Journal of Ethnopharmacology 87 (2003) 3–9

Effect of Catha edulis (khat) chewing on plasma lipid peroxidation

A. Al-Zubairi, M. Al-Habori∗ , A. Al-Geiry
Department of Clinical Biochemistry, Faculty of Medicine and Health Sciences, University of Sanaa, Sanaa, Yemen
Received 24 May 2002; received in revised form 14 November 2002; accepted 14 March 2003

Abstract

The effect of regular khat (Catha edulis) chewing and the combination of khat chewing and smoking on plasma lipid peroxidation as a
biomarker of oxidative stress and free radical activity (measured as plasma malondialdehyde, MDA), as well as on the lipid profiles were
investigated. The fasting plasma levels of MDA were non-significantly higher in both groups (4% in khat chewers and 9.2% in khat chewers
and smokers), whereas these levels were observed to be significantly increased at post meal and 2 h through the khat session. Post meal increase
of plasma MDA could be attributed partially to the meal-induced oxidative stress and the possible decrease in the overall antioxidant capacity.
This increase in plasma levels of MDA in both tested groups were found to be higher in the control group suggesting the presence of other
contributing factors beside the meal-induced oxidative stress. Plasma levels of MDA were observed to fall slightly 2 h through the khat session
over the post meal levels, suggesting a lack of additive effect of khat consumption. Plasma triglycerides, total cholesterol, and LDL-cholesterol
were shown to be non-significantly affected in this study by khat chewing or by the combination of khat chewing and smoking.
© 2003 Elsevier Science Ireland Ltd. All rights reserved.

Keywords: Catha edulis; Khat; Lipid peroxidation; Plasma lipid profile

1. Introduction enzymes and increase non-specific permeability to ions such

It has been suggested, in the pathogenesis of many
diseases and toxicity’s of numerous chemicals, the partic-
ipation of radicals and oxidants (Kehrer, 1993). The most
common oxidants are the superoxide and hydroxyl radicals
and hydrogen peroxide which are referred to as reactive
oxygen species (ROS) (Halliwell and Gutteridge, 1989;
Sies, 1991; Halliwell, 1996). Superoxide radical can induce
important reducing reactions in biological material and its
formation leads to a cascade of other ROS (Grisham, 1992;
Moslen, 1994). Lipids, proteins, and DNA are all capable of
reacting with radicals and oxidants. Lipids have been exten-
sively studied because of their critical, structural, and func-
tional role in membranes and because of the relative ease
with which products of lipid peroxidation can be measured
(Gutteridge, 1988). Polyunsaturated fatty acids (PUFA)
are particularly susceptible to peroxidation and that, once
initiated the process proceeds as a free radical chain reac-
tion (Gutteridge and Halliwell, 1990). Lipid peroxidation
of biological membranes causes impairment of membrane
function (Gutteridge, 1988; Halliwell and Gutteridge, 1989)
decreased fluidity, inactivate membrane bound receptors and
∗ Corresponding author. Tel.: +967-1-440-910; fax: +967-1-440-842.
E-mail address: malhabori@hotmail.com (M. Al-Habori).
as calcium ions. Moreover, cellular oxidants can target DNA
in the cell, and initiation of ROS with DNA appears to affect
the regulation of certain genes (Cerutti and Trump, 1991;
Harris, 1992). These interactions may involve direct modi-
fications of DNA or they may be mediated through changes
in transcription factors or enzymes involved in regulating
gene expression (Esterbauer et al., 1990; Cao et al., 1995).
The habit of khat chewing has prevailed for centuries
among populations in the horn of east Africa and the Arabian
peninsula including The Yemen. Fresh leaves of khat (Catha
edulis Forsk) are customarily chewed to attain a state of
stimulation (Kalix, 1984; Al-Meshal et al., 1985; Al-Bekairi
et al., 1991). Although the use of khat is widespread, it
has until recently remained mostly confined to the regions
where the plant is grown since only fresh leaves have the
potency (of cathinone) to produce the desired effects. The
fact that cathinone has a closer structural similarity with
amphetamine, and both share common pharmacodynamic
features, led to the conclusion that cathinone is the most
important active ingredient of khat which causes the major
pharmacological effects (Hollister, 1995).
The common adverse effects of khat include insomnia,
anorexia, hyperthermia, mydriasis, and endocrinological
disturbances (Nencini et al., 1983; Brenneisen et al., 1990).
The detrimental effects of the active principle of khat on

0378-8741/03/$ – see front matter © 2003 Elsevier Science Ireland Ltd. All rights reserved.
doi:10.1016/S0378-8741(03)00101-6
4 A. Al-Zubairi et al. / Journal of Ethnopharmacology 87 (2003) 3–9

man and animals have been described by Kalix and Khan
(1984). Khat-induced analgesia has been reported (Connor
et al., 2000), although it is not known whether the mech-
anism is central or peripheral. Acute autonomic responses,
such as elevated blood pressure and tachycardia, have been
reported (Duke, 1985; Widler et al., 1994). Clinical trial
have shown khat to delay gastric emptying period after khat
chewing (Heymann et al., 1995).
Although investigations into the khat effects have spanned
various physiological and metabolic effects, none has yet
investigated the effects of khat chewing on lipid peroxi-
dation/free radical generation. The aim of this study was,
therefore, to investigate the effect of regular khat chew-
ing and the combination of khat chewing and smoking on
plasma lipid peroxidation and that of the lipid profile in
healthy Yemeni individuals.
2. Materials and methods
In this study, 107 Yemeni male subjects aged 20–45 years
old (mean age 29) with a Body Mass Index of 17–25 kg/m2
were randomly selected and divided into three main groups:
the first group included 40 individuals that were classified
as khat chewers on daily basis (>2 years) without smok-
ing, the second group included 40 individuals that were
classified as khat chewers on daily basis and smokers of
at least 10 cigarettes per day, and the third group included
27 individuals classified as non-khat chewers, non-smokers
(control group). All the subjects in the above groups were
subjected to a standard meal (lunch) of equal lipid contents.
Three blood samples were collected from each individual
(after an overnight fast, post meal—after lunch, and after
2 h through the khat session, respectively). Collected blood
were divided into two tubes, the first tube were with antico-
agulant ethylene diamine tetra acetic acid-dipotassium salt
(EDTA) (Wong et al., 1987) and were used for the measure-
ment of lipid peroxidation products (lipid peroxidation assay
kit, Oxford, USA). The malondialdehyde (MDA) estima-
tion was based on the reaction of MDA with two molecules
of N-methyl-2-phenylindole to give a colored complex. The
second tube were plain and were used for the analysis of lipid
profiles (cholesterol, triglycerides, HDL-cholesterol assay
kits, Randox Labs, UK). LDL-cholesterol were calculated
using the Friedewald equation (Friedewald et al., 1972):
LDL-cholesterol

HDL-cholesterol + TG
= total cholesterol −
5
2.1. Statistical analysis
Samples were measured in duplicates and were expressed
as means ± S.D. Statistical analysis was carried out by Epi
Info version-6 (EPI6), for windows. One-way ANOVA was
used to test the statistical significance between two indepen-
dent groups.
3. Results
Table 1 shows the fasting plasma levels of MDA and lipid
profile in both khat chewers and khat chewers and smokers.
The fasting plasma MDA was non-significantly higher by 3.9
and 9.2% in khat chewers and khat chewers and smokers, re-
spectively, with respect to the control group. Along the same
line, fasting plasma triglycerides non-significantly higher by
9 and 13% in khat chewers and khat chewers and smokers,
respectively. In contrast, fasting total plasma cholesterol
non-significantly lower by approximately 10 and 13% in
khat chewers and khat chewers and smokers, respectively.
Similarly, the calculated fasting plasma LDL-cholesterol

Table 1
Fasting plasma levels of MDA and lipid profile in both khat chewers and khat chewers and smokers
Control Khat chewers Khat chewers and smokers

Malondialdehyde (␮mol/l) 0.508 ± 0.101 0.528 ± 0.510 0.555 ± 0.185

Triglycerides (mg/dl) 85.15 ± 36.73 92.77 ± 49.26 96.00 ± 55.80
Total cholesterol (mg/dl) 146.58 ± 37.53 132.60 ± 43.40 127.10 ± 34.30
HDL-cholesterol (mg/dl) 35.23 ± 4.64 40.85 ± 9.85 33.46 ± 8.13
LDL-cholesterol (mg/dl) 90.00 ± 37.84 68.70 ± 39.79 74.54 ± 30.00

Table 2
Post meal plasma levels of MDA and lipid profile in both khat chewers and khat chewers and smokers
Control Khat chewers Khat chewers and smokers

Malondialdehyde (␮mol/l) 0.564 ± 0.176 0.678 ± 0.123∗ 0.804 ± 0.160∗∗

Triglycerides (mg/dl) 147.90 ± 71.87 134.50 ± 57.70 188.00 ± 69.00
Total cholesterol (mg/dl) 157.90 ± 41.28 164.00 ± 47.40 166.00 ± 38.20
HDL-cholesterol (mg/dl) 39.20 ± 9.34 41.00 ± 14.00 37.54 ± 6.95
LDL-cholesterol (mg/dl) 93.00 ± 24.40 92.60 ± 43.60 87.92 ± 36.99
∗ P < 0.02.
∗∗ P < 0.0001.
 A. Al-Zubairi et al. / Journal of Ethnopharmacology 87 (2003) 3–9 5

Table 3
Plasma levels of MDA and lipid profile after 2 h of khat chewing in both tested groups
Control Khat chewers Khat chewers and smokers

Malondialdehyde (␮mol/l) 0.510 ± 0.151 0.640 ± 0.179∗ 0.763 ± 0.130∗∗

Triglycerides (mg/dl) 172.00 ± 87.00 128.80 ± 57.00 169.80 ± 62.90
Total cholesterol (mg/dl) 182.17 ± 39.18 150.80 ± 52.20 168.70 ± 41.20
HDL-cholesterol (mg/dl) 36.80 ± 8.80 42.70 ± 11.50 38.96 ± 6.22
LDL-cholesterol (mg/dl) 105.00 ± 27.50 82.60 ± 51.50 94.20 ± 39.90
∗ P < 0.03.
∗∗ P < 0.0002.

were lower in both khat chewers and khat chewers and smok-
ers by 24 and 17%, respectively. The levels of fasting plasma
HDL-cholesterol were not significantly different from that of
the control, although it was higher by 15% in the khat chew-
ers and lower by 5% in the khat chewers and smokers group.
Table 2 examines the changes of plasma MDA and lipid
profile at post meal. Of all the factors tested only the post
meal plasma MDA was significantly higher in the khat chew-
ers group by approximately 21% and in the khat chewers and
smokers group by 43%. On the other hand, post meal plasma
triglycerides was non-significant lower in the khat chewers
by 9% and non-significantly higher in the khat chewers and
smokers by 27% with respect to the control group. In con-
trast, post meal plasma total cholesterol, HDL-cholesterol,
and LDL-cholesterol were non-significantly affected in both
groups as compared to the control group.
Changes of the plasma levels of MDA and lipid profile
at 2 h through khat session in both khat chewers and khat
chewers and smokers are highlight in Table 3. Like that of
the post meal, plasma MDA at 2 h through khat session was
significantly higher in both khat chewers and khat chewers
and smokers by 25.5 and 49%, respectively. Plasma triglyc-
erides at 2 h through the khat session were non-significantly
lower by 25% in khat chewers but were not much different
in the khat chewers and smokers from that of the control
group. Plasma cholesterol were non-significantly lower by
17% in khat chewers and by 7% in khat chewers and smok-
ers group. Similarly, the calculated plasma LDL-cholesterol

Fig. 1. Percentage increase of plasma MDA in both tested groups compared to the fasting levels.

Fig. 2. Percentage changes of MDA levels with respect to the control group.
6 A. Al-Zubairi et al. / Journal of Ethnopharmacology 87 (2003) 3–9
were non-significantly lower in both groups by 21 and 10%,
respectively. On the other hand, plasma HDL-cholesterol at
2 h through the khat session non-significantly higher by 16%
in khat chewers and by 6% in khat chewers and smokers.
Fig. 1 highlight the percentage increase of plasma MDA
in both khat chewers and khat chewers and smokers at post
meal and 2 h through khat chewing with respect to their
corresponding fasting levels. The data presented shows the
levels of MDA in the control group (non-khat chewers,
non-smokers) to increase by 11% at post meal (2 h from the
meal) and returns back to their levels of fasting, 4 h after the
meal. Whereas in both khat chewers and khat chewers and
smokers, the levels of MDA though increased post meal by
28.8 and 45%, respectively; the levels of MDA were only
dropped slightly at 2 h through the khat session by ∼7.5%
in both groups. Fig. 2 depicts the percentage changes of
MDA levels at post meal and 2 h through khat chewing with
respect to the corresponding control levels. This shows the
levels of MDA to increase in both khat chewers and khat
chewers and smokers with respect to the control group at
fasting, post meal and 2 h through khat session; though the
increase is much significant at post meal and 2 h through
khat session. The levels of MDA were also observed to be
much higher in the khat chewers and smokers when com-
pared with the khat chewers only. The increase was about
two-folds at post meal and at 2 h through khat session.
4. Discussion
In this study plasma MDA, the most frequently used
marker of lipid peroxidation (Janero, 1990; Gutteridge and
Halliwell, 1990) and a biomarker of oxidative stress (Nielsen
et al., 1997), have been used to investigate the effect of
regular khat chewing and the combination of khat chew-
ing and smoking on oxidative stress/free radical activity.
Our results showed the fasting plasma levels of MDA to
be non-significantly increased by 4% in khat chewers and
by 9.2% in khat chewers and smokers as compared to the
plasma levels of MDA in the control (non-khat chewers and
non-smokers) group.
In contrast to the non-significant differences in the fasting
plasma MDA levels, post meal MDA levels in khat chewers
were significantly increased (P < 0.02) by 21% when com-
pared to the corresponding control group. These levels were
even greater (increase of 42%) in the group that regularly
chewed khat and smoked (P < 0.0001). This significant
increase in the post meal MDA levels in both groups could
be attributed partially to the meal-induced oxidative stress.
This is observed on examining the changes of plasma MDA
levels within the control group, where an 11% increase was
observed 2 h following the meal (Fig. 1). Recent studies
have reported an increase in the oxidative stress following
meals in normal subjects (Ceriello et al., 1998a; Ursini et al.,
1998) with consumption of antioxidant defenses (Ceriello
et al., 1998a; Ceriello, 2000) particularly reduction in plasma
glutathione (Ceriello, 2000). Moreover, the plasma concen-
trations of protein-bound sulfhydryl groups, Vitamin C and
uric acid as well as total radical-trapping antioxidant param-
eters were observed to decrease significantly during an oral
glucose tolerance test in both diabetic and non-diabetic sub-
jects (Ceriello et al., 1998b). Other reports have shown that
MDA increased in non-diabetic hyperlipidaemic patients
compared to healthy subjects (Nacitarhan et al., 1995). Since
the percentage increase of post meal MDA levels within
each of the tested groups (∼29% in khat chewers and ∼45%
in khat chewers and smokers with respect to their corre-
sponding fasting levels) were greater than that of the control
group. This would suggest the presence of other contributing
factors beside the meal-induced oxidative stress in both khat
chewers and khat chewers and smokers. In the case of the
khat chewers only, there may be an overall decrease in the
antioxidant capacity as suggested by the observed reduction
of glutathione in khat fed rabbits (Farag et al., 1989).
Analysis of the plasma MDA levels 2 h through the khat
session revealed a further significant increase in both khat
chewers (25.5%) and khat chewers and smokers (50%) (P <
0.03 and 0.0002, respectively) (Fig. 2). This might also be
partly due to meal-induced oxidative stress as a consequence
of the decrease motility of the food and delayed absorption
(Heymann et al., 1995) caused by khat chewing. Alterna-
tively, the increased plasma MDA after 2 h of khat chewing
might be due to the reported increase of thyroid hormones
(Islam et al., 1990), which have been proved to induce an
increase in plasma MDA (Seven et al., 1996).
Since the levels of plasma MDA were not further in-
creased 2 h through the khat session than those levels of
post meal may suggest no additive effect for khat chew-
ing. On calculating the percentage change with respect to
the corresponding fasting levels, it becomes evident that
in the case of the control (non-khat chewers, non-smokers)
group the level of MDA falls back to the base-line level of
the fasting sample (Fig. 1). Whereas in both khat chewers
and khat chewers and smokers, the MDA levels dropped
by ∼7.5%. This may suggest that khat chewing may not
provoke lipid peroxidation, and hence may have some
antioxidative property. This would follow, since khat has
been known to contain polyphenolic (proanthocynidines)
constituents that have emerged recently to play a role as
antioxidants (Hagerman et al., 1998; Koga et al., 1999).
Smoking has been suggested to be one of the promi-
nent risk factors for increased lipid peroxidation, because of
the presence of free radicals in cigarette smoke (Halliwell
and Gutteridge, 1989), that increase plasma MDA. Previ-
ous studies of smoking and oxidative stress in humans have
been difficult to interpret. Harats et al. (1989) and Pre’ and
Le Floch (1990) found no significant differences between
smokers and non-smokers in the levels of thiobarbituric acid
reacting substances in freshly prepared plasma. Whereas,
other groups have reported significantly higher levels of
thiobarbituric acid reacting substances in smokers compared
to non-smokers (Kalra et al., 1991; Bridges et al., 1993).
 A. Al-Zubairi et al. / Journal of Ethnopharmacology 87 (2003) 3–9
Plasma MDA levels were also found to be 10% greater in
smokers compared to non-smokers (Nielsen et al., 1997).
The latter findings were further confirmed by animal work
of Helen and Vijayammal (1997) who found increased con-
centrations of MDA, conjugated dienes and hydroperoxides
in rats exposed to cigarette smoke. Our results may indi-
rectly tend to support findings of smoking increasing plasma
MDA levels. This is evident by the higher increase of MDA
in the khat chewers and smokers group. Whether khat chew-
ing helps to reduce the risk of increased lipid peroxidation in
the khat chewers and smokers group cannot be determined
from this study. This is because of the difficulty in finding
smokers that do not chew khat in the Yemeni population.
Since the majority of people tend to smoke only when they
chew khat.
Fasting serum triglycerides were found to be non-signifi-
cantly increased in both khat chewers (9%) and in khat
chewers and smokers (13%) compared to the control
group. Other studies have shown fasting triglycerides to be
significantly increased in smokers by 9.1% (Craig et al.,
1989) and by 12–15.6% (Hughes et al., 1998) as compared
to non-smokers. Fasting samples of khat chewers in both
groups represent an 18 h sample after the start of the last
khat session and this would suggest that the plasma cathi-
none should have been cleared 9 h prior to this sampling
according to the study of Widler et al. (1994). The latter
study reported maximal plasma concentration of cathinone
reached at 1.5–2.5 h with a half-life in plasma of 4 h as
confirmed later on by Halket et al. (1995) who stated that
the peak levels of plasma cathinone being reached after
1.5–3.5 h of the start of khat chewing and declined rapidly
by 7.5 h. This would, therefore, suggest that cathinone, the
main active constituent of khat leaves, does not contribute
to the observed results on fasting triglycerides.
On the other hand, post meal serum triglycerides of khat
chewers were non-significantly lower by 9% as compared
to the control group. This decrease in the levels of plasma
triglycerides were even more prominent and marked (25%),
though not significant, after 2 h of the start of khat chewing
with respect to the control group. This lowering effect of khat
on triglycerides can be explained by the amphetamine-like
sympathomimetic effects of cathinone, which favors lipoly-
sis mediated through stimulation of ␤-adrenergic receptors
(Tariq et al., 1989). In this context, cathinone was also found
to increases the metabolic rate and oxygen consumption of
rats (Knoll, 1979) and enhances lipolysis in vitro and in vivo
(Nencini, 1980). In contrast, post meal plasma triglycerides
were non-significantly higher by 27% in the khat chewers
and smokers group. This is in line with previous findings
showing that smokers in whom the delivery of fatty acids
to the liver is stimulated are likely to have a high levels of
VLDL synthesis and triglycerol concentration (Craig et al.,
1989; Cade, 1989). Interestingly, 2 h after the start of khat
chewing, serum triglycerides of khat chewers and smokers
group drops back to the same level as that of the control
group. This normalization of the plasma triglycerides in this
7
group (khat chewers and smokers) may be attributed to the
opposing effects of khat and smoking on plasma triglyceride
levels.
Total cholesterol in this study tended to be non-signifi-
cantly affected in both khat chewers and khat chewers and
smokers groups compared with the corresponding control
groups at fasting, post meal or after 2 h of the khat chew-
ing. This observed decrease, though non-significant, in
serum cholesterol concentration in khat chewers may be at-
tributed to the increase in c-AMP that has inhibitory effect
on cholesterol synthesis (Mayes, 2000). The stimulation
of ␤-adrenergic receptors by the amphetamine-like effect
of cathinone (Tariq et al., 1989) results in activation of
adenylyl cyclase and consequently increased conversion of
ATP to c-AMP (Mayes, 2000), in addition to its stimulatory
effect on adrenocorticotrophic hormone (ACTH), that have
been reported to be increased in rabbits given Catha edulis
extract (Ahmed and El-Qirbi, 1993). ACTH is also believed
to be mediated by the activation of adenylyl cyclase with
subsequent increase in c-AMP concentration.
HDL-cholesterol in khat chewers was found to be
non-significantly higher at fasting, post meal and 2 h of khat
chewing when compared with the corresponding control
group. Calculated serum levels of LDL-cholesterol of khat
chewers were non-significantly lower with respect to the
control group in the fasting and after 2 h of khat chewing.
These findings were similar to that observed by Ramadan
et al. (1979) who reported that total cholesterol, ␣- and
␤-lipoproteins were not greatly affected by khat consump-
tion. The observed reciprocal relationship between plasma
HDL-cholesterol and triglycerides in khat chewers, at post
meal and 2 h through khat chewing, are in support of re-
cent data demonstrating HDL-cholesterol concentrations
to vary reciprocally with plasma triglycerides concentra-
tion, and directly with lipoprotein lipase (Mayes, 2000).
This could be explained by the effect of cathinone and its
amphetamine-like effect on adrenergic receptors increasing
c-AMP that in turn stimulate lipoprotein lipase (Ramadan
et al., 1979).
HDL-cholesterol in the khat chewers and smokers group
were seen to be non-significantly affected compared with
the control group, being slightly lower at fasting and at post
meal while increased after 2 h of khat chewing. Similar re-
ductions in HDL-cholesterol have been observed in smokers
only (Craig et al., 1989; Hughes et al., 1998). The calculated
LDL-cholesterol was not affected in the khat chewers and
smokers to the extent seen in the khat chewers only. This
could be explained by the opposing effects of khat chewing
and smoking on plasma lipids or due to the pattern of smok-
ing and the number of cigarettes smoked. The disturbance
of plasma lipid levels found in smokers only was attributed
by many authors to the dietary differences between smokers
and non-smokers (Craig et al., 1989; Cade, 1989; Freeman
and Packard, 1995). Smoking was demonstrated to have
a strong independent influence on HDL-cholesterol (Craig
et al., 1989) and the evidence for this comes from smoking
8 A. Al-Zubairi et al. / Journal of Ethnopharmacology 87 (2003) 3–9
cessation studies. After ceasing to smoke for more than
2–4 weeks, plasma HDL-cholesterol concentration rise to
the level of that seen in non-smokers (Moffat, 1988). On
comparing the HDL- and LDL-cholesterol of both khat
chewers, non-smokers and smokers, there were no signifi-
cant differences observed except for the fasting serum levels
of HDL-cholesterol in khat chewers and smokers being sig-
nificantly (P < 0.04) lower by 18% as compared with khat
chewers only. This effect may be attributed to the effect of
smoking through triglyceride-dependent and -independent
mechanisms in addition to genetic polymorphism (Freeman
and Packard, 1995).
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