Effect of the curcumin and piperine co-administration on the blood lipid levels and the cardiovascular risk: a systematic review





Cardiovascular risk; Dyslipidemia; Phenolic compound; Piperidine alkaloid.


Some plant species show medicinal potential in atherosclerosis and other coronary diseases. Curcumin (CUR) is a yellow-colored phenolic compound from rhizomes of Curcuma longa L. that is mainly used as anti-inflammatory, antioxidant, and anticancer. Piperine (PIP) is an alkaloid from the fruits and the seeds of Piper nigrum L. and Piper longum L. It has several pharmacological activities, including the antioxidant and the immunomodulatory properties. PIP also increases the nutrients absorption. This review aims at investigating the effect of the CUR and PIP co-administration on the lipid profile and the cardiovascular events based on animal and human studies. This study was performed in the main scientific search bases. Among the 4,992 references found, 2,004 papers were initially chosen for the partial reading and 15 of them filled all the selection criteria for the entire reading. The CUR and PIP co-administration generally demonstrated positive effects on lipid profile in animals and humans by reducing total cholesterol, triglycerides, and LP(a) and by increasing HDL-c. In spite of no long-term clinical trial was carried out for investigating the effect of CUR and PIP co-administration on cardiovascular events, the reduction of glucose, AST, and ALP, and the increase of CAT and SOD were recorded as secondary serum markers to avoid the cardiovascular risk. Therefore, the studies usually report that co-administration of CUR and PIP shows efficacy for reducing serum lipids. The effect on preventing cardiovascular events by reducing the cardiovascular risk is lacking of direct evidence.


Abou-Elkhair, R., Ahmed, H. A., & Selim, S. (2014). Effects of Black Pepper (Piper Nigrum), Turmeric Powder (Curcuma Longa) and Coriander Seeds (Coriandrum Sativum) and Their Combinations as Feed Additives on Growth Performance, Carcass Traits, Some Blood Parameters and Humoral Immune Response of Broiler Chickens. Asian-Australas. J. Anim. Sci, 27(6):847-854. doi:10.5713/ajas.2013.13644

Aguiar, C., Alegria, E., Bonadonna, R.C., Catapano, A.L., Cosentino, F., Elisaf, M., Farnier, M., Ferrières, J., Filardi, P.P., Hancu, N., Kayikcioglu, M., Mello e Silva, A., Millan, J., Reiner, Z., Tokgozoglu, L., Valensi, P., Viigimaa, M, Vrablik, M., Zambon, A., Zamorano, J.L. (2015). A review of the evidence on reducing macrovascular risk in patients with atherogenic dyslipidaemia: a report from an expert consensus meeting on the role of fenofibrate-statin combination therapy. Atheroscler Suppl, 19:1-12. 10.1016/S1567-5688(15)30001-5

Ahmad, N. (2012). Biological role of Piper nigrum L. (Black pepper): A review. Asian Pac J Trop Med, S: 1945-53.

Akbarian, A., Golian, A., Kermanshahi, A.G., Moradi, S. (2012). Influence of turmeric rhizome and black pepper on blood constituents and performance of broiler chickens. Afr. J. Biotechnol, 11(34):8606-8611. 10.5897/AJB11.3318

Alwi, I., Santoso, T., Suyono, S., Sutrisna, B., Suyatna, F.D., Kresno, S.B., Ernie, S. (2008). The effect of curcumin on lipid level in patients with acute coronary syndrome. Acta Med Indones, 40(4): 201-210

Anand, P., Kunnumakkara, A. B., Newman, R. A., Aggarwal, B. B. (2007). Bioavailability of curcumin: problems and promises. Mol Pharm, 4:807-818. doi:10.1021/mp700113r

Arcaro, C. A., Gutierres, V. O., Assis, R. P., Moreira, T. F., Costa, P. I., Baviera, A. M., Brunetti, I. L. (2014). Piperine, a Natural Bioenhancer, Nullifies the Antidiabetic and Antioxidant Activities of Curcumin in Streptozotocin-Diabetic Rats. PLoS ONE, 9(12):e113993.10.1371/journal.pone.0113993

Atal, N., & Bedi, K. (2010). Bioenhancers: Revolutionary concept to market. J. Ayurveda Integr Med, 1(2): 96-99. 10.4103/0975-9476.65073

Banerji, A., Chakrabarti, J., Mitra, A., & Chatterjee, A. (2004). Effect of curcumin on gelatinase A (MMP-2) activity in B16F10 melanoma cells. Cancer Lett, 211:235-242.

Barbalho, S. M., Bechara, M. D., Quesada, K., Gabaldi, M. R., Goulart, R. A., Tofano, R. J., & Gasparini, R. G. (2015). Síndrome metabólica, aterosclerose e inflamação: tríade indissociável? J Vasc Bras, 14(4):319-327. 10.1590/1677-5449.04315

Basatemur, G. L., Jorgensen, H. F., Clarke, M. C. H., Bennett, M. R., & Mallat, Z. (2019). Vascular smooth muscle cells in atherosclerosis. Nat. Rev. Cardiol, 16(12): 727–744. 10.1038/s41569-019-0227-9

Baum, L., &Ng, A. (2004). Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer’s disease animal models. J Alzheimer’s Dis, 6(4):367–377. 10.3233/jad-2004-6403

Best, L., Elliott, A.C., Brown, P.D. (2007). Curcumin induces electrical activity in rat pancreatic beta-cells by activating the volume-regulated anion channel. Biochem Pharmacol, 73(11),1768–1775.10.1016/j.bcp.2007.02.006

Burgos-Morón, E., Calderón-Montaño, J. M., Salvador, J., Robles, A., & López-Lázaro, M. (2010). The dark side of curcumin. Int. J. Cancer, 126(7):1771-1775. 10.1002/ijc.24967

Chakraborty, M., Bhattacharjee, A., Kamath, J.V. (2017). Cardioprotective effect of curcumin and piperine combination against cyclophosphamide-induced cardiotoxicity. Indian J Pharmacol, 49(1):65–70. 10.4103/0253-7613.201015

Chen, A., & Zheng, S. (2008). Curcumin inhibits connective tissue growth factor gene expression in activated hepatic stellate cells in vitro by blocking NF‐κB and ERK signalling. Br J Pharmacol, 153(3):557‐567. 10.1038/sj.bjp.0707542

GBD, Contributors to the incidence and prevalence of GBD diseases and injuries 2017 (2018) Global, regional and national incidence, prevalence and years of living with 354 diseases and injuries in 195 countries and territories, 1990-2017: a systematic analysis for the global burden of diseases Study 2017. The Lancet 392(10159), 1789-1858

Dieberger, A., Rooij, S. R., Korosi, A., &Vrijkotte, T. G. M. (2018). Maternal lipid concentrations during early pregnancy and eating behavior and energy intake in the offspring. Nutrientes, 10:1026. 10.3390/nu10081026

Duangjai, A., Ingkaninan, K., Praputbut, S., &Limpeanchob, N. (2013). Black pepper and piperine reduce cholesterol uptake and enhance translocation of cholesterol transporter proteins. J. Nat Med. 67(2):303-310. 10.1007/s11418-012-0682-7

Egger, M., & Smith, G. D. (1997). Meta-Analysis. Potentials and promise. BMJ, 315(7119):1371-1374. 10.1136/bmj.315.7119.1371

Ejaz, A., Wu, D., Kwan, P., & Meydani, M. (2009). Curcumin inhibits adipogenesis in 3T3-L1 adipocytes and angiogenesis and obesity in C57/BL mice. J Nutr, 139(5): 919–925.10.3945/jn.108.100966

Filho, D. B. F., Paranhos, R., Júnior, J. A. S., Rocha, E. C., & Alves, D. P. (2014). O que é, para que serve e como se faz uma meta-análise? Teoria & Pesquisa: Revista de Ciência Política, 23(2):205-228

Fujiwara, H., Hosokawa, M., Zhou, X., Fujimoto, S., Fukuda, K., Toyoda, K., Nishi, Y., Fujita, Y., Yamada, K., Yamada, Y., Seino, Y., &Inagaki, N. (2008). Curcumin inhibits glucose production in isolated mice hepatocytes. Diabetes Res Clin Pract, 80(2):185-191. doi:10.1016/j.diabres.2007.12.004

Galkina, E., & Ley, K. (2009). Mecanismos imunológicos e inflamatórios da aterosclerose. Annu. Rev. Immunol, 27:165-197

Graham, A. (2009). Curcumin adds spice to the debate: lipid metabolism in liver disease. Br J Pharmacol, 157(8):1352‐1353. 10.1111/j.1476-5381.2009.00335.x

Gondim, F. M. L., & Souza, B. E. S. de (2021) The use of laser therapy in the prevention and treatment of oral mucositis: a literature review. Research, Society and Development, [S. l.], 10(1): e5910110149. 10.33448/rsd-v10i1.10149

Higgins, J. P. T., Thomas, J., Chandler, J., Cumpston, M., Li, T., Page, M. J., & Welch, V. A. (2019). Cochrane Handbook for Systematic Reviews of Interventions. (2th ed.),, John Wiley and Sons. 728p.

Hlavačková, L., Janegová, A., Uličná, O., Janega, P., Černá, A., & Babál, P. (2011). Spice up the hypertension diet - curcumin and piperine prevent remodeling of aorta in experimental L-NAME induced hypertension. Nutr. Metab, 8(72):1-10.10.1186/1743-7075-8-72

Kang, Q., & Chen, A. (2009a). Curcumin inhibits srebp-2 expression in activated hepatic stellate cells in vitro by reducing the activity of specificity protein-1. Endocrinology, 150:5384-5394. 10.1210/en.2009-0517

Kang, Q., & Chen, A. (2009b). Curcumin suppresses expression of low‐ density lipoprotein (LDL) receptor, leading to the inhibition of LDL‐induced activation of hepatic stellate cells. Br J Pharmacol, 157(8):1354‐1367. 10.1111/j.1476-5381.2009.00261

Li, Y., Li, M., Wu, S., & Tian, Y. (2015). Combination of curcumin and piperine prevents formation of gallstones in C57BL6 mice fed on lithogenic diet: whether NPC1L1/SREBP2 participates in this process? Lipids Health Dis, 14(100):1-8. 10.1186/s12944-015-0106-2

Meghana, K., Sanjeev, G., & Ramesh, B. (2007). Curcumin prevents streptozotocin-induced islet damage by scavenging free radicals: A prophylactic and protective role. Eur J Pharmacol, 577(1-3):183–191. 10.1016/j.ejphar.2007.09.002

Miyazawa, T., Nakagawa, K., Kim, S. H., Thomas, M. J., Paul, L., Zingg, J-M., Dolnikowski, G. G., Roberts, S. B., Kimura, F., Miyazawa, T., Azzi, A., & Meydani, M. (2018). Curcumin and piperine supplementation of obese mice under caloric restriction modulates body fat and interleukin-1β. Nutr. Metab, 15(12):1-9. 10.1186/s12986-018-0250-6

Moher, D., Liberati, A., Tetzlaff, J., & Altman, D. G. (2009). Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement. Open Medicine, 3(2): 123-130. doi:10.1016/j.jclinepi.2009.06.005

Moohebati, M., Yazdandoust, S., Sahebkar, A., Mazidi, M., Sharghi-Shahri, Z., Ferns, G., & Ghayour-Mobarhan, M. (2014). Investigation of the effect of short-term supplementation with curcuminoids on circulating small dense low-density lipoprotein concentrations in obese dyslipidemic subjects: A randomized double-blind placebo-controlled cross-over trial. ARYA Atheroscler, 10(5):280-286

Nascimento, T. C. F., Casa, D. M., Dalmolin, L. F., Mattos, A. C., Khalil, N. M., & Mainardes, R. M. (2012). Development and Validation of an HPLC Method Using Fluorescence Detection for the Quantitative Determination of Curcumin in PLGA and PLGA-PEG Nanoparticles. Curr. Pharm. Anal, 8(4): 324-333. 10.2174/157341212803341654

Oliveira, G., Mendes, R. T., & Boccaletto, E. M. A. (2009). Alimentação, Atividade Física e Qualidade de Vida. Campinas: Ipês Editorial, 1(5): 39-46

Panahi, Y., Khalili, N., Hosseini, M. S., Abbasinazari, M., & Sahebkar, A. (2014). Lipid-modifying effects of adjunctive therapy with curcuminoids—piperine combination in patients with metabolic syndrome: Results of a randomized controlled trial. Complement. Ther. Med, 22:851-857. 10.1016/j.ctim.2014.07.006

Panahi, Y., Khalili, N., Sahebi, E., Namazi, S., Karimian, M. S., Majeed, M., & Sahebka, A. (2016). Antioxidant effects of curcuminoids in patients with type 2 diabetes mellitus: a randomized controlled trial. Inflammopharmacol, 25(1):25-31. 10.1007/s10787-016-0301-4.

Panahi, Y., Khalili, N., Sahebi, E., Namazi, S., Reiner, Z., Majeed, M., & Sahebkar, A. (2017). Curcuminoids modify lipid profile in type 2 diabetes mellitus: A randomized controlled trial. Complement. Ther. Med, 33:1-5. 10.1016/j.ctim.2017.05.006

Panahi, Y., Khalili, N., Sahebi, E., Namazi, S., Simental-Mendía, L.E., Majeed, M., & Sahebkar. A. (2018). Effects of Curcuminoids Plus Piperine on Glycemic, Hepatic and Inflammatory Biomarkers in Patients with Type 2 Diabetes Mellitus: A Randomized Double-Blind Placebo-Controlled Trial. Drug Res, 68(7):403-409. 10.1055/s-0044-101752

Panahi, Y., Valizadegan, G., Ahamdi, N., Ganjali, S., Majeed. M., & Sahebkar, A. (2019). Curcuminoids plus piperine improve nonalcoholic fatty liver disease: A clinical trial. J Cell Biochem, 1-8. 10.1002/jcb.28877

Patil, T. N., & Srinivasan, M. (1971). Hypocholesterolaemic effect of curcumin in induced hypocholesterolaemic rats. Indian J. Exp. Biol, 9:167-169. doi:0.4162/nrp.2010.4.3.191

Pereira, A. S., Shitsuka, D. M., Pereira, F. J., & Shitsuka, R. (2018). Scientific research methodology. UAB / NTE / UFSM.

Piyachaturawat, P., Glinsukon, T., & Toskulkao, C. (1983). Acute and subacute toxicity of piperine in mice, rats and hamsters. Toxicol Lett, 16(3–4):351–359. 10.1016/0378-4274(83)90198-4

Reiner, Z. (2013). Managing the residual cardiovascular disease risk associated with HDL-cholesterol and triglycerides in statin-treated patients: a clinical update. Nutr. Metabol. Cardiovasc. Dis. NMCD, 23(9):799-807. 10.1016/j.numecd.2013.05.002

Rudnik, L. A. C., Farago, P. V., Budel, J. M., Lyra, A., Barboza, F. M., Klein, T., Kanunfre, C. C., Nadal, J. M., Bandéca, M. C., Raman, W., Novatski, A., Loguércio, A. D., Zanin, S. M. W. (2020). Co-loaded curcumin and methotrexate nanocapsules enhance cytotoxicity against non-small-cell lung cancer cells. Molecules. 25: 1913. 10.3390/molecules25081913

Seo, K. I., Choi, M. S., Jung, U. J., Kim, H. J., Yeo, J., Jeon, S. M., & Lee, M. K. (2008). Effect of curcumin supplementation on blood glucose, plasma insulin, and glucose homeostasis related enzyme activities in diabetic db/db mice. Mol Nutr Food Res, 52(9):995–1004. 10.1002/mnfr.200700184

Shin, S. K., Ha, T. Y., Mcgregor, R. A., & Choi, M. S. (2011). Long-term curcumin administration protects against atherosclerosis via hepatic regulation of lipoprotein cholesterol metabolism. Mol Nutr Food Res, 55:1829-1840. 10.1002/mnfr.201100440

Shoba, G., Joy, D., Joseph, T., Majeed, M., Rajendran, R., & Srinivas, P. S. (1998). Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med, 64:353-356. 10.1055/s-2006-957450

Soliman Ghada, Z. A. (2005) Effect of Curcumin, Mixture of Curcumin and Piperine and Curcum (Turmeric) on Lipid Profile of Normal and Hyperlipidemic Rats Egypt. J. Hosp. Med. 21(1):145-161. 10.12816 / EJHM.2005.18057

Soudamini, K. K., Unnikrishnan, M. C., Soni, K. B., & Kuttan, R. (1992). Inhibition of lipid peroxidation and cholesterol levels in mice by curcumin. Indian J. Physiol. Pharmacol, 36(4):239-243

Sreejayan, M. N. R. (1994). Curcuminoids as potent inhibitors of lipid peroxidation. J Pharm. Pharmacol, 46(12):1013-1016. doi:10.1111/j.2042-7158.1994.tb03258.x.

Srinivasan, K. (2007). Black pepper and its pungent principle-piperine: a review of diverse physiological effects. Crit Rev Food Sci Nutr, 47(8):735-748. 10.1080/0408390601062054

Suresh, D., & Srinivasan, K. (2010). Tissue distribution & elimination of capsaicin, piperine & curcumin following oral intake in rats. Indian J Med Res, 131:682-691

Torres, N., Guevara-Cruz, M., Velazquez-Villegas, L. A., & Tovar, A. R. (2015). Nutrição e aterosclerose. Arch. Med. Res, 46(5):408-426

Tu, Y., Sun, D., Zeng, X., Yao, N., Huang, X., Huang, D., & Chen, Y. (2014). Piperine potentiates the hypocholesterolemic effect of curcumin in rats fed on a high fat diet. Exp. Ther. Med, 8(1):260-266. 10.3892/etm.2014.1717

Um, M. Y., Hwang, K. H., Ahn, J., & Ha, T. Y. (2013). Curcumin attenuates diet‐ induced hepatic steatosis by activating AMP‐activated protein kinase. Basic Clin Pharmacol Toxicol, 113(3):152‐157. 10.1111/bcpt.12076

Wang, L., Palme, V., Rotter, S., Schilcher, N., Cujak, M., Wang, D., Ladurner, A., Heiss, E. H., Stangl, H., Dirsch, V. M., & Atanasov, A. G. (2016). Pipperine Innhibits ABCA1 Degradation and Promotes Cholesterol Efflux from THP-1-derived Macrophages. Mol. Nutr. Food Res. 61(4): 1500960. 10.1002/mnfr.201500960

WHO, Wourd Health Statistics (2011). < https://www.who.int/gho/publications/world_health_statistics/2011/en/>

Yan, C., Zhang, Y., Zhang, X., Aa, J., Wang, G., & Xiem Y. (2018). Curcumin regulates endogenous and exogenous metabolism via Nrf2‐ FXR‐LXR pathway in NAFLD mice. Biomed Pharmacother, 105:274‐281. 10.1016/j.biopha.2018.05.135

Yiu, W. F., Kwan, P. L., Wong, C. Y., Kam, T. S., Chiu, S. M., Chan, S. W., & Chan, R. (2011). Attenuation of fatty liver and prevention of hypercholesterolemia by extract of Curcuma longa through regulating the expression of CYP7A1, LDL-receptor, HO-1, and HMG-CoA reductase. J Food Sci, 76(3): H80-H89. 10.1111/j.1750-3841.2011.02042.x

Zhao, J., Sun, X. B., Ye, F., & Tian, W. X. (2008). Suppression of fatty acid synthase, differentiation and lipid accumulation in adipocytes by curcumin. Mol Cell Biochem 351:19-28. 10.1007/s11010-010-0707-z




How to Cite

SIMIONATTO, M.; RECH, K. S.; GOMES, M. L. S. .; MANFRON, J.; FARAGO, P. V. Effect of the curcumin and piperine co-administration on the blood lipid levels and the cardiovascular risk: a systematic review. Research, Society and Development, [S. l.], v. 10, n. 1, p. e27310111682, 2021. DOI: 10.33448/rsd-v10i1.11682. Disponível em: https://www.rsdjournal.org/index.php/rsd/article/view/11682. Acesso em: 29 jan. 2023.



Health Sciences