New study offsets toxic findings
A hot desert wind blows across the Kgalagadi desert in Namibia, bringing with it sand and the scent of rotting flesh. This arid region, like parts of the Western and Northern Cape in South Africa, is home to Hoodia gordonii, a spiny succulent plant whose pink flowers smell like carrion. For thousands of years Bushmen chewed the plant to suppress their thirst and hunger on long hunts, but for South Africa this little plant has been a constant headache.
As the world gets fatter, scientists are searching for a “cure” for obesity. About one in three people in the world are overweight or obese, according to research published in the medical journal Lancet. In South Africa this situation is worse: the study found nearly 70% of the population is overweight or obese – more than double the global rate. This extra weight brings with it the risk of diseases such as heart disease and diabetes.
Hoodia was seen as South Africa’s opportunity to break into this market, and offer indigenous knowledge as a way to solve a modern problem.
In 1977 the Council for Scientific and Industrial Research (CSIR) isolated what was believed to be the plant’s active weight-loss ingredient – P57, a complex sugar within Hoodia gordonii – and patented it in 1996, unbeknown to the San.
Hoodia hit international headlines when the San discovered their knowledge had been used and licensed to a British pharmaceutical development company, Phytopharm, without their consent. In 2010, the commercialisation rights were returned to the CSIR, which brokered a benefit-sharing deal with the San.
That was when Hoodia gordonii began to lose its shine: each new scientific study cast doubt not only on the plant’s efficacy as a weight-loss aid, but also on its safety.
Unreported side effects
“The fact that several prominent pharmaceutical companies that were initially involved in the commercial development of Hoodia gordonii have subsequently withdrawn their interest raises the question of whether this plant may have as yet unreported side effects,” says Professor Carine Smith, head of the multidisciplinary stress biology research group in the department of physiological science at Stellenbosch University.
Smith, who has authored several papers on the physiological effects of Hoodia gordonii, notes that although pharmaceutical companies have apparently given up on Hoodia gordonii it is still being marketed worldwide as a weight-loss supplement.
The global weight management market, which includes traditional pharmaceuticals and herbal products, was estimated at $385.1-billion in 2010 and is expected to reach $650.9-billion next year, according to American consultancy Transparency Market Research.
This week, the CSIR told the Mail & Guardian that even they had in effect given up on Hoodia gordonii. “Since the CSIR took over the lead commercialisation role of Hoodia gordonii in 2010, an expert panel was appointed to conduct a review of clinical data from several trials pertaining to the use of Hoodia gordonii as an appetite suppressant,” said Fanie Marais, commercialisation manager at the CSIR.
This panel’s recommendation was that “detailed clinical efficacy studies needed to be conducted … [to] indicate whether a safe and efficacious appetite suppressant could be developed”, but these studies would require “substantial investments that have not materialised”.
Marais said partners were approached, but they “indicated a lack of interest based on the clinical data”. He is referring to Unilever’s 2011 study, published in the American Journal of Clinical Nutrition, that found that in a sample of 49 healthy overweight women, those who were given two doses of purified Hoodia Gordonii extract for 15 days showed “significant adverse changes in some vital signs and laboratory parameters”, such as significant increases in blood pressure and heart rate.
The extract was “less well tolerated than the placebo [with reports of nausea and vomiting] and did not show any effects on energy intakes or body weights relative to the placebo”.
Loss of muscle fibre
Yet Smith’s study on rats, published in the Journal of Ethnopharmacology in September this year, has possibly even more concerning findings. Twelve lean rats and 12 fat rats were given different doses of Hoodia gordonii extract over two weeks. Both groups showed significant weight loss, but not only because of losing fat: lean rats lost about 35% of their muscle fibre, and obese rats lost 20% (those that were given a small dose of the extract) and 30% (those on a high dose).
“We saw severe abnormalities in heart function, as well as delayed stomach emptying … The food remains undigested in the stomach, which literally results in the rats feeling too bloated to eat,” says Smith.
“Your body will experience starvation because food is not digested and nutrients do not become available. That is why our rats, for example, lost muscle mass – they were digesting their own skeletal muscle for food, much like what we see in anorexics.”
But Hoodia gordonii may experience a revival, following a study out of China’s Shanghai Institute of Materia Medica.
To date, interest in the plant has centred on P57, one of many naturally occurring compounds in Hoodia gordonii. This team, headed by Dr Xin Xie, tested six compounds, and found one – Gordonoside F, which, like P57, is a complex sugar – that was a suitable candidate for further study. It had a remarkable effect on the insulin system of rats. Insulin is necessary to remove excess glucose – the result of eating sugars and carbohydrates – from the bloodstream, and store it as muscle or fat.
GordonosideF was found to affect a naturally occurring receptor in the body called GPR119, which is implicated in glucose-stimulated glucose secretion. “GRP119 activation leads to increased insulin secretion and reduced feeding; both are beneficial to weight maintenance,” says Xie.
Their tests, conducted on mice, showed that a low dose of Gordonoside F (which this Chinese team has successfully synthesised) inhibited the food intake of mice with GRP119, but did not have an effect on mice whose GRP119 had been genetically deleted.
But in high doses, Gordonoside F reduced food intake in mice with and without GPR119.
“We can’t conclude that this is definitely a toxic effect, but it’s possible,” Xie told the M&G. “Also, high-dose Gordonoside F might activate other pathways [other than GPR119 activation] to reduce food intake.”
The next step is to “screen for more of these naturally occurring compounds from [Hoodia gordonii] to see if there are any more GPR119-activating compounds”, he says.
Smith describes this latest research as “brilliant”.
“Scientists should concentrate on identification and isolation of the real [active compounds] … before we can try to apply indigenous medicine out of the context in which it is described by indigenous populations.
“A small dose of pure compound is less likely to produce side effects because the cellular targets are so specific,” she says.
That Gordonoside F can be synthetically manufactured is good news for this succulent plant.
“We can use ‘optimised’ indigenous knowledge without using the Hoodia gordonii plant, which may become extinct should harvesting in the wild continue unabated.”