Short communicationThe effect of Khat (Catha edulis) as an appetite suppressant is independent of ghrelin and PYY secretion
Introduction
The increasing levels of obesity in Western societies has led to a great interest in the factors that control appetite and indeed pharmaceutical interventions that may decrease appetite and subsequently aid weight loss. An example of a substance that is chewed but not swallowed and affects appetite is the khat plant. Chewing leaves of the khat plant (C. edulis) is a prevalent social custom in the Republic of Yemen and parts of East Africa. The khat plant contains tannins and various alkaloids including cathine and cathinone. Experiments have demonstrated that the predominant active ingredient is cathinone, a compound with similarities to amphetamine, with up to 90% being absorbed during chewing, predominantly via the oral mucosa (Toennes, Harder, Schramm, Niess, & Kauert, 2003).
The effects of khat and its constituent alkaloids on appetite have been previously well documented (Hoebel, 1977, Hoebel, 1978, Zelger and Carlini, 1980). The main alkaloids released by khat chewing, cathine and cathinone are structurally similar to amphetamine. Chewing releases the active constituents quickly, with the major proportion of alkaloids being rapidly absorbed from the buccal mucosa, and very little remaining in the leaf residue at the end of chewing (Halket, Karasu, & Murray-Lyon, 1995; Toennes et al., 2003).
Chewed predominantly for its pleasurable effects, khat leaves play a major role in social life of the communities who consume it. The young fresh leaves of khat are considered the most desirable, presumably due to their higher cathinone content (Toennes et al., 2003). Being related in structure to amphetamine, khat does have some sympathomimetic effects including increasing heart rate and blood pressure (Hassan et al., 2000). However, in addition it also decreases appetite. It is known that amphetamine-like compounds affect appetite centrally, by acting in the arcuate nucleus of the hypothalamus, but cathinone also has effects on gut motility which may compound this effect (Heymann et al., 1995).
The central effects of sympathomimetic substances on appetite are well described (Russek, Stevenson, & Mogenson, 1968). Given that khat has an effect on gastrointestinal function what is not known is whether the sympathomimetic constituents released by chewing khat have any effect on appetite mediated by gut-derived hypothalamic peptides. There are multiple gut-derived peptides thought to play a role in appetite, but two peptides that appear to have opposing effects on appetite are the anorexigenic peptide YY and the orexigenic ghrelin. Peptide YY is released predominantly from the lower intestine following a meal and has been shown to decrease appetite in both lean and obese subjects (Batterham et al., 2003). Conversely ghrelin (Kojima et al., 1999) is predominantly released from the stomach and its levels increase in times of hunger and decrease immediately post-prandially (Tschop et al., 2001). Administration of ghrelin to rats and humans increases appetite (Wren et al., 2001a, Wren et al., 2001b).
These peripheral mediators exert central feedback at specific hypothalamic nuclei. Regulation of this feedback is at the forefront of research into obesity and control of appetite.
We hypothesise that in addition to central sympathomimetic effects chewing khat decreases appetite and that this in some part would be associated with appropriate changes in ghrelin and PYY levels.
Section snippets
Subjects
Six subjects (all men; age range 33–56, median 40 years; body mass index 20–27, who habitually chewed khat, with no history of gastrointestinal illness and taking no regular medication, were recruited. Two of six subjects were smokers but all subjects refrained from smoking within 24 h of each study day. They attended on two occasions 2 weeks apart. The study days commenced at 0900 h following an overnight fast. On the first occasion they received khat leaves, and on the second they were asked to
Subjective symptoms
Chewing khat led to a significant decrease in hunger and an increase in fullness VAS scores in all subjects (p < 0.05, ANOVA, Fig. 1). Chewing lettuce as a control had no significant effects on subjective symptoms.
Blood pressure
Systolic BP increased during khat chewing and was maintained throughout the study (111 ± 5 mmHg vs. 132 ± 12 mmHg, control vs. khat, mean ± S.D., 180 min) whereas there was only a difference in diastolic BP at 60 min (76 ± 8 mmHg vs. 86 ± 8 mmHg, control vs. khat) (Table 1).
Pulse
Chewing khat increased pulse
Discussion
We have demonstrated that chewing khat acutely decreases hunger, but that these subjective symptoms are not associated with a change in ghrelin or PYY levels.
The main alkaloids released by khat chewing, cathine and cathinone are structurally similar to amphetamine. Chewing releases the active constituents quickly, with the major proportion of alkaloids being rapidly absorbed from the buccal mucosa, and very little remaining in the leaf residue at the end of chewing (Halket et al., 1995, Toennes
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2015, Journal of EthnopharmacologyCitation Excerpt :These include orexigenic factors such as orexin and ghrelin and the anorexigenic factors such as leptin, peptide YY (PYY), bombesin and glucagon-like peptide-1 (GLP-1). In one of the few studies of appetite hormones, khat chewing, at least by habitual users, decreased subjective feelings of hunger and increased subjective feelings of fullness despite no change in ghrelin or PYY secretion (Murray et al., 2008). This is in contrast to AMPH where leptin has been called into question as a mediator of food restriction sensitization of d-amphetamine׳s reward effects (Hao et al., 2006).