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Licensed Unlicensed Requires Authentication Published by De Gruyter August 30, 2021

Efficacy of lettuce seed syrup on insomnia in patients with breast cancer: a pilot double blind randomized placebo controlled clinical trial

  • Seyed Hamdollah Mosavat , Hamid Reza Mirzaei , Bahram Mofid , Reyhaneh Gharehgozlou , Mohammad Mahdi Parvizi , Ryan Bradley , Mehdi Pasalar ORCID logo EMAIL logo and Ghazaleh Heydarirad EMAIL logo



Insomnia and sleep disorders are common and can be severe amongst patients with cancer, especially during chemotherapy. The aim of this study was to evaluate the efficacy of lettuce seed syrup in breast cancer patients who suffer from insomnia or disordered sleep.


This pilot study was a double-blinded randomized controlled clinical trial conducted in Shoha-e-Tajrish Hospital (Tehran, Iran) from September 2018 to June 2019. 50 adult patients with breast cancer with insomnia or sleep disorders were enrolled. Participants were randomly allocated to lettuce seed syrup (5 mL twice daily), or placebo syrup at the same dose for four weeks. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality before and after the intervention.


Compared to placebo, the mean of the total PSQI score decreased significantly in participants who received lettuce seed syrup (p=0.014). In addition, there were statistically significant reductions in the mean scores of subject quality sleep (p=0.002), sleep duration (p=0.038), habitual sleep efficacy (p=0.029) and sleep disturbance (p=0.032) in patients who received lettuce seed syrup.


Lettuce seed syrup may improve self-reported sleep quality in participants with breast cancer. Larger trials are indicated in diverse samples of participants with caner to learn if these finds are generalizable.

Corresponding author: Ghazaleh Heydarirad, MD, PhD, Traditional Medicine and Materia Medica Research Center, No.8 Shams Alley, Vali-e-Asr Street, 1516745811, Tehran, Iran, Phone/Fax: +98(21) 88776027, E-mail: ; and Mehdi Pasalar, MD, MPH, PhD, Research Center for Traditional Medicine and History of Medicine, Shiraz University of Medical Sciences, Faculty of Medicine, Zand St., 7134845794, Shiraz, Iran, Phone/Fax: +98(71)32338476, E-mail:

Award Identifier / Grant number: 1396-01-64-15514


The authors would like to thank the Traditional Medicine and Materia Medica Research Center, school of traditional medicine, Shahid Beheshti University of Medical Sciences, and the office of the Vice-chancellor for Research of Shiraz University of Medical Sciences.

  1. Research funding: Shiraz University of Medical Sciences was supporting this research project through grant No. 1396-01-64-15514.

  2. Author contributions: SHM, HRM and GH designed the research project; SHM, BM, RG, MMP, GH, and MP conducted the research project, including recruitment, intervention and biochemical analysis; MP and GH performed statistical analysis and together with MMP and RB., drafted the manuscript. All authors provided critical comments, read and approved the final version.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The protocol of this study was approved by The Ethics committee of Shiraz University of Medical Sciences (code: IR.SUMS.REC.1397.417) on July 29, 2018. Furthermore, this clinical trialwas registered at Iranian Registry of Clinical Trials (IRCT) website by IRCT20150825023753N13 code.


1. Sateia, M, Doghramji, K, Hauri, P, Morin, C. Evaluation of chronic insomnia. An American academy of sleep medicine review. Sleep 2000;23:243–308. in Google Scholar

2. Moline, ML, Broch, L, Zak, R, Gross, V. Sleep in women across the life cycle from adulthood through menopause. Sleep Med Rev 2003;7:155–77. in Google Scholar PubMed

3. Yennurajalingam, S, Carmack, C, Balachandran, D, Eng, C, Lim, B, Delgado, M, et al.. Sleep disturbance in patients with cancer: a feasibility study of multimodal therapy. BMJ Support Palliat Care 2020. in Google Scholar PubMed

4. Luskin, M, Zhou, E, Zhang, Z, DeAngelo, DJ, Stone, R, Wadleigh, M, et al.. Sleep Disturbance Among Patients with Myelodysplastic Syndromes and Acute Leukemia. DC: Am Soc Hematol Washington; 2019.10.1182/blood-2019-125147Search in Google Scholar

5. Hinds, PS, Hockenberry, M, Rai, SN, Zhang, L, Razzouk, BI, McCarthy, K, et al.. editors. Nocturnal awakenings, sleep environment interruptions, and fatigue in hospitalized children with cancer. Oncol Nurs Forum; 2007.10.1188/07.ONF.393-402Search in Google Scholar PubMed

6. Linder, LA, Christian, BJ, editors Nighttime sleep disruptions, the hospital care environment, and symptoms in elementary school-age children with cancer. Oncol Nurs Forum; 2012. NIH Public Access.10.1188/12.ONF.553-561Search in Google Scholar PubMed PubMed Central

7. Savard, J, Morin, CM. Insomnia in the context of cancer: a review of a neglected problem. J Clin Oncol 2001;19:895–908. in Google Scholar PubMed

8. Theobald, DE. Cancer pain, fatigue, distress, and insomnia in cancer patients. Clin Cornerstone 2004;6:S15–S21. in Google Scholar PubMed

9. Leproult, R, Copinschi, G, Buxton, O, Van Cauter, E. Sleep loss results in an elevation of cortisol levels the next evening. Sleep 1997;20:865–70. in Google Scholar

10. Avidan, AY, Palmer, LA, Doan, JF, Baran, RW. Insomnia medication use and the probability of an accidental event in an older adult population. Drug Healthc Patient Saf 2010;2:225. in Google Scholar PubMed PubMed Central

11. Pagel, J, Pandi-Perumal, SR, Monti, JM. Treating insomnia with medications. Sleep Sci Prac 2018;2:5. in Google Scholar

12. Bourin, M. Hypnotic drugs: pharmacological and therapeutic issues. SOJ Pharm Pharm Sci 2018;5:1–4. in Google Scholar

13. Jezdic, Z, Vulinac, SO, Racz, A, Kovacevic, I, Sedic, B, Jadranka, P. Influence of aromatherapy on alleviation of insomnia symptoms. Complement Alter Med 2018;2018:1–5.Search in Google Scholar

14. Sarris, J, Byrne, GJ. A systematic review of insomnia and complementary medicine. Sleep Med Rev 2011;15:99–106. in Google Scholar PubMed

15. Pearson, NJ, Johnson, LL, Nahin, RL. Insomnia, trouble sleeping, and complementary and alternative medicine: analysis of the 2002 national health interview survey data. Arch Intern Med 2006;166:1775–82. in Google Scholar PubMed

16. Heydarirad, G, Keyhanmehr, AS, Mofid, B, Nikfarjad, H, Mosavat, SH. Efficacy of aromatherapy with Rosa damascena in the improvement of sleep quality of cancer patients: a randomized controlled clinical trial. Compl Ther Clin Pract 2019;35:57. in Google Scholar PubMed

17. Arzani, MA. Teb-e-akbari. Qom, Iran: Jalaledin Publication; 2008.Search in Google Scholar

18. SE, J. Zakhireh kharazmshahi. Qom: Ehyae tebe tabiei; 2012.Search in Google Scholar

19. AM, K. Eksir-e-Azam (The great elixir) Tehran. Iran: Institute of medicine historical studies, Islamic and complementary medicine; 2007.Search in Google Scholar

20. Haghjoo, E, Shojaii, A, Parvizi, MM. Efficacy of topical herbal remedies for insomnia in Iranian traditional medicine. Pharmacogn Res 2019;11:188.10.4103/pr.pr_163_18Search in Google Scholar

21. Yakoot, M, Helmy, S, Fawal, K. Pilot study of the efficacy and safety of lettuce seed oil in patients with sleep disorders. Int J Gen Med 2011;4:451. in Google Scholar PubMed PubMed Central

22. Pour, ZS, Hosseinkhani, A, Asadi, N, Shahraki, HR, Vafaei, H, Kasraeian, M, et al.. Double-blind randomized placebo-controlled trial on efficacy and safety of Lactuca sativa L. seeds on pregnancy-related insomnia. J Ethnopharmacol 2018;227:176–80. in Google Scholar PubMed

23. Ghorbani, A, Rakhshandeh, H, Sadeghnia, HR. Potentiating effects of Lactuca sativa on pentobarbital-induced sleep. Iran J Pharm Res 2013;12:401.Search in Google Scholar

24. Sateia, MJ. International classification of sleep disorders-third edition: highlights and modifications. Chest 2014;146:1387–94. in Google Scholar PubMed

25. Nazifi, M, Mokarami, H, Akbaritabar, A, Kalte, HO, Rahi, A. Psychometric properties of the Persian translation of Pittsburgh sleep quality index. Health Scope 2014;3:e15547. in Google Scholar

26. Ranjbar, M, Afsharypuor, S, Shakibaei, F. Effect of topical lettuce (Lactuca sativa L.) seed oil on childhood sleep disorders: a randomized double-blind controlled trial. Res J Pharmacogn 2020;7:47–54.Search in Google Scholar

27. Kim, H-W, Suh, HJ, Choi, H-S, Hong, K-B, Jo, K. Effectiveness of the sleep enhancement by green romaine lettuce (Lactuca sativa) in a rodent model. Biol Pharmaceut Bull 2019;42:1726–32. in Google Scholar PubMed

28. Murillo-Rodríguez, E, Arias-Carrión, O, Zavala-García, A, Sarro-Ramírez, A, Huitrón-Reséndiz, S, Arankowsky-Sandoval, G. Basic sleep mechanisms: an integrative review. Cent Nerv Syst Agents Med Chem 2012;12:38–54. in Google Scholar PubMed

29. Salmannezhad, H, Mojahedi, M, Ebadi, A, Montazeri, A, Mozaffarpur, SA, Saghebi, R, et al.. An assessment of the correlation between happiness and Mizaj (temperament) of university students in Persian medicine. Iran Red Crescent Med J 2017;19. in Google Scholar

30. Nimrouzi, M, Daneshfard, B, Tafazoli, V, Akrami, R. Insomnia in traditional Persian medicine. Acta Med His Adriatica 2019;17:45–54. in Google Scholar PubMed

31. Zare, R, Shams, M, Heydari, M, Najarzadeh, A, Zarshenas, M. Analysis of the efficacy of cinnamon for patients with diabetes mellitus type II based on traditional Persian medicine syndrome differentiation: a randomized controlled trial. Shiraz E-Med J 2020;21. in Google Scholar

32. Ameri, A, Heydarirad, G, Mahdavi Jafari, J, Ghobadi, A, Rezaeizadeh, H, Choopani, R. Medicinal plants contain mucilage used in traditional Persian medicine (TPM). Pharmaceut Biol 2015;53:615–23. in Google Scholar PubMed

33. MH, AAK. Makhzan al-Advieh. Tehran: Tehran University of Medical Sciences; 2009:328 p.Search in Google Scholar

34. Avicenna. The canon of medicine. Great Books of the Islamic World; 1999.Search in Google Scholar

35. Akbar, S, Lactuca sativa, L. (Asteraceae/Compositae). Handbook of 200 Medicinal Plants. Springer; 2020:1067–75 pp. in Google Scholar

36. García-Macías, P, Ordidge, M, Vysini, E, Waroonphan, S, Battey, NH, Gordon, MH, et al.. Changes in the flavonoid and phenolic acid contents and antioxidant activity of red leaf lettuce (Lollo Rosso) due to cultivation under plastic films varying in ultraviolet transparency. J Agric Food Chem 2007;55:10168–72. in Google Scholar PubMed

37. Silva, CKC, da Silva, KB, de Miranda, PRB, Gomes, TCA, da Silva Júnior, JM, Souza, MA, et al.. Fertilizer source influence on antioxidant activity of lettuce. Afr J Agric Res 2018;13:2855–61.Search in Google Scholar

38. Razi, MZ. Al-Havi Fi Al-Tibb (Arabic). Beirut: Dar Al Kotob Al-islmiyah; 2000.Search in Google Scholar

39. Whirl‐Carrillo, M, McDonagh, EM, Hebert, J, Gong, L, Sangkuhl, K, Thorn, C, et al.. Pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Therapeut 2012;92:414–7. in Google Scholar PubMed PubMed Central

40. Espie, CA, Barrie, LM, Forgan, GS. Comparative investigation of the psychophysiologic and idiopathic insomnia disorder phenotypes: psychologic characteristics, patients’ perspectives, and implications for clinical management. Sleep 2012;35:385–93. in Google Scholar PubMed PubMed Central

Received: 2021-05-01
Accepted: 2021-08-19
Published Online: 2021-08-30

© 2021 Walter de Gruyter GmbH, Berlin/Boston

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