Hoodia Gordonii Extract (cactus)
Mechanism of Action +
### The P57 Steroidal Glycoside The primary bioactive compound identified in Hoodia gordonii is an oxypregnane steroidal glycoside known as P57AS3, or simply P57. Discovered in the 1980s by the South African Council for Scientific and Industrial Research (CSIR), P57 was isolated as the putative appetite-suppressing agent responsible for the traditional use of the raw cactus by the San bushmen.
### Hypothalamic ATP Signaling The proposed mechanism of action for P57 centers on the central nervous system, specifically the hypothalamus, which acts as the brain's master regulator of energy balance and appetite. In animal models, when P57 is injected directly into the brain (intracerebroventricular injection), it significantly increases the intracellular content of adenosine triphosphate (ATP) in hypothalamic neurons. This localized surge in ATP mimics the physiological state of being fed, signaling to the brain's energy-sensing pathways that caloric intake is sufficient, thereby suppressing the drive to eat.
### The Bioavailability Bottleneck Despite the elegant mechanism observed in vitro and in rodent brain-injection models, the pharmacokinetics of oral Hoodia gordonii extract in humans represent a catastrophic failure of translation. Steroidal glycosides like P57 are highly susceptible to enzymatic degradation and acidic hydrolysis in the human gastrointestinal tract. Consequently, oral bioavailability is exceptionally poor. The intact P57 molecule fails to reach systemic circulation in therapeutic concentrations, and even less crosses the blood-brain barrier to exert its effects on the hypothalamus. This pharmacokinetic reality explains why oral supplementation fails to replicate the appetite-suppressing effects seen in traditional use (where the raw plant is chewed, potentially allowing for sublingual absorption) or in animal models.
### Physiological Stress and Toxicity Pathways While failing to suppress appetite, oral ingestion of concentrated Hoodia gordonii extract triggers significant peripheral side effects. Clinical data indicates that high doses (e.g., 2,220 mg per day) induce sympathetic nervous system activation, leading to elevated heart rate and blood pressure. Furthermore, the extract places a notable burden on hepatic metabolism. Human trials have recorded significant elevations in serum bilirubin and alkaline phosphatase (ALP), which are clinical markers of liver stress or hepatotoxicity. The exact metabolic pathways causing this hepatic strain remain unmapped, but they strongly suggest that the liver struggles to process the degraded metabolites of the extract.
What does hoodia do to your body? +
What are the concerns with Hoodia gordonii? +
How long does it take for hudiya to work? +
What is Hoodia gordonii? +
Does hoodia raise blood pressure? +
What medications should you not take with garcinia cambogia? +
Is Hoodia safe for the liver? +
Why did Pfizer drop Hoodia? +
Are Hoodia supplements fake? +
Can I take Hoodia while pregnant? +
What is P57? +
Did the San bushmen use Hoodia? +
What is the recommended dose of Hoodia? +
Does Hoodia cause nausea? +
Is Hoodia an endangered plant? +
Everything About Hoodia Gordonii Extract (cactus) Article
## Introduction to Hoodia Gordonii
Hoodia gordonii is a rare, succulent plant native to the harsh environments of the Kalahari Desert in southern Africa. Often mistaken for a cactus due to its leafless, spiny, and swollen stems, it actually belongs to the Apocynaceae (dogbane) family. For centuries, the indigenous San people (often referred to as bushmen) chewed the bitter flesh of the raw plant to suppress hunger and thirst during arduous, multi-day hunting expeditions.
In the early 2000s, this traditional knowledge caught the attention of the Western world. Pharmaceutical companies and supplement manufacturers raced to isolate the active compounds, leading to a massive boom in Hoodia-based weight loss products. It was marketed as a miracle appetite suppressant, promising effortless weight loss without the jittery side effects of traditional stimulants. However, the reality of Hoodia gordonii as a dietary supplement is a stark contrast to the marketing hype.
## The Science of P57: How It Was Supposed to Work
The intense interest in Hoodia led to the discovery of its primary bioactive compound: an oxypregnane steroidal glycoside named P57AS3, commonly referred to simply as P57.
Researchers hypothesized that P57 worked directly on the brain's master control center for appetite—the hypothalamus. In laboratory settings, when P57 was injected directly into the brains of rodents, it caused a significant spike in the intracellular production of adenosine triphosphate (ATP) within hypothalamic neurons. ATP is the primary energy currency of the cell. By artificially raising ATP levels in the hypothalamus, P57 tricked the brain into sensing a state of caloric abundance. The brain believed the body had just consumed a massive meal, thereby shutting down the drive to eat.
This mechanism was elegant and highly effective in rats. It prompted major pharmaceutical companies, including Pfizer, to invest heavily in developing P57 as a prescription anti-obesity drug.
## The Bioavailability Bottleneck: Why Oral Supplements Fail
If P57 works so well in the brain, why is Hoodia gordonii considered a failed supplement? The answer lies in pharmacokinetics—specifically, bioavailability.
When the San bushmen consumed Hoodia, they chewed the raw plant, potentially allowing the active glycosides to be absorbed sublingually (under the tongue) directly into the bloodstream, bypassing the digestive system.
In contrast, commercial Hoodia supplements are swallowed as dried extracts in capsules. Steroidal glycosides like P57 are highly fragile when exposed to the harsh environment of the human gastrointestinal tract. Stomach acid and digestive enzymes rapidly break down the P57 molecule before it can be absorbed into the systemic circulation. Even if a fraction of the compound survives digestion, it struggles to cross the blood-brain barrier in sufficient concentrations to influence the hypothalamus.
Because the active ingredient never reaches its target, oral Hoodia supplements fail to suppress appetite in humans.
## Clinical Evidence: The Nail in the Coffin
The definitive blow to Hoodia's reputation came from a 2011 double-blind, placebo-controlled human trial conducted by Blom et al. This study is widely regarded as the most rigorous investigation into the efficacy and safety of Hoodia gordonii extract.
The researchers administered 1,110 mg of purified Hoodia extract twice daily (totaling 2,220 mg per day) to healthy, overweight women for 15 days. The results were highly disappointing for the supplement industry:
1. **No Weight Loss:** The Hoodia group experienced no significant reduction in body weight compared to the placebo group. 2. **No Appetite Suppression:** There was no significant decrease in ad libitum (free-feeding) energy intake.
More alarmingly, the study revealed severe safety concerns that had not been fully appreciated in animal models.
## Safety, Side Effects, and Toxicity
While Hoodia failed to deliver on its weight-loss promises, it succeeded in causing a host of adverse physiological reactions. The 2011 clinical trial documented several concerning side effects:
* **Cardiovascular Stress:** Participants taking Hoodia experienced significant increases in both blood pressure and heart rate. For a supplement marketed to overweight individuals—a population already at higher risk for cardiovascular disease—this is a dangerous contraindication. * **Hepatic (Liver) Strain:** Blood tests revealed significant elevations in bilirubin and alkaline phosphatase (ALP). These are clinical markers of liver stress, indicating that the liver was struggling to metabolize the degraded components of the extract. * **Physical Discomfort:** Users reported moderately severe nausea, vomiting, dizziness, and bizarre, altered skin sensations.
Due to these findings, major pharmaceutical companies abandoned their research into Hoodia, and authoritative bodies like Examine.com classify it as a failed, potentially dangerous supplement.
## The Epidemic of Fake Hoodia
Beyond the lack of efficacy and safety concerns, consumers face another massive hurdle: widespread adulteration.
Hoodia gordonii is a rare, slow-growing plant that requires specific desert conditions to thrive. Due to the explosion in demand in the early 2000s, the plant was pushed to the brink of overexploitation. Consequently, it was listed in Appendix II of the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES), making it illegal to harvest or export without strict permits.
Because real Hoodia is incredibly scarce and expensive, the supplement market was quickly flooded with counterfeit products. Independent analyses of commercial Hoodia supplements between 2005 and 2013 revealed that a vast majority of products sold online contained absolutely no Hoodia gordonii. Instead, they were filled with cheap fillers, undisclosed stimulants, or entirely different plant species.
## Conclusion
Hoodia gordonii stands as a cautionary tale in the dietary supplement industry. It highlights the danger of assuming that traditional ethnobotanical practices will seamlessly translate into commercial, encapsulated products.
Despite the fascinating mechanism of its active compound, P57, the reality of human digestion renders oral Hoodia extracts useless for weight loss. Coupled with the documented risks of cardiovascular and hepatic stress, and the high likelihood of purchasing a counterfeit product, Hoodia gordonii is a supplement that should be strictly avoided.