CURCUMIN

Extracted from the indian spice tumeric and most known for anti-inflammatory activity. The most promising results have so far been small phase II trials in colorectal cancer at 2g daily which showed significantly lower cancer progression following chemotherapy. Branded formulae for high absorption have been developed such as BCM-95/Curcugreen, Longvida, Meriva, available in branded supplements. There is a positive trial of of Meriva in pancreatic cancer treatment supporting chemotherapy (see Highlights). Overall though, there is a lack of evidence from the many varied clinical trials completed, many studies showing no effects.

There is, however, very good evidence that curcumin in sufficient levels can suppress many of the systemic inflammatory and metabolic markers associated with progression of cancer. Most clearly reducing inflammatory marker c-reactive protein, and insulin resistance but tends also to lower leptin , IL-6. All of which are linked with both higher incidence and more aggressive progression rates of several cancers. Supporting this are promising findings in pilot studies for late stage liver cancer combined with taurine (see Examples)

Though clinical trial findings can vary, the weight of evidence shows that sufficient doses sustained over time deliver substantial improvements in these drivers of cancer progression. And, research shows such effects can be important in reducing risks of treatment side effects such as stroke. (see References). Trials vary in terms of use of curcumin extracts or high absorption formulae, the latter do seem to provide better penetration in clinical testing. Curcumin as a mild natural copper chelator, for instance in relation to risk and progression in breast cancer. (see Concerns). Use of copper chelators has been suggested following meta-analysis linking copper levels to cancer progression rates. (see also Citrus Pectin)

TYPICAL ABSORPTION LEVELS

1 – 5%

EXAMPLES OF IMPROVED OUTCOMES

YES
ANALYSIS

PRE-DIAGNOSIS OR PREVENTION

PENDING

Highlighted Studies

Addition of daily oral curcumin to FOLFOX chemotherapy was safe and tolerable (primary outcome). Similar adverse event profiles were observed for both arms. In the intention-to-treat population, the HR for PFS was 0.57 (95% CI: 0.24, 1.36; P = 0.2) (median of 171 and 291 d for FOLFOX and CUFOX, respectively) and for OS was 0.34  (median of 200 days and 502 days for FOLFOX and CUFOX, respectively). There was no significant difference between arms for quality of life or neurotoxicity . Curcumi...

Link

In conclusion, the results of the present work support the notion that altered expression of serum IL-10, miR-21, and miR-141 may be prognostic biomarkers that may help to guide treatment in HCC. Further, in a population of patients with fairly advanced HCC, the administration of a combined treatment composed of curcumin, piperine, and taurine for three successive months was able to decrease the circulating level of IL-10 and miR-21, with no effect on miR-141 expression level, which may be re...

Link

We observed 27.3% of response rate and 34.1% of cases with stable disease, totalizing a disease control rate of 61.4%. [Meriva branded curcumin] The median progression free survival and overall survival were 8.4 and 10.2 months, respectively. Higher IL-6 and sCD40L levels before treatment were associated to a worse overall survival (p < 0.01). Increases in sCD40L levels after 1 cycle of chemotherapy were associated with a reduced response to the therapy.. In conclusion, the complementa...

Link

..at least some improvements were observed in most patients [advanced stage breast cancer], with biological (decrease in CEA tumor marker across the treatment) and clinical (regression of non measurable lesions) responses. Based on these observations, we could expect a response rate up to 50% in a population of all evaluable patients treated with the combination docetaxel/curcumin. However further investigation is needed to confirm the eventually increased response rate to this combination in...

Link
BACK TO INDEX

TABLE OF REFERENCES

Help grow the evidence. Login and use the form, or try Feedback and Ideas below.

URLRatingHighlightHighlight 2Visuals (click)
https://pmc.ncbi.nlm.nih.gov/articles/PMC6602900/3.5Human study - adjunctAddition of daily oral curcumin to FOLFOX chemotherapy was safe and tolerable (primary outcome). Similar adverse event profiles were observed for both arms. In the intention-to-treat population, the HR for PFS was 0.57 (median of 171 and 291 days for FOLFOX and CUFOX, respectively) and for OS was 0.34 (median of 200 and 502 days for FOLFOX and CUFOX, respectively). There was no significant difference between arms for quality of life or neurotoxicity ..Curcumin glucuronide was detectable at concentrations >1.00 pmol/mL in 15 of 18 patients receiving CUFOXIn conclusion, here we present the first randomized controlled trial for curcumin in combination with FOLFOX chemotherapy for patients with metastatic colorectal cancer. Despite significant caveats that relate to the small study size, combination of curcumin with FOLFOX chemotherapy represents a safe and tolerable treatment with potential to provide patient benefit. To further assess curcumin as an adjunct to standard-of-care platinum-based chemotherapy, a phase III trial is now warranteScreenshot from 2024-11-16 15-51-55
https://www.sciencedirect.com/science/article/abs/pii/S1043661818301609?via%3Dihub3.5Human study - adjunctWe observed 27.3% of response rate and 34.1% of cases with stable disease, totalizing a disease control rate of 61.4%. The median progression free survival and overall survival were 8.4 and 10.2 months, respectively. Higher IL-6 and sCD40L levels before treatment were associated to a worse overall survival (p < 0.01). Increases in sCD40L levels after 1 cycle of chemotherapy were associated with a reduced response to the therapy. Grade 3/4 toxicity was observed (neutropenia, 38.6%; anemia, 6.8%). There were no significant changes in quality of life during therapy. In conclusion, the complementary therapy to gemcitabine with phytosome complex of curcumin is not only safe but also efficiently translate in a good response rate in first line therapy of advanced pancreatic cancer.Besides clinical evidence, we also investigated the role of inflammation asking whether circulating inflammation-related biomarkers can predict the outcome of the disease. Results clearly indicate that the use of curcumin as Meriva® is safe and increases the efficiency of GEM translating in a response rate (RR) in the first line therapy of advanced PC superior to that described to GEM as single agent and similar to that produced by the more toxic treatment with nab-P + G
https://jgo.amegroups.org/article/view/27856/html3.5Human study - adjunct In conclusion, the results of the present work support the notion that altered expression of serum IL-10, miR-21, and miR-141 may be prognostic biomarkers that may help to guide treatment in HCC. Further, in a population of patients with fairly advanced HCC, the administration of a combined treatment composed of curcumin, piperine, and taurine for three successive months was able to decrease the circulating level of IL-10 and miR-21, with no effect on miR-141 expression level, which may be reflected on the OS rate positively.The results of the current study revealed that high IL-10 level was a poor prognostic sign where the median OS of patients in the low IL-10 sub-group was 1.6 folds more than that of patients in the high IL-10 sub-group. This echoes previous studies indicating that the serum IL-10 level was an adverse prognostic factor for patients with inoperable HCC and in those after surgical resection (42-44), confirms a predominantly immunosuppressive role of IL-10 for circulating dendritic cells in patients with HCC, and thus may indicate the aspects of tumor immune evasion (45). The combined treatment was able to decrease IL-10 serum level significantly after 2 cycles of administrationScreenshot from 2025-06-23 20-51-59
https://aacrjournals.org/clincancerres/article/14/14/4491/72572/Phase-II-Trial-of-Curcumin-in-Patients-with3.5Human study - adjunct..curcumin was detectable as drug in glucuronide and sulfate conjugate forms, albeit at low steady-state levels, suggesting poor oral bioavailability. Two patients showed clinical biological activity. One had ongoing stable disease for >18 months; interestingly, one additional patient had a brief, but marked, tumor regression (73%) accompanied by significant increases (4- to 35-fold) in serum cytokine levels (IL-6, IL-8, IL-10, and IL-1 receptor antagonists). No toxicities were observed. Curcumin down-regulated expression of NF-κB, cyclooxygenase-2, and phosphorylated signal transducer and activator of transcription 3 in peripheral blood mononuclear cells from patients Phase I studies of curcumin have shown that this agent can be administered safely at oral doses of up to 8 g/d (14, 15). There was no dose-limiting toxicity; dosing was limited by the number of pills that patients could or would swallow daily. However, the usefulness of curcumin may be attenuated because of its poor oral bioavailability (16). Therefore, we did the present phase II study to determine whether oral curcumin has biological activity in patients with pancreatic cance
https://www.mdpi.com/2072-6643/16/11/17283Meta-analysisIn conclusion, we evaluated the effects of curcumin intake on chronic inflammatory metabolic disease by reviewing meta-analyses of RCTs...Curcumin intake significantly reduced TC levels in 14 of 19 meta-analyses. Our results reveal that curcumin intake effectively and protectively exerts chronic inflammatory metabolic diseases through improved levels of glucose homeostasis, MDA, TC, and inflammation (CRP, IL-6, TNF-α, and adiponectin). The safety and efficacy of curcumin indicate that it is possible to prevent and treat chronic inflammatory metabolic diseases.This review clearly observed that curcumin intake could significantly reduce major inflammatory markers of CRP (seven of ten meta-analyses of RCTs), IL-6 (five of eight meta-analyses of RCTs), and TNF-α (six of nine meta-analyses of RCTs). In light of this review finding that curcumin intake significantly lowered MDA levels in five of six meta-analyses, curcumin intake appeared to have antioxidant activity. Consistent with our findings, Naghsh et al. 2023 [273] found the effects of curcumin on inflammatory biomarkers in an umbrella meta-analysis of 10 RCTs , in which curcumin doses ranging from 100 to 1900 mg/day were supplemented for 4.5 to 10.5 weeks
https://link.springer.com/article/10.1007/s00228-024-03764-93Meta-analysisAlthough studies showed some beneficial effects of curcumin administration on cancer therapy-related side effects, especially oral symptoms and weight loss, there were clear methodological weaknesses decreasing the reliability of these results. Furthermore, the studies included in this analysis had heterogeneous designs, evaluated different scores when assessing the same endpoints, and many were of poor quality. Various standard therapies, including different chemotherapeutic agents and RTx regimens, were utilized, which makes it difficult to compareApart from mild gastrointestinal symptoms, the included studies do not report side effects resulting from the administration of curcumin. However, serious AEs associated with the use of curcumin have been reported in other publications. Due to its antioxidant properties, curcumin may potentially interfere with the efficacy of CTx or RTx. In view of the unclear efficacy and possible risks, the clinical use of curcumin in cancer therapy should be critically scrutinized according to the current state of knowledge
https://nutritionj.biomedcentral.com/articles/10.1186/s12937-023-00905-13Human studyResults of the current study indicated that curcumin-piperine co-supplementation has beneficial effects on CIMT, systolic and diastolic blood pressure as well as serum levels of hs-CRP, TC, TG, and TAC. No significant changes were observed between the two groups in terms of serum fibrinogen, LDL, HDL, and most of the quality-of-life indicators. More well-designed and long-term randomized controlled trials are needed to confirm the present resultsThe results of this study showed that 12 weeks of curcumin-piperine supplementation reduced CIMT, hs-CRP, TC, TG, systolic and diastolic blood pressure, weight, waist circumference, and increased TAC in patients with stroke. Based on our knowledge, this study is the first clinical trial that examined the effect of curcumin-piperine on clinical as well as biochemical risk factors in patients with stroke. The findings of this study might help improve the health status of stroke patients.
https://pubmed.ncbi.nlm.nih.gov/37980942/3Meta-analysisThirteen RCT with fourteen treatment arms were eligible for inclusion in this meta-analysis. Curcumin supplementation was effective in increasing serum adiponectin (SMD = 0·86, 95 % CI (0·33, 1·39), P < 0·001; I2 = 93·1 %, P < 0·001) and reducing serum leptin (SMD = −1·42, 95 % CI (−2·29, −0·54), P < 0·001; I2 = 94·7 %, P < 0·001). In conclusion, curcumin supplementation significantly increased circulating adiponectin and decreased leptin levels in adultsOur results suggest that curcumin supplementation can decrease and increase circulating leptin and adiponectin, respectively. High doses of curcumin (up to 3000 mg/d in tumeric form, 1500 mg/d in curcuminoid form and 1000 mg/d in highly bioavailable form) in a highly bioavailable form including nano-curcumin, phospholipidated curcumin, theracurmin, curcumin+piperine or curcumin+soluble fiber has a better effect on adipokines level
https://pmc.ncbi.nlm.nih.gov/articles/PMC9870680/3Meta-analysisIn terms of mean age, subgroup analysis showed that curcumin supplementation in people who are older than 45 years had a significant decreasing effect on inflammatory biomarkers in comparison with younger participants. As oxidative imbalance and inflammation increase with aging, more improving effect of curcumin on inflammation in this subgroup was not a surprising finding. According to this promising finding, curcumin can be considered as a useful agent for longevity through the reduction of oxidative stresA meta-analyses of ten studies with 5,870 participants indicated a significant decrease in C-reactive protein (CRP) (ES = −0.74), interleukin 6 (IL-6) (ES = −1.07), and tumour necrosis factor α (TNF-α) levels (ES: −1.92) following curcumin supplementation. Greater effects on CRP and TNF-α were evident in trials with a mean age >45 years and a sample size >300 participants.
https://www.sciencedirect.com/science/article/pii/S096522992400013X3Meta-analysisCurcumin supplementation in doses of 50−3000 mg/day over 8–12 weeks was associated with significant reductions in levels of FBG, HOMA-IR, TG, TC, LDL, weight and BMI in patients with NAFLD. Previous studies have reported curcumin as a safe complementary therapy for several diseases. We would suggest that should curcumin supplements be used clinically in specific conditions, it should be used with caution.In conclusion, our study indicated that curcumin supplementation in doses of 50 − 3000 mg/day over 8–12 weeks was associated with significant changes in FBG, HOMA-IR, TG, TC, LDL, weight and BMI in adults with NAFLD. Although, there is no significant change in HbA1C, insulin, QUICKI, HDL, SBP, DBP, IL-6, CRP, TNF-α, and WC after curcumin therapy. Further studies are required in subjects with different degress of NAFLD drawn from more diverse populations for a definitive conclusion to be made.
https://iris.unito.it/bitstream/2318/1633548/3/curcumin%20rev.pdf3Meta-analysisThere was a significant reduction of circulating IL-6 concentrations following curcuminoids supplementation (WMD: −0.60 pg/mL, 95% CI: −1.06, −0.14, p = 0.011). Meta-regression did not suggest any significant association between the circulating IL-6 lowering effects of curcuminoids with either dose or duration of treatment. There was a significant association between the IL-6-lowering activity of curcumin and baseline IL-6 concentration (slope: −0.51; 95% CI: −0.80, −0.23; p = 0.005). This meta-analysis of RCTs suggested a significant effect of curcumin in lowering circulating IL-6 concentrations. This effect appears to be more evident in patients with higher degrees of systemic inflammations expected, greater plasma IL-6 reductions have been obtained in patients with high-grade systemic inflammation receiving the potent anti-inflammatory methotrexate [64]. In this regard, our meta-regression showed that there was a significant association between the IL-6-lowering activity of curcumin and baseline IL-6 concentration. Therefore, we must consider that the anti-inflammatory effect of curcumin might be more evident in patients with a greater degree of systemic inflammation. Overall, our results of a significant IL-6 reduction by curcumin supplementation support the idea that this nutraceutical may have a role in suppressing pro-inflammatory pathways linked with different diseases.
https://pmc.ncbi.nlm.nih.gov/articles/PMC3476912/3Meta-analysisAfter 9 months of treatment, 16.4% of subjects in the placebo group were diagnosed with T2DM, whereas none were diagnosed with T2DM in the curcumin-treated group. In addition, the curcumin-treated group showed a better overall function of β-cells, with higher HOMA-β (61.58 vs. 48.72; P < 0.01) and lower C-peptide (1.7 vs. 2.17; P < 0.05). The curcumin-treated group showed a lower level of HOMA-IR (3.22 vs. 4.04; P < 0.001) and higher adiponectin (22.46 vs. 18.45; P < 0.05) when compared with the placebo group.HOMA-IR level is a clinical representative of insulin resistance (22). HOMA-IR from both placebo and curcumin-treated groups was examined. The means of HOMA-IR of the curcumin-treated group were lower than those of placebo group at all follow-up visits (3, 6, and 9 months) (Fig. 1F). The differences were significant, particularly at the 6- and 9-month visits. Levels of adiponectin, an anti-inflammatory cytokine, in the placebo-treated group were virtually unchanged, whereas those of the curcumin-treated group were gradually elevated (at 3 and 6 months) and became significantly different from that of placebo-treated group at the final visit
https://pubmed.ncbi.nlm.nih.gov/34586711/3Meta-analysisCRP concentration significantly decreased after >10-week intervention compared with placebo.hs-CRP concentration in the intervention group was significantly lower than that of placebo group. A significant effect of curcumin consumption was detected on the serum level of hs-CRP in studies with prescribing ≤1,000 mg/day, and those with ≤10-week duration of intervention. Curcumin consumption resulted in a reduction of hs-CRP in a non-linear fashion with stronger effects with less than 2000 mg curcumin per day. Curcumin seems to be beneficial in decreasing the hs-CRP and CRP levels in proinflammatory settings. It has been suggested that curcumin is a potential agent for lowering the levels of C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP), as markers of inflammation. In the current meta-analysis, we attempted to clarify the efficacy of curcumin supplementation in lowering the concentrations of CRP and hs-CRP in patients with autoinflammatory conditions. Nine studies were found evaluating the effect of curcumin on CRP levels, while 23 studies were identified for hs-CRP. CRP concentration was decreased significantly compared to the placebo (WMD = -3.67 mg/L, 95% CI = -6.96 to -0.38, p = 0.02). There was a significant effect of curcumin at dose ≤1,000 mg/day on the CRP concentration.
https://onlinelibrary.wiley.com/doi/abs/10.1002/pros.237662Human study - adjunct Six months’ intake of oral curcumin did not significantly affect the overall off-treatment duration of IAD. However, PSA elevation was suppressed with curcumin intake during the curcumin administration period. Curcumin at this dose was well tolerated and safe.The proportion of patients with PSA progression during the active curcumin treatment period (6 months) was significantly lower in the curcumin group than the placebo group (10.3% vs 30.2%, P = 0.0259). The change of PSA, testosterone levels during 6 months, and HRQOL scores at 6 months were not different between curcumin and placebo groups
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10392087/1Lab study, Lab study- adjunct We show that topical GZ21T [includes curcumin] inhibits AK [aktinic keratosis] growth in a murine model of skin carcinogenesis. Mechanistically, GZ21T downregulates the pathways involved in DNA synthesis, protein synthesis, metabolism, and cell cycle progression. Our results also show that GZ21T prevents the progression of AK to cSCC [skin cancer] a.... this study demonstrates its efficacy in a topical formulation. It is thought that topical administration of curcumin may have superior efficacy to that of oral dosing because the compound is susceptible to a large first-pass metabolism resulting in less than 1% of oral curcumin entering the plasma. ...topical medications do not require significant systemic concentrations to reach the skin... combination of a topical route of administration and the inherent synergism among components of GZ21T makes it an effective drug in the treatment of cutaneous disorders.Loss of HIF-1α results in decreased tumorigenesis as knockout mice exhibit an increased rate of DNA repair processes, slowing the accumulation of carcinogenic alterations (Mahfouf et al., 2019). Aberrant Wnt signaling has also been shown to be a major factor in cSCC development and progression as it allows the transcription factor β-catenin to escape proteasomal degradation to promote a stem-like phenotype and hyperproliferation of KCs (Lang et al., 2019). Finally, ERBB (EGFR) alterations are common in epithelial cancers because they provide a growth stimulus to promote self-renewal and propagation of malignant tissues (Ciardiello and Tortora, 2008). Previous studies have shown that numeric aberrations in EGFR expression may be present in up to 52% of AKs and 77% of cSCC (Toll et al., 2010). Interestingly, these pathways were not altered in NL skin, suggesting that GZ21T may preferentially suppress their signaling in AK lesions while sparing healthy tissue.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673136/1Lab studyCurcumin treated animals had a significant reduction in tumor growth as measured by the decrease in size of the subcutaneous xenografts compared to untreated animals. Moreover, the amount of exosomes collected from plasma of treated mice was higher than control mice and these exosomes are enriched in miR-21 compared to control exosomes. Overall, these data indicated an antineoplastic role of Curcumin in CML cells, by a selective packaging of miR-21 in exosomes and an increase of miR-196b in CML cells suggesting that Curcumin could be a potential therapeutic agent for CML.Our results indicate that Curcumin might exert anticancer effects through elimination of miR-21, via exosomes. We showed that Curcumin caused a decrease of miR-21, but not pre-miR-21, in CML cells after Curcumin treatment. On the contrary, we observed an increase of miR-21 in the exosomes released by CML cells after addition of Curcumin (Figure ​(Figure2).2). Our results are in line with other studies that demonstrated the effects of Curcumin on cancer cell survival through down-regulation of miR-21 and increase of PTEN. PTEN up regulation, caused by non-genomic mechanisms, such as post transcriptional regulation by non-coding RNA, antagonizes the PI3K-AKT pathway [39]. This inhibitory effect acts on the PI-3K-AKT pathway, which controls cell proliferation and survival.Screenshot from 2024-02-08 16-10-30
https://www.hindawi.com/journals/jsc/2012/147863/fig1/1Lab studyAntiproliferative effects of curcumin were demonstrated in an aggressive skin cancer cell line SRB12-p9 ( compared to control). Topical formulation was as effective as oral curcumin at suppressing tumor growth in a mouse skin cancer model. Curcumin at 15 mg administered by oral, topical, or combined formulation significantly reduced tumor growth compared to controlIn this study we found significant and complete inhibition of SRB12-p9 cell proliferation after treatment with curcumin at a dose 20 μM or higher (Figure 1(a)) suggesting a highly potent anticarcinogenic effect of curcumin in skin cancer. Additionally, we found that the inhibitory effect of curcumin on skin cancer proliferation was associated with inhibition of AKT/mTOR and ERK signaling

Help grow the community

Join the Pubmedders subscriber base

Get our monthly email newletter – designed so you can give us your opinions, thoughts and feedback…

ALL contributions are invested into growing the site to help others.