Hoodia species are one of many succulent plants that grow in arid climates. In the Kalahari Desert in Africa, the juice/sap of Hoodia spp. has enjoyed ethnobotanical use as an appetite and thirst suppressant among certain indigenous peoples. In the 1960s, Xhomani tribesmen disclosed the ethnobotanical use of Hoodia to the South African army. The Pretoria-based Council for Scientific and Industrial Research (CSIR), a partially state-funded laboratory in South Africa, then undertook animal studies with Hoodia in the 1980s and found striking weight loss, not due to toxicity but to appetite suppression.1 CSIR later filed its first of several patents on Hoodia spp. and a related succulent, Trichocaulon spp., describing compositions containing a steroidal glycoside bioactive for appetite suppression, weight loss and metabolic syndrome.2
Rights to CSIR?s patent suite were then licensed to Phytopharm PLC, a UK-based botanical pharmaceutical company. In 1998, Phytopharm signed a sublicensing agreement with Pfizer, allowing the pharma giant to commercialise an obesity drug based on Hoodia?s bioactive and related semisynthetic congeners. Five years later, Pfizer ended its relationship with Phytopharm, ushering in the opportunity for Phytopharm to align with food/meal replacement product marketers and pursue a nutritional matrix with Hoodia extracts.
Very little bioactivity research on Hoodia has been published. The first report was presented by researchers from the US, where they added four different Hoodia spp. (crude slurry or semipurified) extracts to the diet of a specific genetic strain of lean and obese rats.3 They noted both acute and chronic reductions in food intake, with body weight dropping markedly over three weeks. A follow-up study by the same group found that the addition of a crude homogenate of dried Hoodia gordonii again produced sustained reductions in food intake.4 After three weeks of feeding, body weight among the obese animals, which was initially twice that of the lean rats, was normalised while the lean rats fed Hoodia displayed a 20 per cent drop in body weight. Regional (gonadal) body fat dropped more than 50 per cent in both the lean and obese Hoodia-supplemented rats, compared to those on the conventional diet.
Phytopharm has undertaken several clinical trials, assessing pharmacokinetics, safety and tolerability of different H. gordonii extracts and fractions. In one clinical efficacy trial with Phytopharm?s powdered Hoodia extract (P57), 20 overweight individuals were housed in a metabolic ward (to definitively assess energy intake) for two weeks and given either a placebo or P57.5 Subjects were allowed to eat ad libitum and did not engage in any vigorous activity. Average daily energy intake in the P57 group was reduced by 1,000kcal/day, attended by a fat loss of approximately 2kg. Both fasting blood sugar and triglycerides fell in this group.
The prodigious appetite reduction with P57 demands confirmation in longer-term clinical trials, along with a more rigorous assessment of its effect on metabolism and body composition. Animal studies with the purified steroidal glycoside bioactive in Hoodia gordonii have shown that its injection into the brain (intracerebroventricular) dose-dependently induces up to a 50-60 per cent reduction in food intake over 24 hours.6 Injection of the compound into the abdominal lining (intraperitoneal) was without effect on food intake. The investigation also revealed a novel observation: a normalisation of decreased ATP content within the brain and liver as induced by food deprivation and an increase in brain and liver ATP, both by injections of the bioactive into the brain. This suggests that if this Hoodia bioactive is indeed orally bioavailable to the brain, then it could at least acutely alter the brain?s energy-sensing function, an ?ergostat.?
It remains to be seen if Hoodia can exert a sustained, safe, appetite-suppressive effect when integrated into a nutritional matrix like a meal replacement product. To date, none of the available Hoodia-containing dietary supplements appear to contain the bioactive steroidal glycoside and none have been subjected to any controlled clinical trials to confirm efficacy.
Anthony Almada, MSc, is president and chief scientific officer of IMAGINutrition Inc. Respond: [email protected] All correspondence will be forwarded to the author.
1. Habeck M. A succulent cure to end obesity. Drug Discov Today 2002;7: 280-1.
2. Van Heerden F, et al. Pharmaceutical compositions having appetite-suppressant activity. WO 9846243, 1998 Oct 22.
3. Tulp OL, et al. Effect of Hoodia plant on food intake and body weight in lean and obese LA/Ntul//-cp rats. FASEB J 2001; 15: A404.
4. Tulp O, et al. Effect of plant on weight loss in congenic obese LA/Ntul//-cp rats. FASEB J 2002; 16: A648.
5. Dixey R. Presentation at sixth annual Rodman and Renshaw techvest healthcare conference, 2004 Oct 26, New York City.
6. MacLean DB, Luo L-G. Increased ATP content/production in the hypothalamus may be a signal for energy-sensing of satiety: studies of the anorectic mechanism of a plant steroidal glycoside. Brain Res 2004; 1020:1-11.