Pharmacology & Pharmacy, 2012, 3, 447-452
http://dx.doi.org/10.4236/pp.2012.34060 Published Online October 2012 (http://www.SciRP.org/journal/pp) 1
The Reproductive and Thyroid Hormonal Profile of Khat
(Catha edulis) Chewers
Saeed S. Al-Ghamdi
Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah, KSA.
Received June 14th, 2012; revised July 20th, 2012; accepted August 18th, 2012
ABSTRACT
The effects of khat on the hormonal levels have been established; however, the effects on human beings are controver-
sial. The aim of our study was to investigate the possible effects of khat on the levels of serum thyroid hormones, tes-
tosterone, estradiol (E2), prolactin and cortisol in men. A total of 50 blood samples were collected from healthy males
who referred to chew khat for more than 10 years and analyzed for the above hormones. The results were compared to
the hormonal levels of 35 non khat chewers. Chewing khat causes significant increases in the testosterone (P < 0.03),
prolactin (P < 0.05), E2 (P < 0.00005), FT3 (P < 0.04), and TSH (P < 0.05) levels. No significant differences were
found in the serum level of FT4 between the two groups. The level of cortisol were significantly lower (P < 0.001) in
the khat chewers grou p compared to th e contro l group. Th is study sugg ests that khat chew ing can cause r educ tion in the
cortisol level, which may cause increases of testosterone, prolactin an d E2. In add ition , chewing khat in creases the level
of TSH and FT3 serum levels. Therefore, khat may contribute to the relevant disorders caused by abnormal levels of the
studied hormones in the people who are chewing khat
Keywords: Estradiol (E2); Free Thyroxine (FT4); Free Triiodothyronine (FT3); Thyrotropin Stimulating Hormone
(TSH); Prolactin; Testosterone; Cortisol; Khat
1. Introduction
Khat [also spelled qat, kat, or g hat] is the name generally
used for Catha edulis plant, which is a green large shrub
that belongs to Celastraceae family. It grows wild at alti-
tudes of 1500 to 2000 m above sea level, and usually
reaching six to seven meters in height in Middle East,
Somalia East Africa (Ethiopia, Kenya) and the south-
western part of the Arabian Peninsula [1]. Khat harvested
during dry and sunny season is more potent than that
harvested during cool months of the year [2]. It is a high
cash income crop and is profitable to the huge number of
people involved in its production and marketing includ-
ing farmers, dist ri butors and merchants.
Previous studies focus on frequency of use but not on
amount of khat used. Therefore, data on prevalence of
unproblematic versus problematic use, or dependence,
are lacking. Study of Ali et al. [3] and Al-Motarr eb et al.
[4] that was conducted in Yemen has shown that 61% of
subjects were consuming khat on daily basis for more
than three hours. Chewing of kh at leaves was found to be
more common among adult men than women [5], and
found to be common among children as well [4]. Khat
leaves contain alkaloids, terpenoids, flavonoids, sterols,
glycosides, and tannins. The phenylalkylamines and the
cathedulins are the major alkaloids. The cathedulins are
based on a polyhydroxylated sesquiterpene skeleton and
are basically polyesters of euonyminol; 62 different
cathedulins have recently been characterized from fresh
khat leaves. The khat phenylalkylamines comprise cathi-
none (s-[-] cathinone), which is the primary constituent
of khat as well as two diastereoisomers: cathine (1S,
2S-[+]-norpseudoephedrine or [+] norsendoephedrine)
and norephedrine (1R, 2S-[-]-norephedrine), which are
the secondary constituents. These compounds are struc-
turally and pharmacologically related to amphetamine
and noradren a l ine . Cathinone is found mainly in the young
leaves and shoots [6-9].
In the gastrointestinal tract, the astringent characteris-
tics of the tannins in khat accounts for periodontal dis-
ease, stomatitis, oesophagitis and gastritis [1 0,11]. Delay
in intestinal absorption contributes to some degree to
malnutrition. Tannins and norpseudoephdrine contribute
to constipation, the most common medical complaint of
the khat user [12]. Khat chewing has also been shown to
be a risk factor for duodenal ulcers [13]. Another report
also described a patient with impaired liver function at-
tributed to khat chewing [14]. A rather unusual adverse
effect on the liver of chewing khat was a parasitic infec-
tion of the liver b y Fasciola hepatica as a contamin ant of

The Reproductive and Thyroid Hormonal Profile of Khat (Catha edulis) Chewers
448
the khat leaves [15].
Habitual administration of khat extracts showed a de-
ranged systemic capacity to handle oxidative radicals and
induces cytotoxic effects in cells of liver and kidney
[16-20], low birth-weight babies [21,22], and increases
blood pressur e [23].
The most comprehensive controlled study evaluating
the adverse effects of khat-chewing on different health
aspects is that by Kennedy et al. [2]. The study was con-
ducted on 371 males and 335 females from the Republic
of Yemen. The participants were categorized as non-
light and heavy chewers and then subjected to a stan-
dardized medical history and physical examination, in-
volving each organ system of the body. The results
showed that gastrointestinal disorders, namely gastritis,
constipation and anorexia, were associated significantly
with khat-chewing. Emotional problems including in-
somnia, headaches and emotional instability were also
associated significantly with khat use, especially among
males. Khat chewers also had a higher prevalence of res-
piratory problems, namely bronchitis that the author at-
tributed to smoking accompanying khat-chewing rather
than to the habit itself. Female chewers had a higher
prevalence of urinary problems. Cardiovascular problems
and liver diseases, except for histories of jaundice among
female s, were not associated wi th khat use.
There are suspected effect of khat on various repro-
ductive health parameters which can lead to diminished
sex performance. Khat consumption may lower libido
and sexual performance [17]. Another study revealed that
the testicles, epididymis and seminal vesicles of rats were
smaller than controls [24]. Khat consumption has been
found to reduce semen volume, and sperm malformation
[25,26]. Effects of khat on reproductive and thyroid
hormones have been studied [24,27-30]. However, lim-
ited studies have been performed to measure the hormo-
nal profile of people chewing khat. The present study
was specifically designed to investigate whether the khat
consumption has any detectable effects on reproductive
and thyroid hormones.
2. Materials and Methods
2.1. Subjects
This study was carried out in the Department of Phar-
macology and Toxicology, Faculty of Medicine, Umm
Al-Qura University in association with Hera General
Hospital, Makkah. The Study included 50 male khat
chewers and 35 controls (healthy volunteers). Subjects
were 25 - 45 years old (Table 1).
2.2. Blood Sampling
Blood samples (5 mL) were collected in heparinized
tubes from each subject. The plasma were separated,
Table 1. Background data of khat chew res and control sub-
jects.
Khat chewers Control
No. of subjects 50 35
Age (years) 35 ± 2 34 ± 4
Weight (kg) 65 ± 6 63 ± 7
Duration of use ( years)10 ± 1 0
frozen quickly, and stored at –20˚C until the time of
analysis.
2.3. Hormonal Assay
Hormonal assays were performed using the reagents,
protocol and quality controls provided by World Health
Organization Matched Reagent Program (WHO-MRP)
and the assays done according to the protocol described
by Sufi et al. [31]. Radio Immuno Assay (RIA) described
below was carried out on a pair of approximately same
numbers of serum specimens from patients and controls.
Serum aliquots were analyzed for Estradiol (E2), Free
thyroxine (FT4), Free triiodothyronine (FT3), Thyrotro-
pin stimulating hormone (TSH), Prolactin; Testosterone,
Cortisol using commercially available kits (DPC, Los
Angeles, CA, USA).
Briefly, the plasma samples were thawed and well
mixed and 200 µL of each sample was mixed with 200
µL of assay buffer (phosphate-buffered saline, containing
1% gelatin and 0.1% thiomersal). The hormones were
then extracted from the samples for 3 min using 4 mL of
diethyl ether. The aqueous phase was frozen using dry
ice and then organic phase, containing extracted hormone
was decanted into 5 mL tubes. The solvent was evapo-
rated and the hormones reconstitu ted using 500 µL of the
assay buffer. The tubes were vortex and left to stand for
10 min, then vortex again. 100 µL of the re-dissolved
sample extract was then pipette into assay tubes and as-
sayed for the above hormones.
2.4. Statistical Analysis
Results are presented as mean ± SD. The results were
analyzed statistically using the Student’s t-test for un-
paired variables to evaluate the significance of differ-
ences between the mean values of the two studied groups.
Statistical significance was assured when P < 0.05.
3. Results
The level of E2 in serum in this study was found to be
significantly (P < 0.00003) higher in khat chewers than
that in normal controls. The mean concentrations of FT3
and TSH were significantly (P < 0.02) higher in khat
chewers than in corresponding control groups, whereas

The Reproductive and Thyroid Hormonal Profile of Khat (Catha edulis) Chewers 449
the levels of FT4 were not significantly different between
the khat ch ewers and the con trol group. Th e serum levels
of testosterone and prolactin were significantly higher in
khat chewer s than the co n tro l group (P < 0.03). How ever,
the mean level of serum cortisol was significantly (P <
0.001) lower in khat chewer’s serums than that in normal
controls (Figure 1).
4. Discussion
Previous investigations of the khat effects have spanned
various physiological and metabolic effects. However,
most of the previous studies were performed on experi-
mental animals. This study focused on effects of khat
using a human as model to measure the reproductive and
thyroid hormones, due to the believing of people that
khat can play a positive ro le in sexual activity and main-
taining cultural identity. Some fathers who are chewing
khat are known to give their own children khat leaves to
make them more energetic and stimulated believing that
khat chewing increases the abilit y to stud y better [1]. The
real psychological effects of khat consumption include
euphoria, hallucinations and feeling of paranoia [32] and
physiological effects are lowering libido and sexual per-
formance [24].
In this study, I evaluated the plasma level of testoster-
one, prolactin, E2, cortisol, TSH, FT3, and FT4 in 50
volunteers of Saudi men who are known to chew khat for
more than 10 years. Khat chewers and non-chewers men
studied in the present study were judged not to be under
Figure 1. Plasma levels of the FT3, FT4, TSH, prolactine,
testosterone, E2 and cortisol hormones of the khat chewers
and the control group.
any unusual cond itions such as hormone therapy, th yroid
and reproductive diseases. I observed an increase in
plasma testosterone, prolactin, E2, TSH, and FT3, levels
in the khat chewers while the level of plasma cortisol
was decreased. However, I did not find any significant
difference in the serum level of FT4 between the khat
chewers and control groups in the present study. How-
ever, it should be noted that even if the plasma levels of
the studied hormones are increased or decreased, these
changes are still within normal ranges. These findings are
in contrast to earlier observations in humans [33], mice
[24] and rabbit [34] in which khat consumption resulted
in a decrease in plasma testosterone levels, but in agree
with Mwenda et al. [27]. Cathinone, which is one of the
active ingredients in khat, was responsible for the de-
crease in testosterone concentration [35]. This could be
due to the decrease in cortisol levels. Previou s studies by
Hall [36] showed that high cortisol cause a reduction in
testosterone levels. Thus, the decrease in cortisol levels
may have been responsible for the increase of testoster-
one. Effects of khat on testosterone have been shown to
be dose dependent. Albert et al. [34] found that low con-
centrations of khat extract significantly increased whereas
high concentrations suppressed testosterone production,
compared to controls.
Increasing in testosterone level however, does not
mean that khat may improve the sexual fitness. Previous
studies have shown that khat addicts had a reduced se-
men volume, low sperm count and reduced sperm motil-
ity [25,37]. However, limited experiments have also been
performed in humans. High level of prolactin in blood
stream can also affect male fertility. It has an adverse
affect on the function of testicles and can cause de-
creased testosterone levels or abnormal sperm. This can
cause serious problems when it comes time to conceive.
Interestingly, prolactin was found to be slightly but sig-
nificantly elevated in this study in khat chewrs, which is
in contrast to earlier observations in the baboon [27],
where khat consumption leads to decreasing in the levels
of prolactin. high levels of prolactin (hyperprolactinemia)
in men leads to gynecomastia, a condition in which the
breasts enlarge and look similar to a women. These sign
where absent in the subjects of this study. Elevated
prolactin levels in men are usually the result of overac-
tive prolactin cells in the pituitary gland. These cells be-
gin to grow into a tumor, called a prolactinoma, on the
male pituitary gland and leads to prolactin secretion. No
medical history of malignancy was recorded in the stud-
ied group; however, induction of prolactinoma by khat
cannot be excluded. Such assumption needs to be further
investigated.
Testosterone hormone is pharmacologically working
as an antagonist to E2, where the high level of one is
decreases the level other. In this study, E2 level was

The Reproductive and Thyroid Hormonal Profile of Khat (Catha edulis) Chewers
450
found to be highly elevated but the level of testosterone
remains significantly high as well. The concurrent in-
crease of estradiol levels creates very serious hormonal
imbalances such as adiposity, breast development, many
cancers, prostate problems, baldness and many other
problems commonly associated with advanced age. This
result is in agreement with the study of Aziz et al. [38]
which was conducted on female rats.
The subjective experience associated with khat-chewing
is complex. The effects experienced by chewers can be
divided into desirable and non-desirable. The desirable
effects are experienced during the first hours of the
chewing session. The euphoric state associated with re-
lief from fatigue, energy, feelings of elation and en-
hanced imagination , and the capability to asso ciate ideas,
improved communication ability and high confidence is
the primary desirable experiences. Whereas the non-de-
sirable experiences start near its end and continue for
some hours, i.e. negative aftermaths [2,11,33]. The com-
mon adverse effects of khat include insomnia, anorexia,
hyperthermia, mydriasis, and endocrineological distur-
bances [39,40].
Hyperthermia may be explained partially by the thy-
roid-stimulating effect of khatamines [33]. In this study,
FT3 and TSH level were higher in khat chewers. Islam et
al. [30] have shown in there experimental study that khat
induces T3 in dose dependent manner. T4 in that study
however was induced after high dose of khatamines. In
this study, no significant difference in the serum level of
FT4 between the khat chewers and control groups were
found. However, this might be due to the adapted doses
of khat consumed and does not exclude the hypothesis of
high dose of khat could increase FT4 level. Vorherr [41]
has stated that thyroid hormones may influence metabo-
lism of estrogen. Results of this study suggest that the
increase in the serum FT3, and TSH levels, which is
coincides with elevation in the serum level of free E2
may be one of the risk factors metabolic disorders.
Discrimination of khat effects on hormonal profiles in
previous studies might be attributed to some factors. First,
khat chewers have claimed that khat effects are different
according to the area of cultivation. They assume that
khat cultivated in some areas has stronger effects than
others based on this fact. However, this needs to be
proven scientifically. Second, u sing of pesticides by khat
famers may contribute to exaggeration effects [42]. Third,
effects of smoking habit and genetic polymorphism also
should be considered. Tobacco smoking was found to
increase the serum levels of various sex hormones in-
cluding, E2, follicle stimulating hormone, prolactin, tes-
tosterone and [43-45].
In conclusion, khat was found to increase the leve ls of
thyroid and reproductive hormones and decreases the
level of cortisol. Therefore, it could be a major factor of
disorders that caused by such hormonal imbalances.
Others factors such as smoking and diet habits, genetic
polymorphism, physiological or pathological conditions
and chronic medication should not be also neglected.
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