Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 May 11;16(5):730.
doi: 10.3390/ph16050730.

Synergistic Effects of Caffeine in Combination with Conventional Drugs: Perspectives of a Drug That Never Ages

Davide Ialongo  1 , Valeria Tudino  1 , Merve Arpacioglu  1 , Antonella Messore  1 , Elisa Patacchini  1 , Roberta Costi  1 , Roberto Di Santo  1 , Valentina Noemi Madia  1
Affiliations
Review

Synergistic Effects of Caffeine in Combination with Conventional Drugs: Perspectives of a Drug That Never Ages

Davide Ialongo et al. Pharmaceuticals (Basel). .

Abstract

Plants have been known since ancient times for their healing properties, being used as preparations against human diseases of different etiologies. More recently, natural products have been studied and characterized, isolating the phytochemicals responsible for their bioactivity. Most certainly, there are currently numerous active compounds extracted from plants and used as drugs, dietary supplements, or sources of bioactive molecules that are useful in modern drug discovery. Furthermore, phytotherapeutics can modulate the clinical effects of co-administered conventional drugs. In the last few decades, the interest has increased even more in studying the positive synergistic effects between plant-derived bioactives and conventional drugs. Indeed, synergism is a process where multiple compounds act together to exert a merged effect that is greater than that of each of them summed together. The synergistic effects between phytotherapeutics and conventional drugs have been described in different therapeutic areas, and many drugs are based on synergistic interactions with plant derivatives. Among them, caffeine has shown positive synergistic effects with different conventional drugs. Indeed, in addition to their multiple pharmacological activities, a growing body of evidence highlights the synergistic effects of caffeine with different conventional drugs in various therapeutic fields. This review aims to provide an overview of the synergistic therapeutic effects of caffeine and conventional drugs, summarizing the progress reported to date.

Keywords: anti-inflammatory drugs; anti-obesity drugs; anticancer drugs; antidiabetic drugs; antimicrobial drugs; caffeine; multidrug therapy; neurodegenerative diseases; opioids; synergism.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Depiction of the main mechanisms involved in synergism between plant derivatives and conventional drugs.
Figure 2
Figure 2
Chemical structure of 1,3,7-trimethylxanthine (caffeine).
Figure 3
Figure 3
Chemical structures of antibacterial agents showing synergism with caffeine.
Figure 4
Figure 4
Chemical structure of fluconazole (15).
Figure 5
Figure 5
Coffee components target the hallmarks of cancer, according to Hanahan and Weinberg’s hallmarks of cancer (2011), with modifications.
Figure 6
Figure 6
Chemical structures of anti-inflammatory drugs showing synergism with caffeine.
Figure 7
Figure 7
Chemical structures of opioids showing synergism with caffeine.
Figure 8
Figure 8
Chemical structures of anti-PD drugs showing synergism with caffeine.
Figure 9
Figure 9
Chemical structure of ephedrine (33).
Figure 10
Figure 10
Chemical structure of pioglitazone (34).
See this image and copyright information in PMC

References

    1. Doos L., Roberts E.O., Corp N., Kadam U.T. Multi-drug therapy in chronic condition multimorbidity: A systematic review. Fam. Pract. 2014;31:654–663. doi: 10.1093/fampra/cmu056. - DOI - PMC - PubMed
    1. Pezzani R., Salehi B., Vitalini S., Iriti M., Zuñiga F.A., Sharifi-Rad J., Martorell M., Martins N. Synergistic effects of plant derivatives and conventional chemotherapeutic agents: An update on the cancer perspective. Medicina. 2019;55:110. doi: 10.3390/medicina55040110. - DOI - PMC - PubMed
    1. Foucquier J., Guedj M. Analysis of drug combinations: Current methodological landscape. Pharmacol. Res. Perspect. 2015;3:e00149. doi: 10.1002/prp2.149. Erratum in Pharmacol. Res. Perspect. 2019, 7, e00549. - DOI - PMC - PubMed
    1. Obodozie-Ofoegbu O. Readings in Advanced Pharmacokinetics—Theory, Methods and Applications. IntechOpen; London, UK: 2012. Pharmacokinetics and Drug Interactions of Herbal Medicines: A Missing Critical Step in the Phytomedicine/Drug Development Process.
    1. Dzobo K. The Role of natural products as sources of therapeutic agents for innovative drug discovery. Compr. Pharmacol. 2022;2:408–422. doi: 10.1016/B978-0-12-820472-6.00041-4. - DOI

LinkOut - more resources