Did you know that black pepper, with its potent compound called piperine, can positively affect your health?

Black pepper, one of the most commonly used spices in the world, may be underappreciated for its health benefits. Piperine, a powerful compound found in black pepper, has gastroprotective, antioxidant, cardioprotective, neuroprotective, anti-inflammatory, immunomodulatory and anticancer properties that keep you healthier.^[i],[ii]

Five Advantages of the Pepper Powerhouse Piperine

1. Improves Gut Health

Grinding fresh peppercorns is the best way to gain the health advantages of piperine. Recent research shows piperine increases digestive efficiency, enzymes and gut health.^[iii],[iv] In a mouse study, black pepper showed effectiveness for treating gastrointestinal disorders.^[v]

In addition, piperine increased the small intestine’s absorptive surface in a rat model, which suggests eating pepper may help more nutrients be released from the food you eat.^[vi] In a mouse model, piperine reduced colon inflammation, a precursor to inflammatory bowel disease.^[vii]

2. Protects Your Brain

Chronic inflammation plays a major role in the development of various neurodegenerative conditions such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, epilepsy and depression. Piperine protects your brain by targeting inflammatory pathways.^{[viii], [ix]}

Dementia is often associated with age-related lapses in memory, selective attention and emotional processing,^[x] extensive neuroinflammation and oxidative stress in the brain.^[xi] Piperine dramatically improved these factors in an aging mouse research study, within four weeks.^[xii]

Quercetin (25 milligrams (mg)) combined with piperine (2.5 mg) for 28 days significantly enhanced antioxidant, anti-inflammatory and neuroprotective effects in an experimental Parkinson’s rat model when compared to quercetin alone.^[xiii]

In a streptozotocin-induced Alzheimer’s rat model, piperine enhanced cognition. The rats increased their maze performance and path memory after taking piperine daily for two to three at a dose of 2.5 mg/kg. The improvements were similar to those achieved via 10 mg/kg of daily memantine, an Alzheimer’s drug.^[xiv]

A similar Alzheimer’s mouse study showed piperine (2.5 to 10 mg/kg daily for 15 days) reversed oxidative stress, restored neurotransmissions, improved cognitive performance and reduced neuroinflammation.^[xv] In another animal model, in addition to cognitive improvements, piperine restored the acetylcholinesterase enzyme balance affecting brain and muscle functions.^[xvi]

In epilepsy research, piperine improved awareness, senses and mood. This chronic neurologic condition is characterized by seizures involving abnormal electrical discharges in the brain.^[xvii] Antioxidant piperine inhibited monoamine oxidase, which lowers dopamine, norepinephrine and serotonin neurotransmitters, all linked to depression and anxiety,^[xviii] and outperformed the antidepressant fluoxetine.^[xix]

3. Anticancer

Cancer emerges from a microenvironment, where tumors and host cells evolve together, cells proliferate, grow and metabolize, and cause angiogenesis (growth of new blood vessels) and hypoxia (low blood oxygen).^[xx]

In their research reviews, scientists found that piperine was chemopreventive, antioxidant (detoxified enzymes and suppressed cancer stem cells), inhibited cancer cells (stemmed blood and oxygen flow) and lowered multidrug resistance. ^{[xxi], [xxii]}

Studying human prostate cancer cells, piperine effectively blocked voltage gated K channels, which regulate cancer cell proliferation and apoptosis (cell death).^[xxiii] In another human in vitro study, piperine was an antitumor agent in lung cancer without host toxicity.^[xxiv]

Piperine demonstrated strong antitumor and antimetastatic effects through in vitro studies of human breast, ^[xxv] liver and lung cancer cells by inhibiting important signaling pathways and disrupting tumor progression.^[xxvi]

In a colorectal cancer animal study, piperine enhanced curcumin’s effectiveness. Cancer-fighting enzymes increased fourfold with curcumin but sixfold with piperine and curcumin together, achieving a 50% cancer cell reduction.^[xxvii] Combined piperine-curcumin positively affected breast cancer cell growth too.^[xxviii]

4. Helps Prevent Heart Disease

Targeting metabolic syndrome, which involves the combined risks of obesity, high blood pressure, imbalanced cholesterol and diabetes, is one approach to preventing coronary heart disease.^[xxix] Research on piperine shows strong cardioprotective, antioxidant and anti-inflammatory properties.^[xxx]

Modelling human metabolic syndrome, scientists fed rats a high carbohydrate, high fat diet for 16 weeks and the animals developed high blood pressure, elevated oxidative stress and inflammation-induced cardiac changes, along with reduced responsiveness of aortic rings, impaired glucose tolerance and abdominal obesity together with liver fibrosis, fat deposits and increased plasma liver enzymes.

Piperine (30 mg) treatment improved all of these markers.^{[xxxi],[xxxii]} In a human trial of 117 metabolic syndrome subjects, a daily curcuminoid (1 gram)-piperine (10 mg) combination for eight weeks significantly improved oxidative stress and inflammatory status.^[xxxiii]

In a chemically-induced Type 2 diabetes rat model, piperine and quercetin were significant bioavailability enhancers of curcumin as a treatment to reduce plasma glucose and lipid profile and improve diabetic control over curcumin alone or the diabetes drug glibenclamide.^[xxxiv]

Previous animal and in vitro studies showed piperine as an effective treatment for obesity, high cholesterol and Type 2 diabetes.^{[xxxv],[xxxvi],[xxxvii]} In a randomized trial of 118 Type 2 diabetic patients, curcumin (1,000 mg) combined with piperine (10 mg) daily over 12 weeks significantly improved adipokine levels (a measure of obesity) and decreased inflammation compared to the control group.^[xxxviii]

5. Boosts Immune System

A strong immune system helps your body fight infections and diseases, oxidative stress from environmental toxins and chemicals, or effects of chemotherapy, radiation and other drug treatments.^[xxxix] Piperine has been shown to prevent and mitigate autoimmune diseases^[xl] like rheumatoid arthritis,^[xli],[xlii] lupus,^[xliii] thyroid disorders^[xliv] and psoriasis.^[xlv]

In a study comparing piperine with curcumin in cell-damaged rats given a pesticide, piperine was better than curcumin under immunocompromised conditions due to its increased antioxidative, anti-apoptotic and chemoprotective properties.^[xlvi]

Bacterial sepsis, a serious infection, decreased with piperine due to its significant inhibition of pyrotosis (proinflammatory programmed cell death)^[xlvii] and systemic inflammation.^[xlviii]

Power of Piperine in Black Pepper

Black pepper should remain a dining staple and be valued for its many health advantages. As a strong fighter for your brain, gut, heart and entire body, piperine boosts your immune system and inhibits inflammation. For scientific studies about this powerhouse, see GreenMedInfo.com’s piperine database.

---

References

[i] Meghwal M, Goswami TK. Piper nigrum and piperine: an update. Phytother Res. 2013 Aug;27(8):1121-30. doi: 10.1002/ptr.4972. Epub 2013 Apr 29. PMID: 23625885.

[ii] Christian Rafael Quijia & Marlus Chorilli (2020) Characteristics, Biological Properties and Analytical Methods of Piperine: A Review, Critical Reviews in Analytical Chemistry, 50:1, 62-77, doi.10.1080/10408347.2019.1573656

[iii] Christine T Peterson, Dmitry A Rodionov, Stanislav N Iablokov, Meredith A Pung, Deepak Chopra, Paul J Mills, Scott N Peterson. Prebiotic Potential of Culinary Spices Used to Support Digestion and Bioabsorption. Evid Based Complement Alternat Med. 2019 ;2019:8973704. Epub 2019 Jun 2. PMID: 31281405

[iv] Srinivasan K. Black pepper and its pungent principle-piperine: a review of diverse physiological effects. Crit Rev Food Sci Nutr. 2007;47(8):735-48. doi: 10.1080/10408390601062054. PMID: 17987447.

[v] Malik Hassan Mehmood, Anwarul Hassan Gilani. Pharmacological basis for the medicinal use of black pepper and piperine in gastrointestinal disorders. Anticancer Res. 2009 Dec;29(12):4981-8. PMID: 20828313

[vi] Usha N S Prakash, Krishnapura Srinivasan. Beneficial influence of dietary spices on the ultrastructure and fluidity of the intestinal brush border in rats. Br J Nutr. 2010 Feb 24:1-9. Epub 2010 Feb 24. PMID: 20178671

[vii] Donghua Hu, Yuguang Wang, Zhiwu Chen, Zengchun Ma, Qing You, Xianxie Zhang, Qiande Liang, Hongling Tan, Chengrong Xiao, Xianglin Tang, Yue Gao. The protective effect of piperine on dextran sulfate sodium induced inflammatory bowel disease and its relation with pregnane X receptor activation. J Ethnopharmacol. 2015 Jul 1 ;169:109-23. Epub 2015 Apr 21. PMID: 25907981

[viii] Kannappan R, Gupta SC, Kim JH, Reuter S, Aggarwal BB. Neuroprotection by spice-derived nutraceuticals: you are what you eat! Mol Neurobiol. 2011 Oct;44(2):142-59. doi: 10.1007/s12035-011-8168-2. Epub 2011 Mar 1. PMID: 21360003; PMCID: PMC3183139.

[ix] Chavarria D, Silva T, Magalhães e Silva D, Remião F, Borges F. Lessons from black pepper: piperine and derivatives thereof. Expert Opin Ther Pat. 2016;26(2):245-64. doi: 10.1517/13543776.2016.1118057. Epub 2015 Dec 5. PMID: 26560940.

[x] Jackson C.E. (2011) Cholinergic System. In: Kreutzer J.S., DeLuca J., Caplan B. (eds) Encyclopedia of Clinical Neuropsychology. Springer, New York, NY. https://doi.org/10.1007/978-0-387-79948-3_1113

[xi] Mylonas C, Kouretas D. Lipid peroxidation and tissue damage. In Vivo. 1999 May-Jun;13(3):295-309. PMID: 10459507.

[xii] Che Wang, Zhengxu Cai, Wei Wang, Min Wei, Xinhong Si, Yuting Shang, Zhaofei Yang, Tianbai Li, Huishu Guo, Song Li. Piperine regulates glycogen synthase kinase-3β-related signaling and attenuates cognitive decline in D-galactose-induced aging mouse model. J Nutr Biochem. 2020 Jan ;75:108261. Epub 2019 Oct 27. PMID: 31710934

[xiii] Shakshi Sharma, Khadga Raj, Shamsher Singh. Neuroprotective Effect of Quercetin in Combination with Piperine Against Rotenone- and Iron Supplement-Induced Parkinson’s Disease in Experimental Rats. Neurotox Res. 2019 Oct 25. Epub 2019 Oct 25. PMID: 31654381

[xiv] Mohsen Khalili-Fomeshi, Mohammad Golparvar Azizi, Mohammad Reza Esmaeili, Mohammad Gol, Sohrab Kazemi, Manouchehr Ashrafpour, Ali Akbar Moghadamnia, Soheila Hosseinzadeh. Piperine restores streptozotocin-induced cognitive impairments: Insights into oxidative balance in cerebrospinal fluid and hippocampus. Behav Brain Res. 2018 Jan 30 ;337:131-138. Epub 2017 Sep 20. PMID: 28939403

[xv] Che Wang, Zhengxu Cai, Wei Wang, Min Wei, Daqing Kou, Tianbai Li, Zhaofei Yang, Huishu Guo, Weidong Le, Song Li. Piperine attenuates cognitive impairment in an experimental mouse model of sporadic Alzheimer’s disease. J Nutr Biochem. 2019 Aug ;70:147-155. Epub 2019 May 24. PMID: 31207354

[xvi] Chonpathompikunlert P, Wattanathorn J, Muchimapura S. Piperine, the main alkaloid of Thai black pepper, protects against neurodegeneration and cognitive impairment in animal model of cognitive deficit like condition of Alzheimer’s disease. Food Chem Toxicol. 2010 Mar;48(3):798-802. doi: 10.1016/j.fct.2009.12.009. 2009 Dec 23. Epub 2009 Dec 23. PMID: 20034530

[xvii] Brain and Life, Disorders A to Z, Epilepsy. https://www.brainandlife.org/disorders-a-z/epilepsy/

[xviii] Drugs, Drug Class, Monoamine Oxidase Inhibitors. https://www.drugs.com/drug-class/monoamine-oxidase-inhibitors.html

[xix] Seon A Lee, Seong Su Hong, Xiang Hua Han, Ji Sang Hwang, Gab Jin Oh, Kyong Soon Lee, Myung Koo Lee, Bang Yeon Hwang, Jai Seup Ro, Piperine from the Fruits of Piper longum with Inhibitory Effect on Monoamine Oxidase and Antidepressant-Like Activity, Chemical and Pharmaceutical Bulletin, 2005, Volume 53, Issue 7, Pages 832-835, Released July 01, 2005, Online ISSN 1347-5223, Print ISSN0009-2363, https://doi.org/10.1248/cpb.53.832, https://www.jstage.jst.go.jp/article/cpb/53/7/53_7_832/_article/-char/en

[xx] Sagar SM, Yance D, Wong RK. Natural health products that inhibit angiogenesis: a potential source for investigational new agents to treat cancer-Part 1. Curr Oncol. 2006 Feb;13(1):14-26. PMID: 17576437; PMCID: PMC1891166.

[xxi] Stephanie C Casey, Amedeo Amedei, Katia Aquilano, Asfar S Azmi, Fabian Benencia, Dipita Bhakta, Alan E Bilsland, Chandra S Boosani, Sophie Chen, Maria Rosa Ciriolo, Sarah Crawford, Hiromasa Fujii, Alexandros G Georgakilas, Gunjan Guha, Dorota Halicka, William G Helferich, Petr Heneberg, Kanya Honoki, W Nicol Keith, Sid P Kerkar, Sulma I Mohammed, Elena Niccolai, Somaira Nowsheen, H P Vasantha Rupasinghe, Abbas Samadi, Neetu Singh, Wamidh H Talib, Vasundara Venkateswaran, Richard L Whelan, Xujuan Yang, Dean W Felsher. Cancer prevention and therapy through the modulation of the tumor microenvironment. Semin Cancer Biol. 2015 Apr 10. Epub 2015 Apr 10. PMID: 25865775

[xxii] Manayi A, Nabavi SM, Setzer WN, Jafari S. Piperine as a Potential Anti-cancer Agent: A Review on Preclinical Studies. Curr Med Chem. 2018;25(37):4918-4928. doi: 10.2174/0929867324666170523120656. PMID: 28545378.

[xxiii] Kiran George, Nisha Susan Thomas, Raman Malathi. Piperine blocks voltage gated K current and inhibits proliferation in androgen sensitive and insensitive human prostate cancer cell lines. Arch Biochem Biophys. 2019 Apr 29 ;667:36-48. Epub 2019 Apr 29. PMID: 31047869

[xxiv] Yi Lin, Jianping Xu, Hehe Liao, Lu Li, Lei Pan. Piperine induces apoptosis of lung cancer A549 cells via p53-dependent mitochondrial signaling pathway. Tumour Biol. 2014 Apr ;35(4):3305-10. Epub 2013 Nov 24. PMID: 24272201

[xxv] Minh Truong Do, Hyung Gyun Kim, Jae Ho Choi, Tilak Khanal, Bong Hwan Park, Thu Phuong Tran, Tae Cheon Jeong, Hye Gwang Jeong, Antitumor efficacy of piperine in the treatment of human HER2-overexpressing breast cancer cells, Food Chemistry, Volume 141, Issue 3, 2013, Pages 2591-2599, ISSN 0308-8146, https://doi.org/10.1016/j.foodchem.2013.04.125.

[xxvi] Leonardo Marques da Fonseca, Lucas Rodrigues Jacques da Silva, Jhenifer Santos Dos Reis, Marcos André Rodrigues da Costa Santos, Victoria de Sousa Chaves, Kelli Monteiro da Costa, Julliana de Nazareth Sa-Diniz, Celio Geraldo Freire de Lima, Alexandre Morrot, Tatiany Nunes Franklim, Douglas Chaves de Alcântara-Pinto, Marco Edilson Freire de Lima, Jose Osvaldo Previato, Lucia Mendonça-Previato, Leonardo Freire-de-Lima. Piperine Inhibits TGF-β Signaling Pathways and Disrupts EMT-Related Events in Human Lung Adenocarcinoma Cells. Medicines (Basel). 2020 Apr 8 ;7(4). Epub 2020 Apr 8. PMID: 32276474

[xxvii] Zeynep Busra Bolat, Zeynep Islek, Bilun Nas Demir, Elif Nur Yilmaz, Fikrettin Sahin, Mehmet Hikmet Ucisik. Curcumin- and Piperine-Loaded Emulsomes as Combinational Treatment Approach Enhance the Anticancer Activity of Curcumin on HCT116 Colorectal Cancer Model. Front Bioeng Biotechnol. 2020;8:50. Epub 2020 Feb 11. PMID: 32117930

[xxviii] Kakarala M, Brenner DE, Korkaya H, Cheng C, Tazi K, Ginestier C, Liu S, Dontu G, Wicha MS. Targeting breast stem cells with the cancer preventive compounds curcumin and piperine. Breast Cancer Res Treat. 2010 Aug;122(3):777-85. doi: 10.1007/s10549-009-0612-x. Epub 2009 Nov 7. PMID: 19898931; PMCID: PMC3039120.

[xxix] National Institute of Health, Health Topics, Coronary Heart Disease. https://www.nhlbi.nih.gov/health-topics/coronary-heart-disease

[xxx] Jie Yan, Si-Chi Xu, Chun-Yan Kong, Xiao-Yang Zhou, Zhou-Yan Bian, Ling Yan, Qi-Zhu Tang, Piperine Alleviates Doxorubicin-Induced Cardiotoxicity via Activating PPAR-γ in Mice. PPAR Research, vol. 2019, Article ID 2601408, 11 pages, 2019. https://doi.org/10.1155/2019/2601408.

[xxxi] Vishal Diwan, Hemant Poudyal, Lindsay Brown. Piperine Attenuates Cardiovascular, Liver and Metabolic Changes in High Carbohydrate, High Fat-Fed Rats. Cell Biochem Biophys. 2011 Oct 30. Epub 2011 Oct 30. PMID: 22038304

[xxxii] Shah SS, Shah GB, Singh SD, Gohil PV, Chauhan K, Shah KA, Chorawala M. Effect of piperine in the regulation of obesity-induced dyslipidemia in high-fat diet rats. Indian J Pharmacol. 2011 May;43(3):296-9. doi: 10.4103/0253-7613.81516. PMID: 21713094; PMCID: PMC3113382.

[xxxiii] Yunes Panahi, Mahboobeh Sadat Hosseini, Nahid Khalili, Effat Naimi, Muhammed Majeed, Amirhossein Sahebkar. Antioxidant and anti-inflammatory effects of curcuminoid-piperine combination in subjects with metabolic syndrome: A randomized controlled trial and an updated meta-analysis. Clin Nutr. 2015 Jan 7. Epub 2015 Jan 7. PMID: 25618800

[xxxiv] Ginpreet Kaur, Mihir Invally, Meena Chintamaneni. Influence of Piperine and Quercetin on Antidiabetic Potential of Curcumin. J Complement Integr Med. 2016 Jun 25. Epub 2016 Jun 25. PMID: 27343476

[xxxv] Parim BrahmaNaidu, Harishankar Nemani, Balaji Meriga, Santosh Kumar Mehar, Sailaja Potana, Sajjalaguddam Ramgopalrao. Mitigating efficacy of piperine in the physiological derangements of high fat diet induced obesity in Sprague Dawley rats. Chem Biol Interact. 2014 Sep 25 ;221:42-51. Epub 2014 Jul 31. PMID: 25087745

[xxxvi] Acharaporn Duangjai, Kornkanok Ingkaninan, Sakonwun Praputbut, Nanteetip Limpeanchob. Black pepper and piperine reduce cholesterol uptake and enhance translocation of cholesterol transporter proteins. J Nat Med. 2013 Apr ;67(2):303-10. Epub 2012 Jun 27. PMID: 22736065

[xxxvii] Shubham Atal, Sarjana Atal, Savita Vyas, Pradeep Phadnis. Bio-enhancing Effect of Piperine with Metformin on Lowering Blood Glucose Level in Alloxan Induced Diabetic Mice. Pharmacognosy Res. 2016 Jan-Mar;8(1):56-60. PMID: 26941537

[xxxviii] Amirhossein Sahebkar, Yunes Panahi, Nahid Khalili, Ebrahim Sahebi, Soha Namazi, Stephen L Atkin, Muhammed Majeed. Curcuminoids plus piperine modulate adipokines in type 2 diabetes mellitus. Curr Clin Pharmacol. 2018 Jan 3. Epub 2018 Jan 3. PMID: 29299989

[xxxix] Penn Medicine, Updates, Health and Wellness, What Is Means to be Immunocompromised. https://www.pennmedicine.org/updates/blogs/health-and-wellness/2020/may/what-it-means-to-be-immunocompromised

[xl] Carolyn D. Doucette, Anna L. Greenshields, Robert S. Liwski, David W. Hoskin, Piperine blocks interleukin-2-driven cell cycle progression in CTLL-2 T lymphocytes by inhibiting multiple signal transduction pathways, Toxicology Letters, Volume 234, Issue 1, 2015, Pages 1-12, ISSN 0378-4274, https://doi.org/10.1016/j.toxlet.2015.01.020.

[xli] Bang, J.S., Oh, D.H., Choi, H.M. et al. Anti-inflammatory and antiarthritic effects of piperine in human interleukin 1β-stimulated fibroblast-like synoviocytes and in rat arthritis models. Arthritis Res Ther 11, R49 (2009). https://doi.org/10.1186/ar2662

[xlii] M.R. Bhalekar, A.R. Madgulkar, P.S. Desale, G. Marium Formulation of piperine solid lipid nanoparticles (SLN) for treatment of rheumatoid arthritis. Drug Dev Ind Pharm, 43 (2017), pp. 1003-1010, 10.1080/03639045.2017.1291666

[xliii] Pannu, N., Bhatnagar, A. Combinatorial therapeutic effect of resveratrol and piperine on murine model of systemic lupus erythematosus. Inflammopharmacol 28, 401–424 (2020). https://doi.org/10.1007/s10787-019-00662-w

[xliv] Panda S, Kar A. Piperine lowers the serum concentrations of thyroid hormones, glucose and hepatic 5’D activity in adult male mice. Horm Metab Res. 2003 Sep;35(9):523-6. doi: 10.1055/s-2003-42652. PMID: 14517767.

[xlv] Web MD, A to Z Guides, Autoimmune Diseases. https://www.webmd.com/a-to-z-guides/autoimmune-diseases

[xlvi] Anoop Kumar, Neelima Sharma. Comparative efficacy of piperine and curcumin in deltamethrin induced splenic apoptosis and altered immune functions. Pestic Biochem Physiol. 2015 Mar ;119:16-27. Epub 2015 Mar 10. PMID: 25868812

[xlvii] Susan L. Fink, Brad T. Cookson. Apoptosis, Pyroptosis, and Necrosis: Mechanistic Description of Dead and Dying Eukaryotic Cells. Infection and Immunity. Mar 2005, 73 (4) 1907-1916; doi: 10.1128/IAI.73.4.1907-1916.2005.

[xlviii] Yi-Dan Liang, Wen-Jing Bai, Chen-Guang Li, Li-Hui Xu, Hong-Xia Wei, Hao Pan, Xian-Hui He, Dong-Yun Ouyang. Piperine Suppresses Pyroptosis and Interleukin-1β Release upon ATP Triggering and Bacterial Infection. Front Pharmacol. 2016 ;7:390. Epub 2016 Oct 20. PMID: 27812336

---