IngredientesHoodia gordonii (Masson) Sweet ex Decne., also known as Bushman's hat, is a leafless spiny succulent plant claimed to have therapeutic properties in folk medicine. It grows naturally in Botswana, South Africa, and Namibia. It belongs to the family Apocynaceae and is indigenous to South Africa and Namibia. The genus Hoodia encompasses multiple species, of which H. gordonii is the most commercially studied.
The indigenous San people of the Namib desert call this plant ǁhoba (pronounced [kǁʰɔbɑ] — the initial sound is a lateral click). It is also encountered under the common names "Bushman's hat," "Queen of the Namib," and in commerce as simply "Hoodia." Hoodia gordonii is a cactus-like succulent plant, native to the Kalahari Desert in southern Africa. Due to over-harvest and slow growth, Hoodia is now considered an endangered species.
Hoodia gordonii is a clump-forming perennial succulent plant growing to around 1 metre tall, with up to 50 grey-green ribbed and spined stems in a clump. The flowers smell like rotten meat and are pollinated mainly by flies.
H. gordonii is marketed as a functional food and products are available in many different dosage forms including tablets, capsules, powders, sprays, tea, fruit and chocolate bars, patches, topical gel formulations, and even lollipops. In traditional use, the plant was consumed directly; medicinally, Hoodia was typically consumed fresh or dried, and sometimes included in simple remedies aimed at promoting endurance and well-being.
Hoodia gordonii is traditionally used by the San people (Bushmen) of the Namib desert as an appetite suppressant as part of their indigenous knowledge about survival in the harsh desert conditions. Historically, Hoodia has been used for centuries by the San people (also known as Bushmen) as a traditional remedy to suppress hunger and thirst during long hunting expeditions. The indigenous use of Hoodia was not only practical but also deeply integrated into cultural practices, helping these communities survive harsh desert conditions with limited resources.
The appetite suppressant effects of Hoodia were first observed in 1937 by a Dutch anthropologist studying the San Bushmen of the Kalahari Desert. It was noticed that the nomadic Bushmen (who call it Xhoba) ate the stem of the Hoodia plant to stave off hunger during long hunting trips in the sparsely vegetated area. Generations of hunter-gatherer peoples used Hoodia gordonii for millennia when on long hunting trips, the soft fruit-like branches of the Hoodia being perfectly edible once the cactus-like spines are cut away.
Traditionally used by the Khoi-San of South Africa and Namibia as a hunger and thirst suppressant while on long hunting trips, the commercialisation of this plant has been highly controversial due to intellectual property rights and benefit sharing issues, as well as the fact that several prominent pharmaceutical companies involved in its development have withdrawn their interest.
Shaped like a spiny cucumber, they cut away the spines with their crude knives, and ate the flesh, thus sustaining themselves for days at a time. The plant was consumed raw, as a whole food rather than as a processed extract. Its reputation as an appetite suppressant has been passed down through generations, contributing to its later popularity as a natural aid for weight management in modern nutritional products.
Hoodia gordonii is traditionally used in South Africa for its appetite suppressant properties. P57AS3 (P57), an oxypregnane steroidal glycoside, is the only reported active constituent from this plant as an appetite suppressant. The pioneering group of scientists who investigated Hoodia species, Van Heerden et al. (1998), identified two steroidal glycosides from the extracts prepared from Hoodia species, one of which was named P57 (12-O-Tigloyl-3ß,12ß,14ß-pregn-5-en-20-one-3-O-ß-d-thevetopyranosyl-(1→4)-ß-d-cymaropyranosyl-(1→4)-ß-d-cymaropyranoside).
It has been termed 'P57' because it was the 57th plant-derived compound investigated for commercial development by the British pharmaceutical company Phytopharm. P57 has been patented by Phytopharm and developed in collaboration with the CSIR (South African Council of Scientific and Industrial Research).
Hoodigosides A–K (1–11), eleven new oxypregnane glycosides and the previously reported oxypregnane glycoside P57AS3, were isolated from the aerial parts of Hoodia gordonii. Whole-Hoodia powder contains variable amounts of fibre, organic material, antioxidants, and biologically active substances including steroidal glycosides. The chemical composition of Hoodia is not yet fully mapped. In the literature, primarily pregnane glycosides are in the focus; however, other potentially active constituents with sympathomimetic activity may also be present in the plant.
Certain identified marker compounds known as oxypregnane glycosides have been employed to determine the presence of Hoodia species. Although the best known of these, P57, has been used as a marker for Hoodia gordonii, it is not necessarily diagnostic for this species alone because P57 can be found in other Hoodia species.
In a study on rats at Brown Medical School, intracerebroventricular injections of the purified P57 demonstrated that the compound has a likely central nervous system (CNS) mechanism of action like that of neuroactive steroids. The studies demonstrated that the compound increases the content of ATP by 50–150% in hypothalamic neurons. In addition, third ventricle administration of P57 reduced subsequent 24-hour food intake by 40–60%.
It is hypothesized that neurons in the basal hypothalamus may be sensitive to changes in ATP levels and regulate food intake. There is no evidence of P57AS3 binding to or altering activity of known receptors or proteins, including Na/K-ATPase, the putative target of cardiac glycosides.
P57's proposed mechanism of action — increased ATP production in the hypothalamus after intracerebroventricular administration — is debatable, as there was no detectable P57 in the brain after oral administration in CD1 female mice according to Madgula et al. The intracerebroventricular route used in animal studies does not reflect the pharmacokinetics of oral supplementation in humans, raising serious questions about the relevance of this mechanism to real-world use.
H.g.-12, a steroid glycoside purified from H. gordonii extract, initiated cholecystokinin (CCK) secretion both ex vivo in rat intestine and in vitro in the human enteroendocrine cell line HuTu-80. CCK is known to exert central effects on appetite suppression via the vagus nerve, which afferents terminate in the gut wall. Based on the bitter taste of H. gordonii purified extracts, researchers assessed whether H.g.-12 could activate human bitter receptors. The steroid glycoside activated selectively TAS2R7 and TAS2R14, both heterologously expressed in HEK 293 cells. These results point to a potential route of action by which components of Hoodia might influence appetite control.
A study including both ex vivo rat and in vitro experiments using human cells illustrated the ability of H.g.-12 purified from Hoodia gordonii extract to induce cholecystokinin (CCK) secretion in the gut, possibly through activation of bitter sensors in the gut. CCK from the gut can facilitate central appetite suppression via the vagus nerve, supporting the notion of P57 as an anorectic compound in Hoodia gordonii. To date, the clinical relevance of this result remains to be evaluated in vivo.
Recently, alarming side effects of H. gordonii products — increased blood pressure and elevated pulse rate — have been reported. The aim of one study was to elucidate the underlying mechanism of these symptoms. A H. gordonii-containing product was tested for sympathomimetic activity. Isolated organ experiments on rat uterine rings revealed smooth muscle relaxant effect with a substantial component mediated through β-adrenergic receptors. Hoodia spray was found to possess sympathomimetic effects, which can manifest in both appetite suppression and increased thermogenesis, resulting in weight loss.
Bioavailability, pharmacokinetics, and tissue distribution of P57 were determined in CD1 female mice after administration of a single dose of enriched methanolic extract of Hoodia gordonii (equivalent to a dose of 25 mg of P57/kg) by oral gavage or a single dose of purified P57 (25 mg/kg) intravenously. The level of P57 in plasma and tissues (brain, liver, kidney, and intestine) was determined by UPLC-MS. After oral administration of Hoodia extract, the peak plasma level of P57 was achieved in 0.6 h. The oral bioavailability was 47.5% and the half-life of the absorption phase was 0.13 h. In conclusion, P57 showed moderate bioavailability and was eliminated rapidly.
P57 was rapidly distributed and eliminated from the tissues within 4 hours. The level of tissue distribution was highest in the kidney followed by liver and brain.
In simulated gastric fluid, the aglycone hoodigogenin A was stable (2% degradation in 60 minutes) whereas P57 was unstable (45% degradation in 30 minutes). In simulated intestinal fluid, P57 was degraded to an extent of 8% in 180 minutes, while hoodigogenin A was stable. This gastric instability of P57 itself has significant implications for the amount of intact active compound that can reach systemic circulation after oral dosing.
Of three scientific reports on animal studies involving P57, only one has been published in a peer-reviewed journal (MacLean & Luo, 2004). The other two have only appeared in abstract form in conference presentations (Tulp et al., 2001, 2002). Tulp et al. (2001, 2002) showed a 50% reduction in ad libitum food intake in rats fed Hoodia compared with control. The mean effective dose for appetite suppression in rats during a 4-hour feeding test ranged from 1.8 to 2.7 g per kg body weight for the various Hoodia species.
Extracts from Hoodia gordonii have been shown to decrease food intakes and body weights in animals and were proposed as a food supplement or ingredient for weight management. Healthy, overweight women, who were stratified by percentage body fat, received either HgPE (n = 25) or a placebo (n = 24) for 15 days. Subjects were resident in a clinic for a 4-day run-in period and a 15-day treatment period in which they received 2 servings/day of 1110 mg HgPE or a placebo formulated in a yogurt drink 1 hour before breakfast and dinner.
Mean effects on ad libitum energy intakes and body weights did not differ significantly between the HgPE- and placebo-treatment groups (P > 0.05). In comparison with a matched placebo, the consumption of HgPE for 15 days appeared to be associated with significant adverse changes in some vital signs and laboratory parameters. HgPE was less well tolerated than was the placebo and did not show any significant effects on energy intakes or body weights relative to the placebo.
This trial is the only published, peer-reviewed randomized controlled trial in humans. Only one small study has been done on the effects of hoodia supplements in people. The one small study of hoodia involved 49 women who were overweight. Those who took hoodia for 15 days didn't lose more weight than those who took a placebo.
As of 2018, there is no high-quality clinical research showing that hoodia has actions as an appetite suppressant or is effective for weight loss. No large-scale, high-quality randomised controlled trials have demonstrated that hoodia weight loss pills produce clinically meaningful or sustained weight loss in humans. The theoretical mechanism involving P57 has not been reliably replicated in robust human studies. The overall evidence is rated as weak and preliminary; the single published human RCT showed no efficacy and raised safety concerns.
Studies performed on obese participants have shown a reduction in appetite and weight loss along with a decrease in blood glucose and triglycerides. The major appetite regulatory peptides — leptin, ghrelin, neuropeptide Y (NPY), and cholecystokinin (CCK) — are altered in response to reduction in food intake on administration of H. gordonii. Effect of H. gordonii was seen under caloric restriction at a dose of 100 mg/kg body weight of crude extract. Changes were observed in ghrelin, CCK, blood glucose, liver glycogen, CPT-1, and AMPK. Altered metabolic responses confirm its anorectic action under caloric restriction. These data are from animal/in vitro models, and their human relevance has not been confirmed.
In the human RCT (Blom et al., 2011), blood pressure, pulse, heart rate, bilirubin, and alkaline phosphatase showed significant (P < 0.05) increases in the HgPE group. Statistical analysis of the electrocardiogram data showed that the PR interval in the HgPE group was statistically significantly (P < 0.05) higher on day −2 and from days 1–16 (mean difference ranged from 6.3 to 22.9 ms) than that with the placebo. Roza et al. (2013) reported alarming adverse effects of products from H. gordonii, revealing an elevated pulse rate and increased blood pressure. Sympathomimetic effects using isolated organ experiments on rat uterine rings demonstrated smooth muscle relaxant effects of H. gordonii-containing products, with a considerable component mediated through β-adrenergic receptors.
In the Blom et al. (2011) RCT, there were no serious adverse events, but HgPE was less well tolerated than the placebo because of episodes of nausea, emesis, and disturbances of skin sensation. Blood pressure, pulse, heart rate, bilirubin, and alkaline phosphatase showed significant (P < 0.05) increases in the HgPE group. Elevated bilirubin and alkaline phosphatase are liver function markers, suggesting potential hepatic effects at the doses studied, though no serious hepatic events were reported in that 15-day trial.
Hoodia gordonii extract (0, 5, 15, or 50 mg/kg body weight/day) was orally administered by gavage to female CD-1 mice from gestation days 5–17. On gestation day 18 the females were euthanized and examined. Treatment at 50 mg/kg/day caused a marked reduction in feed intake and body weight gain. Feed consumption was sporadically reduced at 15 mg/kg/day. At 50 or 15 mg/kg/day, fetal weights, ossification of some bones, and full and empty uterus weights were reduced. There were no clear maternal or fetal effects at 5 mg/kg/day. The overall study no-observed-adverse-effect level was set at 5 mg/kg/day. In summary, at doses that reduced maternal feed consumption, H. gordonii extract delayed fetal development.
Products are available in many different dosage forms including tablets, capsules, powders, sprays, tea, fruit and chocolate bars, patches, topical gel formulations, and even lollipops.
In the only published human RCT: participants received 2 servings/day of 1110 mg HgPE (Hoodia gordonii purified extract), formulated in a yogurt drink 1 hour before breakfast and dinner — giving a total daily dose of 2220 mg HgPE.
In the animal studies: the mean effective dose for appetite suppression in rats during a 4-hour feeding test ranged from 1.8 to 2.7 g per kg body weight for the various Hoodia species. Effect of H. gordonii was also studied at a dose of 100 mg/kg body weight of crude extract in a metabolic study in rats. In the developmental toxicity study, Hoodia gordonii extract was orally administered by gavage to female CD-1 mice at doses of 0, 5, 15, or 50 mg/kg body weight/day.
In pharmacokinetic studies in mice: bioavailability was studied after administration of a single dose of enriched methanolic extract of Hoodia gordonii equivalent to a dose of 25 mg of P57/kg by oral gavage, or a single dose of purified P57 (25 mg/kg) intravenously.
In the one small study in people, participants taking hoodia had more adverse effects, including nausea, vomiting, dizziness, and odd skin sensations, than those taking placebos. The researchers saw clinical and safety concerns for hoodia related to blood pressure and heart measures.
There were no serious adverse events in the Blom et al. (2011) RCT, but HgPE was less well tolerated than the placebo because of episodes of nausea, emesis, and disturbances of skin sensation. Blood pressure, pulse, heart rate, bilirubin, and alkaline phosphatase showed significant (P < 0.05) increases in the HgPE group.
An in-vitro study showed that intestinal transport of P57 was mediated by P-glycoprotein and multidrug resistance proteins MRP1/MRP2. P57 exhibited weak inhibition of the liver cytochrome P450 3A4 enzyme. The potential for clinically significant drug interactions is unknown. P57 also inhibited CYP 3A4 activity. In another study, pregnane glycosides specifically suppressed steroidogenesis by strongly inhibiting 11β-hydroxylase.
P57, the glycoside thought to suppress appetite, shows low bioavailability and rapid degradation in the body. In simulated gastric fluid, P57 was unstable, showing 45% degradation in 30 minutes. This raises questions about how much intact P57 reaches systemic circulation after oral dosing.
Little is known about whether it's safe to use hoodia during pregnancy or while breastfeeding. In animal studies, at doses that reduced maternal feed consumption, H. gordonii extract delayed fetal development.
Although Hoodia gordonii seems to have a desired effect on appetite and weight loss, this effect may at least in part be a secondary symptom of the serious adverse effects that are associated with consumption of the high doses required to achieve therapeutic clinical effect.
Adulteration is caused by several factors including unscrupulous companies concerned only with profit, the limited availability of H. gordonii, the slow maturation cycle of the plant, the need for a CITES permit to cultivate and export raw material, and high demand by consumers. Independent laboratory analyses have found that many commercially available hoodia products contain little or no authentic Hoodia gordonii. Adulteration and mislabelling are recognised problems in the unregulated supplement market. Even where genuine hoodia is present, the concentration of P57 may be insufficient to produce any meaningful physiological effect.
In October 2011, the FDA notified consumers that the "P57 Hoodia" product marketed by Huikng Pharmaceutical was found to contain sibutramine, a controlled substance that was removed from the U.S. market due to cardiovascular risks — illustrating the broader problem of pharmaceutical adulteration in hoodia weight-loss products.
Hoodia gordonii is listed under Appendix II of the Convention on International Trade in Endangered Species (CITES), requiring permits for international trade to prevent further depletion. This has limited legal exports but fueled a black market. Sustainable farming programs in South Africa and Namibia have been established to reduce pressure on wild populations.
One of the most iconic biopiracy cases globally is that of Hoodia gordonii, a succulent plant first researched in the early 1960s by the South African state-funded Council for Scientific and Industrial Research (CSIR) for its appetite and thirst-quenching properties. The CSIR was granted a patent for these properties, and commercial agreements commenced with the UK-based company Phytopharm and pharmaceutical giant Pfizer to develop an anti-obesity drug. However, the agreements occurred without the consent, knowledge, or involvement of Indigenous San, notwithstanding their knowledge being the basis for the research.
The San's traditional knowledge of Hoodia's appetite suppressive qualities was published by apartheid-era botanists and used by CSIR in isolating the appetite suppressing molecule P57. CSIR patented the extraction process and licensed it to UK pharmaceutical firm Phytopharm. Phytopharm then developed a new "cure" for obesity on the basis of P57 and obtained a patent for its application, which they licensed to Pfizer for US$21 million.
In 2003, the South African San Council entered into a benefit sharing agreement with CSIR in which they would receive from 6 to 8% of the revenue from the sale of H. gordonii products, money which would be deposited in a trust for all San peoples across Southern Africa. After dropping the development of Hoodia, Pfizer sold the rights back to Phytopharm for a nominal amount. Phytopharm then partnered with Unilever to produce a Hoodia-based weight management product, licensed in the EU as a functional food. Unilever withdrew four years later due to safety and efficacy concerns.
It is not clear yet that Hoodia does actually work, as few studies have been carried out. It has reached the market without adequate testing on the basis that it is a supplement, not a medicine. Because hoodia products are sold as food supplements rather than licensed medicines in the UK, they are not required to undergo pre-market safety testing. Publications based on scientific studies of key aspects such as in vivo biopharmaceutics, the biological activity of all chemical constituents, clinical efficacy, and especially safety are insufficient or completely absent, causing great concern as H. gordonii is one of the most widely consumed anti-obesity products of natural origin.
Condiciones de salud que Hoodia puede ayudar a apoyar.
Hoodia gordonii has been used by the San (Bushmen) people of southern Africa for centuries to suppress appetite and thirst during long hunting expeditions. Its proposed active compound P57 is thought to mimic glucose signaling in hypothalamic neurons to reduce hunger. Rigorous human clinical trial evidence is very limited; the best-designed RCT did not demonstrate significant appetite reduction and raised safety concerns.
Hoodia gordonii is a succulent used traditionally by the San people of southern Africa as an appetite suppressant during long hunts. The NIH ODS documents this traditional use and notes animal studies show reduced food intake; however, published human clinical trial evidence for weight loss is limited and mixed.
Sistemas corporales que Hoodia puede ayudar a apoyar.
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