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Hoodia:: Review Article
Hoodia:: Review Article
säuresekretion. Die ursprünglich geplante Entwicklung von Hoodia als Arzneimittel wurde 2004 was followed by a patent on pharma-
aufgegeben, in die Kategorie Nahrungsergänzungsmittel verschoben und mit Ende 2008 vorüber- ceutical compositions with appetite
gehend eingestellt. Die Kenntnis über die chemische Zusammensetzung konzentriert sich auf
Pregnanglykoside, von denen eine Verbindung als verantwortlich für die Wirkung angesehen wird. suppressant activity granted by the
Es wurden analytische Methoden entwickelt, die Screening-Untersuchungen der pflanzlichen World Intellectual Property Organisa-
Droge sowie von Formulierungen daraus erlauben. Bei einer grossen Anzahl von Nahrungsergän- tion in 1998 [10]. In 1998, the CSIR li-
zungsmitteln, die überprüft wurden und die vorgaben, Hoodia zu enthalten, konnten keine Pregnan- censed use of P57 to Phytopharm, a
glykoside detektiert werden. Diese Präparate gelten somit als Verfälschungen. Die Datenlage zu
den behaupteten gesundheitszuträglichen Wirkungen ist dünn. Es wurden die metabolische Sta- British pharmaceutical research com-
bilität des Hauptsteroidglykosids und dessen Wechselwirkung mit metabolisierenden Enzymen pany specialised in the development of
in vitro gemessen. In vivo zeigte diese Verbindung eine Reduktion der Kalorienaufnahme und des phytomedicines [4,9]. The aim was to
Körpergewichts nach intracerebroventrikularer Injektion oder oraler Gabe. Bis heute sind weder
promote the worldwide development
zu Klinik noch zur Toxikologie Daten in wissenschaftlich referierten Zeitschriften veröffentlicht.
Berichte über unerwünschte Wirkungen nach der Einnahme von Hoodia-haltigen Präparaten lie- and marketing of the patented extract
gen in zwei Fällen vor (anticholinerges Syndrom, akute Hepatitis). Schlussfolgerungen: Die P57 from Hoodia for suppressing ap-
gegenwärtige Datenlage zu Hoodia und Produkten daraus ist unzureichend. Das phytochemische petite, treatment of eating disorders,
Profil muss neben den bisher gut untersuchten Pregnanglykosiden noch eingehend auf weitere
adipositas and type-II-diabetes. The
Substanzklassen überprüft werden. Es gibt keine verlässlichen Angaben zu Toxizität, Sicherheit
und Klinik. Der Fall Hoodia ist untrennbar verbunden mit Fragen, die die Convention of Biological realisation of this ambitious project re-
Diversity (CBD) und den Artenschutz betreffen: Die mit den San unterzeichneten Übereinkommen quired the involvement of a solvent
zur Aufteilung eines potentiellen Gewinns sind international zu respektieren, ebenso wie die Tat- partner, therefore, Phytopharm sub-li-
sache, dass für Aufsammlung, Kultivierung, Transport oder Export behördliche Genehmigungen ein-
geholt werden müssen, da Hoodia unter Schutz steht.
censed the pharmaceutical giant Pfizer
in the very same year [4]. Press re-
Schlüsselwörter: Hoodia, San, Appetitzügler, Sicherheit, Qualitätskontrolle, Pharmakognosie
leases launched by Phytopharm re-
ported on completed pre-clinical stud-
ies (October 1998) and on a proof-of-
put a registered herbal remedy to the Botswana and, to a lesser extent, in principle clinical study with three suc-
market. The present paper reviews the South Africa. The San as well as other cessfully completed stages [11]. Al-
current scientific knowledge on Hoodia indigenous peoples in the region have though Phytopharm and Pfizer agreed
(Fig. 1) in terms of phytochemistry, sci- been using Hoodia and related species on a future development program for
entific evidence and health-related as a food and, especially, as a drink P57 in July 2002, only one year later
claims. A historic overview about the substitute and appetite suppressant, as Pfizer decided to discontinue its in-
succulent and its development as poten- well as for a variety of other purposes [4]. volvement upon the merger with Phar-
tial anoretic cure is given and intellec- The first reference to the use of macia, which resulted in the shutdown
tual property rights are addressed. Hoodia dates back to 1796 [6], whereas of its Natureceuticals group [4]. All
its use as thirst quencher and appetite rights were returned to Phytopharm
suppressant was recorded centuries who began discussions with potential
Historical development later [7, 8]. The above mentioned CSIR, licensing partners to develop the extract
South Africa’s national laboratory, had as a weight-control food supplement.
The commercialisation of biodiversity been established in 1945 by an act of In December 2004, Phytopharm en-
in Southern Africa was the topic of a Parliament in order to engage in in- tered together with Unilever into a li-
PhD study performed by WYNBERG at dustrial and scientific development to cence and joint development agree-
the University of Strathclyde, Scotland, improve the quality of life of African ment for the Hoodia extract [12], its de-
who laid down her compilation up to people [9]. This organisation obtained velopment as a pharmaceutical ceased.
the year 2004 in a detailed overview information about the properties of the The both companies aimed at bringing
[4]. According to WYNBERG, the San plant during a project on edible wild a new weight management product to
(Fig. 2) represent the oldest human in- plants and, therefore, included Hoodia the functional food market. The collab-
habitants in Southern Africa living in species in this project in 1963 [4]. Even oration comprised a five-stage pro-
small nomadic groups as hunters and though information from literature and gramme including safety and efficacy
gatherers for thousands of years. A laboratory tests on mice suggested studies. In September 2007, Phytopharm
long history of dispossession and relo- Hoodia as a promising non-toxic ap- announced the successful progress into
cation has accompanied the San which petite suppressant scientific evidence stage three, the final stage prior to sub-
started with their persecution upon to file for a patent was insufficient at mission for regulatory approval [13].
colonisation in 1652 followed by dis- that time. The issue was postponed un- However, data of a clinical study using
crimination along with other people of til further investigations including iso- Hoodia extract in a drink-based prod-
colour during South Africa’s apartheid lation and structure elucidation led to uct led Unilever to conclude that it is
regime and which continues today a “revival”: more than 30 years later, unsuitable to move forward with the
through permanent political marginal- in 1995, the CSIR was assigned a product concept [14]. In December 2008,
ization [4]. At present, the approxi- patent in South Africa which guaran- a mutual termination agreement was
mately 90.000 San in Southern Africa tees the use of the active components concluded between the parties and all
mainly live in the Kalahari Desert and of the plant – referred to as “P57” – re- the original Phytopharm patents and
its surrounding regions in Namibia, sponsible for suppressing appetite. This rights reverted to Phytopharm [14,15,
[38], HPLC-MS [39], UPLC-UV-MS [37] port and absorption [41]. The authors Conclusions
and HPTLC [5] are useful methods to conclude that the intestinal transport
perform qualitative analysis and to of P57AS3 is mediated by P-glycopro- Hoodia has been of increasing interest
quantify respective steroid glycosides tein and multidrug resistance-associ- within the past decade due to its at-
[40] from H. gordonii preparations. ated protein transporters. The com- tractive indication profile. It originates
The new methods developed for chem- pound was metabolically stable and from Southern African indigenes, the
ical fingerprint analysis allow a quick showed weak inhibition of CYP 3A4 [41]. San, who have been using the plant
and reliable assessment of various ma- A study in rats showed that the intra- since centuries as thirst and appetite
trices: Hoodia species, plants from gen- cerebroventricular injection of P57AS3 quencher. The South African Council
era related to Hoodia and dietary sup- (0.07 mg 5 per injection) reduced the for Scientific and Industrial Research
plements that claim to contain H. gor- food-intake during 24h after extract (CSIR) together with the British com-
donii may be screened. According to application by 40–60%. The effect was pany Phytopharm have been aiming at
RUMALLA et al., the HPTLC analysis of dose-dependent and suggested a likely the development of Hoodia as phar-
thirteen commercially available dietary central (CNS) mechanism of action for maceutical or food supplement but
supplements confirmed the presence of P57AS3 [42]. In a later study this com- were not successful to date. Meanwhile
H. gordonii for only two samples, pound was applied orally to rats over a considerable amount of patents has
eleven products did not show any of the a three-day period (6.25–50 mg/kg). been issued protecting the rights on an
scrutinised pregnane glycosides [5]. Compared to the animals who were extract and compounds out of Hoodia
Quantification analyses showed vari- either treated with the vehicle or with for its appetite reducing, anti-diabetic
ability and big differences in the con- the appetite suppressor fenfluramine and gastro-protective activity. Benefit
tents: an extract of dried H. gordonii was food consumption and body mass gain sharing agreements with the San have
determined by 2.1% of total steroid gly- of the P57AS3 treated rats decreased been signed in order to share in profit
cosides [40]. The content of the single significantly during a monitoring period from cultivation and potential commer-
compound P57AS3 (5) was found to be of eight days [3]. cialisation of Hoodia. To prevent the
0.05% and 0.005% in two H. gordonii The utmost recent patent filed by slow-growing plant from over exploit-
plant samples. Two of ten commercially Unilever reports on polysaccharides ation and to guarantee sustainable
available dietary supplements which obtainable from plants of the Asclepi- supply, Hoodia species were included
claimed to consist of H. gordonii con- adoideae subfamily (Hoodia, H. gordo- into Appendix II of the Convention on
tained 0.17% and 0.005% of P57AS3, nii, Stapelia) which are said to exhibit International Trade in Endangered
but in the remaining eight prepara- a not otherwise specified immunostim- Species of Wild Fauna and Flora (CITES).
tions it was not detectable at all [39]. ulating effect [43]. Collection, cultivation, transport and
These data show the diverse quality of According to the author’s knowl- export are subjected to strict rules
the offered products and should raise edge, no papers in peer-reviewed jour- which need to be respected by all coun-
the consumer’s awareness of potential nals have been published to date on tries who signed the Convention of Bio-
adulterations because they represent a clinical trials with Hoodia. The only logical Diversity (CBD). However, obe-
potential health risk. available information are press re- sity concerns many people in the civi-
leases by Phytopharm which report on lized countries and as presently only
a double-blind, placebo-controlled clini- few drugs are available to treat this
Effects, mode of action, cal study on overweight male volun- condition efficiently a break-through
clinical trials teers who showed a statistically signif- would open a big potential market.
icant reduction in the average daily Some institutions see this chance and
The main reason why Hoodia became calorie intake and in body fat [11,13]. provide Hoodia preparations disregard-
so popular within the last decade is its There is scarce evidence in literature ing the above-mentioned patents and
use for suppressing appetite. Various about serious adverse effects. A recent agreements even though there are no
patents were filed comprising extracts, publication from Italy reports on prepa- data on successful clinical studies.
constituents and preparations of H. rations containing Hoodia and con- Preparations are available in Europe
gordonii which cover suppression of comitant drugs related to one case of and the US. Valuable phytochemical in-
appetite, anti-diabetic activity and treat- acute hepatitis and one case of anti- vestigations focusing on one class of
ment of gastric acid secretion damage. cholinergic syndrome [44]. compounds, the pregnane glycosides,
However, there is little data on Hoodia’s Recently a monograph of H. gordonii allow the quality control of the crude
mechanism of action even though this has been prepared and compiled by drug and preparations containing
would be of substantial interest. The VAN WYK. The monograph on general Hoodia. The results of these screenings
metabolic stability of P57AS3 (5) in hu- description, identity/quality, use/efficacy give rise to serious concern about the
man liver microsomes and its interac- and safety is planned to be published safety of such products as a consider-
tion with drug metabolising enzymes in the African Herbal Pharmacopoeia able amount seems to lack Hoodia.
were determined [41]. Intestinal trans- by the third quarter of 2009 [45]. Even though Hoodia itself might be
port of P57AS3 was studied in the safe, if slim-down products claimed to
Caco-2 cell model of intestinal trans- contain Hoodia obviously lack this
agent, what else do these preparations 10 Van Heerden FR, Vleggaar R, Horak RM, Lear- 33 Abrahamse SL, Povey KF, Rees DD. Appetite
month RA, Maharaj V, Whittal RD: Steroidal gly- suppressant compositions. 2007: patent; WO
contain? This involves a clear safety cosides, methods for their production and prepa- 2007096239.
risk and has to be assessed critically. ration, pharmaceutical compositions containing 34 Shukla YJ, Fronczek FR, Pawar RS, Khan IA.
them, and their use as appetite suppressants. Hoodigogenin A from Hoodia gordonii. 2008:
The consumers’ attention should be 1998: patent; WO9846243. Acta Cryst E64; o1643–o1644.
drawn to the fact that they run danger 11 Phytopharm pld, Successful Completion of Proof 35 Avula B, Wnag YH, Pawar RS, Shukla YJ, Smillie
of Principle Clinical Study of P57 for Obesity, TJ, Khan IA. Identification and structural charac-
to be affected by adverse reactions due Press release, 5 Dec 2001; available at: www. terization of steroidal glycosides in Hoodia gor-
to unspecified constituents with a com- Phytopharm.co.uk/press (accessed Sept 14th donii by ion-trap tandem mass spectrometry and
2005). liquid chromatography coupled with electrospray
pletely unknown chemical and phar- 12 Phytopharm and Unilever enter into a Licence ionization time-of-flight mass spectrometry.
macological profile. Who would take and Joint Development Agreement for Hoodia Rapid Com Mass Spec 2008;22:2587–2596.
gordonii Extract, Press release, 15 Dec 2004; 36 Shukla YJ, Pawar RS, Ding Y, Li XC, Ferreira D,
the responsibility in this case? available at: www.phytopharm.co.uk/news/ Khan IA. Pregnane glycosides from Hoodia gor-
Apart from this ethical issue, several newsreleases (accessed May 18th 2009). donii. Phytochemistry 2009;70:675–683.
13 Phytopharm, Portfolio, Weightmanagement Hoodia 37 Avula B, Wang YH, Pawar RS, Shukla YJ, Smillie
other questions remain open: Why did extract; available at: www.phytopharm. com/port- TJ, Khan IA: A rapid method for chemical finger-
two big companies who participated in folio/?id=2244 (accessed May 18th 2009). print analysis of Hoodia species, related genera,
14 Neutraceuticals World, Braking News, Unilever and dietary supplements using UPLC-UV-MS. J
the development abandon? Why did abandons hoodia project; available at: http:// Pharm Biomed Anal 2008;48:722–731.
they not succeed in publishing data www.nutraceuticalsworld.com/news/2008/11/2 38 Avula B, Wang YH, Pawar RS, Shukla YJ, Khan
6 (accessed June 24th 2009). IA: Chemical Fingerprinting of Hoodia Species
about safety, toxicology and clinics? 15 Phyotpharm, News, News Releases, Unilever and Related Genera: Chemical Analysis of
Does Hoodia have an effect or not? returns rights to Hoodia extract, Press release, 12 Oxypregnane Glycosides Using High-
Dec 2008; available at: www.phytopharm. Performance Liquid Chromatography with UV
Which other compounds are contained com/news/newsreleases/?id=16553 (accessed Detection in Hoodia gordonii. Journal of AOAC
in Hoodia and what effects/adverse ef- June 24th 2009). International 2007;90(6): 1526–1531.
16 Phyotpharm, News, News Releases, Interim 39 Avula B, Wang YH, Pawar RS, Shukla YJ,
fects do they have? To date, we are not Management Statement for the three month Schaneberg B, Khan IA: Determination of the
able to answer these questions but sup- period ended 31 December 2008, Press release, Appetite Suppressant P57 in Hoodia gordonii
17 Feb 2009; available at: www.phytopharm. Plant Extracts and Dietary Supplements by
pliers, customers as well as govern- com/news/newsreleases/ ?id=16706 (accessed Liquid Chromatography/Electrospray Ionization
ments should not forget about the sen- June 24th 2009). Mass Spectrometry (LC-MSD-TOF) and LC-UV
17 Phyotpharm, News, News Releases, Interim Methods. Journal of AOAC International
sitive background of this potential Results for the six months ended 31 March 2006;89(3):606–611.
“slimming agent”. 2009, Press release, 20 May 2009; available at: 40 Janssen HG, Swindells C, Gunning P, Wang W,
www.phytopharm.com/news/newsreleases/ Grün C, Mahabir K, Maharaj VJ, Apps PJ:
?id=17403 (accessed June 24th 2009). Quantification of appetite suppressing steroid
Acknowledgements 18 Martin G, Vermeylen S: Intellectual Property, glycosides from Hoodia gordonii in dried plant
My thanks go to Prof. K. Eloff, Prof. B-E. Van Indigenous Knowledge, and Biodiversity. Capital- material, purified extracts and food products
ism Nature Socialism 2005;(16)3:27–48. using HPLC-UF and HPLC-MS methods. Anal
Wyk and Dr. T. Brendler for their willingness
19 Anonymous: Protecting traditional knowledge: Chim Act 2008;617;200–207.
and promptness to answer my questions
the San and hoodia. Bulletin of the World Health 41 Madgula VLM, Avula B., Pawar RS, Shukla YJ,
concerning the Hoodia monograph in the Organization 2006;84(5):345. Khan IA, Walker LA, Khan SI: In Vitro Metabolic
African Herbal Pharmacopoeia. Dr. F. Peter- 20 Schoeder D, Chennells R: Benefit sharing and Stability and Intestinal Transport of P57AS3 (P57)
sen took his time to discuss the Hoodia is- access to essential health care: a happy mar- from Hoodia gordonii and its Interaction with
sue with me, which helped a lot. I am deeply riage? Medicine and Law 2008;27(1):53–69. Drug Metabolizing Enzymes. Planta Med
indebted to DI. W. Wurzinger and Dr. Ch. 21 Van Heerden FR. Hoodia gordonii: A natural 2008;74:1269–1275.
Reisch for providing me with photographs. appetite suppressant. J Ethnopharmacol 2008; 42 MacLean DB, Luo LG: Increased ATP content/ pro-
119:434–437. duction in the hypothalamus may be a signal for
22 Bruyns PV: A revision of Hoodia and Lavrania energy-sensing of satiety: studies of the anorec-
(Asclepiadaceae-Stapelieae). Botanische Jahr- tic mechanism of a plant steroidal glycoside.
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