Research

Piperine

39 peer-reviewed studies curated from PubMed and Semantic Scholar.

1
Meta-analyses
3
Systematic reviews
14
RCTs
21
Other studies
Meta-analyses (3%)
Systematic reviews (8%)
RCTs (36%)

Studies

Sorted by quality and recency

2025·Central nervous system agents in medicinal chemistry·Nasim Rahimi-Dehkordi, Saeid Heidari-Soureshjani, Sahar Rostamian

A Systematic Review of the Anti-seizure and Antiepileptic Effects and Mechanisms of Piperine.

Systematic review

This systematic review investigates piperine's anti-seizure and antiepileptic effects and mechanisms. Piperine shows antiepileptic activity by affecting antioxidant, anti-inflammatory, and anti-apoptotic activity in the brain, modulating BDNF and GABAergic activity, and increasing antiepileptic drug bioavailability. The review highlights the need for more clinical studies.

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2025·European journal of pharmacology·Fernanda Brunetto, Gabriel de Oliveira Vaz da Costa, Vitoria Soares Oehler, et al

Piperine and its derivatives as a therapeutic alternative against leishmaniasis: A comprehensive review.

Systematic review

This comprehensive review evaluates the potential of piperine and its derivatives as therapeutic agents against leishmaniasis. It focuses on their mechanisms of action, effectiveness in experimental models, and advancements in drug delivery. Piperine shows promising antileishmanial effects, with structural modifications and novel delivery systems enhancing potency and bioavailability. Synergistic effects with meglumine antimoniate and amphotericin B are also noted.

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2025·Journal of complementary & integrative medicine·Yuwadee Manjit, Pranee Sriraj, Areeya Changthong, et al

Assessing the impact of massage and herbal therapies on chronic low back pain: a randomized controlled trial.

RCTn = 66Joint Bone Health

A single-blind RCT with 66 participants assessed the efficacy of Thai massage combined with the traditional herbal formula YTPS in reducing chronic low back pain. The combined therapy group showed the greatest improvements in pain and disability scores, with enhanced antioxidant activity and no significant adverse biochemical changes.

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2024·BMC gastroenterology·Chao Zhang, Dao Lai Huang, Kun Zhou, et al

Human blood metabolites and gastric cancer: a Mendelian randomization analysis.

Meta-analysis

Mendelian randomization analysis using GWAS datasets to investigate the causal relationship between circulating metabolites and gastric cancer. Significant associations were found between 3-methyl-2-oxovalerate, piperine, and Phe-Phe dipeptide with gastric cancer risk. Elevated levels of 3-methyl-2-oxovalerate and piperine may increase risk, while Phe-Phe dipeptide may be protective.

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2024·Scientific reports·Masoud Nouri-Vaskeh, Payam Hashemi, Naser Hataminia, et al

The impact of piperine on the metabolic conditions of patients with NAFLD and early cirrhosis: a randomized double-blind controlled trial.

RCT

RCT investigating the impact of 5 mg piperine consumption for 12 weeks on patients with NAFLD and early cirrhosis. Piperine significantly decreased hepatic enzymes, glucose, and alleviated dyslipidemia, reducing HOMA levels and insulin resistance compared to placebo.

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2022·Journal of cosmetic dermatology·Yaqi Mao, Ziqian Xu, Jun Song, et al

Efficacy of a mixed preparation containing piperine, capsaicin and curcumin in the treatment of alopecia areata.

RCTn = 60Skin Hair Health

RCT evaluating the efficacy and safety of a mixed preparation containing piperine, capsaicin, and curcumin for treating alopecia areata in 60 patients. Both the mixed preparation and minoxidil groups showed significant hair regrowth, with the mixed preparation group having a 63.33% effective rate compared to 70% for minoxidil. No serious adverse events were reported.

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2021·Molecular nutrition & food research·Katharina N Diaye, Marcel Debong, Jürgen Behr, et al

Dietary Piperine is Transferred into the Milk of Nursing Mothers.

RCT

Intervention trial investigating the transfer of piperine from a curry dish into the milk of breastfeeding mothers. Piperine was identified in human milk, but concentrations were below the human taste threshold. The study suggests potential sensory programming effects through frequent exposure.

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2019·Critical reviews in food science and nutrition·Heerasing Takooree, Muhammad Z Aumeeruddy, Kannan R R Rengasamy, et al

A systematic review on black pepperL.): from folk uses to pharmacological applications.

Systematic reviewImmunity Inflammation Brain Health Heart Health Longevity

This systematic review compiles scientific data on the traditional uses, phytochemical composition, and pharmacological properties of black pepper. It highlights black pepper's antimicrobial, antioxidant, anticancer, antidiabetic, hypolipidemic, anti-inflammatory, analgesic, anticonvulsant, and neuroprotective effects, with piperine identified as a major bioactive compound.

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2017·The Journal of the Association of Physicians of India·Naresh Patel, K Jagannath, Agam Vora, et al

A Randomized, Controlled, Phase III Clinical Trial to Evaluate the Efficacy and Tolerability of Risorine with Conventional Rifampicin in the Treatment of Newly Diagnosed Pulmonary Tuberculosis Patients.

RCTn = 216

RCT comparing Risorine (Rifampicin + Isoniazid + Piperine) to conventional anti-TB therapy in 216 newly diagnosed pulmonary tuberculosis patients. Risorine showed a higher sputum conversion rate and cure rate compared to the control group, with a better safety profile and tolerability.

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2021·International journal of food sciences and nutrition·Joana Furtado de Figueiredo Neta, Vivian Saraiva Veras, Danilo Ferreira de Sousa, et al

Effectiveness of the piperine-supplementedL. in metabolic control of patients with type 2 diabetes: a randomised double-blind placebo-controlled clinical trial.

RCTn = 71Nutrition

A randomised double-blind placebo-controlled clinical trial in Brazil with 71 participants evaluated the effectiveness of piperine-supplemented L. in metabolic control of type 2 diabetes. The piperine group showed significant decreases in glycaemia, glycated haemoglobin, HOMA index, and triglycerides over 120 days.

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2018·Phytotherapy research : PTR·Anoosh Shafiee, Mahmood Hoormand, Mohammad Shahidi-Dadras, et al

The effect of topical piperine combined with narrowband UVB on vitiligo treatment: A clinical trial study.

RCTn = 63

Double-blind clinical trial evaluating the effect of topical piperine combined with narrowband UVB on vitiligo treatment in 63 patients. The case group treated with piperine showed significantly higher repigmentation levels compared to the control group. Temporary side effects included burning sensation and redness.

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2025·Analytical methods : advancing methods and applications·G R Advaya, Gaurav Banerjee, Jobin Cyriac

Surface enhanced Raman scattering (SERS) for the detection of piperine, an active component in herbal formulations.

Study

The study demonstrates the use of surface-enhanced Raman scattering (SERS) with Ag@citrate nanoparticles for detecting piperine, a major alkaloid in black pepper and long pepper. The method shows high sensitivity, repeatability, and specificity, and is applied for quality assurance and authenticity verification in the pharmaceutical sector.

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2025·Scientific reports·Mrinalini Prasad, Shivangi Mathur, Deeksha Singh, et al

De novo transcriptome profiling revealing genes involved in piperine biosynthetic pathway in Piper longum L.

Study

The study used high-throughput sequencing and de novo transcriptome assembly to analyze the transcriptomes of Piper longum leaves, roots, and spikes, focusing on piperine biosynthesis. It identified key pathways, genetic markers, and transcription factors involved in piperine production, with spikes showing the highest piperine content.

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2025·Chemistry & biodiversity·Santosh Prasad Chaudhary Kurmi, Dipanjan Karati

Molecular Targets and Mechanisms of Piperine Against Breast Cancer: A Network Pharmacology, Molecular Docking Analysis, and Toxicity Prediction.

StudyWomens Health

The paper investigates the molecular targets and mechanisms of piperine against breast cancer using network pharmacology, molecular docking analysis, and toxicity prediction. Piperine modulates cancer signaling pathways and enzymes, demonstrating potential as a therapeutic agent for breast cancer treatment.

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2023·Sustainable Chemistry·Charles Lwamba, Saied A. Aboushanab, R. Ambati, et al

Innovative Green Approach for Extraction of Piperine from Black Pepper Based on Response Surface Methodology

Study

The study assessed the extraction of piperine from black pepper using natural deep eutectic solvents and ultrasound-assisted extraction. The optimal extraction conditions were determined, and the piperine extract purity was found to be 90%. The study suggests that black pepper could be used as a functional food application.

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2021·Molecular nutrition & food research·Roland Wedekind, Pekka Keski-Rahkonen, Nivonirina Robinot, et al

Pepper Alkaloids and Processed Meat Intake: Results from a Randomized Trial and the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort.

RCTn = 12

A randomized cross-over dietary intervention study with 12 healthy volunteers identified pepper alkaloid metabolites, including piperine, as major discriminants of salami intake. The study also tested associations with processed meat intake in a cross-sectional study within the EPIC cohort, finding that piperine is associated with habitual intake of sausages.

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2017·Journal of controlled release : official journal of the Controlled Release Society·Irina Cherniakov, Dvora Izgelov, Dinorah Barasch, et al

Piperine-pro-nanolipospheres as a novel oral delivery system of cannabinoids: Pharmacokinetic evaluation in healthy volunteers in comparison to buccal spray administration.

RCTn = 9

A two-way crossover clinical study in 9 healthy volunteers evaluated the pharmacokinetic profile of a THC-CBD-piperine-PNL formulation compared to Sativex®. The piperine-PNL formulation increased Cmax and AUC for both THC and CBD, demonstrating improved oral bioavailability.

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2016·Drug research·S K Bedada, R Appani, P K Boga

Effect of Piperine on the Metabolism and Pharmacokinetics of Carbamazepine in Healthy Volunteers.

RCTn = 12

An open-label, 2 period, sequential study in 12 healthy volunteers investigated the effect of piperine on the metabolism and pharmacokinetics of carbamazepine. Piperine significantly enhanced the maximum plasma concentration, area under the curve, and half-life of carbamazepine, while decreasing its elimination rate constant and apparent oral clearance. The study suggests a potential pharmacokinetic interaction due to piperine-mediated inhibition of CYP3A4 enzyme.

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2016·Xenobiotica; the fate of foreign compounds in biological systems·Satish Kumar Bedada, Praveen Kumar Boga

Effect of piperine on CYP2E1 enzyme activity of chlorzoxazone in healthy volunteers.

RCTn = 12

An open-label, two-period sequential study in 12 healthy volunteers investigated the effect of piperine on CYP2E1 enzyme activity and pharmacokinetics of chlorzoxazone. Piperine significantly altered the pharmacokinetics of chlorzoxazone, suggesting a pharmacokinetic interaction due to CYP2E1 enzyme inhibition by piperine.

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2013·Journal of gastroenterology·Laia Rofes, Viridiana Arreola, Alberto Martin, et al

Effect of oral piperine on the swallow response of patients with oropharyngeal dysphagia.

RCTn = 40Nutrition

RCT assessing the effect of piperine on the swallow response in 40 dysphagic patients. Piperine improved the safety of swallow by reducing unsafe swallows and shortening the time to laryngeal vestibule closure, with a maximal effect at 1 mM concentration.

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2009·Phytotherapy research : PTR·Smita Pattanaik, Debasish Hota, Sudesh Prabhakar, et al

Pharmacokinetic interaction of single dose of piperine with steady-state carbamazepine in epilepsy patients.

RCTn = 20

The study evaluated the effect of piperine on the pharmacokinetics of carbamazepine in epilepsy patients. Piperine significantly increased the mean plasma concentrations and oral bioavailability of carbamazepine, suggesting it acts as a bioavailability-enhancer.

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2007·Drugs in R&D·Ravisekhar Kasibhatta, M U R Naidu

Influence of piperine on the pharmacokinetics of nevirapine under fasting conditions: a randomised, crossover, placebo-controlled study.

RCTn = 8

Randomised, crossover, placebo-controlled study in 8 healthy adult males examining the effect of piperine on the pharmacokinetics of nevirapine. Piperine increased the bioavailability of nevirapine, with significant increases in plasma concentration and area under the curve metrics.

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2026·Journal of pharmaceutical and biomedical analysis·Xue-Ling Zhang, Qian Li, Run-Qin Wang, et al

Discovery of anti-renal fibrosis quality markers from Piperis longi fructus: An integrated strategy of hollow fibre cell trapping method coupled with liquid chromatography-mass spectrometry and in vitro efficacy verification.

In vitro

The study used a hollow fiber cell trapping method coupled with liquid chromatography-mass spectrometry to identify anti-renal fibrosis quality markers in Piperis longi fructus. Piperlonguminine and piperlongumine were determined as key markers, demonstrating the extract's potential therapeutic use for renal fibrosis.

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2025·European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V·Nuttapol Risangud, Nisachon Jangpromma, Phraepakaporn Kunnaja, et al

Enhancing the therapeutic efficacy of piperine in colorectal cancer: development and evaluation of piperine-loaded PLGA-b-PEG copolymer nanoparticles.

In vitro

The study developed piperine-encapsulated PLGA-b-PEG nanoparticles (Pip-PLNP) to enhance piperine's anti-cancer efficacy in colorectal cancer. Pip-PLNP showed significant dose- and time-dependent cytotoxicity in HCT116 human colorectal carcinoma cells, with improved potency compared to free piperine. It induced early and late apoptosis more effectively and caused G0/G1 phase arrest, enhancing piperine's bioavailability and apoptotic activity.

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2025·Journal of pharmacopuncture·Seok-Hwan Sung, Seung-Min Shin, Yunna Kim, et al

's Neuroprotective Role Against Amyloid-β and Okadaic Acid-Induced Toxicity in U87MG Cells Through the Lipocalin-2 Pathway.

In vitroBrain Health

The study investigated the neuroprotective effects of piperine on U87MG cells exposed to amyloid-β and okadaic acid. Piperine increased cell viability and decreased levels of LCN2 and phosphorylated tau, suggesting its potential to alleviate neuroinflammation and toxicity associated with Alzheimer's disease.

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2025·Chinese medicine·Boyu Pan, Ling Liu, Xiaofeng Wang, et al

Multi-omics analysis reveals ACOT1 as the key target of piperine in Piper Longum-mediated gastric cancer treatment.

Animal studyGut Health

The study used a multi-omics framework to investigate Piper longum's anti-cancer mechanisms against gastric cancer. Piperine was identified as the key active compound, with ACOT1 as a critical molecular target. Piper longum showed dose-dependent inhibition of gastric cancer growth, superior to conventional chemotherapy, and modulated gut microbiota composition.

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2024·Heliyon·Aref L Zayed, Mohammad Hadieh, Jomana Al Hroot, et al

Development of a rapid HPLC-fluorescence method for monitoring warfarin metabolites formation: In vitro studies for evaluating the effect of piperine on warfarin metabolism and plasma coagulation.

In vitro

The study investigated the effect of piperine on warfarin metabolism using a rapid HPLC-Fluorescence method in liver microsomes. Piperine inhibited the formation of the major metabolite, 7-hydroxywarfarin, in human and rat liver microsomes, suggesting a potential drug interaction with warfarin at the metabolism level. However, piperine did not affect prothrombin time (PT) and activated partial thromboplastin time (aPTT) in rat plasma.

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2024·Scientific reports·Protha Biswas, Devendra Kumar Pandey, Mahipal S Shekhawat, et al

Tissue-specific variations of piperine in ten populations of Piper longum L.: bioactivities and toxicological profile.

In vitroInflammation

The study analyzed intra-specific variation in piperine content among different chemotypes of Piper longum from West Bengal. It found that fruit chemotypes contain higher piperine levels, with PL9 showing the highest antioxidant activity. The Allium cepa root tip assay indicated no significant genotoxic effects.

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2024·Biochemical and biophysical research communications·Jianyu Xia, Pengju Guo, Jing Yang, et al

Piperine induces autophagy of colon cancer cells: Dual modulation of AKT/mTOR signaling pathway and ROS production.

In vitro

The study investigates the effects of piperine on colorectal cancer cells in vitro and in a mouse xenograft model. Piperine inhibited CRC cell viability, suppressed tumor weight and volume, and induced autophagy-dependent cell death by increasing ROS production and inhibiting Akt/mTOR signaling.

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2023·Biological & pharmaceutical bulletin·Kazuo Noguchi, Moka Teramura, Ayano Kitagawa, et al

Relaxant Effects of Piperine and Piperlongumine from Piper longum Fruits on Porcine Coronary Artery.

In vitro

The study investigates the effects of piperine and piperlongumine from Piper longum fruits on porcine coronary arteries. Piperlongumine, unlike piperine or diltiazem, concentration-dependently inhibited basal contractile tone in endothelium-denuded coronary arteries. Both compounds inhibit tonic contractions induced by high potassium chloride concentrations, with piperlongumine showing additional effects on histamine-induced contractions in a Ca-free medium.

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2023·Frontiers in pharmacology·Oluwafemi Adeleke Ojo, Akingbolabo Daniel Ogunlakin, Gideon Ampoma Gyebi, et al

GC-MS chemical profiling, antioxidant, anti-diabetic, and anti-inflammatory activities of ethyl acetate fraction of(Schumach. and Thonn.) C.D. Adams leaves: experimental and computational studies.

StudyInflammation Nutrition

The study investigates the chemical profile and biological activities of the ethyl acetate fraction of leaves (EFSFL), focusing on its antioxidant, anti-diabetic, and anti-inflammatory properties. EFSFL showed significant inhibition of α-amylase, α-glucosidase, and DPP-IV activities, and restored antioxidant enzyme levels in tissues. GC-MS profiling identified piperine as the most abundant compound, with strong binding tendencies to key enzymes.

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2023·Journal of ethnopharmacology·Lan Yu, Xiaolu Hu, Rongrong Xu, et al

Piperine promotes PI3K/AKT/mTOR-mediated gut-brain autophagy to degrade α-Synuclein in Parkinson's disease rats.

Animal studyBrain Health Gut Health

The study investigates the role of piperine in promoting gut-brain autophagy to reduce α-Synuclein levels in Parkinson's disease model rats. Piperine improved autonomic movement and gastrointestinal functions, reduced α-Syn aggregation, and attenuated dopaminergic neuron loss by activating the PI3K/AKT/mTOR-mediated autophagy pathway.

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2021·Indian Journal of Animal Research·H. Patel, U. Patel, C. Modi, et al

Pharmacokinetics of Marbofloxacin Following Oral Administration in Piperine, Quercetin Alone and Both in Combination Pretreated Broiler Chickens

Animal study

The study investigated the pharmacokinetics of marbofloxacin following oral administration in broiler chickens pretreated with piperine, quercetin, and their combination. The combination pretreatment improved the pharmacokinetic profile of marbofloxacin, suggesting a bio-enhancing effect of piperine and quercetin.

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2018·Journal of Ayurveda and integrative medicine·Alok K Hazra, Banti Chakraborty, Achintya Mitra, et al

A rapid HPTLC method to estimate piperine in Ayurvedic formulations.

Study

The study developed a simple, accurate, and sensitive HPTLC method for detecting and quantifying piperine in various Ayurvedic formulations for standardization. Piperine was quantified in all samples, with P. nigrum showing higher piperine content than P. longum and P. chaba. Hingavastaka churna had the highest piperine content among the formulations tested.

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2026·Frontiers in oncology·Wamidh H Talib, Mohanad Jawad Kadhim, Hadeel Shaher Al Junaidi, et al

Piperine as a modulator of cancer hallmarks: mechanistic insights and therapeutic potential.

Review

This narrative review summarizes preclinical studies on piperine's impact on cancer hallmarks. Piperine has shown anticancer activity by modulating cell growth, apoptosis, angiogenesis, invasion, metastasis, inflammation, and oxidative stress. It may enhance chemotherapy effectiveness by improving drug bioavailability and reducing resistance. However, its therapeutic use is limited by poor solubility, low bioavailability, and lack of clinical research.

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2025·Therapeutic delivery·Girish Kumar, Beatriz Ruivinho, Tarun Virmani, et al

Unlocking the full potential of piperine-loaded nanocarriers for cancer treatment.

Review

The review discusses the potential of piperine-loaded nanocarriers in cancer treatment, addressing limitations of current chemotherapeutic treatments. It highlights the pharmacological characteristics of piperine and the benefits of nanoformulations in improving its therapeutic effectiveness and bioavailability.

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2024·Molecular biology reports·Devika Tripathi, Tanya Gupta, Prashant Pandey

Exploring Piperine: Unleashing the multifaceted potential of a phytochemical in cancer therapy.

Review

The paper reviews the potential of piperine, a compound found in black and long pepper, as a chemopreventive agent in cancer therapy. Piperine modulates key signaling pathways, inhibits cancer cell migration and invasion, and enhances sensitivity to ionizing radiation, offering a dual role in radiosensitization and radioprotection.

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2020·Nutrients·Diego Fernández-Lázaro, J. Mielgo-Ayuso, A. Córdova Martínez, et al

Iron and Physical Activity: Bioavailability Enhancers, Properties of Black Pepper (Bioperine®) and Potential Applications

ReviewPhysical Performance

The paper reviews the impact of black pepper (piperine) on the bioavailability of iron in physically active individuals. It discusses how piperine may enhance iron absorption, potentially benefiting athletic performance by improving oxygen transport and utilization. The review highlights the need for more research but suggests piperine could advance oral iron supplementation.

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1981·Journal of ethnopharmacology·C K Atal, U Zutshi, P G Rao

Scientific evidence on the role of Ayurvedic herbals on bioavailability of drugs.

In vitro

Experiments evaluated the trikatu group of acrids (long pepper, black pepper, and ginger) on drug bioavailability. Piper longum increased blood levels of vasicine by 233%, and piperine increased sparteine levels by over 100%, suggesting enhanced drug bioavailability.

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