Curcumin supplementation in the treatment of patients with cancer: a systematic review

Anunciação, Taise Andrade da; Garcez, Laís Spindola; Pereira, Emile Miranda; Queiroz, Valterlinda Alves de Oliveira; Costa, Priscila Ribas de Farias; Oliveira, Lucivalda Pereira Magalhães de

doi:10.1590/s2175-979020200004181008

Feeding with high levels of phytochemicals, including curcumin, may be a therapeutic option for diseases such as cancer which is a public health problem. The aim of this study was to systematically review the results of clinical trials investigating the effect of oral curcumin supplementation on anti-inflammatory and antioxidant profiles, reduction of PSA levels and degree of dermatitis in radiotherapy treatment in cancer patients. The review was carried out based on the items of the PRISMA Statement. A bias risk assessment was performed according to Cochrane Collaboration criteria. Six studies met the eligibility criteria and were included in the systematic review. The results of this study are based on those obtained in the literature on the effect of curcumin on the anti-inflammatory profile, on reducing dermatitis, on PSA alteration and on anti-oxidant profile for a total of 450 individuals, comprising 259 in the intervention group and 191 in the control group. Some studies have reported improvement in biochemical and clinical indicators, with limited adverse effects and good tolerance. It was not possible to determine, with the desired degree of evidence, the effect of curcumin supplementation in the treatment of cancer patients. It is important to consider the great heterogeneity and methodological weaknesses of the studies, and that it was not possible to perform a meta-analysis of the data available in the literature.

Keywords:
Curcumin; Cancer; Systematic review; Anti-inflammatory profile; Anti-oxidant profile.

[1] *Correspondence
: T. A. da Anunciação. Faculdade de Nutrição. Universidade Federal da Bahia. Rua Basílio da Gama, s/n Canela, CEP 40110-907 - Salvador, Bahia, Brasil - Phone: (55) 71 3283 7719. E-mail: tai.anunciacao@hotmail.com.

Author and location	Intervention duration	Population	Dose	Type of associated treatment	Intervention	Outcomes
^{He et al., 2011}17. He ZY, Shi CB, Wen H, Li FL, Wang BL, Wang J. Upregulation of p53 expression in patients with colorectal cancer by administration of curcumin. Cancer Invest. 2011;29(3):208-13. USA	10, 20 and 30 days (depending on preoperative period)	71 adult patients with colorectal CA	Capsules with 360 mg curcumin 3x/day (1.08g/day curcumin)	Radiotherapy or chemotherapy or combination of both	Curcumin vs. control	Body weight, TNF-α, P-53 protein expression, pro-apoptotic gene levels, and apoptosis death repressor and inducer proteins.
^{Hejazi et al., 2016}18. Hejazi J, Rastmanesh R, Taleban FA, Molana SH, Hejazi E, Ehtejab G, et al. Effect of Curcumin Supplementation During Radiotherapy on Oxidative Status of Patients with Prostate Cancer: A Double Blinded, Randomized, Placebo-Controlled Study. Nutr Cancer. 2016;68(1):77-85. Iran	One week before start of radiotherapy until its conclusion (2 years)	45 patients with prostate CA without metastasis.	Capsules of 500 mg of BCM95, Biocurcumin 6x/day (3g/day of curcumin)	Radiation therapy with 74 Gy dose	Curcumin vs. Control with rice bran	Body weight, PSA levels, SOD, catalase, GPx.
^{Panahi et al., 2014}26. Panahi Y, Saadat A, Beiraghdar F, Sahebkar A. Adjuvant therapy with bioavailability-boosted curcuminoids suppresses systemic inflammation and improves quality of life in patients with solid tumors: a randomized double-blind placebo-controlled trial. Phytother Res. 2014;28(10):1461-7. Iran	8 weeks	80 patients diagnosed with solid tumors	3x 300 mg Meriva capsules per day (180 mg/day curcumin)	Chemotherapy specific for each CA type	Curcumin vs. control	IL-6, IL-8, calcitonin gene, TNF-α, MCP-1, TGFβ, CRP and quality of life evaluation using the University of Washington scale (UW-QoL).
^{Ryan et al., 2013}30. Ryan JL, Heckler CE, Ling M, Katz A, Williams JP, Pentland AP, et al. Curcumin for radiation dermatitis: a randomized, double-blind, placebo-controlled clinical trial of thirty breast cancer patients. Radiat Res. 2013;180(1):34-43. USA	During radiotherapy treatment (16-33 sessions)	35 adult patients with breast CA	4x 500 mg capsules of C3 Complex® 3x/day (2g/day of curcumin)	Radiation therapy with a dose of 42.6-50.4 Gy, not associated with surgical or chemotherapy treatment	Curcumin vs. Dicalcium phosphate control	Severity score of RDS dermatitis and digital image of skin alterations and application of two self-report questionnaires: SI and SF-MPQ.
^{Thomas et al., 2014}37. Thomas R, Williams M, Sharma H, Chaudry A, Bellamy P. A double-blind, placebo-controlled randomised trial evaluating the effect of a polyphenol-rich whole food supplement on PSA progression in men with prostate cancer--the U.K. NCRN Pomi-T study. Prostate Cancer Prostatic Dis. 2014;17(2):180-6. United Kingdom	6 months	199 men with prostate cancer	1 capsule with: powder of broccoli 100 mg, turmeric powder 100 mg, pomegranate 100 mg and green tea extract 100 mg, 3x/day (300 mg/day of curcumin)	No information	Curcumin, Broccoli, Pomegranate and Green Tea vs. Control containing the same volume and anti-caking agent, with 10 mg of watercress extract	Serum levels of PSA
^{Van Die et al., 2017}39. Van Die MDV, Williams SG, Emery J, Bone KM, Taylor JM, Lusk E, et al. A Placebo-Controlled Double-Blinded Randomized Pilot Study of Combination Phytotherapy in Biochemically Recurrent Prostate Cancer. Prostate . 2017;77(7):765-775. Australia	12 weeks	20 adult patients with prostate CA	2 capsules, 2x/day of curcumin (400 mg/d); resveratrol (120 mg/d); green tea (400 mg/d); broccoli (8g/d).	Surgery, radiotherapy or both	Curcumin, Resveratrol, Green Tea and Broccoli vs. Control containing oats	Serum levels of PSA

Study and year	Outcomes of interest	Main results	Adverse effects
*He et al.,* 2011	TNF- α	Statistically significant reduction in serum TNF alpha levels observed in patients in the curcumin group, but not in those treated with placebo. Administration with curcumin induced apoptosis, increased p53 expression and reduced Bax and Bcl-2 levels in colorectal CA cells.	Reported occurrence of diarrhea in 2 patients, one in the intervention group and one in the placebo group.
*Ryan et al.,* 2013	Decrease in severity of dermatitis	Significant decrease in scores on RDS scale in curcumin group compared to placebo, with decrease after the fourth week. In addition, lower number of patients in the curcumin group had moist desquamation compared to the placebo group, however, with no change in the skin redness. There was no significant difference between groups regarding local pain.	The Symptom Inventory questionnaire was used, where no statistical difference was observed between the curcumin and placebo groups for 17 symptoms present in the questionnaire.
*Panahi et al.,* 2014	IL-6, IL-8, TNF- α	Statistically significant reduction in serum levels of TNF-α, IL-6 and IL-8 in both groups. Reductions in TNF-α and IL-6 were significantly higher in the curcuminoid group compared to control group. In contrast, IL-8 reduction was significantly higher in the placebo group, changes in serum IL-8 levels were a predictor of quality of life in the placebo group. In both groups, reduction in TNF-α levels were predictors of quality and life improvement.	Eight patients reported mild gastrointestinal effects. However, there was no abandonment as a result of adverse reactions to treatment.
*Thomas et al.,* 2014	PSA, CRP	There was a significant reduction in serum PSA levels in the intervention group compared to placebo. The mean percentage of PSA increased more slowly in the supplemented group, compared to placebo, a result with statistical significance. An analysis of the subgroup of men under active surveillance also revealed that after the intervention, mean PSA fell while the placebo increased, with a significant difference. For the subgroup of men managed with watchful waiting, PSA had a smaller increase in the intervention group than the placebo group, with statistical difference. Regarding CRP levels, there were no significant differences at the beginning or end of the study between the supplement and control groups.	There were adverse effects such as diarrhea, agitation, tremors and insomnia in both groups, but with no statistical difference.
*Hejazi et al.,* 2016	PSA, SOD, catalase, GPx.	There was a statistically significant increase in total antioxidant capacity and a reduction in SOD activity in the curcumin group. PSA levels were significantly reduced in both groups. There was a decrease in catalase activity, but not statistically significant. There were no changes in GPx activity.	No adverse effects were reported in the two groups.
*Van Die et al.,* 2017	PSA	There was variation in serum PSA levels for both groups. The supplemented group showed a non-significant improvement in PSA values, whereas the placebo group showed no change.	Adverse events were reported in both groups, with no statistical difference, such as "heartburn", and one case of restlessness that persisted throughout the treatment phase. Two men experienced a nocturia increase initially, but this symptom was resolved.

Brasil

Brasil

Curcumin supplementation in the treatment of patients with cancer: a systematic review