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Hoodia gordonii

Hoodia gordonii is a small shrub (falsely said to be a cactus) that is claimed to suppress appetite. It seems the main bioactive (P57) cannot easily reach the brain to do this, and aside from failures of hoodia to suppress the appetite it may also be mildly toxic and imprudent to supplement.

Our evidence-based analysis on hoodia gordonii features 33 unique references to scientific papers.

Research analysis led by Kamal Patel .
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Summary of Hoodia gordonii

Primary Information, Benefits, Effects, and Important Facts

Hoodia gordonii is a small plant that is used as a famine food (to suppress appetite and thirst, to make suffering a famine a bit more bearable) and due to that is sought after for possible appetite suppressive effects. The first introduction of Hoodia to the first world (Europe and North America) was based on preliminary studies associated with the company producing Hoodia, and the lone independent study on Hoodia has noted that active dose recommended for a supplement not only failed to reduce appetite but was also associated with some mild and irregular toxic effects that need to be further investigated.

This plant appears to be a source of a large amount (well over 30) steroidal glycosides, and only one is said to be the activ ingredient (P57) yet most of the steroidal glycosides have no research on them. Due to this, the possible toxic effects in humans (confirmed in mice), and both the inefficacy on reducing appetite while having no other apparent marketable effects Hoodia gordonii does not appear to hold any promise for a dietary supplement.

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Things To Know & Note

Is a Form Of

Primary Function:

Also Known As

Hoodia, Veldkos, Slimming cactus, Trichocaulon gordonii, Stapelia gordonii

Do Not Confuse With

Garcinia Cambogia (another ineffective appetite suppressant)

  • Possible CYP3A4 inhibition in vitro at a concentration that is relevant; no human studies have yet been conducted

How to Take Hoodia gordonii

Recommended dosage, active amounts, other details

Recommended doses of Hoodia Gorgonii tend to be around one gram of an extract of 70% steroidal glycosides or more, taken twice a day with each dose about an hour before a meal.

There is no evidence to suggest an optimal dose nor to support the above as being active, and the toxic dose in mice (as well as preliminary human evidence) is the exact same as the supplemental dose.

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Human Effect Matrix

The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects hoodia gordonii has on your body, and how strong these effects are.
Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
grade-c Notable - See study
The increase in blood pressure noted with hoodia gordonii in otherwise healthy persons reached 5.9-15.9mmHg systolic and 4.6-11.5mmHg diastolic; a worrying increase
grade-c Minor - See study
The increase in bilirubin seen with hoodia is thought to be a biomarker of possible hepatotoxicity, although it was not met with hemolysis (usually accompanies)
grade-c Minor - See study
Both heart rate and pulse rate are increased with hoodia ingestion, which are thought to be related to toxic effects of the herb
grade-c Minor - See study
ALP was noted to be increased in otherwise healthy women given the standard dose of hoodia, although the other liver enzymes were not affected significantly
grade-c - - See study
No significant reduction in appetite was seen with hoodia relative to placebo
grade-c - - See study
No significant reductions in fat mass are noted, secondary to a lack of influence on appetite
grade-c - - See study
No significant modifications in lean mass during weight loss with hoodia relative to placebo
grade-c - - See study
No significant influence on overall body weight (due to no fluctuations in appetite and thus no significant fat loss)

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Research Breakdown on Hoodia gordonii

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Hoodia gordonii (of the family Apocynaceae and formerly the Trichocaulon or Stapelia genera) is a small desert 'cactus' (actually part of the milkweed family[1]) that has traditional usage as a food product and thrist quencher in Africa[1][2] and has similar traditional usage and effects in the body as the related species hoodia pilifera[3] and similar bioactives to the forementioned and the officinale, currorii, and lugardii species.[4][5] The entire genera of Hoodia is sometimes known as veldkos (food from the veld) and due to its usage as a supplement hoodia gordonii may also be called Slimming Cactus.[6] When it blooms, the flowers give off the scent of raw meat which has led to the name of the flower sbeing carrion flowers.[1]

The hoodia plant is widely distributed in arid areas of South Africa and Namibia, and it is used as a food product due to its multi-stemmed succulent with thick, erect, cylindrical, fleshy and fairly hard, glabrous, grey-green to grey-brown stems; it is spiny, but not actually a cactus (cactuses are things in the Cactaceae family).[2] Hoodia gordonii appears to be a protected plant.[7]

The main bioactive appears to be able to be synthesized[8][7] although this may be subject to patent,[4] and industry specifications for hoodia gordonii growers suggest it should be at 0.3% of the plant's dry weight.[9]

Hoodia gordonii is a desert plant that resembles a cactus although it is not phylogenetically related to such. It is a vegetable more than anything, and appears to be traditionally used to suppress the desire to eat or drink water (similar to other famine foods such as Caralluma fimbriata)

Hoodia gordonii has some atypical methylated sugars in the glycosides including D-Thevetose (The), D-Cymarose (Cym), D-Oleandrose (Ole), D-digitoxose (Dig), and 3-O-methyl-6-deoxy-D-allose (MDA) as well as glucose;[2] these abbreviations are used below to illustrate the side chain, with the first one mentioned being the one connected to the basic steroid structure (either the molecule in the first bullet, or Calogenin).

The steroid glycosides contained in Hoodia include:

  • Hoodigogenin A and Gordonoside A, both are the same molecule (12β-tygloyl-14β-hydroxy-pregn-5-en-20-one) and form the base of all Gordonosides and most Hoodigosides (those not based on Calogenin)[10][11][12] and is sometimes also called Tigloyloxydigipurpurgenin II[3]

  • The glycoside based off of the aforementioned known as P57, P57A53, or Glycoside number 12 (Hg.12) with the glycoside chain of Cym-Cym-The;[3][2] known to have appetite suppressing properties, said to be at 0.3% (Industry Spec[9]) and measured from undetectable to 0.43% (4% of samples had over 0.3%[9] and elsewhere the dry weight of the plant itself was noted to be 0.24%[13])

  • Other Hoodigosides are based of the Hoodigogenin A structure and vary by their glycosides including Hoodigoside A (The-Cym), Hoodigoside B (The-The-Cym), Hoodigoside C (The-Cym-Cym-Cym), Hoodigoside D (The-The-Cym-Cym), Hoodigoside E (Glu-The-Cym-Cym), Hoodigoside F (Glu-Ole-The-Cym-Cym), Hoodigoside G (Glu-Cym-The-Cym-Cym), Hoodigoside H (Glu-Cym-Cym-Cym-Cym), Hoodigoside I (Glu-Ole-Cym-Cym-Cym), Hoodigoside J (Glu-Ole-Dig-Cym-Cym), Hoodigoside K (Glu-Glu-Cym)[11][2] Hoodigoside W (Ole-The-Cym-Cym), and Hoodigoside X (The-Cym-Cym)[14]

  • Gordonosides, which are also based off the Hoodigogenin A steroid. These include Gordonoside B (The-Ole-Cym-Cym), Gordonoside C (side chain unidentified), Gordonoside D (Dig-Ole-Cym-Cym), Gordonoside E (Ole-Ole-Cym-Cym), Gordonoside F (Ole-Cym-Cym-Cym), Gordonoside G (four Cyms), Gordonoside H (side chain unidentified), Gordonoside I (Dig-Ole-Ole-Cym-Cym), and Gordonoside L (Ole and four Cyms)[10][2]

  • Hoodigosides that are based off of Calogenin (pregn-5-ene-3β,14β,20β-triol) rather than Hoodigogenin A, but most have glucosides on the opposite side of the Calogenin chain. The most basic is Hoodigoside N (The-Ole; no secondary chain) and adding a diglucoside to the second site produces Hoodigoside M (The-Ole; Glu-Glu). All other structures have either an initial side chain of plus a tigloyl (Tig) group on the end and these include Hoodigoside V (The-Ole-Tig;Glu), Hoodigoside O (The-Ole-Tig;Glu-Glu), Hoodigoside L (The-Ole-Tig;Glu-Glu-Glu), Hoodigoside P (Ole-Cym-Tig;Glu-Glu-Glu), Hoodigoside R (Ole-Ole-Cym-Tig;Glu-Glu-Glu), Hoodigoside Q (Cym-Cym-The-Tig;Glu-Glu-Glu), Hoodignoside T (Cym-Cym-Cym-Ole-Tig;Glu-Glu), Hoodigoside S (Cym-Cym-Cym-Ole-Tig;Glu-Glu-Glu), Hoodigoside U (Cym-Cym-Cym-Cym-Tig;Glu-Glu-Glu)[15] Hoodigoside Y (The-Ole;Glu), and Hoodigoside Z (The-Cym-Cym;Glu-Tig)[14]

  • Unnamed Hoodigogenin A glycosides with the side chains Cym-The-Cym-Cym (18mg/kg),[3] Ole-Mda-Cym-Cym, Cym-Mda-Cym-Cym, Ole-Dig-Cym-Cym, and Ole-Cym-Cym-Cym[2]

  • Hoodistanalosides based on an Orostanol backbone (3,5,14,20-tetrahydroxy-5{6→7}abeo-pregnan-7-al[16]) of which the glycosides that exist are Hoodistanaloside A and Hoodistanaloside B, both with a similar glycoside chain (Tig-The-Ole;Glu) but differ by hydroxyls on the backbone[14]

Total steroids in the raw plant have been noted to reach 2.1% dry weight with P57 being about 11% of total steroids,[13] although supplements are usually standardized to much higher levels (33-80% steroidal glycosides).

Note: The above glycoside chains are named working outwards from the steroid, hence why P57 is listed as Cym-Cym-The while the picture below depicts The-Cym-Cym (as the chain extends out to the left)
The steroidal glycosides in Hoodia are either based off of Hoodigogenin A (synonymous with Gordonoside A) or they are based off of Calogenin. They only differ by what sugars (atypical methylated sugars) are included in their side chains and in what order they exist, having these sugars makes then 'glycosides' (without the sugars, they are 'aglycones' meaning 'without sugar')

Other constituents of Hoodia gordonii that do not fall in the steroidal glycoside category are:

  • Cholesterol and β-sitosterol (collectively 0.5% of an extract of 33% steroidal glycoside[17] or inclusive of stigmasterol they are at 0.39% of an 80% steroidal glycoside extract[18])

  • Fatty acids (collectively; palmitic, linolenic, oleic, stearic, arachidonic, behenic, henatriacontylic, lacceroic, psyllic, and geddic acids) at 20% of a 33% steroidal glycoside extract[17] or 3.12% of an 80% steroidal glycoside extract[18]

  • Alkanes (C31, C33) at 2.9% of a 33% steroidal glycoside extract[17]

  • Vitamin E (as alpha-tocopherol)[18]

The bioactives in Hoodia that do not belong to the steroidal glycosides are not well studied, and at this moment in time there does not appear to be anything remarkable about them; some of the saturated fatty acids get quite long though (34 carbons) which is mildly interesting

P57 is confirmed to activate the bitter receptor (TAS2R14).[19] Ligands of the bitter taste receptors tend to induce secretion of either GLP-1[20] or CCK,[21] and P57 has been noted to induce CCK as well.[19]

Hoodia is noted to activate the bitter taste receptors, which may have a gustatory influence on appetite regulation

Storage of hoodia gordonii extract at ambient temperature (21-24°C) less than 60% humidity for 19 months does not degrade the bioactive steroidal glycosides.[18]

Should be preserved at room temperature and normal humidity for little over a year and a half

In vitro, intestinal absorption of P57 appears to be less than 2% when alongside Caco-2 cells at 100-200μM.[22] It appears to be taken up via P-glycoprotein and MRP transporters[23] and is subject to intestinal efflux;[24] the aglycone (Hoodigogenin A) is passively diffused.[25]

Bioavailability of steroidal glycosides (measured in P57 equivalents) in the pig intestine following ingestion of 7.9mg/kg of a hoodia gordonii extract (79.3% steroidal glycosides) appears to be in the range of 41.9-54.2% with a mean value of 46%.[26] Coingestion with a meal slowed the Tmax of the steroidal glycosides,[26] and a similar bioavailability has been noted in mice (47.5%).[27]

While the steroidal glycosides are not perfectly absorbed (and subject to intestinal efflux), there does appear to be absorption of the steroidal glycosides (as glycosides) which has reached 50% in pigs

Buccal absorption has been noted in vitro with P57, suggesting that oral absorption may be possible.[24]

A possible oral route of absorption appears to be possible with the main bioactive

In rats, 15mg/kg of isolated P57 has reached Cmax concentrations in the range of 0.1-3μM.[26]

In pigs, oral ingestion of 7.9mg/kg of steroidal glycosides (79.3% purity) has resulted in a Cmax of 73–115ng/mL P57 at a Tmax of 93-120 minutes.[26]

Oral ingestion of 1,110mg hoodia gordonii to females results noted a Cmax of steroidal glycosides of 92+/-47ng/mL after a Tmax of 45-50 minutes and a half-life of 50 minutes, conferring an AUC of 366-439ng/mL/h (with a trend for increased AUC after 15 days relative to a single dose).[28] The steroidal glycosides were measured in P57 equivalents.[28]

In humans, the standard recommended dose of hoodia appears to increase plamsa concentrations of steroidal glycosides to the low nanomolar range (although within the concentration range where it may act on the hypothalamus, assuming it reaches the brain in similar quantities)

Oral ingestion of a hoodia gardonii extract (conferring 25mg/kg P57) to mice has been noted to increase tissue concentrations of P57 in the liver, intestines, and kidneys to a low level and there was no detectable increase in brain tissue.[27] The tissue:plasma ratios were calculated for the liver (0.02), intestines (0.11), and kidney (0.06) although none could be calculated for the brain.

P57 does not appear to be well distributed to tissues well following oral ingestion, and none has been detected in the brain (which is required for its supposed appetite suppressing effects, thought to be due to direct stimulation of the hypothalamus)

P57 appears to be metabolically stable in the presence of liver cells[23] but appears to be unstable in the stomach (45% degratation in 60 minutes) and moderately unstable in intestinal fluid (8% degradation in 120 minutes);[25] Hoodigogenin A tends to be formed when P57 is degraded, and it itself is stable under all conditions.[25]

P57 appears to be stable in liver cells but instable in the stomach, while the aglycone (Hoodigogenin A) appears to be stable in the stomach and intestines

P57 has been noted to inhibit CYP3A4 with an IC50 of 45μM while it has no inhibitory effect on CYP1A2, CYP2C9, and CYP2D6.[23] The aglycone, Hoodigogenin A, appears to be significantly more potent at inhibiting CYP3A4 with an IC50 of 3μM.[25]

Possible CYP3A4 inhibition may occur with Hoodigogenin A, and it is plausible that this may occur to a limited degree following oral ingestion of high doses of hoodia

Supplementation of 1,110mg of hoodia gordonii (79.5% steroidal glycosides) was noted to increase pulse and heart rate relative to placebo when taken over 15 days alongside a controlled diet.[28]

An increase in pulse and heart rate has been noted with hoodia ingestion in otherwise healthy persons, which is thought to be associated with possible toxic effects (not clear at the moment)

Supplementation of 1,110mg of hoodia gordonii (79.5% steroidal glycosides) was noted to increase blood pressure relative to placebo when taken over 15 days alongside a controlled diet;[28] the magnitude of increase in these normotensive persons ranging from 5.9-15.9 (systolic) and 4.6-11.5mmHg (diastolic) on an individual basis.[28]

An increase in blood pressure has been noted with hoodia ingestion in otherwise healthy persons, but the magnitude of blood pressure increase is actually quite large and a concern

Mechanistically, injections of isolated P57 into the rat hypothalamus have increased intracellular ATP concentrations which were associated with reductions in food intake (40-60%);[29] Hoodigogenin A appears to be inactive, and the increase in ATP is thought to underlie appetite reduction seen with P57.[29]

It is thought that P57 increases ATP concentration in the hypothalamus, which is a mechanism known to reduce appetite; this has been seen with intracerebral injections of P57 to rats

6.25–50mg/kg of P57e from hoodia gordonii over one week was able to reduce food intake with more potency on day one (49-55% reduction) than after seven days (12-45%) with irregular dose dependency;[3] 30mg/kg of this bioactive appeared to be more potent than 15mg/kg fenfluramine.[3]

One study mentions preclinical (unpublished) data from a trial where 1,800mg of a Hoodia gordonii extract (79.5% steroidal glycosides) taken twice daily for 15 days reduced appetite by 30% associated with a serum concentration of 100ng/mL total steroidal glycosides; when the authors themselves a trial in mildly overweight women given 1,110mg hoodia gordonii (79.3% steroidal glycosides, said to hit 100ng/mL) twice daily (hour before meals) in a clinical setting for 15 days failed to find significantly more appetite suppression with Hoodia (24%) than placebo (18%).[28]

Although one animal study (using oral supplementation rather than intracerebral injections) has noted positive effects, the human study has failed to outperform placebo

In rats subject to 6.25-50mg/kg of the isolated pregnane triglycoside, body weight appears to be attenuated which is thought to be secondary to reduced food intake.[3]

In women given 1,110mg of the hoodia gordonii extract (79.5% steroidal glycosides) over 15 days, the lack of appetite suppression was met with a failure to decrease weight or body fat more than placebo.[28] There appear to be some small trials (not found online, but mentioned in this report[30]) which showed promise but were funded by PhytoPharm, a producer of Hoodia gordonii supplements.

Secondary to the influences on appetite (best evidence says that this does not occur to a large degree in humans) there are modifications in weight; no human evidence supports a weight loss effect of hoodia

Pregnane glycosides from hoodia gordonii (25% purity) at 4-100µg/mL (IC50 in the range of 75-90µg/mL) is able to inhibit forskolin-induced secretion of corticosterone, with 100µg/mL needed to suppress secretion of cortisol or androstenedione.[31] It was noted to reduce HSD3B2 mRNA levels (no include on P450 enzymes nor StAR)

Inhibition of steroidogenesis from pregnane type steroids appears to be reduced 8-fold when the tigloyl group is added to C12, while glycosides on C3 (mostly D-cyamarose) seem to increase it.[31]

There may be an inhibitory effect on steroid synthesis in isolated adrenal cells with a high concentration of steroidal glycosides from Hoodia gordonii (may not be relevant following oral ingestion due to the high concentration)

In mice, while 400mg/kg appears to be a well tolerated dose of hoodia gordonii (33% steroidal glycosides and 4.7% P57) it appears that 500-1,000mg/kg was associated with some mortality (none at the 750mg/kg dose oddly).[17]

There is apparent toxicity in mice at higher doses, which (if converted to human equivalents and standardized for the steroidal glycoside content) are within the ranges used for nutritional supplementation

Supplementation of 1,110mg of hoodia gordonii extract (79.5% steroidal glycosides) in women over 15 days has resulted in increased serum ALP (a liver enzyme) in the range of 4.7 to 8.8 U/L and was also able to increase total and indirect bilirubin by 0.20mg/dL to 0.58mg/dL and 0.18mg/dL to 0.49mg/dL (respectively).[28] The authors noted that they were unable to find a causative agent (either the steroidal glycosides of something in the unidentified 9.4% of the supplement), and due to no hemolysis nor inductions of other liver enzymes the clinical significance of these findings were uncertain.[28]

Limited human evidence has found changes in serum biomarkers that indicate toxicity, although at this moment the clinical relevance is unknown

Supplementation of 100-400mg/kg hoodia gordonii extract to mice (33% steroidal glycosides and 4.7% P57 overall) failed to exert genotoxic effects (higher doses not tested due to lethality with 1,000mg/kg).[17]

One mouse study (duplicated in Medline[32][33]) used 15-50mg/kg of hoodia gordonii extract (70% steroidal glycosides and 10% P57) during pregnancy noted reductions in maternal food intake associated with reductions in fetal size, with no noticeable effect from 5mg/kg. No dose of hoodia gordonii was associated with deformations to the fetus, nor was pregnancy state altered.

No apparent genotoxicity (damange to the DNA) nor teratogenicity (damage to the fetus), although this may be because higher doses were not tested due to killing mice


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