Effects of Khat (Catha edulis) chewing on seminal fluid parameters: findings from a fertility clinic cohort and cessation trial

Background: Khat (Catha edulis) chewing is a culturally ingrained practice in Yemen and has been associated with potential impairment of male reproductive function. However, rigorous quantitative assessments of its effects on seminal parameters are limited. This study investigates the relationship between khat consumption and semen characteristics and examines the reversibility of any adverse effects following cessation. 
Methods: A prospective two-phase study was conducted at Dr. Najat Al-Malas IVF Center in Sana’a, Yemen (2019-2024). Phase 1 compared semen volume and related parameters across four age-, BMI-, education-, and socioeconomic-matched cohorts: infertile khat chewers (n=91), infertile non-chewers (n=60), fertile khat chewers (n=91), and fertile non-chewers (n=32). Phase 2 involved a three-month supervised khat cessation intervention among infertile chewers. Semen samples were obtained via standardized collection methods. Associations between khat use and seminal parameters were analyzed using univariate and multivariate regression models. 
Results: Khat chewers demonstrated significantly reduced semen volumes compared to non-chewers in all comparisons. Infertile chewers had lower volumes (1.94±0.48 mL) than fertile chewers (2.36±0.52 mL; p<0.001, d=0.85) and infertile nonchewers (3.07±0.74 mL; p<0.001, d=1.72). Pooled analysis indicated that chewers (n=182) had 29.6% lower semen volumes than non-chewers (n=92) (2.15±0.89 mL vs. 3.04 ± 0.76 mL; p<0.001). Notably, cessation of khat chewing led to a 35% increase in volume among infertile chewers (from 1.94±0.48 mL to 2.62 ± 0.52 mL; p<0.001, d=1.21). Hormonal analysis (n=15) showed increased testosterone and decreased prolactin post-cessation (p<0.05).
Conclusions: Khat chewing is significantly associated with reduced semen volume and impaired seminal fluid parameters in men. Importantly, cessation of khat use leads to a marked improvement in semen volume and favorable hormonal changes, indicating partial reversibility of its adverse effects. These findings highlight khat’s detrimental impact on male reproductive health and underscore the potential benefits of quitting khat for fertility restoration.

Silva B, Soares J, Rocha-Pereira C, et al. On behalf of the oemonom R. Khat, a cultural chewing drug: a toxicokinetic and toxicodynamic summary. Toxins (Basel) 2022;14:71.

Gibbons S, Arunotayanun W. Natural product (fungal and herbal) novel psychoactive substances. In: Dargan PI, Wood DM, editors. Novel psychoactive substances. Boston, Academic Press; 2013. p. 345-62.

Algutaini SA, Al-Ameri A, Mahyoub Abdo BA. The impact of Qat chewing on health and social life: a cross-sectional study among Yemeni adults. J Med Health Res Psychiatr 2024;1:1-11.

Thomas S, Williams T. Khat (Catha edulis): A systematic review of evidence and literature pertaining to its harms to UK users and society. Drug Sci Pol Law 2013; 1:1-25.

Alzahrani MA, Alsahli MA, Alarifi FF, et al. A Narrative review of the toxic effects on male reproductive and sexual health of chewing the psychostimulant, Catha edulis (Khat). Med Sci Monit. 2023; 29:e939455.

Ahmed F, Alnadhari I, Ghabisha S, et al. The effects of khat (Catha edulis) use on the genitourinary system: A systematic review and meta-analysis. J Ethn Subst Abuse. 2024:1-13.

Tanga BM, Qamar AY, Raza S, et al. Semen evaluation: methodological advancements in sperm quality-specific fertility assessment - A review. Anim Biosci. 2021; 34:1253-70.

Cooper TG, Noonan E, von Eckardstein S, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2010; 16:231-45.

Assidi M. Infertility in men: advances towards a comprehensive and integrative strategy for precision theranostics. Cells. 2022;11:1711.

Kassim S, Croucher R. Khat chewing amongst UK resident male Yemeni adults: an exploratory study. Int Dent J. 2006; 56:97-101.

el-Shoura SM, Abdel Aziz M, Ali ME, et al. Deleterious effects of khat addiction on semen parameters and sperm ultrastructure. Hum Reprod. 1995; 10:2295-300.

Nyachieo A, Kiraithe MM, Spiessens C, et al. Short-term effects of high-dose khat on sperm parameters and reproductive hormonal levels in olive baboons (Papio anubis). Gynecol Obstet Invest. 2013;

:109-14.

Mohammed A, Engidawork E. Reproductive parameters are differentially altered following subchronic administration of Catha edulis F. (Khat) extract and cathinone in male rats. J Ethnopharmacol. 2011;134:977-83.

Zegers-Hochschild F, Adamson GD, de Mouzon J, et al. International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) revised glossary of ART terminology, 2009. Fertil Steril. 2009;92:1520-4.

Halpern JA, Thirumavalavan N, Kohn TP, et al. Distribution of semen parameters among adolescent males undergoing fertility preservation in a multicenter international cohort. Urology 2019;127:119-23.

World Health Organization. WHO laboratory manual for the examination and processing of human semen. 6th ed. Geneva: WHO; 2021.

Nyongesa AW, Patel NB, Onyango DW, et al. Khat (Catha edulis) lowers plasma luteinizing hormone (LH) and testosterone secretion, but increases cortisol levels in male rabbits. J Ethnopharmacol. 2008; 116:245-50.

Dhaifalah I, Santavý J. Khat habit and its health effect. A natural amphetamine. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2004; 148:11-5.

Hakim LY. Influence of khat on seminal fluid among presumed infertile couples. East Afr Med J. 2002; 79:22-8.

Costa VM, Grando LGR, Milandri E, et al. Natural sympathomimetic drugs: from pharmacology to toxicology. Biomolecules. 2022; 12:1793.

Mason MM, Schuppe K, Weber A, et al. Ejaculation: the process and characteristics from start to finish. Curr Sex Health Rep. 2023; 15:1-9.

Abdulwaheb M, Makonnen E, Debella A, Abebe D. Effect of Catha edulis foresk (khat) extracts on male rat sexual behavior. J Ethnopharmacol. 2007; 110:250-6.

Kelly JP. Cathinone derivatives: a review of their chemistry, pharmacology and toxicology. Drug Test Anal. 2011; 3:439-53.

Engidawork E. Pharmacological and Toxicological Effects of Catha edulis F. (Khat). Phytother Res. 2017; 31:1019-28.

Al-Motarreb A, Al-Habori M, Broadley KJ. Khat chewing, cardiovascular diseases and other internal medical problems: the current situation and directions for future research. J Ethnopharmacol. 2010; 132:540-8.

Toennes SW, Harder S, Schramm M, et al. Pharmacokinetics of cathinone, cathine and norephedrine after the chewing of khat leaves. Br J Clin Pharmacol. 2003; 56:125-30.

Michel MC, Vrydag W. Alpha1-, alpha2- and beta-adrenoceptors in the urinary bladder, urethra and prostate. Br J Pharmacol 2006;147:S88-119.

Sun XQ, Xu C, Leclerc P, et al. Spinal neurons involved in the control of the seminal vesicles: a transsynaptic labeling study using pseudorabies virus in rats. Neuroscience. 2009; 158:786-97.

Safhi MM, Alam MF, Hussain S, et al. Cathinone, an active principle of Catha edulis, accelerates oxidative stress in the limbic area of Swiss albino mice. J Ethnopharmacol. 2014; 156:102-106.

Hisasue S, Furuya R, Itoh N, et al. Ejaculatory disorder caused by alpha-1 adrenoceptor antagonists is not retrograde ejaculation but a loss of seminal emission. Int J Urol. 2006; 13:1311-6.

Schifano N, Chiappini S, Mosca A, et al. Recreational drug misuse and its potential contribution to male fertility levels' decline: a narrative review. Brain Sci. 2022; 12:1582.

Mwenda JM, Arimi MM, Kyama MC, Langat DK. Effects of khat (Catha edulis) consumption on reproductive functions: a review. East Afr Med J. 2003; 80:318-23.

Kalix P. Cathinone, a natural amphetamine. Pharmacol Toxicol. 1992; 70(2):77-86.

Rasool A, Manzoor R, Ullah K, et al. Oxidative stress and dopaminergic metabolism: a major PD pathogenic mechanism and basis of potential antioxidant therapies. CNS Neurol Disord Drug Targets. 2024; 23:852-64.

Shulman LM, Spritzer MD. Changes in the sexual behavior and testosterone levels of male rats in response to daily interactions with estrus females. Physiol Behav. 2014; 133:8-13.

Mwenda JM, Owuor RA, Kyama CM, et al. Khat (Catha edulis) up-regulates testosterone and decreases prolactin and cortisol levels in the baboon. J Ethnopharmacol. 2006; 103:379-84.

Nyongesa AW, Oduma JA, Nakajima M, et al. Dose-response inhibitory effects of purified cathinone from khat (Catha edulis) on cortisol and prolactin release in vervet monkeys (Chlorocebus aethiops). Metab Brain Dis. 2014; 29:451-8.