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Efficacy of forskolin as a promising therapy for chronic olfactory dysfunction post COVID-19

  • Rhinology
  • Published:
European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

Purpose

Olfactory dysfunction is increasingly common among COVID-19 patients, impacting their well-being. Reports have demonstrated decreased levels of cyclic adenosine monophosphate and cyclic guanosine monophosphate among patients with chronic olfactory dysfunction. A prospective randomized clinical trial was developed to demonstrate the efficacy of an oral forskolin regimen treatment, an adenylyl cyclase activator that raises intracellular levels of cyclic adenosine monophosphate, for the treatment of olfactory dysfunction following COVID-19, compared to placebo regimen.

Methods

The study enrolled 285 participants with persistent olfactory dysfunction post COVID-19 infection, randomly assigning them to receive either placebo capsules (n = 120) or oral forskolin capsules (n = 165). Follow-up was conducted to track progress, with 18 participants from the placebo group and 12 from the forskolin group lost during this period. Olfactory function was assessed using the “Sniffin’ Sticks” test, measuring threshold, discrimination and identification scores before and after treatment.

Results

Subjects administered forskolin capsules demonstrated a significant enhancement in their composite TDI (threshold, discrimination and identification) score, suggesting a notable amelioration in olfactory functionality. Moreover, the discrimination and identification scores notably improved within the forskolin group. Conversely, no significant alterations were observed in the threshold scores.

Conclusion

This study suggests that forskolin can contribute potentially to improve chronic olfactory dysfunction post COVID-19.

Trial registration

DFM-IRB00012367-23-10-001.

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References

  1. Whitcroft KL, Hummel T (2020) Olfactory dysfunction in COVID-19: diagnosis and management. JAMA 323(24):2512–2514

    Article  CAS  PubMed  Google Scholar 

  2. Saniasiaya J, Islam MA, Abdullah B (2021) Prevalence of olfactory dysfunction in Coronavirus Disease 2019 (COVID-19): a Meta‐analysis of 27,492 patients. Laryngoscope 131(4):865–878

    Article  CAS  PubMed  Google Scholar 

  3. Butowt R, Bilinska K, von Bartheld CS (2023) Olfactory dysfunction in COVID-19: new insights into the underlying mechanisms. Trends Neurosci

  4. Yuki K, Fujiogi M, Koutsogiannaki S (2020) COVID-19 pathophysiology: a review. Clin Immunol 215:108427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Neta FI, Fernandes ACL, Vale AJM, Pinheiro FI, Cobucci RN, de Azevedo EP et al (2021) Pathophysiology and possible treatments for olfactory-gustatory disorders in patients affected by COVID-19. Curr Res Pharmacol Drug Discovery 2:100035

    Article  Google Scholar 

  6. Beyerstedt S, Casaro EB, Rangel ÉB (2021) COVID-19: angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV-2 infection. Eur J Clin Microbiol Infect Dis 40:905–919

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Uversky VN, Elrashdy F, Aljadawi A, Ali SM, Khan RH, Redwan EM (2021) Severe acute respiratory syndrome coronavirus 2 infection reaches the human nervous system: how? J Neurosci Res 99(3):750–777

    Article  CAS  PubMed  Google Scholar 

  8. Dibattista M, Reisert J (2016) The odorant receptor-dependent role of olfactory marker protein in olfactory receptor neurons. J Neurosci 36(10):2995–3006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Boccaccio A, Menini A, Pifferi S (2021) The cyclic AMP signaling pathway in the rodent main olfactory system. Cell Tissue Res 383(1):429–443

    Article  CAS  PubMed  Google Scholar 

  10. Henkin R, Velicu I (2008) cAMP and cGMP in nasal mucus: relationships to taste and smell dysfunction, gender and age. Clin Invest Med. :E71–E7

  11. Lechien JR, Journe F, Hans S, Chiesa-Estomba CM, Mustin V, Beckers E et al (2020) Severity of anosmia as an early symptom of COVID-19 infection may predict lasting loss of smell. Front Med. :716

  12. Hosseinpoor M, Kabiri M, Rajati Haghi M, Ghadam Soltani T, Rezaei A, Faghfouri A et al (2022) Intranasal corticosteroid treatment on recovery of long-term olfactory dysfunction due to COVID‐19. Laryngoscope 132(11):2209–2216

    Article  CAS  PubMed  Google Scholar 

  13. Hummel T, Rissom K, Reden J, Hähner A, Weidenbecher M, Hüttenbrink KB (2009) Effects of olfactory training in patients with olfactory loss. Laryngoscope 119(3):496–499

    Article  PubMed  Google Scholar 

  14. Hummel T, Whitcroft KL, Rueter G, Haehner A (2017) Intranasal vitamin A is beneficial in post-infectious olfactory loss. Eur Arch Otorhinolaryngol 274:2819–2825

    Article  PubMed  Google Scholar 

  15. Alasbahi R, Melzig M (2012) Forskolin and derivatives as tools for studying the role of cAMP. Die Pharmazie-An Int J Pharm Sci 67(1):5–13

    CAS  Google Scholar 

  16. Otsuguro K-i, Gautam SH, Ito S, Habara Y, Saito T (2005) Characterization of forskolin-induced Ca2 + signals in rat olfactory receptor neurons. J Pharmacol Sci 97(4):510–518

    Article  CAS  PubMed  Google Scholar 

  17. Ríos-Hoyo A, Gutiérrez-Salmeán G (2016) New dietary supplements for obesity: what we currently know. Curr Obes Rep 5:262–270

    Article  PubMed  Google Scholar 

  18. Salehi B, Staniak M, Czopek K, Stępień A, Dua K, Wadhwa R et al (2019) The therapeutic potential of the labdane diterpenoid forskolin. Appl Sci 9(19):4089

    Article  CAS  Google Scholar 

  19. Majeed M, Nagabhushanam K, Natarajan S, Vaidyanathan P, Karri SK, Jose JA (2015) Efficacy and safety of 1% forskolin eye drops in open angle glaucoma–An open label study. Saudi J Ophthalmol 29(3):197–200

    Article  PubMed  PubMed Central  Google Scholar 

  20. Sniffin’Sticks HT (1997) Olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold. Chem Senses 22(1):39–52

    Article  Google Scholar 

  21. Hummel T, Sekinger B, Wolf SR, Pauli E, Kobal G (1997) Sniffin’sticks’: olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold. Chem Senses 22(1):39–52

    Article  CAS  PubMed  Google Scholar 

  22. Kobal G, Hummel T, Sekinger B, Barz S, Roscher S, Wolf S (1996) Sniffin’sticks: screening of olfactory performance. Rhinology 34(4):222–226

    CAS  PubMed  Google Scholar 

  23. Busner J, Targum SD (2007) The clinical global impressions scale: applying a research tool in clinical practice. Psychiatry (Edgmont) 4(7):28

    PubMed  Google Scholar 

  24. Dunlop BW, Gray J, Rapaport MH (2017) Transdiagnostic clinical global impression scoring for routine clinical settings. Behav Sci 7(3):40

    Article  PubMed  PubMed Central  Google Scholar 

  25. Burks SM, Rosas-Hernandez H, Ramirez-Lee MA, Cuevas E, Talpos JC (2021) Can SARS-CoV-2 infect the central nervous system via the olfactory bulb or the blood-brain barrier? Brain, behavior, and immunity. 95:7–14

  26. Wolfensberger M (2000) Sniffin’sticks: a new olfactory test battery. Acta Otolaryngol 120(2):303–306

    Article  CAS  PubMed  Google Scholar 

  27. Rumeau C, Nguyen D, Jankowski R (2016) How to assess olfactory performance with the Sniffin’sticks test®. Eur Annals Otorhinolaryngol Head Neck Dis 133(3):203–206

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Otolaryngology, Faculty of Medicine, Al-Azhar University, Damietta, Egypt

    Mohamed H. Abdelazim

  2. Department of Pharmaceutical Sciences, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia

    Faisal Alsenani

  3. Pharmaceutical Practices Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia

    Mohammed Alnuhait, Abdullah S. Alshammari & Adnan Alharbi

  4. Department of Family and Community Medicine, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia

    Abdullah H. Altemani

  5. Department of pharmaceutical care, King Fahad General Hospital, Jeddah, Saudi Arabia

    Eyad A. Althagafi

  6. Department of Pathological Sciences, Fakeeh College for Medical Sciences, Jeddah, Saudi Arabia

    Dania S. Waggas

  7. Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt

    Ahmed H. Abdelazim

Authors
  1. Mohamed H. Abdelazim
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  2. Faisal Alsenani
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  3. Mohammed Alnuhait
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  4. Abdullah S. Alshammari
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  5. Abdullah H. Altemani
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  6. Eyad A. Althagafi
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  7. Dania S. Waggas
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  8. Ahmed H. Abdelazim
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  9. Adnan Alharbi
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Corresponding author

Correspondence to Ahmed H. Abdelazim.

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Ethical approval

The Damietta Faculty of Medicine’s Ethical Committee of Al Azhar University in Egypt granted the study approval (DFM-IRB00012367-23-10-001).

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Abdelazim, M.H., Alsenani, F., Alnuhait, M. et al. Efficacy of forskolin as a promising therapy for chronic olfactory dysfunction post COVID-19. Eur Arch Otorhinolaryngol (2024). https://doi.org/10.1007/s00405-024-08802-x

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