Curcumin

 Longevity:

 

• In ITP, curcumin extended genetically-heterogeneous mice lifespan by 3.69% (link), but this result wasn’t statistically significant. Mice lifespan +10% (p < 0.01) in another study. (ref)

 

Metabolic effects:

 

• Lowers chronic inflammation. C-reactive protein (−1.55 mg/L; −1.81 to −1.30), IL6 (−1.69 pg/mL, −2.56 to −0.82), tumor necrosis factor α (−3.13 pg/mL; −4.62 to −1.64), IL-8 (−0.54 pg/mL; −0.82 to −0.28), and an increase in IL-10 (0.49 pg/mL; 0.10 to 0.88) (ref)

• Increases total antioxidant capacity. A significant increase of SOD activities (WMD: 1.46 U/mL, 95%CI: 0.60–2.32, p = 0.0009),  significantly reduced serum lipid peroxides (WMD: −6.35 nmol/mL, 95%CI: −11.06 to −1.64, p = 0.008), increased GSH concentrations (WMD: 5.39 µg/mL, 95%CI: 1.17–9.60, p = 0.01), and catalase activity (WMD: 51.78 U/mL, 95%CI: 15.71–87.85, p = 0.005) (ref)

• Helps with weight loss. Significantly reduced body mass index (BMI) (SMD −0.37; 95% CI, −0.61, −0.13; P < 0.01), weight (SMD −0.23; 95% CI, −0.39, −0.06; P < 0.01), waist-circumference (WC) (SMD −0.25; 95% CI, −0.44, −0.05; P = 0.01), leptin levels (SMD −0.97; 95% CI, −1.18, −0.75; P < 0.001) and increased adiponectin levels (SMD 1.05; 95% CI, 0.23, 1.87; P = 0.01). (ref)

• Helps with blood sugar. Significantly decreased fasting blood glucose (p < 0.01), HbA1c (p = 0.031), and insulin resistance index (HOMA-IR) (p < 0.01) in type 2 diabetic patients. Curcuminoids also led to a significant decrease in serum total FFAs (p < 0.01), triglycerides (P = 0.018), an increase in LPL activity (p < 0.01). (ref)

• In NAFLD, trend toward significant reduction of ALT blood concentrations in subgroup with ≥1000 mg/day curcumin supplementation (-11.36 IU/L, 95% CI: -22.75 to 0.02; ); significant reduction of AST in studies with 8-weeks administration (-9.22 IU/L, 95% CI: -12.77 to -5.67;). (ref)

Anti-cancer effects:

• Curcumin Promotes Cell Cycle Arrest and Inhibits Survival of Human Renal Cancer Cells by Negative Modulation of the PI3K/AKT Signaling Pathway.

• Curcumin induces apoptosis and autophagy inhuman renal cell carcinoma cells via Akt/mTOR suppression.

• Curcumin Has Asymmetrical Effects on Cancer Stem Cells.

• Curcumin induces apoptosis in JAK2-mutated cells by the inhibition of JAK2/STAT and mTORC1 pathways

• Successful case report against Myeloma using 8g(!) curcumin per day. 

Curcumin Promotes Cell Cycle Arrest and Inhibits Survival of Human Renal Cancer Cells by Negative Modulation of the PI3K/AKT Signaling Pathway, 2015

 

Curcumin possesses anti-cancer effects. In the current study, we tested the effect of curcumin on cell proliferation, viability, apoptosis, cell cycle phases, and activation of the PI3K/Akt pathway in the renal cell carcinoma (RCC) cell line RCC-949. We observed that cell proliferation and viability were markedly inhibited by curcumin, while cell apoptosis was promoted. The latter effect was associated with increased expression of Bcl-2 and diminished expression of Bax (both: mRNA and protein). The cells treated with curcumin increasingly went into cell cycle arrest, which was likely mediated by diminished expression of cyclin B1, as seen in curcumin-treated cells. In addition, curcumin decreased activation of the PI3K/AKT signaling pathway. In conclusion, our results demonstrate that curcumin exerts anti-cancer effects by negative modulation of the PI3K/AKT signaling pathway and may represent a promising new drug to treat RCC.

 

Curcumin induces apoptosis and autophagy inhuman renal cell carcinoma cells via Akt/mTOR suppression, 2021

 

The work assessed the effects of RCC treatment with Curcumin, Curcumin+3-MA, Curcumin+ CQ or curcumin+ Z-VAD in vitro and in vivo, and the mechanisms involved in inhibition of tumor cells proliferation. The study used ACHN tumor cells and C57BL/6 nude mice for results validation. Cell proliferation was determined through MTT assays while apoptosis was investigated using Annexin V-FITC/PI kit and flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was used to detect IL-6, IL-8, and TNF-α cytokines expressions. AKT/mTOR and autophagy proteins expressions were investigated through western blot and immunofluorescence. The results indicated significantly inhibited cell viability following ACHN tumor cells treatments with curcumin alone, or with the various combinations, as compared to the control. Apoptosis was significantly increased following curcumin treatment, but was significantly reversed after treatment with curcumin+ 3-MA. Likewise, AKT/mTOR proteins expression were significantly reduced while the autophagy-related proteins were significantly elevated following curcumin treatment. The tumor size, weight and volumes were also significantly suppressed following treatment with curcumin. In conclusion, the investigation demonstrated that curcumin suppressed ACHN cell viability, induced apoptosis and autophagy, through the suppression of AKT/mTOR pathway. Use of curcumin to target AKT/mTOR pathway could be an effective treatment alternative for renal cell carcinoma.

 

Curcumin and Cancer Stem Cells: Curcumin Has Asymmetrical Effects on Cancer and Normal Stem Cells, 2015

Wide range of molecular mechanisms identified by which curcumin attacks cancer stem cells (CSCs), which are the minority subpopulation of self-renewing cells within a tumor colony, and which alone are capable of producing all the other cells within a tumor.

 

Curcumin enhances temsirolimus-induced apoptosis in human renal carcinoma cells through upregulation of YAP/p53, 2016

The combined effect of curcumin and temsirolimus treatment on apoptosis in human renal cell carcinoma (RCC) cells was investigated. It was demonstrated that curcumin combined with temsirolimus markedly induced apoptosis in RCC cells, however this effect was not observed following curcumin or temsirolimus treatment alone.

Effects Of Curcumin On Lifespan

In a study involving the roundworm C. elegans, growth media containing a low concentration of curcumin increased mean (average) lifespan by 39 percent. In a study looking at flies, curcumin increased the median and maximum lifespan of flies by up to 25.8% [3]. The curcumin metabolite tetrahydrocurcumin has also been associated with lifespan extension. In male mice supplemented with THC beginning at the age of 13 months, mean lifespan was increased by an average of 84 days.

Interventions in aging and age-associated pathologies by means of nutritional approaches, 2004 (Mice Lifespan +10% via Curcumin, +6.4% via Green Tea)

The effects of tetrahydrocurcumin and green tea polyphenol on the survival of male C57BL/6 mice, 2007 

[Liposomal Curcumin Is 5.6x More Bioavailable Than Other Curcumin]

Curcumin induces apoptosis in JAK2-mutated cells by the inhibition of JAK2/STAT and mTORC1 pathways, 2019

Myeloproliferative neoplasms are chronic myeloid cancers divided in Philadelphia positive and negative. The JAK2 V617F is the most common mutation in Philadelphia negative patients and results in a constitutive activation of the JAK/STAT pathway, conferring a proliferative advantage and apoptosis inhibition. Recent studies identified a functional crosstalk between the JAK/STAT and mTOR pathways. The identification of an effective therapy is often difficult, so the availability of new therapeutic approaches might be attractive. Previous studies showed that curcumin, the active principle of the Curcuma longa, can suppress JAK2/STAT pathways in different type of cancer and injuries. In this study, we investigated the anti-proliferative and pro-apoptotic effects of curcumin in JAK2 V617F-mutated cells. HEL cell line and cells from patients JAK2 V617F mutated have been incubated with increasing concentrations of curcumin for different time. Apoptosis and proliferation were evaluated. Subsequently, JAK2/STAT and AKT/mTOR pathways were investigated at both RNA and protein levels. We found that curcumin induces apoptosis and inhibition of proliferation in HEL cells. Furthermore, we showed that curcumin inhibits JAK2/STAT and mTORC1 pathways in JAK2 V617F-mutated cells. This inhibition suggests that curcumin could represent an alternative strategy to be explored for the treatment of patients with myeloproliferative neoplasms.

Pure curcumin increases the expression of SOCS1 and SOCS3 in myeloproliferative neoplasms through suppressing class Ι histone deacetylases 

Suppressors of cytokine signaling, SOCS1 and SOCS3, are important negative regulators of Janus kinase 2/signal transducers and activators of transcription signaling, which is constitutively activated in myeloproliferative neoplasms (MPNs) and leukemia. Curcumin has been shown to possess anticancer activity through different mechanisms. However, whether curcumin can regulate the expression of SOCS1 and SOCS3 is still unknown. Here, we found that curcumin elevated the expression of SOCS1 and SOCS3 via triggering acetylation of histone in the regions of SOCS1 and SOCS3 promoter in K562 and HEL cells. As a novel histone deacetylases (HDACs) inhibitor, curcumin inhibited HDAC enzyme activities and decreased the levels of HDAC1, 3 and 8 but not HDAC2. Knockdown of HDAC8 by small interfering RNA markedly elevated the expression of SOCS1 and SOCS3. Moreover, ectopic expression of HDAC8 decreased the levels of SOCS1 and SOCS3. Thus, HDAC8 plays an important role in the modulation of SOCS1 and SOCS3 by curcumin. Also, trichostatin A (TSA), an inhibitor of HDACs, increased the levels of SOCS1 and SOCS3. Furthermore, curcumin increased the transcript levels of SOCS1 and SOCS3 and significantly inhibited the clonogenic activity of hematopoietic progenitors from patients with MPNs. Finally, curcumin markedly inhibited HDAC activities and decreased HDAC8 levels in primary MPN cells. Taken together, our data uncover a regulatory mechanism of SOCS1 and SOCS3 through inhibition of HDAC activity (especially HDAC8) by curcumin. Thus, being a relative non-toxic agent, curcumin may offer a therapeutic advantage in the clinical treatment for MPNs.

Dieneke Ferguson (link)

Dieneke Ferguson was diagnosed with the blood cancer myeloma in 2007 and underwent three rounds of chemotherapy as well as four stem cell transplants. After five years of living with cancer and the ravages of side-effects from repeated unsuccessful treatment, Dieneke Ferguson thought she was finally losing the battle. She had a serious relapse and there seemed little hope.

‘Nothing worked: there was just too much cancer — all my options were exhausted, and there was nothing else I could do,’ she says.

Dieneke is still taking 8g of curcumin in tablet form daily — the equivalent of about two teaspoonfuls of pure powdered curcumin. As kitchen turmeric contains 2 per cent curcumin, it would be physically impossible to eat enough of the curry spice to get the same dose of curcumin.

‘When you review her chart, there’s no alternative explanation [for her recovery] other than we’re seeing a response to curcumin,’ Jamie Cavenagh, professor of blood diseases at London’s Barts Hospital, said

Dieneke took eight grams of curcumin each night on an empty stomach.

Surprising results of a supportive integrated therapy in myelofibrosis (link)

Objectives: Myelofibrosis (MF) is characterized by shortened survival and a greatly compromised quality of life. Weight loss and cachexia seem to be the most important factors influencing survival in patients with MF. The aim of this study was to assess the efficacy of an integrated supportive therapy in improving cachexia and MF-related symptoms.

Methods: We reported on a case of a patient with MF who presented with weight loss and cachexia associated with severe anemia, fatigue, fever, and bone pain. The circulating levels of inflammatory, oxidative stress parameters, hepcidin, and erythropoietin were evaluated and were above normal ranges. The patient was treated with a multitargeted approach specifically developed for cachexia including oral l-carnitine, celecoxib, curcumin, lactoferrin, and subcutaneous recombinant human erythropoietin (EPO)-α.

Results: Surprisingly, after 1 y, cachexia features improved, all MF symptoms were in remission, and inflammatory and oxidative stress parameters, hepcidin, and EPO were reduced.

Conclusions: Because our protocol was targeted at inflammation and the metabolic state, its effectiveness may emphasize the role of inflammation in the pathogenesis of MF symptoms and demonstrates a need for the study of new integrated therapeutic strategies.

Inflammation (NF-kB) Aspirin and ibuprofen are least potent, while resveratrol, curcumin, celecoxib, and tamoxifen are the most potent anti-inflammatory and antiproliferative agents of NF-kB.

Interferon-α resistance can be reversed by inhibition of IFN-α-induced COX-2 expression potentially via STAT1 activation in A549 cells, 2006

The current study demonstrates that COX-2 expression is positively regulated by IFN-α, which is mediated by activation of STAT1 in A549 cells. The IFN-α-induced COX-2 expression and STAT1 activation were markedly inhibited by the addition of curcumin to the IFN-α-pretreated cells. While IFN-α or COX-2 inhibitors alone did not result in growth inhibition of A549 cells, the combination of IFN-α and celecoxib or curcumin resulted in a significant growth inhibition of A549 cells, which was associated with down-regulation of CDK2, 4, and 6 and up-regulation of p27. We demonstrate that the expression of COX-2 was induced by IFN-α possibly via STAT1 activation in the A549 human non-small cell lung cancer cell line, which may partly account for its IFN-α resistance. The addition of curcumin or celecoxib to the IFN-α-pretreated A549 cells altered the IFN-α sensitivity of cell growth inhibition.

Long-term stabilisation of myeloma with curcumin, 2017

Myeloma is a haematological malignancy which typically follows a relapsing-remitting course. While treatment can control the myeloma and improve quality of life for given periods of time, remissions generally become progressively shorter with subsequent relapses, and patients ultimately enter a final refractory phase. To help control symptoms and enhance quality of life, some patients use complementary therapies as an adjunct to their conventional therapy. Here, we describe a myeloma patient who started a daily dietary supplement of curcumin when approaching her third relapse. In the absence of further antimyeloma treatment, the patient plateaued and has remained stable for the last 5 years with good quality of life.

Background

Myeloma is a B-cell malignancy that is characterised by the monoclonal expansion and accumulation of abnormal plasma cells within the bone marrow. Clinical manifestations include bone pain, renal impairment, recurrent infections and anaemia.1 Over the past decade, advances in the understanding of the disease, together with the development of several novel treatments, have led to significant improvements in overall survival.2

Despite this, myeloma remains incurable, with a median overall survival of 5.2 years from diagnosis.3 The course of the disease is typically one of recurrent remission and relapse. However, patients progressively acquire resistance to treatment and subsequent remissions become shorter and shorter. Eventually, either they run out of treatment options or become refractory to them.

In an effort to improve long-term outcomes, some myeloma patients seek to use dietary supplements, mostly for palliative purposes. While they may help to improve quality of life, there is little evidence they can increase survival.4 Among them, curcumin, the active constituent of turmeric, has gained popularity as a complementary therapy in several cancers.

Here, we present a case of a heavily pretreated relapsing myeloma patient who, in the absence of further treatment options at the time, started daily curcumin and has since remained stable for the past 5 years.

Curcumin Downregulates NF-kB and Related Genes in Patients with Multiple Myeloma: Results of a Phase I/II Study.

Although the role of NF-kB and STAT3 pathways in proliferation/metastasis of various tumor cells is well established, no agent has been described which could downregulate the activation of these transcription factors in cancer patients (pts). Curcumin has been shown to potently suppress the activation of these transcription factors in cultured cells. Based on these observations, we initiated a clinical trial of curcumin alone (administered orally at 2, 4, 6, 8, or 12 grams/day in 2 divided doses) or in combination with Bioperine (10 mg in 2 divided doses) for 12 weeks in multiple myeloma (MM) pts. The objectives of this study were to evaluate the clinical safety and biologic effects in MM pts who had asymptomatic, relapsed/refractory, or plateau phase disease. Blood was collected for PK/PD and PBMCs were examined (baseline and during treatment) for evaluating the effect of treatment on expression of NF-kB (p65), COX-2 and phospho-STAT3 as surrogate biomarkers. NF-kB activation status was also measured by electrophoretic mobility shift assay. At least 6 pts are enrolled at each dose level; 3 on the curcumin arm and 3 on the curcumin + bioperine arm. Pts with at least stable disease were allowed to continue treatment up to one year. Treatment with curcumin and bioperine has been well tolerated, with no significant adverse events. At the 12 grams dose level, 2 of the 5 pts had difficulty swallowing the large number of capsules. Of the 29 evaluable pts treated so far, no objective responses have been seen. Twelve pts continued treatment for more than 12 weeks and 5 (1 patient at 4 grams, 2 pts at 6 grams, and 2 pts at 8 grams dose levels) completed one year of treatment with stable disease. With few exceptions, little if any free drug was found in the plasma. Total curcumin levels (mostly conjugated drug) were dependent on both dose and the duration of administration. PBMCs from 28 MM pts examined showed constitutively active NF-kB (mean ± STD, 74.2% ± 14.0 positive cells), COX2 (66% ± 15.4), and STAT3 (52.8% ± 19.2). Oral administration of curcumin significantly downregulated the constitutive activation of NF-kB (at 3 months a median reduction of 77%, p<0.0001) and STAT3 (69%, p<0.001), and suppressed COX2 (66%, p<0.0001) expression in most of the pts at each of the monthly time points.

Conclusions: This is the first report to indicate that curcumin, a highly safe agent, is bioavailable and can downregulate NF-kB, STAT3 and COX2 in MM pts. These findings suggest a potential therapeutic role for curcumin that can be further investigated either alone or as a modulator of chemo-resistance in combination with other active agents.

Should I Take TURMERIC/CURCUMIN For Inflammation In 2020? (link)

Efficacy of curcumin/turmeric on liver enzymes in patients with non-alcoholic fatty liver disease: A systematic review of randomized controlled trials.

Meta-analysis of 4 randomized controlled trials including 228 subjects showed a trend toward significant reduction of ALT blood concentrations in subgroup with ≥1000 mg/day curcumin supplementation (-11.36 IU/L, 95% CI: -22.75 to 0.02; ). Meta-analysis showed a significant reduction of AST in studies with 8-weeks administration (-9.22 IU/L, 95% CI: -12.77 to -5.67;).

Curcuminoids exert glucose-lowering effect in type 2 diabetes by decreasing serum free fatty acids: a double-blind, placebo-controlled trial, 2012

Overweight/obese type 2 diabetic patients (BMI ≥ 24.0; fasting blood glucose ≥ 7.0 mmol/L or postprandial blood glucose ≥11.1 mmol/L) were randomly assigned to curcuminoids (300 mg/day) or placebo for 3 months. Bodyweight, glycosylated hemoglobin A1c (HbA1c ,% ), serum fasting glucose, FFAs, lipids, and lipoprotein lipase (LPL) were determined. A total of 100 patients (curcuminoids, n = 50; placebo, n = 50) completed the trial. Curcuminoids supplementation significantly decreased fasting blood glucose (p < 0.01), HbA1c (p = 0.031), and insulin resistance index (HOMA-IR) (p < 0.01) in type 2 diabetic patients. Curcuminoids also led to a significant decrease in serum total FFAs (p < 0.01), triglycerides (P = 0.018), an increase in LPL activity (p < 0.01).

Antioxidant Potential of Curcumin—A Meta-Analysis of Randomized Clinical Trials, 2020

Background: Antioxidant potential is defined as the ability to neutralize oxygen free radicals that are generated in excess due to environmental influences. The body’s defense mechanisms often require support in preventing the effects of oxidative stress. The literature data suggest that curcumin has antioxidant activity that can significantly reduce oxidative stress levels. The aim was to assess the impact of curcumin on oxidative stress markers. Methods: PubMed and Embase were searched from database inception until 27 September 2019 for randomized clinical trials in >20 patients treated with curcumin supplements and randomized to placebo/no intervention/physical activity to verify the antioxidant potential of curcumin. Results: Four studies were included in the meta-analysis, three of which were double-blind and one single-blind. A total of 308 participants took part in the research. A total of 40% of the respondents were men. The average age of participants was 27.60 ± 3.79 years. The average supplementation time was 67 days and the average dose of curcumin administered was 645 mg/24 h. Curcumin significantly increased total antioxidant capacity (TAC) (SMD = 2.696, Z = 2.003, CI = 95%, p = 0.045) and had a tendency to decrease malondialdehyde (MDA) concentration (SMD = −1.579, Z = −1.714, CI = 95%, p = 0.086). Conclusions: Pure curcumin has the potential to reduce MDA concentration and increase total antioxidant capacity.

Anti-inflammatory effects of oral supplementation with curcumin: a systematic review and meta-analysis of randomized controlled trials, 2021

Data Extraction

Thirty-two trials (N = 2,038 participants) were included and 28 were meta-analyzed using a random-effects model; effect sizes were expressed as Hedges’ g (95%CI).

Data Analysis

Pooled data (reported here as weighted mean difference [WMD]; 95%CI) showed a reduction in C-reactive protein (−1.55 mg/L; −1.81 to −1.30), interleukin-6 (−1.69 pg/mL, −2.56 to −0.82), tumor necrosis factor α (−3.13 pg/mL; −4.62 to −1.64), IL-8 (−0.54 pg/mL; −0.82 to −0.28), monocyte chemoattractant protein-1 (−2.48 pg/mL; −3.96 to −1.00), and an increase in IL-10 (0.49 pg/mL; 0.10 to 0.88), with no effect on intracellular adhesion molecule-1.

Conclusion

These findings provide evidence for the anti-inflammatory effects of curcumin and support further investigation to confirm dose, duration, and formulation to optimize anti-inflammatory effects in humans with chronic inflammation.

Effect of curcuminoids on oxidative stress: A systematic review and meta-analysis of randomized controlled trials, 2015

The aim of the meta-analysis was to evaluate the efficacy of purified curcuminoids supplementation on plasma activities of superoxide dismutase (SOD), catalase and glutathione (GSH) and lipid peroxides as parameters of oxidative stress. Seven randomized controlled trials were finally selected for the meta-analysis. There was a significant increase of serum SOD activities after curcuminoids supplementation (weighted mean difference [WMD]: 1.15 U/mL, 95% confidence interval [CI]: 0.49–1.82, p = 0.0007). In a subgroup analysis, no significant effects was observed in the subset of studies administering curcuminoids for <6 weeks (WMD: 0.75 U/mL, 95%CI: −0.56–2.05, p = 0.26), but a significant increase of SOD activities was found with supplementation duration ≥6 weeks (WMD: 1.46 U/mL, 95%CI: 0.60–2.32, p = 0.0009). The curcuminoids significantly reduced serum lipid peroxides (WMD: −6.35 nmol/mL, 95%CI: −11.06 to −1.64, p = 0.008), increased GSH concentrations (WMD: 5.39 µg/mL, 95%CI: 1.17–9.60, p = 0.01), and catalase activity (WMD: 51.78 U/mL, 95%CI: 15.71–87.85, p = 0.005). This meta-analysis showed a significant effect of curcuminoids in elevating serum SOD and catalase activities, GSH concentrations, and reduction of serum lipid peroxides.

Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)-κB and NF-κB-regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis

Scope: The incidence of cancer is significantly lower in regions where turmeric is heavily consumed. Whether lower cancer incidence is due to turmeric was investigated by examining its effects on tumor cell proliferation, on pro-inflammatory transcription factors NF-κB and STAT3, and on associated gene products.

Methods and results: Cell proliferation and cell cytotoxicity were measured by the MTT method, NF-κB activity by EMSA, protein expression by Western blot analysis, ROS generation by FACS analysis, and osteoclastogenesis by TRAP assay. Turmeric inhibited NF-κB activation and down-regulated NF-κB-regulated gene products linked to survival (Bcl-2, cFLIP, XIAP, and cIAP1), proliferation (cyclin D1 and c-Myc), and metastasis (CXCR4) of cancer cells. The spice suppressed the activation of STAT3, and induced the death receptors (DR)4 and DR5. Turmeric enhanced the production of ROS, and suppressed the growth of tumor cell lines. Furthermore, turmeric sensitized the tumor cells to chemotherapeutic agents capecitabine and taxol. Turmeric was found to be more potent than pure curcumin for cell growth inhibition. Turmeric also inhibited NF-κB activation induced by RANKL that correlated with the suppression of osteoclastogenesis.

Conclusion: Our results indicate that turmeric can effectively block the proliferation of tumor cells through the suppression of NF-κB and STAT3 pathways.