Aframomum melegueta

Aframomum melegueta (Grains of Paradise) is a spice with a similar composition as Ginger that belongs to the same Zingiberaceae family. It shows some promise in fat-mass control at doses possibly consumable via food products.

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Aframomum melegueta (Alligator Pepper, Grains of Paradise) is a herb where the seeds have traditional usage mostly as a pungent spice to season foods with. This herb is botanically in the same family as Ginger and shares many bioactives, and has been (medicinally speaking) traditionally used mostly for digestive and intestinal health with some other sporadic uses not related to food.

When looking at the evidence, most of it is preliminary and a full compositional analysis does not appear to exist at this moment in time. It seems very related to Ginger, and has many of the same bioactives.

Aframomum melegueta appears to have some anti-diabetic and anti-obese mechanisms, although neither are remarkable (the one human study conducted in humans has confirmed an increase in metabolic rate, but required both cold exposure as well as brown fat on the person in question as prerequisites). The aphrodisiac and testosterone boosting properties are both preliminary (with the former not appearing too potent, relative to other herbs) and the anti-estrogen mechanisms are still fairly preliminary and of unknown practical relevance.

Aframomum melegueta may be promising for a spice to add to a diet in hopes of body recomposition and particularly for men, but there is overall a lack of evidence to support its usage as a supplement and higher oral doses may still have some toxicity associated with them (which needs to be more thoroughly investigated)

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Also Known As

Grains of Paradise, melegueta pepper, alligator pepper, Guinea pepper, Guinea grain


Is a Form of


Goes Well With

  • Cold Exposure (was a prerequisite for the lone human study to increase the metabolic rate)

Caution Notice

  • Appears to potently inhibit select CYP3A enzymes including CYP3A4, and thus confers a high risk for adverse drug-drug interactions
  • High doses have once been implicated in anti-fertility actions in females
Examine.com Medical Disclaimer

The only current human study used a 95%-ethanolic extract of Aframomum melegueta at 10 mg daily. There is no evidence to suggest whether this is the optimal dose, but it appears to be a low enough dose that the spice itself can be used on top of food.


The Human Effect Matrix looks at human studies (excluding animal/petri-dish studies) to tell you what effect Aframomum melegueta has in your body, and how strong these effects are.
GradeLevel of Evidence
ARobust research conducted with repeated double blind clinical trials
BMultiple studies where at least two are double-blind and placebo controlled
CSingle double blind study or multiple cohort studies
DUncontrolled or observational studies only
Level of Evidence
EffectChange
Magnitude of Effect Size
Scientific ConsensusComments
CMetabolic Rate

Minor

Requires more evidence, and the increase in metabolic rate was wholly conditional on cold therapy also being used (where supplementation with aframomum melegueta increased... show


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Table of Contents:


Edit1. Sources and Composition

1.1. Sources

Aframomum melegueta (of the family Zingiberaceae) is a spice in the Ginger family with the common name of 'Grains of Paradise' or 'Alligator Pepper'. The spice is used in West Africa for the purposes of alleviating stomachache and diarrhea[1] as well as hypertension[2] with some limited reports on it being used for Tuberculosis[3] and a remedy for snakebites and scorpion stings.[4] These seeds are also used for culinary reasons (due to the pungency of the seeds, it is common used as seasoning on food products[1][5]).

The seeds also tend to have general anti-microbial properties similar to many spices,[5][6] and has some molluscicidal[7] and repellant[8][9] properties as well. It is one of many pungent herbs said to aid in sexuality and aphrodisia[10] (although the class of 'pungent herb' appears to be mentioned more than this particular seed).

Grains of Paradise are a spice botanically related to Ginger, and have usage for gastrointestinal/digestive health as well as being used to season foods

1.2. Composition

Aframomum melegueta tends to contain:

  • 6-Gingerol (19.5% of ethanolic extract[1]), 8-Gingerol,[11] and Methyl-6-Gingerol[11]
  • 6-Shogaol (12.5% of ethanolic extract[1])
  • 6-Paradol (30.5% of ethanolic extract[1]) and Rac-6-Dihydroparadol[11]
  • 6-Gingeredione[12]
  • {2-(5-butylfuran-2-yl)ethyl}-2-methoxyphenol (structurally related to the above)[11]

Aframomum melegueta appears to have a polyphenolic content of 2.28+/-0.02mg/g (0.2% dry weight) with 0.55mg/g (0.06%) flavonoids; which is comparatively high to other African spices tested although low relative to other herbs.[13] This study also determined a Saponin and Flavanoid content in Aframomum melegueta and failed to detect any Alkaloids, Tannins, Phlobatanins, or Anthraquinones (qualitative rather than quantitiative analysis).[13]


Edit2. Pharmacology

2.1. Enzymatic Interactions

Aframomum melegueta (as well as Aframomum cuspidatum and Harrisonia abyssinica) have been noted to, in vitro, inhibit CYP3A enzymes with Aframomum melegueta at 10mg/mL concentration inhibiting CYP3A4 (Full inhibition with ethanolic extract, 98.85+/-0.1% with tea), CYP3A5 (99.87+/-0.3%), and CYP3A7 (97.24+/-0.2%).[14]

Appears to inhibit CYP3A enzymes, and is remarkably potent at doing so. Although preliminary, there is a high possibility of drug-drug interactions with Aframomum melegueta

6-shogaol and 6-paradol, two components of Aframomum melegueta as well as Ginger, appear to active TRPA1 and TRPV1 receptors with the respective EC50 values of 6-shogaol (11.2µM and 0.2µM) and 6-paradol (71µM and 0.7µM)[15] suggesting they are weaker than Evodiamine from Evodia rutaecarpa (856nM) and Capsaicin (45nM).[16]

Appears to activate TRPV1 recpetors, with less potency relative to other TRPV1 agonists; also appears to activate TRPA1 receptors


Edit3. Neurology

3.1. Mechanisms

Aframomum melegueta extract has been shown to moderately inhibited acetylcholinesterase activity with an IC50 of 373.33μg/mL.[17]

3.2. Aphrodisia

115mg/kg of Aframomum melegueta daily for 8 days noted an increase in the penile erection index (PEI), frequency of genital grooming and genital sniffing, and an increase in mounting frequency by 54%.[10] Intromission latency was reduced by 32% while ejaculation latency was increased (delayed) by 60% (with no significant influence on post-ejaculatory interval), and while all these effects were greater than control they were simultaneously lesser than the other herb tested, Piper guineense (although not by a statistically greater degree).[10]


Edit4. Interactions with Glucose Metabolism

4.1. Absorption

Aframomum melegueta has been noted to inhibit the α-amylase enzyme with an IC50 of 4.83+/-0.56mg/mL,[13] which may be related to the bioactives shared with Ginger as this has been noted to a similar degree with Red and White ginger plants.[18] Aframomum melegueta has also been noted to inhibit α-glucosidase with an IC50 of 2.14+/-1.08mg/mL.[13]

4.2. Mechanisms

Aframomum melegueta is able to attenuate the rate of glycation ex vivo by 73.4% at 0.25mg/mL with an IC50 of 0.125mg/mL; although an antioxidative effect may contribute (DPPH assay noted an IC50 value of 0.11mg/mL) this study noted that Ginger was more antioxidative yet less protective against glycation (suggesting other mechanisms are involved).[19]

In the pancreas of rats treated with Sodium Nitroprusside (SNP) ex vivo, aframomum melegueta was noted to have concentration-dependent protection of pancreatic β-cells thought to be via anti-oxidative properties.[13]

4.3. Interventions

A toxicological study in rats feeding Aframomum melegueta dailt for 28 days noted that, in male rats only, a dose-dependent decrease in blood glucose was observed at 450mg/kg (7.3%) and 1500mg/kg (20%) of the ethanolic extract.[1]


Edit5. Fat Mass and Obesity

5.1. Mechanisms

5.2. Interventions

An intervention in 19 otherwise healthy men noted that in persons with a response to Cold Exposure therapy (19°C with light clothing) that administration of an ethanolic extract of Aframomum melegueta (10mg of 15.2% 6-gingerol, 12.5% 6-paradol, 1.7% 6-shogaol and 4.0% 6-gingeredione) was able to increase the metabolic rate after 4 weeks of supplementation with 2 hours of cold exposure therapy.[12] Persons with no response to cold exposure (without substantial brown fat adipose tissue) failed to show a response to Aframomum melegueta supplementation.[12]

May augment the increase in metabolic rate in response to cold exposure therapy without per se influencing metabolic rate


Edit6. Interactions with Hormones

6.1. Testosterone

Cholesterol level was noted to be increased in the testes of rats treated with Aframomum melegueta (151.48% and 165.75% at 8 days for 115mg/kg and 230mg/kg, respectively; 93.34% at 55 days with 115mg/kg) which was associated with a 278-316% increase in testosterone after 8 days in serum (no dose dependence) with no measurements taken after 55 days.[20]

At least one study has supported an increase in testosterone in rats given 115-230mg/kg Aframomum melegueta daily for 8 days

6.2. Estrogen

Aframomum meleguita methanolic extract has been noted to inhibit 56.7+/-3.4% of estrogenic activity in a yeast assay when at the concentration of 100μg/mL; this was decreased with naringinase pretreatment.[21] Despite Aframomum meleguita outperforming all other herbs in this study, it underperformed relative to the active control of Tamoxifen (78% inhibition at 10µM).[21]

May have anti-estrogenic properties


Edit7. Interactions with Organs

7.1. Liver

In rats given a large amount of Alcohol (4.8g/kg) for 15 days, coingestion of Aframomum melegueta (100-200mg/kg water extracts) noted that the higher dose was able to prevent an increase in liver weight and fully abolish lipid peroxidation as assessed by MDA while preserving both GSH and GST; hepatic superoxide dismutase (SOD) was not significantly influenced by Aframomum melegueta despite it being reduced with ethanol.[22] The increase in serum AST and ALT was also fully normalized.[22]

An ethanolic extract of Aframomum melegueta at an oral dose of 450-1500mg/kg for 28 days in rats was noted to cause dose-dependent increases in liver weight with a mild increase in LDH (liver enzyme) and nonsignificant increases in AST; there was no apparent toxicity as assessed by histological examination (no detectable necrosis, steatohepatitis, or cirrhosis).[1]

7.2. Male sex organs

115 and 230mg/kg of Aframomum melegueta (dry weight) for 8 days or 115mg/kg for 55 days noted that the relative weights of the epididymis, seminal vesicle and prostate at the lower dose increased 10.81%, 6.40%, 30.49% (respectively) after 7 days and the testes and seminal vesicle appeared to further grow after 55 days (3.6% and 23.5%, respectively) although the prostatic growth attenuated.[20] An increase in fertility could not be measured as both control and Aframomum melegueta groups were highly fertile (and thus, no significant difference).[20]

At least one rat study has noted increases in seminal vesicle and testicle size associated with oral ingestion of 115mg/kg of Aframomum melegueta (human dose of at least 18.4mg/kg)


Edit8. Interactions with Cancer

8.1. Pancreatic

One study has noted that Aframomum melegueta methanolic and chloroform extracts held cytotoxic potential against PANC-1 pancreatic cancer cells in vitro with IC50 values of 13.8µg/mL and 47.8µg/mL, respectively.[23]


Edit9. Safety and Toxicity

9.1. General

In a brine shrimp cytotoxicity test, there was little to no cytotoxic potential at 10µM with moderate (20%) at 100µM and significant (50%) at 1,000µM; aframomum melegueta was comparatively more toxic than nutmeg but less than Ginger.[19]

28 days of intake of 120mg/kg in rats appears to be free of all side-effects, which 450mg/kg and 1500mg/kg were associated with increased liver weight without apparent toxicity.[1] No significant alterations were noted in body weight, food intake, or blood cells with other changes (inorganic phosphorus, serum protein, thrombin clotting time) were sporadic and not dose-dependent which were deemed not clinically relevant.[1]

One study (cannot be located online but cited here;[24] Igwe et al, 1999) noted that 350mg wholeseed Grains of Paradise caused diplopia and blurred vision in healthy Igbo men.

9.2. Pregnancy

A study in rats that used 50mg of Aframomum melegueta mixed in 20g rat chow (1% of feed; the food lasted 4 days and then normal chow was fed) to rats noted that while the control group had an average litter size of 7, the experimental group fed the Seeds of Paradise failed to deliver pups although no other side-effects appeared apparent.[24] This dose equated to 286-345mg/kg in rats,[24] and lower doses (0.5-2mg injections) have since failed to adversely affect litter size.[25]

High doses of Aframomum melegueta have been noted to abolish live births in rats according to one study, and a later study noted that this did not occur at a much lower dose; possible contraceptive properties at higher oral doses (which have not necessarily been cleared for being safe)

References

  1. Ilic N, et al. Toxicological evaluation of grains of paradise (Aframomum melegueta) (Roscoe) K. Schum. J Ethnopharmacol. (2010)
  2. Gbolade A. Ethnobotanical study of plants used in treating hypertension in Edo State of Nigeria. J Ethnopharmacol. (2012)
  3. Ogbole OO, Ajaiyeoba EO. Traditional management of tuberculosis in Ogun State of Nigeria: the practice and ethnobotanical survey. Afr J Tradit Complement Altern Med. (2009)
  4. Lans C, et al. Medicinal and ethnoveterinary remedies of hunters in Trinidad. BMC Complement Altern Med. (2001)
  5. van Andel T, Myren B, van Onselen S. Ghana's herbal market. J Ethnopharmacol. (2012)
  6. Konning GH, Agyare C, Ennison B. Antimicrobial activity of some medicinal plants from Ghana. Fitoterapia. (2004)
  7. Ndamukong KJ, et al. Molluscicidal activity of some Cameroonian plants on Bulinus species. East Afr Med J. (2006)
  8. Ukeh DA, et al. Repellent activity of alligator pepper, Aframomum melegueta, and ginger, Zingiber officinale, against the maize weevil, Sitophilus zeamais. Phytochemistry. (2009)
  9. Ukeh DA, et al. Behavioural responses of the maize weevil, Sitophilus zeamais, to host (stored-grain) and non-host plant volatiles. Pest Manag Sci. (2010)
  10. Kamtchouing P, et al. Effects of Aframomum melegueta and Piper guineense on sexual behaviour of male rats. Behav Pharmacol. (2002)
  11. Gröblacher B, et al. Putative mycobacterial efflux inhibitors from the seeds of Aframomum melegueta. J Nat Prod. (2012)
  12. Sugita J, et al. Grains of paradise (Aframomum melegueta) extract activates brown adipose tissue and increases whole-body energy expenditure in men. Br J Nutr. (2013)
  13. Adefegha SA, Oboh G. Inhibition of key enzymes linked to type 2 diabetes and sodium nitroprusside-induced lipid peroxidation in rat pancreas by water extractable phytochemicals from some tropical spices. Pharm Biol. (2012)
  14. Agbonon A, et al. In vitro inhibitory effect of West African medicinal and food plants on human cytochrome P450 3A subfamily. J Ethnopharmacol. (2010)
  15. Riera CE, et al. Compounds from Sichuan and Melegueta peppers activate, covalently and non-covalently, TRPA1 and TRPV1 channels. Br J Pharmacol. (2009)
  16. Pearce LV, et al. Evodiamine functions as an agonist for the vanilloid receptor TRPV1. Org Biomol Chem. (2004)
  17. Adefegha SA, Oboh G. Acetylcholinesterase (AChE) inhibitory activity, antioxidant properties and phenolic composition of two Aframomum species. J Basic Clin Physiol Pharmacol. (2012)
  18. Inhibitory effects of aqueous extract of two varieties of ginger on some key enzymes linked to type-2 diabetes in vitro
  19. Kazeem M, et al. Antiglycation, antioxidant and toxicological potential of polyphenol extracts of alligator pepper, ginger and nutmeg from Nigeria. Asian Pac J Trop Biomed. (2012)
  20. Massoma Lembè D, et al. Effect of the ethanolic extract from Fagara tessmannii on testicular function, sex reproductive organs and hormone level in adult male rats. Andrologia. (2011)
  21. El-Halawany AM, et al. Screening for estrogenic and antiestrogenic activities of plants growing in Egypt and Thailand. Pharmacognosy Res. (2011)
  22. Nwozo SO, Oyinloye BE. Hepatoprotective effect of aqueous extract of Aframomum melegueta on ethanol-induced toxicity in rats. Acta Biochim Pol. (2011)
  23. Dibwe DF, et al. Damnacanthal from the Congolese medicinal plant Garcinia huillensis has a potent preferential cytotoxicity against human pancreatic cancer PANC-1 cells. Phytother Res. (2012)
  24. Inegbenebor U, et al. Effect of alligator pepper (Zingiberaceae aframomum melegueta) on first trimester pregnancy in Sprague Dawley rats. Niger J Physiol Sci. (2009)
  25. Inegbenebor U, et al. Effect of aqueous extract of alligator pepper (Zingiberaceae aframomum melegueta) on gestational weight gain. Niger J Physiol Sci. (2009)

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