mg capsule (1 g/day) containing 95% curcuminoid and 1% piperine given for 12 to 24 weeks. Primary outcomes were determined using the Response Evaluation Criteria in Solid Tumors (RECIST) to determine the objective response rate (ORR), progression-free survival (PFS), and time to tumor progression (TTP), including safety and adverse events, while the quality of life (QoL) and physical activity were secondary outcomes. ORR was significantly higher in the curcumin group than in those who received standard chemotherapy (38.33% vs. 8.33%, p < 0.01) at 4 weeks follow-up post-treatment, which further improved (43.40% vs. 10.64%, p < 0.0031) upon completion of 12 weeks post-treatment. Curcumin-treated women displayed higher physical performance, better prognosis and QoL, better tolerance to chemotherapy, fewer adverse effects, and better PFS. The study suggests that curcumin can be used as a safe adjuvant along with chemotherapeutic drugs for a better treatment outcome in breast cancer and also in other cancers. © 2025 John Wiley & Sons Ltd.

Postpartum depression and anxiety are common problems in primiparous women, which can negatively affect Maternal-infant bonding and lead to sexual disorders. It's important to prevent and treat these issues, especially since medication options during breastfeeding may be limited. Our study aimed to investigate the effect of curcumin, a natural substance known for its beneficial properties, on postpartum depression and anxiety in primiparous women. A randomized controlled clinical trial was conducted on 96 primiparous women in Tabriz City. Participants were randomly assigned to either the intervention group (n = 48) or the control group (n = 48) using the random block method. The intervention group received curcumin capsules with a dose of 500 mg, while the control group received a placebo with the same dose once daily for eight weeks. Data was collected using the Edinburgh Postnatal Depression Scale (EPDS) and postpartum-specific Anxiety Scale research short-form (PSAS-RSF) questionnaires. After the intervention, the mean score of depression (mean difference: -2.5; 95% confidence interval: -3.3 to -1.7; P < 0.001) and anxiety (Mean difference: -1.4; 95% confidence interval: -2.1 to -0.7; P < 0.001) in the intervention group were significantly lower than the control group. It seems that curcumin can improve the mental health and quality of life of primiparous women postpartum due to its efficacy in reducing postpartum anxiety and depression, easy accessibility, and cost-effectiveness. © 2025. The Author(s).

BACKGROUND: Endometriosis is a chronic gynecological disorder characterized by significant pain and reduced quality of life (QOL). Current treatments, such as dienogest, are not fully effective, prompting the investigation of curcumin as a potential adjunct therapy. Although curcumin has demonstrated promise in preclinical studies, its clinical efficacy in endometriosis, particularly in combination with standard therapies like dienogest, remains underexplored. PURPOSE: This is the first study aimed to evaluate the add-on effect of curcumin in combination with dienogest on pain relief, QOL, and sexual function in women with endometriosis. STUDY DESIGN: A randomized, double-blind, placebo-controlled trial was conducted to compare the efficacy of curcumin combined with dienogest versus dienogest alone with a placebo. METHODS: Eighty-six women aged 18-45 with stage 2-3 pelvic endometriosis and moderate to severe pain (visual analogue scale (VAS) ≥ 4) were randomly assigned in a 1:1 ratio to receive either nanocurcumin soft gel capsules (80 mg/day) or a placebo, along with dienogest (2 mg/day), for 8 weeks. Outcomes were assessed using adjusted mean differences (aMD) and 95 % confidence intervals (CIs). RESULTS: After 8 weeks, the curcumin and dienogest group demonstrated significantly greater improvements in pain scores compared to the placebo group: dysmenorrhea (aMD: -1.55, 95 %CI: -2.04 to -1.06; p < 0.001), dyspareunia (aMD: -0.93, 95 %CI: -1.37 to -0.49; p < 0.001), chronic pelvic pain (aMD: -1.55, 95 %CI: -2.04 to -1.06; p < 0.001), and dyschezia (aMD: -0.30, 95 %CI: -0.58 to -0.03; p = 0.030). Additional benefits were observed in QOL and Female Sexual Function Index (FSFI) scores, except for the orgasm domain. Differences in endometrioma size were not statistically significant. CONCLUSION: The combination of curcumin and dienogest significantly reduced pain and improved QOL and sexual function in women with endometriosis, suggesting curcumin as an effective adjunct therapy.

BACKGROUND: Radiation-induced dermatitis, a common radiotherapy (RT) complication, affects 95% of breast cancer patients, with 10% experiencing severe reactions. Despite advancements, radiation dermatitis remains a challenge, disrupting treatment schedules and compromising patients' quality of life. Exploring herbal compounds, particularly Curcumin, has shown promise in addressing radiation-induced dermatitis, with its non-toxic and anti-inflammatory properties offering the potential for clinical trials to prevent these reactions. METHODS: This phase II randomized, double-blinded, placebo-controlled trial focused on adult females undergoing conventional fractionated RT. The main objective was to assess the efficacy of topical Curcumin in reducing the severity of radiation dermatitis. RESULTS: During a five-month study, 52 breast cancer patients completed the research. Participants were divided into Curcumin and placebo groups. In the first week, a significant difference in redness (P-value = 0.001) and irritation (P-value = 0.017) was observed, with the Curcumin group showing lower percentages. This trend continued in the second, third, and fourth weeks (P-value = 0.001). No statistical difference was found in itching (P-value = 0.446), and the occurrence of dryness (P-value = 1.000) remained constant in both groups throughout the four weeks. In pain the differences were significant in the second, third, and fourth weeks (P-value = 0.001). CONCLUSION: The study highlights the success of a 2% Curcumin gel in reducing skin side effects during breast cancer radiation therapy, suggesting its potential to enhance patients' quality of life. TRIAL REGISTRATION: IRCT20181208041882N3, 06/11/2020 (https://en.irct.ir/trial/49228).

Bacterial vaginosis (BV) is the prevailing infection. With the growing resistance of vaginal infections to routinely prescribed antibiotics, herbal medicine can be helpful. Researchers have conducted to compare the efficacy of curcumin and metronidazole in the treatment of BV as natural product. This study was a double-blind randomized clinical trial that involving 100 married women aged 18-49 who were not pregnant that sought treatment at two private outpatient clinics from January to September 2021 recruited in study. Individuals who met Amsel's clinical and paraclinical criteria for BV were randomly allocated to the intervention or control groups. Both groups were instructed to take their respective medications every 12 h for seven days. Subsequently, two weeks following the treatment, the efficacy of the treatment was assessed utilizing Amsel's clinical and paraclinical criteria. The data was analyzed using SPSS 26. The data was analyzed using the intention-to-treat (ITT) approach. The clinical (discharge (RD: 0.21; CI95%: 0.17-0.90; P = 0.01), whiff test (RD: 0.31; CI95%: 0.19-0.98; P = 0.03), and pH (RD: 0.18; CI95%: 0.19-1.04; P = 0.03)) and paraclinical variables of Amsel criteria (clue cells (RD: 0.19; CI95%: 0.13-1.03; P = 0.02) showed significant differences between groups. The curcumin consumer group exhibited a complete improvement rate of 82%, in contrast to the metronidazole group which had a rate of 42% two weeks after intervention. This study found curcumin have comparable efficacy to metronidazole in treating BV while demonstrating superior effectiveness and fewer adverse effects in alleviating symptoms. © 2025. The Author(s).

We investigate the role of homeostatic mechanisms involved in acute, postprandial nutrient metabolism and nutrient-induced systemic inflammation in CKD presence and progression in Metabolic dysfunction-associated steatohepatitis (MASH). We assessed postprandial incretins (GLP-1 and GIP), intestinotropic hormone GLP-2, endotoxin LPS, Zonulin (a marker of intestinal permeability), hepatokines, adipokines and NF-kB activation in circulating MNCs during a meal tolerance test in 52 biopsy proven MASH patients randomized to curcumin Meriva or placebo and 26 matched controls. At baseline, MASH-CKD had a lower GLP-2 response and a 2-fold higher postprandial LPS and NF-kB activation in MNCs than MASH patients without CKD, but similar remaining postprandial or fasting parameters. Postprandial IAUC GLP-2 predicted the presence of CKD in MASH (OR = 0.43, 95%CI:0.32-0.80, p = 0.008) independently of liver histology and traditional risk factors. After 72 weeks, changes in IAUC GLP-2 independently predicted the presence of CKD (OR = 0.49, 95%CI:0.21-0.73, p = 0.010) and eGFR changes [β(SE) = 0.510(0.007, p = 0.006] at end-of-treatment, In MASH, an impaired GLP-2 response to meals is associated with intestinal barrier dysfunction, endotoxemia and NF-kB-mediated systemic inflammation and may promote renal dysfunction and CKD. These data provide the rationale for evaluating GLP-2 analogues in MASH-related CKD.

INTRODUCTION: Even after the peak of the COVID-19 pandemic, the number of mild cases remains high, requiring continuous control. Curcumin, owing to its anti-inflammatory properties, can suppress vital proliferation and cytokine secretion in animal models. We developed a highly absorbable curcumin, curcuRouge® (cR), which is approximately 100 times more orally bioavailable than conventional curcumin. We evaluated the effect of cR on the inhibition of disease progression in asymptomatic or mildly symptomatic COVID-19 patients. METHODS: This study evaluated the effect of 7-day oral intake of cR (360 mg twice daily). Patients within 5 days of COVID-19 diagnosis were randomly assigned to a placebo or cR group in a double-blind manner. RESULTS: Primary endpoint events [body temperature (BT) ≥ 37.5 °C and saturation of percutaneous oxygen (SpO2) < 96%] were fewer than expected, and the rate of these events was 2.8% in the cR group (2/71) and 6.0% in the placebo group (4/67); hazard ratio (HR) = 0.532, 95% confidence interval (CI) 0.097-2.902. Patients receiving cR tended to take fewer antipyretic medications than those receiving placebo (HR = 0.716, 95% CI 0.374-1.372). Among patients with a normal range of BT at baseline, the BT change rate was significantly (p = 0.014) lower in the cR group (- 0.34%) versus placebo (- 0.01%). CONCLUSION: The relative suppression of event rates and antipyretic medications taken, and significant decrease of subclinical BT support the anti-inflammatory effects of cR in asymptomatic or mildly symptomatic patients with COVID-19. TRIAL REGISTRATION: Japan Registry of Clinical Trials (CRB5200002). © 2024. The Author(s).

BACKGROUND AND AIMS: NASH confers an increased liver-related and kidney morbidity. Phospholipid curcumin (Meriva) is a phospholipid formulation with ameliorated systemic curcumin absorption and delivery. We assessed the safety and efficacy of Meriva in NASH. APPROACH AND RESULTS: In this double-blind trial, 52 patients with biopsy-proven NASH (71% with stage ≥F2 fibrosis, 58% with stage A2-G2/A2-G3a chronic kidney disease) were randomized 1:1 to receive Meriva 2 g/d or placebo for 72 weeks. The primary endpoint was NASH resolution with no worsening of fibrosis. The secondary endpoints included a ≥1 stage liver fibrosis improvement with no NASH worsening; regression of significant (ie, stage ≥F2) fibrosis and CKD; and improvement in renal, glucose, lipid, and inflammatory parameters. We also explored the treatment effect on hepatic activation of NF-kB, a key proinflammatory transcription factor and a major target of curcumin. Fifty-one patients (26 on Meriva and 25 on placebo) completed the trial. Sixteen (62%) patients on Meriva versus 3 (12%) patients on placebo had NASH resolution (RR = 5.33 [95% CI = 1.76-12.13]; p = 0.003). Thirteen (50%) patients on Meriva versus 2 (8%) patients on placebo had ≥1 stage fibrosis improvement (RR = 6.50 [1.63-21.20]; p = 0.008). Eleven (42%) patients on Meriva versus 0 (0%) on placebo had regression of significant liver fibrosis (RR = 18.01 [1.43-36.07]; p = 0.02). Hepatic NF-kB inhibition predicted NASH resolution (AUC = 0.90, 95% CI = 0.84-0.95) and fibrosis improvement (AUC = 0.89, 95% CI = 0.82-0.96). Thirteen (50%) patients on Meriva versus 0 (0%) on placebo had chronic kidney disease regression (RR = 10.71 [1.94-17.99)]; p = 0.004). Compared with placebo, Meriva improved eGFR (difference in adjusted eGFR change: +3.59 [2.96-4.11] mL/min/1.73 m 2 /y, p = 0.009), fasting glucose(-17 mg/dL; 95% CI = -22, -12), HbA1c (-0.62%; 95% CI = -0.87%, -0.37%), LDL-C (-39 mg/dL; 95% CI = -45, -33), triglycerides (-36 mg/dL, 95% CI = -46, -26), HDL-C (+10 mg/dL; 95% CI = +8, +11), and inflammatory markers. Adverse events were rare, mild, and evenly distributed. CONCLUSIONS: In patients with NASH, Meriva administration for 72 weeks was

BACKGROUND AND OBJECTIVE: Sepiapterin, also known as PTC923 and CNSA-001, is a synthetic form of endogenous sepiapterin being developed as a novel oral treatment for phenylketonuria. Sepiapterin is a natural precursor of tetrahydrobiopterin (BH4) and, when orally administered, is converted to BH4 via the pterin salvage pathway. In vitro studies have demonstrated that both sepiapterin and BH4 are both substrates and inhibitors of the breast cancer resistance protein (BCRP) transporter. This phase I study investigated BCRP-mediated drug-drug interactions of sepiapterin as a victim and as a perpetrator. METHODS: An open-label, fixed-sequence, four-period, crossover, single-dose study was conducted in adult male and female healthy volunteers (18-55 years of age). In a given treatment period, subjects received a single oral dose of sepiapterin (20 mg/kg), sepiapterin (20 mg/kg) plus curcumin (2 g), rosuvastatin (10 mg), or rosuvastatin (10 mg) plus sepiapterin (60 mg/kg). The pharmacokinetics of sepiapterin, its metabolite BH4, and rosuvastatin were studied, and geometric mean ratios of exposures in the presence and absence of the BCRP inhibitor curcumin or sepiapterin were estimated. The presence of the BCRP c.421C>A polymorphism was evaluated in all subjects. RESULTS: A total of 29 subjects were enrolled and included in the safety analysis. Among them, 26 subjects were included in the pharmacokinetic and drug-drug interaction analyses. Following oral administration 20 mg/kg sepiapterin, sepiapterin was rapidly and extensively converted to BH4, and BH4 maximum observed concentration (415.0 ng/mL) was observed 4.95 h (time to maximum observed concentration) post-dose. Sepiapterin maximum observed concentration and area under the concentration-time curve from time 0 to time of the last quantifiable measurement or the last sample collection time (AUClast) were <1% of BH4 values. Coadministration of the BCRP inhibitor curcumin (2 g) increased BH4 maximum observed concentration, AUClast, and area under the concentration-time curve from time 0 extrapolated to infinity by 24%, 21%, and 20%, respectively. When sepiapterin was coadministered with the BCRP substrate rosuvasta

BACKGROUND: Drug combination therapy is preferred over monotherapy in clinical research to improve therapeutic effects. Developing a new nanodelivery system for cancer drugs can reduce side effects and provide several advantages, including matched pharmacokinetics and potential synergistic activity. This study aimed to examine and determine the efficiency of the gemini surfactants (GSs) as a pH-sensitive polymeric carrier and cell-penetrating agent in cancer cells to achieve dual drug delivery and synergistic effects of curcumin (Cur) combined with tamoxifen citrate (TMX) in the treatment of MCF-7 and MDA-MB-231 human BC cell lines. METHODS: The synthesized NPs were self-assembled using a modified nanoprecipitation method. The functional groups and crystalline form of the nanoformulation were examined by Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and dynamic light scattering (DLS) used to assess zeta potential and particle size, and the morphological analysis determined by transmission electron microscopy (TEM). The anticancer effect was evaluated through an in vitro cytotoxicity MTT assay, flow cytometry analysis, and apoptosis analysis performed for mechanism investigation. RESULTS: The tailored NPs were developed with a size of 252.3 ± 24.6 nm and zeta potential of 18.2 ± 4.4 mV capable of crossing the membrane of cancer cells. The drug loading and release efficacy assessment showed that the loading of TMX and Cur were 93.84% ± 1.95% and 90.18% ± 0.56%, respectively. In addition, the drug release was more controlled and slower than the free state. Polymeric nanocarriers improved controlled drug release 72.19 ± 2.72% of Tmx and 55.50 ± 2.86% of Cur were released from the Tmx-Cur-Gs NPs after 72 h at pH = 5.5. This confirms the positive effect of polymeric nanocarriers on the controlled drug release mechanism. moreover, the toxicity test showed that combination-drug delivery was much more greater than single-drug delivery in MCF-7 and MDA-MB-231 cell lines. Cellular imaging showed excellent internalization of TMX-Cur-GS NPs in both MCF-7 and MDA-MB-231 cells and synergistic anticancer effect

BACKGROUND: To treat diseases like cancer, conventional Paclitaxel (PTX)- based monotherapy treatment regimens are becoming less effective due to the development of resistance. In this aspect, the phytomolecule curcumin (Cur), having ethnopharmacological importance in traditional South Asian remedies, like Ayurveda and Chinese traditional medicine, has been studied as a promising chemo-sensitizing and synergistic partner of PTX. AIM: This study aimed to evaluate the combined effect of PTX and Cur compared to PTX therapy alone in the in vitro and in vivo environments. MATERIALS AND METHODS: An extensive PubMed search was performed wherein 169 papers were shortlisted and screened to identify 30 studies that have reported the effect of PTX and Cur either in vitro, in vivo, or both. The pooled Odds Ratio (OR) was calculated at a 95% Confidence Interval (CI) for determining the effect of combination therapy. RESULTS: The meta-analysis has indicated PTX and Cur combination therapy to be associated with a significant decrease in cell viability (OR: 0.37, 95% CI: 0.27-0.51; p < 0.01) and tumor volume (OR: 0.32, 95% CI: 0.15-0.71; p = 0.01). Additionally, the effect of this combination on drug-resistant cell lines has exhibited a significant decrease in the odds of cell viability (OR: 0.45, 95% CI: 0.35-0.57; p < 0.01). CONCLUSION: Overall, the current meta-analysis has shown PTX and Cur combination to effectively inhibit the viability of cancer cells, reduce tumor volume, and diminish the growth of drug-resistant cancer cells. Synergistic antioxidant effects of resveratrol and curcumin against fipronil-triggered oxidative damage in male albino rats. AlBasher G(1), Abdel-Daim MM(2)(3), Almeer R(1), Ibrahim KA(4), Hamza RZ(5), Bungau S(6), Aleya L(7). Author information: (1)Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia. (2)Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia. [email protected]. (3)Department of Pharmacology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, 41522, Egypt. [email protected]. (4)Mammalian

43. Environ Sci Pollut Res Int. 2020 Feb;27(6):6505-6514. doi: 10.1007/s11356-019-07344-8. Epub 2019 Dec 23. Synergistic antioxidant effects of resveratrol and curcumin against fipronil-triggered oxidative damage in male albino rats. AlBasher G(1), Abdel-Daim MM(2)(3), Almeer R(1), Ibrahim KA(4)

Advanced colon cancer is extremely difficult to cure, underscoring the need to develop novel therapeutic agents. Prenylated curcumins that are semisynthetic curcumin derivatives with significant anti-cancer potential have been studied herein to assess their therapeutic potential for colon cancer and tested to this aim in vitro for their growth inhibitory properties against 5-fluorouracil + oxaliplatin resistant human colon cancer CR-HT29 and HCT-116 cells. The resulting most active product, gercumin (mono-O-geranylcurcumin), has been further tested for its synergistic effects with FOLFOX (a combination of 5-fluorouracil and oxaliplatin) on the same cell lines. Activity of this combination on colonosphere formation was also investigated. Gercumin was able to suppress the growth of cancer cells with a potency similar to that of curcumin. A synergistic effect of this compound and FOLFOX was also observed. doses tested for synergy in the colonosphere assays did not show greater suppression of colonosphere formation than independent treatment with either reagent alone. Only one of the combinations was shown to be more effective at suppressing colonosphere formation [gercumin 5 μM + FOLFOX (2x)]. Thus, the growth inhibitory effects of curcumin against human cancer cells can be modulated and enhanced by the introduction of hydrophobic chains, normally found in several natural compounds, like the geranyl one. Such compounds are also able to synergize with known chemotherapeutics.

Ayurvedic system of medicine is using Berberis aristata and Curcuma longa herbs to treat different diseases including cancer. The study was performed to evaluate the synergetic anticancer activity of Berberine and Curcumin by estimating the inhibition of the cell proliferation by cytotoxicity assay using MTT method on specified human cell lines (A549, Hep-G2, MCF-7, Jurkat, and K562). All the cells were harvested from the culture and seeded in the 96-well assay plates at seeding density of 2.0 × 10(4) cells/well and were incubated for 24 hours. Test items Berberine with Curcumin (1 : 1), Curcumin 95% pure, and Berberine 95% pure were exposed at the concentrations of 1.25, 0.001, and 0.5 mg/mL, respectively, and incubated for a period of 48 hours followed by dispensing MTT solution (5 mg/mL). The cells were incubated at 37 ± 1°C for 4 hours followed by addition of DMSO for dissolving the formazan crystals and absorbance was read at 570 nm. Separate wells were prepared for positive control, controls (only medium with cells), and blank (only medium). The results had proven the synergetic anticancer activity of Berberine with Curcumin inducing cell death greater percentage of >77% when compared to pure curcumin with <54% and pure Berberine with <45% on average on all cell line models.

This work investigated the potential of curcumin (CCM) and (-)-epigallocatechin gallate (EGCG) to inhibit N-acyl homoserine lactone (AHL)-mediated biofilm formation in gramnegative bacteria from membrane bioreactor (MBR) activated sludge. The minimum inhibitory concentrations (MICs) of CCM alone against all the tested bacteria were 200-350 μg/ml, whereas those for EGCG were 300-600 μg/ml. Biofilm formation at one-half MICs indicated that CCM and EGCG alone respectively inhibited 52-68% and 59-78% of biofilm formation among all the tested bacteria. However, their combination resulted in 95-99% of biofilm reduction. Quorum sensing inhibition (QSI) assay with known biosensor strains demonstrated that CCM inhibited the expression of C4 and C6 homoserine lactones (HSLs)-mediated phenotypes, whereas EGCG inhibited C4, C6, and C10 HSLs-based phenotypes. The Center for Disease Control biofilm reactor containing a multispecies culture of nine bacteria with onehalf MIC of CCM (150 μg/ml) and EGCG (275 μg/ml) showed 17 and 14 μg/cm(2) of extracellular polymeric substances (EPS) on polyvinylidene fluoride membrane surface, whereas their combination (100 μg/ml of each) exhibited much lower EPS content (3 μg/cm(2)). Confocal laser scanning microscopy observations also illustrated that the combination of compounds tremendously reduced the biofilm thickness. The combined effect of CCM with EGCG clearly reveals for the first time the enhanced inhibition of AHL-mediated biofilm formation in bacteria from activated sludge. Thus, such combined natural QSI approach could be used for the inhibition of membrane biofouling in MBRs treating wastewaters.

Apigenin, a natural flavone, present in many plants sources, induced apoptosis and cell death in lung epithelium cancer (A549) cells with an IC50 value of 93.7 ± 3.7 μM for 48 h treatment. Target identification investigations using A549 cells and also in cell-free system demonstrated that apigenin depolymerized microtubules and inhibited reassembly of cold depolymerized microtubules of A549 cells. Again apigenin inhibited polymerization of purified tubulin with an IC50 value of 79.8 ± 2.4 μM. It bounds to tubulin in cell-free system and quenched the intrinsic fluorescence of tubulin in a concentration- and time-dependent manner. The interaction was temperature-dependent and kinetics of binding was biphasic in nature with binding rate constants of 11.5 × 10(-7) M(-1) s(-1) and 4.0 × 10(-9) M(-1) s(-1) for fast and slow phases at 37 °C, respectively. The stoichiometry of tubulin-apigenin binding was 1:1 and binding the binding constant (Kd) was 6.08 ± 0.096 μM. Interestingly, apigenin showed synergistic anti-cancer effect with another natural anti-tubulin agent curcumin. Apigenin and curcumin synergistically induced cell death and apoptosis and also blocked cell cycle progression at G2/M phase of A549 cells. The synergistic activity of apigenin and curcumin was also apparent from their strong depolymerizing effects on interphase microtubules and inhibitory effect of reassembly of cold depolymerized microtubules when used in combinations, indicating that these ligands bind to tubulin at different sites. In silico modeling suggested apigenin bounds at the interphase of α-β-subunit of tubulin. The binding site is 19 Å in distance from the previously predicted curcumin binding site. Binding studies with purified protein also showed both apigenin and curcumin can simultaneously bind to purified tubulin. Understanding the mechanism of synergistic effect of apigenin and curcumin could be helped to develop anti-cancer combination drugs from cheap and readily available nutraceuticals.

PURPOSE: Curcumin, a plant-derived natural polyphenol, could be a promising anti-cancer drug and shows synergic effects with cytotoxic agents. We evaluated the safety and feasibility of combination therapy using curcumin with gemcitabine-based chemotherapy. METHODS: Gemcitabine-resistant patients with pancreatic cancer received 8 g oral curcumin daily in combination with gemcitabine-based chemotherapy. The primary endpoint was safety for phase I and feasibility of oral curcumin for phase II study. RESULTS: Twenty-one patients were enrolled. No dose-limiting toxicities were observed in the phase I study and oral curcumin 8 g/day was selected as the recommended dose for the phase II study. No patients were withdrawn from this study because of the intolerability of curcumin, which met the primary endpoint of the phase II study, and the median compliance rate of oral curcumin was 100% (Range 79-100%). Median survival time after initiation of curcumin was 161 days (95% confidence interval 109-223 days) and 1-year survival rate was 19% (4.4-41.4%). Plasma curcumin levels ranged from 29 to 412 ng/ml in five patients tested. CONCLUSIONS: Combination therapy using 8 g oral curcumin daily with gemcitabine-based chemotherapy was safe and feasible in patients with pancreatic cancer and warrants further investigation into its efficacy.

BACKGROUND: Curcumin is a kind of plant polyphenol that is extracted from the rhizome of Curcuma longa. Studies about the effect of curcumin on the activity of drug-metabolizing enzymes in humans are lacking. OBJECTIVE: To investigate the effect of curcumin on the activities of CYP1A2, CYP2A6, N-acetyltransferase (NAT2), and xanthine oxidase (XO) in vivo, using caffeine as a probe drug. METHOD: Sixteen unrelated, healthy Chinese men were recruited for the study. There were 2 phases in the study. In the first phase, volunteers orally received 100 mg caffeine and 0- to 12-hour blood and urine samples were collected. In the second phase, volunteers received 1000 mg curcumin once daily for 14 continuous days, and blood and urine samples were collected on day 15, following the same procedure used on the first day. Urinary caffeine metabolite ratios were used as the indicators of the activities of CYP1A2, CYP2A6, NAT2, and XO. The pharmacokinetics of caffeine and its metabolites were determined by high-performance liquid chromatography. RESULTS: In the curcumin-treated group, CYP1A2 activity was decreased by 28.6% (95% CI 15.6 to 41.8; p < 0.000), while increases were observed in CYP2A6 (by 48.9%; 95% CI 25.3 to 72.4; p < 0.000). Plasma area under the curve from zero to 12 hours of 1,7-dimethylxanthine (17X) was decreased by 27.2% (95% CI 6.1 to 48.3; p = 0.014). The urinary excretion of 17X and 1-methylxanthine was significantly decreased by 36.4% (95% CI 19.4 to 53.6; p < 0.000) and 31.2% (95% CI 8.5 to 54.1; p = 0.010), respectively. The excretion of 1,7-dimethylurate (17U) was significantly increased by 77.3% (95% CI 5.6 to 148.8; p = 0.036). No significant changes were observed for caffeine, 1-methylurate, and 5-acetylamino-6-formylamino-3-methyluracil between the 2 study phases. CONCLUSIONS: The results indicated that curcumin inhibits CYP1A2 function but enhances CYP2A6 activity. Simultaneously, some pharmacokinetic parameters relating to 17X were affected by curcumin. If this finding is confirmed by other studies, the possibility of herb-drug interactions associated with curcumin should be considered in clinical practice.